Miracle-dz/UniFAR-FTUs huggingface dataset:
Introduction of Two Novel Stiffness Parameters and Interpretation of Air Puff-Induced Biomechanical Deformation Parameters With a Dynamic Scheimpflug Analyzer.

PURPOSE To investigate two new stiffness parameters and their relationships with the dynamic corneal response (DCR) parameters and compare normal and keratoconic eyes. METHODS Stiffness parameters are defined as Resultant Pressure at inward applanation (A1) divided by corneal displacement. Stiffness parameter A1 uses displacement between the undeformed cornea and A1 and stiffness parameter highest concavity (HC) uses displacement from A1 to maximum deflection during HC. The spatial and temporal profiles of the Corvis ST (Oculus Optikgeräte, Wetzlar, Germany) air puff were characterized using hot wire anemometry. An adjusted air pressure impinging on the cornea at A1 (adjAP1) and an algorithm to biomechanically correct intraocular pressure based on finite element modelling (bIOP) were used for Resultant Pressure calculation (adjAP1 - bIOP). Linear regression analyses between DCR parameters and stiffness parameters were performed on a retrospective dataset of 180 keratoconic eyes and 482 normal eyes. DCR parameters from a subset of 158 eyes of 158 patients in each group were matched for bIOP and compared using t tests. A P value of less than . 05 was considered statistically significant. RESULTS All DCR parameters evaluated showed significant differences between normal and keratoconic eyes, except peak distance. Keratoconic eyes had lower stiffness parameter values, thinner pachymetry, shorter applanation lengths, greater absolute values of applanation velocities, earlier A1 times and later second applanation times, greater HC deformation amplitudes and HC deflection amplitudes, and lower HC radius of concave curvature (greater concave curvature). Most DCR parameters showed a significant relationship with both stiffness parameters in both groups. CONCLUSIONS Keratoconic eyes demonstrated less resistance to deformation than normal eyes with similar IOP. The stiffness parameters may be useful in future biomechanical studies as potential biomarkers. [J Refract Surg. 2017;33(4):266-273. ].
Excess Mortality among HIV-Infected Individuals with Cancer in the United States

Background: Human immunodefieciency virus (HIV)-infected persons are living longer in the era of effective HIV treatment, resulting in an increasing cancer burden in this population. The combined effects of HIV and cancer on mortality are incompletely understood. Methods: We examined whether individuals with both HIV and cancer have excess mortality using data from the HIV/AIDS Cancer Match Study and the National Center for Health Statistics (1996–2010). We compared age, sex, and race-stratified mortality between people with and without HIV or one of the following cancers: lung, breast, prostate, colorectum, anus, Hodgkin lymphoma, or non-Hodgkin lymphoma. We utilized additive Poisson regression models that included terms for HIV, cancer, and an interaction for their combined effect on mortality. We report the number of excess deaths per 1,000 person-years for models with a significant interaction (P < 0.05). Results: For all cancers examined except prostate cancer, at least one demographic subgroup of HIV-infected cancer patients experienced significant excess mortality. Excess mortality was most pronounced at younger ages (30–49 years), with large excesses for males with lung cancer (white race: 573 per 1,000 person-years; non-white: 503) and non-Hodgkin lymphoma (white: 236; non-white: 261), and for females with Hodgkin lymphoma (white: 216; non-white: 136) and breast cancer (non-white: 107). Conclusions: In the era of effective HIV treatment, overall mortality in patients with both HIV and cancer was significantly higher than expected on the basis of mortality rates for each disease separately. Impact: These results suggest that HIV may contribute to cancer progression and highlight the importance of improved cancer prevention and care for the U.S. HIV population. Cancer Epidemiol Biomarkers Prev; 26(7); 1027–33. ©2017 AACR.
Effects of a reduced dose of injected iron on health, iron status and growth of suckling piglets with access to iron enriched soil.

INTRODUCTION The effects of the recommended dose of 200 mg iron and of half that dose injected on the first day of life on health, iron status and performance during the 4 week suckling period were studied in 2'123 piglets. All piglets received creep feed and soil which was supplemented with 14 g iron per kg. Neither mortality nor the prevalence of arthritis, meningitis and foot abscess (each disease affecting about 1% of the piglets) differed between the two groups. The low dose of 100 mg iron decreased blood haemoglobin concentration at weaning (110 ± 19 vs.120 ± 15 g/l), but did not affect growth rate.
Trends in thyroid cancer incidence and mortality in Portugal

The objective was to quantify thyroid cancer incidence and mortality trends in Portugal. The number of thyroid cancer cases and incidence rates were retrieved from the Regional Cancer Registries for the period 1989–2011. The number of deaths and mortality rates were obtained from the WHO cancer mortality database (1988–2003 and 2007–2012) and Statistics Portugal (2004–2006; 1988–2012 by region). Joinpoint regression of the standardized incidence and mortality rates was performed. A significant, rapid and continued increase in incidence was observed for both sexes in each of the Regional Cancer Registries, with annual per cent changes (APCs) ranging between 2 and 9. Incidence in Portuguese women is higher than estimates for the world and Europe. Mortality decreased for women (APC: −1.5), with the greatest decrease in the North, and increased marginally for men (APC: +0.2), with a greater increase in the South. The significant increases in incidence in Portugal are predominantly because of the increase in incidence among women from the North. These trends, combined with an overall low mortality and high 5-year relative survival, raise concerns on the extent to which overdiagnosis may be taking place. Further research is needed, quantifying the importance of the most likely determinants of these trends as well as the extent and potentially deleterious effects of overdiagnosis and overtreatment in the Portuguese setting.
Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry

Background: Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry. Methods: We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT). Results: Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant (P < 0.05). Through fine-mapping, in six regions (3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions (11q13, 16q12/TOX3), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality. Conclusions: Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry. Impact: The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. Cancer Epidemiol Biomarkers Prev; 26(7); 1016–26. ©2017 AACR.
Functional interactions between transient receptor potential M8 and transient receptor potential V1 in the trigeminal system: Relevance to migraine pathophysiology

Background Recent genome-wide association studies have identified transient receptor potential M8 (TRPM8) as a migraine susceptibility gene. TRPM8 is a nonselective cation channel that mediates cool perception. However, its precise role in migraine pathophysiology is elusive. Transient receptor potential V1 (TRPV1) is a nonselective cation channel activated by noxious heat. Both TRPM8 and TRPV1 are expressed in trigeminal ganglion (TG) neurons. Methods We investigated the functional roles of TRPM8 and TRPV1 in a meningeal inflammation-based migraine model by measuring the effects of facial TRPM8 activation on thermal allodynia and assessing receptor coexpression changes in TG neurons. We performed retrograde tracer labeling to identify TG neurons innervating the face and dura. Results We found that pharmacological TRPM8 activation reversed the meningeal inflammation-induced lowering of the facial heat pain threshold, an effect abolished by genetic ablation of TRPM8. No significant changes in the heat pain threshold were seen in sham-operated animals. Meningeal inflammation caused dynamic alterations in TRPM8/TRPV1 coexpression patterns in TG neurons, and colocalization was most pronounced when the ameliorating effect of TRPM8 activation on thermal allodynia was maximal. Our tracer assay disclosed the presence of dura-innervating TG neurons sending collaterals to the face. Approximately half of them were TRPV1-positive. We also demonstrated functional inhibition of TRPV1 by TRPM8 in a cell-based assay using c-Jun N-terminal kinase phosphorylation as a surrogate marker. Conclusions Our findings provide a plausible mechanism to explain how facial TRPM8 activation can relieve migraine by suppressing TRPV1 activity. Facial TRPM8 appears to be a promising therapeutic target for migraine.
Low-Rank and Sparse Structure Pursuit via Alternating Minimization

In this paper, we present a nonconvex alternating minimization optimization algorithm for low-rank and sparse structure pursuit. Compared with convex relaxation based methods, the proposed algorithm is computationally more e cient for large scale problems. In our study, we define a notion of bounded di↵erence of gradients, based on which we rigorously prove that with suitable initialization, the proposed nonconvex optimization algorithm enjoys linear convergence to the global optima and exactly recovers the underlying low rank and sparse matrices under standard conditions such as incoherence and sparsity conditions. For a wide range of statistical models such as multi-task learning and robust principal component analysis (RPCA), our algorithm provides a principled approach to learning the low rank and sparse structures with provable guarantee. Thorough experiments on both synthetic and real datasets backup our theory.
The Effect of Hip Joint Angle on Isometric Midthigh Pull Kinetics

Abstract Dos'Santos, T, Thomas, C, Jones, PA, McMahon, JJ, and Comfort, P. The effect of hip joint angle on isometric midthigh pull kinetics. J Strength Cond Res 31(10): 2748–2757, 2017—The aim of this study were to compare isometric midthigh pull (IMTP) peak force (PF), time-specific force values (100-, 150-, and 200 ms), rate of force development (RFD) at predetermined time bands (0–100, 0–150, and 0–200 ms) and net forces between 2 commonly adopted hip joint angles (145°[hip145] and 175°[hip175]) with a 145° standardized knee angle. Twenty-eight collegiate athletes (age: 21.7 ± 1.5 years, height: 1.75 ± 0.08 m, mass: 81.5 ± 8.4 kg) performed 2 IMTP trials at each hip joint angle in a randomized counterbalanced order. A subgroup (n = 10) performed the IMTP testing 7 days later to establish the between-session reliability. Intraclass correlation coefficients (ICCs) and coefficient of variation (CV) demonstrated high within-session reliability and acceptable variability for all IMTP kinetics at each posture (ICC ≥ 0.86, CV ⩽ 13.7%), excluding hip175 RFD 0–100 ms and net force at 100 ms which demonstrated greater variability (CV = 18.1–18.5%). High between-session reliability and acceptable variability were observed for all IMTP kinetics at each posture (ICC = 0.72–0.97, CV = 4.5–12.8%), excluding RFD 0–100 ms which demonstrated greater variability for both postures. Hip145 produced significantly greater time-specific force values (p ⩽ 0.025, g = 0.25–0.28), RFD at predetermined time bands (p ⩽ 0.001, g = 0.59–0.78), and net forces (p ⩽ 0.001, g = 0.57–0.74) compared with hip175. Trivial nonsignificant differences were demonstrated between postures for PF and force at 100 ms (p > 0.05, g ⩽ 0.14). Significantly greater body weights (weighing period force) were observed with hip175 compared with hip145 (p < 0.001, g = 0.74). Coaches should consider administering a hip145 for IMTP testing as greater IMTP kinetics and lower levels of pretension during the weighing period are achieved with this posture.
Effects of conditioning time and sodium bentonite on pellet quality, growth performance, intestinal morphology and nutrient retention in finisher broilers

ABSTRACT 1. This study was carried out to evaluate the effect of steam-conditioning time and different levels of processed sodium bentonite (PSB) on pellet quality, growth performance, intestinal development and morphology, and nutrient digestibilities in broilers during finisher period (d 24–45). 2. A total of 810 male chicks were reared in commercial conditions on floor pens till d 24. Then, birds were weighed and used in a completely randomised design experiment with a 3 × 3 factorial arrangement, including three levels of conditioning times (0, 2 and 4 min) and three PSB levels (0, 7.5 and 15 g/kg diet). Each of the 9 diets fed to 6 replicates group of 15 birds each. 3. The results showed that 2-min steam conditioning and 15 g/kg PSB supplementation significantly increased pellet durability index (PDI) and hardness, and decreased electrical consumption of pelleting. Diets had no significant effects on body weight, feed intake and feed conversion ratio. Although dietary treatments did not influence relative weight and length of three segments of small intestine, 2-min steam conditioning significantly improved villus height (VH) and crypt depth. Steam conditioning of diet for 2 min significantly increased apparent metabolisable energy (AME), ether extract (EE), calcium (Ca) and dry matter (DM) retention in birds measured during 38–42 d of age. 4. It could be concluded that 2-min steam conditioning improved PDI and hardness, VH and nutrient retention (AME, EE, Ca and DM), but did not affect growth performance in broilers during finisher period.
Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity

Significance A well-investigated mechanism regulating synapse protein turnover and remodeling is the classical ubiquitin–proteasome system by which polyubiquitin (polyUb) chains linked through ubiquitin lysine 48 (K48) tag substrates for proteasomal degradation. Little is known about the role of nondegradable polyUb linkages, e.g., K63-linked chains, in the synapse, although these chains represent the second most abundant polyUb linkage in mammalian brain. We identified a bona fide K63-polyUb substrate in PSD-95, a major postsynaptic scaffold. K63-polyUb conjugation markedly augments PSD-95’s scaffolding capability and promotes its synaptic targeting and anchorage. We identify a K63-linkage–specific E3 ligase–deubiquitinase complex that controls activity-dependent assembly and disassembly of K63-polyUb chains on PSD-95. We show that this unconventional polyUb linkage promotes synapse maturation, efficacy, and plasticity. Ubiquitination-directed proteasomal degradation of synaptic proteins, presumably mediated by lysine 48 (K48) of ubiquitin, is a key mechanism in synapse and neural circuit remodeling. However, more than half of polyubiquitin (polyUb) species in the mammalian brain are estimated to be non-K48; among them, the most abundant is Lys 63 (K63)-linked polyUb chains that do not tag substrates for degradation but rather modify their properties and activity. Virtually nothing is known about the role of these nonproteolytic polyUb chains at the synapse. Here we report that K63-polyUb chains play a significant role in postsynaptic protein scaffolding and synaptic strength and plasticity. We found that the postsynaptic scaffold PSD-95 (postsynaptic density protein 95) undergoes K63 polyubiquitination, which markedly modifies PSD-95’s scaffolding potentials, enables its synaptic targeting, and promotes synapse maturation and efficacy. TNF receptor-associated factor 6 (TRAF6) is identified as a direct E3 ligase for PSD-95, which, together with the E2 complex Ubc13/Uev1a, assembles K63-chains on PSD-95. In contrast, CYLD (cylindromatosis tumor-suppressor protein), a K63-specific deubiquitinase enriched in postsynaptic densities, cleaves K63-chains from PSD-95. We found that neuronal activity exerts potent control of global and synaptic K63-polyUb levels and, through NMDA receptors, drives rapid, CYLD-mediated PSD-95 deubiquitination, mobilizing and depleting PSD-95 from synapses. Silencing CYLD in hippocampal neurons abolishes NMDA-induced chemical long-term depression. Our results unveil a previously unsuspected role for nonproteolytic polyUb chains in the synapse and illustrate a mechanism by which a PSD-associated K63-linkage–specific ubiquitin machinery acts on a major postsynaptic scaffold to regulate synapse organization, function, and plasticity.
Moving Beyond Cancer: Immediate Impact on-the Health-Related Quality of Life of Breast Cancer Patients After Mastectomy.

During the last decade, survival rates for breast cancer have increased as a result of earlier detection and increased use of adjuvant therapy. Limited data exist on the post mastectomy quality of life in the process of transition from health to cancer in its different phases of treatment. The aim of current study was to evaluate the changes of health-related quality of life (HRQoL) after mastectomy and to measure their impression about future perspectives in Bangladeshi Breasts cancer patients. A group of 250 women with a diagnosis of primary breast cancer who was admitted in the department of surgical oncology in National Institute of Cancer Research and Hospital, Dhaka were enrolled in this study from January 2012 to March 2013. Two-point interview like pre(MI) and post mastectomy(M2) was taken using the structured questionnaire made by European Organization for Research and Treatment of Cancer (EORTC)- EORTC Q30 and BR23. The mean age of the patients was 44.7? 9.87 years, 52.6% were locally advanced. HRQoL scores of breast cancer patients deteriorated after mastectomy, general features like presence of fatigability, nausea, apatite loss, sleeplessness and pain has got tremendous effect on the quality of life(p<.005). Financial difficulties and sleep disorders did not affect much. Four of the Global Health status/QOL parameters like physical functioning, role functioning, emotional functioning, cognitive functioning deteriorated but only physical functioning status affected significantly(p<0.005). Breast symptoms like body image problem, general breast symptoms like pain, arm swelling and sexual feeling affected their (HRQOL) after mastectomy. A diagnosis of cancer and associated treatments affects multiple domains of life. The complicated transitions between health, illness and living with cancer can often be challenged with a preoperative information for the patient confronted with breast cancer should include possible psychological effects of cancer diagnosis, surgery, and other treatment. Breast conservation particularly in the young group may give a better outcome in the treatment protocol of breast cancer patients.
Adipocyte Model of Mycobacterium tuberculosis Infection Reveals Differential Availability of Iron to Bacilli in the Lipid-Rich Caseous Environment

ABSTRACT Mycobacterium tuberculosis, a successful human pathogen, utilizes multiple carbon sources from the host but adapts to a fatty-acid-rich environment in vivo. We sought to delineate the physiologic response of M. tuberculosis to a lipid-rich environment by using differentiated adipocytes as a model system. Global transcriptome profiling based on RNA sequencing was performed for bacilli from infected adipocytes and preadipocytes. Genes involved in de novo fatty acid synthesis were downregulated, while those predicted to be involved in triglyceride biosynthesis were upregulated, in bacilli isolated from adipocytes, indicating reliance on host-derived fatty acids. Transcription factor network analysis indicated suppression of IdeR-regulated genes, suggesting decreased iron uptake by M. tuberculosis in the adipocyte model. This suppression of iron uptake coincided with higher ferritin and iron levels in adipocytes than in preadipocytes. In accord with the role of iron in mediating oxidative stress, we observed upregulation of genes involved in mitigating oxidative stress in M. tuberculosis isolated from adipocytes. We provide evidence that oleic acid, a major host-derived fatty acid, helps reduce the bacterial cytoplasm, thereby providing a safe haven for an M. tuberculosis mutant that is sensitive to iron-mediated oxidative stress. Via an independent mechanism, host ferritin is also able to rescue the growth of this mutant. Our work highlights the inherent synergy between macronutrients and micronutrients of the host environment that converge to provide resilience to the pathogen. This complex synergy afforded by the adipocyte model of infection will aid in the identification of genes required by M. tuberculosis in a caseous host environment.
Barriers and Facilitators to Integrating Health Service Responses to Intimate Partner Violence in Low‐ and Middle‐Income Countries: A Comparative Health Systems and Service Analysis

This systematic review synthesizes 11 studies of health‐sector responses to intimate partner violence (IPV) in low‐ and middle‐income countries. The services that were most comprehensive and integrated in their responsiveness to IPV were primarily in primary health and antenatal care settings. Findings suggest that the following facilitators are important: availability of clear guidelines, policies, or protocols; management support; intersectoral coordination with clear, accessible on‐site and off‐site referral options; adequate and trained staff with accepting and empathetic attitudes toward survivors of IPV; initial and ongoing training for health workers; and a supportive and supervised environment in which to enact new IPV protocols. A key characteristic of the most integrated responses was the connection or “linkages” between different individual factors. Irrespective of their service entry point, what emerged as crucial was a connected systems‐level response, with all elements implemented in a coordinated manner.