Miracle-dz/UniFAR-FTUs huggingface dataset:
Rhesus Macaques Infected with Macrophage-Tropic Simian Immunodeficiency Virus (SIVmacR71/17E) Exhibit Extensive Focal Segmental and Global Glomerulosclerosis

ABSTRACT We previously showed that inoculation of rhesus macaques with molecularly cloned lymphocytetropic simian immunodeficiency virus (SIVmac239) results in SIV-associated nephropathy (SIVAN) and that the glomerulosclerotic lesions were associated with the selection of macrophagetropic (M-tropic) variants (V. H. Gattone et al., AIDS Res. Hum. Retroviruses 14:1163–1180, 1998). In the present study, seven rhesus macaques were inoculated with M-tropic SIVmacR71/17E, and the renal pathology was examined at necropsy. All SIVmacR71/17E-infected macaques developed AIDS, and most developed other systemic complications, including SIV-induced encephalitis and lentivirus interstitial pneumonia. There was no correlation between the length of infection (42 to 97 days), circulating CD4+ T-cell counts, and renal disease. Of the seven macaques inoculated with SIVmacR71/17E, five developed significant mesangial hyperplasia and expansion of matrix and four were clearly azotemic (serum urea nitrogen concentration of 40 to 112 mg/dl). These same five macaques developed focal segmental to global glomerulosclerotic lesions. Increased numbers of glomerular CD68+ cells (monocytes/macrophages) were found in glomeruli but not the tubulointerstitium of the macaques inoculated with SIVmacR71/17E. All macaques had glomerular deposits of immunoglobulin G (IgG), IgM, and tubuloreticular inclusions, and six of seven had IgA deposition. However, there was no correlation between the presence of circulating anti-SIVmac antibodies, immunoglobulin deposition, and glomerular disease. Tubulointerstitial infiltrates were mild, with little or no correlation to azotemia, while microcystic tubules were evident in those with glomerulosclerosis or azotemia. The four most severely affected macaques were positive for diffuse glomerular immunostaining for viral core p27 antigen, and there was intense staining in the glomeruli of the two macaques with the most severe glomerulosclerosis. Viral sequences were isolated from glomerular and tubulointerstitial fractions from macaques with severe glomerulosclerosis but only from the tubulointerstitial compartment of those that did not develop glomerulosclerosis. Interviral recombinant viruses generated with env sequences isolated from glomeruli confirmed the M-tropic nature of the virus found in the glomeruli. The correlation between the increased number of CD68+ cells (monocytes/macrophages) in the glomeruli, the localization of p27 antigen in the glomeruli, and the glomerular pathology confirms and extends our previous observations of an association between glomerular infection and infiltration by M-tropic virus and SIVAN.
Budgetary Impact of Treating Acute Promyelocytic Leukemia Patients with First-Line Arsenic Trioxide and Retinoic Acid from an Italian Payer Perspective

The objective of this study was to estimate the net cost of arsenic trioxide (ATO) added to all-trans retinoic acid (ATRA) compared to ATRA plus chemotherapy when used in first-line acute promyelocytic leukemia (APL) treatment for low to intermediate risk patients from the perspective of the overall Italian healthcare systemA Markov model was developed with 3 health states: stable disease, disease event and death. Each month, patients could move from stable to disease event or die from either state. After a disease event, patients discontinued initial treatment and switched to the other regimen as second-line therapy. Treatment regimens, efficacy and adverse events were derived from published sources and expert opinion; unit costs were collected from standard Italian sources. Clinical outcomes and costs for pre-ATO and post-ATO scenarios were combined with population and product utilization information to calculate the total budgetary impact using a 3-year time horizon; one-way sensitivity analyses were conducted. Three-year cumulative pharmacy costs for ATO+ATRA were €46,700 per-patient versus €6,500 for ATRA+chemotherapy; however, medical costs for ATO+ATRA were €12,300 per-patient versus €30,200 for ATRA+chemotherapy. The total budgetary impact was estimated to be an additional €127,300, €312,500 and €477,800 in the first, second and third years, respectively. The model was most sensitive to changes in the cost of the ATO+ATRA regimen during the consolidation phase. Budgetary impact models are valuable to payers making formulary decisions regarding the access and affordability of new medicines. The cost of treatment analysis showed that pharmacy costs for ATO+ATRA were higher than for ATRA+chemotherapy, while all other evaluated costs were lower for ATO+ATRA treated patients. The average budgetary impact was €305,900 per year overall, representing a 3.5% increase. Further research is needed to determine the cost-effectiveness of ATO+ATRA compared to the current first-line standard of care in APL.
Geometric characteristics of hydrogen bonds involving sulfur atoms in proteins

Sulfur atoms have been known to participate in hydrogen bonds (H‐bonds) and these sulfur‐containing H‐bonds (SCHBs) are suggested to play important roles in certain biological processes. This study aims to comprehensively characterize all the SCHBs in 500 high‐resolution protein structures (≤1.8 Å). We categorized SCHBs into six types according to donor/acceptor behaviors and used explicit hydrogen approach to distinguish SCHBs from those of nonhydrogen bonding interactions. It is revealed that sulfur atom is a very poor H‐bond acceptor, but a moderately good H‐bond donor. In α‐helix, considerable SCHBs were found between the sulphydryl group of cysteine residue i and the carbonyl oxygen of residue i‐4, and these SCHBs exert effects in stabilizing helices. Although for other SCHBs, they possess no specific secondary structural preference, their geometric characteristics in proteins and in free small compounds are significantly distinct, indicating the protein SCHBs are geometrically distorted. Interestingly, sulfur atom in the disulfide bond tends to form bifurcated H‐bond whereas in cysteine‐cysteine pairs prefer to form dual H‐bond. These special H‐bonds remarkably boost the interaction between H‐bond donor and acceptor. By oxidation/reduction manner, the mutual transformation between the dual H‐bonds and disulfide bonds for cysteine‐cysteine pairs can accurately adjust the structural stability and biological function of proteins in different environments. Furthermore, few loose H‐bonds were observed to form between the sulphydryl groups and aromatic rings, and in these cases the donor H is almost over against the rim rather than the center of the aromatic ring. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Identification of a Wzy Polymerase Required for Group IV Capsular Polysaccharide and Lipopolysaccharide Biosynthesis in Vibrio vulnificus

ABSTRACT The estuarine bacterium Vibrio vulnificus is a human and animal pathogen. The expression of capsular polysaccharide (CPS) is essential for virulence. We used a new mini-Tn10 delivery vector, pNKTXI-SceI, to generate a mutant library and identify genes essential for CPS biosynthesis. Twenty-one acapsular mutants were isolated, and the disrupted gene in one mutant, coding for a polysaccharide polymerase (wzy), is described here. A wecA gene initiating glycosyltransferase was among the genes identified in the region flanking the wzy gene. This, together with the known structure of the CPS, supports a group IV capsule designation for the locus; however, its overall organization mirrored that of group I capsules. This new arrangement may be linked to our finding that the CPS region appears to have been recently acquired by horizontal transfer. Alcian Blue staining and immunoblotting with antisera against the wild-type strain indicated that the wzy::Tn10 mutant failed to produce CPS and was attenuated relative to the wild type in a septicemic mouse model. Interestingly, immunoblotting revealed that the mutant was also defective in lipopolysaccharide (LPS) production. However, the core-plus-one O-antigen pattern typical of wzy mutations was apparent. CPS production, LPS production, and virulence were restored following complementation with the wild-type wzy gene. Hence, Wzy participates in both CPS and LPS biosynthesis and is required for virulence in strain 27562. To our knowledge, this is the first functional demonstration of a Wzy polysaccharide polymerase in V. vulnificus and is the first to show a link between LPS and CPS biosynthesis.
Automation‐assisted cervical cancer screening in manual liquid‐based cytology with hematoxylin and eosin staining

Current automation‐assisted technologies for screening cervical cancer mainly rely on automated liquid‐based cytology slides with proprietary stain. This is not a cost‐efficient approach to be utilized in developing countries. In this article, we propose the first automation‐assisted system to screen cervical cancer in manual liquid‐based cytology (MLBC) slides with hematoxylin and eosin (H&E) stain, which is inexpensive and more applicable in developing countries. This system consists of three main modules: image acquisition, cell segmentation, and cell classification. First, an autofocusing scheme is proposed to find the global maximum of the focus curve by iteratively comparing image qualities of specific locations. On the autofocused images, the multiway graph cut (GC) is performed globally on the a* channel enhanced image to obtain cytoplasm segmentation. The nuclei, especially abnormal nuclei, are robustly segmented by using GC adaptively and locally. Two concave‐based approaches are integrated to split the touching nuclei. To classify the segmented cells, features are selected and preprocessed to improve the sensitivity, and contextual and cytoplasm information are introduced to improve the specificity. Experiments on 26 consecutive image stacks demonstrated that the dynamic autofocusing accuracy was 2.06 μm. On 21 cervical cell images with nonideal imaging condition and pathology, our segmentation method achieved a 93% accuracy for cytoplasm, and a 87.3% F‐measure for nuclei, both outperformed state of the art works in terms of accuracy. Additional clinical trials showed that both the sensitivity (88.1%) and the specificity (100%) of our system are satisfyingly high. These results proved the feasibility of automation‐assisted cervical cancer screening in MLBC slides with H&E stain, which is highly desirable in community health centers and small hospitals. © 2013 International Society for Advancement of Cytometry
Vitamin K and childhood cancer: a population based case-control study in Lower Saxony, Germany

Abstract Objective: To confirm or refute a possible association of parenteral vitamin K prophylaxis and childhood cancer. Design: Population based case-control study. Comparison of vitamin K exposure in children with leukaemia or other common tumours with two control groups. Setting: State of Lower Saxony (north western part of Germany); case recruitment from the German childhood cancer registry. Subjects: 272 children with leukaemia, nephroblastoma, neuroblastoma, rhabdomyosarcoma, and tumours of the central nervous system diagnosed between 1 July 1988 and 30 June 1993; children were aged between 30 days and 15 years at diagnosis. 334 population based controls without diagnoses of cancer matched to the leukaemia cases for age and sex. Main exposure measures: Parenteral vitamin K prophylaxis (intramuscular and subcutaneous) versus oral and no vitamin K prophylaxis. Results: An association between parenteral vitamin K exposure and childhood cancer (leukae-mias and other tumours combined) could not be confirmed (odds ratio 1.04, 95% confidence interval 0.74 to 1.48). For leukaemias the observed odds ratio was only 0.98 (0.64 to 1.50) (comparison of leukaemia cases with local controls 1.24 (0.68 to 2.25); state controls 0.82 (0.50 to 1.36)). These odds ratios remained almost unchanged when several potential confounders were considered in the logistic regression model. Conclusions: This population based study adds substantial evidence that there is no association between parenteral vitamin K and childhood cancer. Key messages The study size was sufficient to detect a cancer risk of at least 1.55 The cumulative evidence from this and previous studies almost excludes an association of intramuscular vitamin K prophylaxis and childhood cancer
Bcl‐2 regulatory pathway is functional in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is characterized by accumulation of clonal, malignant CD5+, CD23+ B cells. In vivo, these cells have an antiapoptotic phenotype (high levels of Bcl‐2 and low levels of proapoptotic Bcl‐2 family proteins, such as Bax). Abnormal B cells accumulate due to altered apoptosis regulation rather than to increased proliferation. However, it is unclear whether there are inherent Bcl‐2 apoptotic pathway defects. With in vitro culture, these B cells rapidly apoptosis.
Photosensitivity: The Magnitude of the Problem

Summary: Very few studies of photosensitivity or visual sensitive epilepsy could be called epidemiologic in the strict sense, that is, giving well‐based incidence and prevalence rates of a well‐defined clinical and electroencephalographic syndrome or group of syndromes. The available data suggest that photosensitivity is rare in the population as a whole, with an annual incidence rate around one case per 100,000 population. The incidence goes up to almost six per 100,000 in the late adolescent period, the age group at the highest risk. Well‐established concepts, such as statements that one in 4,000 of the general population or that 10% of all epilepsy patients would be photosensitive, should be reevaluated. The more likely figures are a lifetime prevalence of one in 10,000 in the general population, perhaps as low as 2%, of the epilepsy population. Further epidemiologic studies, sensu strictu, are warranted to settle the basic question of the real incidence and prevalence of photoparoxysmal responses (PPRs) and epilepsy with seizures provoked by visual stimuli in the community.
Does aid educate? Dynamic panel evidence on the role of official development assistance in determining outcomes in primary education

This research evaluates the effectiveness of Official Development Assistance in determining primary education enrolment and completion, as well as the differential role that the quality of recipient country governance and presence of conflict play in influencing its impact. A panel dataset is constructed to allow analysis of educational and aid data for 61 countries over the period 1970-2013 using the dynamic panel system Generalised Methods of Moments estimator. The macro analysis is complemented by analysis of the disaggregated panel data and a review of education aid evaluations for select countries in order to profile the patterns of educational aid and enrolment growth. The results find education aid to be a highly significant predictor of enrolment, with a US$ 1 increase in education aid equated with a 0.3 rise in the primary net enrolment rate. Aid committed to countries with more stable governance is shown to be significant in the production of higher levels of primary enrolment as is education aid given during times of conflict. Both the results of the macro analysis and the four case studies - Pakistan, India, Malawi and Mozambique - point to aid effectiveness being highly dependent upon the context to which it is delivered. By analysing how differing ‘structural vulnerabilities’ have influenced the impact of aid for education, the thesis encourages the global debate to move on from asking whether or not aid works to looking at when aid works and how it can work better, arguing that increased emphasis will need to be placed on the strategic allocation of aid if the new ambitious sustainable education goal is to be met. The implications of the research for the practice of donor aid-giving post-2015 are important, as the results question current aid allocation practices and the proposed benefits of earlier calls to adopt a ‘big push’ approach to scaling-up education aid. It is argued that aid should be allocated on the basis of educational need and the focus ought primarily to be on ensuring the effectiveness of education aid projects where governance and/or political will is weak by identifying innovative and context-appropriate aid delivery mechanisms.
Development and Implementation of a Multiplex Single-Nucleotide Polymorphism Genotyping Assay for Detection of Virulence-Attenuating Mutations in the Listeria monocytogenes Virulence-Associated Gene inlA

ABSTRACT The virulence factor internalin A (InlA) facilitates the uptake of Listeria monocytogenes by epithelial cells that express the human isoform of E-cadherin. Previous studies identified naturally occurring premature stop codon (PMSC) mutations in inlA and demonstrated that these mutations are responsible for virulence attenuation. We assembled >1,700 L. monocytogenes isolates from diverse sources representing 90 EcoRI ribotypes. A subset of this isolate collection was selected based on ribotype frequency and characterized by a Caco-2 cell invasion assay. The sequencing of inlA genes from isolates with attenuated invasion capacities revealed three novel inlA PMSCs which had not been identified previously among U.S. isolates. Since ribotypes include isolates with and without inlA PMSCs, we developed a multiplex single-nucleotide polymorphism (SNP) genotyping assay to detect isolates with virulence-attenuating PMSC mutations in inlA. The SNP genotyping assay detects all inlA PMSC mutations that have been reported worldwide and verified in this study to date by the extension of unlabeled primers with fluorescently labeled dideoxynucleoside triphosphates. We implemented the SNP genotyping assay to characterize human clinical and food isolates representing common ribotypes associated with novel inlA PMSC mutations. PMSCs in inlA were significantly (ribotypes DUP-1039C and DUP-1045B; P < 0.001) or marginally (ribotype DUP-1062D; P = 0.11) more common among food isolates than human clinical isolates. SNP genotyping revealed a fourth novel PMSC mutation among U.S. L. monocytogenes isolates, which was observed previously among isolates from France and Portugal. This SNP genotyping assay may be implemented by regulatory agencies and the food industry to differentiate L. monocytogenes isolates carrying virulence-attenuating PMSC mutations in inlA from strains representing the most significant health risk.
Integration of homeostatic signaling and food reward processing in the human brain.

BACKGROUND Food intake is guided by homeostatic needs and by the reward value of food, yet the exact relation between the two remains unclear. The aim of this study was to investigate the influence of different metabolic states and hormonal satiety signaling on responses in neural reward networks. METHODS Twenty-three healthy participants underwent functional magnetic resonance imaging while performing a task distinguishing between the anticipation and the receipt of either food- or monetary-related reward. Every participant was scanned twice in a counterbalanced fashion, both during a fasted state (after 24 hours fasting) and satiety. A functional connectivity analysis was performed to investigate the influence of satiety signaling on activation in neural reward networks. Blood samples were collected to assess hormonal satiety signaling. RESULTS Fasting was associated with sensitization of the striatal reward system to the anticipation of food reward irrespective of reward magnitude. Furthermore, during satiety, individual ghrelin levels were associated with increased neural processing during the expectation of food-related reward. CONCLUSIONS Our findings show that physiological hunger stimulates food consumption by specifically increasing neural processing during the expectation (i.e., incentive salience) but not the receipt of food-related reward. In addition, these findings suggest that ghrelin signaling influences hedonic-driven food intake by increasing neural reactivity during the expectation of food-related reward. These results provide insights into the neurobiological underpinnings of motivational processing and hedonic evaluation of food reward. TRIAL REGISTRATION ClinicalTrials.gov NCT03081585. FUNDING This work was supported by the German Competence Network on Obesity, which is funded by the German Federal Ministry of Education and Research (FKZ 01GI1122E).
The safety and tolerability of sumatriptan: an overview.

Safety information was pooled from 4,859 patients, mainly treated in controlled clinical trials with a dispersible tablet of sumatriptan or by a subcutaneous injection, and from 1,164 patients who received placebo by these routes. Safety monitoring involved collection of all adverse events, regardless of their relationship to treatment, and included routine laboratory screening tests and some special investigations. Individuals experienced several groups of symptoms that might be considered to be features of migraine itself or of the post-migraine period or due to treatment. The commonest complaints were an unpleasant taste or pain on injection. After oral sumatriptan (100-300 mg), some events (nausea, malaise) were characteristic of migraine and others (fatigue, sedation, weakness) were characteristic of the recovery period. With subcutaneous sumatriptan (4-8 mg) similar events were observed, but certain distinctive symptoms variously described as heaviness, pressure sensation, tingling, feelings of heat or warmth, were more common and affected various parts of the body. Their early onset and transient nature suggests some pharmacological mechanism, as yet not identified. Despite the mixed picture of symptoms recorded after treatment, they were not serious, they were transient and they were accepted by patients. Close patient monitoring allowed detailed evaluation of any possible cardiovascular side-effects as seen with other anti-migraine agents, particularly ergotamine. The evidence is reassuring but, since experience in patients with symptomatic ischaemic heart disease is limited, it is recommended that they should initially be treated with sumatriptan under medical supervision for their first two or three attacks. (ABSTRACT TRUNCATED AT 250 WORDS)
Traditional gender roles, forced sex and HIV in Zimbabwean marriages

Little is known on how forced sex contributes to the sexual transmission of HIV in marriage. This paper describes traditional gender norms surrounding forced sex in Zimbabwean marriage. Data were collected from 4 focus group discussions and 36 in-depth interviews with married women and men in Harare. Results indicate that hegemonic masculinity characterised by a perceived entitlement to sex, male dominance and being a provider contributed to forced sex in marriage. A femininity characterised by a tolerance of marital rape, the desire to please the husband and submission contributed to women experiencing forced sex. An alternative femininity characterised by sexual pleasure-seeking contributed to women forcing their spouses to have sex. Future HIV interventions must go beyond narrowly advocating for safer sex within marriage and instead address practices that increase risk as well as promote positive marital relationship needs such as mutual respect, love and friendship.