Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
these conditions may be life - threatening ( e.g. oral cancers ) or not , progressing ( caries , periodontitis , etc . ) or not , dealing with aesthetics ( staining in anterior teeth such as molar
incisor hypomineralisation ( mih ) ) or pain ( pulpitis , mih in posterior teeth , etc . ) .
ohrqol is highly subjective and has to be assessed within the framework of patients conditions , sociocultural environments and own experiences and states of mind : because ohrqol is related to daily life and is unique to each individual , even patients with severe conditions can report having good quality of life .
furthermore , quality of life is by itself multi - faceted , showing variation over time for each individual .
ohrqol should therefore be assessed longitudinally to take into account changes over time , using versatile tools .
this means having relevant questions with well - defined items and being able to analyse answers in a good way .
many limitations can be found to the current validation testing , including relevance of the questions , validity and sensitivity to change , risk of misinterpretations ( role of the ethnocultural environment ) , problems of translation of english questionnaires and difficulty to interpret the significance of a psychometric measurement when reported simply as a numerical score or a mean [ 1 , 2 ] .
this latter point is of importance since the same score can be obtained from people answering in a different way to a majority of questions . finally , patient - based outcome measures ( as named by fitzpatrick et al . )
should provide the opportunity to measure the extent or intensity of the changes in ohrqol .
various psychometric instruments have also been used to measure ohrqol ( tables  1 and 2 ) [ 1 , 4 ] .
these are based on different criteria that enable them to be more or less patient- or expert - centred .
some are generic ( ohip1 - 49 , ohip-14 , oidp , oh - qol , sf-362 ) and can be considered as core indicators ; others are adapted to specific conditions / domains ( orthognathic qol questionnaire , sooq for orthodontic surgery , ohip - aesthetic,3 ohrqol for dental hygiene ) or populations ( cohqol and child - oidp for children , gohai for elderly people , etc.).table 1conceptual and structural basis of psychometric instruments used in dentistry ( adapted from brondani and mcentee ) instrumentsacronymstructural originsempirically basedconnotation of questionsnumber of questionssocial impacts of dental diseasesiddsipyesn14oral health impact profileohipicidhyesn49geriatric ( generic ) oral health assessment indexgohaiicidh and sipyesn and p12oral health - related qol instrumentohrqlmultiplenon36oral impact on daily performancesoidpicidhnon8dental impact on daily livingdidlsipyesn and nt and p36dental impact profiledipsipyesn and nt and p25oral health - related quality of life measureohqolmultiplenon3oral health quality of life inventoryoh - qolsipunclearp15rand dental questionnaireunspecifiedsipnon3oral health questionnaireunspecifiedicidhunclearn and nt and p70oral health quality of life ukohqol - ukicidh2yesn and p16subjective oral health status indicatorssohsimultiplenon and nt34liverpool oral rehabilitation questionnairelorqunclearnon40self - rated oral healthsrohicidhnon and p3dentaldentalunclearnon15dental health status quality of life questionnaireds - qolgeneric qol instrumentnon and punclearn 1/4 negative , nt neutral , p positive , sip sickness impact profile , icidh international classification of impairments , disabilities and handicapsinformation derived from open - ended interviewssome indicators present shorter or extended forms other than the original versionhealth - related models : natural history of disease model and sipdeveloped from existing measures ( rand , oral facial pain index , etc.).table 2oral health outcome measures developed before 2007 ( adapted from locker and allen ) pre-1997 ( presented at the 1997 conference ) social impacts of dental diseasegeneral ( geriatric ) oral health assessment index ( gohai)dental impact profile ( dip)oral health impact profile ( ohip)oral impacts on daily performances ( oidp)subjective oral health status indicators ( sohsi)oral health - related quality of life measuredental impact on daily living ( didls)oral health quality of life inventoryrand dental questionspost-1997ohqol - ukchild oral health quality of life questionnaire ( cohqol)child oidpohrqol for dental hygieneorthognathic qol questionnairesurgical orthodontic outcome questionnaire ( sooq ) conceptual and structural basis of psychometric instruments used in dentistry ( adapted from brondani and mcentee ) n 1/4 negative , nt neutral , p positive , sip sickness impact profile , icidh international classification of impairments , disabilities and handicaps information derived from open - ended interviews some indicators present shorter or extended forms other than the original version health - related models : natural history of disease model and sip developed from existing measures ( rand , oral facial pain index , etc . ) .
oral health outcome measures developed before 2007 ( adapted from locker and allen ) the ohip , also called ohip-49 , is the most widely used , and this has enabled investigators to modify forms that can be subsequently adapted to populations or conditions .
the initial 49-question form was constructed to assess the  social impact of oral disorders .
each of the set of 49 statements represented one of seven domains : it is mainly expert - centred and constructed to select items according to their fit with a conceptual framework rather than on the basis of their importance to the patients from whom they were derived .
a shorter version of ohip restricted to 14 items ( ohip-14 ) was later proposed .
one major question is to know if we need to use either a generic questionnaire , an adapted form of a generic questionnaire or to construct a new questionnaire specific to the population or condition to be studied .
constructing or using one of these specific questionnaires may lead to many questions , for example , ( 1 ) is it made specifically for the purpose of research or for clinical practice ? or ( 2 ) how to adapt each questionnaire to local languages and cultures ?
this may subsequently lead us to consider the impact of dentin hypersensitivity ( dhs ) or exposed cervical dentin ( ecd ) on ohrqol of those individuals being assessed .
very few studies have been devoted to this aspect of dhs / ecd as recently shown , with only two papers written in english specifically dedicated to the evaluation of ohqol in dhs / ecd patients .
one paper provided results using a generic questionnaire   and the second paper constructed a specific questionnaire to evaluate ohqol in dhs / ecd patients but provided no epidemiological results . these studies are more extensively described in an accompanying paper . in the future ,
studies using validated questionnaires specifically constructed to evaluate the impact of the condition on ohqol should be employed .
these questionnaires should be patient - centred and derived from interviews with patients who are expected to complete the questionnaire [ 4 , 10 ] . furthermore , if these studies also attempt to evaluate the efficacy of desensitising agents in reducing dhs / ecd and its subsequent impact on ohqol , then it is imperative that the condition should be clearly diagnosed by trained and calibrated dentists experienced in conducting clinical studies using recognised and accepted clinical criteria for the evaluation of dhs / ecd . due to the cultural and language differences between countries ,
there is also a need of norm or reference value(s ) for each population to be studied .
for example , when constructing a questionnaire for a non - english - speaking population , the questionnaire should be initially written in english , then translated by two people of the designated native ( foreign ) language and subsequently translated back into english by two native english - speaking people to identify any potential issues that may have arisen from the translation . finally , as indicated above , any future study attempting to evaluate the efficacy of a desensitising agent in reducing dhs / ecd and its subsequent impact on ohqol
should be conducted by experienced and calibrated examiners using established guidelines for conducting dhs / ecd clinical studies .
such studies should also be based on a randomised clinical study design and include both placebo or control groups .
patients suffering from dhs / ecd have been reported to have a significantly impaired ohrqol ; this may however be improved following treatment with a desensitising agent as reported by several authors .
it is therefore of the upmost importance that the use of the ohrqol as a quality control tool in the dental office be established in robust clinical studies .
furthermore , because of its ability to reflect a patient s satisfaction with any proposed treatment , it may prove to be a valuable asset for practitioners when assessing their patients quality of life before , during and after treatment of various clinical conditions such as dhs / ecd .

Answer:
objectivesoral health - related quality of life ( ohrqol ) can be considered as the scientific expression of that part of a person s well - being that is affected by his / her oral health .
 the aim of this paper was to evaluate how to use the data available in the field of research to make a link between ohrqol and dentin hypersensitivity ( dhs ) in the dental office.materials and methodsresearch papers in the field of ohrqol and dhs and reviews and research papers about ohrqol were used for analysis in this short review , with a particular insight on the instruments used to evaluate ohrqol.resultsvarious psychometric instruments have been used to measure ohrqol that are more or less patient- or expert - centred .
 some are generic , others are adapted to specific conditions / domains or populations .
 the impact of dhs or exposed cervical dentin ( ecd ) on ohrqol has been assessed in very few studies .
 it is therefore of the upmost importance that the use of the ohrqol as a quality control tool be established in robust clinical studies.conclusions/clinical relevancefuture studies evaluating the impact of the dhs / ecd on ohqol or evaluating the efficacy of desensitising agents should respect some key points , including study design ( randomization , placebo / control group , etc . ) , validated specific questionnaires and trained calibrated practitioners .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
streptococcus pneumoniae remains a major cause of childhood morbidity and mortality worldwide , particularlyin lower income countries .
pneumococcal diseases are the leading source of vaccine preventable deaths , mostly due to community - acquired pneumonia ( cap ) , accounting for approximately 11% of all deaths in children under 5 years old ( 1 ) .
colonization of the nasopharynx is a necessary step along the path to pneumococcal disease ( pd ) ( 2 ) .
pneumococcal conjugate vaccines ( pcv ) reduce nasopharyngeal carriage of serotypes which included in the vaccine by conferring capsular - specific immunity .
experience from countries where conjugate vaccines have been introduced has shown rapid and sustained carriage reduction of vaccine serotypes ( vt ) following vaccination ( 3 ) .
the microorganism produces a plethora of virulence factors , including the polysaccharide capsule , several surface - located proteins , and the toxin pneumolysin ( 5 , 6 ) .
the polysaccharide capsule is highly efficient in protecting the bacteria from opsonophagocytosis ( 7 ) .
surface proteins of s. pneumoniae ( pneumococcus ) have been investigated for their role in pneumococcal pathogenicity and as candidate antigens for protein based vaccines ( 8) . among the surface - associated proteins ,
the pneumococcal surface protein a ( pspa ) andc ( pspc ) are the best characterised choline - binding proteins ( 6 , 9 ) .
pneumolysin is a cytoplasmic toxin released by autolysis of the cell and it is a very important virulence factor with multiple effects .
the major autolytic enzyme of the pneumococcus is lyta ( nacetylmuramoyl - l - alanine - amidase ) , which is responsible for the deoxycholate- and penicillin induced cell lysis in the stationary phase , having a great clinical importance ( 10 ) . the lyta - encoded major autolysin of s. pneumoniae is a member of a widely distributed group of cell wall - degrading enzymes located in the cell envelope and postulated to play roles in avariety of physiological functions ( 11 ) .
rrga is a virulence factor in a murine lung infection model and has a varied distribution among serotypes of s.pneumoniae ( 12 ) .
s. pneumoniae adherence was significantly enhanced by expression of an extracellular pilus composed of three subunits , rrga , rrgb and rrgc ( 13 ) .
some of the pneumococcal virulence factors are potential targets for protein- based pneumococcal vaccine production .
thus , in this study the presence of three genes were detected among the isolates of s. pneumoniae .
a total of 260 samples from nasopharynx of healthy children under 6 years old were taken carefully and transferred under cold condition to the laboratory .
these samples were collected from children attending day care centers in different geographical areas of mashhad , iran .
both plates were incubated at 37c in an atmosphere of 5% co2 for 24 hours .
the plates were examined and -haemolytic colonies suspected to be streptococcus pneumoniae were confirmed by optochin test and pcr for cpsa gene as described earlier ( 14 ) .
the optochin - susceptibility test was performed using a 6.5 mm diameter disc containing 5 mg optochin ( oxoeid ) in an atmosphere of 5% co2 .
the genomic dna of the bacterial isolates were extracted by dnaase tissue kit ( kiagen , tehran , iran ) .
the presence of rrga , pspc and lyta genes were detected among confirmed s. pneumoniae isolates by three single pcr assays .
oligonucleotides which were used as primers to amplify particular sequences of s. pneumoniae amplification conditions for lyta and pspc genes were : 94 c for 2 min , 25cycles of 94 c for 10 s , 58 c for 15 s , and 72c for1 min , followed by a final extension at 72 c for 5 min .
amplification conditions for rrga gene were : 95c for 2 min , 25cycles of 95c for 30 s , 51c for 30 s , and 72c for 90 s , followed by a final extension step at 72c for 5 min .
one amplicon from s. pneumoniae with the gene rrga was sequenced by macrogen company ( south korea ) .
sequences were examined for identity with published sequence data from national center for biotechnology information ( ncbi ) .
a total of 260 samples from nasopharynx of healthy children under 6 years old were taken carefully and transferred under cold condition to the laboratory .
these samples were collected from children attending day care centers in different geographical areas of mashhad , iran .
both plates were incubated at 37c in an atmosphere of 5% co2 for 24 hours .
the plates were examined and -haemolytic colonies suspected to be streptococcus pneumoniae were confirmed by optochin test and pcr for cpsa gene as described earlier ( 14 ) .
the optochin - susceptibility test was performed using a 6.5 mm diameter disc containing 5 mg optochin ( oxoeid ) in an atmosphere of 5% co2 .
the genomic dna of the bacterial isolates were extracted by dnaase tissue kit ( kiagen , tehran , iran ) .
the presence of rrga , pspc and lyta genes were detected among confirmed s. pneumoniae isolates by three single pcr assays .
amplification conditions for lyta and pspc genes were : 94 c for 2 min , 25cycles of 94 c for 10 s , 58 c for 15 s , and 72c for1 min , followed by a final extension at 72 c for 5 min .
amplification conditions for rrga gene were : 95c for 2 min , 25cycles of 95c for 30 s , 51c for 30 s , and 72c for 90 s , followed by a final extension step at 72c for 5 min .
one amplicon from s. pneumoniae with the gene rrga was sequenced by macrogen company ( south korea ) .
sequences were examined for identity with published sequence data from national center for biotechnology information ( ncbi ) .
among 260 nasopharanx samples from healthy children under 6 years , 59 isolates were confirmed as s. pneumoniae .
distribution of the lyta , rrga and pspc genes among isolates of s.pneumoniae were determined .
rrga and pspc were also found in17 ( 28.81% ) , and 2 ( 3.38% ) isolates respectively .
five patterns of these genes were seen among s. pneumoniae isolates : lyta ( n=33 , 55.93% ) , rrga ( n=2 , isolates , 3.38% ) , pspc ( n=1 1.69% ) , lyta+rrga ( n=16 , 27.11% ) and lyta+ rrga+ pspc ( n=1 , 1.69% ) .
the amplicon represented expected sequences with more than 90% identity with published data from ncbi ( genbank : ef 560634.1 ) .
the amplicon represented expected sequences with more than 90% identity with published data from ncbi ( genbank : ef 560634.1 ) .
it remains unclear , however , why some children develop invasive disease , whereas in the majority of cases , colonization remains asymptomatic , a combination of bacterial virulence and host factors may be responsible ( 18 ) .
we studied the s. pneumoniae isolates giving special reference to identification and distribution of virulence markers such as autolysin among the isolates from nasopharynx .
this exercise may help in understanding the factors contributing to the pathogenicity of s. pneumoniae .
further , there are numerous reports giving us increasing evidences on the role of lyta in pneumococcal pathogenesis suggesting that this might be more appropriate as vaccine antigen against s. pneumoniae infections .
the cpsa was used as a novel genetic marker specific for identification of s. pneumoniae and to differentiate it from the closely viridans group streptococci as well as other pneumococcus - like streptococci such as s. pseudopneumoniae ( 19 ) .
many virulence genes contribute to the colonization of s. pneumoniae ; however , our study only demonstrates this for pspc , rrga and lyta genes .
thus , synergistic effect and correlation of these virulence factors is necessary for our future work .
our results showed that most of the isolates had lyta gene ( 84.74% ) which has an important role in colonization .
this observation is in concordance with previous report which was showed that all of the unencapsulated isolates of s. pneumoniae were negative for lyta and psaa by pcr .
detection of lyta and psaa in six encapsulated isolates for which a serotype could be determined was negative ( 9 ) .
false negative results were obtained by the pcr assays for these two genes may be due to mutations or sequence variation . on the other hand , lyta is essentially a rather conserved gene displaying limited genetic variation ( 11 ) . in the study of whatmore ,
33 out of 62 isolates of s. pneumoniae were selected to represent a diverse range in terms of serotype , clinical association , and time and place of isolation .
autolysin which was found in all strains , might appear to be a suitable target virulence , and apparently highly conserved , for inclusion in a potential vaccine ( 11 ) .
the pneumococcal protein lyt a is the major autolysin of s. pneumoniae , it has an important function in pathogenesis by releasing pneumolysin and plays a fundamental biological role in bacterial lysis after exposure to certain antibiotics ( 19 ) .
it has been reported that the lyta gene has higher specificity than the pspc for identification of s. pneumoniae ( 15 , 20 ) . in our study , only 2 out of 59 isolates of s. pneumoniae ( 3.38% ) had pspc gene .
given the high sequence diversity of pspc , it is unlikely that pspc alone can be a vaccine antigen to provide protection from across different pneumococcal strains ( 16 ) .

it was showed that rrga is central in pilus - mediated adherence and disease , even in the absence of polymeric pilus production ( 13 ) .
however , it has been demonstrated that numerous protein virulence factors are involved in the pathogenesis of pneumococcal disease ( 21 ) .
hence , new vaccine designs are focused on the surface proteins ( e. g. , pspa and pspc ) , cytolysin , and pneumolysin ( 22 ) .
we concluded that the gene cpsa was specific and highly conserved among s. pneumoniae isolates which were colonized in nasopharynx . on the other hand
, we showed that lyta gene was the most frequent genes among the s. pneumoniae isolates , and combination of rrga , lyta was the most observed pattern.thus this should allow for appropriate screening of adhesin - based vaccines to prevent infections by streptococci .

Answer:
background and objectives : many surface proteins are implicated in nasopharyngeal colonization and pathogenesis of streptococcus pneumoniae .
 some of these factors are candidate antigens for protein based vaccines .
 new vaccine designs focus on the surface proteins ( e. g. , pspa and pspc ) and also cytolysin , and pneumolysin . in this study ,
 3 key virulence genes , lyta , pspc , and rrga , which encoded surface proteins , were detected among s. pneumoniae isolates.materials and methods : a total of 260 nasopharyngeal swabs were collected from healthy children under 6 years old attending day care centers in mashhad , iran .
 isolates of s. pneumoniae were confirmed by optochin susceptibility and colony appearance and also by pcr for cpsa gene .
 the presence of lyta , pspc , and rrga genes were also detected by pcr.results:a total of 59 isolates were confirmed as s. pneumoniae . among these isolates , 50 ( 84.74% ) , 19 ( 32.20% ) , and 2 ( 3.38% )
 were positive for lyta , rrga , and pspc genes respectively .
 the presence of these genes among s.pneumoniae isolates were as follows : 1 ) rrga , lyta , pspc ( 1 isolate ) , 2 ) rrga , lyta(17isolates ) , 3 ) pspc ( 2 isolate ) , 4 ) lyta ( 50 isolates).conclusion : cpsa gene was specific for detection of s. pneumoniae isolates which were colonized in nasopharynx .
 the lyta gene was the most frequent gene among the s. pneumoniae isolates , and combination of rrga , lyta was the most observed pattern .
 thus , it is important for future monitoring of vaccine formulation in our country .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
lung cancer is the main cause of mortality related to cancer in the most developed countries .
however , some of the patients at initial stages of disease ( stage i , ii ) are curable .
one of the most important factors in deciding for treatment of these patients is preoperative staging with the most common form being tnm staging .
since surgical resection is the basic treatment of the patients at stage i , ii and is associated with good results of survival ( long - term survival of 50 - 65% ) , determining of a preoperative accurate staging method is effective in planning the treatment strategy .
although for tnm staging , history , clinical examination , chest ct scan , pet scan , mediastinoscopy , and endobronchial ultrasound are routinely performed ; the results are not accurate enough for determining the stage and can be associated with over and under staging . since nowadays
multi - modality treatments require accurate staging ; more invasive methods in staging have been suggested . among these methods
is vats which can more accurately evaluate t , n , and m in the patients and can prevent unneeded surgeries .
the aim of this study was to evaluate the role of vats in staging of non small cell lung cancer ( nsclc ) patients and detection of vats diagnosis accuracy for accurate evaluation of preoperative surgery .
in this prospective study , all the patients with lung cancer type nsclc referred to ghaem hospital of mashhad university of medical sciences were evaluated in terms of preoperative staging ( history , clinical examination , chest ct scan , cardiac evaluation , pet , mediastinoscopy , routinely and chest or brain mri , and bone scan if needed ) .
before main surgery , the patients immediately underwent vats surgery with single port and were evaluated in terms of t ( tumor extending to mediastinal elements , plural involvement ) , n ( n2 station involvement ) , and m ( satellite lesion that involved other lobe ) . if the patients had no contraindication for surgery , such as other metastatic plural involvement confirmed by pathology or satellite lesion at involved lobe confirmed by pathology or + n2 station lymph node involvement confirmed by pathology , thoracotomy by posterolateral incision
if the patients were not candidates for surgery according to the results of vats with mentioned criteria , the surgery would be terminated and the patients were referred to oncology department for appropriate treatment .
the data were collected and evaluated in terms of age , sex , type of tumor pathology , method of pathology , results of ct scan , results of vats ( t : plural involvement or mediastin elements ) , n2 involvement , m1 involvement ( satellite lesion of involved lobe ) , results of main thoracotomy surgery , type of pulmonary resection , and vats diagnosing accuracy . to evaluate mediastinal extension in vats ,
the patients were divided into three groups based on the results of preoperative ct scan , and vats .

patients with confirmatory ct scan findingpatients without confirmatory ct scan findingimpossible to confirm ct scan finding .
  patients with
confirmatory ct scan finding patients without confirmatory ct scan finding impossible to confirm ct scan finding .
data were statistically analyzed by spss software version 11.5 and to evaluate vats diagnosing accuracy , we also used distribution , mean , and standard deviation for quantitative variables and frequency for qualitative variables .
diagnostic accuracy was estimated by table of test validity , for calculating diagnostic accuracy we devided the summation of true positive and true negative by the number of total cases .
mediastinoscopy was performed with standard technique in the patients at supine position under general anaesthesia by a small incision in supra sternal notch .
sampling was classically performed for all patients from ( 2l , 2r , 4l , 4r , 7 ) areas , and were sent for pathology evaluation .
vats was also performed immediately before main surgery by double lumen ventilation and evaluation was performed by single port vats ( in terms of plural involvement , tumoral adhesion satellite lesion , n2 station ln involvement ) ; in case of any doubt , sampling was performed and were sent for frozen section and decision was made based on the results of pathology .
if there was no contra - indication for main surgery , final surgery was performed by standard posterolateral thoracotomy incision and open technique .
mediastinoscopy was performed with standard technique in the patients at supine position under general anaesthesia by a small incision in supra sternal notch .
sampling was classically performed for all patients from ( 2l , 2r , 4l , 4r , 7 ) areas , and were sent for pathology evaluation .
vats was also performed immediately before main surgery by double lumen ventilation and evaluation was performed by single port vats ( in terms of plural involvement , tumoral adhesion satellite lesion , n2 station ln involvement ) ; in case of any doubt , sampling was performed and were sent for frozen section and decision was made based on the results of pathology .
if there was no contra - indication for main surgery , final surgery was performed by standard posterolateral thoracotomy incision and open technique .
a total of 40 patients entered the study with ratio of m / f = 21/19 .
mean age of the patients was 57.2  16.64 yrs ( min 15 and max 65 yrs ) .
other symptoms were hemoptysis in 27 patients ( 67.5% ) and exertion dyspnea in 33 cases ( 82.5% ) and pleuritic chest pain in 17 cases ( 42.5% ) . in the preoperative evaluation ,
important findings in ct scan with iv contrast were as follows : observation of mass lesion in 40 patients ( 100% ) , observation of hilar or mediastinal lymphadenopathy in 17 cases ( 42.5% ) , and observation of effusion in 9 cases ( 22.5% ) which cytology of pleural liquid and pleural biopsy were negative in all of these 9 patients .
there was the possibility of involvement of mediastinal elements ( direct extension ) ( 22.5% ) .
flexible bronchoscopy and bal were performed for all patients before surgery and 29 patients ( 72.5% ) had endobronchial mass and biopsy was performed for them . for 11 cases ( 27.5% ) because of peripherally located lesions and no endobronchial mass , tissue samples were taken by the method of ttnb under the guide of ct scan .
all the patients underwent standard mediastinoscopy with samples from ( 2l , 2r , 4l , 4r , 7 ) areas and the results of pathology were negative in all .
the patients who were candidates for main surgery underwent vats immediately before final surgery and the results of vats immediately before final surgery were unresectable tumors in 6 patients ( 3 cases ( 7.5% ) due to seeding plural metastasis confirmed by pathology , 2 cases ( 5% ) due to n2 station ( one case in station 4 and one cases in station 9 ) , and one case ( 2.5% ) due to satellite mass that involved other lobe ) .
the remainder 34 patients ( 85% ) underwent thoracotomy immediately after vats and surgical resection was performed successfully in 31 cases ( 77.5% ) , but in 3 cases ( 7.5% ) due to adhesion of tumor to hilum , tumor was not resectable .
table 1 shows type of surgical resection and the frequency of pulmonary resection in 31 patients underwent surgery .
table 2 shows the frequency of pathological results . in terms of diagnosing accuracy of vats for evaluation of tumor direct extension based on the results of ct scan , in 9 patients ( 22.5% )
there was report by ct scan that involvement of hillum of the lung and mediastin elements ; vats showed that in 5 cases ( 12.5% ) , tumor was resectable ( not confirmed by ct scan finding ) , and in 4 cases ( 10% ) , we could nt determine whether tumor was resectable or not ( impossible to confirm ct scan finding ) . frequency and type of pulmonary resection frequency and type of pathological result based on the final results of surgery , all the patients in the group of non confirmatory ct scan findings ) ( 5 cases = 12.5% ) had successful pulmonary resection . in 4 cases ( 10% ) which we could nt determine whether tumor was resectable or not ( impossible to confirm ct scan finding ) , tumor was resectable in 1 case ( 2.5% ) and not resectable in 3 cases ( 7.5% ) . according to the above results , vats diagnosing accuracy for accurate evaluation of preoperative surgery was 92.5% .
performing tnm staging in lung cancer type nsclc is important for deciding the patients treatment and prognosis .
one of the criteria for determining preoperative staging is t and m stage which can be evaluated by bronchoscopy , ct scan , mri , and needle biopsy .
nevertheless , some of the patients which are considered to be at stage iiib can be in lower stages and the patients which are estimated to be at stage i and stage ii can be at higher stage and more accurate evaluation is needed .
the study of passlick and co - workers reported that vats was a suitable method in evaluation of pleural involvement , finding lymph node ( n2 ) , or pulmonary ( n1 ) metastases on the other side .
they even reported that in patients with effusion and negative cytology , vats can confirm plural spreading in 60% of cases and recommended performing vats before thoracotomy for prevention of un - needed thoracotomies .
the main problem in treatment planning of these patients is evaluation of n stage , since an important factor for treatment planning and survival estimation is n2 or 3 stations involvement .
de langen , et al . performed a study in 2006 about evaluation of n staging .
they attempted to answer the question of whether lymph node size observed in ct scan is a criterion for performing complementary methods to obtain tissue samples .
they showed that it is better for all of these patients to undergo fdg - pet after ct scan and divided the patients into three groups : group i : 10 - 15 mm , group ii : 16 - 20 mm , group iii : > 20 mm .
they found that the patients with tumor size : 10 - 15 mm with negative pet ( the possibility of lymph metastasis is < 5% ) were not candidates for other methods for obtaining tissue samples ; other patients with either positive or negative pet scans were candidates for mediastinoscopy .
another study by bill , et al . in 2009 showed that lymph node size and the results of negative pet were not accurate for evaluation of the patients in terms of n2 stage involvement and they recommended routinely performing of mediastinoscopy for all patients .
standard mediastinoscopy is a gold standard method and is confirmed by the most researchers for all patients with lung cancer , and tissue sampling should be performed in 5 areas : ( 2l , 2r , 4l , 4r , 7 ) ; for increasing the diagnosing accuracy of mediastinoscopy , other methods are mentioned .
block and colleagues in 2010 reported that performing endobronchial ultrasound is a complementary method in n staging and declared that biopsy of all stations is performable by ebu and it is better to perform two biopsies of each station to increase diagnosing accuracy .
in study performed by gomez et al . using ebus with needle biopsy is considered helpful to diagnose central lymphadenopathy .
kuzdza , et al . in 2007 mentioned that performing transcervical extended mediastinal lymphadenectomy is a suitable method in mediastinoscopy for n evaluation . the results of this method were similar to mediastinoscopy and the rate of invasion was also similar to mediastinoscopy .
of course , these studies were limited and the more studies are required . to increase diagnosing accuracy ,
vats is usually combined with mediastinoscopy to cover the areas which mediastinoscopy can not observe .
since vats can perform sampling of lymph nodes in these areas , it is a good replacement for extended mediastinoscopy .
of course , standard mediastinoscopy has sensitivity of 81% and specificity of 91% and can not evaluate some patients . a study performed by witte , et al . on combination of mediastinoscopy with vats
to increase diagnosing accuracy showed that this combination was helpful to increase diagnosing accuracy of standard mediastinoscopy . among accurate
diagnosing methods in n2 station is dye injection in tumor and evaluation of sentinel lymph nodes by vats . in the study of yamashita , et al . in 2011
, they could find sentinel lymph nodes by injection of indocyanine green fluorescence image guide surgery and recommended to dissect the lymph node if they were not involved ; diagnosing accuracy of this method was 80.7% .
since treatment planning and prognosis determination require accurate evaluation of tnm staging , it seems that preoperative vats can help to determine tnm staging and prevents unnecessary thoracotomy in some patients and we recommend this method .
however , the numbers of the patients in our study are limited and a definite conclusion needs further studies .

Answer:
introduction : since determining of prognosis and treatment method is related to accurate evaluation of tnm staging of non small cell lung cancer ( nsclc ) , we aimed to evaluate the role of video - assisted thoracic surgery ( vats ) in staging of nsclc.materials and methods : this study was performed on 40 patients with nsclc who had undergone preoperative staging and were candidate for curative surgery between 2008 - 2010 . they underwent vats immediately before the surgery . after performing vats , the patients underwent thoracotomy by posterolateral incision unless any criteria of inoperability were present . diagnostic accuracy of vats for confirmation or modification of preoperative
 staging was evaluated.results:m/f ratio was 21/19 .
 mean age of the patients was 57.2  16.64 yrs .
 the most common symptom was coughing in 90% of patients .
 72.5% of the patients had endobronchial mass and only for 27.5% tissue sample was obtained by transthoracic needle biopsy ( ttnb ) method . after performing vats ,
 6 patients were excluded from surgery ( 3 cases ( 7.5% ) due to seeding plural metastasis , 2 cases ( 5% ) due to n2 involvement and one case ( 2.5% ) due to satellite lesion in other lobes ) .
 other 34 patients underwent surgery .
 surgical resection was performed successfully in 31 cases ( 77.5% ) , but in 3 cases ( 7.5% ) due to adhesion to hillum of the lung tumor was not resectable . according to the above results , vats diagnosing accuracy was 92.5%.conclusion : vats can help to determine tnm staging and prevent unnecessary thoracotomy in some patients and we recommend this method for accurate staging of nsclc .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
alzheimer s disease ( ad ) is a progressive and the most prominent old - age debilitating disease which had a notable epidemic growth in recent years . according to statistical analyses
, it is estimated that the number of people suffering from ad will double every twenty years ; and by 2050 , the number of sufferers from ad in the world would reach 115 million ( 1 , 2 ) .
one - eighth of people aged 65 and older and half of people aged 85 and older were diagnosed with ad , approximately ; its death toll from 2000 to 2008 has increased by 66% ( 3 ) .
the costs for this disease are so high that one percent of global gdp is spent on ad s consequences ( 4 ) .
diagnosed patient with ad usually dies after 5 to 7 years ( 2 ) . in iranian traditional medicine ( itm )
manuscripts , diseases in which forgetfulness is the main symptom are categorized under nesyan label . in itm manuscripts ,
one of the types of nesyan which originates from coldness and dryness of the brain has the same symptoms as ad . forgetting recent events and remembering old happenings , cognitive disturbance , problems in constant talking ( language disability ) , and insomnia are of its most important signs ( 5 , 6 ) which are similar to ad s according to nincds - adrda criterion ( 7 ) .
itm takes nourishment as one of the six pillars of health ( 8 , 9 ) ; therefore , itm manuscripts have dedicated a considerable part of their content to nutritional recommendations . in the first volume of canon of medicine , avicenna ( 970 - 1051 a.d . ) , the great persian scholar , described those in detail ( 10 ) .
he urged elderly people not to take foods producing black bile ( sowd ) such as lentil , eggplant , beef , dried meat , and salted foods ; and phlegmatic foods such as fish , watermelon , melon , and cucumber .
on the other hand , taking milk , shirberenj ( an iranian dish consists of milk , rice , sugar , and rosewater ) , honey milk , and milk with ginger are recommended .
apart from preventive recommendations , nutritional therapeutic recommendations are included to boost medication and shorten illness - period ; and nesyan is no exception .
muhammad ibn zakariy rz ( rhazes ) ( 865 - 925 a.d . ) , another great persian scholar , in his book  al - hawi  recommended to have poultry ( such as chicken , dull - yellow partridge , hoopoe , pheasant , and sparrow meat ) , their brains , and yolks for people affected to nesyan . at the same time
the patients were prohibited from having beef , mutton , goat meat , camel meat , and rabbit meat because they produce black bile ; and fish as well for producing phlegm ( balgham ) . moreover , having nuts such as almond , hazelnut , coconut , and walnut were recommended ( 12 ) .
it is worth mentioning that some other persian scholars such as aghili korasani and chishti had the same idea as rhazes ( 5 , 6 ) .
there have been remarkable either observational or experimental studies on the role of diet and nutrients in prevention and treatment of dementia , especially ad .
studies on effects of different kinds of fat such as saturated fatty - acids ( sfa ) , unsaturated fatty - acids ( ufa ) , and cholesterol on ad have been conducted recently .
unsaturated fatty - acids and cholesterol play an important role in the brain ; 60 percent of dry weight of the brain is consisted of fat which 20% of it is of unsatu - rated fatty - acids ( 13 ) .
although the brain is only 2% of the total body mass , it carries 25% of cholesterol of the whole body ( 14 ) . in the light of
the fact that most of the brain is consisted of fat and it uses nutrients as other organs , types and amounts of fat consumption could be vitally important in the brain s health .
studying multi - nutrient diets ( instead of one or more nutrients ) has a notable importance .
one of the multi - nutrient diets which have been frequently studied is the mediterranean diet ( table 1 ) ( 15 ) .
studies have shown that it has preventive effect on ad ( 16 , 17 ) .
taking types of fat into consideration , this diet has a great deal of ufas and lesser amounts of sfas and cholesterol .
ufas positive impact has been reported in several other researches ( 18 ) . while the results of studies on therapeutic role of ufas ( especially omega-3 ) on ad are controversial ( 19 , 20 ) , ufas
multi - nutrient diets like the mediterranean diet which contains high levels of ufas have abated the incidence of ad ( 16 , 17 ) ; the abatement is 13% according to sofi et al .
study on the relationship between the mediterranean diet and health status in 2008 ( 17 ) . about cholesterol
, it plays a vital role in cell membranes , yet its functions in neurons are more prominent .
cholesterol is amassed within lipid rafts in the neuronal cell membrane and is involved in the formation and maintenance of synaptic connections ( 21 ) . several studies on the effect of cholesterol on ad had ambiguous results . according to the importance of diets
especially fats - in ad , this study attempted to analyze the fat content of itm recommended diet for nesyan ( itm equivalent of alzheimer s disease ) . since traditional physicians used to recommend distinctive diets based on their own clinical experiences , analyzing these diets would eventuate in new nutritional regimen to improve ad sufferers quality of life .
in order to study the traditional recommended diet for nesyan , itm prominent books including al - hawi ( rhazes , 10th century ) , canon of medicine ( avicenna , 11th century ) , zakhire - ye - khawrazmshahi ( jorjani , 12th century ) , kholasat - ul - hekma ( aqilikhorasani , 18th century ) , and exir - e - azam ( chishti , 19th century ) were searched for recommended and abstinent foods and diets traditionally prescribed for patients afflicted by senescence and/or nesyan ( 5 , 8 , 11 , 12 , 22 ) . to quantify the results ,
the content of fatty components of each food ( including polyunsatu - rated ( pufa ) , monounsaturated ( mufa ) , and saturated fatty acids ( sfa ) and also cholesterol ) were extracted from the database of the department of agriculture of the usa ( usda ) ( 23 ) .
the content of fatty elements per 100 gr of each recommended food was compared with that of the abstinences and statistically analyzed by mann - whitney test via spss ( version 16 ) .
about the diet , the sum of the nutrients of recommended and abstinent diets for daily consumption was also measured .
ad dietary recommendations and abstinences which currently published in medical journals were also searched via scopus .
finally , traditional and new dietary suggestions were compared with each other and the results presented as tables and figures .
the results show that the recommended foods ( presented in the first column of table 2 ) are fattier than the abstinent ones ( presented in the first column of table 3 ) ( p<0.001 ) .
there are also meaningful differences between unsaturated fatty acids ( p<0.001 ) , saturated fatty acids ( p<0.001 ) , and cholesterol ( p<0.05 ) of recommended foods and abstinent foods ( fig .
these foods form recommended and abstinent diets for nesyan . this recommended diet is fattier than the abstinent diet ( 4.5 times ) ( see the last row of table 2 and 3 ) ; polyunsaturated fatty acids of recommended diet
it is the same story for monounsaturated fatty acids and cholesterol ( 11 and 1.4 times more than abstinent diet , respectively ) ( fig .
2 ) . fatty components in 100 gr of each food traditionally recommended or forbidden for people afflicted by nesyan . *
error bars indicate sem comparison between nutritional factors of recommended and abstinent diet in nesyan the results of searching scopus database show that recent studies emphasize on diets with high amounts of unsaturated fatty acids for ad sufferers .
a considerable number of papers but not all of them - emphasizes on probable positive role of cholesterol on ad .
nutritional factors of daily diet recommended for patients affected with nesyan in iranian traditional medicine .
the last row of the table presents the amounts of nutrients in daily recommended diet nutritional factors of daily diet forbidden for patients affected with nesyan in iranian traditional medicine .
the last row of the table presents the amounts of nutrients in daily abstinent diet .
iranian traditional medicine has nutritional recommendations to help curing nesyan ( ad equivalent in traditional medicine ) . in this study , evaluating the ingredients of the recommended foods highlights that it is ufas - rich because of having nuts .
the types of meat in the recommendations are mostly poultry ( chicken , pheasant , and sparrow ) ; their remark is their greater amount of cholesterol compared to the abstinences .
some recent studies substantiate that cholesterol is a boost to improve memory function ( 24 , 25 ) .
when cholesterol is consumed with ufas , it will turn into hdl ( 26 , 27 ) . in 2004 ,
reitz and colleagues have concluded that there is no connection between serum cholesterol level and ad ( 28 ) .
however , some other studies have shown that the higher the serum cholesterol level in the elderly , the better memory functions ( 24 , 25 ) .
some studies also have shown the decline in serum total cholesterol levels is associated with increased dementia risk ( 29 , 30 ) .
furthermore , in a cohort study conducted on 1130 people ( published 2010 ) , reitz et al .
conclude that high hdl levels in elderly individuals may be associated with a decreased rate of ad ( 31 ) .
prior to reitz , singh - manoux and colleagues ( 2008 ) indicated that a low level of hdl could be considered as a risk factor of memory dysfunction ( 32 ) .
bear in mind , there has been no study on hdl destructive effect on ad , so far ( 33 ) .
therefore , prescribing more amounts of cholesterol along with ufas in itm is in accordance with recent studies . on the other side ,
recent studies have shown that cholesterol and all of its precursors in cerebrospinal fluid ( csf ) and its precursorslanosterol , lathosterol , and desmosterol in plasma abate in ad sufferers ( 34 , 35 ) . in 2010 , klsch et al . determined csf and plasma levels of cholesterol and its precursors in ad diagnosed people compared to those of healthy individuals .
the results showed that csf levels of cholesterol and all of its precursors and also plasma levels of two of the precursors named lanosterol and lathosterol are lower in ad diagnosed people than those of healthy individuals ( 34 ) .
sato et al . showed in 2012 that plasma levels of desmosterol , another precursor of cholesterol , are also lower in alzheimer s sufferers than the levels in healthy ones ( 35 ) .
this casts doubt whether the cholesterol reducing agents have preventive effect on ad or not .
there are some studies highlighting that cholesterol reducing agents such as statins are ineffective on ad incidence ( 36 , 37 ) . in a prospective study conducted by zandi et al .
( 2005 ) on 5000 elderly people in the usa , the relationship between statins consumption and the onset of dementia or ad has been violated ( 36 ) . along the lines of zandi
s study , mcguinness and colleagues ( 2009 ) co - evaluated two randomized double blind clinical trials containing 26 thousand participants which resulted that there is no relationship between statins consumption and the risk of ad incidence ( 37 ) .
also , reduction in serum total cholesterol could be considered as a risk factor of dementia in the elderly ( 29 , 30 ) .
there are other ingredients in the abstinences which are not considerable in having fats and cholesterol .
pumpkin , lettuce , melon , garlic , onion , cabbage , beans , broad beans , and mushroom are of its examples .
according to iranian cuisine in the past , there were foods in itm that have no place in eating habit nowadays ; so there is not much information about them .
hoopoe , lark , dull - yellow partridge meat and their brain are of the examples .
this diet contains high amounts of unsaturated fatty acids and cholesterol to boost treatment of nesyan ( traditional equivalent of alzheimer disease ) .
according to new scientific findings , this kind of diet could be useful as a complementary therapy of alzheimer disease .
ethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , etc . ) have been completely observed by the authors .

Answer:
abstractbackgrounddietary notifications have been introduced recently for alzheimer disease ( ad ) . in iranian old medical manuscripts , there are some nutritional recommendations related to nesyan ( ad equivalent ) .
 the aim of this article was to compare dietary recommendations of iranian traditional medicine ( itm ) with novel medical outcomes.methods1 ) searching for dietary recommendations and abstinences described in itm credible manuscripts ; 2 ) extracting fatty components of itm diet according to the database of the department of agriculture of the usa ; 3 ) statistical analysis of fatty elements of traditionally recommended foods via mann - whitney test in comparison with elements of the abstinent ones ; 4 ) searching for ad dietary recommendations and abstinences which currently published in medical journals ; 5 ) comparing traditional and new dietary suggestions with each other.results1 ) traditionally recommended foods are fattier than abstinent ones ( p<0.001 ) .
 there are meaningful differences between unsaturated fatty acids ( ufas ) ( p<0.001 ) , saturated fatty acids ( p<0.001 ) , and cholesterol ( p<0.05 ) of recommended foods and abstinent ones .
 2 ) traditionally recommended diet is also fattier than the abstinent diet ( 4.5 times ) ; ufas of the recommended diet is 11 times more than that of the abstinent one ; it is the same story for cholesterol ( 1.4 times ) ; 3 ) recent studies show that diets with high amounts of ufas have positive effects on ad ; a considerable number of papers emphasizes on probable positive role of cholesterol on ad ; 4 ) traditional recommended diet is in agreement with recent studies.conclusionitm recommended diet which is full of unsaturated fatty acids and cholesterol can be utilized for complementary treatment of ad .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
bicycle riding is popular throughout the world for transportation , recreation , sports , and health - related benefits .
53% are men . in korea , according to the needs of the times , such as economic development and increased leisure time , a trend for preferring environmentally friendly sports , and growing interest in health and well - being , the awareness of cycling as a leisure sport has recently increased .
there were 24,406 recreational bicycle riders in 911 bicycle clubs in korea as of january 2010 .
bicycling is an ideal form of aerobic , nonimpact exercise with established protective cardiovascular effects and a beneficial influence on the risk of hypertension , diabetes , and stroke .
although there are controversies about changes to the genitourinary system in subjects who cycle , bicycle riding has been known as a common source of acute traumatic injuries as well as overuse injuries [ 4 - 6 ] .
bicycling studies suggest perineal trauma , pressure , or both may have a role in these genitourinary hazards .
many of them directly affect the genitourinary tract , causing genital numbness , erectile dysfunction ( ed ) , priapism , infertility , hematuria , and effects on serum prostate - specific antigen ( psa ) levels .
many healthy recreational bicycle riders have questioned urologists about the relationship between bicycle riding and prostate - related lower urinary tract symptoms ( luts ) .
but to the best of our knowledge , there has been no study of luts in male recreational bicyclists . with this study ,
our goal was to evaluate the impact of bicycle riding on luts and sexual dysfunction in men with the use of amateur marathoners as a control group of physically equivalent individuals with a low level of perineal pressure or trauma .
a total of 22 healthy male amateur bicycle riders from two bicycling clubs in jeonju , korea , were studied .
the recruitment criteria were age between 40 and 50 , bicycling period of more than 1 year before the study , three or more times of cycling per week , and 30 minutes or more of cycling duration per time .
the controls were 17 healthy male marathoners from an amateur marathon club in jeonju , korea .
, all subjects were informed about the experimental procedures , which were in accordance with the ethical standards of chonbuk national university hospital , and were required to give written informed consent .
the evaluation contained a study questionnaire assessing sports participation habits , urological and medical history , the international prostate symptom score ( ipss ) , the international index of erectile function ( iief ) , the international continence society ( ics ) male questionnaire - short form , the overactive bladder symptom score ( oabss ) , and the premature ejaculation diagnostic tool ( pedt ) .
an ipss of more than 7 defined the voiding dysfunction ( vd ) group , and erectile ed was defined as a score of 21 or less on the iief-5 , an abridged 5-item version of the iief-15 , which ensured identification of the mildest forms of ed .
furthermore , we examined serum total prostate - specific antigen ( tpsa ) , free prostate - specific antigen ( fpsa ) , uroflowmetric values , postvoid residual ( pvr ) urine volume , and transrectal ultrasound ( trus , b&k medical , herlev , denmark ) of the prostate in all subjects .
chicago , il , usa ) . to test differences between the two groups in serum tpsa , fpsa , uroflowmetric values , pvr urine volume , calculated volume of the prostate using trus , and the total or subscale score of each questionnaire , we used independent - sample t - tests with statistical significance as p<0.05 .
also , we compared the two groups for the prevalence of vd and ed by using the chi - square or fisher 's exact tests with statistical significance as p<0.05 .
a total of 22 healthy male amateur bicycle riders from two bicycling clubs in jeonju , korea , were studied .
the recruitment criteria were age between 40 and 50 , bicycling period of more than 1 year before the study , three or more times of cycling per week , and 30 minutes or more of cycling duration per time .
the controls were 17 healthy male marathoners from an amateur marathon club in jeonju , korea .
, all subjects were informed about the experimental procedures , which were in accordance with the ethical standards of chonbuk national university hospital , and were required to give written informed consent .
the evaluation contained a study questionnaire assessing sports participation habits , urological and medical history , the international prostate symptom score ( ipss ) , the international index of erectile function ( iief ) , the international continence society ( ics ) male questionnaire - short form , the overactive bladder symptom score ( oabss ) , and the premature ejaculation diagnostic tool ( pedt ) .
an ipss of more than 7 defined the voiding dysfunction ( vd ) group , and erectile ed was defined as a score of 21 or less on the iief-5 , an abridged 5-item version of the iief-15 , which ensured identification of the mildest forms of ed .
furthermore , we examined serum total prostate - specific antigen ( tpsa ) , free prostate - specific antigen ( fpsa ) , uroflowmetric values , postvoid residual ( pvr ) urine volume , and transrectal ultrasound ( trus , b&k medical , herlev , denmark ) of the prostate in all subjects .
chicago , il , usa ) . to test differences between the two groups in serum tpsa , fpsa , uroflowmetric values , pvr urine volume , calculated volume of the prostate using trus , and the total or subscale score of each questionnaire , we used independent - sample t - tests with statistical significance as p<0.05 .
also , we compared the two groups for the prevalence of vd and ed by using the chi - square or fisher 's exact tests with statistical significance as p<0.05 .
a total of 22 recreational bicyclists ranging in age from 42 to 57 years completed the questionnaires and were included in the assessment .
the riders had cycled for a period of 1 to 10 years ( range , 4.052.04 years ) , 3 to 6 times per a week ( range , 4.231.19 times ) , and with 60 to 240 minutes of cycling duration per time ( range , 9159 minutes ) .
the subjects ' body mass index ( bmi ) ranged from 22.8 to 34.6 kg / m ( range , 25.92.67 kg / m ) .
there were no significant differences between the two groups in age , bmi , comorbidities , or exercise habits ( table 1 ) .
there were no significant differences in the total and subscale scores of the ipss between the two groups .
the prevalence of vd on the basis of the ipss was not significantly different between the two groups ( 8/22 vs. 4/17 , p=0.494 ) .
there were no significant differences in total and subscale scores of the iief between the two groups .
the prevalence of ed based on the iief was not significantly different between the two groups ( 11/22 vs. 10/17 , p=0.748 ) .
also , we found no statistical differences in other questionnaires such as the oabss , ics male questionnaire - short form , and pedt ( table 2 ) .
as shown in table 3 , there were no significant differences between the two groups regarding uroflowmetric parameters such as peak urinary flow rate ( qmax ) , voided urine volume , or pvr urine volume . in all subjects ,
prevoid urine volume was at least 150 ml and voided urine volume was at least 125 ml . in the cyclists ,
the mean calculated volume of the prostate by trus was 23.32 cc and there was no statistically significant difference between the two groups ( 23.32 vs. 23.71 , p=0.848 ) .
also , the serum tpsa level was within the normal range in all subjects and there was no significant difference between the two groups ( 0.800 vs. 0.888 , p=0.470 ) . the prevalence of a significantly low qmax , excess pvr , or benign prostatic hyperplasia was not significantly different between the two groups ( table 3 ) .
the most common bicycling - associated urogenital problems are nerve entrapment syndromes presenting as genitalia numbness , which was reported in 50% to 90% of cyclists , followed by erectile dysfunction in 13% to 24% .
other less common symptoms include priapism , penile thrombosis , infertility , hematuria , torsion of the spermatic cord , prostatitis , perineal nodular induration , and elevated psa , which are reported only sporadically .
bicycle riding is used throughout the world for well - known exercise , fitness , and recreational benefits . as such
, it is not surprising that these statements have created much controversy . in our study population , we investigated in particular the relationship between bicycle riding and luts or sexual dysfunction by use of questionnaires ; thus , we did not ask the study group about complications such as genitalia numbness . to date
recently , saka et al reported that bicycle riding has no impact on serum psa levels and urinary flow parameters .
the goal of their study was to investigate whether professional bicycle riding altered plasma concentration of tpsa , fpsa , percent free psa ( f / t psa ) , and urinary flow parameters in healthy men .
we present a cross - sectional study of the effects of bicycle riding , a sport with perineal impact , on genitourinary function in men . in our study ,
the subjects were amateur recreational bicycle riders from clubs , and we aimed to find any hazards of bicycle riding in male luts or sexual dysfunction .
our hypothesis was that if bicycle riding had any impact on the genitourinary tract there would be significant differences in genitourinary functional parameters between a regular long - term bicycle - riding group and control group of physically equivalent individuals with a low level of perineal pressure or trauma , such as a regular long - term marathon running group .
however , there were no significant differences between the two groups regarding the questionnaires , uroflowmetric parameters , pvr urine volume , prostate volume , or serum psa level .
thus , we found the inverse of our hypothesis : that bicycle riding may have no hazardous impact on genitourinary health in recreational male bicycle riders .
the prevalence of luts or vd as defined by an ipss of 8 was not significantly different between the two groups .
physical activity has been documented to be protective against luts in previous studies , and the perineal impact of bicycle riding does not seem to offset that effect .
many of the bicyclists enrolled were very energetic and confident of their health , and there were no significant differences in the uroflowmetric analysis results , trus - measured prostate volume , or serum psa level .
bicycle - riding - induced perineal impacts do not have enough influence on the prostate mechanically or physiologically .
previous reports about the effect of bicycling on serum psa concentrations were not conclusive , but in recent studies the dominant finding was that there was no statistically or clinically significant change in psa levels regardless of cycling [ 7 - 12 ] .
no other published data have compared questionnaires evaluating luts , uroflowmetric analysis results , or trus - measured prostate volume of regular long - term amateur bicycle riders with a control group of physically equivalent individuals with a low level of perineal pressure or trauma such as a regular long - term runner group .
previous studies have reported an association between bicycling and sexual dysfunction , but those studies were based on biological measurements such as penile blood flow , focused on sexual dysfunction after prolonged exposure to perineal impact , or suggested a trend but no strong association .
the results of our study support the observation of others that bicycle riding has no effect on luts and male sexual function .
first , the cross - sectional study structure may have affected the validity of the results .
we did not collect baseline data about luts and sexual dysfunction parameters before activity from either group .
we implemented a cross - sectional study design as an efficient and cost - effective investigation to perform a preliminary exploration for an association with the potential to generate additional hypotheses for more structured research .
second , the small number of subjects may have introduced some selection bias into the results .
however , we suspect that the influence of the bias may be weak because almost all of the 5th and 6th decades of each club participated in our study . we plan to do vertical , annual follow - up studies of the subjects .
the fact that the results of our study are consistent with data from other studies in similar sports supports the validity of our results and decreases the chance of systemic errors .
more assessment of the effect of bicycle riding on the human pelvic anatomy and genitourinary complaints is warranted to further validate the results of this study .
concern about bicycle riding as a leisure sport has recently increased as many urological outpatients and healthy recreational bicyclists have questioned urologists about the relationship between bicycle riding and prostate - related luts and sexual dysfunction . in our opinion , bicycle riding seems to have no statistically measurable effect on luts or sexual functioning in men , at least in amateur recreational bicyclists .
there is a need for further large - scale research on this subject and study of the underlying mechanisms leading to cycling - related luts and sexual dysfunction .

Answer:
purposethis study was designed to determine whether men who engaged in recreational bicycle riding are more likely to be affected by lower urinary tract symptoms ( luts ) and sexual dysfunction than are man who exercised by amateur marathon running with less perineal impact.materials and methodsa total of 22 healthy male amateur bicyclists and 17 healthy male amateur marathoners were enrolled in the study .
 we evaluated questionnaires including the international prostate symptom score ( ipss ) and the international index of erectile function ( iief ) , serum prostate - specific antigen ( psa ) , uroflowmetric values , postvoid residual ( pvr ) urine volume , and transrectal ultrasound of the prostate in all subjects .
 we also compared the prevalence of urination disorders ( ud ) and erectile dysfunction ( ed).resultsthere were no significant differences between the two groups in age , body mass index , comorbidities , or exercise habits ( p>0.05 ) .
 mean total and subscale scores of the ipss and iief and the prevalence of ud ( 8/22 vs. 4/17 , p=0.494 ) and ed ( 11/22 vs. 10/17 , p=0.748 ) were not significantly different between the two groups .
 also , there were no significant differences between the two groups in uroflowmetric parameters such as peak urinary flow rates , voided urine volume , pvr urine volume , prostate volume , or serum psa level.conclusionsbicycle riding seems to have no measurable hazardous effect on voiding function or sexual function in men who cycled recreationally .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
warfarin is the most commonly used oral anticoagulant both for prophylaxis as well as treatment for arterial and venous thromboembolic conditions .
it has a narrow therapeutic index and is metabolized by hepatic cytochrome p450 2c9 enzyme ( cyp2c9 ) .
various polymorphisms exist in the gene that code for cyp2c9 , of which * 1 is the wild form expressing normal activity . amongst the variants , * 2 and * 3 are more common than the rest and exhibit lesser enzymatic activity .
the anticoagulant effect of warfarin is measured by prothrombin time - international normalized ratio ( pt - inr ) .
warfarin exerts its anticoagulant effect by reducing the regeneration of active vitamin k through inhibition of vitamin k epoxide reductase , encoded by vitamin k epoxide reductase complex subunit 1 gene ( vkorc1 ) .
increased risk of deranged inr or bleeding has been reported in patients harboring mutant form of either cyp2c9 or vkorc1 .
this case report describes a patient on low - dose warfarin , who succumbed to a subdural hematoma and was found to have polymorphic cyp2c9 ( * 1/*3 ) .
a 49-year - old male patient , who was a known case of superior sagittal sinus thrombosis for the past 8 years on tablet warfarin 2.5 mg every night , was brought to the hospital unconscious .
the patient was non - compliant in not following up with his physician nor did he check his pt - inr levels regularly for the past 1 year .
the patient 's relative , however , maintained that the patient was regular in taking the prescribed dose of warfarin ( 2.5 mg ) every night . on physical examination
, he was found to be unconscious ( glasgow coma scale score of 3 ) , pulse was feeble and the blood pressure was not recordable .
a plain computed tomography ( ct ) brain revealed 24.2 mm hyperdense cresentic subdural hematoma in left fronto - temporo - parieto - occipital region with subfalcine extension and midline shift [ figure 1 ] .
his pt - inr was found to be 9 [ normal ( in the absence of anticoagulation therapy ) is 1 and it has to be maintained between 2 and 3 for an appropriate therapeutic effect for warfarin ] .
fresh frozen plasma was initiated at a dose of 15 ml / kg / day .
blood ( 5 ml ) was collected from the patient and genotyping was done for both cyp2c9 and vkorc1 .
cyp2c9 was found to be polymorphic for * 3 ( * 1/*3 ) and vkorc1 was found to be wild - type ( normal ) .
plain ct brain revealing 24.2 mm hyperdense cresentic subdural hematoma ( red arrow ) in left fronto - temporo - parieto - occipital region
pharmacogenetics is the study of genetic influence on inter - individual variation in the response of a drug .
pharmacogenetics has been shown to be of value in detecting an optimal response as well as in preventing adverse reactions following drugs such as warfarin , clopidogrel , and phenytoin .
warfarin is metabolized by cyp2c9 and over 30 polymorphic alleles have been identified in the gene coding for cyp2c9 .
the wild form of the gene is * 1 and the most common polymorphic forms include * 2 and * 3 .
allelic frequency of cyp2c9 * 2 and * 3 in various populations including indians were found to be in the range of 0 - 20% .
a recent systematic review concluded that in comparison to the patients with cyp2c9 * 1/*1 genotype , the cyp2c9 * 1/*2 , cyp2c9 * 1/*3 , cyp2c9 * 2/*2 , cyp2c9 * 2/*3 , and cyp2c9 * 3/*3 patients required warfarin doses that were 19.6 , 33.7 , 36.0 , 56.7 , and 78.1% lower , respectively .
similarly , in the vkorc1 gene , two alleles have been identified in vkorc1 namely g and a. patients with gg ( wild type ) are resistant requiring a higher dose of the drug whereas aa are sensitive requiring a lesser dose and ga requires intermediate .
a randomized clinical trial has also shown that pharmacogenetic - based dosing of warfarin was associated in maintaining the pt - inr levels within the acceptable range for a longer time than by the standard dosing .
united states food and drug administration ( fda ) has recently modified the warfarin labeling by suggesting cyp2c9 and vkorc1 genotyping before initiating the drug to ensure warfarin safety .
our patient had a fatal subdural hematoma despite low - dose ( 2.5 mg hs ) of warfarin .
he had massively deranged inr of 9 , was brought in with glasgow coma scale of 3 .
the * 1/*3 variant cyp2c9 explained this serious adverse event with low - dose warfarin . the * 3 variant is less than 5% as active as the wild type whereas * 2 retains around 12% of the activity .
a recent indian review of oral anticoagulant use revealed lack of proper laboratory facilities , with irregular pt - inr monitoring in 25% patients and deranged inr values in a high proportion of patients .
pharmacogenetic testing needs to be done only once and hence can be considered cost - effective .
studies have shown that along with age , gender , body weight , cyp2c9 and vkorc1 polymorphisms account for almost 64% of the variability in the dose of warfarin required for an individual .
hence , by doing these genetic testing a priori to the treatment initiation , there is a high possibility that the patients may receive an appropriate dose than just by routine practice .
even , several international algorithms for predicting dose of warfarin have been developed with these predicting factors of which , gage 's and wadelius algorithms have been shown to be the most accurate .
recently , an algorithm for indian patients has also been developed , which was found to be more accurate , sensitive and significantly reduced the risk of overestimation of dose of warfarin .
this algorithm can be used for predicting the appropriate dose of warfarin in our population with the genotype details of cyp2c9 and vkorc1 . to conclude
, this case highlights the necessity of adopting the practice of routine genetic testing for cyp2c9 and vkorc1 while initiating warfarin therapy .

Answer:
warfarin is the most common and cheap oral anticoagulant currently used in clinical practice .
 a high inter - individual variation is seen in the response to warfarin .
 recently , pharmacogenetics has gained importance in managing patients on warfarin , both in predicting the optimum required dose as well as in decreasing the risk of bleeding .
 this case report is a description of a 49-year - old patient who had a lethal subdural hematoma with low - dose warfarin .
 he was subsequently found to have cyp2c9 gene polymorphism ( * 1/*3 ) .
 this case report stresses the importance of pre - prescription assessment of genetic analysis for those initiated on warfarin .


Question:
You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.

Title:
Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

Paper sections:
Introduction

Cyclic β-amino acids have for the past few decades aroused widespread synthetic interest owing to their diverse biological activities, especially applications in the field of medicinal chemistry. β-Amino acids (i.e., amino acids containing an extra methylene group in the backbone) occur naturally in peptidic structures [1][2][3][4][5] and have been used in peptide design to obtain mixed peptides that retain their biological activities [6,7].

Moreover, they can be used as starting substances for different heterocycles, as precursors for the synthesis of polymers, as potential pharmacons, for the synthesis of natural products or analogues, and also as building blocks in drug research [8][9][10][11]. Furthermore, some β-amino acid derivatives have antibiotic (oryzoxymycin) and antifungal activities (Figure 1) [12,13]. Among the cyclic β-amino acids, the most widely investigated derivatives are the five-and six-membered derivatives [8][9][10]14,15], but only a few synthetic methods are available for the synthesis of β-amino acids containing seven- [14][15][16], and eight- [14,17,18] membered rings. Only one of these studies previously reported by Fülöp and co-workers was on the synthesis of hydroxylated cyclooctane amino acids starting from 1,5-cyclooctadiene [17], the others were on the synthesis of non-hydroxylated cyclooctane amino acids [14,18]. Also in other ring systems, only non-hydroxylated cyclic amino acids and derivatives were synthesized [8][9][10]15,16]. Therefore, we were inspired to develop new methods for the synthesis of hydroxylated β-amino acid derivatives containing eight-membered rings. We have recently reported the synthesis of various eight-membered aminocyclitols and their derivatives [19][20][21][22][23][24][25]. In the present paper, we describe the synthesis of some hydroxyl-ated β-amino acid derivatives containing eight-membered rings starting from cis,cis-1,3-cyclooctadiene.

Results and Discussion

Initially, we focused on the synthesis of β-lactam 2, which was prepared by the cycloaddition of chlorosulfonyl isocyanate (CSI) to cis,cis-1,3-cyclooctadiene, as described in the literature [26]. β-Lactam 2 was transformed into cis-amino ester 3 by cleavage of the lactam ring with HCl(g) in MeOH (Scheme 1).

N-Boc protection of cis-amino ester 3 with (Boc) 2 O in pyridine and 4-(dimethylamino)pyridine (DMAP) gave N-Boc-amino ester 4 (yield 95%). The 1 H and 13 C NMR spectroscopic data of 4 were in agreement with the proposed structure. Treatment of 4 with OsO 4 /NMO gave the expected diol 5 as a single isomer in 91% yield. We assume that the trans selectivity of hydroxyl- ation in ester 4 is due to the steric effect of the presence of the bulky Boc group. The structure of 5 was determined with the help of 1D ( 1 H and 13 C) and 2D (COSY and HMQC) NMR spectra. The diagonal peak at 4.10 ppm has cross peaks with the protons resonating at 2.96, 3.95, and 5.39 ppm, respectively, in the COSY spectrum. The cross peak between H-2 and H-3/H-4 suggests that the proton H-2 should have a trans configuration relative to the proton H-3. Removal of the Boc protection by HCl resulted in the formation of the target β-amino acid 6, which was characterized based on its NMR spectra (Scheme 1).

The N-Boc-amino ester 4 was reacted with m-CPBA to give epoxide 7 as the sole product in 94% yield (Scheme 2). The structure of 7 was assigned based on its NMR spectra. Epoxide 7 was used as the precursor material in the synthesis of the other isomer of β-amino acid 6. The ring-opening reaction of 7 with HCl(g) in MeOH resulted in a mixture of products 8 and 9 in a 9:1 ratio ( 1 H NMR). The product 8 in the reaction mixture was purified by recrystallization from ethanol/ether, but all attempts to purify the expected product 9 failed. The product 8 was obtained as the major product in 80% yield, and the expected product 9 was formed as the minor product in 4% yield. We propose that diol isomer mixture 9 can be formed by solvolysis. The presence of the lactone ring in 8 was determined by 2D NMR spectroscopic data (COSY and HMQC). The diagonal peak at 4.62 ppm has cross peaks with the protons resonating at 4.26 and 4.39 ppm, respectively, in the COSY spectra of 8. The cross peak between H-7 and H-6 showed strong correlation, which clearly supports the trans relation of the proton H-6. The cross peak between H-7 and H-10 also showed weak correlation, which clearly supports the cis relation of the proton H-10. In this reaction, lactonization and hydrolysis of the Boc group to the corresponding amine were observed. The formation of lactone 8 as the major product can be explained by nucleophilic attack of the neighbouring carboxyl group, which was formed by hydrolysis of the corresponding methyl ester.

For the synthesis of other isomeric β-amino acid derivatives, epoxide 7 was treated with two equivalent amounts of NaHSO 4 [27] in methylene chloride/MeOH at room temperature (Scheme 3). The formation of a mixture of products 10 and 11 in a 7:3 ratio was determined by NMR spectroscopy. The reaction mixture was purified using preparative silica gel TLC on a chromatotron with ethyl acetate/hexane (50:50) as the eluent to give carbamate 10 and diol isomer mixture 11 in 65% and 25% yields, respectively. However, all attempts to isolate isomer mixture 11 failed. Again, we suggest that diol isomer mixture  clearly supports the trans relation of the proton H-7. Furthermore, its structure was unambiguously confirmed by single crystal X-ray analysis (Figure 2) [28]. The formation of lactone 10 can again be explained by participation of the neighbouring group, as discussed above. However, during the purification on silica gel of the lactone-Boc product, its transesterification also resulted in corresponding methyl carbamate 10.

We then investigated the epoxide-ring-opening reaction of 7 with sodium azide, to introduce an extra amino group in position 4 on the cyclooctane skeleton. For this, epoxide 7 was treated with NaN 3 in the presence of NH 4 Cl/DMF and this formed lactone 13 as the sole product in 80% yield (Scheme 4). The epoxide 7 was treated with NaN 3 and NH 4 Cl/DMF to obtain compound 12. From this reaction, the formation of unexpected lactone 13 was observed. The reaction was repeated again with only NH 4 Cl and DMF, and the reaction resulted in formation of compound 13. This experiment shows that NaN 3 / DMF does not to play any role in this transformation. The structure of 13 was elucidated with the help of the 2D NMR (COSY and HMQC) experiments. Finally, removal of the Boc group Scheme 5: Suggested mechanism for the reaction of epoxide 7 with NaHSO 4 .

from 13 with HCl(g)-MeOH resulted in the formation of cyclic β-amino acid derivative 8 in high yield.

Our suggested mechanism for the reaction of epoxide 7 with NaHSO 4 in a mixture of methylene chloride/MeOH proceeded as described in Scheme 5. First, the C=O group of the ester prefers to attack the protonated epoxide to give intermediate 15.

Then, water, which is available in methanol as an impurity, attacks the oxonium ion to give dealkylation product 10, which is a typical transesterification reaction.

To explain the formation of lactone 10, we performed a series of DFT computations using the Gaussian 16 software [29]. For this purpose, we performed geometry optimizations using the B3LYP functional [30][31][32][33]. Vibrational frequencies were computed to characterize each stationary structure. In all the computations, Pople's polarized triple-ζ split valence basis set with diffuse functions, 6-311++G(d,p) [34][35][36], was utilized. The solvation model based on density (SMD) [37] was used to investigate the effects of methanol (ε = 32.613) and dichloromethane (ε = 8.93) on the computed Gibbs energies. For the TS between species A and B, the TSA-B notation is used throughout the article.

According to the given mechanism in Scheme 5, there are two possible paths for the attack of the carboxyl group on the epoxide ring. For the formation of the five-membered lactone 15 (path a), 14 → 15, the reaction proceeds via a barrierless path and the solvent corrected reaction free energies are −17.5 and −18.1 kcal mol −1 with methanol and dichloromethane, respectively. For the formation of the six-membered lactone 16 (path b), 14 → 16, the solvent corrected reaction free energy and barrier are −9.5 and 14.5 kcal mol −1 with methanol, respectively and −11.1 and 13.5 kcal mol −1 with dichloromethane, respectively (Figure 3). For the formation of the five-membered lactone 18 (path a), 17 → 18, the reaction proceeds via a barrierless path and the solvent corrected reaction free energies are −17.2 and −18.0 kcal mol −1 with methanol and dichloromethane, respectively. For the formation of the six-membered lactone 19 (path b), 17 → 19, the solvent corrected reaction free energy and barrier are −5.4 and 14.5 kcal mol −1 in methanol, respectively and −7.1 and 13.4 kcal mol −1 in dichloromethane, respectively (Figure 4). These results indicate that the formation of the methyl carbamate may occur before or after the attack by the carboxyl group. Overall, our computations demonstrate that the 14 → 15 and 17 → 18 conversions are kinetically more favourable, by about 14.0 kcal mol −1 , compared to the 14 → 16 and 17 → 19 conversions. These results rule out the formations of 16 and 19 at room temperature. Therefore, we conclude that the final product is lactone 10, and the formation of lactone 20 is not feasible under the experimental conditions. Furthermore, lactone 10 is energetically more stable, by 5.0 kcal mol −1 in methanol and by 3.7 kcal mol −1 in dichloromethane, than lactone 20. The computations were in good agreement with the experimental results (Figure 3 and Figure 4).

To explain why lactone 10 is formed, a conformational analysis for the epoxide 7 was performed. It is seen that the conformation is quite appropriate for the formation of lactone 10. The hydrogen bond between the C=O group of methoxy ester and NH group of the carbamate in 7 provides an appropriate conformation for the formation of lactone 10. Additionally, according to the conformational analysis of epoxide 7, the relative free energy of 7b is higher by 10.3 kcal mol −1 than that of 7a (Figure 5).

Conclusion

In summary, we successfully synthesized hydroxylated cyclooctane β-amino acid 6 and its derivatives 8, 10, and 13 starting from β-lactam 2. The regioselective synthesis of lactone 8, which is a cyclic β-amino acid derivative, was achieved by oxirane ring opening in epoxide 7 with HCl(g)-MeOH, NaHSO 4 , or NH 4 Cl-DMF. The regioselectivity of oxirane ringopening in 7 was attributed to the conformational effects. The mechanism for the formation of compound 10 was elucidated with DFT computations. Our computations demonstrate that the  formation of the five-membered lactone is kinetically more favourable, and the formation of six-membered lactone is not feasible under the experimental conditions. The conformation of epoxide 7 is quite appropriate for the formation of the five-membered lactone 10, in contrast to the formation of the sixmembered lactone 20. In addition, these novel compounds synthesized may be used as intermediates to design pharmacological tools.

Answer: The first synthesis of 2-amino-3,4-dihydroxycyclooctane-1-carboxylic acid, methyl 6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10yl)carbamate, and 10-amino-6-hydroxy-8-oxabicyclo[5.2.1]decan-9-one starting from cis-9-azabicyclo[6.2.0]dec-6-en-10-one is described. cis-9-Azabicyclo[6.2.0]dec-6-en-10-one was transformed into the corresponding amino ester and its protected amine. Oxidation of the double bond in the N-Boc-protected methyl 2-aminocyclooct-3-ene-1-carboxylate then delivered the targeted amino acid and its derivatives. Density-functional theory (DFT) computations were used to explain the reaction mechanism for the ring opening of the epoxide and the formation of five-membered lactones. The stereochemistry of the synthesized compounds was determined by 1D and 2D NMR spectroscopy. The configuration of methyl 6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10-yl)carbamate was confirmed by X-ray diffraction.


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
liquid - based cytology ( lbc ) as a technique was introduced and tried on pap smears .
thereafter , this technique was performed for non - gynecological cytology , including conventional fine needle aspiration cytology ( fnac ) , guided fnac and fluid cytology .
the thin - prep ( tp ) smears were consistently devoid of obscuring elements and the cells were adequately preserved and evenly dispersed .
pitfalls noticed as cytomorphologic alterations in lbcs are small - sized cell clusters , with more single cells than sheets .
the cells are generally smaller , occasionally show spindling , chromatin detail is attenuated , nucleoli are more prominent , intranuclear inclusion is difficult to visualize , decrease of extracellular particles is seen , there is a decrease in the number of small mononuclear cells / red blood cells / myoepithelial cells and the background matrix is altered
. the pathologist should be cautious in interpreting fine needle aspirations prepared using tp if that is the only methodology employed .
the advantages of lbc , independent of diagnostic accuracy and morphology , have been well described .
although studies on lbc are documented for breast , non - gynecological specimen , thyroid , salivary gland and soft tissues , the authors supplemented bone lesions to all the above in their study .
lbc in fnac smears can be performed on aspirates from different organs like salivary gland , thyroid , lymph nodes , breast , bone and soft tissue and other usual and guided fnac samples .
processing of the samples is carried out using the tp kit , marketed by cytec corporation , malborough , ma , usa . in a comparison study , usually two passes are made .
the first pass is performed for the conventional preparation ( cp ) and the second pass is for the tp preparation .
tp smears are superior to cp smears in fnac ; this fact can be proved by performing a wilcoxon 's signed rank test , p value < 0.001 .
tp preparations are nowadays used in some sophisticated investigations like immunohistochemistry studies in breast lesions , non - hodgkin 's lymphoma ( nhl ) and hodgkin 's lymphoma ( hl ) in effusions , analysis of proliferating cell nuclear antigen ( pcna ) , cell blocks from scraping of cytosmears and comparison with conventional cell blocks .
the aim of our study was to determine the efficacy of lbc technology over conventional smear methods in fnac samples .
the study was performed on patients attending the cytology outpatient department ( opd ) of the hospital over a period of 2 years .
, samples were processed using the liquiprep processing kit and a special kit marketed by cytec corporation .
processing was performed manually in three steps , i.e. collection , concentration and cellular encapsulation .
the lp cytology processing kit contains a preservative solution and a cellular base . using the lbc processing kit ,
, the samples were pushed into a preservative solution , approximately three - times the volume of the sample , and left as such for at least 1 h. this is followed by the next step , i.e. concentration , where the preserved sample is centrifuged at 3000 rpm for 30 min . for cystic fluids , the supernatant fluid is discarded and , after adding the cleaning solution , it is again centrifuged for 15 min to increase its concentration .
a pellet is produced , the supernatant fluid is discarded and a base solution of about 50 microl is added to the pellet to make a thin , homogenous suspension .
this suspension was placed on an ethanol - cleaned glass slide and two circular smears of 1 cm diameter were made .
the second option , which uses a cellular base solution , was used in certain cases , particularly if the sample contains necrotic substance or mucin .
about 4 ml of cleansing solution was used in selected cases , along with the preservative solution , and the processing was performed in a similar fashion .
two passes were performed , the first pass was for cp and the second pass yielded material for the tp preparation , which was processed by the tp kit marketed by cytcec corporation .
different stains were used for staining the cp and lp smears , like he , pap and diff quick .
the representative cs and lb preparations were compared by a semiquantitative scoring system using several criteria [ table 1 ] .
the concentration method used in the procedure was useful in the diagnosis of cystic lesions like aneurysmal bone cysts , warthin 's tumor of salivary glands and metastatic carcinoma .
statistical analysis was performed using the wilcoxon signed rank test on the spss program ( chicago , il , usa ) .
every cytological diagnosis was recorded and tabulated and compiled to yield the p - value .
a total of 110 cases were studied , which were distributed among 30 cases of breast ( 10 fibroadenoma , four mastitis and 12 ductal carcinoma ) , 40 cases of lymph node ( 20 reactive hyperplasia , 12 granulomatous lymphadenitis , three lymphoma and five metastatic carcinoma ) , 10 cases of salivary gland ( two sialadenitis , five mixed tumor , one warthin 's tumor and two mucoepidermoid carcinoma ) , 18 cases of thyroid ( 10 colloid goiter , four thyroiditis and four carcinoma cases ) and 12 cases of soft tissue and bone lesions ( five benign and seven malignant ) .
comparison between cytological features in lbc and cs was carried out using the wilcoxon signed rank test separately for each organ in a tabular form , as shown in table 2 . in our study , in two cases of pleomorphic adenoma , one case of warthin 's tumor and two cases of colloid goiter , a support of cs was needed due to pitfalls in lbc described above .
wilcoxon signed rank test statistics of lbc versus cp for breast cases , fibroadenoma , mastitis and ductal carcinoma were better diagnosed on lbc preparations due to clarity of the nuclear features [ figure 1 ] .
comparison data for lymph nodes suggested that the rs cells were more easily diagnosed on lbc smears due to monolayering .
liquiprep cytosmear of the breast showing pleomorphic - looking ductal epithelial cells in a cluster and acinar pattern in a clear background in case of salivary gland lesions , the mixed salivary tumor was better visualized in the conventional smear because of preservation of the stromal component .
cystic neoplasms of the salivary glands were better appreciated in lbc smears because of concentration . in sialoadenitis ,
lbcs were not very useful in goiter and infectious lesions , but they proved very useful in neoplastic lesions [ figure 2 ] . in lytic bone lesions like aneurismal bone cyst ( abc ) , giant cell tumor ( gct ) and metastasis ,
liquiprep cytosmear showing papillary carcinoma of the thyroid in a clear background with nuclear grooving the study conducted by mygdakos et al .
lbc was favored over cs for evaluating gynecological specimens , which was approved by the fda in 1996 .
thereafter , lbc has been found to be useful in non - gynecological cytologic specimens like fnac and body fluids , both small and large volume , which have drawn variable conclusions . in conventional fnac
smears , cells are admixed with debris , blood and exudates , which make the interpretation difficult .
there is suboptimal preservation of cells and cellular obscuring by unwanted material , leading to a high proportion of cases reported as inadequate or unsatisfactory for assessment . to overcome this problem , the lbc technique was introduced , which preserves cells in a liquid medium and removes all debris , blood and exudates , either by filtration or density gradient interpretation
, there is even distribution of cell material , lack of obscuring factors , no drying artifact and monolayering . in our study , fnac was performed from various sites like breast , lymph node , salivary glands , thyroid and bone and soft tissue . in fibroadenoma breasts , although stromal fragments were lost , lbc proved to be useful in the diagnosis based on visualization of ductal aggregates and bipolar cells . for duct carcinomas ,
the wilcoxon signed ranked test for thyroid lesions [ table 2 ] , lbc was not useful in goiter and infectious lesions .
lbc was not useful in cystic neoplasms like warthin 's tumor , mucoepidermoid and adenoid cystic carcinoma and comparable to the study by parfitt et al . for bone and soft tissues , good results were obtained in lbc because of background clearing and concentration phenomenon . in all lesions of the lymph node ,
lbc proved to be a better option . because of the pitfalls of lbc , as described above , in some selected cases of granulomatous lymphadenitis ( lacking epitheloid cells ) , mucinous tumors ( lack of mucin ) , colloid goiter ( thin colloid fragmented ) and pleomorphic adenomas of the salivary gland ( myxoid background poor and present in droplets ) , a support on cs may prove useful .
as observed by the authors , lbc of bony lesions do not require support of cs .
tp preparations are superior to cps with regard to clear background , monolayer cell preparation and cell preservation .
it is easier and less time consuming to screen and interpret tp preparations because the cells are limited to smaller areas on clear backgrounds , with excellent cellular preservation .
however , tp preparations are more expensive than cp and require some experience for interpretation .
lbc is strongly advocated in the best interest of public health , by improving the quality of the sample and reducing the likelihood of false - negative cytology results .

Answer:
background : liquid - based cytology ( lbc ) is fast becoming a useful method in evaluating both gynecological and non - gynecological preparations , including fine needle aspiration ( fna ) cytology
 . even distribution of cells , decreasing obscuring background elements like blood and mucus , well preserved nuclear and cytoplasmic details and rapid fixation helps in better visualization of cells.aim:this study was conducted to asses the diagnostic accuracy of liquid  based cytology versus conventional smears in fine needle aspiration samples.study design : in this prospective study , we had 110 cases , including 30 cases of breast , 40 of lymph node , 10 of salivary glands , 18 of thyroid and 12 of bone and soft tissue . in each case , two passes were performed .
 the first pass was for conventional preparation ( cp ) and the second pass yielded material for thin - prep ( tp ) preparation .
 both cp and tp smears were compared for cellularity , background blood and necrotic cell debris , cell architecture , informative background , presence of a monolayer of cells and nuclear and cytoplasmic details by a semiquantitative scoring system .
 wilcoxon 's signed rank test on an spss program was used for statistical analysis.results:diagnostic accuracy was better in lbc smears compared with cp smears due to lack of background debris and better cell morphology , which was performed according to wilcoxon 's signed rank test , yielding a p - value of < 0.001 .
 however , in some cases , because of a decrease in cell size , clustering and altered background in lbc , a support of cp was essential.conclusion:lbc performed on fna samples can be a simple and valuable technique . only in few selected cases , where background factor is an essential diagnostic clue , a combination of both cp and tp is necessary .