Miracle-dz/UniFAR-FTUs huggingface dataset:
Control-coping goodness-of-fit and chronic illness: a systematic review of the literature

ABSTRACT Chronic illnesses such as cancer, diabetes, and chronic pain often create intense and pervasive stress. Although much research has focused on the importance of coping in managing chronic illness, the importance of controllability appraisals in determining the efficacy of various coping strategies (i.e., the ‘goodness-of-fit hypothesis’) for individuals living with chronic illness has yet to be established. To evaluate support for the goodness-of-fit hypothesis, we conducted a systematic literature review, identifying and synthesising results of 15 studies that reported on conditional effects of problem-, emotion-, and meaning-focused coping strategies, depending on controllability appraisals. Results across studies were mixed, with some coping strategies but not others demonstrating significant interaction effects with controllability appraisals in models predicting psychological and physiological markers of health. Studies demonstrated considerable heterogeneity in design and measurement, with the majority reliant on cross-sectional design and thus unable to infer temporality in the effects of coping on adjustment. In addition, lack of consensus regarding the measurement and categorisation of coping precluded definitive conclusions regarding contextual effects of many strategies. To better understand these patterns of coping as they unfold in daily experience, future work should incorporate contemporary methods such as experience sampling and multilevel statistical modeling.
Resveratrol-loaded PLGA nanoparticles: enhanced stability, solubility and bioactivity of resveratrol for non-alcoholic fatty liver disease therapy

Resveratrol (3, 4′, 5-trihydroxy-trans-stilbene, RSV), a nutraceutical, has recently attracted lots of attention because of its outstanding pharmacological potential. The effects of RSV on non-alcoholic fatty liver disease (NAFLD) remain inconclusive, although a wealth of research has been done. The major obstacle presented was RSV's poor bioavailability due to its poor aqueous solubility, chemical instability and intestinal metabolism. In this study, nanotechnology was used to encapsulate RSV to enhance its stability, water solubility and bioactivity, which can be used to treat NAFLD by HepG2 hepatocytes-induced in vitro. RSV-loaded poly (d, l-lactide-co-glycolide acid) (PLGA) nanoparticles (RSV-PLGA-NPs) were prepared according to an oil/water (O/W) emulsion technique. The RSV-PLGA-NPs were of spherical morphology with an average size of 176.1 nm and a negative charge of −22.6 mV. These nanoparticles exhibited remarkable encapsulation efficiency (EE%) (97.25%) and drug loading (14.9%) for RSV. A sustained RSV release from RSV-PLGA-NPs could be achieved especially in acidic conditions when simulating transporting through the gastrointestinal tract. In addition, these nanoparticles were stable enough to store at 4°C for a least six months with unchanged EE%. Moreover, RSV-PLGA-NPs were more efficient in alleviating lipogenesis, promoting lipolysis and reducing hepatocellular proliferation than free RSV due to its improved stability, water solubility and bioactivity. These findings indicated that the RSV-PLGA-NPs provided superb and stable drug delivery with small particle size, high capsulation efficiency, well-controlled drug release, which greatly enhanced the stability, water solubility and bioactivity. Besides, the discovery that the inhibitory effect of RSV-PLGA-NPs on hepatocellular proliferation and lipid accumulation in steatotic HepG2 cells may provide a new way to study the mechanism of NAFLD. Therefore, RSV-PLGA-NPs have a promising potential for NAFLD therapy.
AKT/mTORC2 Inhibition Activates FOXO1 Function in CLL Cells Reducing B-Cell Receptor-Mediated Survival

Purpose: To determine whether inhibition of mTOR kinase-mediated signaling represents a valid therapeutic approach for chronic lymphocytic leukemia (CLL). Experimental Design: Stratification of mTOR activity was carried out in patients with primary CLL samples and an aggressive CLL-like mouse model. The potency of dual mTOR inhibitor AZD8055 to induce apoptosis in primary CLL cells was assessed in the presence/absence of B-cell receptor (BCR) ligation. Furthermore, we addressed the molecular and functional impact of dual mTOR inhibition in combination with BTK inhibitor ibrutinib. Results: Differential regulation of basal mTORC1 activity was observed in poor prognostic CLL samples, with elevated p4EBP1T37/46 and decreased p70S6 kinase activity, suggesting that dual mTORC1/2 inhibitors may exhibit improved response in poor prognostic CLL compared with rapalogs. AZD8055 treatment of primary CLL cells significantly reduced CLL survival in vitro compared with rapamycin, preferentially targeting poor prognostic subsets and overcoming BCR-mediated survival advantages. Furthermore, AZD8055, and clinical analog AZD2014, significantly reduced CLL tumor load in mice. AKT substrate FOXO1, while overexpressed in CLL cells of poor prognostic patients in LN biopsies, peripheral CLL cells, and mouse-derived CLL-like cells, appeared to be inactive. AZD8055 treatment partially reversed FOXO1 inactivation downstream of BCR crosslinking, significantly inhibiting FOXO1T24 phosphorylation in an mTORC2-AKT–dependent manner, to promote FOXO1 nuclear localization, activity, and FOXO1-mediated gene regulation. FOXO1 activity was further significantly enhanced on combining AZD8055 with ibrutinib. Conclusions: Our studies demonstrate that dual mTOR inhibitors show promise as future CLL therapies, particularly in combination with ibrutinib.
Nutrition in Ultra-Endurance: State of the Art

Athletes competing in ultra-endurance sports should manage nutritional issues, especially with regards to energy and fluid balance. An ultra-endurance race, considered a duration of at least 6 h, might induce the energy balance (i.e., energy deficit) in levels that could reach up to ~7000 kcal per day. Such a negative energy balance is a major health and performance concern as it leads to a decrease of both fat and skeletal muscle mass in events such as 24-h swimming, 6-day cycling or 17-day running. Sport anemia caused by heavy exercise and gastrointestinal discomfort, under hot or cold environmental conditions also needs to be considered as a major factor for health and performance in ultra-endurance sports. In addition, fluid losses from sweat can reach up to 2 L/h due to increased metabolic work during prolonged exercise and exercise under hot environments that might result in hypohydration. Athletes are at an increased risk for exercise-associated hyponatremia (EAH) and limb swelling when intake of fluids is greater than the volume lost. Optimal pre-race nutritional strategies should aim to increase fat utilization during exercise, and the consumption of fat-rich foods may be considered during the race, as well as carbohydrates, electrolytes, and fluid. Moreover, to reduce the risk of EAH, fluid intake should include sodium in the amounts of 10–25 mmol to reduce the risk of EAH and should be limited to 300–600 mL per hour of the race.
Barriers to Postpartum Glucose Intolerance Screening in an Italian Population

Background: Gestational diabetes mellitus (GDM) is a strong risk factor for type 2 diabetes mellitus (T2D) and the postpartum period is crucial for early treatment in at-risk women. However, despite recommendations, only a fraction of women undergo a postpartum screening for glucose intolerance (ppOGTT). The present study aims to verify the reason(s) for poor adherence in our population. Research design and methods: This retrospective study includes 451 women in which GDM was diagnosed between 2015–2016. During 2017, we verified by phone interview how many women underwent ppOGTT at 6–12 weeks postpartum, as recommended by the Italian guidelines. The non-compliant women were asked about the reason(s) for failing to screen. The non-parametric Mann-Whitney test and the 2-tailed Fisher exact test were used to compare continuous and categorical features, respectively, among women performing or non-performing ppOGTT. Results: Out of 451 women with GDM diagnosis, we recorded information from 327. Only 97 (29.7%) performed ppOGTT. The remaining 230 women (70.3%) provided the following explanation for non-compliance: (1) newborn care (30.4%); (2) misunderstood importance (28.3%); (3) oversight (13.0%); (4) unavailability of test reservation in the nearest centers (10.4%); (5) normal glycemic values at delivery (8.3%); (6) discouragement by primary care physician (5.6%). Conclusions: In our population, most women with recent GDM failed to perform ppOGTT. Our results indicated that the prominent barriers could potentially be overcome.
Robust Loss Functions: Defense Mechanisms for Deep Architectures

Current deep learning methods and technologies have reached the level of deployment in softwares and hardwares for real-life applications. However, recent studies have shown deep learning architectures are highly vulnerable to attacks and exploitation via input perturbations. In this works, we investigate the effects of these attacks on the outputs of each layer of deep architectures and on theirs performance in term of classification accuracy measures. The results show that without defense mechanism, even simple attacks devastated deep architectures’ outputs in every layer and theirs classification performance. We then propose multiple defense mechanisms in order to protect deep architectures and to make them more robust to input perturbation attacks.
You Cannot Fix What You Cannot Find! An Investigation of Fault Localization Bias in Benchmarking Automated Program Repair Systems

Properly benchmarking Automated Program Repair (APR) systems should contribute to the development and adoption of the research outputs by practitioners. To that end, the research community must ensure that it reaches significant milestones by reliably comparing state-of-the-art tools for a better understanding of their strengths and weaknesses. In this work, we identify and investigate a practical bias caused by the fault localization (FL) step in a repair pipeline. We propose to highlight the different fault localization configurations used in the literature, and their impact on APR systems when applied to the Defects4J benchmark. Then, we explore the performance variations that can be achieved by "tweaking" the FL step. Eventually, we expect to create a new momentum for (1) full disclosure of APR experimental procedures with respect to FL, (2) realistic expectations of repairing bugs in Defects4J, as well as (3) reliable performance comparison among the state-of-theart APR systems, and against the baseline performance results of our thoroughly assessed kPAR repair tool. Our main findings include: (a) only a subset of Defects4J bugs can be currently localized by commonly-used FL techniques; (b) current practice of comparing state-of-the-art APR systems (i.e., counting the number of fixed bugs) is potentially misleading due to the bias of FL configurations; and (c) APR authors do not properly qualify their performance achievement with respect to the different tuning parameters implemented in APR systems.
Abnormal Presentation of Aggressive Fibromatosis After Radiotherapy for Keloids: Case Report and Brief Literature Review.

RATIONALE Keloids, dermal fibroproliferative lesions, often occur secondary to skin injury and extend beyond the margins of the original lesion. Aggressive fibromatosis (AF) is a rare condition arising from fibroblasts and is characterized clinically as a nonmetastasizing but locally invasive tumor. In this work, we present the case of a patient who developed AF in the chest 3 years after surgery and postoperative radiotherapy for keloids. PATIENT CONCERNS A 15-year-old female patient who underwent surgery and postoperative radiotherapy for keloids presented with AF in the chest 3 years after intervention. DIAGNOSES AND OUTCOMES Physical examination revealed a fan-shaped scar on the manubrium sterni with a radius of 7 cm, as well as a 9 (L) × 2-cm (W) longitudinal reddish and irregularly surfaced scar arising from previous incisions. By comparing this case with similar cases reported previously, we infer that a history of exposure to radiation is the main factor that contributes to the development of AF in patients suffering from keloid scars. We also discussed the clinical characteristics of AF and treatment options and suggest factors that should be considered when using radiotherapy in patients with keloids. LESSONS To our knowledge, this is the first reported case of AF developing in a patient after radiotherapy for keloids. Radiotherapy may be a causal factor of AF.
Refined Multiscale Fuzzy Entropy to Analyse Post-Exercise Cardiovascular Response in Older Adults With Orthostatic Intolerance

Orthostatic intolerance syndrome occurs when the autonomic nervous system is incapacitated and fails to respond to the demands associated with the upright position. Assessing this syndrome among the elderly population is important in order to prevent falls. However, this problem is still challenging. The goal of this work was to determine the relationship between orthostatic intolerance (OI) and the cardiovascular response to exercise from the analysis of heart rate and blood pressure. More specifically, the behavior of these cardiovascular variables was evaluated in terms of refined composite multiscale fuzzy entropy (RCMFE), measured at different scales. The dataset was composed by 65 older subjects, 44.6% (n = 29) were OI symptomatic and 55.4% (n = 36) were not. Insignificant differences were found in age and gender between symptomatic and asymptomatic OI participants. When heart rate was evaluated, higher differences between groups were observed during the recovery period immediately after exercise. With respect to the blood pressure and other hemodynamic parameters, most significant results were obtained in the post-exercise stage. In any case, the symptomatic OI group exhibited higher irregularity in the measured parameters, as higher RCMFE levels in all time scales were obtained. This information could be very helpful for a better understanding of cardiovascular instability, as well as to recognize risk factors for falls and impairment of functional status.
Localization of Welding Defects using a Weakly Supervised Neural Network

Traditionally, defect inspections during industrial processes such as assembling and welding have been done by skilled technicians despite the fact that such processes are time-consuming and easily influenced by the environment. Recently, however, as the performance of machine learning improves, numerous studies related to inspection systems involving machine learning are actively under way. Moreover, detecting areas of defective welding must be done to improve the quality of the welding process. Therefore, in this work we developed a defect inspection system for use during the transmission welding process which relies on a deep neural network based on a convolution neural network (CNN) [1]. We use two algorithms, one for a classification model and the other for a post-processing model, for localization. With regard to the classification model, a global average pooling (GAP) layer is added to the last convolution layer, enabling localization despite the training being done only with image-level label data. It is very cost-efficient to enable this process with only minimal data information. Lastly, we compared the performances of existing classification models and modified models for our task.
Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring

Importance Evidence for the fetal safety of ondansetron, a 5-HT3 receptor antagonist that is commonly prescribed for nausea and vomiting during pregnancy, is limited and conflicting. Objective To evaluate the association between ondansetron exposure during pregnancy and risk of congenital malformations. Design, Setting, and Participants A retrospective cohort study nested in the 2000-2013 nationwide Medicaid Analytic eXtract. The cohort consisted of 1 816 414 pregnancies contributed by 1 502 895 women enrolled in Medicaid from 3 months before the last menstrual period through 1 month or longer after delivery; infants were enrolled in Medicaid for at least 3 months after birth. The final date of follow-up was December 31, 2013. Analyses were conducted between November 1, 2017, and June 30, 2018. Propensity score stratification was used to control for treatment indication and other confounders. Exposures Ondansetron dispensing during the first trimester, the period of organogenesis. Main Outcomes and Measures Primary outcomes were cardiac malformations and oral clefts diagnosed during the first 90 days after delivery. Secondary outcomes included congenital malformations overall and subgroups of cardiac malformations and oral clefts. Results Among 1 816 414 pregnancies (mean age of mothers, 24.3 [5.8] years), 88 467 (4.9%) were exposed to ondansetron during the first trimester. Overall, 14 577 of 1 727 947 unexposed and 835 of 88 467 exposed infants were diagnosed with a cardiac malformation, for an absolute risk of 84.4 (95% CI, 83.0 to 85.7) and 94.4 (95% CI, 88.0 to 100.8) per 10 000 births respectively. The absolute risk of oral clefts was 11.1 per 10 000 births (95% CI, 10.6 to 11.6; 1921 unexposed infants) and was 14.0 per 10 000 births (95% CI, 11.6 to 16.5; 124 exposed infants). The risk of any congenital malformation was 313.5 per 10 000 births (95% CI, 310.9 to 316.1; 54 174 unexposed infants) and was 370.4 (95% CI, 358.0 to 382.9; 3277 exposed infants). The adjusted relative risk (RR) for cardiac malformations was 0.99 (95% CI, 0.93 to 1.06) and the adjusted risk difference (RD) was −0.8 (95% CI, −7.3 to 5.7 per 10 000 births). For oral clefts, the adjusted RR was 1.24 (95% CI, 1.03 to 1.48) and the RD was 2.7 (95% CI, 0.2 to 5.2 per 10 000 births). The adjusted estimate for congenital malformations overall was an RR of 1.01 (95% CI, 0.98 to 1.05) and an RD of 5.4 (95% CI, −7.3 to 18.2 per 10 000 births). Conclusions and Relevance Among offspring of mothers enrolled in Medicaid, first-trimester exposure to ondansetron was not associated with cardiac malformations or congenital malformations overall after accounting for measured confounders but was associated with a small increased risk of oral clefts.
CritICs Critiquing Criticality in Mobile Apps

In this paper, we conduct a systematic analysis to show that existing CPU optimizations targeting scientific/server workloads are not always well suited for mobile apps. In particular, we observe that the well-known and very important concept of identifying and accelerating individual critical instructions in workloads such as SPEC, are not as effective for mobile apps. Several differences in mobile app characteristics including (i) dependencies between critical instructions interspersed with non-critical instructions in the dependence chain, (ii) temporal proximity of the critical instructions in the dynamic stream, and (iii) the bottleneck shifting to the front from the rear of the datapath pipeline, are key contributors to the ineffectiveness of traditional criticality based optimizations. Instead, we propose the concept of Critical Instruction Chains (CritICs) – which are short, critical and self contained sequences of instructions, for aggregate level optimization. With motivating results, we show that an offline profiler/analysis framework can easily identify these CritICs, and we propose a very simple software mechanism in the compiler that exploits ARM’s 16-bit ISA format to nearly double the fetch bandwidth of these instructions. We have implemented this entire framework - both profiler and compiler passes, and evaluated its effectiveness for 10 popular apps from the Play Store. Experimental evaluations show that our approach is much more effective than two previously studied criticality optimizations, yielding a speedup of 12.65%, and energy savings of 15% in the CPU (translating to a system wide energy savings of 4.6%), requiring very little additional hardware support.
Retinal Vasculopathy With Cerebral Leukodystrophy: Clinicopathologic Features of an Autopsied Patient With a Heterozygous TREX 1 Mutation

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an autosomal-dominant disorder involving the cerebral, retinal, renal, and other systemic microvessels due to frameshift mutations in the TREX1 gene. Under physiological conditions, the TREX1 protein is localized in the cellular cytoplasm and perinuclear area, but translocates into the nucleus in response to oxidative DNA damage. It has been speculated that aberrant localization of the protein may be associated with systemic microangiopathy in patients with RVCL. However, cellular expression of TREX1 in the brain and visceral organs of patients with RVCL has been unclear. Here, we report the clinicopathologic features of an autopsied patient with a heterozygous T249fs mutation in TREX1. The patient showed the clinical phenotype of vasculopathy with retinopathy, nephropathy, and stroke. CT with contrast enhancement demonstrated a tumorous lesion in the subcortical white matter. Histologically, the lesion consisted of confluent foci of necrosis with calcification and fibrous thickening of small vessel walls. TREX1 immunohistochemistry demonstrated positivity in the nuclei of cells in the CNS and visceral organs, indicating aberrant localization of the truncated protein, and the expression was remarkable in oligodendrocytes within the lesion, suggesting possible involvement of the protein in the pathomechanism of vasculopathy leading to white matter degeneration.
Rapid Recapitulation of Nonalcoholic Steatohepatitis upon Loss of Host Cell Factor 1 Function in Mouse Hepatocytes

Host cell factor 1 (HCF-1), encoded by the ubiquitously expressed X-linked gene Hcfc1, is an epigenetic coregulator important for mouse development and cell proliferation, including during liver regeneration. We used a hepatocyte-specific inducible Hcfc1 knockout allele (called Hcfc1hepKO) to induce HCF-1 loss in hepatocytes of hemizygous Hcfc1hepKO/Y males by 4 days. ABSTRACT Host cell factor 1 (HCF-1), encoded by the ubiquitously expressed X-linked gene Hcfc1, is an epigenetic coregulator important for mouse development and cell proliferation, including during liver regeneration. We used a hepatocyte-specific inducible Hcfc1 knockout allele (called Hcfc1hepKO) to induce HCF-1 loss in hepatocytes of hemizygous Hcfc1hepKO/Y males by 4 days. In heterozygous Hcfc1hepKO/+ females, owing to random X-chromosome inactivation, upon Hcfc1hepKO allele induction, a 50/50 mix of HCF-1-positive and -negative hepatocyte clusters is engineered. The livers with Hcfc1hepKO/Y hepatocytes displayed a 21- to 24-day terminal nonalcoholic fatty liver (NAFL), followed by nonalcoholic steatohepatitis (NASH) disease progression typical of severe NAFL disease (NAFLD). In contrast, in livers with heterozygous Hcfc1hepKO/+ hepatocytes, HCF-1-positive hepatocytes replaced HCF-1-negative hepatocytes and revealed only mild NAFL development. Loss of HCF-1 led to loss of PGC1α protein, probably owing to its destabilization, and deregulation of gene expression, particularly of genes involved in mitochondrial structure and function, likely explaining the severe Hcfc1hepKO/Y liver pathology. Thus, HCF-1 is essential for hepatocyte function, likely playing both transcriptional and nontranscriptional roles. These genetically engineered loss-of-HCF-1 mice can be used to study NASH as well as NAFLD resolution.