Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovering early diabetic neuropathy from epidermal nerve fiber patterns

Epidermal nerve fibre (ENF) density and morphology are used to study small fibre involvement in diabetic, HIV, chemotherapy induced and other neuropathies. ENF density and summed length of ENFs per epidermal surface area are reduced, and ENFs may appear more clustered within the epidermis in subjects with small fibre neuropathy than in healthy subjects. Therefore, it is important to understand the spatial structure of ENFs. In this paper, we compare the ENF patterns between healthy subjects and subjects suffering from mild diabetic neuropathy. The study is based on suction skin blister specimens from the right foot of 32 healthy subjects and eight subjects with mild diabetic neuropathy. We regard the ENF entry point (location where the trunks of a nerve enters the epidermis) and ENF end point (termination of the nerve fibres) patterns as realizations of spatial point processes, and develop tools that can be used in the analysis and modelling of ENF patterns. We use spatial summary statistics and shift plots and define a new tool, reactive territory, to study the spatial patterns and to compare the patterns of the two groups. We will also introduce a simple model for these data in order to understand the growth process of the nerve fibres. Copyright © 2016 John Wiley & Sons, Ltd.
<inline-formula><tex-math notation="LaTeX">$\ell _0$</tex-math><alternatives><inline-graphic xlink:href="yuan-ieq1-2783936.gif"/></alternatives></inline-formula>TV: A Sparse Optimization Method for Impulse Noise Image Restoration

Total Variation (TV) is an effective and popular prior model in the field of regularization-based image processing. This paper focuses on total variation for removing impulse noise in image restoration. This type of noise frequently arises in data acquisition and transmission due to many reasons, e.g., a faulty sensor or analog-to-digital converter errors. Removing this noise is an important task in image restoration. State-of-the-art methods such as Adaptive Outlier Pursuit(AOP) <xref ref-type="bibr" rid="ref1">[1]</xref> , which is based on TV with <inline-formula><tex-math notation="LaTeX">$\ell _{02}$</tex-math><alternatives><inline-graphic xlink:href="yuan-ieq2-2783936.gif"/></alternatives></inline-formula>-norm data fidelity, only give sub-optimal performance. In this paper, we propose a new sparse optimization method, called <inline-formula><tex-math notation="LaTeX">$\ell _0TV$</tex-math><alternatives><inline-graphic xlink:href="yuan-ieq3-2783936.gif"/></alternatives></inline-formula>-PADMM, which solves the TV-based restoration problem with <inline-formula><tex-math notation="LaTeX">$\ell _0$</tex-math><alternatives><inline-graphic xlink:href="yuan-ieq4-2783936.gif"/></alternatives></inline-formula>-norm data fidelity. To effectively deal with the resulting non-convex non-smooth optimization problem, we first reformulate it as an equivalent biconvex Mathematical Program with Equilibrium Constraints (MPEC), and then solve it using a proximal Alternating Direction Method of Multipliers (PADMM). Our <inline-formula><tex-math notation="LaTeX">$\ell _0TV$</tex-math><alternatives><inline-graphic xlink:href="yuan-ieq5-2783936.gif"/></alternatives></inline-formula>-PADMM method finds a desirable solution to the original <inline-formula><tex-math notation="LaTeX">$\ell _0$</tex-math><alternatives><inline-graphic xlink:href="yuan-ieq6-2783936.gif"/></alternatives></inline-formula>-norm optimization problem and is proven to be convergent under mild conditions. We apply <inline-formula><tex-math notation="LaTeX">$\ell _0TV$</tex-math><alternatives><inline-graphic xlink:href="yuan-ieq7-2783936.gif"/></alternatives></inline-formula>-PADMM to the problems of image denoising and deblurring in the presence of impulse noise. Our extensive experiments demonstrate that <inline-formula><tex-math notation="LaTeX">$\ell _0TV$</tex-math><alternatives><inline-graphic xlink:href="yuan-ieq8-2783936.gif"/></alternatives></inline-formula>-PADMM outperforms state-of-the-art image restoration methods.
Responding to emotional scenes: effects of response outcome and picture repetition on reaction times and the late positive potential

ABSTRACT Processing the motivational relevance of a visual scene and reacting accordingly is crucial for survival. Previous work suggests the emotional content of naturalistic scenes affects response speed, such that unpleasant content slows responses whereas pleasant content accelerates responses. It is unclear whether these effects reflect motor-cognitive processes, such as attentional orienting, or vary with the function/outcome of the motor response itself. Four experiments manipulated participants’ ability to terminate the picture (offset control) and, thereby, the response’s function and motivational value. Attentive orienting was manipulated via picture repetition, which diminishes orienting. A total of N = 81 participants completed versions of a go/no-go task, discriminating between distorted versus intact pictures drawn from six content categories varying in positive, negative, or neutral valence. While all participants responded faster with repetition, only participants without offset control exhibited slower responses to unpleasant and accelerated responses to pleasant content. Emotional engagement, measured by the late positive potential, was not modulated by attentional orienting (repetition), suggesting that the interaction between repetition and offset control is not due to altered emotional engagement. Together, results suggest that response time changes as a function of emotional content and sensitivity to attention orienting depends on the motivational function of the motor response.
Resistance to PARP inhibitors by SLFN11 inactivation can be overcome by ATR inhibition

Poly(ADP-ribose) polymerase inhibitors (PARPIs) kill cancer cells by trapping PARP1 and PARP2. Talazoparib, the most potent PARPI inhibitor (PARPI), exhibits remarkable selectivity among the NCI-60 cancer cell lines beyond BRCA inactivation. Our genomic analyses reveal high correlation between response to talazoparib and Schlafen 11 (SLFN11) expression. Causality was established in four isogenic SLFN11-positive and -negative cell lines and extended to olaparib. Response to the talazoparib-temozolomide combination was also driven by SLFN11 and validated in 36 small cell lung cancer cell lines, and in xenograft models. Resistance in SLFN11-deficient cells was caused neither by impaired drug penetration nor by activation of homologous recombination. Rather, SLFN11 induced irreversible and lethal replication inhibition, which was independent of ATR-mediated S-phase checkpoint. The resistance to PARPIs by SLFN11 inactivation was overcome by ATR inhibition, mechanistically because SLFN11-deficient cells solely rely on ATR activation for their survival under PARPI treatment. Our study reveals that SLFN11 inactivation, which is common (~45%) in cancer cells, is a novel and dominant resistance determinant to PARPIs.
Defining the molecular pathology of pancreatic body and tail adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease, with very little improvement in survival over the past 50 years. Recent large‐scale genomic studies have improved understanding of the genomic and transcriptomic landscape of the disease, yet very little is known about molecular heterogeneity according to tumour location in the pancreas; body and tail PDACs especially tend to have a significantly worse prognosis. The aim was to investigate the molecular differences between PDAC of the head and those of the body and tail of the pancreas.
Elevated level of Interleukin-35 in colorectal cancer induces conversion of T cells into iTr35 by activating STAT1/STAT3

IL-35 is a novel heterodimeric and inhibitory cytokine, composed of interleukin-12 subunit alpha (P35) and Epstein-Barr virus -induced gene 3 (EBI3). IL-35 has been reported to be produced by a range of cell types, especially regulatory T cells, and to exert immunosuppressive effects via the STATx signaling pathway. In this study, we demonstrated that IL-35 expression was elevated in both serum and tumors in patients with colorectal cancer. IL-35 mainly expressed in CD4+ T cells in human colorectal cancer tumors and adjacent tissues. Increased IL-35 expression in tumor-adjacent tissues was significantly associated with tumor metastasis. IL-35 inhibited the proliferation of CD4+CD25− T effector cells in vitro in a dose-dependent manner, and its suppression was partially reversed by applying IL-35-neutralizing antibodies. IL-35 treatment activated the phosphorylation of both STAT1 and STAT3 in human CD4+ T cells. Meanwhile, IL-35 induced a positive feedback loop to promote its own production. We observed that Tregs obtained from colorectal cancer patients were capable of inducing more IL-35 production. In addition, EBI3 promoter-driven luciferase activity was higher than that of the mock plasmid after IL-35stimulation. Thus, our study indicates that the high level of IL-35 in colorectal cancer promotes the production of IL-35 via STAT1 and STAT3, which suppresses T cell proliferation and may participate in tumor immunotolerance.
Fate of abstracts presented at an International Commission on Occupational Health (ICOH) congress--followed by publication in peer-reviewed journals?

OBJECTIVES Presentations at international meetings offer an excellent way to disseminate current research findings. One measure of the quality of research is its subsequent publication. Our study aimed to determine the publication rate of abstracts presented at a congress of the International Commission of Occupational Health (ICOH), and to identify predictive factors of publication and differences between presented abstracts and -subsequently published papers. METHODS We identified a random sample of 318 abstracts presented at the 2000 ICOH meeting from the book of abstracts. Using Medline and Embase, we assessed their publication rate in the period ranging from 1998 to 2006 and investigated the factors associated with publication rate. RESULTS Of 318 abstracts originating from 51 countries, 105 articles [33%, 95% confidence interval (95% CI) 27-38)] were subsequently published in 67 journals indexed in Medline or Embase. Mean time to publication was 17 months (95% CI 13-21). Multivariate analysis revealed that abstracts with quantitative data and written by authors originating from developed countries were significantly more published. From the time of abstract presentation to publication in a peer-reviewed journal, both the study sample size and the first author frequently changed (respectively 25% and 29%), but the overall conclusions remained stable, except in one case. CONCLUSIONS Most of the abstracts presented at the 2000 ICOH congress were not subsequently published as full research reports. If this is the case for most abstracts submitted to conferences, this may limit the ability of a reader to judge the validity, reliability, and generalizability of the research presented. Caution is advised when referencing or generalizing from abstracts that have not been subsequently published in full.
Influence of conformity on the wear of total knee replacement: An experimental study

Wear of total knee replacement continues to be a significant factor influencing the clinical longevity of implants. Historically, failure due to delamination and fatigue directed design towards more conforming inserts to reduce contact stress. As new generations of more oxidatively stable polyethylene have been developed, more flexibility in bearing design has been introduced. The aim of this study was to investigate the effect of insert conformity on the wear performance of a fixed bearing total knee replacement through experimental simulation. Two geometries of insert were studied under standard gait conditions. There was a significant reduction in wear with reducing implant conformity. This study has demonstrated that bearing conformity has a significant impact on the wear performance of a fixed bearing total knee replacement, providing opportunities to improve clinical performance through enhanced material and design selection.
The quaternary state of polymerized human hemoglobin regulates oxygenation of breast cancer solid tumors: A theoretical and experimental study

A major constraint in the treatment of cancer is inadequate oxygenation of the tumor mass, which can reduce chemotherapeutic efficacy. We hypothesize that polymerized human hemoglobin (PolyhHb) can be transfused into the systemic circulation to increase solid tumor oxygenation, and improve chemotherapeutic outcomes. By locking PolyhHb in the relaxed (R) quaternary state, oxygen (O2) offloading at low O2 tensions (<20 mm Hg) may be increased, while O2 offloading at high O2 tensions (>20 mm Hg) is facilitated with tense (T) state PolyhHb. Therefore, R-state PolyhHb may deliver significantly more O2 to hypoxic tissues. Biophysical parameters of T and R-state PolyhHb were used to populate a modified Krogh tissue cylinder model to assess O2 transport in a tumor. In general, we found that increasing the volume of transfused PolyhHb decreased the apparent viscosity of blood in the arteriole. In addition, we found that PolyhHb transfusion decreased the wall shear stress at large arteriole diameters (>20 μm), but increased wall shear stress for small arteriole diameters (<10 μm). Therefore, transfusion of PolyhHb may lead to elevated O2 delivery at low pO2. In addition, transfusion of R-state PolyhHb may be more effective than T-state PolyhHb for O2 delivery at similar transfusion volumes. Reduction in the apparent viscosity resulting from PolyhHb transfusion may result in significant changes in flow distributions throughout the tumor microcirculatory network. The difference in wall shear stress implies that PolyhHb may have a more significant effect in capillary beds through mechano-transduction. Periodic top-load transfusions of PolyhHb into mice bearing breast tumors confirmed the oxygenation potential of both PolyhHbs via reduced hypoxic volume, vascular density, tumor growth, and increased expression of hypoxia inducible genes. Tissue section analysis demonstrated primary PolyhHb clearance occurred in the liver and spleen indicating a minimal risk for renal damage.
Recent Progress on the SUMMIT System

The SUMMIT system is a speaker-independent, continuous-speech recognition system that we have developed at MIT [12]. To date, the system has been ported to a variety of tasks with vocabulary sizes up to 1000 words and perplexities up to 73. The architecture of this system is a product of two guiding principles. First, we desired a framework that could be flexible and modular so that we could explore alternative strategies for embedding speech knowledge into the system. Second, we required that the system be stochastic and trainable from a large body of speech data to account for our current incomplete knowledge of the acoustic realization of speech. The current implementation of the system is a reflection of both of these ideas. SUMMIT differs from the majority of prevailing HMM approaches in many respects ranging from its use of auditory models and selected acoustic measurements, to its segmental framework and use of pronunciation networks. In time, the specific implementation of these ideas will undoubtedly be modified as we discover superior techniques and approaches. Until phonetic and word recognition accuracies are competitive with those of human listeners however, we believe it will be appropriate to incorporate both notions of flexibility and trainability into the system.
Isolation of Mycoplasma genitalium from endocervical swabs of infertile women

Objectives: To determine the occurrence of Mycoplasma genitalium (M. genitalium) infection in infertile women attending infertility clinic and its association to infertility. Methods: Endocervical specimens were collected from women presenting with primary and secondary infertility and from fertile women as control group. Real-time polymerase chain reaction (PCR) assay was performed to detect the presence of M. genitalium from these endocervical specimens. Results: Mycoplasma genitalium was detected in 3% of infertile women. There was no statistically significant difference between infertility and control group as to signs and symptoms except for signs of cervicitis were presented only among infertile group. We found no significant differences among fertile and infertile women for M. genitalium infection. Conclusion: An association between M. genitalium infection and infertility may exist. Screening of women for M. genitalium infection is recommended as part of investigations for infertility.
Long-term Low-Density Lipoprotein Cholesterol–Lowering Efficacy, Persistence, and Safety of Evolocumab in Treatment of Hypercholesterolemia: Results Up to 4 Years From the Open-Label OSLER-1 Extension Study

Importance The Open-Label Study of Long-term Evaluation Against LDL-C (OSLER-1) evaluated the durability of long-term efficacy and safety during long-term therapy with evolocumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9). Objective To determine whether LDL-C level reductions with evolocumab persist across different populations. Secondary objectives included assessment of adverse events, antidrug antibodies, and factors contributing to treatment discontinuation. Design, Setting, and Participants This ongoing, randomized open-label extension trial (OSLER-1) was conducted at 192 sites in 18 countries. A total of 1324 of 1666 patients randomized into 1 of 5 12-week double-blind phase 2 parent studies completed a parent study and chose to participate in OSLER-1; 1255 received 1 or more evolocumab doses. As of August 2016, 812 of 1324 (61%) had 208 weeks of follow-up. This current study was conducted from October 2011 to August 2016, with a data cutoff of August 26, 2016. Interventions During year 1, patients were randomized to evolocumab, 420 mg, plus standard of care (SOC) or SOC alone. After year 1, all patients continuing the study received evolocumab, 420 mg, plus SOC. Main Outcomes and Measures Lipids, safety, and tolerability every 12 weeks. A multivariate model identified factors associated with discontinuation of evolocumab. Results At parent study baseline, the mean (SD) age of the population was 57.1 (11.6) years, with 52.9% being women. The median LDL-C level was 133 mg/dL (to convert to millimoles per liter, multiply by 0.0259). After 52 weeks, evolocumab plus SOC was associated with a significant reduction in LDL-C level by 61% (95% CI, −63% to −60%) vs 2% (95% CI, −5% to −0.2%) with SOC alone (P < .001). At approximately 2, 3, and 4 years of study follow-up, the median LDL-C level was reduced by 59% (95% CI, −60% to −57%), 59% (95% CI, −61% to −58%), and 57% (95% CI, −59% to −55%), respectively, from parent study baseline. For patients receiving statin therapy unchanged from baseline, at week 208, the median LDL-C level reduction was 58%. No neutralizing antibodies to evolocumab were detected. The annualized incidence of new-onset diabetes was 4% in the SOC alone group and, adjusting for duration of evolocumab exposure, 2.8% in the evolocumab plus SOC group. Neurocognitive event rates were 0% (SOC alone) and 0.4% (evolocumab plus SOC). A total of 79% of patients persisted with evolocumab treatment, with a mean exposure duration of 44 months. Conclusions and Relevance In the longest clinical trial exposure to a PCSK9 inhibitor to date, evolocumab produced sustained reductions in LDL-C levels. The annual frequency of adverse events did not occur more frequently with cumulative exposure during open-label observation. Trial Registration clinicaltrials.gov Identifier: NCT01439880
Semen quality associated with subsequent hospitalizations – Can the effect be explained by socio‐economic status and lifestyle factors?

Semen quality is suggested to be a universal biomarker for future health. Previous studies have mostly been registry based excluding the possibility to address the importance of lifestyle, fertility status, health and socio‐economic status. We aimed to investigate whether the association between semen quality and subsequent risk of hospitalization could be explained by differences in occupation, education, fertility, cryptorchidism, BMI or smoking; 1423 men with first semen sample at Fertility Clinic, Frederiksberg Hospital, Denmark, from 1977 to 2010 responded to a questionnaire in 2012 about current health, lifestyle, educational level and occupation. They were followed in the Danish National Patient Registry to first‐time hospitalizations using ICD‐8 and ICD‐10 classification. Data were analysed by Cox proportional hazard regression models to adjust for the possible confounding factors. We found a significant higher risk of being hospitalized with decreasing sperm concentrations (0–15 mill/mL: HR1.78, 95% CI:1.51–2.09; 16–50 mill/mL: HR 1.37 95% CI: 1.17–1.60; 51–100 mill/mL: HR1.25 95% CI: 1.07–1.45). Same significant association of being hospitalized with decreasing total sperm counts was seen. The dose–response increase in risk in hospitalization with decreasing sperm concentration and total sperm count remained constant after further individual adjustment for occupation, marital status, fertility, cryptorchidism, BMI or smoking. The association between semen quality and subsequent morbidity was not explained by differences in lifestyle, behavioural or fertility status. We were unable to adjust for all possible confounders simultaneously due to limited sample size, and reverse causation is a possible explanation as information about education and lifestyle was obtained after semen analysis and hospitalizations occurred and may have changed as consequence of both. Semen quality may be a universal biomarker for future health not explained by lifestyle and socio‐economic status, but this needs to be addressed further in future studies.
A survey of the double‐fetch vulnerabilities

Race conditions widely exist in concurrent programs, and concurrency errors caused by harmful races could lead to severe system failures. A double fetch is a typical situation when the system kernel inevitably accesses user space data multiple times, and it turns into a vulnerability when the data consistency is violated under a special race condition between kernel and user space. In this survey, we present the first (to the best of our knowledge) comprehensive study on double‐fetch vulnerabilities in the real world. Our study is based on the investigation of 91 real‐world double‐fetch vulnerabilities collected from the CVE database and other relevant reports, which covers a period of recent 12 years. Our work reveals some interesting findings on the double‐fetch vulnerabilities, ranging from the various occurrences across different kernels and system levels to the involvement of specific patterns. We also divide the consequences that are usually caused by the double‐fetch vulnerabilities into four categories and discuss each, summarize viable exploitation techniques from existing works, provide useful guidances to detect and practical strategies to prevent double‐fetch vulnerabilities.