Miracle-dz/UniFAR-FTUs huggingface dataset:
Does Discontinuous Involvement of a Prostatic Needle Biopsy Core by Adenocarcinoma Correlate With a Large Tumor Focus at Radical Prostatectomy?

When prostate needle biopsies are involved discontinuously by tumor, no consensus remains on the optimal method of tumor quantification. We investigated whether discontinuous biopsy involvement usually results from a large tumor focus or multiple small foci. Prostate needle biopsies with discontinuous tumor and corresponding whole-mounted radical prostatectomies from 2008 to 2013 were analyzed. Linear length and percentage of biopsy involvement were measured both including and subtracting the benign intervening tissue. The corresponding region of the prostatectomy specimen was evaluated for tumor size and multifocality. From over 800 biopsy sets and 400 prostatectomies performed annually, 40 patients met inclusion criteria. Excluding benign tissue, length and percentage of biopsy involvement ranged from 1 to 7 mm and 5% to 66% (median 2.5 mm, 20%), whereas including intervening tissue yielded 4 to 15.5 mm and 25% to 100%, (median 7 mm, 70%), respectively. Benign intervening tissue measured from 2 to 10.5 mm (median 3.5 mm). In 31 patients (78%), a single tumor focus was present in the corresponding region of the prostate (the dominant tumor in 25/31). In 9 patients, multiple small foci were present. Eleven patients could have been excluded from active surveillance eligibility by measuring tumor from end to end (>50% involvement), of whom only 1 met criteria for clinically insignificant cancer at prostatectomy. Discontinuous tumor in a prostate biopsy often results from a single tumor focus in the corresponding region of the prostate (78%). Therefore, we recommend that an end-to-end measurement be provided, with accompanying diagnostic comment that this often correlates with the size of a single tumor focus.
Assessing the mental state through a blog: psychiatry in the 21st century?

Blogs have become increasingly popular over the past 15 years, especially with young people. In this editorial we discuss how the blogosphere is reshaping information exchange in healthcare. More specifically, blogs may change the doctor-patient relationship and provide clinically relevant information to mental health practitioners. However, the use of blogs as a source of clinical material raises ethical and legal issues.
The Burden of Stroke in Nigeria

Stroke is a leading cause of morbidity and mortality worldwide, and it is likely to worsen in developing countries over the next two decades based on the projections by the World Health Organization (WHO). With the current scourge of HIV/AIDS and the battle against other communicable diseases like multi-drug resistant malaria and tuberculosis; Nigeria, the most populous black nation in the world, stands to risk the further straining of its resources as a result of the increasing prevalence of stroke and other cardiovascular diseases due to epidemiological transition. The current prevalence of stroke in Nigeria is 1.14 per 1000 while the 30-day case fatality rate is as high as 40%. Management of the disease is largely conservative while there is little or no funding for high-quality research. Primary prevention is the key to reducing the burden of the disease in a country with such poor resources.
Prostate Biopsy Specimens With Gleason 3+3=6 and Intraductal Carcinoma: Radical Prostatectomy Findings and Clinical Outcomes

Although intraductal carcinoma of the prostate (IDC-P) is typically present on biopsies in which there is also invasive prostate carcinoma of Gleason pattern 4 or 5 and an associated unfavorable outcome, there are limited studies on IDC-P in needle core biopsies or transurethral resections (TURP) with only a concomitant low-grade invasive component. There are differing opinions on incorporating IDC-P into the Gleason score in such cases. The aim of this study was to investigate clinical outcomes and radical prostatectomy (RP) findings in patients with Gleason 3+3=6 and IDC-P on biopsy or TURP. We identified 73 patients in our consult files (2001 to 2014) who had IDC-P and Gleason score 6 carcinoma on biopsy or TURP with no invasive higher Gleason grade component. Clinical follow-up information was available in 62 patients. Treatment was RP in 14 patients, radiation therapy in 31 patients, androgen deprivation therapy in 1 patient, and cryotherapy in 1 patient. Four patients were found to have metastatic disease at the time of diagnosis and were treated with chemotherapy. Eleven patients underwent active surveillance after diagnosis, of which 6 were eventually treated for progressive disease. The 14 RP specimens were centrally reviewed, and 86% had extensive IDC-P present. The Gleason grades in these 14 RP cases were 3+3=6 in 21%, 3+4=7 in 36%, 4+3=7 in 29%, and 4+4=8 in 14%. Pathologic stage was pT2 in 36%, pT3a in 36%, and pT3b in 28%. After 3 years, there was a 20% actuarial rate of disease progression in men who underwent either RP or radiation therapy. In summary, most men with IDC-P on biopsy/TURP have aggressive tumors, even when the invasive tumor on biopsy is Gleason score 6. As a minority of men may only have Gleason 6 invasive cancer at RP and a favorable prognosis, we recommend that IDC-P on biopsy/TURP be reported separately and not assigned a Gleason score.
Metabolic Syndrome Increases Carotid Artery Stiffness: the Northern Manhattan Study

Background Arterial stiffness, an intermediate pre-clinical marker of atherosclerosis, has been associated with an increased risk of stroke and cardiovascular disease. The metabolic syndrome and its components are established cardiovascular disease risk factors and may also increase arterial stiffness; however, data regarding this are limited. Aim The goal of this study was to determine the association between the metabolic syndrome and carotid artery stiffness in an elderly multi-ethnic cohort. Methods Carotid artery stiffness was assessed by carotid ultrasound as part of the Northern Manhattan Study, a prospective population-based cohort of stroke-free individuals. Carotid artery stiffness was calculated as [In (systolic BP/diastolic BP)/strain], where strain was [(systolic diameter diastolic diameter)/diastolic diameter]. Metabolic syndrome was defined by the National Cholesterol Education Program: Adult Treatment Panel III criteria. LogSTIFF was analysed as the dependent variable in linear regression models, adjusting for demographics, education, current smoking, presence of carotid plaque and intima-media thickness. Results Carotid artery stiffness was analysed in 1133 Northern Manhattan Study subjects (mean age 65 ± 9 years; 61% women; 58% Hispanic, 22% Black and 20% Caucasian). The prevalence of the metabolic syndrome was 49%. The mean LogSTIFF was 2·01±0·61 among those with the metabolic syndrome and 1·90 ± 0·59 among those without the metabolic syndrome (P = 0·003). The metabolic syndrome was significantly associated with increased logSTIFF in the final adjusted model (parameter estimate β = 0·100, P = 0·01). Among individual metabolic syndrome components, waist circumference and elevated blood pressure were most significantly associated with a mean increase in logSTIFF (P < 0·01). Conclusion The metabolic syndrome is significantly associated with increased carotid artery stiffness in a multiethnic population. Increased carotid artery stiffness may, in part, explain a high risk of stroke among individuals with the metabolic syndrome.
SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type

The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors. Among primary ovarian tumors, SATB2 staining was observed in 0/22 mucinous cystadenomas that lacked a component of mature teratoma, 4/12 mucinous cystadenomas with mature teratoma, 1/60 mucinous borderline tumors, 0/17 mucinous adenocarcinomas, 0/3 endometrioid borderline tumors, and 0/72 endometrioid adenocarcinomas. Among ovarian metastases, SATB2 staining was observed in 24/32 (75%) colorectal adenocarcinomas; 8/10 (80%) low-grade appendiceal mucinous neoplasms; and 4/4 (100%) high-grade appendiceal adenocarcinomas. No SATB2 staining was observed in any ovarian metastasis of pancreatic, gastric, gallbladder, or endocervical origin. Evaluation of primary extraovarian tumors showed the highest incidences of SATB2 staining among primary colorectal adenocarcinomas (71%), primary appendiceal low-grade mucinous neoplasms (100%), and primary appendiceal high-grade adenocarcinomas (100%). Similar to their metastatic counterparts, none of the primary pancreatic or gastric adenocarcinomas showed any SATB2 staining. In a subset of tumors for which CK7, CK20, and CDX2 were available, SATB2 was never positive in any tumor of any origin that was CK7+CK20−CDX2−. Among tumors that coexpressed all 3 markers (CK7+CK20+CDX2+), 6/7 SATB2+ tumors were of colorectal or appendiceal origin, and 1/7 was a primary ovarian borderline tumor. We conclude that ovarian tumors with mucinous or endometrioid features that express SATB2 are unlikely to be of primary ovarian origin unless there is a component of mature teratoma in the ovary; instead, attention should be directed to a colorectal or appendiceal origin. SATB2 may be of particular value in ovarian mucinous tumors that are positive for all 3 markers (CK7+CK20+CDX2+), as SATB2 staining strongly implicates a colorectal or appendiceal origin.
Low Birth Weight. A Medical, Psychological, and Social Study

This is an outstanding book. It covers numerous difficult topics usually left out of conventional disease-orientated paediatric textbooks and thus fills an important gap, particularly for clinical medical officers, general practitioners, and paediatricians in training. It is indeed a handbook, centred on 'the assessment of hearing, seeing, thinking and growing' and packed with practical information. It begins with a good chapter on normal growth and a discussion of the factors that may influence growth with, for example, straightforward information about how to evaluate an underweight child or an obese one. This is followed by equally useful chapters on practical medical genetics, nutrition and metabolism, and interviewing children and parents. Three chapters cover normal neurological development, mental handicap, and neurological disorders (divided into eight sections). Especially good are the sections on 'The child who does not walk' and 'The child who fails at school'. There are two chapters on visual and hearing development and assessment, followed by a three section chapter on language and speech containing another excellent contribution by Ruth Day on 'The child who does not talk'. There are chapters on social development, emotional development, behaviour disorders, educational medicine (in three parts), immunisation, epidemiology, the environment (school and physical), and a five part chapter on social paediatrics (with particularly good sections on the law, adoption and child abuse, and on disabled school leavers). There are two chapters on common infections, two on death and cot death, and a final one on malformations and orthopaedic conditions which includes tables of teratogens and their effect; and a table about drugs and breast feeding. The remaining 100 pages contain particularly useful appendices including a huge list of voluntary organisations for children with disabilities; helpful tables of biochemical and haematological normal ranges; growth, head circumference, and puberty staging charts; an innovative table of variations in growth patterns; a timetable of normal milestones and motor developments; details of the Goodenough-Harris drawing test, the Cardiff modifications of the Denver developmental screening test and the Woodside assessment test; information about neonatal reflexes and their possible significance if abnormal, accompanied by details of the Dubowitz score for clinical assessment of gestational age in newborns; a list of anticonvulsants, their dosage, their therapeutic range, and their side effects.
Numerical Analysis of Turbulent Forced Convection of Nanofluid Flow Over a Heated Shallow Cavity

This work presents a numerical investigation of turbulent forced convection of a nanofluid over a heated cavity in a horizontal duct. Heat transfers in separated flows are frequently encountered in engineering applications, such as: heat exchangers, axial and centrifugal compressor blades, gas turbines blades, and microelectronic circuit boards. Thus, it is very essential to understand the mechanisms of heat transfer in such regions in order to enhance heat transfer. Different volume fractions of nanoparticles are presented in the base fluid and different types of nanoparticles are used. The objective of this study is to check the effect of nanofluid on heat transfer in such a configuration. Numerical simulations are performed for pure water and four nanofluids (Cu, CuO, Ag, and Al2O3). The results are analyzed through the thermal and dynamical fields with a particular interest to the skin friction coefficient and Nusselt number evolutions. The average Nusselt number increases with the volume fraction of nanoparticles for the whole tested range of Reynolds number. A correlation of average Nusselt number versus Reynolds number and volume fraction of each type of nanoparticles over the cavity wall is proposed in this paper.
Thrombolytic Therapy for Acute Ischemic Stroke after Recent Transient Ischemic Attack

Background and aim Safety and efficacy of intravenous thrombolysis in stroke patients with recent transient ischemic attack are hotly debated. Patients suffering transient ischemic attack may present with diffusion-weighted imaging lesions, and although normal computed tomography would not preclude thrombolysis, the concern is that they may be at higher risk for hemorrhage ***post-thrombolysis treatment. Prior ipsilateral transient ischemic attack might provide protection due to ischemic preconditioning. We assessed post-thrombolysis outcomes in stroke patients who had prior transient ischemic attack. Methods Multicentered prospective study of consecutive acute stroke patients treated with intravenous tissue plasminogen activator (tPA). Ipsilateral transient ischemic attack, baseline characteristics, risk factors, etiology, and time-lapse to treatment were recorded. National Institutes of Health Stroke Scale at seven-days and modified Rankin Scale at three-months, symptomatic intracranial hemorrhage, and mortality were compared in patients with and without transient ischemic attack. Results There were 877 patients included, 60 (6.84%) had previous ipsilateral transient ischemic attack within ***one-month prior to the current stroke (65% in the previous 24 h). Transient ischemic attack patients were more frequently men (70% vs. 53%; P = 0.011), younger (63 vs. 71 years of age; P = 0.011), smokers (37% vs. 25%; P = 0.043), and with large vessel disease (40% vs. 25%; P = 0.011). Severity of stroke at onset was similar to those with and without prior transient ischemic attack (median National Institutes of Health Stroke Scale score 12 vs. 14 P = 0.134). Those with previous transient ischemic attack were treated earlier (117 $pL 52 vs. 144 $pL 38 mins; P #< 0.005). After adjustment for confounding variables, regression analysis showed that previous transient ischemic attack was not associated with differences in stroke outcome such as independence (modified Rankin Scale 0–2) (odds ratios: 1.035 (0.57–1.93) P = 0.91), mortality (odds ratios: 0.99 (0.37–2.67) P = 0.99), or symptomatic intracranial hemorrhage (odds ratios: 2.04 (0.45–9.32) P = 0.36). Conclusions Transient ischemic attack preceding ischemic stroke does not appear to have a major influence on outcomes following thrombolysis. Patients with prior ipsilateral transient ischemic attack appear not to be at higher risk of bleeding complications.
Identification of protein binding partners of small molecules using label-free methods

ABSTRACT Introduction: Drug discovery efforts across the globe are chasing new drug targets and novel mechanisms of action. To support the identification of novel mechanisms of action, phenotype-based drug screening has significantly increased over the last decade. Along with the rise in phenotypic screening, methods and technologies that can help to identify drug targets of phenotypically screened ‘hits’ have also evolved significantly. Areas covered: This article provides an overview of successful examples, limitations and advances in small-molecule target identification methodologies. Primarily, the methods are described, where small-molecules without derivatization are used as test-molecules for identifying their direct binding protein partners, the targets, in detail. A brief discussion of other affinity chromatography coupled mass-spectrometry based target identification methods are also presented for comparative appreciation of label-free methods. Expert opinion: Label-free methods do not require (a) extensive structure activity analysis of phenotypically screened ‘hits’ and (b) preparation of tool compounds or target capturing probes for target identification. These methods are significantly shortening the time required for the identification and the downstream validation of targets and hence are gaining popularity as the method of choice for target identification.
K45R variant of squalene synthase increases total cholesterol levels in two study samples from a French Canadian population

Squalene synthase is an important component of the cholesterol biosynthetic pathway, and inhibitors of this enzyme have been shown to lower plasma cholesterol levels. Previously, we sequenced the squalene synthase gene, FDFT1 (farnesyl‐diphosphate farnesyltransferase), and identified several SNPs, including a nonsynonymous variant, rs11549147:A>G (K45R). To examine the possible association of K45R with plasma lipid traits, we tested 887 individuals from 149 families from the founder population of Saguenay‐Lac St. Jean (SLSJ), Quebec. K45R was associated with increased total cholesterol (TC) (P=0.035) and non‐high‐density lipoprotein cholesterol (non‐HDL‐C) (P=0.01). These results were replicated in an independent sample of unrelated individuals (P=0.0008 for TC, P=0.004 for non‐HDL‐C). This SNP also influenced low‐density lipoprotein cholesterol (P=0.042) and HDL‐C (P=0.025) in the family‐based sample, and triglycerides (TG) (P=0.007) in the unrelated subjects. The lysine (K) in codon 45 is conserved across 11 mammals and lies in a potential exonic splicing enhancer (ESE) site. These results suggest that this coding variant in the squalene synthase gene influences plasma cholesterol levels, possibly by affecting the intracellular production of cholesterol. Hum Mutat 29(5), 689–694, 2008. © 2008 Wiley‐Liss, Inc.
Homozygous mutation of the PHOX2B gene in congenital central hypoventilation syndrome (Ondine's Curse)

Homozygosity for a dominant allele is relatively rare and preferentially observed in communities with high inbreeding. According to the definition of true dominance, similar phenotypes should be observed in patients heterozygous and homozygous for a dominant mutation. However, the homozygous phenotype usually tends to be more severe than the heterozygous one. In these cases, the wild‐type and mutant alleles are semi‐dominant. Here we report a patient with a Congenital Central Hypoventilation Syndrome (CCHS) phenotype and homozygosity for a PHOX2B gene mutation leading to an alanine expansion shorter than the threshold hitherto observed in CCHS patients with a heterozygous mutation. This observation adds the concept of mutational threshold per se to the discussion about dominant and recessive alleles. © 2008 Wiley‐Liss, Inc.
A Multicentre, Randomized, Double-Blinded, Placebo-Controlled Phase III Study to Investigate Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND)

Background and hypothesis Thrombolytic therapy with tissue plasminogen activator is effective for acute ischaemic stroke within 4·5 h of onset. Patients who wake up with stroke are generally ineligible for stroke thrombolysis. We hypothesized that ischaemic stroke patients with significant penumbral mismatch on either magnetic resonance imaging or computer tomography at three- (or 4·5 depending on local guidelines) to nine-hours from stroke onset, or patients with wake-up stroke within nine-hours from midpoint of sleep duration, would have improved clinical outcomes when given tissue plasminogen activator compared to placebo. Study design EXtending the time for Thrombolysis in Emergency Neurological Deficits is an investigator-driven, Phase III, randomized, multicentre, double-blind, placebo-controlled study. Ischaemic stroke patients presenting after the three- or 4·5-h treatment window for tissue plasminogen activator and within nine-hours of stroke onset or with wake-up stroke within nine-hours from the midpoint of sleep duration, who fulfil clinical (National Institutes of Health Stroke Score ≥4–26 and prestroke modified Rankin Scale <2) will undergo magnetic resonance imaging or computer tomography. Patients who also meet imaging criteria (infarct core volume <70 ml, perfusion lesion : infarct core mismatch ratio >1·2, and absolute mismatch >10 ml) will be randomized to either tissue plasminogen activator or placebo. Study outcome The primary outcome measure will be modified Rankin Scale 0–1 at day 90. Clinical secondary outcomes include categorical shift in modified Rankin Scale at 90 days, reduction in the National Institutes of Health Stroke Score by 8 or more points or reaching 0–1 at day 90, recurrent stroke, or death. Imaging secondary outcomes will include symptomatic intracranial haemorrhage, reperfusion and or recanalization at 24 h and infarct growth at day 90.