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:
the annual frequency of drug shortages increased 200% from 2006 to 2010 . furthermore , in 2012 the food and drug administration ( fda ) reported a record number of 251 drugs on shortage .
the increasing problem of drug shortages has the potential to adversely affect patient care , delay medical procedures , result in medication errors , and burden the health care system with additional costs [ 35 ] .
when these medications are unavailable , it may lead to significant patient harm when clinicians must resort to second- or third - line agents that may have inferior or less evidence for use .
this is especially true for shortages of often non - interchangeable , curative therapies such as antimicrobials and oncologic agents , which comprise the majority of shortages .
a 2013 survey of infectious disease physicians found that 78% ( n  =  489 ) of respondents had to modify their choices of antimicrobial therapy because of a drug shortage in the previous 2  years .
poor patient outcomes due to a shortage were reported by 55% ( n  =  345 ) of responding physicians who reported having to use alternative agents which were less effective , more toxic , or more costly .
the growing magnitude of drug shortages and the risk of patient harm they pose have gained much attention from the government , media , and researchers as strategies are developed to mitigate their effects . while progress has been made on quantifying the magnitude and causes of drug shortages , a lack of data exists on the causality of shortages on patient outcomes as well as the development of a system for reporting and monitoring patient harm on a real - time basis .
there remains a need for appropriate tracking of the relationship between drug shortages and patient outcomes in the long term [ 1 , 4 ] .
specifically , the need remains for a system where clinicians can report specific instances of patient harm they believe to be due to a drug shortage .
traditionally , adverse event reporting is managed through the adverse events reporting system ( aers ) of the fda ; however , aers is known to under - represent actual events due to infrequent clinician reporting .
furthermore , drug shortages that lead to patient harm may not be recognized as adverse events .
we have suggested that a novel method for maximizing the reporting of adverse events due to drug shortages would be simple , anonymous , use standardized terminology for easy tabulation , and have a mechanism for attributing causality of the adverse event to a drug shortage [ 1 , 4 ] .
we focused on shortages of antimicrobial drugs as they are often non - interchangeable , curative , and represent a large portion of overall shortages , thus making them particularly sensitive to shortages that result in patient harm .
we hypothesized that a novel method for reporting patient harm due to antimicrobial shortages would aid in anonymous and convenient reporting of these cases of patient harm .
clinicians were asked anonymously to report occurrences of patient harm related to antimicrobial drug shortages through an online survey ( surveymonkey ; surveymonkey , palo alto , ca , usa ) consisting of 11 questions ( table  1 ) .
the survey was distributed through an editorial in pharmacotherapy , a letter in the american journal of health - system pharmacy , and through the american college of clinical pharmacy ( accp ) infectious diseases practice and research network ( i d prn ) email listserv .
reports from the survey were tabulated from august 2012 through october 2013 , and three reminder emails were sent to the accp i d prn during this timeframe .
this study was approved as exempt by the midwestern university institutional review board.table  1survey questions1please list the full name of your institution ( for de - duplicating purposes)2how many inpatient beds does your institution currently have?3which of the following best describes the location of your institution ?
if yes , please list the patient s age5sex : male or female6which antimicrobial was unavailable for your patient?7please list the infection for which treatment or prophylaxis was needed8what adverse event did your patient experience?9please attribute the causality of the shortage to the adverse event that occurred in your patient  unrelated : the adverse event is clearly not related to the shortage  unlikely : the adverse event is doubtfully related to the shortage  possible : the adverse event may be related to the shortage  probable : the adverse event is likely related to the shortage10please attribute a severity to the adverse event that occurred in your patient  death  disabling  hospitalization  life threatening  required intervention  other ( please specify)11what was the final patient outcome ?
please check all that apply  death  treatment failure / development of resistance  readmission due to treatment failure  increased length of hospitalization  patient transferred to an institution with a supply of antimicrobial  delay of therapy  suboptimal treatment  other ( please specify ) respondents were surveyed regarding : institution ( for de - duplication purposes ) , patient age ( if < 90  years old ) , sex , antimicrobial on shortage , type of infection requiring treatment or prophylaxis , adverse event , and patient outcome .
criteria for causality attribution were obtained from the common terminology criteria for adverse events ( ctcae ) of the national cancer institute . using these criteria
, the reporter assessed the relationship between the adverse event and the antimicrobial shortage as unrelated ( clearly not related ) , unlikely ( doubtfully related ) , possible ( may be related ) , or probable ( likely related ) .
the severity of the adverse event was also assessed using standardized aers criteria , modified for the setting of infectious diseases . using these criteria , the reporter classified the severity of the adverse event according to the following terminology : death , treatment failure or development of antibiotic resistance , readmission due to treatment failure , increased length of hospital stay , patient transfer to an institution with a supply of antimicrobial , delay of active therapy , canceled care , or other .
overall , there were seven de - duplicated reports of adverse events related to antimicrobial shortages .
the incomplete reports did not provide the level of causality due to a shortage but did report an instance of patient harm .
all institutions were in urban settings with 500740 beds ( n  =  3 ) or 100249 beds ( n  =  1 ) .
the infections for which these patients were being treated or receiving prophylaxis included stenotrophomonas maltophilia bacteremia , pneumocystis jirovecii pneumonia , neonatal sepsis of unknown etiology , and cytomegalovirus colitis .
final patient outcomes included death , delay of therapy , readmission , and limited access to treatment .
two adverse events ( a delay in treatment and an inability to treat with other antimicrobials due to resistance ) were attributed to have probable causality due to a shortage , while the remaining adverse events ( death and an inability to tolerate high oral doses ) were attributed to have unlikely and possible causalities due to a shortage , respectively .
the antimicrobials on shortage in the incomplete reports included three cases of a shortage of sulfamethoxazole  trimethoprim .
the infections for which these patients were being treated or receiving prophylaxis were p. jirovecii pneumonia and stenotrophomonas spp.table  2patient vignettes of complete reports detailing adverse drug events due to antimicrobial shortagespatientage ( sex)antimicrobial on shortageinfection being treatedade experiencedcausality due to shortageseverity of adefinal patient outcome1<90 ( f)sulfamethoxazole  trimethoprim iv
 stenotrophomonas maltophilia bacteremiadeathunlikelydeathdeath245 ( f)sulfamethoxazole - trimethoprim ivpcp pneumonianausea / vomiting / diarrhea when given high oral dosepossiblerequired interventiondelay of therapy3<90 ( f)gentamicinempiric neonatal sepsis1  h delay of treatmentprobablerequired interventionreadmission425 ( m)foscarnetcmv colitisuntreatable due to resistanceprobableother : disease still presentother : obtained foscarnet outside the united states
 ade adverse drug event , cmv cytomegalovirus , f female , iv intravenous , m male , pcp
 pneumocystis jirovecii pneumonia patient vignettes of complete reports detailing adverse drug events due to antimicrobial shortages
 ade adverse drug event , cmv cytomegalovirus , f female , iv intravenous , m male , pcp
 pneumocystis jirovecii pneumonia
the methodology demonstrated in this study illustrates a successful system capable of capturing real - time instances of patient harm and attributing the causality of that harm to antimicrobial shortages . by maintaining a database where the specialists most likely to manage shortages can continuously report instances of patient harm anonymously and conveniently ,
we believe our methodology offers an ability to capture harmful effects of antimicrobial drug shortages on patient outcomes .
clinicians wishing to report on future harms due to antimicrobial shortages can do so at : http://www.surveymonkey.com/s/antimicrobialshortages .
the instances of patient harm reported in this study further underline the harmful effects of drug shortages reported elsewhere in the literature .
these effects include utilization of less effective or more toxic alternative medications , medical errors , delays in procedures , and higher healthcare costs [ 35 ] .
for example , two of the drugs on shortage reported in our survey are first - line agents for their respective indications ( i.e. , sulfamethoxazole  trimethoprim for p. jirovecii pneumonia prophylaxis , and foscarnet for cytomegalovirus colitis ) .
it is worth noting that two of the three antimicrobials reported to be on shortage in our survey required clinicians to follow special instructions to obtain a supply .
trimethoprim was available through drop shipments from the manufacturer only after the need for therapy was documented to the manufacturer .
as there may be significant time lags associated with obtaining such products , special measures are required to ensure ready access to the product at the time of need . of further note ,
the number of full - time equivalents allocated to shortage management has increased in many healthcare institutions ; this has not seemed to curb the inability of some institutions to procure drugs on shortage .
one potential solution may be increased education about procuring drugs on shortage and how best to mitigate their harmful effects , which antimicrobial stewardship programs could potentially provide .
this survey methodology , a quick and anonymous online survey , offers an advantageous alternative over conventional surveys which may only provide a snapshot of the incidence of patient harm and not specific patient characteristics .
the benefits of the fda aers system include that it is a publically available system for reporting adverse events and it provides a form that prompts reporters for pertinent information . however , due to issues such as prescriber disinclination to report for fear of identification and litigation , lack of time to submit reports , and lack of knowledge of the reporting structure , most adverse drug events are never reported .
it has been estimated that under - reporting exists over 90% of the time . specifically in regards to the aers system
, an original study found that only 57% of prescribers were aware of aers , likely leading to reporting rates ranging from 1% to 5% .
we have written about the need for standardization of assessing the impact of antimicrobial shortages on patient outcomes and suggested that the traditional method of reporting adverse events is likely under - reporting the true impact due to the time required for submissions , the complexity of the system , and the personally identifying nature of the report [ 1 , 4 ]
. a 2009 review of the determinants of under - reporting of adverse events found under - reporting to be influenced in part by a lack of suitable means to report the event in 75% ( n  =  45 ) of all studies , and that the available system was considered to be too bureaucratic or not easy enough in 25% ( n  =  45 ) of all studies . the methodology presented here may also be useful in assessing patient harm due to shortages in other drug classes .
reports may have been limited as respondents may have not wished to disclose medication errors or adverse events which occurred at their institutions .
accuracy of self - reporting is an inherent liability to which all surveys , including the fda aers database , are subject . the results from our survey were driven by large institutions in urban settings ; however , results from elsewhere in the literature clearly demonstrate that institutions of all sizes and settings are affected by shortages [ 6 , 11 ] . despite these limitations , the results of this survey provide valuable information regarding patient harm due to antimicrobial drug shortages .
our study demonstrated a novel method for encouraging providers to report patient harm due to antimicrobial shortages .
this method is standardized , anonymous , convenient , and capable of de - duplicating responses .
this pilot study has revealed unique instances of patient harm with assessed causality attributed to antimicrobial shortages .
such studies may help gage the true impact of shortages and may help guide policies aimed at allocating appropriate resources to control and prevent patient harm caused by future shortages .
milena m. mclaughlin , erik skoglund , zachary pentoney , and marc h. scheetz have no conflicts of interest to disclose pertaining to the subject matter of this manuscript .
this article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and the source are credited .

Answer:
introductionthe number of drug shortages in the united states has increased in recent years . while some literature exists on factors that contribute to antimicrobial shortages , the need remains to accurately gage the level of patient harm incurred as a result of realized antimicrobial shortages .
 furthermore , current methods of reporting adverse drug events are known to under - report instances of patient harm .
 we sought to develop an ongoing and accurate method of reporting patient harm due to antimicrobial shortages , which was convenient , anonymous , and allowed clinicians to estimate the causality due to a shortage.methodswe distributed a public surveymonkey ( surveymonkey , palo alto , ca , usa ) link to gather information regarding institution ( for de - duplicating purposes ) , patient age , sex , antimicrobial product on shortage , type of infection requiring treatment or prophylaxis , adverse event , and patient outcome.resultsto date complete data were reported on four patients being treated for infections that included stenotrophomonas maltophilia bacteremia , pneumocystis jirovecii pneumonia , neonatal sepsis of unknown etiology , and cytomegalovirus colitis .
 antimicrobials that were unavailable to patients included sulfamethoxazole
 trimethoprim , gentamicin , and foscarnet .
 two adverse events ( a delay in treatment and an inability to treat with other antimicrobials due to resistance ) were attributed with probable causality due to a shortage , while the remaining adverse events ( death and an inability to tolerate high oral doses ) were attributed to have unlikely and possible causalities due to a shortage , respectively.conclusionthese methods encourage reports of antimicrobial shortage harms.electronic supplementary materialthe online version of this article ( doi:10.1007/s40121 - 014 - 0040-z ) contains supplementary material , which is available to authorized users .


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 june 2014 , a 61-year - old female was admitted to keimyung university dongsan medical center because of a severe dry cough that had lasted for over 20 days . according to her medical history ,
she had undergone a hysterectomy in 2005 , and the pathologic diagnosis was leiomyoma of the uterus . in 2006 ,
chest computed tomography ( ct ) findings demonstrated multiple nodules in both lungs ( fig .
microscopic examination revealed a proliferating spindle cell tumor showing relatively bland nuclei , no pleomorphism , and no mitoses .
in addition , immunohistochemical staining analysis was positive for smooth muscle actin , desmin , vimentin , estrogen receptor ( er ) , and progesterone receptor ( pr ) , and negative for cd34 , pan - ck , and s100 proteins . the result of the pathologic study was benign leiomyoma , and the nodules were diagnosed as pulmonary benign metastasizing leiomyoma ( pbml ) .
, the patient did not return to our outpatient clinic for follow - up . upon the patient s return ,
a posteroanterior chest x - ray showed a very large mass on the right cardiac border ( fig .
chest ct demonstrated a 101-mm mass on the right lower lobe that compressed the posterobasal segmental bronchus ( fig .
a ct - guided needle biopsy of the huge mass revealed it to be leiomyoma .
after right thoracotomy , a very large mass , 100 mm in size , originating from the visceral pleura of the right lower lobe was observed ( fig .
the mass was in contact with the parietal and diaphragmatic pleura , but no invasion was noted . near the mass , multiple fine ,
scattered , whitish nodules measuring less than 1 cm were found on the diaphragmatic , parietal , and visceral pleura .
we performed an excision of the mass in the right lower lobe and excised fine nodules from the parietal and diaphragmatic pleura for biopsy .
intrapulmonary nodules found in the middle lobe and upper lobe were not excised , because they had not increased in size .
the necrotic lesion showed severe cellular atypia , frequent mitoses ( more than 15 per 10 high power fields [ hpfs ] ) , and continuity of the leiomyoma and leiomyosarcoma ( fig . 2c ) .
immunohistochemical staining revealed that the tumor was positive for smooth muscle actin ( sma ) , er , and pr , but negative for cd34 , pan - ck , s100 , and hmb45 ( fig .
the nodular lesions taken from the parietal and diaphragmatic pleura showed no malignant cells . the patient was discharged 8 days after the operation without complications .
large heterogeneous hypermetabolic masses were found from the left para - aortic area to the left pelvic cavity ( fig .
3 ) , and we diagnosed them as metastatic leiomyosarcoma . additionally , increased fluorodeoxyglucose ( fdg ) uptake was observed in the peribronchial lymph nodes , the mediastinum , and the supraclavicular lymph nodes .
two months later , en - bloc resection of the retroperitoneal masses with left nephrectomy was performed , and the pathologic diagnosis was metastatic leiomyosarcoma .
we decided to continue observing fdg uptake in the mediastinal and peribronchial lymph nodes rather than prescribing chemotherapy , because metastasis of leiomyosarcoma to the lymph nodes is rare . a chest ct scan done 1 year after surgery demonstrated no changes in the pulmonary nodules and no recurrence of the mass .
benign metastasizing leiomyoma ( bml ) results from metastasis of a uterine leiomyoma ; thus , bml patients have a history of uterine leiomyoma
. the condition may occur at any age , but occurs most often in women from 30 to 74 years old .
bml can occur in a number of different areas of the body , including but not limited to the lungs , para - aortic lymph nodes , abdominal lymph nodes , heart , breast , liver , and esophagus .
the most common site of occurrence is in the lungs , in which case it is known as pbml .
the pathogenesis of pbml is unknown , but the most common theory is hematogenous spreading of leiomyoma during uterine surgery .
immunohistochemical staining of affected tissue is positive for desmin , sma , pr , and er . most cases of pbml do not require treatment , but pbml that metastasizes or increases in size does need to be treated , as it can cause respiratory failure , chest pain , or hemoptysis .
surgical excision is the treatment of choice , but this is only possible in cases of resectable pbml .
in some cases of pbml that a repositive for er or pr , reducing hormone release via hysterectomy , bilateral adnexectomy , and/or hormone therapy may decrease the tumor s size .
the incidence of the sarcomatous transformation of benign uterine leiomyomas is only 0.1%0.8% , and is most often seen in women in their 50s .
pbml can also undergo malignant transformation ; excluding our case , just 1 case of the malignant transformation of pbml has been reported .
radiologically , it is difficult to differentiate between normal pbml and pbml that has become malignant .
on fdg pet - ct , heterogeneous fdg uptake of the tumor may reflect necrosis within the leiomyosarcoma . in our case ,
pathologically , the current criteria used to differentiate a malignant smooth muscle tumor from a benign mass are the presence of necrosis , a high mitotic index ( > 5 mitoses seen in 50 hpfs ) , nuclear atypia , cellularity , and an ill - defined tumor border .
however , in primary pulmonary leiomyosarcoma ( ppl ) , progress is slow , and metastasis of ppl occurs late in the disease process .
if the condition is diagnosed early , wide excision with negative margins ( r0 ) is the standard treatment .
the 5-year survival rate in ppl patients who undergo complete resection is over 50% , and recurrence is rare .
lymph node resections are generally not necessary because ppl rarely shows lymph node involvement . for advanced lesions , depending on the size and grade of the tumor , radiation therapy , chemotherapy , or both may be indicated as an adjuvant therapy . however , the median survival of patients with an unresectable sarcoma or metastatic disease is about 12 months .
overall , early diagnosis and complete mass resection are vital in cases of the malignant transformation of pbml .
however , preventive resection or diagnostic excisional biopsy is not recommended for all pbml patients , since the occurrence of a malignant change is extremely rare
if there is a very large , newly developed mass that is increasing in size rapidly , or if a malignant mass is found on pet - ct , diagnostic mass resection should be considered .

Answer:
pulmonary benign metastasizing leiomyoma ( pbml ) is defined as metastasis of a leiomyoma to lung tissue .
 it was first reported in 1937 .
 p bml is known as a benign disease , but can undergo malignant transformation . only 1 case of the malignant transformation of pbml to leiomyosarcoma has been reported previously . in this report , we present a case of malignant transformation of pbml .


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:
cough is one of the most distressing symptoms in cancer patients with lung or mediastinal metastasis or due to complications of cancer treatment .
twenty to 42% of cough do not respond to conventional medications and are referred to as refractory cough and these are often a medical challenge .
it shows features such as abnormal throat sensation ( laryngeal parasthesia ) , increased cough sensitivity to tussigens ( hypertussia ) , and cough triggered by nontussive stimuli such as cold or talking ( allotusia ) .
gabapentin is known to be effective in treating neuropathic pain with central sensitization and findings from the present case predicts its effectiveness in treating refractory cancer related cough .
it further affirms the fact that vagal neuropathy may be associated with refractory chronic cough .
a 15-year - old boy , who had previously been diagnosed with malignant spindle cell sarcoma , was referred to the department of palliative care and psycho - oncology for chronic refractory cough .
following histopathological diagnosis of spindle cell sarcoma of right lower limb in the year 2014 , he had undergone surgery followed by radiotherapy for local control . in may 2015 , he presented to the clinical oncology department with a history of persistent dry cough of 6 months duration .
a computed tomography scan of thorax [ figure 1 ] revealed a large heterogenous hypodense soft tissue mass ( 10.5 cm  10.3 cm ) in the right lower lobe with extension to the left atrium through the right inferior pulmonary vein .
in addition , there were enlarged right paratracheal , subcarinal , and hilar lymph nodes . computed tomography scan of thorax showing the mass in the right lower lobe with extension to the left atrium through the inferior pulmonary vein the child had persistent cough for the duration of 6 months .
the cough intensity on a numerical rating scale ( nrs ) was 10 ( out of 10 ) .
each bout of cough lasted for 30 s and there were 20 such bouts in a day .
cough was severe in the morning and was triggered by activities that involved walking , talking , or exposure to the cold environment .
his eastern cooperative oncology group ( ecog ) performance status score at the time of presentation was 3 .
a trial of codeine phosphate started by the primary treating team did not reduce cough but instead caused excessive drowsiness and giddiness due to which he had to stop the medicines .
patient was started on gabapentin 50 mg 3 times a day and advised to increase the dose by 50 mg every 3 days until response was obtained or the child felt drowsy ( in the latter case , the drug dose would be decreased ) .
the patient responded significantly well with 200 mg / day of gabapentin after 1 week without any side effects such as drowsiness or giddiness and he continues to improve .
there was a decrease in the cough intensity to 2 ( out of 10 on nrs ) and both cough duration and bouts ( 2/day ) .
the child is now able to enjoy his routine life and socialize with friends and relatives .
patients with primary or metastatic cancer of the lung often present with distressing symptoms such as breathlessness and cough which significantly impacts their quality of life
. there are multimodal options for treatment in cancer related cough which include corticosteroids , bronchodilators , brachytherapy , laser therapies , and opioids .
our patient had an extensive mass crossing the mediastinum which precluded radiation to the mass as this involved significant risk to the mediastinal structures .
opioids are commonly used in cancer patients for the management of pain , cough , and breathlessness .
opioids act by stimulating the mu receptors in the cough centers of the brain and helps in suppressing the cough . in one study ,
slow release morphine sulfate showed a significant improvement in the cough related quality of life as compared to placebo and this was not associated with cough reflex sensitivity which is consistent with central action of morphine .
the treatment , on the contrary , caused significant drowsiness and giddiness affecting his quality of life .
cough reflex is mediated by the stimulation of the vagal primary afferent nerve distributed along the tracheobronchial tree . thus , rapidly adapting receptors of the vagal afferents are known to be evoked by mechanical stimuli and deformity in the airway epithelium , which results in cough .
thus , an unresectable mass in the mediastinum acts as a constant source of irritation for the airway which in turn triggers cough .
we used gabapentin in our patient with successful control in cough intensity , duration , and frequency .
gabapentin is a lipophilic structural analog of the neurotransmitter gamma aminobutyric acid which is proven to have a central action .
it is known to act on the alpha 2 and delta receptor of calcium channel inhibiting the release of neurotransmitters such as substance p , a tussigenic agent , and possibly inhibits the n - methyl - d - aspartate receptors .
recent trials have shown the superiority of gabapentin in reducing the frequency and intensity of cough .
peripheral cough sensitivity to capsaicin was not changed by gabapentin which proves its central effect . in the same study
, there was a significant improvement in cough related quality of life in the gabapentin arm .
the common side effects of gabapentin include dizziness , fatigue , headache , and confusion which was not reported by our patient .
there is , thus , a need to explore the use of neuromodulatory agents in symptom conditions which are known to have a neural origin such as cough , pruritus , and hiccoughs .

Answer:
vagal sensory neuropathy or vagal hypersensitivity has been implicated in the pathophysiology of chronic cough .
 earlier reports have shown gabapentin to be effective in sensory laryngeal neuropathy and symptom conditions that have a proven neural origin .
 we present a case report of a patient with chronic refractory cough due to a soft tissue mass in the lung that caused compression of the mediastinal structures .
 the patient was successfully treated with gabapentin with reduction in the cough intensity , duration , and frequency .


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:
approximately 24% of non - hodgkin 's lymphomas are considered to be of extranodal origin .
primary uterine non - hodgkin 's lymphomas are extremely rare accounting for < 1% of all extranodal non - hodgkin 's lymphomas .
however , the diagnosis of primary uterine lymphoma is often delayed due to its low incidence and nonspecific clinical presentation .
, we present magnetic resonance imaging ( mri ) and fluorine-18-fluorodeoxyglucose ( f - fdg ) positron emission tomography ( pet)/ct findings in a patient with primary uterine peripheral t - cell lymphoma .
a 27-year - old female was admitted to our hospital because of intermittent fever with neutropenia for 7 months .
laboratory tests showed decreased white blood cell count ( 1.4    10/l ; range 410    10/l ) .
serum cancer antigen 125 was elevated ( 193  u / ml ; range < 35  u / ml ) .
mri showed an ill - defined mass involved both the uterine corpus and cervix , resulting in diffuse enlargement of the uterus .
this mass showed inhomogeneous hypointensity on unenhanced t1-weighted images , hyperintensity on diffusion - weighted imaging , relative hypointensity compared to the surrounding myometrium on t2-weighted images , and lower enhancement than the surrounding myometrium on enhanced t1-weighted images ( figure 1 ) .
, f - fdg pet / ct was performed showing intense fdg uptake in the thickened wall of the uterine corpus and cervix with suvmax of 26.9 .
there were multiple hypermetabolic lymph nodes in the pelvis and retroperitoneum ( figure 2 ) .
transverse unenhanced t1-weighted image ( a ) showed an inhomogeneous hypointense mass ( arrows ) in the uterus . corresponding transverse diffusion - weighted imaging ( b ) showed peripheral hypointensity of the mass .
saggital t2-weighted mr image ( c ) showed the mass ( arrows ) involved both the endomerium and myometrium , resulting in diffuse enlargement of the uterus .
this mass showed relative hypointensity compared to the surrounding myometrium . on transverse ( d ) , coronal ( e ) , and saggital ( f ) enhanced t1-weighted images , this mass showed lower enhancement ( arrows ) than the surrounding myometrium .
maximum intensity projection pet ( a ) showed intense fdg uptake of the enlarged uterus ( arrow ) and multiple hypermetabolic lymph nodes ( arrowheads ) in the pelvis and retroperitoneum .
transverse ct ( b , c ) , corresponding pet ( d , e ) , and fused ( f , g ) images showed intense fdg uptake in the thickened wall of the uterine corpus ( arrows ) and cervix ( arrowhead ) with suvmax of 26.9 .
ct  =  computed tomography , fdg  =  fluorodeoxyglucose , mri  =  magnetic resonance imaging , pet  =  positron emission tomography .
microphotograph revealed diffuse myometrial infiltration by small round tumor cells with multifocal coagulative necrosis ( figure 3a ) .
the tumor cells were positive for cd2 , cd3 ( figure 3b ) , cd43 , and lat , and negative for cd19 and cd20 .
the imaging and pathologic findings were consistent with primary peripheral t - cell lymphoma of the uterus ( stage , ii e ) . after 3 circles of chemotherapy , a follow - up mri showed decreased thickness of the uterine wall ( figure 4 ) .
histopathology at higher magnification ( a , hematoxylin - eosin , original magnification    400 ) revealed diffuse myometrial infiltration by small round tumor cells .
the tumor cells were positive for cd3 staining ( b , original magnification    400 ) .
a follow - up enhanced t1-weighted image showed decreased thickness of the uterine wall after 3 circles of chemotherapy .
primary uterine non - hodgkin 's lymphomas are extremely rare accounting for < 1% of all extranodal non - hodgkin 's lymphomas .
the mean age of patients with primary uterine non - hodgkin 's lymphoma at presentation is 55 years and abnormal uterine bleeding is the most frequent complaint .
the combination of chemotherapy and irradiation is the most effective treatment regimen for uterine lymphomas . on mri , diffuse enlargement of the uterus , relatively homogeneous signal intensity , and multinodular growth pattern
are helpful for diagnosing uterine lymphoma . in this case , on t2-weighted mr images , the tumor showed relative hypointensity compared to the surrounding myometrium , which may be due to the hypercellularity and less necrosis of the tumor . on diffusion - weighted imaging ,
the tumor showed remarkable hyperintensity indicating marked restricted diffusion of the water molecules due to the dense microstructure . on enhanced t1-weighted mr images , the tumor showed lower enhancement than the surrounding myometrium , which may be due to the minimal tumor angiogenesis and destroying of the normal uterine vessels .
mri may be helpful for the differential diagnosis between uterine lymphoma and uterine leiomyosarcoma or abscess . unlike uterine lymphoma , hemorrhage and necrosis are common in uterine leiomyosarcoma .
therefore , uterine leiomyosarcoma commonly manifests as a large infiltrating myometrial mass with heterogeneous hypointensity on t1-weighted mr images , and intermediate - to - high signal intensity with central hyperintensity on t2-weighted mr images .
uterine abscesses commonly show high - signal intensity on t2-weighted mr images , which is different from relative hypointensity of uterine lymphoma .
fdg pet / ct may be useful for detection , staging , and treatment evaluation of uterine lymphoma .
high - grade uterine lymphomas usually show intense fdg uptake , whereas the low - grade ones show lower fdg uptake . therefore , fdg pet / ct may be helpful for assessment of the tumor grade .
this case indicates uterine lymphoma should be included in the differential diagnosis of abnormal uterine fdg accumulation along with physiological endometrial uptake , postpartum uterus , adenomyosis , endometrial hyperplasia , leiomyoma , cervical cancer , endometrial cancer , choriocarcinoma , uterine sarcoma , and uterine metastasis . in conclusion , primary uterine non - hodgkin 's lymphoma should be taken into consideration when a uterine tumor shows large size , relative hypointensity on both t2-weighted images and enhanced t1-weighted images compared to the surrounding myometrium , and intense fdg uptake on pet / ct .
ethical approval was obtained from the ethics committee of changhai hospital , shanghai , china .
written informed consent was obtained from the patient for publication of this case report and any accompanying images .

Answer:
abstractprimary uterine non - hodgkin 's lymphoma is extremely rare accounting for < 1% of all extranodal non - hodgkin 's lymphomas .
 imaging findings of primary uterine lymphoma have rarely been reported before .
 we present magnetic resonance imaging ( mri ) and fluorine-18-fluorodeoxyglucose ( 18f - fdg ) positron emission tomography ( pet)/ct findings in a patient with primary uterine peripheral t - cell lymphoma.a 27-year - old female presented with intermittent fever with neutropenia for 7 months .
 mri showed an ill - defined mass involved both the uterine corpus and cervix , resulting in diffuse enlargement of the uterus .
 this mass showed inhomogeneous hypointensity on unenhanced t1-weighted images , hyperintensity on diffusion - weighted imaging , relative hypointensity compared to the surrounding myometrium on t2-weighted images and lower enhancement than the surrounding myometrium on enhanced t1-weighted images .
 fdg pet / ct showed intense fdg uptake in the thickened wall of the uterine corpus and cervix with suvmax of 26.9 .
 there were multiple hypermetabolic lymph nodes in the pelvis and retroperitoneum .
 uterine curettage and ct - guided biopsy of the uterine mass revealed peripheral t - cell lymphoma .
 bone marrow biopsy revealed no evidence of lymphomatous involvement .
 the imaging and pathologic findings were consistent with primary uterine lymphoma .
 after 3 circles of chemotherapy , follow - up enhanced mri showed decreased thickness of the uterine wall.despite its rarity , primary uterine non - hodgkin 's lymphoma should be taken into consideration when a uterine tumor shows large size , relative hypointesity on both t2-weighted images and enhanced t1-weighted images compared to the surrounding myometrium , and intense fdg uptake on pet / ct .
 mri may be helpful for describing the relationship between the tumor and adjacent structures .
 fdg pet / ct may be useful for tumor detection and staging .


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:
isotretinoin is a systemic synthetic retinoid used to treat moderate to severe nodulocystic acne vulgaris that is not responding to other therapies , as well as a number of other dermatologic diseases , including psoriasis , hidradenitis suppurativa , ichthyosis , lesions associated with lupus erythematosus , some cases of severe acne rosacea , and various skin cancers , or even adjunctive therapy for acute promyelocytic leukemia.1 among other adverse effects , isotretinoin has repeatedly been associated with depression , suicidality , and psychotic symptoms , although the link between isotretinoin use and psychiatric events remains controversial.2 remarkably , when affective psychosis and obsessive - compulsive disorder ( ocd ) occur following isotretinoin treatment , associated psychopathology is generally severe and eventually poorly responsive to conventional treatment , as highlighted by recent , large , retrospective studies.3 also , although patients suffering from bipolar disorder may be at increased risk for mood symptom exacerbations due to isotretinoin therapy , including suicidal ideation , even with a concurrent antimanic therapy,3 less is known about the risk for developing ex novo affective psychosis and antidepressant manic vulnerability when isotretinoin treatment is used during adolescence . furthermore , acne itself often occurs during adolescence , and can be eventually induced by lithium , a standard treatment for bipolar disorder , which , in turn , usually has its onset at the same age .
a 25-year - old caucasian male came to his first psychiatric consultation at the age of 23 years at the suggestion of his general practitioner due to complaints about intrusive obsessive thoughts starting about one year earlier .
obsessive symptoms essentially consisted of self - reproachment about his  ineptitude  in sitting academic examinations and consequent overwhelming feelings of guilt toward his parents .
there were no associated physical problems , although he reported a history of severe acne vulgaris that had been successfully treated by a dermatologist with isotretinoin 10 mg / day since the age of about 16 years .
initial evaluation led to a diagnosis of ocd , after excluding a personal or family history for psychiatric disorders .
diagnosis was also made on the basis of the mini international neuropsychiatric interview4 and yale - brown obsessive - compulsive scale,5 the total score for which was 26 ( 24 indicates severe ocd ) .
he was prescribed fluvoxamine 100 mg / day , having agreed to the proposal of dose augmentation within the following weeks .
two weeks later he had an unexpected precocious response with a marked ego - dystonic reaction , so current therapy was maintained .
more surprisingly , two weeks later , intrusive thoughts reappeared , now associated with loss , concomitant intractable delusions of grandeur , flight of ideas , and an increase in goal - directed activity ( eg , a sudden desire to start guitar lessons and to leave law school to become a theatrical agent ) .
a diagnosis of mixed state with psychotic features was made on the basis of a young mania rating scale6 total score of 24 ( 12 indicates mania , although mixed state assessment may be roughly estimated ) .
therapy was then revised , halving the antidepressant dose and adding 1200 mg / day of carbamazepine ( lithium , a neuroprotective antisuicidal drug having the potential to worsen psoriasis , and typical antipsychotic augmentation options being disregarded due to a likely lack of compliance and the patient s concerns about potential dermatologic recurrences ) . despite the proposal of cognitive behavioral therapy augmentation or other nonpharmacologic interventions , the patient refused to take advantage of any therapy likely to be free of side effects , apparently for compliance reasons . after a further month
the patient had a relapse of obsessive symptoms , with a substantial persistence of elation ( despite considerably high carbamazepine serum levels , usually increasing by up to 60% in case of fluvoxamine coadministration ) , so he was prescribed fluvoxamine 25 mg / day and olanzapine 5 mg / day .
doses were then increased every three weeks , reaching a final amount of 300 mg / day and 15 mg / day , respectively .
both obsessive and mood symptoms progressively remitted until almost complete resolution was observed six months later .
patients with ocd and related disorders , eg , body dysmorphic disorder , may have excessive concern about minor variations in skin color or texture , ordinary moles , or thinning hair.7 a minority of cases , eg , some patients with severe psychotic body dysmorphic disorder and acne vulgaris , may abuse dermatologic drugs and cosmetics to inhibit normal seborrhea , as in the  dorian gray syndrome  ( dream of eternal youth ) , eventually increasing the risk of long - term development of other psychiatric disorders , including affective psychosis.8 on the other hand , acne , alopecia areata , atopic dermatitis , and psoriasis may be associated with psychiatric conditions such as depression and suicidal ideation , as well as with the use of some psychotropic medications , possibly suggesting a substantial immunoneuroendocrine overlap.9 nonetheless , when a psychiatric comorbidity is diagnosed , patients seeking dermatologic care may interpret a suggestion to see a psychiatrist as indicating that the dermatologist thinks they are  crazy  or wants to get rid of them , thereby further reducing the chance of appropriate treatment . concerning the relationship between isotretinoin and the potential for subsequent onset of psychopathology ,
positive dechallenge and rechallenge cases have been reported , prompting physicians to look out for the onset or worsening of psychiatric symptoms , including bipolar disorder.10,13 nonetheless , the neurotoxicity of the synthetic retinoic acid analogs is supported by a considerable body of literature .
in fact , retinoids may lead to a decrease in dopaminergic orbitofrontal functioning via their effect on the hippocampus , which modulates dopaminergic function in the medial prefrontal cortex .
retinoic acid - induced deficits in hippocampal function may lead to a downstream effect on orbitofrontal function .
however , evidence regarding the effects of retinoic acid in the serotonin pathways is controversial , although higher doses have resulted in decreased or complete loss of serotonergic neurons.1 this finding has psychiatric implications because the prefrontal dopaminergic imbalance may be closely associated with depression .
recent evidence from positron emission tomography studies in human subjects showed isotretinoin to be associated with a decrease in orbitofrontal metabolism , which is known to play a major role in the symptomatology of both ocd and bipolar disorder .
in fact , the molecular components required for retinoic acid signaling are expressed in the adult brain , and the overlap of brain areas implicated in retinoic acid function , stress , and depression suggests that retinoids could play a role in affective and anxiety disorders,14 which are often comorbid . in this case , the choice of the selective serotonin reuptake inhibitor fluvoxamine was based on its proven efficacy in ocd and on its modulatory effects on -1 receptors , which might increase the antipsychotic effect of atypical antipsychotic drugs , possibly contributing to the early psychotic resolution showed by the patient described here.15,16 naturally occurring neurosteroids , as well as many psychotropic drugs , bind to -receptors , which may mediate some neuroprotective action , including mood and cognition improvement.17,18 although olanzapine and other atypical antipsychotic augmentation strategies for selective serotonin reuptake inhibitor - refractory , psychotic ocds and/or concomitant mood disorder are supported by an increasing body of literature,19,20 the choice of a single agent is often difficult.21 given their higher affinity for 5-ht2a receptors than for dopamine receptors , it has been speculated that atypical antipsychotics may induce ocd , even at low doses , due to high 5-ht2a antagonism , whereas improvement is thought to occur only at high doses in response to high dopaminergic antagonism.22 the choice of olanzapine augmentation for fluvoxamine therapy was also suggested by pharmacokinetic considerations .
fluvoxamine increases the olanzapine plasma concentration by approximately two - fold via cyp1a2 inhibition . on the other side , the alternative strategy of adding carbamazepine ( even at low doses ) to fluvoxamine and olanzapine
was discounted for compliance reasons . moreover , the patient did not originally show a satisfactory response to this antiepileptic drug even at 1200 mg / day ( whereas olanzapine was indeed more effective , especially in reducing psychotic features ) .
there were also pharmacokinetic considerations in the decision not to add carbamazepine , because it increases the renal clearance of olanzapine by about 45% and reduces the half - life of olanzapine by about 20%.23 in this case , the unusually rapid exacerbation on antidepressants , as well as the presence of plausible iatrogenic - induced depression with flights of ideas,24 pointed to a bipolar diathesis related to previous treatment with isotretinoin , suggesting the switch to an atypical antipsychotic that is associated with a rapid positive antipsychotic response .
indeed , antidepressant lability could occur even without any previous or current isotretinoin exposure , and it may be difficult to discriminate whether mood switches and rapid exacerbation phenomena are due to isotretinoin or not .
it is noteworthy that the patient had no prior familial or personal predictors of bipolar disorder , including during adolescence , which is the usual age of onset .
moreover , in this case it is remarkable that even a considerable dose of carbamazepine was not able to prevent the mood switch . also ,
the use of antidepressants such as fluvoxamine in the course of mixed states is debatable , although they are apparently well established in the management of ocd symptoms .
although the demonstration of a def initive causal relationship between isotretinoin use and increased risk for subsequent ocd development characterized by iatrogenic vulnerability for affective psychosis is beyond the scope of this report , the modern pathogenic concept of the vulnerability stress model25 ( with isotretinoin considered an essential stress factor ) of psychiatric disease may prompt further controlled research on this association .
finally , in addition to the suggestion of a relationship between isotretinoin and psychiatric disorders , this case report suggests that we should consider carefully both the course of illness and psychopharmacologic choices for patients reporting long - term use of isotretinoin during adolescence and complicated by ocd .

Answer:
isotretinoin , a drug used for moderate to severe acne , has been repeatedly associated with various psychiatric complications , although a definitive causal relationship has not been established to date .
 this case report describes a 25-year - old male who developed obsessive - compulsive disorder at the age of 23 years following isotretinoin treatment for acne ( 1020 mg / day ) since the age of 16 years .
 although standard treatment for obsessive - compulsive disorder caused mood swings , the combination of fluvoxamine 300 mg / day and olanzapine 15 mg / day significantly improves the clinical picture .
 although rare , severe adulthood psychiatric complications may occur following isotretinoin treatment , requiring management which is individually tailored to the patient .


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:
colloidal iv  vi semiconductor nanocrystals ( also known as quantum dots , qds ) are of increasing potential applications in telecommunication , photoelectronic device , and biomedical labeling , etc .
pbse qds are important materials because of the strong confinement effect due to their large bohr radius and the small band gap in near infrared region .
several approaches have been developed to prepare pbse qds with uniform size and high quantum yields [ 3 - 5 ] .
pbse / pbs   and pbse / sio2 core / shell structures have been synthesized to stabilize pbse qds .
but cdse should be a better shell material due to the higher stability under air condition , the lower lattice mismatch of ~1% , and the little change of the surface chemistry and physics .
it is difficult to grow cdse shells upon pbse cores using typical cadmium oleate anion precursor because of high reaction temperatures needed .
hollingsworth s group recently developed a method of ion exchange to form pbse / cdse core / shell structures in which cd atoms replaced pb atoms in the outlayers of large pbse qds .
however , it may not be easy to control the thickness of the cdse layers . in this work , we employed the  successive ion layer adsorption and reaction ( silar )  technology   to form air - stable pbse / cdse qds with strong photoluminescence
two solutions were prepared for cdse shell growth . a cadmium injection solution ( 0.04 m )
was prepared by heating cadmium cyclohexanebutyrate ( 0.1804 g ) in oleyamine ( 8.130 g ) at 60c under n2 flow to obtain a clear colorless solution . a selenium injection solution ( 0.04 m )
was prepared by mixing selenium powder ( 0.0316 g ) in octadecene ( 7.880 g ) at 220c under n2 flow until a clear yellow solution was obtained .
, pbse qds ( 4.8 nm in diameter , 1.01  10 mmol of particles ) dispersed in 5 ml of hexanes were loaded into a 25-ml three - neck flask and mixed with 1.500 g of octadecylamine and 5.000 g of octadecene .
a mechanical pump was employed at room temperature for 30 min to remove hexanes from the flask .
then , the predetermined amounts of the cadmium and selenium solutions were alternatively injected into the three - neck flask drop by drop with syringes using standard air - free procedures .
transmission electron microscope ( tem ) was used to characterize pbse and pbse / cdse core / shell qds as shown in fig .
1 . tem images and histograms of 4.8 nm pbse ( a , b ) and 6.2 nm pbse / cdse ( c , d ) qds .
the pbse and pbse / cdse qd samples shown here have narrow size distributions of 8.1% ( b ) and 6.9% ( d ) , respectively figure 2 shows the evolution of absorption and photoluminescence spectra of the pbse / cdse qds upon the series growth of three monolayers of cdse shells on the 4.8 nm pbse cores .
a consistent red shift of the peak wavelength was observed in both the absorption and pl spectra .
the red shifts of the first excitonic absorption peak for three layers were 11 , 10 , and 11 nm , respectively .
the red shift of absorption and pl spectra depends on several factors including ( 1 ) the connection between pbse and cdse renders the expansion of the carriers wavefunctions out of the core region with different expansion probabilities resulting in the increase of exciton distance and ( 2 ) the surface polarization due to the different dielectric constants of pbse and cdse materials . absorption ( a ) and photoluminescence ( b ) spectra recorded during cdse shell growth . a consistent red shift of the peak wavelength ( 11 , 10 , 11 nm ) was observed when one to three monolayers of cdse shells grown on 4.8 nm pbse cores the optical gap ( egap ) of pbse qds is the minimum energy needed to excite an electron from the valence band to the conduction band .
the optical gap is given by   where   are bulk material kinetic energies of the electron and hole , respectively ;   is band gap of bulk material ;   are the confinement kinetic energies of electron and hole , respectively ;   are the surface - polarization energies of the electron and hole , respectively ; and jeh is the direct electron
the size of the pbse qds ( 4.8 nm ) is much smaller than the bohr radius ( 46 nm ) ; therefore , in the strong confinement realm , the energy difference between the electron and hole should be as followed   where r is the radius of quantum dot particle ; and mr is the reduced mass of the electron and hole .
the energy of coulomb attraction is given by where   are the wavefunctions of the electron and hole , respectively ; and   is the potential function of the electron and hole .
the surface - polarization energies of the electron and hole are where   is the surface polarization potential where   is the screened coulomb potential of the qd at point   due to a point charge located at   and   is the same quantity in the corresponding bulk material system .
when two semiconductors contact , both electron and hole will induce tunnelling effect and the wavefunctions will diffuse into cdse shells .
the transmission coefficient can be given as   where e is energy barrier at the interface of core / shell structure ; m is the effective mass of diffusing particle ; a is the thickness of energy barrier . because the wavefunctions diffuse into shells , the confinement energy will change with the increase in shell thickness . according to eq .
2 , where t is the difference of transmission coefficients of electron and hole . from the energy levels shown in fig .
3[16 - 18 ] , the expansion probability of electron is bigger than that of hole because of the lower barriers of electron according to the very closed effective masses of electron and hole ( me = 0.070 , mh = 0.068 ) . in this case
, one nanometer shell barrier will result in a decrease in 17.55 mev for the confinement energy .
we have also calculated that the increase in coulomb energy is 0.068 mev for one nanometer barrier .
correspondingly , the red shifts of the first excitonic absorption peak for three individual monolayer cdse shells are counted as 10.81 , 9.45 , and 8.36 nm , respectively .
they are in good agreement for the experimental data taking account of the effect of surface polarization energy .
lumo and homo structures for 4.8 nm pbse qds and 0.35 nm cdse shell the third term in eq .
1 is the surface - polarization energy that affects the gap energy egap , which is the stark effect .
a certain number of defect states are expected on the surface of unpassivated pbse qds .
therefore , charge carriers trapped on or near the surface of qds may generate localized electric fields , where delocalized exciton states within the qds can be highly polarizable .
the surface polarization energy   versus local electric field  is given by   where  and  are the resolved exciton dipole and polarizability , respectively .
according to muller et al.s work , the spectrum shift of cdse nanorods depends on the direction of the external electric field .
the positive electric field induces red shift , and the negative one leads to blue shift .
since the qds in this work are spherical ( zero dimensional ) , it is reasonable that their peak shifts are independent of the direction of the electric field .
both positive and negative electric field can cause the emission peak to red shift , and the red shift increases when the electric field is stronger .
it has been known that unpassivated pbse qds surface is a pb atom - rich shell .
therefore , there may be polarization charges on the surface of pbse qds which generate surface - polarization energy .
however , the polarization charges are neutralized , because pb atoms on the surface of pbse qds connect to oleic acid ( the organic ligand used in the synthesis ) .
when the pbse / cdse core / shell was synthesized , cdse contacted with pb atoms instead of oleic acid ; this induced the increase of surface polarization charges .
the spectra shift to red because of the enhancement of the stark effect ( fig .
different crystal lattices and thermal expansivities for pbse and cdse will more or less induce surface defects at the interface of the two materials . the carriers will be trapped and result in the enhancement of the stark effect .
such local fields cause the first exciton peak to shift to red and suppress the emission strength due to a reduced electron  hole wavefunction overlap .
unbalanced charges may also decrease the photoluminescence efficiency ( quantum yield ) via nonradiative auger recombination .
the new traps were induced by surface defects depend on the shell growth . compared with the photoluminescence of one monolayer core / shell qds ,
however , it was found that more shell layers resulted in a decrease in photoluminescence strength ( fig .
that is also because the tensile change at the interface is nonlinear with the shell thickness .
when pbse qds were covered with two layers of cdse , the good lattice tensility at the interface reduced the lattice mismatch and therefore increased the photoluminescence strength .
when pbse qds were covered by three layers of cdse , the lattice tensility was stronger and hence the photoluminescence strength decreased .
even so the quantum yield was still as high as 70% for our pbse / cdse core / shell qds ( ir-26 as the reference ) .
pbse qds are unstable even under the ambient conditions ( room temperature and room light in air ) ( fig .
this process for each particle induces the effective particle size decrease and the blue shift of the spectrum .
when the old oxidized surface is gone , the new surface will be oxidized quickly . for pbse
/ cdse core / shell structures , cdse shells effectively prevent pbse cores from the quick oxidation .
the lifetime of pbse qds under ambient conditions therefore can be extended from a few days to at least a month ( currently available data ) .
the stability of pbse ( a ) and pbse / cdse ( b ) qds .
the cdse shells prevent pbse core from the destructive oxidation . compared with the unstable pbse core ,
the pbse / cdse qds remained unchanged in conclusion , pbse / cdse core / shell qds with a quantum yield of 70% were synthesized .
the surface polarization and the expansion of carriers wavefunctions contributed to the spectral red shift .
the spectra red shifts during the formation of cdse shells were calculated , and they exhibited a good fit to the experimental data .
the funding supports from the state key laboratory on integrated optoelectronics , college of electronic science and engineering , jilin university , the worcester polytechnic institute , and the national 863 projects of china ( 2007aa03z112 , 2007aa06z112 ) are acknowledged .
this article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited .
this article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited .

Answer:
pbse / cdse core / shell nanocrystals with quantum yield of 70% were obtained by the  successive ion layer adsorption and reaction  technology in solution .
 the thickness of the cdse shell was exactly controlled .
 a series of spectral red shifts with the cdse shell growth were observed , which was attributed to the combined effect of the surface polarization and the expansion of carriers wavefunctions .
 the stability of pbse nanocrystals was tremendously improved with cdse shells .


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:
  interhemispheric connections are essential components of the complex neural network in eutherian animals [ 1 , 2 ] . among such connections ,
the corpus callosum ( cc ) is the most prominent commissural connection , composed of callosal axons , in the brain . in humans ,
the corpus callosum consists of about 200 million axons , making it the most prominent fiber tract within the central nervous system [ 3 , 4 ] .
many studies have clarified the molecular mechanism involved in the development of the cc in humans using mouse experiments .
callosal neurons are mostly found in layers ii / iii and layer v of the cerebral cortex in rodents .
recently , molecules related to the identities of the general or subtypes of cortical neurons have been disclosed .
alcamo et al . reported that satb2 , a dna - binding protein , has a key role in the specification of callosal neurons and the formation of corticocortical connections .
developmentally , callosal axons from layer v first start to project to the contralateral targets , and callosal axons from the upper layers follow the preexisting axons .
after the callosal axons start to elongate , they are guided by many cues within their pathfinding route .
although the importance of such cues in the development of callosal axons has been known for over 30 years , it still remained unclear until recently how these cues help callosal axons encountering them to project precisely to their targets .
recent studies have , however , revealed the detailed mechanisms in the regulation of axon guidance by these structures .
midline structures , which consist of glia and neurons , express or secrete short- or long - range guidance molecules . in the contralateral cortex , where the callosal axons terminate
, interactions with postsynaptic neurons play important roles , in an activity - dependent manner , in ensuring proper projections [ 1012 ] .   in this paper , we first focus on how the callosal axons are guided by the cues that they encounter , namely , the ( 1 ) midline structures and ( 2 ) neighboring axons , from the time that they start to grow until they reach their targets in the contralateral cortex . then , we describe the activity - dependent development of the interhemispheric connections .
the midline structures mainly consist of glial populations , but also contain neuronal populations . the role of the midline glial structures in the formation of the cc
in the mouse brain , these glial structures have been shown to already exist on embryonic day ( e ) 15.0 and can guide the growth of callosal axons [ 8 , 14 , 15 ] .
the midline glial structures mainly consist of four structures : the glial wedge ( gw ) , the indusium griseum ( ig ) , the midline zipper ( mz ) , and the glial sling ( gs ) [ 8 , 16 ] ( figure 1 ) .
the mz is thought to be required for the fusion of the two hemispheres , which facilitates the passage of axons across the midline [ 9 , 17 ] .
the other structures are responsible for promoting the crossing of at least the callosal axons [ 1823 ] .
these structures help the callosal axons find their correct path by secreting or expressing guidance molecules .
interestingly , shu and richards have illustrated that correct orientation as well as the presence of the gw is required for callosal axons to turn toward the midline ; in one experiment , when the gw was replaced with 180 rotation ( medial to lateral ) , the axons turned away from the midline .
studies have gradually uncovered the molecules secreted by the midline structures for callosal axon guidance .
the axon guidance cues for callosal neurons secreted by the midline structures have been classified into two types : long range ( figures 2(a)2(c ) ) and short range ( figure 2(d ) ) .
the long - range guidance molecules are secreted by the midline glial populations , forming a concentration gradient and helping callosal axons pass through the cc with attractive ( figure 2(a ) ) and repulsive signals ( figures 2(b ) and 2(c ) ) .
slits [ 15 , 24 , 25 ] , wnts , netrins [ 27 , 28 ] , draxin , and semaphorins   are some of the reported long - range guidance molecules .
have suggested a novel role of slits in regulating the positioning and maturation of the midline glial populations , presumably independent of the activity of its receptor , robo1 , in addition to its role as a repulsive axon guidance cue . wnt5a
not only promotes axon outgrowth as a long - range guidance molecule , but also serves as a short - range repulsive axon guidance cue [ 32 , 33 ] .
in addition to the midline structures , other cell populations have also recently been shown to play roles in the formation of the cc .
gabaergic and glutamatergic neurons that transiently exist within the cc have been shown to be able to attract callosal axons .
the meninges have also been reported to be involved in the development of the cc .
bmp7 secreted by the meninges has been shown to inhibit the outgrowth of callosal axons , potentially preventing early formation of the cc .
the short - range molecules guide axons through transmembrane or membrane - associated proteins ( figure 2(d ) ) .
eph receptors are divided into two subclasses , a and b , according to the sequence homology and binding affinity for their ligands , ephrins a and b , respectively [ 36 , 37 ] .
although the ephrin / eph system signals through eph tyrosine kinase receptors , ephrins can also transduce reverse signals into the cell in which they are expressed . the ephb receptors and ephrin b ligands
have been well studied and shown to play important roles in callosal axon pathfinding [ 39 , 40 ] .
importantly , the complementary expression of multiple ephrin b ligands and ephb receptors in the callosal axons and midline structures has led to the hypothesis that interactions occur between the eph receptors in callosal axons and ephrins in the midline structures or vice versa , although it is also possible that the interactions occur between callosal axonal fibers .
the expression of ephrin b ligands in the callosal axons is suggestive of the involvement of reverse signaling , and bush and soriano showed that ephrin - b1 reverse signaling is critical for callosal axon pathfinding , which requires the binding of the psd-95/dlg / zo-1 ( pdz ) domain - containing proteins for the transduction of this reverse signal .
   pioneer  neurons represent one of the most important players in callosal axon guidance by other preexisting axons during cc development . on e15.5 in mice , the axons of the pioneer neurons , which originate from the cingulate cortex ,
cross the midline and enter the contralateral cortex ( figure 3(a ) ) [ 42 , 43 ] .
it has been shown that cc genesis is triggered by these pioneer axons [ 39 , 4245 ] ; pioneer axons are the first to form the path for the commissural neurons through interactions with several cues , including the midline structures , and on e17.0 , the most early  follower  axons from layer v follow those of these pioneer neurons [ 42 , 43 , 46 ] ( figure 3(a ) ) .
an accepted view is that the  follower  axons utilize their direct interactions with the  pioneer  axons to find their correct path of growth , although the molecular mechanism of such interaction remains unclear .
interestingly , piper et al . described the molecular mechanisms driving the guidance of the cortical pioneers during development .
they demonstrated that neuropilin 1 expressed on the cingulate pioneers plays a crucial role in the crossing of the midline by the  pioneer
while many studies have revealed the indispensable roles of the interactions between the callosal axons and the midline structures , it is still unclear whether axon - axon interactions play important roles in callosal axon pathfinding .
although increasing evidence has revealed the importance of these interactions in other systems , such as the retinal , spinal and olfactory systems [ 4750 ] , the involvement of such axon - axon interactions in cc development remains to be explored in detail .
have recently reported repulsive interactions between callosal axons originating from the medial and lateral cerebral cortices ( figure 3(b ) ) .
based on a previous study by the same group , they focused on epha3 , which is preferentially expressed in the callosal axons from the lateral cerebral cortex , and found that knockdown of epha3 in the lateral cortical axons resulted in their disorganized segregation in the cc and disrupted axon pathfinding .
they have suggested that epha3 mediates , at least in part , the repulsive interactions between the medial and lateral cortical axons .
so far , several studies using knockout and transgenic mice have identified molecules involved in the development of the cc . however , as knockout and transgenic mice show influences of all developmental stages , analyses of these mutant mice are not necessarily sufficient for describing the primary causes of the abnormal phenotypes .
recent studies using in utero electroporation   and various culture experiments , including the stripe assay [ 37 , 54 , 55 ] , have enabled reasonably easy analysis of each specific stage of cc development .
further experiments focusing on each step of development will be essential to understand the entire process of formation of the cc .
to eventually establish interhemispheric connections through the cc , reshaping of the axons is also crucial .
the callosal connections are initially exuberant and brushed up by the selective death of neurons and withdrawal and degeneration of axonal collaterals . since callosal axons start to establish synapses with specific postsynaptic neurons after entering the contralateral hemisphere [ 39 , 57 ] , the involvement of synaptic activity - dependent mechanisms ( as well as nonsynaptic activities ) in this process of reshaping of the axons has been shown by many studies [ 57 , 58 ] . in the visual system , for example , the stimuli from the eyes contribute to the formation of the precise patterns of callosal axonal connections [ 59 , 60 ] .
importantly , although the callosal axons are generally believed to have a simple mirror projection across the cc in the contralateral hemisphere , there are also heterotopic callosal projections . in addition
, the tangential distribution of the callosal axon projections is not even in the adult cortex .
for example , the callosal connections are highly focused at the level of the primary areas .
while these might possibly be established during the later development of the callosal axon projections ( i.e. , refinement and elimination ) , establishment of such uneven projections in the early phase of development can not also be ruled out .
recently , synaptic and non - synaptic activities have also been reported to be involved in the regulation of different aspects of development of the callosal projections besides reshaping of the axons .
blockade of the spontaneous electrical activity of the callosal neurons resulted in abnormal projections in the somatosensory cortex   and visual cortex .
interestingly , blockade of the spontaneous electrical activity of projection neurons such as the motor and olfactory neurons also influenced a variety of guidance and adhesion molecules that are critical for their development [ 6163 ] , suggesting that spontaneous electrical activity of the axons may also have some role in axon guidance .
  as described above , a number of different control mechanisms are involved in the development of the interhemispheric connections , and disruption of any of these mechanisms may cause malformations of the cc .
some examples are knockout mice lacking some of the molecules involved in the formation of the midline glial structures [ 1923 ] , gabaergic neurons [ 34 , 64 , 65 ] or pioneer neurons , or the axon guidance mechanism
. phenotypes of such knockout mice are quite varied and range from hypoplasia or partial dysgenesis of the cc to complete dysgenesis and formation of probst 's bundles [ 40 , 67 ] , which are also observed in partial dysgenesis .
a comparison between mice and humans revealed many similarities in the development of the cc between the mouse brain and human brain .
not only are the midline glial structures conserved in humans , but also the expression profiles of the molecules known to be involved in the formation of the cc are similar between human and mouse brains [ 9 , 69 , 70 ] .    in humans , several psychiatric , neurologic , and metabolic disorders have been shown to be associated with congenital agenesis of the cc or the surgical procedure , callosotomy [ 5 , 71 , 72 ] . among the famous of these reports is the story of the patient with callosotomy who could not verbally describe the stimulation presented to his freshly disconnected right hemisphere . in subjects with complete dysgenesis of the corpus callosum ,
paul et al . described that despite having normal iq , individuals with complete dysgenesis of the cc show impaired social intelligence , analyzing their responses to pictures from the thematic apperception test .
moreover , many studies have reported that major mental disorders , such as autism , attention deficit hyperactivity disorder ( adhd ) , and schizophrenia , may be related to the morphology of the cc [ 7476 ] .
however , the precise nature of these associations remains unclear . how could malformations of the cc have any relation to these disorders ? do the genes associated with these disorders play a role in normal cc development ?
future studies on the development of the cc may help elucidate the precise nature of these associations .
  by integrating information between the right / left hemispheres , interhemispheric connections enable us to accomplish higher brain functions .
development of interhemispheric connections such as the cc is guided by molecules in the axonal environment , under the regulation of a number of different control mechanisms .
it would be of great interest to conduct detailed investigation of the mechanisms underlying cc development , especially in view of their relevance in the pathogenesis of human disorders .

Answer:
numerous studies have investigated the formation of interhemispheric connections which are involved in high - ordered functions of the cerebral cortex in eutherian animals , including humans .
 the development of callosal axons , which transfer and integrate information between the right / left hemispheres and represent the most prominent commissural system , must be strictly regulated . from the beginning of their growth , until reaching their targets in the contralateral cortex , the callosal axons are guided mainly by two environmental cues : ( 1 ) the midline structures and ( 2 ) neighboring ?
 axons .
 recent studies have shown the importance of axona guidance by such cues and the underlying molecular mechanisms . in this paper , we review these guidance mechanisms during the development of the callosal neurons .
 midline populations express and secrete guidance molecules , and  pioneer
 axons as well as interactions between the medial and lateral axons are also involved in the axon pathfinding of the callosal neurons .
 finally , we describe callosal dysgenesis in humans and mice , that results from a disruption of these navigational mechanisms .


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:
an hiv - negative male , in his sixties , originally presented with a 6-month history of an isolated large nodule on the right malleolar region which was confirmed as kaposi 's sarcoma ( ks ) on excision .
subsequently he continued to develop more papules and plaques on the feet and over the following 7 years underwent excision of around 20 skin lesions under local anaesthesia .
more recently he developed , simultaneously , a crop of 5 nodules and a large plaque of ks 5.5 cm in diameter on the dorsum of the right foot with extension to the interdigital spaces and toes ( fig . 1a , fig .
chemotherapy with intravenous liposome - encapsulated doxorubicin was not considered because of the significant comorbidities including mild to moderate heart failure .
therefore , in the following order , we tried two courses of photodynamic therapy , imiquimod 5% cream applied once daily for 8 weeks and a cycle of anti - herpes therapy based on valganciclovir .
it was decided to administer intralesional vinblastine 1 mg / ml diluted 1:5 with saline solution . however , the patient developed side effects such as general malaise , swelling and erythema of the perioral and periocular areas and tingly tongue after the first injection , in keeping with a possible allergic reaction .
at that point , at a bit of a loss for options , we switched to doxorubicin . following a serial dilution test from 1:20 to undiluted ,
this medication was used intradermally at the dose of 2 mg / ml diluted 1:1 with saline solution . the large ks plaque on the dorsum of the right foot
was treated by spacing the intradermal injections every 5 mm , using a similar technique to that used in the treatment of axillary hyperhidrosis with botulinum a toxin .
the treatment led to complete resolution of the ks lesions after 4 treatments spaced 6 weeks apart .
we observed skin necrosis in some well - delimited areas following each injection ( fig .
1b ) , associated with mild to moderate pain which was well controlled with paracetamol 1,000 mg twice daily .
the patient has not developed any new lesions for almost 18 months and continues to remain clear ( fig .
ks is an angioproliferative disease associated with human herpesvirus 8 . the classic variant of ks is characterised by a low mortality and significant morbidity , and treatment needs to be finely balanced between these two aspects . to date
, a curative treatment has yet to be found and therapeutic management includes surgery , radiotherapy , chemotherapy or a combination of all of the above .
although in recent years numerous agents such as thalidomide , imatinib , sirolimus as well as matrix metalloproteinase inhibitors ( col-3 ) , anti - angiogenic factors ( bevacizumab ) and nf-b inhibitors ( bortezomib ) have been tried , the outcome of these treatments remains unsatisfactory .
liposomal anthracyclines ( pegylated or liposomal daunorubicin or doxorubicin ) and taxanes such as paclitaxel therefore remain the cornerstones of systemic therapy against ks .
doxorubicin acts through intercalation of double - stranded dna bases and by inhibiting dna topoisomerase ii whose activity is markedly increased in proliferating cells .
it represents a particularly effective treatment for widespread ks as it accumulates in highly vascularised lesions .
common agents for intralesional use in ks include interferon alpha , and more recently vincristine and vinblastine .
although intralesional doxorubicin is a standard treatment for ks in some centres , there are no publications showing the effectiveness of this treatment in ks .
intralesional doxorubicin was very successful in this case and the persistent remission induced would suggest that doxorubicin might be equally or even more effective than other standard intralesional treatments for ks cutaneous lesions in selected cases . further studies with a large cohort of patients could be helpful to clarify the impact of intralesional doxorubicin in ks .

Answer:
classic kaposi 's sarcoma ( ks ) is a disease with low mortality but high morbidity .
 the optimum treatment of ks depends upon several factors , including location of lesions , disease progression , severity of symptoms and patient preference .
 we report the long - term response to the use of intralesional doxorubicin to successfully treat a large cutaneous lesion of ks on a patient refractory to traditional treatments .


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:
experimental groups of 20 ( 4- to 6-week old ) c57bl/6 female mice ( charles river , l'arbresle , france ) were injected intracerebrally with 20 l of 10% ( weight / volume ) homogenates per mouse prepared from brain stem samples of 3 cattle tse isolates .
two of the isolates were characterized , as previously described ( 7 ) , by a higher molecular mass of unglycosylated prp ( h - type isolates ) and labeling with p4 monoclonal antibody ( table ) .
mice were housed and cared for in an appropriate biohazard prevention area ( a3 ) according to european ( directive 86/609/eec ) and french ethical committee ( decree 87848 ) guidelines .
mice were checked at least weekly for neurologic clinical signs and were killed when they exhibited signs of distress or confirmed evolution of clinical signs .
the whole brain of every second mouse was frozen and stored at 80c before western blot analysis .
frozen mouse brain tissues and fixed brain tissues were examined by western blot analysis and immunohistochemical tests as previously described ( 12,13 ) .
prp extracted from half of whole brain was detected with monoclonal antibodies sha31 ( 1:10 from tesee sheep / goat western blot , bio - rad , hercules , ca , usa ) ( 14 ) and 12b2 ( 340 ng / ml ) ( 15 ) . these antibodies are directed against the 144-wedryyre-151 and 88-wgqgg-92 murine amino acid prp sequences , respectively .
antibody 12b2 , which has an n - terminal specificity similar to that of monoclonal antibody p4 , shows poor binding to bse - derived prp , but unlike p4 , binds with high affinity to prion protein from most mammalian species , including mice and cattle .
bound antibodies were detected by using enhanced enzymatic chemiluminescence ( amersham , little chalfont , uk ) or supersignal ( pierce , rockford , il , usa ) and visualized either on film ( biomax , eastman kodak , rochester , ny , usa ) or directly in an image analysis system ( versadoc , bio - rad ) .
molecular masses of prp glycoforms were determined as the average of the center positions of the bands from at least 3 repeated electrophoretic procedures , as measured by comparison with a biotinylated marker ( b2787 , sigma , saint louis , mo , usa ) included on each gel .
immunologic reactivities of antibodies 12b2 and sha31 were compared in western blots run in parallel with the same samples with both antibodies .
after intracerebral injection of cattle brain samples into c57bl/6 mice , disease was observed in mice with the 2 h - type isolates , as well as with the bse sample .
survival periods of mice and results of prp detection among mice analyzed by western blot are shown in the table .
western blot analysis of prp from h - type  infected mouse brains in comparison with bse - infected mice is shown in figure 1 .
this pattern showed higher molecular mass prp glycoforms in mice infected with h - type isolates than in mice infected with a typical bse agent ( 1.1- to 1.5-da difference in the unglycosylated prp ( figure 1a ) .
studies of prp protease cleavage showed that only the prp of mice infected with h - type isolates was recognized by antibody 12b2 ( figure 1b ) .
this finding is in contrast to the result obtained with monoclonal antibody sha31 directed against an epitope in the central region of the protein , which showed that the 12b2 epitope was preserved in h - type  infected mice .
thus , the molecular features of h - type cattle isolates , which are distinct from those of the bse agent , were maintained after development of disease in mice .
western blot analysis of disease - associated prion protein ( prp ) from proteinase k  treated brain homogenates of c57bl/6 mice infected with type h ( lanes 2 and 4 ) or bovine spongiform encephalopathy isolates ( lanes 3 and 5 ) .
prp of mice infected with an experimental scrapie strain ( c506m3 ) ( 6 ) was used as a control ( lane 1 ) .
monoclonal antibodies used for detection of prp were sha31 in panel a and 12b2 in panel b. lane m , molecular mass markers : 39.8 , 29 , 20.1 , and 14.3 kda .
histopathologic analysis showed vacuolar lesions in the thalamus ( figure 2a ) that were absent from the hypothalamus , cochlear nucleus , and superior collicules .
these 3 neuroanatomic sites were severely affected in c57bl/6 mice brain after primary passage of the bse agent as we and others have reported ( 1 ) .
abnormal prp was detected only in amyloid plaques ( figure 2b ) , in contrast to what was reported after bse transmission in c57bl/6 mice ( 1 ) .
a ) characteristic vacuolar lesions in the thalamus ( hematoxylin and eosin stained , scale bar = 60 m ) .
b ) immunohistochemical analysis of prion protein with monoclonal antibody 12b2 ( diluted 1:200 ) shows the absence of granular deposition , but the presence of plaques in the thalamus .
the inset shows that plaques are amyloids since they bind congo red and show birefringence in polarized light ( scale bar = 60 m , scale bar in inset = 16 m ) .
our data show that the recently identified bovine h - type isolates involve an infectious agent that can induce development of a disease across a species barrier , while maintaining the specific associated prp molecular signature .
this evidence in favor of a new bovine prion strain in cattle suggests that bse is not the only transmissible prion disease in cattle .
these cases suggest either the existence of alternative origins of such diseases in cattle or phenotypic changes of prp after infection with the bse agent .
however , based on analysis of molecular features of prion diseases in cattle , this situation is similar to that in humans ( 5 ) , in which different subtypes of sporadic creutzfeldt - jakob disease agents are found .

Answer:
we previously reported that cattle were affected by a prion disorder that differed from bovine spongiform encephalopathy ( bse ) by showing distinct molecular features of disease - associated protease - resistant prion protein ( prpres ) .
 we show that intracerebral injection of such isolates into c57bl/6 mice produces a disease with preservation of prpres molecular features distinct from bse .