Miracle-dz/UniFAR-FTUs huggingface dataset:
Outdoor air pollution impacts chronic obstructive pulmonary disease deaths in South Asia and China: a systematic review and meta-analysis [version 1; peer review: awaiting peer review]

Background: Chronic obstructive lung disease is among leading causes of death globally. Exposure to outdoor pollution is an important cause for increased mortality and morbidity. Objective: To present a systemic synthesis evidence regarding impact of outdoor pollution on COPD mortality in south asia and china. Methods: A systematic search on studies with statistical power has been conducted from 1990 - June 30 th 2021, in English electronic databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines from MEDLINE and PUBMED databases with terms: Chronic Obstructive Pulmonary disease OR COPD OR Chronic Bronchitis OR Emphysema OR COPD Deaths OR Chronic Obstructive Lung Disease OR Airflow Obstruction OR Chronic Airflow Obstruction OR Airflow Obstruction, Chronic OR Bronchitis, Chronic AND Mortality OR Death OR Deceased AND Outdoor pollution, ambient pollution was conducted. Results: Out of 1899 papers screened only 16 found eligible to be included in the study. Subjects with COPD exposed to higher levels of outdoor air pollution had a 49 % higher risk of death as compared to COPD subjects exposed to lower levels of outdoor air pollution. When taken individual pollutants into consideration, common air pollutants like PM10
Epstein-Barr Virus Regulates Endothelin-1 Expression through the ERK/FOXO1 Pathway in EBV-Associated Gastric Cancer

The relationship between Epstein-Barr virus and gastric cancer has been relatively clear. However, there are still many unresolved mechanisms of the virus in tumorigenesis. ABSTRACT Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma and its unique clinicopathological mechanism is unclear. Herein, the expression of endothelin-1 (ET-1) in EBVaGC was lower than of Epstein-Barr virus-negative gastric carcinoma (EBVnGC) and associated with a low frequency of lymph node metastasis of EBVaGC. Functional studies showed that the activation of ET-1/endothelin receptor type A (ETAR) axis could promote cell growth, migration, and antiapoptosis. The expression of the ET-1 gene was unrelated to methylation of its promoter region and miRNAs (-1, -125a, -125b). After being treated with MEK1/2 inhibitor (PD0325901), the inactivation of ERK1/2 pathway resulted in downregulation of ET-1 and forkhead box O1 (FOXO1) expression. Further, FOXO1 knockdown decreased the ET-1 expression. These findings indicated that ET-1 could be involved in development of gastric cancer and EBV could suppress the expression of ET-1 via the regulation of the transcription factor FOXO1 through the MAPK/ERK pathway. IMPORTANCE The relationship between Epstein-Barr virus and gastric cancer has been relatively clear. However, there are still many unresolved mechanisms of the virus in tumorigenesis. In recent years, activation of the endothelin-1 signaling axis has been found to play an important role in tumorigenesis, which is involved in tumor angiogenesis and epithelial-mesenchymal transition. EBV genes. In our study, we found that ET-1 was low-expressed in EBV-positive gastric cancer cells, which was due to the inhibition of ERK signaling by EBNA1 through the repression of FOXO1 expression. The low expression of ET-1 limits the proliferation, migration, and anti-apoptotic ability of tumor cells. These findings contribute to further understanding of the role of EBV in EBV-associated gastric cancer.
Experiences from 4 Years of Organization of an External Quality Assessment for Mycobacterium tuberculosis Whole-Genome Sequencing in the European Union/European Economic Area

The wider availability of whole-genome sequencing (WGS) coupled to new developments in bioinformatic tools and databases to interpret Mycobacterium tuberculosis complex WGS data has accelerated the adoption of this method for the routine prediction of antimycobacterial drug resistance and genotyping, thus necessitating the establishment of a comprehensive external quality control system. Here, we report 4 years of development and results from such a panel. ABSTRACT Here, we report the development and key features of the first external quality assessment (EQA) scheme for Mycobacterium tuberculosis whole-genome sequencing (WGS). The results of four rounds (2017 to 2020) of implementation within the European tuberculosis reference laboratories network (ERLTB-Net-2) are presented and discussed. EQA panels comprising 10 genomic DNAs were distributed to ERLTB-Net 2 laboratories volunteering to participate in this exercise. Since 2018, five FASTQ files were added to better assess the dry WGS processes, and in 2020, three of the five files were replaced by synthetic files (providing additional flexibility for the mutations included in the panels). Ten National tuberculosis reference laboratories participated in all four EQA rounds, and seven participated in at least one. High-confidence resistance mutations were correctly identified by all laboratories, but challenges remained with respect to the identification of mixed loci and interpretation of rare mutations. M. tuberculosis genotyping and clustering analysis was >90% accurate for pure samples with the main challenges being related to the analysis of mixed genotypes and DNA FASTQ files. The development and implementation of this WGS EQA scheme has contributed to the continuous improvement in performance of participating laboratories in M. tuberculosis WGS and data analysis. This scheme can serve as a model of comprehensive quality assessment for M. tuberculosis WGS that can be replicated in different settings worldwide. IMPORTANCE The wider availability of whole-genome sequencing (WGS) coupled to new developments in bioinformatic tools and databases to interpret Mycobacterium tuberculosis complex WGS data has accelerated the adoption of this method for the routine prediction of antimycobacterial drug resistance and genotyping, thus necessitating the establishment of a comprehensive external quality control system. Here, we report 4 years of development and results from such a panel.
Application of auditory mismatch negativity in tinnitus patients based on high-resolution electroencephalogram signals

Abstract Objective The purpose of this study was to investigate the significance of mismatch negativity (MMN) by comparing high-resolution electroencephalogram signals from tinnitus patients and healthy controls. Methods The study included eight subjects with chronic subjective idiopathic tinnitus and seven healthy controls. Participants with clinical speech (512–2,000 Hz) hearing thresholds less than 25 dB HL and with negative Hospital Anxiety and Depression Scale scores were included in the study. The E-Prime 2.0 software and a 256-electrode EGI Net Station system were used to evoke and record the MMN signal, and the amplitude and latency parameters of the MMN responses were compared between the two groups. Results From 150 ms, there was a significant difference between the amplitude of standard stimulation and deviation stimulation, and the event-related potential amplitude under deviation stimulation in the tinnitus patient group was significantly different from that in the healthy group. The MMN amplitude of the FCz electrode was statistically significantly lower in the tinnitus patients compared to healthy controls. Conclusion MMN has application value in the evaluation of abnormal electrical activity in the auditory pathway, and electroencephalograms are feasible for follow-up monitoring after acoustic therapy.
Interpretation of a few ice event transients

This article discusses some of the observables important to the study of sound radiated into the water by ice fracturing events. Such studies are important in order to understand the mechanisms of Arctic Ocean ambient noise generation. Theoretical work for a homogeneous ice plate indicates that there are three important paths of elastic wave propagation over which energy travels away from an ice event source. These are the flexural wave in the ice, the longitudinal wave in the ice, and the acoustic wave in the water. Each has a distinctive propagation speed, attenuation, and associated pressure field in the water. The experimental work, consisting of the interpretation of four ice events, supports the theoretical description. In each case the event is located and the contributing wave paths identified. In all cases the acoustic wave dominates. The work also demonstrates how event analysis can be used to determine ice properties.
What Drives Knowledge Collaboration? Decomposing Knowledge Contribution Assessment, Finding Antecedents

Knowledge contribution is a positive process in knowledge collaboration. Using what approach to measure the knowledge contribution is critical for improving the efficiency of knowledge collaboration. Based on the studies of knowledge sharing barrier, this paper decomposed knowledge contribution into technological, communication and organization contribution and advocated the peer-assessment for knowledge contribution. Finding antecedents of each contribution is also crucial for accurate and effective knowledge management. Combined with the individual behavior model and IS success model, this paper proposed following antecedents: motivation, perception, ability and personality. Motivation and perception are intentional antecedents, but ability and personality are unintentional. In accordance with a field study of 250 employees, nested into 50 groups, we discover that individual learning motivation and perception of explicit knowledge heterogeneity can promote technological contribution but perception of tacit knowledge heterogeneity has an opposite effect; group motivation of social identity, acquisition ability and agreeableness traits increase communication contribution; group motivation, application ability and agreeableness enhance organization contribution.
The impact of levothyroxine exposure on delivery outcome in hypothyroid pregnant women (PETAL study): A five-year retrospective cohort study

Background Hypothyroidism affects 3% of pregnant women, and to date, no studies have addressed the impact levothyroxine-treated hypothyroidism on delivery outcome. Methods This retrospective cohort study was conducted among 750 women with a singleton pregnancy who gave birth between 2015 and 2019. Delivery modes were compared between 250 hypothyroid women exposed to levothyroxine and 500 euthyroid control women. The aim of this study was to determine the impact of levothyroxine exposure on delivery outcome. Results Multiple logistic regression showed no significant association between exposure to levothyroxine and the overall rate of caesarean delivery (aOR 1.1; 95% CI 0.8 to 1.6). Mean TSH concentrations were significantly higher throughout the pregnancy in hypothyroid women despite levothyroxine treatment. Maternal and neonatal outcomes in both groups were not different. Conclusion Hypothyroidism treated with levothyroxine during pregnancy according to local guidelines is not a significant risk factor for caesarean delivery.
Toward Understanding Task Complexity in Maintenance-Based Studies of Programming Tools

Researchers conducting studies on programming tools often make use of maintenance tasks. The complexity of these tasks can influence the behavior of participants significantly. At the same time, the complexity of tasks is difficult to pinpoint due to the many sources of complexity for maintenance tasks. As a result, researchers may struggle to deliberately decide in which regard their tasks should be complex and in which regard they should be simple. To help researchers make more deliberate decisions about the complexity of their tasks, we discuss different factors of task complexity. We draw these factors from previous user studies on programming tools as well as from a task complexity model from ergonomics research that we apply to maintenance tasks. In the end, task complexity might always be too complex to be fully controlled. Nevertheless, we hope that our discussion helps other researchers to decide in which dimensions their tasks are complex and in which dimensions they want to keep them simple.
Experimental investigation of the laminar boundary layer vortex-shedding noise by an airfoil within a closed-vein wind tunnel

This study concerns the experimental characterization of trailing edge noise, the understanding of which is crucial for mitigating acoustic pollution across major industries. An aeroacoustic experiment is carried out using a closed-vein wind tunnel to investigate the laminar boundary layer vortex-shedding (LBL-VS) noise of a symmetric NACA0021 airfoil in low Reynolds number flows (Re ≤ 163,500). Steady aerodynamic and acoustic measurements are performed, with numerous conditions covered (flow velocity from 10 m/s to 24.5 m/s, airfoil incidence from −10° to 10°). The aerodynamic results reveal that, in the pre-stall regime, the airfoil’ suction side exhibits both a laminar separation bubble (LSB) and a trailing edge detached flow – which both make LBL-VS noise likely to occur. The acoustic results reveal that, when at low speed and moderate incidence, the airfoil emits one to two tones, which can be both attributed to LBL-VS noise. In particular, their respective frequency is seen to scale as the 0.8th power of the flow velocity, whereas varying linearly with the incidence. At higher speeds, these two tones vanish to the profit of other, more intense tonal emissions, whose frequency does not scale with the velocity nor the incidence. These tones are attributed to resonance effects coming from a retroaction of the reverberant environment onto the LBL-VS noise emission, which then locks-on to some of the duct resonant frequencies via an acoustic feedback loop. Revealing indirectly the presence of the pre-existing LBL-VS noise, these resonant tones emerge only when the flow velocity and incidence obey specific conditions, namely a roughly linear relationship.
Why Public Sector Projects Fail or Succeed in Pakistan-A Model for Evaluating Impact of HR Management Practices on Project Success

Employees are an organization's most valuable asset. As quality human resources become scarcer, businesses must pay greater attention to employee satisfaction and motivation. If employees are motivated to work, it is likely that they will produce better results. This research will examine the impact of Human resource management (HRM) practices on new product development (NPD). Technical, marketing, and financial risks are involved in the development of new products and services. Effective project planning and management contribute to sound decision-making. The analysis of the impact of HRM practices on NPD, project success, and organizational benefit is based on data collected using a cross-sectional design via a survey questionnaire. The questionnaire consisted of items related to HR practices, NPD, Project Success, and Organizational benefits adapted from previous studies. Respondents working in 10 large-scale public sector projects executed by National Database & Registration Authority, Pakistan were selected for the study. Therefore, the results of the study can be generalized to similar projects executed by the public sector in Pakistan. According to the findings of the data analysis, there is a significant relationship between HR practices and project success, but there is no significant relationship between new product development and organizational benefit. It can be concluded that HR management practices have a significant influence on the success of public sector projects in Pakistan.
An integrative view on attentional 1 modulation in naturalistic speech 2

Attending to a speaker is a complex process: to hear sound waves that represent 10 acoustic features ; to understand the meaning of words that represent semantic features ; and the 11 listener and speaker need to be aligned to form a common ground, which represents inter-brain 12 features . Little is known about how attention modulates these features from the speaker in an 13 integrative way. Adopting naturalistic speech, combing with natural language processing models 14 and inter-brain EEG analysis methods, we measured how listener responses to different 15 information from the attended speaker simultaneously. Our result reveals that: the sound is the 16 ﬁrst to be processed; the meaning of the attended speech is parsed after that. The listener’s mind 17 aligned to the speaker even seconds before the speech begins. Together, our results illustrated 18 how our brain is selectively entrained to different types of information from the speaker in an 19 integrative view.
Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for lipid raft dynamics in early metaplasticity

Non-epileptic seizures are identified as a common epileptogenic trigger. Early metaplasticity following seizures may contribute to epileptogenesis by abnormally altering synaptic strength and homeostatic plasticity. We now studied how in vitro epileptiform activity triggers early changes in CA1 long-term potentiation (LTP) induced by theta-burst stimulation (TBS) in rat hippocampal slices and the involvement of lipid rafts in these early metaplasticity events. Two forms of epileptiform activity (EA) were induced: 1) interictal-like EA triggered by withdrawal of Mg2+ and K+ elevation to 6mM in the superfusion medium or 2) ictal-like EA induced by bicuculine (10μM) delivery. LTP induced 30 min post EA was impaired, an effect more pronounced after ictal-like EA. LTP recovered to control levels 60 min post interictal-like EA but was still impaired 60 min after ictal-like EA. The synaptic molecular events underlying this altered LTP were investigated 30 min post EA. Synaptosomes isolated from parallel slices showed enhanced AMPA GluA1 Ser831 phosphorylation but decreased Ser 845 phosphorylation and a marked decrease in GluA1/GluA2 ratio. A marked decrease in flotillin-1 and caveolin-1 levels concomitantly with a moderate increase in PSD-95 and marked increase in gephyrin levels. Altogether, EA differentially influences hippocampal CA1 LTP thorough regulation of GluA1/GluA2 levels and AMPA GluA1 phosphorylation suggesting altered LTP post-seizures may be a relevant target of antiepileptogenic therapies. In addition, this metaplasticity is also associated with marked alterations in classic and synaptic lipid raft markers, suggesting these may also constitute promising targets in epileptogenesis prevention.
A long‐acting GDF15 analog causes robust, sustained weight loss and reduction of food intake in an obese nonhuman primate model

GDF15 is a circulating polypeptide associated with cellular stress, and recently linked to metabolic adaptation. GDF15 has a half-life of approximately 3 hours in and acts at the GFRAL receptor selectively expressed in the area postrema. To characterize the effects of sustained GFRAL agonism on food intake (FI) and body weight (BW), we developed a half-life extended analog of GDF15 (Compound H; CpdH) suitable for reduced dosing frequency and tested its effects in obese cynomolgus monkeys. Animals were treated once weekly for 12 weeks with 0.048, 0.16, or 1.6 mg/Kg of CpdH or with 0.02 mg/Kg of the long-acting GLP-1 analog dulaglutide as a positive control. FI was measured daily and BW was measured biweekly. Mechanism-based longitudinal exposure-response (E-R) modeling was performed to characterize the effects of CpdH and dulaglutide on FI and BW. The integrated novel model accounts for both acute, exposure-dependent effects of treatments to reduce FI and the compensatory changes in energy expenditure (EE) and FI that occur over time in response to weight loss. CpdH had approximately linear, dose-proportional pharmacokinetics with a half-life of ≈8 days and treatment with CpdH led to dose- and exposure-dependent reductions in FI and BW. The 1.6 mg/Kg CpdH dose reduced mean FI by 57.5% at 1 week and provided sustained FI reductions of 31.5% from weeks 9-12, leading to a peak reduction in BW of 16±5%. Dulaglutide had more modest effects on FI (reductions between 15-40%) and peak BW loss was 3.8±4.0%. Longitudinal modeling of both the FI and BW profiles suggested reductions in BW observed with both CpdH and dulaglutide were fully explained by the exposure-dependent reductions in FI without any increase in EE. Upon verification of pharmacokinetic/pharmacodynamic relationship established in monkeys and human for dulaglutide, we predicted that CpdH could reach double digit BW loss in human. In summary, treatment with a long-acting GDF15 analog led to sustained dose- and exposure-dependent reductions in food intake in a monkey model of obesity and holds potential for effective clinical obesity pharmacotherapy. Significance Statement GDF15 activation of GFRAL receptors in the hindbrain controls food intake and body weight. Here we describe the effect and durability of a circulating half-life extended analog of GDF15 (Compound H) on food intake and body weight loss in a spontaneously obese cynomolgus monkey model. Inclusion of a translational treatment arm with a weight loss agent, dulaglutide, permitted pharmacokinetic/pharmacodynamic modeling and comparison of both GDF15 and GLP-1 based weight loss mechanisms, and development of an allometric scaling based mathematical model to estimate the efficacy of Compound H in human obese subjects.
Constraining the global niche suitability of the Eusuchia clade across the Cretaceous-Paleogene boundary

The crocodiles and their close relatives, the alligators and gharials, have a compelling evolutionary history. They are a clade of great antiquity, with their most recent common ancestor emerging within the Mesozoic. However, unlike many groups of such a great age, the crocodilians have an extensive crown-group, with around two dozen extant examples. They have a limited ecomorphology, which has varied little since their inception, and their biogeography has been shown to interact closely with climate. The biogeography of crocodilians in deep time remains an outstanding question, which is complicated further by the limitations of the fossil record. The fossil record is fundamentally incomplete yet represents the most common method used to infer biogeography of organisms. The scarcity of fossil remains makes apparent absences difficult to confirm. Preservation bias will promote fossil occurrences in areas with a high sedimentation rate, which may not be the true ecological niche for a given taxon. This study uses species distribution models of extant crocodilians to infer the ecological niche of related taxa in the Maastrichtian and Danian. Models indicate a much wider latitudinal range than is observed among extant examples, and the invasion of new ecospace following the end-Cretaceous mass extinction. In addition, we find that while temperature is of significance to crocodilian biogeography, it is precipitation that is the most influential climatic variable.
Reply on RC2

OBM is good for understanding the local photochemical formation of O3, but it is not good to evaluate the transport, while back trajectories cannot quantify the contributions. Thus, it is important to show the method of how the regional transport contribution is determined. In this study, the differences between observed O3 changes and local formation were treated as regional transport, which is very misleading. A better method representation should be physical processes instead of regional transport.