Miracle-dz/UniFAR-FTUs huggingface dataset:
Potential Role for Osteocalcin in the Development of Atherosclerosis and Blood Vessel Disease

There is increasing evidence for the involvement of the skeleton in the regulation of atherosclerotic vascular disease. Osteocalcin, an osteoblast derived protein, exists in two forms, carboxylated and undercarboxylated osteocalcin. Undercarboxylated osteocalcin has been linked to the regulation of metabolic functions, including glucose and lipid metabolism. Features of atherosclerosis have been associated with circulating osteocalcin; however, this association is often conflicting and unclear. Therefore, the aim of this review is to examine the evidence for a role of osteocalcin in atherosclerosis development and progression, and in particular endothelial dysfunction and vascular calcification. The current literature suggests that undercarboxylated osteocalcin stimulates the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway to upregulate nitric oxide and nuclear factor kappa β (NF-кβ) in vascular cells, possibly protecting endothelial function and preventing atherogenesis. However, this effect may be mediated by metabolic factors, such as improvements in insulin signaling, rather than through a direct effect on the vasculature. Total osteocalcin is frequently associated with vascular calcification, an association that may occur as a result of vascular cells eliciting an osteogenic phenotype. Whether osteocalcin acts as a mediator or a marker of vascular calcification is currently unclear. As such, further studies that examine each form of osteocalcin are required to elucidate if it is a mediator of atherogenesis, and whether it functions independently of metabolic factors.
Task-Related Synaptic Changes Localized to Small Neuronal Population in Recurrent Neural Network Cortical Models

Humans have flexible control over cognitive functions depending on the context. Several studies suggest that the prefrontal cortex (PFC) controls this cognitive flexibility, but the detailed underlying mechanisms remain unclear. Recent developments in machine learning techniques allow simple PFC models written as a recurrent neural network to perform various behavioral tasks like humans and animals. Computational modeling allows the estimation of neuronal parameters that are crucial for performing the tasks, which cannot be observed by biologic experiments. To identify salient neural-network features for flexible cognition tasks, we compared four PFC models using a context-dependent integration task. After training the neural networks with the task, we observed highly plastic synapses localized to a small neuronal population in all models. In three of the models, the neuronal units containing these highly plastic synapses contributed most to the performance. No common tendencies were observed in the distribution of synaptic strengths among the four models. These results suggest that task-dependent plastic synaptic changes are more important for accomplishing flexible cognitive tasks than the structures of the constructed synaptic networks.
Exascale Deep Learning for Climate Analytics

We extract pixel-level masks of extreme weather patterns using variants of Tiramisu and DeepLabv3+ neural networks. We describe improvements to the software frameworks, input pipeline, and the network training algorithms necessary to efficiently scale deep learning on the Piz Daint and Summit systems. The Tiramisu network scales to 5300 P100 GPUs with a sustained throughput of 21.0 PF/s and parallel efficiency of 79.0%. DeepLabv3+ scales up to 27360 V100 GPUs with a sustained throughput of 325.8 PF/s and a parallel efficiency of 90.7% in single precision. By taking advantage of the FP16 Tensor Cores, a half-precision version of the DeepLabv3+ network achieves a peak and sustained throughput of 1.13 EF/s and 999.0 PF/s respectively.
The Self-Assessed Békesy Procedure: Validation of a Method to Measure Intelligibility of Connected Discourse

In clinical practice and research, speech intelligibility is generally measured by instructing the participant to recall sentences. Although this is a reliable and highly repeatable measure, it cannot be used to measure intelligibility of connected discourse. Therefore, we developed a new method, the self-assessed Békesy procedure, which is an adaptive procedure that uses intelligibility ratings to converge to a person’s speech reception threshold. In this study, we describe the new procedure and the validation in young, normal-hearing listeners. First, we compared the results on the self-assessed Békesy procedure to a recall procedure for standardized sentences. Next, we evaluated the inter- and intrasubject variability of our procedure. Furthermore, we compared the thresholds for sentences in three masker types between the self-assessed Békesy and a recall procedure to verify if these procedures resulted in similar conclusions. Finally, we compared the thresholds for two types of sentences and commercial recordings of stories. In general, the self-assessed Békesy procedure is shown to be a valid and reliable procedure as similar thresholds (difference < 1 dB) and test–retest reliability (< 1.5 dB) were observed compared with standard speech audiometry tests. In addition, the time efficiency and similar differences between maskers to a recall procedure support the potential of this procedure to be implemented in research. Finally, significant differences between the thresholds of sentences and connected discourse materials were found, indicating the importance of controlling for differences in intelligibility when presenting these materials at the same signal-to-noise ratios or when comparing studies.
Journey to Death: Are Health Systems Failing Mothers?

Background: Annually, about 44,000 maternal deaths occur in India, which is 20% of the global burden. Despite persistent efforts, India failed to meet the fifth millennium development goal by 2015. Lack of reliable data on maternal mortality demands utilization of tools for counting maternal deaths which is vital to implement preventative actions. Objectives: Our study aims to determine health system-related issues of maternal mortality using the WHO validated tool – Maternal Death Review and demonstrates usefulness of maternal death surveillance and review as a monitoring tool. Methods: Fourteen maternal deaths were evaluated through community based and facility-based audits from July 2013 to June 2014 in three districts of Gujarat. Pathways to death were traced through Global Positioning System (GPS). Factors contributing to the three delays were analyzed. Results: Type III delay, that is, delay in receiving adequate care was frequently observed in our review including weak referral linkages, lack of blood banking services, inadequate surgical facilities. and staff shortages. Mothers succumbed, not because they did not seek treatment or reach facilities in time but because facilities were incapable of providing appropriate medical care. Conclusion: Scaling up of maternal death audits and subsequent use of these findings will help to reduce maternal mortality in India. As we continue to push for institutional deliveries, we need to reevaluate if our health system is prepared to manage an increasing number of facility births and obstetric complications.
Distinct temporal requirements for Sonic hedgehog signaling in development of the tuberal hypothalamus

ABSTRACT Sonic hedgehog (Shh) plays well characterized roles in brain and spinal cord development, but its functions in the hypothalamus have been more difficult to elucidate owing to the complex neuroanatomy of this brain area. Here, we use fate mapping and conditional deletion models in mice to define requirements for dynamic Shh activity at distinct developmental stages in the tuberal hypothalamus, a brain region with important homeostatic functions. At early time points, Shh signaling regulates dorsoventral patterning, neurogenesis and the size of the ventral midline. Fate-mapping experiments demonstrate that Shh-expressing and -responsive progenitors contribute to distinct neuronal subtypes, accounting for some of the cellular heterogeneity in tuberal hypothalamic nuclei. Conditional deletion of the hedgehog transducer smoothened (Smo), after dorsoventral patterning has been established, reveals that Shh signaling is necessary to maintain proliferation and progenitor identity during peak periods of hypothalamic neurogenesis. We also find that mosaic disruption of Smo causes a non-cell autonomous gain in Shh signaling activity in neighboring wild-type cells, suggesting a mechanism for the pathogenesis of hypothalamic hamartomas, benign tumors that form during hypothalamic development. Summary: Requirements for dynamic Sonic hedgehog activity at distinct stages of tuberal hypothalamic development are defined using fate-mapping and conditional deletion models in mice, suggesting a mechanism for the pathogenesis of hypothalamic hamartomas.
Energy-efficient localization and target tracking via underwater mobile sensor networks

Underwater mobile sensor networks (UMSNs) with free-floating sensors are more suitable for understanding the immense underwater environment. Target tracking, whose performance depends on sensor localization accuracy, is one of the broad applications of UMSNs. However, in UMSNs, sensors move with environmental forces, so their positions change continuously, which poses a challenge on the accuracy of sensor localization and target tracking. We propose a high-accuracy localization with mobility prediction (HLMP) algorithm to acquire relatively accurate sensor location estimates. The HLMP algorithm exploits sensor mobility characteristics and the multi-step Levinson-Durbin algorithm to predict future positions. Furthermore, we present a simultaneous localization and target tracking (SLAT) algorithm to update sensor locations based on measurements during the process of target tracking. Simulation results demonstrate that the HLMP algorithm can improve localization accuracy significantly with low energy consumption and that the SLAT algorithm can further decrease the sensor localization error. In addition, results prove that a better localization accuracy will synchronously improve the target tracking performance.
Kinetics of adult hematopoietic stem cell differentiation in vivo

Adult hematopoiesis has been studied in terms of progenitor differentiation potentials, whereas its kinetics in vivo is poorly understood. We combined inducible lineage tracing of endogenous adult hematopoietic stem cells (HSCs) with flow cytometry and single-cell RNA sequencing to characterize early steps of hematopoietic differentiation in the steady-state. Labeled cells, comprising primarily long-term HSCs and some short-term HSCs, produced megakaryocytic lineage progeny within 1 wk in a process that required only two to three cell divisions. Erythroid and myeloid progeny emerged simultaneously by 2 wk and included a progenitor population with expression features of both lineages. Myeloid progenitors at this stage showed diversification into granulocytic, monocytic, and dendritic cell types, and rare intermediate cell states could be detected. In contrast, lymphoid differentiation was virtually absent within the first 3 wk of tracing. These results show that continuous differentiation of HSCs rapidly produces major hematopoietic lineages and cell types and reveal fundamental kinetic differences between megakaryocytic, erythroid, myeloid, and lymphoid differentiation.
Is there any relationship between human foamy virus infections and familial Mediterranean fever?

Background: Familial Mediterranean fever (FMF) is generally defined as an autosomal recessive disease, characterized by the automatic activation of the innate immune system in the absence of a detectable pathogenic stimulant. We hypothesize that the pathogenic factors, besides the genetic causes, may affect the development of FMF symptoms. To test this hypothesis, we examined the effects of human foamy virus (HFV) positivity on the occurrence of the clinical symptoms of FMF. Materials and Methods: Two hundred and twenty-two FMF patients with definitive diagnosis according to Tel Hashomer criteria (study group 1 [SG1]), 205 symptomatic FMF patients who had definitive diagnosis according to the same criteria but did not carry any of the 12 most commonly occurring MEFV gene mutations (study group 2 [SG2]), and 200 healthy individuals were included as control group (study group 3 [SG3]) in the study. The genetic analysis was applied in the Molecular Genetics Laboratory of the Department of Medical Biology, Faculty of Medicine, Ondokuz Mayıs University. This study was designed as a case-control study. HFV positivity was tested by amplifying the HFV bel1 gene sequence with polymerase chain reaction technique. Statistical analyses were conducted using SPSS version 23.0 software. Results: HFV positivity showed significant differences between the study groups (P = 0.002). While 43 (19.02%) of the 222 SG1 patients were positive for the HFV bel1 gene sequence, 33 (16.09%) of the 205 SG2 patients were positive for the same sequence. Only 15 (7.5%) of the SG3 participants were positive for the presence of HFV bel1 gene sequence. Conclusion: The results of our study suggested that HFV positivity can be a stimulant pathogenic factor of natural immune system which can cause the emergence of FMF symptoms.
Detection of enrofloxacine residues by microbiological screening method

The usage of microbiological screening tests is widespread in control of presence of antimicrobial drug residues in meat samples. Screening tests must be capable to detect antimicrobial drug residue of interest and detection limits must comply with MRL (Maximum Residue Limit). The aim of this study was to examine the performance of a microbiological screening test with E. coli as test microorganism: capability of detecting enrofloxacina and it? s main metabolite ciprofloxacine at MRL levels in both fortified and incurred chicken tissue samples. Detection limits of microbiological screening test with E. coli was 50 ng/g for enrofloxacin and 25 ng/g for ciprofloxacin. Screening test had positive results in all samples of fortified and incurred meat with residue concentrations above MRL level. The results of this examinations shows that microbiological screening test with E. coli, as simple and cost effective test, is capable to detect enrofloxacine and it? s metabolite ciprofloxacine in treated poultry at MRL level ie test is capable to detect unsafe poultry meat.
Temporal Contingencies Determine Whether Adaptation Strengthens or Weakens Normalization

A fundamental and nearly ubiquitous feature of sensory encoding is that neuronal responses are strongly influenced by recent experience, or adaptation. Theoretical and computational studies have proposed that many adaptation effects may result in part from changes in the strength of normalization signals. Normalization is a “canonical” computation in which a neuron's response is modulated (normalized) by the pooled activity of other neurons. Here, we test whether adaptation can alter the strength of cross-orientation suppression, or masking, a paradigmatic form of normalization evident in primary visual cortex (V1). We made extracellular recordings of V1 neurons in anesthetized male macaques and measured responses to plaid stimuli composed of two overlapping, orthogonal gratings before and after prolonged exposure to two distinct adapters. The first adapter was a plaid consisting of orthogonal gratings and led to stronger masking. The second adapter presented the same orthogonal gratings in an interleaved manner and led to weaker masking. The strength of adaptation's effects on masking depended on the orientation of the test stimuli relative to the orientation of the adapters, but was independent of neuronal orientation preference. Changes in masking could not be explained by altered neuronal responsivity. Our results suggest that normalization signals can be strengthened or weakened by adaptation depending on the temporal contingencies of the adapting stimuli. Our findings reveal an interplay between two widespread computations in cortical circuits, adaptation and normalization, that enables flexible adjustments to the structure of the environment, including the temporal relationships among sensory stimuli. SIGNIFICANCE STATEMENT Two fundamental features of sensory responses are that they are influenced by adaptation and that they are modulated by the activity of other nearby neurons via normalization. Our findings reveal a strong interaction between these two aspects of cortical computation. Specifically, we show that cross-orientation masking, a form of normalization, can be strengthened or weakened by adaptation depending on the temporal contingencies between sensory inputs. Our findings support theoretical proposals that some adaptation effects may involve altered normalization and offer a network-based explanation for how cortex adjusts to current sensory demands.
Inhibition of cell fate repressors secures the differentiation of the touch receptor neurons of Caenorhabditis elegans

ABSTRACT Terminal differentiation generates the specialized features and functions that allow postmitotic cells to acquire their distinguishing characteristics. This process is thought to be controlled by transcription factors called ‘terminal selectors’ that directly activate a set of downstream effector genes. In Caenorhabditis elegans, the differentiation of both the mechanosensory touch receptor neurons (TRNs) and the multidendritic nociceptor FLP neurons uses the terminal selectors UNC-86 and MEC-3. The FLP neurons fail to activate TRN genes, however, because a complex of two transcriptional repressors (EGL-44/EGL-46) prevents their expression. Here, we show that the ZEB family transcriptional factor ZAG-1 promotes TRN differentiation not by activating TRN genes but by preventing the expression of EGL-44/EGL-46. As EGL-44/EGL-46 also inhibits the production of ZAG-1, these proteins form a bistable, negative-feedback loop that regulates the choice between the two neuronal fates. Summary: ZAG-1, a ZEB family transcription factor, safeguards fate specification of C. elegans touch receptor neurons by inhibiting a TEA domain-containing repressor, revealing its role in neuronal fate choice.
A Review on Cardiovascular Outcome Studies of Dipeptidyl Peptidase-4 Inhibitors

The U.S. Food and Drug Administration issued a guidance for pharmaceutical industry defining preapproval and postapproval requirements for the demonstration of cardiovascular (CV) safety for all new medications developed for glycemic management in type 2 diabetes. However, results published from the studies of dipeptidyl peptidase-4 (DPP-4) inhibitors are conflicting with regard to different CV endpoints. Upcoming CV outcome studies perhaps will be able to provide additional insights related to diabetes management and help to provide the answers to some of these concerns. This article provides a brief overview regarding how various CV safety evidence of DPP-4 inhibitor evolved over time that highlights possible implication in clinical practice and translates them into effective diabetes management.
Bimodal Hearing or Bilateral Cochlear Implants? Ask the Patient

Objective: The objectives of this study were to assess the effectiveness of various measures of speech understanding in distinguishing performance differences between adult bimodal and bilateral cochlear implant (CI) recipients and to provide a preliminary evidence-based tool guiding clinical decisions regarding bilateral CI candidacy. Design: This study used a multiple-baseline, cross-sectional design investigating speech recognition performance for 85 experienced adult CI recipients (49 bimodal, 36 bilateral). Speech recognition was assessed in a standard clinical test environment with a single loudspeaker using the minimum speech test battery for adult CI recipients as well as with an R-SPACETM 8-loudspeaker, sound-simulation system. All participants were tested in three listening conditions for each measure including each ear alone as well as in the bilateral/bimodal condition. In addition, we asked each bimodal listener to provide a yes/no answer to the question, “Do you think you need a second CI? ” Results: This study yielded three primary findings: (1) there were no significant differences between bimodal and bilateral CI performance or binaural summation on clinical measures of speech recognition, (2) an adaptive speech recognition task in the R-SPACETM system revealed significant differences in performance and binaural summation between bimodal and bilateral CI users, with bilateral CI users achieving significantly better performance and greater summation, and (3) the patient’s answer to the question, “Do you think you need a second CI? ” held high sensitivity (100% hit rate) for identifying likely bilateral CI candidates and moderately high specificity (77% correct rejection rate) for correctly identifying listeners best suited with a bimodal hearing configuration. Conclusions: Clinics cannot rely on current clinical measures of speech understanding, with a single loudspeaker, to determine bilateral CI candidacy for adult bimodal listeners nor to accurately document bilateral benefit relative to a previous bimodal hearing configuration. Speech recognition in a complex listening environment, such as R-SPACETM, is a sensitive and appropriate measure for determining bilateral CI candidacy and also likely for documenting bilateral benefit relative to a previous bimodal configuration. In the absence of an available R-SPACETM system, asking the patient whether or not s/he thinks s/he needs a second CI is a highly sensitive measure, which may prove clinically useful.