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 transplantation is an established therapeutic option for patients with advanced cystic fibrosis ( cf ) .
the success of the first transplant for a patient with cf in 1983   spurred further refinement of the management and selection criteria of patients , leading to significant survival benefit .
however , patients with advanced cf present a unique microbiological challenge , with disease characterised by bronchiectasis , severe airflow obstruction , high bacterial loads , and recurrent lower respiratory tract infections [ 46 ] . unsurprisingly
, some centres turn down patients on the basis of colonisation with multiresistant bacteria . the most common respiratory pathogen that colonises patients with cf is pseudomonas aeruginosa , with up to 80% of patients being culture - positive for this organism .
as the presence of this microorganism has negative prognostic implications , it is disturbing to note that levels of resistance to frontline antipseudomonal agents are very high .
the presence of multi- and pan - resistant p. aeruginosa renders methods of single - agent antibiotic susceptibility testing suboptimal .
the conventional manner of managing patients who are colonised with these microorganisms is to empirically treat them with combinations of antibiotics in the peritransplant period .
unfortunately , an empirical approach might lead to inadequate bactericidal levels and the prescription of antibiotics that antagonise each other .
this approach is undesirable , as patients with pan - resistant bacteria have shorter follow - up periods and decreased survival rates after transplant .
an alternative approach is to utilise multiple combination bactericidal testing ( mcbt ) , a technique that had previously been used to systematically test bacterial isolates against multiple combinations of antibiotics to determine susceptibility patterns and identify optimal combinations for potential treatment .
previous studies have demonstrated that using combinations of antimicrobials may generate higher levels of in vitro bactericidal activity against p. aeruginosa   and burkholderia cepacia complex .
our centre currently advocates the use of mcbt ( with modified antimicrobial concentrations ) to determine appropriate prophylactic regimens in patients about to undergo lung transplantation for cf and other lung pathologies that are colonised with antibiotic - resistant gram - negative bacteria .
to evaluate the effectiveness of our strategy , we undertook a retrospective analysis to compare the rates of posttransplant infection in patients whose peritransplant antimicrobial regimens were determined using the mcbt versus those who had their antibiotics chosen via conventional sensitivity testing .
we performed a retrospective analysis of all patients who underwent lung transplantation for cf between january 2000 and august 2010 .
patients were included in the review if they were colonized pretransplant with p. aeruginosa ( as demonstrated by sequential sputum cultures ) and were excluded if they were colonized with b. cepacia complex .
data was collected from patients ' case notes and clinical charts ; looking specifically at incidences of septicaemia at 30 days , posttransplant wound infection at 30 days , empyema at 30 days , all - cause mortality at 30 days , and all - cause mortality at one year .
these were mapped against antibiotic resistance , method of sensitivity testing , and choice of antibiotics that were administered .
infections were defined by combining positive laboratory culture from tissue source ( blood , surgical wound , and pleural fluid ) with at least two of the following four parameters : tachycardia ( heart rate > 90 beats per minute),hypotension ( systolic blood pressure < 90  mmhg),body temperature < 36c or > 38c , abnormal inflammatory markers ( white cell count < 4  10  cells / l or > 12  10  cells / l , c - reactive protein > 10  mg / l ) . tachycardia ( heart rate > 90 beats per minute ) , hypotension ( systolic blood pressure < 90  mmhg ) , body temperature < 36c or > 38c , abnormal inflammatory markers ( white cell count < 4  10  cells / l or > 12  10  cells / l , c - reactive protein > 10  mg
prophylactic antimicrobials were chosen based on disc susceptibility testing using british society for antimicrobial chemotherapy ( bsac ) breakpoints .
if sputum was culture positive for pan - resistant p. aeruginosa or recent culture results were unavailable , patients were treated empirically with aztreonam , an antistaphylococcal agent ( either flucloxacillin or clindamycin ) , and metronidazole .
patients who did not receive peritransplant antibiotics chosen via the mcbt method were deemed to have received antibiotics using  conventional  means .
perioperative antibiotics were continued until the patient was extubated and could demonstrate a good cough , ( two - three days ) to a maximum of seven days .
this was used in conjunction with conventional means of choosing peritransplant antibiotics , but , since 2008 , mcbt became the default method for the determination of bactericidal agents for all patients colonised with antibiotic - resistant gram - negative nonfermenters .
bactericidal activity was determined by testing at least 12 antimicrobials individually and in combination with each other , leading to 66 different combinations .
several morphotypes of p. aeruginosa from at least two pretransplant sputa were selected for testing .
each antimicrobial or combination of antimicrobials was tested in isosensitest broth using systemic breakpoint concentrations as specified by the bsac .
after 48 hours incubation at 37c , the turbidity of each broth was measured at 620  nm .
broths without detectable bacterial growth were subcultured onto blood agar to calculate 99.9% bacterial kill .
peritransplant antibiotic regimens were then chosen based on mcbt results and patients ' allergy history . any other gram - negative species ( including nonfermenters and/or enterobacteriaceae ) that may have isolated alongside p. aeruginosa
were also tested using the mcbt , and antibiotic cocktails were chosen that showed bactericidal activity against such mixtures of species .
our centre used a three - day induction protocol with antithymocyte globulin ( titrated by flow cytometric analysis of peripheral blood t lymphocytes ) and intravenous methylprednisolone at a dose of 2  mg / kg .
alternatives were used in the context of an international clinical trial ( mycophenolate ) or in cases of ciclosporin intolerance ( tacrolimus was used ) .
up to five days of intravenous ciclosporin was given in the context of poor ciclosporin absorption in patients with cf .
between january 27 , 2000 and august 23 , 2010 , 163 lung transplants were performed on patients with cf .
this number included patients who were previously turned down by other centres on the basis of their microbiology .
a total of 129 patients were colonized with p. aeruginosa and not colonized with b. cepacia complex .
fifty patients were given antibiotics that were chosen based on the mcbt , and there were 79 patients in the conventional group .
our patients were colonized with strains of p. aeruginosa with varying degrees of antibiotic resistance .
we defined pan - resistance as resistance to antipseudomonal quinolones , -lactams , aminoglycosides , and colomycin . in this cohort
these organisms were resistant to all single agents tested but bactericidal combinations with colomycin and another agent were identified .
seventy - one patients were colonised with multiresistant p. aeruginosa , and nine patients were colonised with fully susceptible strains .
forty - seven patients were colonised with organisms that were resistant to one or two groups of antimicrobials .

figure 1 shows the relative rates of infectious complications after lung transplantation in both groups .
two patients ( 4% ) who were given antibiotics based on mcbt developed septicaemia compared to 13 ( 16.5% ) in the conventional group ( p  0.05 ) .
the occurrence of gram - negative sepsis was statistically lower in the mcbt group , and p. aeruginosa was responsible for only one case of septicaemia compared with seven in the conventional therapy group ( see table 2 ) .
p. aeruginosa was recovered from the posttransplant pleural fluid of one patient ( 2% ) in the mcbt group , as opposed to six ( 7.6% ) in the conventional group ( p = 0.25 ) .
there were no statistically significant differences in the rates of surgical wound infection ( 6% in the mcbt group , 3.8% in the conventional group ) .
there were no statistically significant differences in all - cause mortality rate at 30 days , with a 10% mortality rate in the mcbt cohort and 6.33% in the conventional group .
this lack of statistical significance was replicated in all - cause mortality rate at one year ( 22% in the mcbt group , 19% in the conventional group ) .
lung transplantation for cf accounts for approximately one - third of all single sequential lung transplants performed at our centre .
the complex microbiology involved in this cohort of patients may lead to anxiety when listing patients with multi- and pan - resistant p. aeruginosa , but this paper demonstrates for the first time that the mcbt may have a significant role in altering posttransplant infective complications for patients with cf .
the data indicates that whilst there may not be evidence for an effect on all - cause mortality , patients who had antibiotics chosen using mcbt had lower rates of morbidity .
the presence of pleural infection and septicaemia not only negatively impacts the patients ' transplant journey but prolongs the hospital length - of - stay and adds substantial economic burden .   we had excluded patients who were colonised with b. cepacia complex for the purposes of this retrospective analysis .
this is due to the tendency of these patients to succumb to overwhelming sepsis with one - year mortality rates of between 50% and 100% [ 18 , 19 ] .
our group had also previously noted that infection with burkholderia cenocepacia in particular led to even poorer mortality outcomes .   unfortunately , we were unable to look at exact causes of death ( septicaemia in particular ) in our patient cohort as causes of death were not readily identifiable in all cases .
this is a reflection of the wide geographical referral area that is covered by our centre as well as the degree of shared care with referring centres ( covering the north of england , scotland , northern ireland , and the republic of ireland ) .
a previous analysis of all patients who underwent lung transplantation for cf at our centre   had identified sepsis as the cause of death in 18 cases ( 26% of all recorded cf transplantation recipient deaths ) .
b. cepacia complex was implicated in seven of these cases . in an additional three cases , clinical sepsis
prospective studies would play an important role in determining if the use of mcbt can significantly decrease the rate of early mortality due to septicaemia .
aaron et al . had compared the efficacy of using antimicrobial combinations derived from mcbt with those derived from conventional susceptibility testing for treatment of acute pulmonary exacerbations of cf .
they concluded that regimens based on mcbt results did not result in a better clinical or bacteriological outcome .
it is difficult to make comparisons between our findings and theirs for both clinical and technical reasons . on the clinical side , the patient populations ( post - lung - transplant cf versus non - lung - transplant cf ) and outcome measures were different .
there are also major differences in the antimicrobial concentrations used in our modified mcbt test and the test as originally described [ 13 , 14 ] .   in our study ,
systemic breakpoint concentrations specified by the bsac to define susceptibility were used in a modified mcbt whereas antimicrobial concentrations in the original mcbt  were chosen on the basis of published estimates of the average peak levels seen in serum after standard single - dose intravenous administration  . as a result ,
the antimicrobial concentrations used in our modified mcbt were typically two- to eightfold lower than those previously described .
as a consequence , fewer isolates would be likely to be classified as susceptible in our study .
it is impossible to conclude whether the use of lower breakpoint concentrations of antimicrobials would have led to more favourable outcomes in the study of aaron et al . .
as this is a retrospective study , we readily acknowledge that there are inherent limitations to our findings .
the ten - year period covered by the study has seen numerous changes with regards to developments in lung transplantation .
these include changes in immunosuppression regimen and the natural progression with regards to peritransplant management as the members of our centre gain more experience . given the nonrandomized nature of this study and temporal confounding factors , we can not definitely conclude that mcbt should be given at induction to all patients colonized with p. aeruginosa .
however , the fact that we are dealing with a unique cohort of patients with significant microbiological challenges might render it unethical to conduct a full randomized control trial .
furthermore , it is unlikely that sufficient numbers are recruited to adequately power such a study .
the data presented is the first indication that patients given antibiotics based on mcbt results had significantly lower rates of septicaemia and lower rates of positive microbiological cultures in their pleural effusions .
this is an encouraging finding , lending credence to the need for multi - centre prospective studies to be performed that will ideally lead to no patients being turned down for a lung transplant on the basis of colonisation with resistant microorganisms .

Answer:
early infection is a recognised complication after lung transplantation in patients with cystic fibrosis ( cf ) .
 our centre uses multiple combination bactericidal testing ( mcbt ) when determining appropriate peritransplant prophylactic regimens . to evaluate our strategy , we compared the incidence of posttransplant infection in patients whose peritransplant antimicrobial regimens were determined using mcbt versus standard sensitivity testing .

 patients with cf who were infected with pseudomonas aeruginosa and underwent lung transplantations between 2000 and 2010 were included .
 data was collected from clinical records and our microbiology database .
 microorganisms cultured were mapped against antibiotic resistance , method of sensitivity testing , and antibiotics administered peritransplant .

 129 patients were identified ( mean age 28 , male  :  female , 63  :  66 ) .
 fifty patients ( 38.8% ) had antibiotics determined by mcbt .
 two patients in the mcbt group developed septicaemia , 13 in the conventional group ( p  0.05 , 2-tailed fisher 's test ) .
 sepsis was attributable to p. aeruginosa in one patient from the mcbt group and seven patients in the conventional group ( p = 0.15 ) .
 p. aeruginosa was recovered from the posttransplant pleural fluid of one patient who received mcbt - guided prophylaxis , six patients in the conventional group ( p = 0.25 ) .
 patients given antibiotics based on mcbt had significantly lower rates of septicaemia and lower rates of empyema .


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:
in a 2009 review paper , puhl and heuer documented the incredible scope of discrimination faced by overweight individuals , including in health care settings , the workplace , and media .
in addition , they discuss the relatively sparse data on interventions aiming to eradicate these conditions ( puhl and heuer , 2009 ) . indeed , the few effective studies that have been published describe approaches primarily delivered to university students .
similarly , the broader literature on curbing rates of victimization and bullying indicate that school - based approaches are most successful ( rigby and slee , 2008 ; ttofi and farrington , 2011 ; vreeman and carroll , 2007 ) .
overall , it appears that intervening in secondary schools or universities may be an opportune time to target body dissatisfaction and discrimination related to weight more globally .
large - scale , school - based interventions have been promising in regard to decreasing victimization among pre - adolescents and adolescents ( busch et al . , 2012 ;
, the utrecht healthy school ( uhs ) program aimed to comprehensively improve healthy behaviors including eating habits , physical activity , and substance abuse , as well as decreasing bullying ( busch et al . , 2012 ) .
the uhs approach emphasizes involvement of students , teachers , parents , and administrators , as well as building external connections with an overall goal of health promotion for all members of the school community . with advisement from these stakeholders ,
uhs was rolled out from 2007 to 2010 , and outcome assessment consisted of comparisons from two cohorts of students reporting in 2007 and 2010 .
results showed improvements in many of the target behaviors , including increased physical activity and lower rates of bullying and victimization ( busch et al . , 2012 ) .
a social and emotional learning ( sel ) curriculum aiming to improve mental health and related outcomes like victimization was developed and tested in sweden ( kimber et al . , 2008 ) .
sel , based on cognitive and behavioral methods , focuses on helping students to develop the following five skills : self - awareness , managing one s emotions , empathy , motivation , and social competence .
using a quasi - experimental design , after 2  years of the program , results showed some important differences between outcomes for students in experimental and control schools including decreases in victimization ( kimber et al . , 2008 ) .
importantly , puhl and colleagues ( puhl et al . , 2013 ) surveyed adolescent recipients of weight - related victimization for their perspectives on intervention
for example , the importance of teaching student bystanders how to prevent rather than reinforce bullying behavior appears to be a desirable strategy that has also been shown to be effective ( rigby and slee , 2008 ; salmivalli et al . , 2011 ) . it may also be useful to consider strategies that have been employed directly to victims or those at risk .
for example , vessey and oneill ( 2011 ) used materials from the us health services resources administration s stop bullying now campaign to develop a group intervention for children with disabilities , who are at high risk for experiencing victimization .
results showed that group members were less bothered by teasing afterwards and also experienced improved self - concept .
similarly , in hong kong , a 10-week cognitive behavioral program was delivered to 68 victims of bullying ( fung , 2012 ) .
the program yielded mixed results with students reporting decreased victimization although parents and teacher reports did not echo these findings .
overall , these programs offer some suggestions for strategies that psychologists can draw from when addressing victim - blaming in therapy .
it may also be useful to consider strategies that have been employed directly to victims or those at risk .
for example , vessey and oneill ( 2011 ) used materials from the us health services resources administration s stop bullying now campaign to develop a group intervention for children with disabilities , who are at high risk for experiencing victimization .
results showed that group members were less bothered by teasing afterwards and also experienced improved self - concept .
similarly , in hong kong , a 10-week cognitive behavioral program was delivered to 68 victims of bullying ( fung , 2012 ) .
the program yielded mixed results with students reporting decreased victimization although parents and teacher reports did not echo these findings .
overall , these programs offer some suggestions for strategies that psychologists can draw from when addressing victim - blaming in therapy .
as marks ( 2015 ) states , the media promotes an unhealthy body image , in which most women seen in magazines and billboards are visibly underweight ( ahern and hetherington , 2006 ) . specifically , the media reinforces the perpetuation of the thin - ideal through the glorification of ultra - thin models , causing those who look to the media for information to internalize this ideal ( thompson and stice , 2001 ) .
the perceived discrepancy between people s ideal and actual body image , as well as the unrealistic nature of the ideal , can lead to body image dissatisfaction ( bessenoff and snow , 2006 ; gluck and geliebter , 2002 ) .
one particularly illuminating study demonstrated that after introducing prolonged television access in fijian adolescent girls , those with exposure to western television demonstrated significantly more disordered eating attitudes and behaviors than those without exposure ( becker et al . , 2002 ) .
 buys into  socially defined ideals of attractiveness and engages in behaviors designed to approximate those ideals ( ahern and hetherington , 2006 ) and is one of the most important risk factors for the development of eating pathology ( stice and shaw , 1994 ) .
the body project , the most successful eating disorder prevention program , is a 4-session group - based intervention that utilizes the principle of cognitive dissonance .
it requires participants to explore the costs of and to reject the thin - ideal , thereby reducing their thin - ideal internalization .
extensive research on the body project has demonstrated a decrease in thin - ideal internalization that has led to significant and clinically meaningful reductions in body image dissatisfaction and negative affect ( two parts of the cod ) , as well as 60  percent reductions in diagnostic and statistical manual of mental disorders ( 4th ed .
; dsm - iv ) eating disorders at 3-year follow up compared to controls ( stice et al . , 2013a , 2013b ) .
a large body of research has demonstrated the efficacy of the body project in reducing thin - ideal internalization , body image dissatisfaction , and negative affect in female college ( e.g. stice et al . , 2011 ) and high school students ( stice et al . , 2011 ) , although it has been less successful among middle school girls ( rohde et al . , 2014 ) .
given its efficacy , efforts have been focused on improving the translatability of this intervention .
recent research has demonstrated support for a train - the - trainer approach to body project dissemination . specifically , when master trainers trained novice trainers to train undergraduate peer leaders , participants showed significantly reduced levels of thin - ideal internalization , body dissatisfaction , and disordered eating at post - treatment and 5-month follow up ( grief et al . , 2015 ) .
2014 ) found that effects of the intervention were not related to facilitator s age , sex , education level , or body mass index ( bmi ) or the size of the group , which is encouraging for dissemination .
other efforts to disseminate the intervention have included an internet - dissonance - based program , which demonstrated similar efficacy to an in - person group intervention at post - test , but improvements were not as well maintained at 1- and 2-year follow ups ( stice et al . , 2014 ) .
although the majority of dissonance - based prevention programs have been geared toward the prevention of eating disorders , this recent study of the internet - based program ( ebody project ) also demonstrated large weight gain prevention effects , significantly more so than the body project , which were comparable to other obesity prevention programs ( stice et al . , 2014 ) .
thus , at least for women and girls , these cognitive - dissonance - based programs can reduce body image dissatisfaction , and in some contexts , prevent weight gain . working toward eliminating obstacles to dissemination of this program may help to break the cod . the most obvious and likely effective way of devalorizing the thin - ideal is on a societal level , by diversifying representations of individuals of varying weights in the media and expanding access to larger sized clothing , for example .
as these societal concerns are tackled , clinicians can also help to devalorize the thin - ideal on a more individual level .
although not designed to target the thin - ideal directly , mirror exposure therapy is currently used to promote body image acceptance and reduce body image dissatisfaction . during exposure ,
patients are asked to look at themselves in a mirror while describing their physical appearance in a neutral manner .
studies of mirror exposure have demonstrated significant reductions in body image dissatisfaction among adults with binge eating disorder ( hilbert et al . , 2002 ) , as well as overweight and obese adolescents ( jansen et al . , 2008 ) .
in conclusion , it is important for psychologists to be aware of effective approaches available to intervene stemming from marks ( 2015 ) novel homeostatic theory .
indeed , the literature has shown that there are both systemic and individual empirically supported interventions that can be employed by psychologists .
in particular , such services can be feasibly and acceptably delivered to adolescents and young adults in school settings .
it seems reasonable to suggest initiating large - scale programs in secondary schools and universities that perhaps can even be packaged together to most impactfully address circumstances intertwined with weight gain .
overall , informed by theory , such  culture changes  may be an ideal way to focus prevention and intervention efforts .
thin - ideal internalization is defined as the extent to which an individual  buys into  socially defined ideals of attractiveness and engages in behaviors designed to approximate those ideals ( ahern and hetherington , 2006 ) and is one of the most important risk factors for the development of eating pathology ( stice and shaw , 1994 ) .
the body project , the most successful eating disorder prevention program , is a 4-session group - based intervention that utilizes the principle of cognitive dissonance .
it requires participants to explore the costs of and to reject the thin - ideal , thereby reducing their thin - ideal internalization .
extensive research on the body project has demonstrated a decrease in thin - ideal internalization that has led to significant and clinically meaningful reductions in body image dissatisfaction and negative affect ( two parts of the cod ) , as well as 60  percent reductions in diagnostic and statistical manual of mental disorders ( 4th ed .
; dsm - iv ) eating disorders at 3-year follow up compared to controls ( stice et al .
a large body of research has demonstrated the efficacy of the body project in reducing thin - ideal internalization , body image dissatisfaction , and negative affect in female college ( e.g. stice et al . , 2011 ) and high school students ( stice et al . ,
2011 ) , although it has been less successful among middle school girls ( rohde et al . , 2014 ) .
given its efficacy , efforts have been focused on improving the translatability of this intervention .
recent research has demonstrated support for a train - the - trainer approach to body project dissemination . specifically , when master trainers trained novice trainers to train undergraduate peer leaders , participants showed significantly reduced levels of thin - ideal internalization , body dissatisfaction , and disordered eating at post - treatment and 5-month follow up ( grief et al . , 2015 )
2014 ) found that effects of the intervention were not related to facilitator s age , sex , education level , or body mass index ( bmi ) or the size of the group , which is encouraging for dissemination .
other efforts to disseminate the intervention have included an internet - dissonance - based program , which demonstrated similar efficacy to an in - person group intervention at post - test , but improvements were not as well maintained at 1- and 2-year follow ups ( stice et al . , 2014 ) .
although the majority of dissonance - based prevention programs have been geared toward the prevention of eating disorders , this recent study of the internet - based program ( ebody project ) also demonstrated large weight gain prevention effects , significantly more so than the body project , which were comparable to other obesity prevention programs ( stice et al . , 2014 ) .
thus , at least for women and girls , these cognitive - dissonance - based programs can reduce body image dissatisfaction , and in some contexts , prevent weight gain . working toward eliminating obstacles to dissemination of this program may help to break the cod .
the most obvious and likely effective way of devalorizing the thin - ideal is on a societal level , by diversifying representations of individuals of varying weights in the media and expanding access to larger sized clothing , for example .
as these societal concerns are tackled , clinicians can also help to devalorize the thin - ideal on a more individual level .
although not designed to target the thin - ideal directly , mirror exposure therapy is currently used to promote body image acceptance and reduce body image dissatisfaction . during exposure ,
patients are asked to look at themselves in a mirror while describing their physical appearance in a neutral manner .
studies of mirror exposure have demonstrated significant reductions in body image dissatisfaction among adults with binge eating disorder ( hilbert et al . , 2002 ) , as well as overweight and obese adolescents ( jansen et al . , 2008 ) .
in conclusion , it is important for psychologists to be aware of effective approaches available to intervene stemming from marks ( 2015 ) novel homeostatic theory .
indeed , the literature has shown that there are both systemic and individual empirically supported interventions that can be employed by psychologists .
in particular , such services can be feasibly and acceptably delivered to adolescents and young adults in school settings .
it seems reasonable to suggest initiating large - scale programs in secondary schools and universities that perhaps can even be packaged together to most impactfully address circumstances intertwined with weight gain .
overall , informed by theory , such  culture changes  may be an ideal way to focus prevention and intervention efforts .

Answer:
marks presents  homeostatic theory  which proposes that weight gain is fostered by a  circle of discontent  consisting of body dissatisfaction , negative affect , and overconsumption .
 this innovative framework offers potential intervention approaches , including victim - blaming , stigma , and discrimination , as well as devalorizing the thin - ideal .
 our article discusses possible ways that clinical health psychologists based in university settings may be uniquely positioned to consider and implement large - scale programs that have shown great promise for addressing these core issues .


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:
in central europe patients with muscle - invasive bladder cancer ( mibc ) have relatively poor prognosis .
this includes also patients initially undergoing radical surgical treatment . in order to find underlying reasons ,
we have previously estimated the timing of radical cystectomy in a multicentre study involving 575 polish patients . however , one of the most important limitations of the abovementioned study was the inclusion criterion of being cystectomised instead of being diagnosed with mibc .
consequently , the data on final treatment in the whole population of mibc patients are still limited . within this short communication
the aim of this study was to describe patterns of care in polish patients with newly diagnosed mibc .
this is a multicentre retrospective cohort study involving 296 consecutive patients with primary mibc diagnosed in the years 20122013 in 13 polish urological centres . in all patients the diagnosis
was made based on histological examination of surgical specimens from transurethral resection of the bladder tumour .
the mean age of the cohort was 72.1 years and male - to - female ratio was 3.2 : 1 ( 225 vs. 71 ) .
differences between cystectomised and non - cystectomised patients were evaluated with u mann - whitney test and  test for quantitative and qualitative variables , respectively .
comparison of patients depending on qualification for radical cystectomy table presents absolute , median , or percentage values .
haemoglobin ; rc  radical cystectomy data on nicotine use was available only in 220 patients ( 77.2% of cohort ) among 121/285 ( 42.5% ) patients disqualified from rc , 32/121 ( 26.4% ) patients were qualified for a second step of transurethral resection of the bladder tumour ( turbt ) intentionally followed by systemic chemotherapy , four ( 3.3% ) patients after complete turbt were qualified for adjuvant intravesical chemotherapy only , while the remaining 85 ( 70.2% ) patients were qualified for palliative treatment in the form of chemotherapy and/or radiotherapy and/or best supportive care .
despite poor outcomes of treatment of patients with mibc in central europe , data on patterns of surgical and medical management , as well as its quality , are still unavailable .
we performed a retrospective study aimed at the description of further treatment in patients diagnosed with primary mibc .
the most important finding of our analysis is the high percentage of patients qualified for radical treatment .
a clinically important fact is that that these numbers would probably be higher if we excluded from the analysis patients with metastatic disease , who are not candidates for rc by definition .
available data on patterns of care in mibc patients published in the last 10 years present significantly lower rates of curative treatment , covering 2152.5% of patients [ 47 ] .
however , the studies cited above included more patients and/or were based on cancer or national registries .
some portion of patients included in these analyses was treated with radiotherapy alone , which nowadays is not regarded as a radical approach .
we have also found that patients disqualified from curative treatment were older , had lower bmi values , lower haemoglobin concentration , and declared lower rate of nicotine abuse and shorter time interval between first symptom to diagnosis . while age alone should not influence clinical decisions , it is suggested that older mibc patients are less frequently qualified for radical surgery , and it is well established that the morbidity related to rc is increased within this group [ 912 ] .
low haemoglobin concentration , as well as malnutrition is associated with shorter survival after rc [ 9 , 13 , 14 ] .
moreover , abnormal bmi value increases the risk of surgical complications [ 12 , 15 , 16 ] .
our findings on nicotine use and time from first symptom to diagnosis are both surprising and unexplainable . considering the pathogenesis and clinical course of the disease
, one can suspect that these results are fortuitous . finally , they are of no practical significance .
the study 's strengths are its multi - institutional character , involvement of both academic and non - academic urological departments , and enrolment of a representative cohort of patients .
the most important limitation of the study is the lack of data on lymph node and distant metastases . as available clinical staging
is limited to regional status , among patients disqualified from surgery there are both patients unfit for surgery and patients with initially metastatic disease . their differentiation in the present study was not performed .
because the majority of polish patients with primary mibc receive curative treatment , the stage of the disease alone seems not to be the leading cause of poor survival .
however , the appropriateness of qualification for rc and treatment quality needs to be assessed for a final conclusion on the factors influencing outcomes of treatment in poland .
the results presented within this paper come from post hoc analysis of data collected during a multicentre study aimed at oncological characterisation of a large cohort of polish patients with primary urothelial carcinoma of the bladder .
the study was produced under the auspices of the residents section of the polish urological association .
all the investigators , but two ( m.s . and p.r . ) , were urologists in training .

Answer:
a potential reason for poor survival among patients with muscle - invasive bladder cancer ( mibc ) in poland is initial disqualification from curative treatment due to advanced stage of the disease or low performance status .
 the aim of this study was to describe patterns of care in patients with newly diagnosed mibc.this is a multicentre retrospective cohort study involving 296 consecutive patients with primary histologically diagnosed mibc . therapeutic decisions and potentially underlying clinical factors were analysed.full clinical data was available for 285 patients .
 one hundred and sixty - four ( 57.5% ) patients were qualified for radical cystectomy ( rc ) , 32 ( 11.2% ) patients for a second step of transurethral resection of the bladder tumour ( turbt ) intentionally followed by systemic chemotherapy , four ( 1.4% ) patients after complete turbt were qualified for adjuvant intravesical chemotherapy only , while the remaining 85 ( 29.8% ) patients were qualified for palliative treatment in the form of chemotherapy and/or radiotherapy and/or best supportive care .
 patients disqualified from curative treatment were older ( 78 vs. 69 years , p < 0.02 ) , had lower bmi values ( 24.5 vs. 25.7 kg / m2 , p < 0.02 ) , lower haemoglobin concentration ( 11.6 vs. 12.9 mg / l , p < 0.02 ) , declared lower rate of nicotine abuse ( 50.5% vs. 72.1% , p < 0.02 ) , and had a shorter time interval between first symptom and diagnosis ( 30 vs. 60 days , p = 0.02).as the majority of polish patients with primary mibc receive curative treatment , the stage of the disease alone seems not to be the leading cause of poor survival .
 however , appropriateness of qualification for rc and treatment quality needs to be assessed for final conclusion on the factors influencing outcomes of treatment in poland .


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:
osteoporosis is a disease characterized by the structural deterioration of bone and low bone mass .
the world health organization defines osteoporosis as a bone mineral density ( bmd ) value of 2.5 standard deviations or more below the young adult mean.1 an estimated 10 million patients in the united states have osteoporosis , and its prevalence is expected to continue to rise in the world population.2 degenerative spondylolisthesis and spinal stenosis , as well as vertebral compression fractures , have been reported at an increased rate in patients with osteoporosis,3 and the disease requires special consideration for any older patient undergoing spine surgery . obtaining optimal fixation in the osteoporotic spine is technically challenging ; osteoporosis may also be associated with a poor fusion rate , with rates as low as 56% in elderly patients.4 however , for appropriately selected patients , the presence of osteoporosis is not a contraindication to surgical intervention . very little available literature exists specifically evaluating the clinical and radiographic outcomes in patients with osteoporosis undergoing transforaminal lumbar interbody fusion ( tlif ) .
in fact , to our knowledge , no previous study has examined the effect that osteoporosis may have on rates of interbody cage subsidence , migration , pedicle screw loosening , or iatrogenic fractures in patients undergoing instrumented tlif .
therefore , we sought to compare the radiographic and clinical outcomes of tlif in patients with and patients without osteoporosis .
after institutional review board approval , we retrospectively reviewed all patients aged 50 years or older undergoing instrumented tlif for any indication at one of three institutions between july 2004 and june 2014 .
only patients with immediate postoperative and follow - up radiographs and computed tomography ( ct ) scans available for evaluation of the interbody cage were included in the study .
we excluded all patients without at least a 6-month follow - up ct scan . utilizing a technique similar to that described by lee et al,5 we measured ct hounsfield units ( hus ) on the lumbar vertebrae for all included patients using preoperative ct scans .
patients were then stratified as either osteoporotic or nonosteoporotic based on average lumbar vertebral body hu values .
the hu cutoff values were previously determined from a separate study at our institution and found to correlate with bmd obtained from dual - energy x - ray absorptiometry ( dexa ) scans ( p.m. formby et al , personal communication ) .
patients with hu    112.4 were considered osteoporotic , and those with hu  >  112.4 were considered nonosteoporotic .
plain radiographs and ct scans were evaluated for evidence of implant subsidence , migration , interbody fusion , iatrogenic fracture , or loosening of posterior pedicle screw fixation .
patient medical records were then reviewed for postoperative symptoms , which were further subdivided into persistence of symptoms or recurrence of symptoms .
we used the student t test to evaluate continuous variables and mid - p exact tests for dichotomous data , and p values 0.05 were considered statistically significant .
twenty - five ( 19.5% ) of these patients were designated as osteoporotic based on the postoperative ct hu measurements versus 103 ( 80.4% ) patients without osteoporosis .
we excluded 40 patients who did not have at least a 6-month follow - up ct imaging , leaving 18 ( 20.5% ) patients with osteoporosis and 70 ( 79.5% ) patients without osteoporosis .
these patients had a mean radiographic follow - up of 35.8    27.9 months .
the mean age was significantly higher in the osteoporotic group ( 65.2 years ) versus the nonosteoporotic group ( 56.9 years , p  <  0.0001 ) .
males comprised 50 and 64.3% of the osteoporotic and nonosteoporotic patient groups , respectively , with a combined mean age of 58.5    7.9 years .
we found no significant differences between the osteoporotic and nonosteoporotic groups with regard to sex ( p  =  0.28 ) , body mass index ( 27.6 versus 29.9 , p  =  0.12 ) , number of identified medical comorbidities ( 2.3 versus 1.8 , p  =  0.15 ) , total number of vertebral levels fused ( 1.9 versus 1.8 , p  =  0.56 ) , or fusion rate ( 83.3 versus 88.6% , p  =  0.56 ) .
there were no statistically significant differences between groups for gross implant migration in the coronal or sagittal planes ( 11.1 versus 1.4% , p  =  0.11 ) , pedicle screw loosening ( 22.2 versus 8.6% , p  =  0.14 ) , revision surgery ( 16.6 versus 14.3% , p  =  0.78 ) , or postoperative symptoms ( 44.4 versus 50.0% , p  =  0.69 ; tables 1 , 2 ) .
there were no statistically significant differences between the osteoporotic and nonosteoporotic groups in persistent or recurrent symptoms , though the rate of recurrence in the nonosteoporotic group was three times higher ( persistent symptoms : 38.9 versus 30.0% , p  =  0.47 , respectively ; recurrent symptoms : 5.6 versus 18.6% , p  =  0.18 , respectively ) . abbreviations :
bmi , body mass index ; ca / vit d , calcium / vitamin d ; dexa , dual - energy x - ray absorptiometry ; hu , hounsfield units .
note : the only significant differences between the osteoporotic and nonosteoporotic groups were for mean patient age and hu measurements .
note : the rates of interbody cage subsidence , iatrogenic fracture , and overall complication rates were higher in the osteoporotic group
. significantly higher rates of subsidence ( 5.6    2.4 [ 72.2% ] versus 5.2    1.9 [ 45.7% ] , p  =  0.05 ) and iatrogenic fractures ( 16.7 versus 1.4% ,
overall , the osteoporotic population had significantly higher radiographic complication rates compared with patients without osteoporosis ( 77.8 versus 48.6% , p  =  0.03 ; table 2 ) .
as the average life expectancy continues to increase in the united states , spine surgeons should expect to manage a greater proportion of elderly patients with degenerative spinal conditions .
concomitant with increasing age is an associated increase in the prevalence of osteopenia and osteoporosis . in a study of patients over the age of 50 years undergoing spinal surgery in south korea ,
chin et al found osteopenia and osteoporosis rates of 41.4 and 51.3% , respectively , based on dexa.3 despite the growing population of elderly patients , however , few studies have evaluated the role that low lumbar bmd may have in the complication rates and overall outcomes of patients undergoing lumbar interbody fusion .
we found that a minority of patients ( 21.5% ) undergoing tlif had any dexa information available at the time of surgery , despite advancing age and clinical risk factors for osteoporosis . utilizing hu measurements to assess lumbar vertebral body bmd
, we found that of the patients with hu values consistent with osteoporosis , only 27.8% had any workup for osteoporosis prior to or following their tlif .
this finding is concerning , particularly because we found a higher overall radiographic complication rate in patients with osteoporosis undergoing tlif , and it suggests that patients are undergoing spinal fusion surgery without being appropriately evaluated for low bmd . although there were few patients with osteoporosis in this study , we found an increased incidence and amount of cage subsidence ( fig .
1 ) , a higher rate of iatrogenic fractures , and more overall radiographic complications in patients with osteoporosis . though our data did not reach statistical significance , we also found a greater propensity for implant migration and posterior pedicle screw loosening .

( a ) immediate postoperative and ( b ) 2-year follow - up sagittal computed tomography ( ct ) scans of a 53-year - old man who underwent l4l5 transforaminal lumbar interbody fusion .
the patient had hounsfield unit ( hu ) measurements on immediate postoperative ct scan consistent with osteoporosis ( average l4 hu  =  105.7 ) .
interbody cage subsidence into the superior end plate of l5 with interspace collapse is evident ( 9.9 mm ) , with evidence of increased fusion mass in the anterior column .
however , at 26-month clinical follow - up , he had no recurrence of symptoms . however , it is important to note that the increased overall radiographic complication rate did not necessarily portend worse clinical outcomes for patients with osteoporosis .
patients with osteoporosis and patients without osteoporosis underwent similar rates of revision surgery ( 16.7 versus 14.3% , respectively ) , and patients without osteoporosis actually had a higher prevalence of postoperative symptoms following tlif , particularly when stratifying the constellation of symptoms based on persistence versus subsequent recurrence of symptoms : we found that the rate of recurrent symptoms was higher in the nonosteoporotic group ( 18.6 versus 5.6% , respectively ) , although this finding also did not reach statistical significance .
it is unclear , however , why this trend was observed , and it may be related to the fact that we only included patients with six - month or later postoperative ct scans in our study , which may have biased our clinical data with an increased proportion of patients with postoperative symptoms . despite a higher interbody cage subsidence rate in the osteoporotic group , which in turn would theoretically lead to loss of foraminal height and eventual recurrence of radiculopathy , there did not appear to be any association between osteoporosis and recurrence of symptoms .
we are unaware of any other studies specifically evaluating postoperative radiographic complications in patients with osteoporosis undergoing tlif .
previous studies have drawn conflicting conclusions regarding whether elderly patients are at increased risk for postoperative complications following lumbar fusion .
carreon et al found a 79.6% rate of postoperative complications in patients 65 years old at the time of posterior lumbar instrumented fusion.6 however , cassinelli et al found a much lower rate of major complications ( 3% ) and minor complications ( 31% ) in a similar cohort of patients 65 years undergoing instrumented and noninstrumented lumbar spine arthrodesis.7 similarly , cavagna et al evaluated patients  >  65 years undergoing instrumented lumbar fusions and found good clinical outcomes and no serious postoperative complications or reoperations in this cohort.8 however , they did find a 10.3% rate of implant failure ( two screws and two rods failed ) at 2-year or later follow - up .
glassman et al investigated clinical outcomes of patients 65 years old compared with those  <  65 years old undergoing single - level instrumented posterolateral lumbar arthrodesis ; the authors found that the older population had similar clinical and health - related quality - of - life improvements when compared with the younger cohort.9 however , the older cohort experienced significantly increased rates of serious ( 38 versus 17% ) and overall adverse postoperative events ( 56 versus 36% ) , although there was no increased risk of revision or reoperation between these groups .
likewise , okuda et al did not find major differences in clinical outcomes between patients 70 years old and those  <  70 years old undergoing instrumented lumbar interbody fusion.10 these authors found no increased risk or instrument failure between groups , although they did find lower rates of fusion and higher rates of collapsed union and delayed union in the elderly group.10
  inherent to any small retrospective study , the possibility of type ii statistical error limits the generalizability of our analysis .
the proportion of patients with osteoporosis in our study was low , which could be a source of bias .
our study was also limited by the quality of the medical records , as well as available radiographs and ct scans .
in addition , despite a minimum age of 50 years for inclusion in this study , our patients were still relatively young and healthy , with few comorbidities and a mean age of only 58.5 years .
we looked at a heterogeneous group of patients with disparate preoperative diagnoses undergoing tlif for any reason , which could contribute to bias in this study .
the use of hu for measurement of bone density has not been validated in the literature , with few reports of its use to date .
further prospective studies are needed to evaluate the role that osteoporosis plays in complication rates and overall clinical outcomes in patients undergoing lumbar fusion surgery .
in conclusion , we found significantly increased rates of cage subsidence , iatrogenic fractures , and overall radiographic complications in patients with osteoporosis undergoing tlif .
however , these radiographic complications did not predispose patients with osteoporosis to worse clinical outcomes , and larger , prospective studies are needed to further evaluate lumbar fusion surgery in patients with osteoporosis .

Answer:
study design  retrospective review .

 objective  to compare clinical outcomes after transforaminal lumbar interbody fusion ( tlif ) in patients with and patients without osteoporosis .

 methods  we reviewed all patients with 6-month postoperative radiographs and computed tomography ( ct ) scans for evaluation of the interbody cage .
 ct hounsfield unit ( hu ) measurements of the instrumented vertebral body were used to determine whether patients had osteoporosis .
 radiographs and ct scans were evaluated for evidence of implant subsidence , migration , interbody fusion , iatrogenic fracture , or loosening of posterior pedicle screw fixation .
 medical records were reviewed for persistence of symptoms or recurrence of symptoms .

 results  the final data analysis included 18 ( 20.5% ) patients with osteoporosis and 70 ( 79.5% ) patients without osteoporosis . males comprised 50% of patients with osteoporosis , and 64.3% of patients without osteoporosis .
 the mean age was significantly higher in the osteoporotic group ( 65.2 years ) versus the nonosteoporotic group ( 56.9 years ; p  <  0.0001 ) .
 we found significantly higher rates of subsidence ( 72.2 versus 45.7% , p  =  0.05 ) and iatrogenic fractures ( 16.7% versus 1.4% ,
 p  =  0.03 ) in the osteoporotic group . in addition , the osteoporotic group had significantly higher radiographic complication rates compared with the nonosteoporotic group ( 77.8 versus 48.6% , p  =  0.03 ) .
 there was no difference between groups for revision surgery ( 16.6 versus 14.3% , p  =  0.78 ) or postoperative symptoms ( 44.4% versus 50.0% , p  =  0.69 ) .

 conclusions  our data demonstrated significantly increased rates of cage subsidence , iatrogenic fracture , and overall radiographic complications in patients with osteoporosis
 . however , these radiographic complications did not predispose patients with osteoporosis to an increased risk of surgical revision or worse clinical outcomes .


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:
nearly , 90% of metastatic tumors occur in jaw bones , especially premolar - molar region of the mandible , whereas metastases to soft tissues are extraordinarily rare and account for 0.1% of all oral malignancies .
most metastatic tumors to the orofacial region are seen in patients aged between 40 and 70 years .
metastasis to the soft tissues mostly involves gingiva and alveolar mucosal sites ( 54% ) followed by tongue ( 30% ) . in some cases ,
oral metastatic tumors are found to be the first sign of metastatic spread and in some instances ; they are an indication for unidentified primary tumor of the distant site .
the primary site differs according to oral site colonization . in men , primary tumor of the lung followed by the prostate gland and kidney
the breast is the most common primary tumor site affecting the jawbones and soft tissues ( 41% and 24.3% , respectively ) , followed by the adrenal and female genital organs .
clinically , these metastatic lesions appear nonaggressive , mimicking reactive or benign lesions or even simple odontogenic infections . the clinical features of these lesions include a bony swelling with tenderness , pain , ulcer , hemorrhage , paresthesia and pathological fracture .
it is important to diagnose the origin of the tumor as the management will depend significantly on the histological type .
although infrequent , oral metastases are rarely encountered as the first sign of occult cancer .
hence , this article emphasizes on detailed dentoalveolar examination and early diagnosis for finding the primary focus of metastatic tumor .
a 60-year - old male patient presented with a swelling in the right lower back teeth region of the jaw since 3 months [ figure 1 ] .
the patient complaints of pain for 10 days , radiating to the right temporal region .
the patient was a known hypertensive since 4 years . a well - defined solitary swelling present on the right side of mandible on extraoral examination , a well - defined , solitary swelling measuring 4 cm
 5 cm was noted on the right side of the mandible , which was hard in consistency and fixed to the underlying skin .
no other pathologic findings were noticed during physical examination . on intraoral examination , firm ,
nontender swelling with ill - defined borders measuring 3 cm  3 cm was noted in the right mandibular premolar - molar region [ figure 2 ] .
there was no ulceration , paresthesia or pathological fracture . on intraoral examination , firm ,
nontender swelling with ill - defined borders measuring 3 cm  3 cm was noted patient was advised for oral pantamograph and computed tomography ( ct ) scan .
ct scan of the face with three - dimension reconstruction revealed a well - defined osteolytic lesion involving the ramus and body of the right half of the mandible , measuring 54 mm  45 mm  50 mm ( anterioposterior  transverse  craniocaudal ) .
it showed speculated periosteal lesion with multiple irregular calcifications and extended into the lingual and mandibular soft tissues [ figure 3 ] .
based on the clinical presentation , a differential diagnosis of inflammatory swelling , odontogenic cyst , odontogenic tumor , soft tissue tumor or metastatic tumor to the jawbones was given .
computed tomography scan of the face with three - dimensional reconstruction revealed a well - defined osteolytic lesion with multiple irregular calcifications that extended into the lingual and mandibular soft tissues incisional biopsy was done for the histopathological diagnosis .
histopathological examination of the h and e stained tissue showed diffuse fibrous connective tissue stroma invaded by the tumor cells which were cuboidal to short columnar with eosinophilic cytoplasm arranged in alveolar / follicular pattern of varying sizes [ figure 4 ] .
bony trabeculae were evident in some areas [ figure 5 ] . based on these features ,
the lesion was diagnosed as a metastatic malignant tumor , probably metastasizing from the lung .
( h&e stain , 100 ) tumor islands along with few bony trabeculae were evident in some areas .
( h&e stain , 40 ) x - ray chest posterior - anterior view revealed consolidation of the right lower zone [ figure 6 ] .
the ct scan of the chest with contrast revealed dense soft tissue mass lesion with speculated margins and focal pleural thickening noted at the right posterior basal segment .
x - ray chest posterior - anterior view revealed consolidation in right lower zone of the lungs treatment for the patient was palliative external beam radiotherapy on linac given to a total dose of 3000 cgy in 10 fractions to jaw by rl / ll for 12 days which was well - tolerated by the patient .
chemotherapy included injection cisplatin ( 75 mg)-intravenous ( iv ) ; injection etoposide ( 150 mg)-iv ; tablet vomiset ( 8 mg ) ; tablet ultracet .
the common primary sources of tumors metastatic to the oral region are the breast , lung and kidney .
the actual incidence of these cancers is unknown since oral metastatic disease is usually a manifestation of advanced disease .
the mean age of occurrence is 54 years with slight male predilection . in our case ,
also the patient was aged about the same age ( 60 years ) as supported in the literature .
most of the patients are aware of primary tumors before the metastatic spread to the oral cavity . in our case ,
the most common primary sites for oral metastases were the lung , kidney , liver and prostate for men ; breast , female genital organs , kidney , and colorectum for women . in our case too , lung was found to be the primary site .
the clinical presentation of the metastatic lesions differed between the various oral sites . in the jawbones ,
most of the patients complain of rapidly progressing swelling , pain , paresthesia , difficulty in chewing , dysphagia , disfigurement and bleeding .
our patient presented with features such as firm , nontender swelling with ill - defined borders .
there was no paresthesia , difficulty in chewing , dysphagia , bleeding and pathological fracture .
pathogenesis of oral metastasis is unclear but thought to be a multistage process in which cells detach themselves from the primary tumor and get transported by lymphatic or blood vessels .
recent studies state that cancer cells metastasizing to bone have shown to alter the physiologic balance between both bone resorption and bone formation .
treatment of oral metastasis depends upon its presentation and the stage during which it has been identified .
management includes chemotherapy , radiotherapy , surgical excision or a combination of the techniques under local anesthesia .
an average survival time for lung cancer metastasis is 4 months to 1 year with a maximum survival rate of 5 years .

Answer:
oral cavity is an uncommon site for metastasis and is usually an evidence of widespread disease .
 the clinical presentation of the metastatic lesions differs between the various sites in the oral region .
 metastatic tumors account for 13% of all oral malignancies .
 the jawbones , particularly the mandibular molar area is more frequently affected than the oral soft tissues ( 2:1 ) . here , we report a case of a 60-year - old male patient with metastasis from lung to the mandible , where the metastasis was detected before primary tumor .


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:
a 60-year - old lady presented to our sister department of medical gastroenterology at a tertiary health care institute with a history of an increasing mass in the right upper abdomen of one and a half year duration .
she also had a history of weight loss due to early satiety and decreasing appetite .
she had been evaluated with abdominal cect 14 months before by some local doctor which had shown a mass lesion in the right lobe of the liver .
all her systemic examinations were normal except a big nodular mass in the right hypochondrium merging with the liver .
the department of medical gastroenterology considered her for a repeat workup , with abdominal mri , rbc trigged nuclear scan of the liver , serum tumor markers and routine base investigations .
mri showed a nodular mass lesion arising from the right lobe of the liver , crossing towards the left lobe with involvement of the right portal vein , with areas of cystic changes and hemorrhage within the lesion ( fig .
her tumor markers , including -fetoprotein , cea , ca 19 - 9 and hcg , were all within normal limits .
she was also subjected to upper and lower gastrointestinal endoscopy to rule out any occult primary lesion in the gastrointestinal tract .
routine laboratory investigations including liver function tests , hemogram , kidney function , chest x - ray and ecg were within fairly normal limits , her coagulogram revealing pt elevated by 3 s. serology was negative for hepatitis b and c. she was also subjected to usg guided fnac which was inconclusive and revealed only blood cells .
after complete workup with a tentative diagnosis of fibrolamellar hepatocellular carcinoma the patient was referred to our department for surgical intervention . she was offered a diagnostic and if possible curative laparotomy after repeat imaging ( abdominal cect ) as she had again lapsed a period of 34 months after her workup . due to monitoring constraints
, her attenders did not agree to get an abdominal ct but were ready for any possible surgical intervention with the minimum of a biopsy to plan further treatment . on exploration
the patient was found to have nodular bilobular disease occupying almost all of the liver .
there were areas of boggy swelling in between firm nodules predominantly on the inferior surface of liver suggestive of bleeding within the tumor on aspiration .
the lesion involving both lobes of the liver was too big and multicentric for any resectional procedure and so a biopsy from the lesion was taken safely .
after getting her histopathological report the patient was referred to a medical oncologist for further treatment .
this is the first case of fibrosarcoma of the liver reported at our institute . on light
microscopy the tumor revealed homogeneous , spindle - shaped cells with abundant collagen fibers showing a classic herringbone pattern ( fig .
tissue samples were then sent to another referral cancer hospital for immunohistochemistry where immunoreactive vimentin was found in the tumor cells .
electron microscopically , the tumor cells were rich in rough endoplasmic reticulum without a basement membrane and were surrounded by large amounts of collagen fibers .
the purpose of this case report is to share information on a rare tumor of the liver , a primary fibrosarcoma , as up to the late seventies the literature about this entity was restricted to autopsy diagnosis . to our knowledge
there are case reports from various parts of the world [ 2 , 3 ] , but there are no series of cases of primary fibrosarcoma of the liver .
etiologically exposure to cadmium has been linked to carcinogenesis of this disease in animal models .
described a series of 20 cases of sarcomatous tumors of the liver , of which angiosarcoma was the commonest , and concluded that primary treatment is surgery with survival depending on the degree of differentiation . from the available literature , primary treatment to be considered for fibrosarcoma of the liver
is surgery with curative intent . in a recent article from sloan - kettering cancer center , between 1981 and 2004 they identified only 30 cases of primary liver sarcomas of which
most cases ( 10 ) were hemangioendotheliomas and only 3 were diagnosed to be primary fibrosarcoma .
only 11 of these patients underwent r0 resection and this group of resected tumors had a 5-year survival rate of 65% .
unfortunately our patient presented quite late in the course of disease even if we consider her first ct scan done one and a half year back .
there is a report of one patient with primary fibrosarcoma presenting with frequent episodes of hypoglycemia , where insulin - like growth factor ii was intensely stained in the golgi area of the tumor cells , suggesting its role in the mechanism of hypoglycemia .
on histopathological examination these neoplasms show typical light microscopic features like that of malignant rhabdoid tumor with filamentous cytoplasmic inclusions ( fig .
4 ) , and on electron microscopic examination show staining for both cytokeratin and vimentin by immunohistochemistry . after making a diagnosis of primary fibrosarcoma of the liver at an inoperable stage ,
an extensive review of the literature regarding the role of other treatment modalities was done which was not encouraging [ 5 , 8 ] . though few reports recommend chemotherapy   in liver metastasis of retroperitoneal fibrosarcoma consisting of cyclophosphamide , vincristine , farmorubicin , and dacarbazine , there is no definite role as treatment for primary lesion of liver .
overall the prognosis reported by most of the authors is dismal [ 1 , 2 , 3 , 10 ] .
we conclude by passing on the message that this rare entity does exist and is an area for workup to make guidelines for management of such tumors .
this may be one of the few reported cases of primary hepatic fibrosarcoma confirmed by immunohistochemistry and electron microscopy .

Answer:
a 60-year - old lady presented to us with a right upper abdominal mass . with a clinical diagnosis of liver tumor , she was evaluated with abdominal ct , mri , nuclear scan , tumor markers , usg guided fnac and other baseline investigations .
 on evaluation she had a massive right lobe tumor crossing the midline . in view of the ambiguous diagnosis
 she was subjected to laparotomy where the lesion was judged unresectable and a biopsy was taken .
 histopathological examination showed the rare pathology of primary fibrosarcoma of the liver with features of homogeneous , spindle - shaped cells with abundant collagen fibers showing a classic herringbone pattern .
 tissue samples were then sent to another referral cancer hospital for immunohistochemistry and immunoreactive vimentin was found in the tumor cells .
 electron microscopically , the tumor cells were rich in rough endoplasmic reticulum without a basement membrane , and were surrounded by large amounts of collagen fibers .
 the fibroblastic character of the tumor cells was suggested by light and electron microscopy .


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:
Design and synthesis of non-hydrolyzable homoisoprenoid \xce\xb1-monofluorophosphonate inhibitors of PPAPDC family integral membrane lipid phosphatases

Paper sections:

Farnesyl diphosphate (FPP, 1) is a key intermediate in the mevalonate pathway for the biosynthesis of cholesterol and is the precursor for the biosynthesis of geranylgeranyl diphosphate (GGPP, 2), ubiquinone, heme and dolichol.1, 2 FPP and GGPP also function as prenyl donors for the isoprenylation of many proteins involved in cell growth and proliferation.3–5 The mevalonate pathway makes these isoprenoid diphosphates without synthesizing the corresponding isoprenols.6 However, isoprenols such as farnesol 3 and geranylgeraniol 4 are produced in cells and tissues by sequential enzymatic dephosphorylation of their diphosphates (Scheme 1).7, 8

PDP1/PAPDC2 in mammalian cells decreases protein isoprenylation and results in defects in cell growth and Cultured cells can incorporate exogenously provided isoprenols into sterols and proteins which requires their conversion to the corresponding diphosphates.7, 9–13 Together, these observations identify a route for interconversion of isoprenols and isoprenoid diphosphates that is independent of the mevalonate pathway. This process may enable recycling of "scavenged" isoprenols or could allow independent regulation of flux or substrate channeling to produce individual mevalonate pathway endproducts which have diverse functions.

Two members of the phosphatidic acid phosphatase domain containing (PPAPDC) class of integral membrane phosphatases are broad specificity lipid phosphomonoesterases that exhibit a preference for lipid diphosphate substrates including isoprenoid diphosphates.7, 14, 15 In vitro, one of these enzymes, PDP1/PPAPDC2 can catalyze the sequential hydrolysis of isoprenoid diphosphates first to the corresponding monophosphate and then to the isoprenol. Overexpression of PDP1/PAPDC2 in mammalian cells decreases protein isoprenylation and results in defects in cell growth and cytoskeletal organization that are associated with dysregulation of isoprenylated Rho family of GTPases suggesting that this enzyme may be a functionally involved in interconversion of isoprenols and isoprenoid diphosphates. Two related proteins PPAPDC1A and PPAPDC1B are also broad specificity enzymes. While their activities against isoprenoid diphosphates have not been reported, in vitro both enzymes actively hydrolyze the plant lipid diacylglycerol pyrophosphate (DGPP). Studying the physiological functions of these PPAPDC2 family proteins is hampered by the lack of small molecule probes and selective inhibitors. Thus, we have prepared a series of metabolically stabilized isoprenoid monophosphate mimics that we show are inhibitors of a representative member of the PPAPDC family of integral membrane lipid phosphatases.

Phosphonates are commonly used as hydrolytically stabilized analogues of phosphate monoesters.16–19 Metabolically stabilized inhibitors of protein farnesyl transferase based on farnesyl-α-difluoromethlenephosphonate have been prepared.20 Recent experimental studies indicate that the α-monofluoromethylene phosphonate is a better mimic of phosphate monoesters than either the methylene or difluoromethylene derivatives and the utility of this moiety as a probe of biochemical function has been demonstrated in recent years.21–24 We had previously shown that analogues of FPP where the isoprene units were replaced by substituted aniline moieties, (Scheme 1, AGPP 5), can serve as substrates for a variety of isoprenoid diphosphate utilizing enzymes, including the PPAPDC family integral membrane phosphatases and the protein prenyl transferases FTase and GGTase.25–27 In addition, an unidentified cellular pathway, possibility involving a kinase, converts isoprenols 3, 4, and AGOH 6 to their corresponding diphosphates 1, 2, and 5.7 We took advantage of this substrate promiscuity to design potential inhibitors based on both natural and unnatural aniline substituted isoprenoids.

The synthetic strategy for the target α-monofluorophosphonates is outlined in scheme 2 and was based on installing the fluorine prior to incorporation of the aniline group, followed by revealing the charged phosphonic acid in the last step by deprotecting the phosphonate esters with trimethylsilyl bromide (TMSBr). This strategy enables the introduction of structural diversity into the isoprenoid moiety after establishing the common α-monofluoromethylene replacement of the bridging phosphate ester oxygen.

Our initial approach was to incorporate the α-fluoromethlenephosphonate diester en bloc. Attempts to alkylate (EtO)2P(O)CFHZnBr or (EtO)2P(O)CFHCu or the α-lithiated α-fluoro-trimethylsilylphosphonate carbainion made from diethyldibromofluoromethylphosphonate with geranyl bromide proved unsuccessful in our hands.28, 29 The failure of these approaches led us to abandon the α-flurophosphonate moiety as a synthon and incorporate the fluorine via electrophilic fluorination with N-fluorobenzenesulfonamide (NFBS). Of the available electrophilic fluorinating agents, NFBS was chosen for its selective reactivity under mild conditions and ease of handling and storage.30,31,32 Accordingly, lithiation of either commercially available dimethyl or diethylmethylphosphonate, followed by alkylation with either geranyl or farnesyl bromide gave 7a-b and 8a-b in quantitative yield.19 Treatment of phosphonate 7a-b with n-butyllithium at -98°C in THF/HMPA generated the lithiated carbanion which was fluorinated using NFBS to give α-fluorophosphonate 9a-b in 71% and 68% yield respectively. The yield of α-monofluorophosphonate was reduced or absent when other bases such as LiHDMS, KHDMS or t-BuLi as well as when different solvent mixtures were employed (Table 1). The yield of α-monofluorophosphonate was also reduced to 38% when the diethyl ester 8a-b was used, suggesting that steric bulk around the phosphonate interferes with anion access to NFBS. Optimum deprotection of α-monofluorophosphonates 9a and 9b was achieved using a 15:30:1 molar ratio of TMSBr, pyridine and the phosphonate diester at 0°C for 45 min. followed by quenching with ice-cold water and stirring for another 4 hr at 0°C. TMSBr alone, other ratios of TMSBr and pyridine or stirring with aq. alkali for several days resulted in difficult to separate mixtures of partially hydrolyzed esters and other byproducts.19, 33 Attempt to optimize deprotection of ethyl esters 10a-b only gave partially hydrolyzed compounds along with starting material.

We then adapted our previously reported strategy for the synthesis of anilinogeraniol derivatives to prepare α-monofluorophosphonates 16a-f as outlined in scheme 2.34 Oxidation of phosphonates 9a with SeO2 provided the corresponding mixture of allylic alcohol 12 and aldehyde 13 respectively.10, 34 The alcohol 12 was recovered and oxidized to the desired aldehyde 13 with manganese dioxide. Reductive amination of the appropriate anilines 14a-f with aldehyde 13 using NaBH(OAc)3 gave α-monofluorophosphonate esters 15a-f. As expected from previous work, reductive amination of the anilines with the α,β-unsaturated aldehyde gives a mixture of cis/trans isomers about the 7,8 double bond in an approximately 1:10 ratio.34 Attempts to separate the isomers by column chromatography, silica-HPLC, or reverse-phase HPLC were unsuccessful. Deprotection of the phosphonate esters with the optimized TMSBr/pyridine conditions gave the desired α-monofluorophosphonic acids 16a-f which were stored at −20°C immediately after purification.

We used membranes from insect cells expressing PPAPDC1b as a source of activity to investigate the ability of the α-monofluorophosphonates to inhibit dephosphorylation of lipid phosphate substrates by this enzyme. Like PPAPDC2, PPAPDC1B hydrolyzes the representative substrate diacylglycerol pyrophosphate presented in mixed phospholipid and detergent micells with an apparent KM of 130 μM (Figure S1, supplementary data). A more detailed characterization of the PPAPDC1B enzyme will be published elsewhere. Phosphatase activity was determined in assays containing a fixed 10 μM concentration of the indicated α-monofluorophosphonates and the data are presented as a % inhibition observed in reactions containing 400 μM 1,2-dioctanoyl-sn-glycerol 3-phosphate (DGPP) substrate. Assuming a purely competitive mode of inhibition, the most potent of these compounds 16d, 16e and 16f inhibit PPAPDC1B activity with Ki values of ~10 μM. (Table 2). Phosphonate analogues of phosphatidic acid are competitive inhibitors of the related enzyme PPAPDC2 with comparable inhibition constants (Ki = 0.4 μM).35 These new inhibitors are therefore promising chemical tools to investigate the biological function and substrate-activity relationship of PPAPDC family of integral membrane lipid phosphatases and may prove to be of value for further investigations of the interconversion of isoprenoid diphosphates and their corresponding isoprenols in regulation of the mevalonate pathway.

Answer: An efficient, diversity oriented synthesis of homoisoprenoid \xce\xb1-monofluorophosphonates utilizing electrophilic fluorination is presented along with their activity as inhibitors of PPAPDC2 family integral membrane lipid phosphatases. These novel phosphatase-resistant analogues of isoprenoid monophosphates are a platform for further structure-activity relationship studies and provide access to other isoprenoid family members where the phosphate ester oxygen is replaced by a \xce\xb1-monofluoromethylene moiety. 2009 Elsevier Ltd. All rights reserved.


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:
it exhibits broad bioactivity including inducing apoptosis of scar cells   and anti - inflammatory   and anticancer [ 3 , 4 ] properties , which have been used in the traditional chinese medicine for treatment of hypertrophic scar , inflammation , cancer , and other diseases without obvious toxicity or side effect in clinic .
several preparions , hydrogel , lotion , injection , and liposome , for example , have been reported in the literature .
we are further interested in the form of liquid crystalline nanoparticles ( cubosome ) , for cubosome consists of a curved bicontinuous lipid bilayer extending in three dimensions and separating two congruent networks of water channels [ 911 ] , which can enclose hydrophilic , amphiphilic , and hydrophobic substances ranging from low - molecular - weight drugs to proteins , peptides , amino acids , and nucleic acids .
compared to liposomes , cubosomes showed better storing stability at room temperature and could endure heat treatment [ 1315 ] .
cubosomes could exist at almost any dilution level in water and drug leakage was less concerned compared with liposome .
reported that cubosomes had a higher permeability coefficient ( 4.5-fold ) compared to eye drops when dexamethasone was used as a model drug .
therefore , we consider that the cubosome might represent a promising vehicle containing matrine for effective ocular drug delivery .
hplc , lc / ms / ms , and esi - qtof - ms / ms methods have been used to determine matrine in samples at present [ 6 , 17 , 18 ] .
the aim of this study is to establish and validate a simple , sensitive , and accurate hplc method to determine matrine combined in liquid crystalline nanoparticles .
glycerol monooleate ( dimodan mo / d kosher , material number 116703 ) was kindly provided by danisco cultor ( brabrand , denmark ) and used as received .
poloxamer 407 ( peo98pop67peo98 ) was a gift from basf ( ludwigshafen , germany ) .
milli - q - grade water purified through a millipore system ( elga labwater , sartorius , uk ) was used throughout this study .
pbs ( ph 6.8 ) was made according to the chinese pharmacopoeia ( 2010 ) .
liquid crystal nanoparticles were prepared through the fragmentation of glycerol monooleate / poloxamer 407 bulk cubic gels .
glycerol monooleate ( 3  g ) and poloxamer 407 ( 300  mg ) were first melted at 60c in a hot water bath until they were homogeneous , after which matrine was added to dissolve / blend under continuous stirring .
water ( 6.7  ml ) was then added gradually and the mixture was vortex - mixed to achieve a homogeneous state .
after equilibration for 48 hours at room temperature , the cubic phase gel was formed . by adding 20  ml of water , the cubic gel was disrupted by mechanical stirring .
subsequently , the crude dispersion was fragmented for 10  min by intermittent probe sonication ( jy-96 iin , ningbo scientz biotechology co. , ltd , china ) at 200  w energy input using a pulse mode ( 9-second pulses interrupted by 18-second breaks ) under cooling in a 20c water bath .
the resulting milky coarse dispersion was homogenized using a high - pressure homogenizer ( avestin em - c3 , ottawa , canada ) at certain high pressures and cycles to obtain an opalescent dispersion of the cubic nanoparticles .
the final dispersion of liquid crystal nanoparticles was stored at room temperature for further studies .
the hplc analysis was carried out using a shimadzu system that is equipped with an lc-20at pump , spd-20a uv / vis detector connected to shimadzu spin chrome software .
the chromatographic assay was performed on a reversed - phase ods - bp c18 column ( 5  m , 4.6  mm  250  mm ) at ambient temperature 25c .
the mobile phase under isocratic mode was a mixture of methanol - pbs ( ph 6.8)-triethylamine ( 50  :  50  :  0.1% , v / v ) .
the mobile phase was degassed by an ultrasonic bath and filtered with 0.45  m membrane under vacuum .
all the calculations concerning the quantitative analysis were carried out by an external standard method based on peak areas . to prepare the stock solution , matrine ( 10  mg )
was accurately weighed into 50  ml volumetric flask , made up to volume with methanol , and then the volume was adjusted to 50  ml .
this solution was further diluted with methanol to yield solutions containing 100.0 , 50.0 , 25.0 , 12.5 , 6.3 , 3.1 , and 1.6  g / ml . the chromatogram peak area of each known concentration was calculated .
results from each analysis were subjected to regression analysis . 0.2  ml ( or  200.0  mg ) of the nanoparticles
was accurately transferred into a 10  ml volumetric flask , dissolved , and made up to volume with methanol .
then , the sample solutions were filtered using a 0.45  m filter membrane and injected ( 10  l ) into the hplc system three times under optimized chromatographic conditions .
the method was validated in terms of parameters of specificity , linearity , sensitivity , accuracy , precision , and reproducibility according to the international conference on harmonisation .
the specificity of the method was assessed by comparing chromatograms of matrine working solution , blank excipients sample without matrine , and equal concentrations samples of compound liquid crystalline nanoparticles made as the previous procedure .
the linearity of the method was studied by injecting seven known concentrations of the standard in the range of 1.6200  g / ml .
the sensitivity of the method was evaluated with limit of detection ( lod ) and limit of quantification ( loq ) .
lod and loq were established at a signal - to - noise ratio ( s / n ) of 3 and 10 , respectively .
the accuracy of the method was tested by comparing the percent analyte recovered by the optimum method at three concentration levels ( 80.0 , 100 , and 120.0  g / ml ) .
intraday precision was determined by injection of standard solutions of matrine at 3 concentration levels ( 50 , 25 , and 12.5  g / ml ) , on the same day .
the specificity was evaluated by analyzing blank excipients sample , matrine standard solution , and liquid crystalline nanoparticles samples .
the retention times of matrine at a flow rate of 1.0  ml / min was 16.3  min .
the calibration curves for matrine were found to be linear within the range of 1.6 to 200.0  g / ml . the regression equation was y = 10706x  2959 ( r = 1.0 ) , where y is peak area and x is the concentration ( g / ml ) of matrine standard solution .
the correlation coefficient indicated a good linear relationship between peak area and concentration over a wide range .
the lod ( signal / noise ratio of 3  :  1 ) was calculated as 1.3  10  g / ml and the loq ( signal / noise ratio of 10  :  1 ) was determined as 3.9  10  g / ml .
mean recovery for matrine at three concentration levels ( 80.0 , 100 , and 120.0  g / ml ) was found to be 102.1  1.9% ( rsd = 1.96% , n = 3 ) , 102.6  1.9% ( rsd = 2.94% , n = 3 ) , 100.5  2.1% ( rsd = 2.12% , n = 3 ) , respectively .
the mean concentration was 9.5  mg / ml ( rsd = 1.4% , n = 3 ) .
several mobile phase systems including methanol - water , ethanol - wate - kh2po4 , and acetonitrile - ethanol - h3po4 systems have been tested in this study .
however , the chromatogram of standard matrine might disappear or appear in a wide range with inaccurate calculation area ( see figure 2 ) .
matrine crystalline has 4 forms , namely ,  ,  ,  , and  matrine .
the incorrect mobile phase may change the matrine solution to nanocrystalline because of the solubility .
the chromatographic method was eventually carried out using an isocratic system with a mobile phase of methanol - pbs ( ph 6.8)-triethylamine ( 50  :  50  :  0.1% ) applied at a flow rate of 1  ml / min with detection wavelength at 220  nm . under these optimum mobile phase conditions ,
elution of analyte was completed in less than 20.0  min and retention time of matrine was 16.3  min .
the method was validated according to ich guidelines with the parameters of specificity , linearity , sensitivity , accuracy , precision , and reproducibility .
a simple , rapid , selective , and sensitive hplc method has been developed and validated for the determination of matrine when formulated in cubosome particles .
the present study is the first report on the matrine determination combined with particle dispersion system .
the method can be used for controlling the quality of the cubosome and helpful for further investigation .

Answer:
a reversed - phase high - performance liquid chromatographic method has been developed to quantitatively determine matrine in liquid crystal nanoparticles .
 the chromatographic method is carried out using an isocratic system .
 the mobile phase was composed of methanol - pbs(ph6.8)-triethylamine ( 50  :  50  :  0.1% ) with a flow rate of 1  ml / min with spd-20a uv / vis detector and the detection wavelength was at 220  nm .
 the linearity of matrine is in the range of 1.6 to 200.0  g / ml . the regression equation is y = 10706x  2959 ( r2 = 1.0 ) .
 the average recovery is 101.7% ; rsd = 2.22%  ( n = 9 ) .
 this method provides a simple and accurate strategy to determine matrine in liquid crystalline nanoparticle .