Miracle-dz/UniFAR-FTUs huggingface dataset:
Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches

Several new direct‐acting antiviral (DAA) drugs are being developed or are already approved for the treatment of chronic hepatitis C virus (HCV) infection. HCV variants presenting drug‐resistant phenotypes were observed both in vitro and during clinical trials. The aim of this study was to characterize amino acid changes at positions previously associated with resistance in the NS3 protease in untreated Brazilian patients infected with HCV genotypes 1a and 1b. Plasma samples from 171 untreated Brazilian patients infected with HCV were obtained from the Department of Gastroenterology of Clinics Hospital (HCFMUSP) in São Paulo, Brazil. Nested PCR and Sanger sequencing were used to obtain genetic information on the NS3 protein. Bioinformatics was used to confirm subtype information and analyze frequencies of resistance mutations. The results from the genotype analysis using non‐NS3 targeted methods were at variance with those obtained from the NS3 protease phylogenetic analyses. It was found that 7.4% of patients infected with HCV genotype 1a showed the resistance‐associated mutations V36L, T54S, Q80K, and R155K, while 5.1% of patients infected with HCV genotype 1b had the resistance‐associated mutations V36L, Q41R, T54S, and D168S. Notably, codons at positions 80 and 155 differed between samples from Brazilian patient used in this study and global isolates. The present study demonstrates that genotyping methods targeting the NS3 protein showed a difference of results when compared to mainstream methodologies (INNO‐LiPA and polymerase sequencing). The resistance mutations present in untreated patients infected with HCV and codon composition bias by geographical location warrant closer examination. J. Med. Virol. 86: 1714–1721, 2014. © 2014 Wiley Periodicals, Inc.
Studies on the prevalence of oncogenic HPV types among Lithuanian women with cervical pathology

Human papillomavirus (HPV) is the main cause of cervical cancer. Therefore, the detection of oncogenic HPV types is important in predicting the risk of cervical cancer. The aim of the current study was to estimate the prevalence of 16 carcinogenic and potentially carcinogenic HPV types in the study group of Lithuanian women with various grades of cervical pathology in comparison to healthy women. A total of 824 cervical specimens were investigated for HPV DNA: 547 specimens of women with abnormal cytology and 277 specimens of healthy women. Cytological diagnosis was confirmed by histology. For the detection of HPV infection, HPV DNA was amplified by PCR using three different primer systems. HPV DNA was detected in 67.6% of specimens collected from women with abnormal cytology and 24.2% of specimens collected from healthy women. The frequency of HPV‐positive specimens correlated with the severity of cervical pathology: it ranged from 50.0% in the subgroup of atypical squamous cells to 80.6% in cervical cancer. In cases confirmed by histology the frequency of HPV‐positive specimens ranged from 68.6% in the subgroup of cervical intraepithelial neoplasia grade 1 to 89.2% in cervical intraepithelial neoplasia grade 3 or carcinoma in situ. HPV DNA‐positive samples were further investigated for the presence of 16 HPV types by multiplex PCR. The most common HPV type was HPV 16 (detected in 42.3% of HPV‐positive specimens) followed by HPV 31 (10.1%), HPV 33 (8.2%), and HPV 56 (5.7%). In contrast, the frequency of HPV 18 was lower as compared to other countries. J. Med. Virol. 87:461–471, 2015. © 2014 Wiley Periodicals, Inc.
Randomized Controlled Trial Comparing Hand-Assisted Retroperitoneoscopic Versus Standard Laparoscopic Donor Nephrectomy

Background Laparoscopic donor nephrectomy (LDN) has become the gold standard for live-donor nephrectomy, as it results in a short convalescence time and increased quality of life. However, intraoperative safety has been debated, as severe complications occur incidentally. Hand-assisted retroperitoneoscopic donor nephrectomy (HARP) is an alternative approach, combining the safety of hand-guided surgery with the benefits of endoscopic techniques and retroperitoneal access. We assessed the best approach to optimize donors’ quality of life and safety. Methods In two tertiary referral centers, donors undergoing left-sided nephrectomy were randomly assigned to HARP or LDN. Primary endpoint was physical function, one of the dimensions of the Short Form-36 questionnaire on quality of life, at 1 month postoperatively. Secondary endpoints included intraoperative events and operation times. Follow-up was 1 year. Results In total, 190 donors were randomized. Physical function at 1 month follow-up did not significantly differ between groups (estimated difference, 1.79; 95% confidence interval, −4.1 to 7.68; P=0.55). HARP resulted in significantly shorter skin-to-skin time (mean, 159 vs. 188 min; P<0.001), shorter warm ischemia time (2 vs. 5 min; P<0.001) and a lower intraoperative event rate (5% vs. 11%, P=0.117). Length of stay (both 3 days; P=0.135) and postoperative complication rate (8% vs. 8%; P=1.00) were not significantly different. Potential graft-related complications did not significantly differ (6% vs. 13%; P=0.137). Conclusions Compared with LDN, left-sided HARP leads to similar quality of life, shorter operating time, and warm ischemia time. Therefore, we recommend HARP as a valuable alternative to the laparoscopic approach for left-sided donor nephrectomy.
Pilot trial of effectiveness of mindfulness meditation for substance abuse patients

Aims, setting and intervention: This pilot study compared outcomes of 18 randomized substance‐abuse recovery house patients who received 8 weeks of mindfulness meditation plus standard treatment with that of 13 patients receiving just standard treatment. Design, measurement and findings: Addiction Severity Index composite scores indicated relatively greater improvement in medical problems over a 5‐month follow‐up period (baseline, 8 weeks and 5 months) for the meditation group, but no other group differences on this multi‐dimensional measure of various life problems. The groups did not differ in urine toxicology results during the study or at 8 weeks and 5 months. No differential group change was found on measures of psychological health. Conclusion: This initial small pilot evaluation yielded relatively little indication that meditation enhanced treatment outcomes for the substance abuse patients studied.
Stellenwert der intensivierten Chemotherapie und der neuen Substanzen in der adjuvanten und palliativen Situation beim kolorektalen Karzinom

Erfreulicherweise haben sich die Behandlungsmöglichkeiten für Patienten mit kolorektalem Karzinom deutlich verbessert. Standardisierte chirurgische Verfahren sind die wichtige Basis für die Prognoseverbesserung. Durch den Einsatz systemischer adjuvant applizierter Chemotherapieregimes kann die Prognose von Patienten mit kolorektalem Karzinom weiter verbessert werden. Studien zum adjuvanten Einsatz von Cetuximab oder Bevacizumab laufen allerdings noch, und deren Abschluss muss abgewartet werden, bevor eine wissenschaftlich abgesicherte Empfehlung ausgesprochen werden kann. In der Behandlung des metastasierten kolorektalen Karzinoms sind die therapeutischen Möglichkeiten durch die Etablierung verschiedener Chemotherapieregimes, die Entwicklung von Zweit-, Dritt- oder Viertlinientherapiekonzepten und den Einsatz von monoklonalen Antikörpern wesentlich verbessert worden. Eine Aufgabe der Zukunft wird es sein, den sequentiellen oder primären Einsatz dieser Medikamente besser zu definieren. Darüber hinaus scheinen aufgrund der unterschiedlichen Wirkmechanismen von Cetuximab und Bevacizumab auch Kombinationen dieser Medikamente möglich, wie kürzlich bereits bei Irinotecan-resistenten Patienten gezeigt werden konnte. Zunehmend wird jedoch auch die interdisziplinäre Zusammenarbeit im Vordergrund stehen, um einen effizienten Einsatz der Ressourcen sowohl für die Palliation als auch für die Kuration kolorektaler Karzinome zu gewährleisten.
Cardiorespiratory Fitness in Early-stage Alzheimer Disease

There is an increasing interest in exercise and fitness in Alzheimer disease (AD) given evidence suggesting a role in the maintenance of cognitive health. There is, however, little data on the objective measure of cardiorespiratory fitness in individuals with AD. Thus, we assessed cardiorespiratory fitness in early AD and its relationship with physical activity levels, health markers, and cognitive performance in nondemented (Clinical Dementia Rating 0, n=31) and early-stage AD (Clinical Dementia Rating 0.5 and 1, n=31) participants. Cardiorespiratory fitness was assessed with maximal exercise testing to determine peak oxygen consumption (VO2peak). Additionally, dual emission x-ray absorptiometry scanning for body composition and glucose tolerance tests were conducted. Despite reductions in physical performance and habitual physical activity levels in early AD, cardiorespiratory fitness (VO2peak) was comparable in the 2 groups (19.8 in early AD vs. 21.2 mL/kg/min in nondemented, P=0.26). AD participants performed well on treadmill tests with similar levels of perceived exertion, maximal heart rate, and respiratory exchange ratio compared with nondemented individuals. After controlling for age and sex, VO2peak was associated with a beneficial glucoregulatory profile and inversely associated with percent body fat, body mass index, and triglycerides. A relationship between cognitive performance measures and VO2peak was not apparent. These results suggest that individuals in the early stages of AD have the capacity for maximal exercise testing and have comparable levels of cardiorespiratory fitness as nondemented individuals. Reduced physical activity associated with early AD underscores the need for further defining the role of exercise as a potential therapeutic intervention in the early stages of AD.
The use of machine learning and nonlinear statistical tools for ADME prediction

Absorption, distribution, metabolism and excretion (ADME)-related failure of drug candidates is a major issue for the pharmaceutical industry today. Prediction of ADME by in silico tools has now become an inevitable paradigm to reduce cost and enhance efficiency in pharmaceutical research. Recently, machine learning as well as nonlinear statistical tools has been widely applied to predict routine ADME end points. To achieve accurate and reliable predictions, it would be a prerequisite to understand the concepts, mechanisms and limitations of these tools. Here, we have devised a small synthetic nonlinear data set to help understand the mechanism of machine learning by 2D-visualisation. We applied six new machine learning methods to four different data sets. The methods include Naive Bayes classifier, classification and regression tree, random forest, Gaussian process, support vector machine and k nearest neighbour. The results demonstrated that ensemble learning and kernel machine displayed greater accuracy of prediction than classical methods irrespective of the data set size. The importance of interaction with the engineering field is also addressed. The results described here provide insights into the mechanism of machine learning, which will enable appropriate usage in the future.
Molecular characterization of hepatitis C virus core region in moroccan intravenous drug users

Intravenous drug users (IDUs) represent a highly‐infected reservoir for Hepatitis C virus (HCV) worldwide, harboring some of the most elevated prevalences and majority of the epidemic in developed nations. Studies aimed at sequencing regions of the viral genome uncovered amino acid mutations, some of which have been implicated in resistance to standard of care pegylated interferon/Ribavirin double therapy. Using the nested PCR method on the Core region of HCV strains in Moroccan IDUs living in the Tangier region this study sought to identify genotype‐specific amino acid mutations, followed by Phylogenetic methods in order to compare them with international strains so as to identify sequences of highest homology. Genotyping was confirmed and recombination events excluded by line‐probe assay. Italy was found most homologous for genotypes 1a and 3a, Iran for genotype 1a and Egypt for genotype 4a. Amino Acid Mutation analysis revealed the following novel genotype 3a‐specific mutations: N16I, L36V, T49A, P71S, T75S, and T110N. The outcome of this work describes the HCV genetic heterogeneity in high‐risk intravenous drug users, and it gives clues to the global migratory flow of genotypes as they cross geographical boundaries between various IDU populations and identifies “signature” amino acid mutations traceable to HCV genotype 3a. Identification of key amino acid positions in the HCV Core region with higher rates of mutations paves the way for eventual clinical trials seeking to establish a link between these recurrent mutations and response to standard of care Interferon and Ribavirin antiviral therapy. J. Med. Virol. 88:1376–1383, 2016. © 2016 Wiley Periodicals, Inc.
Perilymphatic Atrophy of the Skin

To the Editor. — There have been several reports of linear atrophy of the skin running along the lymphatic vessels, starting at the site of corticosteroid injections. 1,2 We would like to report an interesting case. Report of a Case. — A 34-year-old woman with a previous history of alopecia areata in 1967 suddenly developed alopecia areata one week prior to the first examination. She remembered that intradermally administered injections of corticosteroids performed at another hospital were quite effective in 1967. At first examination on June 29, 1973, she had a lesion of alopecia areata on the right side of the forehead, into which we injected 8 mg of triamcinolone acetonide in aqueous suspension. A week later, hair regrowth was evident. On July 14, the same dose of triamcinolone was injected in the same manner. On July 21, or 22 days after the first injection, atrophy and accentuation of the underlying venous pattern were noted. Within the lesion, small areas
Efficacy of Early Identification and Early Intervention

Thi s q u e s t i o n p r e s e n t s a s igni f icant chal lenge to the professions of audiology, speech / l anguage pathology, and deaf education. Professionals providing early intervention to families of children with educationally significant hearing loss respond emphatically in the affirmative to this question. However, pediatric audiologists and pediatricians are quest ioning whether sufficient documentation of the efficacy of early identification of hear ing loss exists (Bess & Paradise, 1994). Review of the l i t e ra ture leads o n e to the conclusion that only a paucity of research is avai lable to d o c u m e n t t h e benef i t s of early identification and in tervent ion. Two comprehensive reviews are available (Carney & Moe l l e r , in p ress ; N o r t h e r n & Hayes , 1994). Both of these reviews come to the conc lus ion tha t b o t h early ident i f ica t ion and early intervention are efficacious. Bess and Paradise (1994) claim that two studies failed to demons t ra te that early identificat i o n a n d i n t e r v e n t i o n h a v e b e n e f i c i a l resul ts . O n e of these s tudies was a study f rom a p r o g r a m in I s r ae l . B o t h s t u d i e s investigated only the oral m e t h o d of communicat ion. These studies lead them to the conclusion that because children with identification of hear ing loss before 2-1/2 years of age did no t differ from those identified after 2 1 / 2 years , i den t i f i ca t ion at b i r t h would yield no better results than identificat ion by 18 m o n t h s of age . Most efficacy s t u d i e s , h o w e v e r , c a n n o t b e c o m p a r e d because of s ignif icant h i s tor ica l c h a n g e s a n d d i f fe rences in i n t e r v e n t i o n m o d e l s . Each study can only describe the condit ions and characteristics of the subset of the popula t ion of deaf a n d h a r d of h e a r i n g child ren from a specific time period.
LACTIC ACID OF SPINAL FLUID IN MENINGITIS: PRACTICAL DIAGNOSTIC AND PROGNOSTIC VALUE

In 1926,1one of us (Dr. Killian) and his associate reported that spinal fluid from cases of meningitis showed unusually high values for lactic acid and low ones for sugar. The source of the increased lactic acid appeared to lie in the metabolic activity of the leukocytes. These studies were continued, and in 19282we came to the conclusion that the changes in lactic acid concentration were a better index of the progress of the infection than the changes in the sugar content. In meningitis the lactic acid of the spinal fluid was greater than that of the blood, but the sugar of the spinal fluid was less than that of the blood. Furthermore, the lactic acid of the spinal fluid may fluctuate within a wide range, although the amount of sugar remains normal. Since our first observations, similar studies have been reported by others.3In the
Conference report: "Functional Glycomics in HIV Type 1 Vaccine Design" workshop report, Bethesda, Maryland, April 30-May 1, 2012.

A vital part of the renewed hope for a vaccine against the human immunodeficiency virus (HIV-1) is based on recent studies that have highlighted major sites of HIV-1 vulnerability that could be effectively targeted by a preventive vaccine. One of these potential vulnerabilities includes the dense cluster of carbohydrates surrounding HIV-1's envelope glycoproteins gp120 and gp41, typically referred to as the "glycan shield. " Recent data from several laboratories have shown that glycans on the HIV-1 envelope form key epitopes for broadly neutralizing antibodies (bNAb). Moreover, HIV-1 envelope glycans play an important role in viral transmission, antigenicity, and immunogenicity. The recent availability of novel tools and technologies has now allowed investigators to leverage glycomic structure-function relationships in the design of candidate HIV-1 vaccines. Additionally, glycans modulate the immune response, playing an essential role in Fc receptor and complement activity. To promote cross-disciplinary collaboration and promote synergistic HIV-1- glycomics research, the National Institutes of Health (NIH) cosponsored and convened a 1.5-day workshop entitled "Functional Glycomics in HIV-1 Vaccine Design. " The meeting focused on the role of glycan interactions with neutralizing antibodies, the influence of immunoglobulin G (IgG) Fc receptor glycosylation, newly available glycomics technologies, and how new information on the role of glycans could be applied in HIV-1 immunogen design strategies. This report summarizes the discussions of this workshop.
Anti-mullerian hormone and inhibin B in the definition of ovarian aging and the menopause transition.

CONTEXT/OBJECTIVE The objective of the study was to determine whether anti-Mullerian hormone (AMH) and inhibin B are viable endocrine biomarkers for framing the menopause transition from initiation to the final menstrual period (FMP). DESIGN We assayed AMH, inhibin B, and FSH in 300 archival follicular phase specimens from 50 women with six consecutive annual visits commencing in 1993 when all women were in the pre- and perimenopausal menopause stages. Subsequently each woman had a documented FMP. The assay results were fitted as individual-woman profiles and then related to time to FMP and age at FMP as outcomes. RESULTS Based on annual values from six time points prior to the FMP, (log)AMH longitudinal profiles declined and were highly associated with a time point 5 yr prior to FMP [including both observed and values below detection (P < 0.0001 and P = 0.0001, respectively)]. Baseline AMH profiles were also associated with age at FMP (P = 0.035). Models of declining (log)inhibin B profiles (including both observed and values below detection) were associated with time to FMP (P < 0.0001 and P = 0.0003, respectively). There was no significant association of (log)inhibin B profiles with age at FMP. CONCLUSIONS AMH, an endocrine marker that reflects the transition of resting primordial follicles to growing follicles, declined to a time point 5 yr prior to the FMP; this may represent a critical biological juncture in the menopause transition. Low and nondetectable levels inhibin B levels also were observed 4-5 yr prior to the FMP but were less predictive of time to FMP or age at FMP.
miR‐29a associates with viro‐immunological markers of HIV infection in treatment experienced patients

MicroRNAs (miRNAs) are small, non‐coding RNA species essential for the post‐translational regulation of gene expression. Several miRNA have been proposed to contribute to Human immunodeficiency virus‐1 (HIV‐1) infection establishment, progression and latency. Among them, miR‐29a seems to be of particular interest. The aim of this study was to investigate the association between miR‐29a expression and immunologic and virologic markers of HIV infection progression in long‐term antiretroviral‐treated individuals. In a homogenous group of 165 young adults, with chronic HIV infection, parenterally acquired during childhood, the expression level of miR‐29a was found to be inversely correlated with HIV viral load and the degree of immunosuppression, expressed by both CD4 cell count and the CD4/CD8 ratio. There was a significant difference in miR‐29a expression according to the patient's response to treatment, with the lowest levels expressed by patients with treatment failure, defined as detectable viremia and CD4 < 350 cells/mm3. No significant correlation was found between miRNA level and the nadir CD4 count or zenith HIV viral load. This study establishes the association between miR‐29a expression and markers of HIV infection in long‐term survivors, treatment‐experienced patients, suggesting its potential use as an indicator for the on‐treatment disease evolution. J. Med. Virol. 88:2132–2137, 2016. © 2016 Wiley Periodicals, Inc.
Rapid-onset Apathy May Be the Only Clinical Manifestation After Dorsal Striatum Hemorrhagic Lesion: A Case Report

Apathy is a common clinical feature of stroke patients and it is often correlated with cognitive deficits, functional impairment and depression. Here we report the case of a 70-year-old woman with no history of neuropsychiatric disorders who showed abrupt onset of pure apathy after the onset of a right brain vascular lesion located in the head of the caudate nucleus, the anterior part of the putamen, and the genu and the anterior limb of the internal capsule. A complete neuropsychological and neurological examination did not show deficits. A comprehensive neuropsychiatric assessment focusing on the post-stroke hospitalization period showed severe motor, cognitive and affective apathy with no depression or other neuropsychiatric symptoms. This case highlights the key role of the dorsal striatum in the development of pure apathy, possibly due to its function in regulating approach-attachment behavior, affect and initiative, which are the emotional, cognitive and motor dimensions of apathy.