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:
patient 1 , a 55-year - old man who had received a diagnosis of ankylosing spondylitis 7
                 years previously , was admitted to laikon hosptal , athens , greece , in may 2005 for
                 evaluation of encrusted vesicular lesions on the face .
the patient had been receiving nonsteroidal antiinflammatory agents
                 until 12 months before admission , when his medications were changed to infliximab ( 3
                 mg / kg ) plus methotrexate ( 10 mg weekly ) because of his deteriorating clinical
                 condition .
he was living in a leishmaniasis - endemic area in athens , had no pets in
                 his house , and had no history of recent travel abroad .
the central scale was removed
                 from one of the lesions , and scrapings from the base of the lesion were stained with
                 giemsa stain , which showed intracellular amastigotes with peripheral nuclei and
                 rod - shaped kinetoplasts .
results of indirect immunoflorescent antibody ( ifa ) testing
                 were positive for leishmania parasites ( titer 6,400 ) .
infliximab
                 and methotrexate therapy was discontinued , and treatment with liposomal amphotericin
                 b was started at a dose of 3 mg / kg , for days 1 to 5 , and 2 additional doses ( 3
                 mg / kg ) on days 14 and 21 .
eighteen months later , treatment with etanercept was begun
                 due to the patient s severe spondyloarthritis ; 2 years after the new
                 anti - tnf treatment , he is well , with no signs or symptoms of leishmaniasis .
patient 2 , a 71-year - old woman who had giant cell arteritis , was admitted to the
                 euroclinic hospital , athens , in may 2005 with a high fever and fatigue .
the patient
                 had been treated with infliximab ( 0.25 mg / kg ) and variable doses of
                 methylprednisolone for the previous 2 years .
she was also living in an athens suburb , which is
                 leishmaniasis - endemic , and had 4 dogs .
laboratory tests showed a high level of
                 c - reactive protein ( 163 mg /
06 mg / l ) , high erythrocyte
                 sedimentation rate ( 77 mm / h ) , pancytopenia ( hemoglobin level 12.5 g / dl , leukocyte
                 count 3,300/mm , platelet count 122,000/ mm ) , and diffuse
                 hyperglobulinemia .
the examination of giemsa - stained smears from bone marrow
                 aspirate demonstrated abundant leishmania parasites , and ifa was
                 marginally positive for leishmania antibodies ( titer 400 ) .
pcr was
                 positive for the detection of the leishmania genome in peripheral
                 blood .
infliximab and methotrexate treatment was discontinued , and treatment with
                 intravenous liposomal amphotericin b was started at a dose of 3 mg / kg for 5 days .

two days later , the fever subsided , and within the next few days , the patient
                 recovered from pancytopenia , while the inflammatory markers showed a gradual
                 decrease .
she received 2 additional doses of liposomal amphotericin b ( 3 mg / kg ) on
                 days 7 and 14 , and by that time , she exhibited no signs or symptoms of visceral
                 leishmaniasis .
we then searched medline , embase , and current contents databases for all reports on
                 leishmaniasis in europe and the mediterranean area among patients with autoimmune
                 rheumatic diseases , which are often treated with anti - tnf agents . in our search
                 strategy , we used medical subject heading terms and text words , including rheumatoid
                 arthritis , juvenile rheumatoid arthritis , still s disease , seronegative
                 arthritis , psoriatic arthritis , behet s disease , ankylosing
                 spondylitis , reactive arthritis , vasculitis , giant cell arteritis ,
                 wegener s granulomatosis ( anca [ anti - neutrophil cytoplasmic
                 antibody]associated vasculitis ) , panarteritis nodosa , leishmaniasis ,
                     leishmania , and anti - tnf .
we found 13 additional cases of
                 leishmaniasis in patients with autoimmune rheumatic diseases ( 214 ) , all published after the introduction of anti - tnf agents in 1998 ( table ) .
all 15 patients ( including our 2
                 patients ) were treated in the past or at the time of the diagnosis of leishmaniasis
                 with > 1 standard immunosuppressive agents , including
                 corticosteroids ( 11/14 [ 78.5% ] ) patients for whom treatment details were reported ) ,
                 methotrexate ( 9/14 [ 64.3% ] ) , cyclosporine ( 3/14 [ 21.4% ] ) , cyclophosphamide ( 3/14
                 [ 21.4% ] ) , azathioprine ( 2/14 [ 14.3 ] ) , and chlorambucil ( 1/14 [ 7.1% ] ) . seven ( 46.6% )
                 patients received an anti - tnf agent along with standard immunosuppressive agents .

two of the 15 reported patients had been treated with a recombinant
                 interleukin1 receptor antagonist ( anakinra ; amgen inc . ,
thousand oaks ,
                 ca , usa ) ( 5,13 ) . in most of the patients ,
visceral leishmaniasis developed ( 13 patients ,
                 86.6% ) , while cutaneous leishmaniasis developed in 2 patients ( 1 was receiving an
                 anti - tnf agent ) .
all patients were living in leishmaniasis - endemic areas of europe
                     ( figure ) . *
reference ; anca , anti - neutrophil
                         cytoplasmic antibody ; na , not applicable .
all
                         biologic treatments had been terminated 6 mo before leishmaniasis
                     occurred . reported cases of leishmaniasis in patients with autoimmune rheumatic
                         diseases in europe , indicated by stars ( 1 case from israel not shown ) .
dark
                         gray shading , distribution of leishmaniasis ; light gray shading ,
                         distribution of leishmaniasis vector sandfly .
the anti - tnf agents were introduced into clinical practice in 1998 , and the first
                 case of leishmaniasis associated with anti - tnf blockade occurred in 2001 ( 4 ) . during the 6-year period ( 19982003 ) ,
a total of 6 reports were
                 made of leishmaniasis in patients with rheumatic diseases ; 1 ( 16.6% ) occurred in a
                 patient treated with an anti - tnf agent . during the ensuing 5 years
                 ( 20042008 )
, 9 cases of leishmaniasis were reported , 6 ( 66.6% ) in
                 patients receiving anti - tnf agents .
the median duration of previous immunosuppressive therapy , before the diagnosis of
                 leishmaniasis , was 60 months ( range 2360 months ) for all 15 patients
                 ( able ) .
for the 7 patients who received anti - tnf agents , the median
                 duration of anti - tnf treatment was 18 months ( range 960 months ) .
six of
                 these 7 patients were receiving anti - tnf agents when symptoms and signs of
                 leishmaniasis occurred . in 1 patient ( 5 ) , biologic treatments had been discontinued 6 months before the diagnosis of
                 leishmaniasis ( table ) . only 1 patient had
                 been tested for antibodies against leishmania spp . before
                 immunosuppressive therapy was begun , and the results were negative ( 6 ) . therefore , this is the only case with compelling evidence that
                 leishmaniasis was a primary infection and not reactivation of a latent
             infection .
our data suggest that the introduction of tnf blockade into the clinical practice is
                 associated with increasing reports of leishmaniasis in patients with autoimmune
                 rheumatic diseases who live in leishmaniasis - endemic areas of europe .
notably , in
                 most reported cases , patients had not received anti - tnf agents but other
                 immunosuppressants .
however , all cases of leishmaniasis in patients with autoimmune
                 rheumatic diseases were reported after 1998 , the year of introduction of anti - tnf
                 agents , and most ( 9/15 ) of the reported leishmaniasis cases occurred during the past
                 5 years ( 20042008 ) , mainly among patients receiving anti - tnf agents ( 6
                 of the 9 patients with leishmaniasis ; 66.6% ) .
this increase coincides with the
                 increasing use of anti - tnf agents during the same period , as prescription practice
                 started changing toward treating patients with lower disease activity ( 15 ) .
another indirect piece of evidence that tnf blockade may increase the risk
                 for leishmaniasis is that the median duration of previous anti - tnf treatment before
                 the diagnosis of leishmaniasis was significantly shorter than the median duration of
                 immunosuppressive therapy for all 15 patients ( 18 vs. 60 months ) .
it is unclear for all cases ( with 1 exception ) presented
                 in this article whether leishmaniasis was primary infection or reactivation of
                 latent disease .
we can not also exclude the possibility that the concomitant ,
                 long - term use of other immunosuppressants , and not the anti - tnf agents per se ,
                 played a crucial role in the development of leishmaniasis .
different prescribing
                 patterns of anti - tnf agents might influence the number of cases reported from each
                 disease - endemic european country .
however , the small number of reported cases and
                 the lack of data on differences in the anti - tnf prescribing policies do not allow
                 any conclusions to be reached .
finally , due to underreporting , the reported cases
                 may underestimate the real incidence of leishmaniasis among patients with autoimmune
                 rheumatic diseases .
prospective studies to estimate the incidence of the disease , the impact of risk
                 factors and the need for serologic screening for leishmaniasis before initiation of
                 anti - tnf agents or any other immunosuppressive treatment are clearly needed .
this is
                 particularly important since currently only a few patients with autoimmune rheumatic
                 diseases receive anti - tnf agents ( 15 ) .
therefore , the use of anti - tnf treatment is likely going to increase ,
                 possibly causing a parallel increase in opportunistic infections such as
                 leishmaniasis .

Answer:
we report 2 cases of leishmaniasis in patients with autoimmune rheumatic diseases
                     in greece . to assess trends in leishmaniasis reporting in this patient
                     population , we searched the literature for similar reports from europe .
 reports
                     increased during 20042008 , especially for patients treated with
                     anti  tumor necrosis factor agents .


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:
parkinson 's disease ( pd ) is a chronic and progressive disorder with an estimated prevalence of 2% in adults over age 60 .
the study of disease progression and its determinants is of great importance to improve our understanding of the disease in order to optimize treatment . a wide variety of correlations between different subtypes of the disease and the progression of motor and nonmotor symptoms
have been reported . a cohort study with an eight - year follow - up found that axial symptoms ( gait and postural instability ) progress more rapidly than other motor features of pd ( tremor , bradykinesia , and rigidity ) .
likewise , a study with a nine - year follow - up reported a greater progression of motor scores in subjects with the following characteristics : male gender , older age at diagnosis , akinetic - rigid subtype , and lower baseline motor score . a slower progression of tremor in comparison to other cardinal features of pd has also been reported . on the other hand ,
nonmotor progression has been less studied . a study derived from the adagio study population demonstrated an increase of 10% in the movement disorder society unified parkinson 's disease rating scale ( mds - updrs ) part i score , which evaluates nonmotor experiences of daily living ( nm - edl ) , in the placebo group through a nine - month follow - up .
another study reported a rate of progression for nm - edl of 0.42 points per year , while progression on the motor experiences of daily living ( m - edl ) was reported to be of 0.8 points per year .
the objective of the present study is to describe the change in motor and nonmotor symptoms assessed by the mds - updrs and the nonmotor symptoms scale ( nmss ) in a real - life cohort of subjects with pd after a 21-month follow - up .
subjects with pd were recruited from the movement disorders clinic of the national institute of neurology and neurosurgery ( mexico city ) .
diagnosis was made according to the uk parkinson 's disease brain bank 's criteria by a movement disorder specialist .
the study was submitted and obtained approval from the institutional review board and local ethics committee .
full signed consent from all participants was obtained in order to participate in the study .
levodopa equivalent daily dose ( ledd ) was also calculated . the spanish version of mds - updrs , the parkinson disease quality of life questionnaire ( pdq-8 ) , and the nmss were applied to all subjects at two different cut - points ( initial evaluation and a follow - up visit at 21  3 months ) .
the full 65-item mds - updrs was applied by a neurologist with expertise in movement disorders .
the mds - updrs consists of four parts : part i , non - motor experiences of daily living ; part ii , motor experiences of daily living ; part iii , motor examination ; and part iv , motor complications .
the pdq-8 is a health status scale covering eight different dimensions of health - related quality of life .
each item is scored using a likert scale ( never , occasionally , sometimes , and always ) .
the nmss is a nine - domain scale for the evaluation of nonmotor symptoms in pd ( cardiovascular , sleep / fatigue , mood / cognition , perceptual problems / hallucinations , attention / memory , gastrointestinal tract , urinary function , sexual function , and miscellaneous ) .
each domain is assessed in terms of severity ( from 0 : none to 3 : severe ) and frequency ( from 1 : rarely to 4 : very frequent ) in the last month .
the score for each domain is obtained by multiplying frequency by severity ; total score is the sum of the nine domains .
disease severity was categorized using the recently published triangulation - based cut - offs classification of mds - updrs severity ( part i : mild 010 , moderate 1121 , and severe 22 ; part ii : mild 012 , moderate 1329 , and severe 30 ; part iii : mild 032 , moderate 3358 , and severe 59 ; part iv : mild 04 , moderate 512 , and severe 13 ) .
quantitative data such as mds - updrs , nmss , and pdq-8 scores were compared using a t - test for related samples .
ordinal data ( use of antiparkinsonian drugs ) were compared using a mcnemar test ; when more than two outcomes were present ( disease severity ) the mcnemar - bowker test was used .
fifty - three patients concluded the follow - up ( 33 women and 20 men ) . in all cases , loss to follow - up was due to migration out of the city resulting in unavailability to attend the follow - up visit . the mean age at the initial visit for the final sample was 64.1  14.3 years and the mean disease duration was 9.1  5.4 years .
comparison of treatment schemes between the initial and follow - up visits is shown in table 1 .
the frequencies for each severity group according to the mds - updrs at the initial and follow - up visits are shown in table 2 .
the comparison of total scores in the mds - updrs , pdq-8 , and nmss between visits is shown in table 3 .
no statistically significant difference was found in regard to disease severity according to the mds - updrs part iii between the initial and follow - up visits .
most of the patients remained in the mild and moderate disease groups , although there was a slight increase in the mild group as a consequence of clinical improvement in subjects initially classified as moderate severity .
the mds - updrs part iii demonstrated a statistically significant decrease of 7.2  2.3 points ( 95% ci , 3.1 to 11.2 , p = 0.001 ) between the initial and follow - up visits . when compared by disease severity , subjects with mild disease had a mean improvement of 5.7  0.1 points ( 95% ci , 3 to 8.4 , p < 0.0001 ) ; subjects with moderate disease also showed improvement although statistical significance was not reached ( 8  3.5 points , 95% ci 4.4 to 20.4 , p = 0.159 ) .
the m - edl assessed by mds - updrs part ii did not show any statistically significant change between visits . in regard to motor complications assessed by the mds - updrs part iv , a mean increase of 0.9  0.6 points ( 95% ci , 0.8 to 1.6 , p = 0.015 ) was observed .
when analyzed by severity , subjects with a mild disease worsened by 0.4  0.2 points ( 95% ci , 0.1 to 0.8 , p = 0.017 ) .
no statistically significant association was found between the mean change in the total mds - updrs score and the predominant motor phenotype ( p = 0.397 ) .
when analyzed independently , no association was found between the different mds - updrs parts and predominant phenotype ( part i p = 0.787 , part ii p = 0.286 , part iii p = 0.578 , and part iv p = 0.994 ) .
no association was found between motor scores and gender ( p = 0.427 ) or disease duration ( p = 0.941 ) .
no statistically significant change in nonmotor severity as assessed by the mds - updrs part i was found between visits with most of the patients remaining in the mild severity group .
moreover , the nm - edl score did not show a statistically significant change between the initial and follow - up visits even when accounting for severity classification .
conversely , all nonmotor symptom domains in the nmss scale showed an increase in the mean score , as shown in table 4 .
an increase of 14.3  11.4 points ( 95% ic , 0.47 to 27.4 , p = 0.043 ) in nmss total score was found between visits . even though there was an increase in the score of all domains , the difference was statistically significant only for the perceptual problems and hallucinations item ( 0.2  0.7 to 0.8  2.1 , p = 0.044 ) . when analyzing by disease severity according to the mds - updrs part i score , no statistically significant increase in nmss total score within groups
the mds - updrs part i and nmss total scores showed a high correlation ( r = 0.611 , p = 0.01 ) .
no statistically significant associations were found between nmss scores and disease duration ( p = 0.677 ) , gender ( p = 0.964 ) , or motor phenotype ( p = 0.427 ) .
no statistically significant changes were found in quality of life as assessed by the pdq-8 between visits .
pd is a progressive neurodegenerative disease . rates of change in motor and nonmotor symptoms appear to progress differently in a nonlinear fashion with a greater increase in the m - edl in comparison to the nm - edl .
traditionally , pd severity is assessed using the hoehn and yahr staging . in this regard ,
the mds - updrs severity scale was preferred instead due to the fact that the hoehn and yahr scale relies mainly on the motor state . in order to evaluate the impact of nonmotor symptoms a severity classification accounting for them was needed .
the recently published cut - off points for pd severity levels based on the mds - updrs had the advantage of including nonmotor symptoms . in the present study ,
the overall improvement of seven points in the mds - updrs part iii can be explained by several factors .
firstly , the study was carried out at a referral center and the initial evaluation was actually the first time the patient was seen at the clinic . as a consequence ,
it should be pointed out that although the ledd increased by 120  mg / d , the actual levodopa daily dose was slightly increased .
the latter means that no major levodopa dosage adjustments were performed but also that antiparkinsonian drugs were added as expected .
for instance , the use of monoamine oxidase inhibitors and the dopamine agonist ledd was doubled .
it also should be emphasized that motor evaluations were performed during the  on  clinical state , in contrast to an  off  state that could be a better index of the disease natural history . on the other hand ,
an increase in motor complications such as  on  time with troublesome dyskinesia and motor fluctuations assessed in the mds - updrs part iv was found .
motor complications related to dopaminergic treatment are expected to increase with disease progression despite better motor scores .
interestingly , no difference in m - edl ( mds - updrs part ii ) was found between visits despite the improvement in motor scales . moreover , health - related quality of life assessed by the pdq-8 also failed to show any improvement . in regard to the nm - edl ,
reported a significant worsening of nm - edl scores in the mds - updrs in the placebo group , but no change in treated patients . on the other hand , a statistically significant increase of 14% in the nmss total score was observed . even though every nmss domain had an increase in its score , only the perceptual changes and hallucinations item had a statistically significant difference .
that is , all the nonmotor symptoms worsened , but only the cumulative effect and hallucinations reached statistical significance .
a possible explanation may be that the worsening in individual nonmotor symptoms was not clinically significant and as a consequence proper management was not initiated .
for instance , use of antidepressants remained the same despite the increase in the mood domain score .
additionally , some symptoms like hallucinations can be an adverse effect of dopaminergic replacement therapy , as well as a consequence of disease progression .
our findings oppose the study of lang et al . , which reported a greater decline in m - edl in comparison to nm - edl based on mds - updrs parts i and ii . this study had a longer follow - up period ( up to 5 years ) and only included subjects with pd in early stages .
it is possible that discrepancy is the result of a shorter follow - up and the inclusion of subjects with varying degrees of severity .
more important is the fact that patients in our study received the best medical treatment in comparison to untreated patients enrolled in a randomized clinical trial setting . as such , our study provides a pragmatic view of the effectiveness of interventions in real - life practice .
it should be highlighted that mds - updrs part i and nmss total scores had a high correlation coefficient , but the mds - updrs part i failed to show any statistically significant difference .
reported a strong convergent validity between mds - updrs part i and nmss but also a lack of concordance in patients with a high burden of nonmotor symptoms .
although it is expected that mds - updrs scores correlate with the disease duration , the patients assessed in our study had different pd durations . while this issue affects direct extrapolation , it also gives a more objective overview of daily clinical practice .
secondly , patients had different therapeutic schemes at the initial evaluation ; thus final outcomes could be influenced by the optimization of the treatment rather than from disease progression . finally ,
as mentioned before , all scales were applied during patients '  on  clinical state in order .
this might not reflect the natural history of the disease and therapeutic effect should be considered . on the other hand , nonmotor symptoms did not change with treatment as much as motor scores . also , nonmotor fluctuations were not assessed . in conclusion , we found a motor improvement during the 21-month follow - up accompanied by an increase in motor complications .
studies assessing motor and nonmotor changes over time in different stages of severity are needed .

Answer:
background .
 parkinson 's disease ( pd ) is a chronic and progressive disorder .
 rates of change in motor symptoms have been more studied compared to nonmotor symptoms .
 the objective was to describe these changes in a real - life cohort of subjects with pd . methods .
 a cohort study was carried out from 2011 to 2013 .
 consecutive patients with pd were recruited from a movement disorders clinic .
 mds - updrs , pdq-8 , and nmss were applied to all subjects at an initial evaluation and a subsequent visit ( 21  3 months ) .
 disease severity was categorized using a recent classification of mds - updrs severity
 . results .
 the mds - updrs part iii showed a significant decrease of 7.2  2.31 points ( p = 0.001 ) between evaluations .
 a mean increase of 0.9  0.6 points ( p = 0.015 ) in the mds - updrs part iv was observed .
 an increase of 14.3  11.4 points ( p = 0.043 ) in the nmss total score was found ; when assessed individually , the difference was statistically significant only for the perceptual problems / hallucinations item .
 quality of life remained unchanged .
 conclusion .
 motor improvement was observed accompanied by an increase in motor complications possibly as a result of treatment optimization .
 nonmotor symptoms worsened as a whole .
 the overall effect in the quality of life was negligible .


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:
patients with heart failure ( hf ) older than 65 years have a two - fold increased risk of cognitive impairment than elders without hf ( 1 ) .
the prevalence of cognitive impairment in adults with chronic heart failure is recognized as a factor contributing to the complexity of care for these patients ( 2 ) .
cognitive impairment may impact the ability to perform heart failure self - care procedures and is associated with an increased risk of re - hospitalization and mortality ( 3 ) .   despite the prevalence of these two conditions , cognitive impairment in hf patients
is usually underestimated by physicians ( 4 ) and currently , there is insufficient evidence to develop recommendations for strategies to improve cognitive impairment for hf patients ( 5 ) .
this study was designed to determine factors related to cognitive impairment among elder with hf .
in this descriptive , correlational , cross - sectional study , 184 patients with chronic heart failure were selected from four mazandaran university of medical sciences teaching hospitals using convenience sampling : imam khomeini hospital in behshahr , fatemeh zahra heart center in sari , imam khomeini hospital in fereydunkenar and imam khomeini hospital in noor .
patients hospitalized for symptomatic heart failure between october 2013 and january 2014 were included in this study and confirmed by the cardiologists .
inclusion criteria were a history of at least six months involvement with heart failure , age  60 , and remaining stable 1 - 2 days after admission .
exclusion criteria were communication problems such as severe hearing impairment ( without hearing aids ) , speech problems , severe cognitive impairment with abbreviated mental test ( amt ) scores < 4 ( 6 ) and uncooperativeness .
after providing written informed consent , each patient was interviewed by an independent data collector who was not involved in the patient s care .
socio - demographic variables consisted of age , gender , location , living status , education level , and income .
clinical variables consisted of left ventricular ejection fraction ( ef ) , poly - pharmacy (  5 different drugs ) , comorbidities ( charlson comorbidity index ) , blood pressure , depressive symptoms , body mass index ( bmi ) , number of hospitalizations during the previous six months , and some biochemical characteristics of the blood . these variables were collected from patients medical records and by interviews .
cognitive status was measured using the iranian version of the abbreviated mental test . the ideal cut - off point reported 6 , while sensitivity and specificity identified at 88 and 99% , respectively ( 6 ) , using a 10-item scale .
each correct answer received a score of 1 and incorrect answers were scored as 0 .
a total score of  6 indicates the presence of cognitive impairment ( a score of 0 - 3 indicates severe cognitive impairment and 4 - 6 indicates moderate cognitive impairment ) .
the severity of comorbid conditions was assessed using the charlson comorbidity index ( 7 ) , which classifies comorbidities based on the number and seriousness of one - year survival , with higher scores indicating greater risk of death .
most diseases are assigned a score of 1 on the index , but more severe conditions are given a weight score of 2 , 3 or 6 .
fisher s exact test and logistic regression were used to compare cognitive status scores with demographic characteristics and disease related variables .
the independent samples t - test was used to compare biochemical characteristics of the blood from the subjects both with and without cognitive impairment .
socio - demographic variables consisted of age , gender , location , living status , education level , and income .
clinical variables consisted of left ventricular ejection fraction ( ef ) , poly - pharmacy (  5 different drugs ) , comorbidities ( charlson comorbidity index ) , blood pressure , depressive symptoms , body mass index ( bmi ) , number of hospitalizations during the previous six months , and some biochemical characteristics of the blood . these variables were collected from patients medical records and by interviews .
cognitive status was measured using the iranian version of the abbreviated mental test . the ideal cut - off point reported 6 , while sensitivity and specificity identified at 88 and 99% , respectively ( 6 ) , using a 10-item scale .
each correct answer received a score of 1 and incorrect answers were scored as 0 .
a total score of  6 indicates the presence of cognitive impairment ( a score of 0 - 3 indicates severe cognitive impairment and 4 - 6 indicates moderate cognitive impairment ) .
the severity of comorbid conditions was assessed using the charlson comorbidity index ( 7 ) , which classifies comorbidities based on the number and seriousness of one - year survival , with higher scores indicating greater risk of death .
most diseases are assigned a score of 1 on the index , but more severe conditions are given a weight score of 2 , 3 or 6 .
test and logistic regression were used to compare cognitive status scores with demographic characteristics and disease related variables .
the independent samples t - test was used to compare biochemical characteristics of the blood from the subjects both with and without cognitive impairment .
the amt mean was 6.18  2.002 ( minimum 4 and maximum 10 ) , with 95% ci ( 5.89 to 6.48 ) . the majority of the elders in the study ( 110 persons , 59.8% ) had scores of 4 - 6 and the others ( 74 persons , 40.2% ) had scores of 7 - 10 .
females made up 61.4% of participants ( 113 persons ) and 38.6% ( 71 persons ) were male .
the 60 - 75 age group comprised 70% of the subjects ( 128 persons ) , 29% ( 54 persons ) were in the 75 - 90 age group and 1% ( 2 persons ) were in the 90 - 94 age group .
the mean ages in women and men were 70.7  8.35 and 70.01  8.99 , respectively ( p = 0.595 ) .
the ci odds ratio was higher in older patients than in the younger ones ( p = 0.002 ) .
in addition , the ci odds ratio was higher in female subjects than male ( p < 0.001 ) ( table 1 )
. there were significant relationships between cognition status scores and living status ( p < 0.001 ) and also between cognition status scores and education level ( p < 0.001 ) ( table 2 ) .
values are expressed as mean  sd . the ci odds ratios were higher in subjects with an ejection fraction of < 40% compared to subjects with an ejection fraction of  40% ( p = 0.002 ) ( table 1 ) .
fisher s exact test results showed a significant relationship between cognitive status scores and hypertension ( p = 0.039 ) and also between cognitive status scores and anemia ( p = 0.046 ) .
although the ci odds ratio was higher among subjects with hypertension and anemia , there was not a significant relationship ( table 1 ) .
there was no significant correlation between biochemical characteristics of the blood and cognitive status scores .
however , there was a near - significant level for hemoglobin , blood urea nitrogen ( bun ) and systolic blood pressure ( table 3 ) .
values are expressed as mean  sd . the mean of charlson comorbidity index and depression symptoms were higher among subjects with cognition impairment ( p < 0.001 ) ( table 4 ) .
the amt mean was 6.18  2.002 ( minimum 4 and maximum 10 ) , with 95% ci ( 5.89 to 6.48 ) . the majority of the elders in the study ( 110 persons , 59.8% ) had scores of 4 - 6 and the others ( 74 persons , 40.2% ) had scores of 7 - 10 .
females made up 61.4% of participants ( 113 persons ) and 38.6% ( 71 persons ) were male .
the 60 - 75 age group comprised 70% of the subjects ( 128 persons ) , 29% ( 54 persons ) were in the 75 - 90 age group and 1% ( 2 persons ) were in the 90 - 94 age group .
the mean ages in women and men were 70.7  8.35 and 70.01  8.99 , respectively ( p = 0.595 ) .
the ci odds ratio was higher in older patients than in the younger ones ( p = 0.002 ) .
in addition , the ci odds ratio was higher in female subjects than male ( p < 0.001 ) ( table 1 ) .
there were significant relationships between cognition status scores and living status ( p < 0.001 ) and also between cognition status scores and education level ( p < 0.001 ) ( table 2 ) .
the ci odds ratios were higher in subjects with an ejection fraction of < 40% compared to subjects with an ejection fraction of  40% ( p = 0.002 ) ( table 1 ) .
fisher s exact test results showed a significant relationship between cognitive status scores and hypertension ( p = 0.039 ) and also between cognitive status scores and anemia ( p = 0.046 ) .
although the ci odds ratio was higher among subjects with hypertension and anemia , there was not a significant relationship ( table 1 ) .
there was no significant correlation between biochemical characteristics of the blood and cognitive status scores .
however , there was a near - significant level for hemoglobin , blood urea nitrogen ( bun ) and systolic blood pressure ( table 3 ) .
values are expressed as mean  sd . the mean of charlson comorbidity index and depression symptoms were higher among subjects with cognition impairment ( p < 0.001 ) ( table 4 ) .
in this study , the prevalence of cognitive impairment was higher among elderly subjects with a lower level of education , patients living alone or with their children , and females .
it seems that fewer years of education contribute to processing speed ( 2 ) . providing social support another important factor that may decrease patient stress and improve cognitive status .
the results of the present study show that comorbidities contribute to cognitive impairment in hf patients .
these findings are consistent with other studies ( 2 , 9 , 10 ) , but differ from that of pressler et al . who found no association between comorbidities and cognitive status ( 11 ) .
in this study , there were significant relationships between cognitive impairment with depression , hypertension , and anemia .
these findings are consistent with some studies ( 9 , 10 ) . in a clinical setting , it is hard to differentiate mild stages of dementia and late life depression , because both situations may have similar presentations ( 12 ) .
few studies have directly examined the association between cognitive impairment and depression in persons with heart failure , despite the likelihood of common mechanisms ( 13 ) .
persons with heart failure exhibit numerous pathological changes on neuro - imaging , including greater atrophy and the presence of white matter hyper - intensities , frequently in frontal brain regions ( 14 ) .
hypertension has a significant impact on cardiovascular function , cerebral structural integrity and associated cognitive deterioration ( 15 , 16 ) .
the most common explanation for the deleterious effect of hypertension on cognition is that hypertension increases cerebrovascular disease ( 17 ) .
some longitudinal studies have shown a positive association between hypertension and cognitive impairment ( 15 , 16 ) .
these effects were independent of clinical strokes and the association was stronger in individuals who did not use antihypertensive drugs ( 15 ) .
the results of some studies indicate that hypertension may be a risk factor dementia , especially alzheimer s disease ( ad ) ( 18 , 19 )
. however , the factors that predispose individuals with hypertension to developed ad are unknown ( 20 ) .
there have been very few studies on the association of anemia with cognitive status ( 22 ) .
the literature on the association between anemia and dementia is also limited and the results are inconsistent ( 23 , 24 ) .
anemia in heart failure may have multiple origins , which are thought to involve reduced erythrocyte production , decreased bmi , and hemodilution ( 25 ) .
further contributors to the risk of anemia in hf are comorbid renal disease and increased inflammation ( 26 ) .
elevated levels of pro - inflammatory cytokines may also inhibit hematopoietic proliferation ( 27 ) .
in addition , some medications , such as angiotensin - converting enzyme ( ace ) inhibitors and angiotensin receptor blockers , reduce erythropoietin production ( 25 ) .
first , this is a cross - sectional study and the correlations can not imply causation relationships between parameters .
moreover , the data represent only the subjects who agreed to participate in the study . identifying factors affecting cognitive impairment in hf may help clinicians in directing educational interventions on disease management to families to possibly prevent readmission of their loved ones .
further research to determine the feasibility and acceptability of cognitive assessment in routine clinical care is suggested .
first , this is a cross - sectional study and the correlations can not imply causation relationships between parameters .
moreover , the data represent only the subjects who agreed to participate in the study .
identifying factors affecting cognitive impairment in hf may help clinicians in directing educational interventions on disease management to families to possibly prevent readmission of their loved ones .
further research to determine the feasibility and acceptability of cognitive assessment in routine clinical care is suggested .

Answer:
backgroundpatients with heart failure ( hf ) older than 65 years have a two - fold increased risk of cognitive impairment than elders without hf .
 identifying factors affecting cognitive impairment in hf may present targets for intervention.objectivesthe aim of the present study was to determine cognitive function and related factors among elderly patients with heart failure.patients and methodsin this cross - sectional study , 184 elderly patients with heart failure were selected from four mazandaran university of medical sciences teaching hospitals using convenience sampling .
 data were collected from patients medical records and by interview , using the abbreviated mental test , geriatric depression scale , and charlson comorbidity index.resultsthere were significant relationships between cognitive status and living arrangement ( p < 0.001 ) , education ( p < 0.001 ) , hypertension ( p = 0.039 ) , anemia ( p = 0.046 ) , charlson comorbidity index ( p < 0.001 ) and geriatric depression scale ( p <
 0.001).conclusionsscreening of cognitive impairment in elderly patients with heart failure seems necessary .


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:

				 olfactory neuroblastoma ( onb ) is a rare malignant tumor arising from the olfactory epithelium of the nasal cavity and the paranasal sinuses .
the anatomic origin in the superior nasal cavity leads to nonspecific symptoms that make early diagnosis difficult .
direct extension of the tumor into the anterior cranial fossa , either at presentation or at disease recurrence , is common .
onb is mostly a locally aggressive tumor that can spread to lymph nodes but metastatic involvement of bone , bone marrow , and other organs was also reported .
the most commonly used staging system proposed by kadish is currently based on computer tomography and magnetic resonance imaging . in stage
a , the tumor is limited to the nasal cavity , in stage b the tumor extends to paranasal sinus , and in stage c the tumor is extending over the nasal cavity and sinus and/or metastasized distantly .
a histological grading system based on microscopic findings proposed by hyams at 1988 showed a clear correlation of survival with histological differentiation of disease .
however most authors believe that craniofacial resection followed by rt offers the gold standard treatment in this disease . despite aggressive therapies , local , regional relapse , and distant metastasis occur frequently and often after extended periods of follow - up .
data for this case series were acquired retrospectively from the files of division of medical oncology , cerrahpasa medical faculty , istanbul university .
additional information regarding the clinical course and outcome was collected from the patients ' charts and phone calls to the patients , their relatives , and their general practitioners . in this study , we have reviewed 19 cases of olfactory neuroblastomas treated over 24-year period and analyzed the clinical features , treatment outcomes , and prognostic factors .
the data of nineteen patients of olfactory neuroblastomas treated and followed up between 1986 and 2010 at division of medical oncology , cerrahpasa medical faculty , istanbul university , were analyzed retrospectively .
patient characteristics , initial symptoms , tumor extent , histologic features , primary therapy , tumor recurrence , and treatments of recurrent disease were determined .
patients were staged according to the kadish staging system . a single pathologist with expertise in head and neck neoplasms reviewed the histological specimens .
local ethics committee 's approval and patients ' or their next of kin 's informed consent were taken before the study .
treatment response was assessed by clinical examinations and computed tomography ( ct ) or magnetic resonance imaging ( mri ) .
survival rates were calculated from diagnosis to the death of the patient using the kaplan - meier life table method .
the madian age at diagnosis was 46 ( range : 19 to 68 years ) .
tumor staging was kadish stage a in 3 , stage b in 5 , and stage c in 11 patients .
four patients had metastasis of cervical lymph nodes , two brains , one bone marrow , one bone and lung metastases , and one bone , mediastinal lymph node , and liver metastases at the time of diagnosis .
tumor localization , clinical symptoms , and presentations at the time of diagnosis are listed in table 1 .
median time from onset of first symptoms until diagnosis was 8.8 months ( range : 1.829 months ) .
the common presenting symptoms were nasal obstruction ( 53% ) , epistaxis ( 31% ) , rhinorrhea , and facial pain ( 26% ) .
patient treatments consisted of surgical resection , radiation therapy , and chemotherapy ( ctx ) ( table 3 ) .
initial treatments included surgery alone in three patients , radiotherapy ( rt ) with or without ctx in five , surgery plus postoperative rt in seven and multimodality therapy ( surgery plus postoperative ctx plus postoperative rt ) in three , and finally ctx alone in one . in 14 patients ,
four of these patients had also radical neck dissection due to cervical lymph nodes involvement .
nasal tumor resection in 2 patients , maxillectomy plus orbital exenteration in 1 , and external ethmoidectomy ( ee ) in 1 were also used as surgical treatments . of these 14 patients who underwent surgical tumor resection ,
4 were treated with surgery alone , 5 with adjuvant radiation therapy after surgery , 2 with adjuvant ctx after surgery , and the remaining 3 with radiation therapy and ctx after surgery . of the remaining 5 patients , four in advanced stage and one in early stage refused surgical treatment .
radiation therapy was administered to two of the patients , radiation therapy followed by ctx to the other two , and ctx alone to one patient .
the average radiation dose was 57.9 gy and the ctx was chosen from cisplatin - based regimens . as a part of the primary treatment modality , 12 patients underwent radiation therapy , so did the five relapsed patients .
as a part of primary treatment modality 8 patients received ctx , so did the three relapsed patients .
fifteen patients died of tumor progression during the follow - up , of whom 9 were at an advanced stage ( stage c ) by the time of diagnosis and 6 at an early stage ( stage a / b ) .
kadish stage c patients had a significantly poorer outcome compared to the stage a / b patients ( 2-year survival rate : 71 versus 25% , resp .
histopathologically high - grade patients ( grade 3/4 ) had a significantly poorer outcome when compared to the lower grade ( grade 1/2 ) patients ( 2-year survival rate : 16 versus 50% , resp .
primary tumor extensions to orbital area had a significantly poorer outcome compared to the tumors with no extension to orbital area ( 2-year survival rate : 22 versus 60% , resp .
there was no statistically significant difference in survival rate between male and female patients ( 2-year survival rate : 40 versus 44% , resp .
patients with age < 45 years had no poorer outcome compared to patients with age > 45 years ( 2-year survival rate : 41 versus 43% ; p = .059 ) .
brain and bone marrow involvements showed poorer outcome compared to those without such involvement ( median survival rate : 9.1 versus 28.8 months , resp . ;
survival rate was not significantly different among pateints of kadish c when stratified according to initial treatment ( p = .8 ) .
locoregional recurrence developed in 6 and distant metastasis in 6 patients . during the follow - up period , these groups exhibited distant metastasis to the brain , spinal cord , bone , bone marrow , meninges , and lungs .
as a treatment for recurrence and metastasis , reoperation of primary site plus radiation therapy in 4 patients and radiation therapy alone in 4 patients were offered .
onb is a rare malignant tumor that comprises 4,65% of malignant nasal and paranasal tumors .
some 1000 cases have been reported in the english literature since it was first introduced in 1924 .
the incidence rate is bimodal , with peaks in the second and third decades of life and in the sixth and seventh decades of life and equal among females and males . as for our study ,
the age at diagnosis was most common in the fourth decade and female - to - male ratio was equal .
the average time between the appearance of the first symptom and the diagnosis was reported as 6 months and this period was similar also in our group .
the most common symptoms at the initial diagnosis were defined as unilateral nasal obstruction and epistaxis in the literature .
this tumor may be misdiagnosed as an undifferentiated small cell carcinoma , melanoma , rhabdomyosarcoma , or other small blue cell neoplasms .
hyam proposed a grading system with grades 14 based on the presence or absence of seven different histopathological parameters .
these are growth , architecture , mitotic activity , necrosis , nuclear pleomorphism , rosette formation , and fibrillary stroma .
. staining paterns for neuron - spesific enolase , chromogranin , synaptophysin , s-100 , and epithelial markers can be helpful .
there is evidence that histological grade of onb influences biologic behavior , particularly because it relates to disease progression , local recurrence , and metastasis . for the well - differentiated tumors a slower disease progression and less tendency for local recurrence have been described . in our study , the 2-year survival rate of this grade i / ii - iii / iv disease was 16 versus 50% , respectively .
more aggressive treatment , such as surgery , radiation , and intensive ctx , may be useful for patients with grade iii / iv disease .
a meta - analysis showed that the median overall survival at 5 years is 45% in 390 patients .
the distribution of onb from 21 studies according to kadish staging system was 12% at stage a , 27% at stage b , and 61% at stage c. the mean 5-year survival is 75% for stage a , 68% for stage b , and 41% for stage c .
the conclusions of the university of virginia stated that kadish stage is predictive of disease - related mortality .
however , in the series of the mayo clinic it was found that kadish stage did not affect the outcome .
danish clinicopathological study found that the staging system of kadish was able to stratify into prognostically significant groups . in our study , the 5-year survival rate of these tumors was 26% and median survival time was 23 months .
the distribution of onb according to kadish staging system was 16% at stage a , 26% stage b , and 58% stage c. however , in our study , the 5-year survival rates of these stage groups were inferior compared to those reported in other studies .
the cause of this poor result was presentation of 5 patients with distant metastases ( 26% ; 2 brain , 1 bone marrow , 2 other sites ) , 4 patients ( 21% ) with cervical lymph node metastasis , 12 patients ( 63% ) with high - grade histology at the time of diagnosis , and inability to evaluate the surgical margins of the resected tumors .
the survival rate of node positive patients is 29% compared with 64% of node negative patients .
distant metastases have been described in the pancreas , the liver , mediastinum , bone marrow , lungs , leptomeninges , skin , and breasts [ 11 , 12 ] .
cervical nodal metastases can develop in 17 to 33% of patients and distant metastases in 10 to 40% of patients over the course of disease
metastatic disease at presentation occurs in 10 to 50% of patients , depending on the study [ 6 , 13 , 14 ] .
we found the local recurrence rate to be 31.5% and distant metastasis 31.5% after initial surgery . during the follow - up periods these groups exhibited distant metastases to the brain , spinal cord , bone , bone marrow , meninges , and lungs .
patients who had brain and bone marrow metastases had poorer prognosis than others having metastatic deposits of other sites .
involvement of the orbit is a serious prognostic factor , but when the orbital periosteum is affected without penetration into the orbital structures themselves , the eye may be preserved by resection and grafting of the periosteum without an adverse effect on survival as compared with orbital clearance .
irrespective to the most sophisticated imaging , involvement of the dura and orbital periosteum can accurately be determined only at surgery . in our study ,
this group 's ( 8 patients ) survival rate is poorer than those with no involvement of the orbita ( p = .042 ) .
the institute of laryngology and otology , university college london , published a study of 42 patients treated over 23 years .
overall and disease - free survival rates were 77 and 61% at 5 years , and 53 and 42% at 10 years , respectively .
late recurrences were seen . based on this experience , combined therapy with craniofacial resection and radiation therapy is recommended by this group . in a retrospective study of 47 patients treated at multiple centers in germany from 1979 to 2001 ,
the 5-year overall survival and event - free survival rate were 64% and 50% , respectively .
patients who received multimodality therapy had a significantly better event - free survival rate compared with those who did not receive multimodality therapy ( 74 versus 41% ) .
the authors recommend a combination therapy including ctx , surgery , and postoperative radiation therapy for kadish stage c patients . in our study ,
initial treatment included surgery alone in three patients , rt with or without ctx in five , surgery plus postoperative rt in seven , and multimodality therapy ( surgery plus postoperative ctx plus postoperative rt ) in three , only ctx in one patient .
however , in our study choice of treatment modality did not show a statistically significant difference in survival rate .
the reasons for that might be including low number of patients in the study , being 5 distant site metastasis , 4 cervical lymph node metastasis at the time of diagnosis , only one orbital exentration ( although there were 8 orbital involvement ) , and 12 patients exhibiting high grade histology and inability to evaluate surgical margins in resected tumors . in conclusion , advanced tumor stage ,
the initial histopathologic grade of iii / iv , and involvement of orbita , brain , or bone marrow metastasis were the statistically significant poor prognostic factors , whereas age , sex , and treatment modality were not prognostic factors .

Answer:
objective .
 the aim of this study was to evaluate clinicopathological findings and the efficacy of the treatment modalities used in patients with olfactory neuroblastomas . study design .
 retrospective record review . setting .
 istanbul university , cerrahpasa medical faculty , medical oncology outpatient clinic .
 subjects and methods .
 there were 3 stage a tumors , 5 stage b and 11 stage c according to the kadish staging system .
 there were 5 grade i / ii and 12 grade
 iii / iv according to the hyams ' histopathologic system .
 involvement to orbita was detected in eight patients at the time of diagnosis .
 results .
 the median follow - up period was 23.7   months .
 the 5-year survival rate for the whole group was 26% .
 the stage a / b groups exhibited a better survival rate than the c group with 2-year survival rates being   25 versus 71% respectively ( p = .008 ) .
 the grade i / ii groups exhibited a better survival rate than the grade iii / iv groups with 2-year survival rates being 50 versus 16% respectively ( p = .001 ) .
 the group who had orbital involvement exhibited a poor survival rate than the group of patients who had no involvement of the orbital .
 conclusion . in our study ,
 tumor stage , histopathologic grading , involvement of the orbita , brain and bone marow metastases were the statistically significant prognostic factors .


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 network querying problem , one is given a small network , corresponding to a known pathway or a complex of interest . the goal is to identify similar instances in a large network , where similarity is measured in terms of sequence or interaction patterns .
previous approaches to the query problem required precise information on the interaction pattern of the query and were usually limited to small queries ( 24 proteins ) .
pathblast  a server for querying linear pathways within a protein  protein interaction ( ppi ) network ( 1)was subsequently extended to allow searching for more general structures ( 2 ) .
a general framework for subnetwork querying was developed ( 3 ) , but it is applicable only to very small queries due to its complexity .
two other methods are netmatch , a cytoscape ( 4 ) plugin implementing the work of ferro et al . ( 5 ) that utilizes fast heuristics for subgraph isomorphism to identify approximate matches of queries within a collection of networks , and netgrep ( 6 ) , a system for searching networks for patterns corresponding to small sets of proteins with specified attributes and topology .
the torque server implements a novel method for querying protein networks that does not require information on the interconnections ( topology ) among the query proteins ( 7 ) ( figure 1 ) .
this makes torque applicable in broader scenarios , such as querying complexes or pathways whose topologies are not completely known , or even when querying from species for which ppi information is not available .
( 8) also studied queries with no topology information , but since their method is enumerative it was applied to very small queries ( 24 proteins ) .
it was tested extensively on hundreds of queries of known complexes from a variety of species ( 7 ) .
it was shown to yield far more matches than the qnet topology - based approach ( 2 ) , while providing results that are highly functionally coherent .

the network induced by the vertices labeled a , b , c , d and e is a match to the query , where vertex c is an insertion and query element 4 is deleted .
( a ) the query proteins ; ( b ) the queried network . colored vertices in the network match nodes of the same color in the query .
the network induced by the vertices labeled a , b , c , d and e is a match to the query , where vertex c is an insertion and query element 4 is deleted .
the torque web server implements the algorithms in ( 7 ) for querying protein sets across species .
it combines three approaches : a dynamic programming method utilizing color coding , integer linear programming and a fast heuristic based on shortest paths .
torque automatically selects the best method to apply at each stage and outputs the highest scoring match .
scores are based on the underlying network structure , on interaction confidence values and on sequence similarities between matching proteins .
the input for torque consists of :
 a query set of proteins in species a;their protein sequences;a ppi network for species b;the sequences of the network proteins .

a query set of proteins in species a ; their protein sequences ; a ppi network for species b ; the sequences of the network proteins .
all inputs are in simple text format :
 the query set can be entered directly as a comma - delimited or whitespace - delimited list.protein sequences are given in the standard fasta format.the ppi network is given as a text file , where each row represents an interaction and contains the ids of the interacting pair and a confidence value for it in the range [ 0 , 1 ] .

the query set can be entered directly as a comma - delimited or whitespace - delimited list .
the ppi network is given as a text file , where each row represents an interaction and contains the ids of the interacting pair and a confidence value for it in the range [ 0 , 1 ] .
it is possible to use a single fasta file ( input 2 ) for many queries , if it contains the sequences for all proteins in all queries .
when the query field is left blank , torque will use all the proteins in input 2 as the query .
if input 1 contains uniprot protein ids ( www.uniprot.org ) , their sequences need not be entered in input 2 ; instead , torque automatically retrieves them from the uniprot database . for several target species ,
currently , the server supports this option for the three target species saccharomyces cerevisiae , drosophila melanogaster and homo sapiens .
the user can indicate one of these target species instead of providing inputs 3 and 4 .
the user can control two parameters of the algorithm , setting a trade - off between speed and sensitivity .
the user can set the threshold for blast similarity ( e - value ) . by setting a lower threshold , less
homologs will be identified for the query proteins , making the algorithm faster but less sensitive .
the second parameter is a threshold for the confidence values of ppi network edges provided as part of input 3 .
edges whose confidence value is lower than the threshold are discarded ; hence , this parameter determines the sparsity of the target network and affects the number of possible matches and the running time .
the running time of torque is typically a few minutes , but may be up to an hour , depending on the size and other properties of the query ( for more details , see ( 7 ) ) .
if several queries are submitted to the server at the same time , they are queued and executed sequentially . rather than waiting for the results online , they can be accessed later , in two ways :
 when a torque job is started , it is assigned a nine - digit job i d .
this i d can be used to access the results later from the main torque page.before submitting a query , the user may enter an email address .
once torque has finished processing the query , the results will be sent to the email address provided .
when a torque job is started , it is assigned a nine - digit job i d .
this i d can be used to access the results later from the main torque page . before submitting a query
once torque has finished processing the query , the results will be sent to the email address provided .
the web server generates a web page ( figure 2 ) with the image of the top - scoring match for the query in the target network , as well as an auxiliary file in.sif format that can be viewed using the cytoscape software ( 4 ) .
the content of the.sif file includes , for each edge , a numerical value representing the confidence in the interaction it represents , as provided in the input .
the image shows the subgraph induced by the top - scoring match in the ppi network .
each vertex is labeled with its protein name in the ppi network and its matching query protein , if such exists .
insertion vertices are shown in gray , and proteins from the query for which there was no match in the solution ( deletions ) are listed separately .

the following example uses as query the mouse dna synthesome complex , downloaded from the corum website ( http://mips.gsf.de/genre/proj/corum/index.html ) . this 13-member complex was queried in the yeast network ( 5430 proteins , 39 936 interactions ) .
examining the subnetwork identified by torque we find that it is functionally coherent ( nucleotidyltransferase activity , p < 1.4e  10 ) and significantly intersects the yeast alpha dna polymerase : primase complex , supporting its biological plausibility .
the input for torque consists of :
 a query set of proteins in species a;their protein sequences;a ppi network for species b;the sequences of the network proteins .

a query set of proteins in species a ; their protein sequences ; a ppi network for species b ; the sequences of the network proteins .
all inputs are in simple text format :
 the query set can be entered directly as a comma - delimited or whitespace - delimited list.protein sequences are given in the standard fasta format.the ppi network is given as a text file , where each row represents an interaction and contains the ids of the interacting pair and a confidence value for it in the range [ 0 , 1 ] .

the query set can be entered directly as a comma - delimited or whitespace - delimited list .
the ppi network is given as a text file , where each row represents an interaction and contains the ids of the interacting pair and a confidence value for it in the range [ 0 , 1 ] .
it is possible to use a single fasta file ( input 2 ) for many queries , if it contains the sequences for all proteins in all queries .
when the query field is left blank , torque will use all the proteins in input 2 as the query .
if input 1 contains uniprot protein ids ( www.uniprot.org ) , their sequences need not be entered in input 2 ; instead , torque automatically retrieves them from the uniprot database . for several target species ,
currently , the server supports this option for the three target species saccharomyces cerevisiae , drosophila melanogaster and homo sapiens .
the user can indicate one of these target species instead of providing inputs 3 and 4 .
the user can control two parameters of the algorithm , setting a trade - off between speed and sensitivity .
the user can set the threshold for blast similarity ( e - value ) . by setting a lower threshold , less
homologs will be identified for the query proteins , making the algorithm faster but less sensitive .
the second parameter is a threshold for the confidence values of ppi network edges provided as part of input 3 .
edges whose confidence value is lower than the threshold are discarded ; hence , this parameter determines the sparsity of the target network and affects the number of possible matches and the running time .
the running time of torque is typically a few minutes , but may be up to an hour , depending on the size and other properties of the query ( for more details , see ( 7 ) ) .
if several queries are submitted to the server at the same time , they are queued and executed sequentially . rather than waiting for the results online , they can be accessed later , in two ways :
 when a torque job is started , it is assigned a nine - digit job i d .
this i d can be used to access the results later from the main torque page.before submitting a query , the user may enter an email address .
once torque has finished processing the query , the results will be sent to the email address provided .
when a torque job is started , it is assigned a nine - digit job i d .
this i d can be used to access the results later from the main torque page . before submitting a query
once torque has finished processing the query , the results will be sent to the email address provided .
the web server generates a web page ( figure 2 ) with the image of the top - scoring match for the query in the target network , as well as an auxiliary file in.sif format that can be viewed using the cytoscape software ( 4 ) .
the content of the.sif file includes , for each edge , a numerical value representing the confidence in the interaction it represents , as provided in the input .
the image shows the subgraph induced by the top - scoring match in the ppi network .
each vertex is labeled with its protein name in the ppi network and its matching query protein , if such exists .
insertion vertices are shown in gray , and proteins from the query for which there was no match in the solution ( deletions ) are listed separately .

the following example uses as query the mouse dna synthesome complex , downloaded from the corum website ( http://mips.gsf.de/genre/proj/corum/index.html ) .
this 13-member complex was queried in the yeast network ( 5430 proteins , 39 936 interactions ) .
examining the subnetwork identified by torque we find that it is functionally coherent ( nucleotidyltransferase activity , p < 1.4e  10 ) and significantly intersects the yeast alpha dna polymerase : primase complex , supporting its biological plausibility .
the torque web server allows users to run topology - free queries on predefined or user - provided target networks .
the result is a subnetwork of the target network most similar to the query , and is presented both graphically and as a downloadable text file .
) ; german - israel foundation grant ( to r.s . ) ; postdoctoral fellowship from the edmond j. safra bioinformatics program at tel aviv university ( to f.h . ) . funding for open access charge

Answer:
torque is a tool for cross - species querying of protein
  protein interaction networks . it aims to answer the following question : given a set of proteins constituting a known complex or a pathway in one species , can a similar complex or pathway be found in the protein network of another species ? to this end , torque seeks a matching set of proteins that are sequence similar to the query proteins and span a connected region of the target network , while allowing for both insertions and deletions . unlike existing approaches
 , torque does not require knowledge of the interconnections among the query proteins .
 it can handle large queries of up to 25 proteins .
 the torque web server is freely available for use at http://www.cs.tau.ac.il/bnet/torque.html .


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 europe , prostate cancer ( pca ) is the most common malignancy in males and the third most common cause of cancer mortality .
currently , more extensive and earlier diagnosis has led to a decrease in pca related mortality [ 1 , 2 ] . despite an extended search for a more specific biomarker than prostate specific antigen ( psa ) , psa still remains the only widely employed diagnostic and follow - up marker for pca .
the predictive capability of the 4 ng / ml psa threshold as a biopsy indicator is deficient since 2040% of pca cases are thereby missed .
thus , other accurate diagnostic pca biomarkers , especially for aggressive and potentially life - threatening pca , are needed .
since increased aerobic glycolysis or the warburg effect has been identified as common to neoplastic cells , this mechanism promises potential for diagnostic and therapeutic targets .
the enzyme transketolase - like 1 ( tktl1 ) , therefore , comes into investigational focus since it is a crucial enzyme for sugar fermentation , linking glucose and fat metabolism without pyruvate dehydrogenase [ 6 , 7 ] .
when overexpressed , tktl1 activates the pentose phosphate pathway ( ppp ) , accelerating tumor cell growth and supporting tumor survival and systemic dissemination .
accordingly , an assay was developed to evaluate tktl1 based on the fluorometric epitope detection of specific antibodies in cd14/cd16 positive monocytes , following tumor cell phagocytosis and digestion ( edim - test ) .
still , the role of tktl1 as a cancer biomarker is controversial [ 10 , 11 ] and the edim - test has not been approved for routine clinical application . nevertheless ,
though tktl1 does not play a role in conventional medicine , it has gained high popularity in alternative / complementary medicine , not only as a diagnostic but also as a prediction marker to assess the risk of metastatic progression .
the goal of the current investigation was to compare the tktl1 serum level in patients with a clinically localized pca to that in healthy controls .
furthermore , the investigation was directed towards establishing whether the tktl1 serum level correlates with clinical and histologic parameters of the tumor , thus facilitating identification of patients harboring life - threatening disease requiring definitive treatment . for this purpose ,
the serum concentration of tktl1 in pca patients and healthy controls was analyzed by means of an enzyme - linked immunosorbent assay ( elisa ) , which is a highly standardized detection system , and correlated to clinical and histologic parameters .
patients ( n = 66 ) undergoing curative radical prostatectomy ( rpe ) for biopsy - proven pca in the department of urology , goethe - university , frankfurt am main , germany , were included in the investigation . controls ( n = 10 ) were healthy , age - matched , male volunteers .
firstly , 10 ml peripheral blood was drawn from patients several days before surgery and from controls .
blood samples were allowed to coagulate and then centrifuged at 3000 rpm at + 4c for 10 minutes .
the concentration of tktl1 was determined in pca patient and control serum using a commercially available elisa kit ( seh018hu , cloud - clone corp , houston , tx , usa ; sensitivity : < 0.055 ng / ml with no significant cross - reactivity or interference between tktl1 and analogues ) .
all assays were done in duplicate and the concentration was calculated from a standard curve using a 4-parameter curve fit ( magellan software , tecan ) .
univariate analysis was performed by the wilcoxon - man - whitney - test for comparison between two groups and the kruskal - wallis - test with the iman - conover - method ( bonferroni - holm - corrected ) for more than two groups .
hanns ackermann , epsilon - publishers , frankfurt , germany ) . the null hypothesis ( tktl1 concentration in serum of pca patients does not differ from that of healthy volunteers ) was rejected if p - values were less than 0.05 .
the clinical tumor stage was classified according to the 7 edition of the ajcc and the pathologic tumor stage was determined according to the 6 edition of the tnm classification .
imaging was carried out according to the currently valid guidelines of the european association of urology .
the median age at tumor diagnosis was 66 years ( range 4688 ) and the median serum psa was 8.0 ng / ml ( range 1.857.0 ) ( median age control group : 60 years ( 5572 ) ; control psa : 2.8 ng / ml ( 2.04.0 ) . nearly all pcas submitted to surgery were clinically significant .
none of the patients had evident clinical signs of infection or acute or chronic inflammation at surgery .
clinical and histopathological demographics of 66 pca patients values expressed as median with range or number ( % ) .
rpe  radical prostatectomy ; dre  digital rectal examination , psad  psa density univariate analysis of the elisa investigation demonstrated that serum tktl1 was significantly lower in the serum of pca patients , compared to healthy controls ( p=0.0001 , effect size indicator r = z / sqr(n ) = 0.4179 , figure 1 ) .
however , correlation between serum tktl1 and serum psa ( p = 0.38 ) , biopsy and prostatectomy gleason sum ( p = 0.79 and 0.89 , respectively ) , prostate volume ( p = 0.23 ) , psa density ( p = 0.80 ) , clinical and pathologic t - stage ( p = 0.66 and 0.65 ) , highest gleason pattern in the biopsy and prostatectomy specimen ( p = 0.83 and 0.74 , respectively ) , upgrade of gleason sum from biopsy to prostatectomy ( p = 0.86 ) , pn- , l- , v- , n- and r status ( p = 0.32 , 0.88 , 0.30 , 0.90 and 0.32 , respectively ) , extracapsular extension , seminal vesicle invasion as well as d`amico classification ( p = 0.75 , 0.89 and 0.34 , respectively ) did not reach statistical significance . tktl1 serum concentration ( ng / ml ) in pca patients and controls .
box : lower line  quartile q1 ( 25%  quantile ) ; middle line
tktl1 , as evaluated by the edim - test , has been propagated as a reliable cancer biomarker , since a positive correlation between tktl1 expression and tumor progression has been reported .
however , investigations negating the reliability of tktl1 have also been published [ 11 , 13 ] , making a definitive assessment regarding tktl1 reliability as a biomarker questionable .
indeed , the decreased serum tktl1 found in pca patients in the present investigation stands in opposition to the increase in monocyte associated tktl1 claimed by the proponents of the edim - test .
however , the different methods and localities , where tktl1 was measured , in serum and in macrophages , could account for the differing results . speculatively , assuming the accuracy of the edim test together with the theoretical background proposed by coy and colleagues , an inverse correlation between tktl1 detected in macrophages and extracellular tktl1 in serum could occur , since tumor cells undergo phagocytosis .
tktl1 could therefore be sequestered in macrophages and the tktl1 level in serum be reduced . still , this hypothesis is speculative and requires further evaluation .
although , in the present investigation , serum tktl1 levels differed in cancer patients and healthy persons , no correlation was apparent between serum tktl1 and clinical or pathologic parameters .
conflicting reports about tktl1 expression associated with various cancer entities and clinical outcome have been published by several investigators [ 10 , 13 , 14 ] .
tktl1 , determined with the same immunohistochemical method in colorectal cancer tissues , has been positively associated with tumor progression and tktl1-expression level in one study , whereas another study pointed to a significant decrease in tktl1-expression associated with metastasis .
recently , the dna demethylating agent 5-aza-2'-deoxycytidine ( 5-aza ) has been reported to augment expression of tktl1 in melanoma cells and was associated with enhanced invasion of the tumor cells , whereas others have demonstrated reduced invasion of melanoma cells under 5-aza treatment .
grimm et al . correlated an increase of edim scores with a metabolic shift from aerobic to anaerobic conditions , whereas this correlation could not be confirmed by others .
possibly , these inconsistencies have led to the recommendation of combining tktl1 quantification with a standardized panel of established blood biomarkers .
the ambivalence of tktl1 expression in so many different investigations shows that the role of tktl1 may be more complex than initially thought .
this study was designed as a pilot investigation and thus includes a limited number of patients .
since patients only underwent a general health check , this could contribute to a potential , though unlikely , bias for the high serum tktl1 expression found in this cohort .
the study was designed to assess the diagnostic potential of tktl1 , not its prognostic ability . since pca , in most cases ,
is associated with slow progression , long - term follow - up would be required to follow the course of serum tktl1 during the course of the disease .
serum tktl1 was decreased in patients with clinically localized pca , but failed to facilitate identification of patients with aggressive disease , who might particularly benefit from definitive cancer treatment .
based on these results , we can not currently advise introducing serum tktl1 into clinical practice .
further long - term studies including larger patient cohorts and simultaneous measurement of serum tktl1 and macrophage sequestered tktl1 are warranted to clarify the role of tktl1 in pca and resolve its applicability as a pca biomarker .

Answer:
introductionmonocyte associated transketolase - like 1 ( tktl1 ) as a cancer biomarker has become popular with alternative practitioners , but plays no role in conventional medicine .
 this investigation evaluates the potential of serum tktl1 as a biomarker for prostate cancer.material and methodspatients ( n = 66 ) undergoing curative radical prostatectomy ( rpe ) for biopsy - pro - ven pca were included in the study .
 controls ( n = 10 ) were healthy , age - matched , male volunteers
 . 10 ml of peripheral blood was drawn from patients several days before surgery and from controls .
 serum tktl1 was measured using the elisa method.resultsthe median age at tumor diagnosis was 66 years and median serum psa was 8.0 ng / ml . nearly 96% of pcas submitted to surgery were clinically significant . compared to healthy controls , serum tktl1 was significantly lower in pca patients ( p = 0.0001 , effect size indicator r = z / sqr(n ) = 0.4179 ) .
 no correlation was apparent between serum tktl1 and serum psa , gleason sum , tumor stage or further clinical and pathologic parameters.conclusionsreduced serum tktl1 in pca patients stands in opposition to tktl1 epitope detection in monocytes ( edim ) based studies , whereby increased tktl1 in monocytes of tumor patients has been reported . since serum tktl1
 does not correlate with clinical parameters in the current investigation , further research is needed to clarify whether serum tktl1 has potential as a biomarker for pca .


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:
placenta accreta is a pathology characterized by abnormal and firm attachment of the placenta to the myometrium.1 the depth of penetration of the placental villi into the myometrium defines three severity levels of placenta accreta ; accreta , increta , and percreta .
accreta , the least severe and most common of the three , occurs when the placental villi attach directly to the myometrium rather than to the decidua basalis .
percreta , the most rare and severe manifestation of accreta , is the invasion of the placental villi through the entire thickness of the myometrium , and even further.2 placenta accreta tends to reoccur ; however , little is known regarding the pathophysiological processes leading to this invasive placentation .
the most severe complication of placenta accreta is spontaneous rupture of the uterus , which poses diagnostic challenges and management dilemmas , and can be a life - threatening event to the mother and fetus .
herein , we describe a woman diagnosed with repeated placenta accreta that was complicated by spontaneous rupture of the uterus .
this case demonstrates increasing placental invasiveness and , to the best of our knowledge , is a first report of this kind .
furthermore , repeated invasive placentation occurred at the same site , and not at the cesarean section ( cs ) scar , which raises a fundamental question regarding the mechanism of trophoblast implantation and location of recurrence of placenta accreta .
understanding the processes that influence the timing and location of this life - threatening complication may set the basis for better diagnosis and management protocols .
a 32-year - old woman in her fourth pregnancy , with parity of 2 , presented at 19 weeks gestation to the gynecologic emergency department with lower abdominal pain for the past 2 days .
her obstetric history included retained placenta in both first and second deliveries , which necessitated manual revision of the uterine cavity and curettage .
she had a perforation of the left posterior uterine wall during curettage in her second delivery that was laparoscopically repaired . in her third pregnancy
, she presented with an acute abdomen at 19 weeks gestation and underwent exploratory laparoscopy that demonstrated a 2.5 cm rupture in the posterior uterine wall at the site of the previous perforation .
laparoscopy was turned into laparotomy ; the rupture was sutured and the patient recovered well . magnetic resonance imaging ( mri )
performed at 21 weeks gestation demonstrated placental tissue penetrating , but not perforating , the myometrium of the posterior uterine wall , which was indicative of placenta increta ( figure 1 ) .
after counseling , the couple chose to terminate the pregnancy , and hysterotomy was performed at 22 weeks gestation . in the current pregnancy , upon admission to the emergency department ,
the patient presented normal vital signs , and the gynecologic examination revealed 19 weeks gestation
this suspicion raised by sonography , together with the patient s history , prompted an mri at 24.2 weeks that demonstrated the presence of placenta percreta at the site of the previous placenta increta ( figure 2a ) . following counseling , the couple decided to continue the pregnancy , and the patient was hospitalized for observation .
rapid bedside ultrasound examination demonstrated intraabdominal bleeding , and emergency cs was performed . during laparotomy ,
massive intraabdominal bleeding was observed , originating from a uterine rupture with a perforating placental tissue ( figure 2b ) .
following the delivery of the fetus and complete placental removal , as well as suturing of the uterine wall , the bleeding stopped and hysterectomy was avoided .
the mother recovered well , while her neonate died of prematurity complications . due to the ominous nature of the patient s obstetric history ,
placenta accreta , at any level of severity , is a rare obstetric complication with an estimated incidence of between 1 in 533 ( as reported by wu et al3 ) and 1 in 2,500 pregnancies ( as reported by miller et al1 ) .
however , once placenta accrete is diagnosed , it has a tendency to reoccur in subsequent pregnancies.4,5 little is known about recurrence of placenta accreta , and specifically its location , histopathological invasiveness , and prognosis .
the only known risk factor for repeated placenta accreta is parity.6 here we report , for the first time , a case of four consecutive pregnancies complicated by abnormal placentation . in primary placenta accreta , the strongest independent risk factor has been found to be previous cs.1,7 this is explained by the tendency of implantation and placentation to occur in the scarred area.1 in the case presented here , recurrence occurred in the left uterine cornu , the site of the previous placenta increta , rather than the cs scar .
additionally , the clinical manifestation was aggravated with each consecutive pregnancy : retained placenta necessitating manual lysis and curettage in the first and second , placenta increta in the third , and spontaneous uterine rupture due to placenta percreta in the fourth .
therefore , this case presents not only placenta accreta recurrence but also increased invasiveness of the placentation .
even though placentation is prone to develop within previous cs scars , other prior uterine injuries may play a similar role , and hence are considered to be a risk factor for placenta accreta.7 it is not known whether injury location affects the risk for placenta accreta . the correlation between scarred uteri and placenta accreta
is explained by a relative hypoxic environment in the scar tissue8 or the histologically abnormal structure of the scar .
this abnormal structure is characterized by defective re - epithelialization and relative abundance of extracellular matrix.9 alternatively , prior uterine injury is associated with dynamic changes in decidual leukocyte distribution,10 which subsequently affects the homing of the blastocyst to its implantation site .
once placenta accreta is diagnosed , proper counseling and discussion with the patient should be undertaken regarding further management of the pregnancy in light of the complications involved.11 the most severe complication is spontaneous rupture of the uterus , as seen in this case , which poses both a diagnostic challenge and an immediate risk to the life of both mother and fetus .
the incidence of spontaneous uterine rupture is reported to be approximately one in 5,000 ; however , this includes etiologies other than placenta accreta.12 uterine rupture due to placenta accreta is extremely rare , and a systematic review of reported cases is yet to be done . in the past ,
most cases were managed by hysterectomy , but conservative treatment is becoming common recently.13,14 during the operation , active bleeding stopped promptly and the patient remained hemodynamically stable . completing the procedure outweighed the risk of blood loss involved in hysterectomy , and uterine repair was technically feasible .
the location where spontaneous uterine rupture occurs has not been thoroughly studied ; however , some reports associate first trimester ruptures with the fundus and third trimester ruptures with the lower uterine segment.15 in case of previous cs , the rupture usually occurs at the site of the old scar.12 in our patient , the rupture appeared in the left uterine cornu , where the placenta was invading through the myometrium , rather than in the cs scar .
this could be explained by the fact that the uterine wall was already disrupted by the placenta percreta prior to the rupture , as was seen in the mri . as with rupture location , factors affecting the timing of uterine rupture due to placenta accreta
while it is well established that spontaneous uterine rupture usually occurs in the third trimester,15 there have been reports of first8 and second1619 trimester ruptures as well . in our case , spontaneous rupture occurred at 24 weeks gestation ; a critical time for the fetus .
this gestational age marks the limit of viability , since preterm delivery around this time results in 50% long - term survival probability of the newborn.20 in the face of immediate risk for the mother , urgent cs was inevitable , even when considering the probable prematurity complications for the fetus . with the increase in conservative management of placenta percreta
although systematic reviews of these complications are not yet available , this insight should be taken into account during counseling following conservative management of placenta accreta .
notes : transabdominal two - dimensional ultrasound in the transverse plane showing an abnormal placenta with thinning of the myometrium in the left posterior uterine wall , indicated by an asterisk .
similar findings are seen in the longitudinal plane in addition to fundal placental lacunas ( arrow head ) with increased blood flow by color doppler scanning .

Answer:
placenta percreta is an obstetric condition in which the placenta invades through the myometrium .
 this is the most severe form of placenta accreta and may result in spontaneous uterine rupture , a rare complication that threatens the life of both mother and fetus . in this case report , we describe a 32-year - old woman in her fourth pregnancy , diagnosed with repeated placenta accreta , which was eventually complicated by spontaneous uterine rupture at 24 weeks gestation .
 this patient had a history of abnormal placentation in prior pregnancies and previous uterine injuries .
 this case demonstrates a pattern of escalating placental invasiveness , and raises questions regarding the process of abnormal placentation and the manifestation of uterine rupture in scarred uteri .