Miracle-dz/UniFAR-FTUs huggingface dataset:
Multifocal Electroretinogram in Keratoconus Patients without and with Scleral Lenses

ABSTRACT Purpose: To investigate changes in the multifocal electroretinogram (mfERG) response in eyes with keratoconus when corrected with scleral lenses (SL) compared with the best correction in glasses. Methods: The mfERG responses in 10 eyes with keratoconus were recorded with the best correction using both a trial frame (baseline) and a hexafocon A SL using an electrophysiological diagnostic system. Electrophysiologic measurements were performed with the pupils fully dilated with instillation of 1% phenylephrine. The implicit time (milliseconds), amplitude (nV), and response density (nV/deg2) of the peaks (N1, P1, and N2) were analyzed for the total mfERG response, six rings and four quadrants of the retina, and compared between the two conditions. Results: All eyes had a significant improvement in visual quality with the SL compared with baseline (mean differences, 0.26 ± 0.17 and 0.22 ± 0.13 logarithm of the minimum angle of resolution for high- and low-contrast visual acuity, respectively). The peaks implicit times of the mfERG responses did not show significant differences (p > .05). The P1 amplitude decreased in all the retinal areas with the SL. Only the total retinal response and the nasal quadrants reached significance (p ≤ 0.044). The P1 response density in ring 1 was on average higher with the SL, but not significantly so. The decline in P1 response density from the center to the periphery was more abrupt with the SL, and was more similar to the response density distribution of a typical subject, without a corneal pathology. Conclusions: mfERG did not show any change associated with retinal disease in young patients with keratoconus. Although the improved visual performance was not associated with changes in the mfERG response, the correction of irregular astigmatism with the SL helps exclude the optical effect induced by keratoconus.
Chaperoning SNARE Folding and Assembly.

SNARE proteins and Sec1/Munc18 (SM) proteins constitute the core molecular engine that drives nearly all intracellular membrane fusion and exocytosis. While SNAREs are known to couple their folding and assembly to membrane fusion, the physiological pathways of SNARE assembly and the mechanistic roles of SM proteins have long been enigmatic. Here, we review recent advances in understanding the SNARE-SM fusion machinery with an emphasis on biochemical and biophysical studies of proteins that mediate synaptic vesicle fusion. We begin by discussing the energetics, pathways, and kinetics of SNARE folding and assembly in vitro. Then, we describe diverse interactions between SM and SNARE proteins and their potential impact on SNARE assembly in vivo. Recent work provides strong support for the idea that SM proteins function as chaperones, their essential role being to enable fast, accurate SNARE assembly. Finally, we review the evidence that SM proteins collaborate with other SNARE chaperones, especially Munc13-1, and briefly discuss some roles of SNARE and SM protein deficiencies in human disease. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Respondent Characteristics and Dietary Intake Data Collected Using Web-Based and Traditional Nutrition Surveillance Approaches: Comparison and Usability Study

Background There are many constraints to conducting national food consumption surveys for national nutrition surveillance, including cost, time, and participant burden. Validated web-based dietary assessment technologies offer a potential solution to many of these constraints. Objective This study aims to investigate the feasibility of using a previously validated, web-based, 24-hour recall dietary assessment tool (Foodbook24) for nutrition surveillance by comparing the demographic characteristics and the quality of dietary intake data collected from a web-based cohort of participants in Ireland to those collected from the most recent Irish National Adult Nutrition Survey (NANS). Methods Irish adult participants (aged ≥18 years) were recruited to use Foodbook24 (a web-based tool) between March and October 2016. Demographic and dietary intake (assessed by means of 2 nonconsecutive, self-administered, 24-hour recalls) data were collected using Foodbook24. Following the completion of the study, the dietary intake data collected from the web-based study were statistically weighted to represent the age-gender distribution of intakes reported in the NANS (2008-2010) to facilitate the controlled comparison of intake data. The demographic characteristics of the survey respondents were investigated using descriptive statistics. The controlled comparison of weighted mean daily nutrient intake data collected from the Foodbook24 web-based study (329 plausible reporters of a total of 545 reporters) and the mean daily nutrient intake data collected from the NANS (1051 plausible reporters from 1500 reporters) was completed using the Wilcoxon–Mann-Whitney U test in Creme Nutrition software. Results Differences between the demographic characteristics of the survey participants across the 2 surveys were observed. Notable differences included a lower proportion of adults aged ≥65 years and a higher proportion of females who participated in the web-based Foodbook24 study relative to the NANS study (P<.001). Similar ranges of mean daily intake for the majority of nutrients and food groups were observed (eg, energy [kilocalorie per day] and carbohydrate [gram per day]), although significant differences for some nutrients (eg, riboflavin [mg/10 MJ], P<.001 and vitamin B12 [µg/10 MJ], P<.001) and food groups were identified. A high proportion of participants (200/425, 47.1%) reported a willingness to continue using Foodbook24 for an additional 6 months. Conclusions These findings suggest that by using targeted recruitment strategies in the future to ensure the recruitment of a more representative sample, there is potential for web-based methodologies such as Foodbook24 to be used for nutrition surveillance efforts in Ireland.
Estrous cycle plasticity in the central clock output to kisspeptin neurons: Implications for the preovulatory surge.

Coordination of ovulation and behavior is critical to reproductive success in many species. During the female estrous cycle, the preovulatory gonadotropin surge occurs when ovarian follicles reach maturity and, in rodents, begins just before the daily onset of activity, ensuring ovulation coincides with sex behavior. Timing of the surge relies on projections from the suprachiasmatic nucleus (SCN), the locus of the central circadian clock, to hypothalamic circuits that regulate gonadotropin secretion. The cellular mechanisms through which the SCN controls these circuits and gates the preovulatory surge to the appropriate estrous cycle stage, however, are poorly understood. We investigated in mice the functional impact of SCN arginine-vasopressin (AVP) neuron projections to kisspeptin (Kiss1) neurons in the rostral periventricular area of the third ventricle (RP3V Kiss1), responsible for generating the preovulatory surge. Conditional anterograde tracing revealed that SCN AVP neurons innervate approximately half of the RP3V Kiss1 neurons. Optogenetic activation of SCN AVP projections in brain slices caused an AVP-mediated stimulation of RP3V Kiss1 action potential firing in proestrus, the cycle stage when the surge is generated. This effect was less prominent in diestrus, the preceding cycle stage, and absent in estrus, following ovulation. Remarkably, in estrus, activation of SCN AVP projections resulted in GABA-mediated inhibition of RP3V Kiss1 neuron firing, an effect rarely encountered in other cycle stages. Together, these data reveal functional plasticity in SCN AVP neuron output that drives opposing effects on RP3V Kiss1 neuron activity across the ovulatory cycle. This might contribute to gating activation of the preovulatory surge to the appropriate estrous cycle stage.
Treatment of chronic diabetic foot ulcers with adipose‐derived stromal vascular fraction cell injections: Safety and evidence of efficacy at 1 year

Diabetes affects multiple systems in complex manners. Diabetic foot ulcers (DFUs) are a result of diabetes‐induced microarterial vessel disease and peripheral neuropathy. The presence of arteriosclerosis‐induced macroarterial disease can further complicate DFU pathophysiology. Recent studies suggest that mesenchymal stromal cell therapies can enhance tissue regeneration. This phase I study was designed to determine the safety and explore the efficacy of local injections of autologous adipose‐derived stromal vascular fraction (SVF) cells to treat nonhealing DFUs greater than 3 cm in diameter. Sixty‐three patients with type 2 diabetes with chronic DFU—all amputation candidates—were treated with 30 × 106 SVF cells injected in the ulcer bed and periphery and along the pedal arteries. Patients were seen at 6 and 12 months to evaluate ulcer closure. Doppler ultrasounds were performed in a subset of subjects to determine vascular structural parameters. No intervention‐related serious adverse events were reported. At 6 months, 51 subjects had 100% DFU closure, and 8 subjects had ≥75% closure. Three subjects had early amputations, and one subject died. At 12 months, 50 subjects had 100% DFU healing and 4 subjects had ≥85% healing. Five subjects died between the 6‐ and 12‐month follow‐up visits. No deaths were intervention related. Doppler studies in 11 subjects revealed increases in peak systolic velocity and pulsatility index in 33 of 33 arteries, consistent with enhanced distal arterial runoff. These results indicate that SVF can be safely used to treat chronic DFU, with evidence of efficacy (wound healing) and mechanisms of action that include vascular repair and/or angiogenesis.
ELVISort: encoding latent variables for instant sorting, an artificial intelligence-based end-to-end solution

Objective. The growing number of recording sites of silicon-based probes means that an increasing amount of neural cell activities can be recorded simultaneously, facilitating the investigation of underlying complex neural dynamics. In order to overcome the challenges generated by the increasing number of channels, highly automated signal processing tools are needed. Our goal was to build a spike sorting model that can perform as well as offline solutions while maintaining high efficiency, enabling high-performance online sorting. Approach. In this paper we present ELVISort, a deep learning method that combines the detection and clustering of different action potentials in an end-to-end fashion. Main results. The performance of ELVISort is comparable with other spike sorting methods that use manual or semi-manual techniques, while exceeding the methods which use an automatic approach: ELVISort has been tested on three independent datasets and yielded average F1 scores of 0.96, 0.82 and 0.81, which comparable with the results of state-of-the-art algorithms on the same data. We show that despite the good performance, ELVISort is capable to process data in real-time: the time it needs to execute the necessary computations for a sample of given length is only 1/15.71 of its actual duration (i.e. the sampling time multiplied by the number of the sampling points). Significance. ELVISort, because of its end-to-end nature, can exploit the massively parallel processing capabilities of GPUs via deep learning frameworks by processing multiple batches in parallel, with the potential to be used on other cutting-edge AI-specific hardware such as TPUs, enabling the development of integrated, portable and real-time spike sorting systems with similar performance to offline sorters.
Interpreting Cancer Survivors’ Perceptions of the Survivor Label Through Social Identity and Communication Accommodation Theories

ABSTRACT This study uses social identity theory and communication accommodation theory as lenses to examine former cancer patients’ perspectives of the “survivor” label, replacement labels for their experience, and use of survivor services. Semi-structured interviews of 43 former cancer patients offer insight into their unique cancer experiences and explain how these events influence their perceptions of the term survivor. Coders used constant comparison methods to capture six themes related to the participants’ impressions of the survivor label. When sharing perceptions of the survivor label, participants expressed language that illustrated convergence (It means everything to me), divergence (I don’t like to be called anything), convergence and divergence (Part of me is happy … Part of me is kind of aggravated), and apathy (I have no feelings toward the label). Participants also generated new labels that captured their cancer experiences and six unique themes emerged from these responses. Most of the former cancer patients were aware of survivorship programs; however, relatively few used these programs regularly and cited reasons for nonuse explained by social identity theory.
Ecological and Evolutionary responses to Antibiotic Treatment in the Human Gut Microbiota

ABSTRACT The potential for antibiotics to affect the ecology and evolution of the human gut microbiota is well recognised and has wide-ranging implications for host health. Here, we review the findings of key studies that surveyed the human gut microbiota during antibiotic treatment. We find several broad patterns including the loss of diversity, disturbance of community composition, suppression of bacteria in the Actinobacteria phylum, amplification of bacteria in the Bacteroidetes phylum, and promotion of antibiotic resistance. Such changes to the microbiota were often, but not always, recovered following the end of treatment. However, many studies reported unique and/or contradictory results, which highlights our inability to meaningfully predict or explain the effects of antibiotic treatment on the human gut microbiome. This problem arises from variation between existing studies in three major categories: differences in dose, class and combinations of antibiotic treatments used; differences in demographics, lifestyles, and locations of subjects; and differences in measurements, analyses and reporting styles used by researchers. To overcome this, we suggest two integrated approaches: (i) a top-down approach focused on building predictive models through large sample sizes, deep metagenomic sequencing, and effective collaboration; and (ii) a bottom-up reductionist approach focused on testing hypotheses using model systems.
Sneathia: an emerging pathogen in female reproductive disease and adverse perinatal outcomes

Abstract Sneathia is an emerging pathogen implicated in adverse reproductive and perinatal outcomes. Although scarce, recent data suggest that vaginally residing Sneathia becomes pathogenic following its ascension into the upper urogenital tract, amniotic fluid, placenta, and foetal membranes. The role of Sneathia in women’s health and disease is generally underappreciated because the cultivation of these bacteria is limited by their complex nutritional requirements, slow growth patterns, and anaerobic nature. For this reason, molecular methods are typically required for the detection and differential diagnosis of Sneathia infections. Here, we review the laboratory methods used for the diagnosis of Sneathia infections, the molecular mechanisms underlying its virulence, and its sensitivity to antibiotics. We further review the evidence of Sneathia’s contributions to the pathogenesis of bacterial vaginosis, chorioamnionitis, preterm prelabour rupture of membranes, spontaneous preterm labour, stillbirth, maternal and neonatal sepsis, HIV infection, and cervical cancer. Collectively, growing evidence indicates that Sneathia represents an important yet underappreciated pathogen affecting the development and progression of several adverse clinical conditions diagnosed in pregnant women and their neonates, as well as in non-pregnant women.
Beyond Sociodemographic and COVID-19-Related Factors: The Association Between the Need for Psychological and Information Support from School and Anxiety and Depression

Background In addition to sociodemographic and COVID-19- related factors, the needs of school support, including material, psychological and information support, have seldom been discussed as factors influencing anxiety and depression among college students during the COVID-19 pandemic. Material/Methods In this cross-sectional study, 3351 college students from China were surveyed through questionnaires about their sociodemographic and COVID-19 characteristics, the needs of school support, and their experiences with anxiety and depression. Results Anxiety and depression were reported by 6.88% and 10.50% of students, respectively. Married, higher education, non-medical, and urban students had significantly higher risks of anxiety or depression. Additionally, symptoms such as cough and fever, especially when following a possible contact with suspected individuals, quarantine history of a personal contact, going out 1–3 times a week, not wearing a mask, and spending 2–3 hours browsing COVID-19-related information were significantly associated with the occurrence of anxiety or depression. Those who used methods to regulate their emotional state, used a psychological hotline, and who had visited a psychiatrist showed higher anxiety or depression. Those who used online curricula and books, used preventive methods for COVID-19, and who had real-time information about the epidemic situation of the school showed lower anxiety and depression. Conclusions In addition to sociodemographic and COVID-19-related aspects, students’ needs for psychological assistance and information from schools were also associated with anxiety and depression among college students.
Variation on a comprehensive theme

The main result concerns a bicategorical factorization system on the bicategory $\mathrm{Cat}$ of categories and functors. Each functor $A\xra{f} B$ factors up to isomorphism as $A\xra{j}E\xra{p}B$ where $j$ is what we call an ultimate functor and $p$ is what we call a groupoid fibration. Every right adjoint functor is ultimate. Functors whose ultimate factor is a right adjoint are shown to have bearing on the theory of polynomial functors.
Analysis of NVMe-SSD to passthrough GPU data transfer in virtualized systems

Non-volatile storage (NVM) technologies provide faster data access compared to traditional hard disk drives and can benefit applications executing on accelerators like general purpose graphics processing units (GPGPUs). Many contemporary GPU-friendly applications process huge volumes of data residing in the secondary storage. Several research work propose techniques to optimize data transfer overheads between devices connected to the same bus e.g., peer-to-peer data transfer between NVMe-SSD and GPU connected to a PCI bus. The applicability of these techniques, extent of their benefit and associated costs in virtualized systems is the scope of this paper. In this paper, we present a comprehensive empirical analysis of different combinations of NVMe-SSD virtualization techniques and data transfer mechanisms between NVMe-SSDs and GPUs. Further, the impact of different data transfer parameters and, root-cause analysis of the resulting performance in terms of data transfer throughput and CPU utilization for different combinations of techniques is presented. Based on the empirical analysis, we provide insights to address several bottlenecks related to different GPU data transfer techniques in different virtualization setups and motivate an alternate design by extending the VirtIO framework for efficient peer-to-peer data transfer.
virtio-mem: paravirtualized memory hot(un)plug

The ability to dynamically increase or reduce the amount of memory available to a virtual machine is getting increasingly important: as one example, cloud users want to dynamically adjust the memory assigned to their virtual machines to optimize costs. Traditional memory hot(un)plug, such as hot(un)plugging emulated DIMMs, and memory ballooning can dynamically resize virtual machine memory. However, existing approaches provide limited flexibility, are incompatible with important technologies like vNUMA and fast operating system reboots, or are unsuitable when hosting untrusted virtual machines. To overcome these limitations, we introduce virtio-mem, a VIRTIO-based paravirtualized memory device, designed for fine-grained, NUMA-aware memory hot(un)plug in cloud environments. To showcase the adaptions needed in a hypervisor and a guest operating system to support virtio-mem, we describe our implementation in the QEMU/KVM hypervisor and Linux guests. We evaluate virtio-mem against traditional memory hot(un)plug and memory ballooning, showing that our approach enables assignment of memory in substantially smaller granularity per NUMA node than traditional memory hot(un)plug, such as 4 MiB on x86-64. In contrast to memory ballooning, virtio-mem is fully NUMA-aware and supports fast operating system reboots by design, while guaranteeing that malicious virtual machines, which try using more memory than agreed upon, can be detected reliably. We conclude that using paravirtualized memory devices for dynamically resizing virtual machine memory significantly increases flexibility and usability compared to state-of-the-art. A first version of virtio-mem for x86-64 has been integrated into upstream Linux and QEMU.
Efficient LLVM-based dynamic binary translation

Emulation of other or newer processor architectures is necessary for a wide variety of use cases, from ensuring compatibility to offering a vehicle for computer architecture research. This problem is usually approached using dynamic binary translation, where machine code is translated, on the fly, to the host architecture during program execution. Existing systems, like QEMU, usually focus on translation performance rather than the overall program execution, and extensions, like HQEMU, are limited by their underlying implementation. Conversely, performance-focused systems are typically used for binary instrumentation. E.g., DynamoRIO reuses original instructions where possible, while Instrew utilizes the LLVM compiler infrastructure, but only supports same-architecture code generation. In this short paper, we generalize Instrew to support different guest and host architectures by refactoring the lifter and by implementing target-independent optimizations to re-use host hardware features for emulated code. We demonstrate this flexibility by adding support for RISC-V as guest architecture and AArch64 as host architecture. Our performance results on SPEC CPU2017 show significant improvements compared to QEMU, HQEMU as well as the original Instrew.
Regulation of Synaptic Transmission and Plasticity by Protein Phosphatase 1

Protein phosphatases, by counteracting protein kinases, regulate the reversible phosphorylation of many substrates involved in synaptic plasticity, a cellular model for learning and memory. A prominent phosphatase regulating synaptic plasticity and neurologic disorders is the serine/threonine protein phosphatase 1 (PP1). PP1 has three isoforms (α, β, and γ, encoded by three different genes), which are regulated by a vast number of interacting subunits that define their enzymatic substrate specificity. In this review, we discuss evidence showing that PP1 regulates synaptic transmission and plasticity, as well as presenting novel models of PP1 regulation suggested by recent experimental evidence. We also outline the required targeting of PP1 by neurabin and spinophilin to achieve substrate specificity at the synapse to regulate AMPAR and NMDAR function. We then highlight the role of inhibitor-2 in regulating PP1 function in plasticity, including its positive regulation of PP1 function in vivo in memory formation. We also discuss the distinct function of the three PP1 isoforms in synaptic plasticity and brain function, as well as briefly discuss the role of inhibitory phosphorylation of PP1, which has received recent emphasis in the regulation of PP1 activity in neurons.