Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of extracellular vesicles in lung diseases

Abstract Extracellular vesicles (EVs) are anuclear particles composed of lipid bilayers that contain nucleic acids, proteins, lipids, and organelles. EVs act as an important mediator of cell-to-cell communication by transmitting biological signals or components, including lipids, proteins, messenger RNAs, DNA, microRNAs, organelles, etc, to nearby or distant target cells to activate and regulate the function and phenotype of target cells. Under physiological conditions, EVs play an essential role in maintaining the homeostasis of the pulmonary milieu but they can also be involved in promoting the pathogenesis and progression of various respiratory diseases including chronic obstructive pulmonary disease, asthma, acute lung injury/acute respiratory distress syndrome, idiopathic pulmonary fibrosis (IPF), and pulmonary artery hypertension. In addition, in multiple preclinical studies, EVs derived from mesenchymal stem cells (EVs) have shown promising therapeutic effects on reducing and repairing lung injuries. Furthermore, in recent years, researchers have explored different methods for modifying EVs or enhancing EVs-mediated drug delivery to produce more targeted and beneficial effects. This article will review the characteristics and biogenesis of EVs and their role in lung homeostasis and various acute and chronic lung diseases and the potential therapeutic application of EVs in the field of clinical medicine.
NP-hard Sets are P-Superterse Unless R = NP

A set A is p-terse (p-superterse) if, for all q, it is not possible to answer q queries to A by making only q ? 1 queries to A (any set X). Formally, let PF A q-tt be the class of functions reducible to A via a polynomial-time truth-table reduction of norm q, and let PF A q-T be the class of functions reducible to A via a polynomial-time Turing reduction that makes at most q queries. A set A is p-terse if PF A q-tt 6 6 PF A (q? 1)-T for all constants q. A is p-superterse if PF A q-tt 6 6 PF X q-T for all constants q and sets X. We show that all NP-hard sets (under p tt-reductions) are p-superterse, unless it is possible to distinguish uniquely satissable formulas from satiss-able formulas in polynomial time. Consequently, all NP-complete sets are p-superterse unless P = UP (one-way functions fail to exist), R = NP (there exist randomized polynomial-time algorithms for all problems in NP), and the polynomial-time hierarchy collapses. This mostly solves the main open question in 4]. Allowing the number of queries q to be a function of the input length n, we obtain nontrivial partial answers to a question posed by Krentel: Namely, for all NP-complete sets A and all sets X, PF A q(n)-tt 6 6 PF X (q(n)? 1)-T unless SAT 2 RTIME(n O(q(n))) This is interesting whenever q(n) = o(n= log n). As a special case, PF A log i n-tt 6 6 PF X (log i n? 1)-T unless NTIME(n polylogn) = RTIME(n polylogn): 1 We extend the preceding results to tt-helpers; this allows us to isolate the key properties of NP-complete sets used in the proofs. Finally, we deene pbtt-cylinders, a natural class that includes all p m-complete sets for NP, PSPACE, and exponential time. For pbtt-cylinders, we show that p-terseness is equivalent to p-superterseness. We also prove a translational lemma for non-p-terse sets; this allows us to extend the preceding result to p btt-complete sets for NP, PSPACE, and exponential time.
The Role of Local Health Departments in Strengthening the Alignment Between Nonprofit Hospitals' Community Health Needs Assessments and Their Implementation Strategies

Nonprofit hospitals frequently partner with their local health department on developing community health needs assessments (CHNAs); yet, little is known about the role that such partnerships play in strengthening the alignment between needs identified in hospitals' assessments and the strategies adopted by hospitals to address identified needs. Using data for 486 hospitals from the third round of CHNAs (spanning the years 2018-2021), this study showed strong alignment between the health needs identified in the CHNAs and those addressed in hospitals' implementation strategies, independent of collaboration with the local health department. One noteworthy exception to this finding was that hospital-public health collaboration remained important for improved alignment of needs related to substance use. Involvement of the local health department may strengthen hospitals' capacity to address needs outside their traditional areas of expertise, such as substance use.
Impact of gut microbiome on skin health: gut-skin axis observed through the lenses of therapeutics and skin diseases

ABSTRACT The human intestine hosts diverse microbial communities that play a significant role in maintaining gut-skin homeostasis. When the relationship between gut microbiome and the immune system is impaired, subsequent effects can be triggered on the skin, potentially promoting the development of skin diseases. The mechanisms through which the gut microbiome affects skin health are still unclear. Enhancing our understanding on the connection between skin and gut microbiome is needed to find novel ways to treat human skin disorders. In this review, we systematically evaluate current data regarding microbial ecology of healthy skin and gut, diet, pre- and probiotics, and antibiotics, on gut microbiome and their effects on skin health. We discuss potential mechanisms of the gut-skin axis and the link between the gut and skin-associated diseases, such as psoriasis, atopic dermatitis, acne vulgaris, rosacea, alopecia areata, and hidradenitis suppurativa. This review will increase our understanding of the impacts of gut microbiome on skin conditions to aid in finding new medications for skin-associated diseases.
Clinical and biochemical distinctions for a metabolite repair disorder caused by NAXD or NAXE deficiency

The central cofactors NAD(P)H are prone to damage by hydration, resulting in formation of redox‐inactive derivatives designated NAD(P)HX. The highly conserved enzymes NAD(P)HX dehydratase (NAXD) and NAD(P)HX epimerase (NAXE) function to repair intracellular NAD(P)HX. Recently, pathogenic variants in both the NAXD and NAXE genes were associated with rapid deterioration and death after an otherwise trivial fever, infection, or illness in young patients. As more patients are identified, distinct clinical features are emerging depending on the location of the pathogenic variant. In this review, we carefully catalogued the clinical features of all published NAXD deficiency patients and found distinct patterns in clinical presentations depending on which subcellular compartment is affected by the enzymatic deficiency. Exon 1 of NAXD contains a mitochondrial propeptide, and a unique cytosolic isoform is initiated from an alternative start codon in exon 2. NAXD deficiency patients with variants that affect both the cytosolic and mitochondrial isoforms present with neurological defects, seizures and skin lesions. Interestingly, patients with NAXD variants exclusively affecting the mitochondrial isoform present with myopathy, moderate neuropathy and a cardiac presentation, without the characteristic skin lesions, seizures or neurological degeneration. This suggests that cytosolic NAD(P)HX repair may protect from neurological damage, whereas muscle fibres may be more sensitive to mitochondrial NAD(P)HX damage. A deeper understanding of the clinical phenotype may facilitate rapid identification of new cases and allow earlier therapeutic intervention. Niacin‐based therapies are promising, but advances in disease modelling for both NAXD and NAXE deficiency may identify more specific compounds as targeted treatments. In this review, we found distinct patterns in the clinical presentations of NAXD deficiency patients based on the location of the pathogenic variant, which determines the subcellular compartment that is affected by the enzymatic deficiency.
Occupational Health Hazards in Small and Medium-scale Manufacturing Industries in Anambra State, South East, Nigeria

Background: The World Health Organization (WHO) defined "occupational health” as dealing with all aspects of health and safety in the workplace and has a strong focus on primary prevention of hazards. A hazard is any source of potential damage, harm or adverse health effects on something or someone under certain conditions at work. Globally, there are 2.9 billion workers who are exposed to hazardous risk at their work places. Annually, there are two million deaths that are attributable to occupational diseases and injuries, while 4% of Gross Domestic Product (GDP) is lost due to occupational diseases and injuries. Objectives: To assess the occupational health hazards in small and medium-scale manufacturing industries in Anambra State. Methodology: This was a comparative descriptive cross-sectional study amongst registered medium and small-scale manufacturing industries in Anambra State. Data were collected using an interviewer administered semi-structured questionnaire and were analyzed using SPSS version 17. An inspection of the industries was done and the measurement of noise level, dust and psychosocial hazards within the factory floor was carried out. Results: A preponderance of male staff was found in the small scale (77.6%) and medium scale (75.0%) industries. The medical staffs constituted 7.4% in the medium scale industries and 2.1% in the small scale industries. The medical staff in both the small and medium scale industries constituted only 3.9% of the total work force. The average noise level was found to be higher in the medium scale industries (76.2) as compared to the small scaled industries (72.6). The average environmental dust concentration and psychosocial hazards were found to be higher in the small scale industries (2.3mg/m3 and 52.1%); as compared to the medium scale industries (1.1mg/m3 and 26.3%) respectively. Cuts and injuries constituted 41.2%; 35.4 and 25.9%; 30.0 of complaints by workers associated with hazards in the small and medium scale industries respectively. Conclusion: The average noise level was higher in the medium scale industries and generally lower than the threshold limits value (TLV) for noise of 85dB over an 8 hour working period. The average environmental dust concentration and psychosocial hazards were higher in the small scale industries. There was high potentials for accidents and injuries.
Analysis of predictors of stress during confinement by COVID–19 in Spain

Introduction. Confinement has had a great emotional impact on the population, especially in terms of stress. Factors such as the presence of previous mental or physical illness, resilience or emotional intelligence may influence the occurrence or increase of stress. The aim was to assess predictors of stress by comparing two statistical methodologies (one linear and one non-linear). Method. 802 Spaniards (65.50% women) who completed the questionnaires autonomously after signing the informed consent form participated. Stress (PSPP), COVID-19 threat perception (BIPQ-5), resilience (CD-RISC-10) and emotional intelligence (TMMS-24) were assessed. Descriptive statistics, hierarchical regression (HRM) and fuzzy set comparative qualitative analysis (fsQCA) were conducted. Results. Data obtained by HRM showed that the presence of previous mental illness, low resilience and emotional clarity, high emotional alertness and COVID-19 threat perception predicted 51% of the variance in stress. On the other hand, the results of the QCA showed that different combinations of these variables explained 71% of high stress and 56% of low stress. Pointing out how the presence of previous mental illness, high resilience, high emotional clarity and repair, low emotional alertness and low COVID-19 threat perception play a key role in explaining stress. Conclusions. These aspects will help to promote personal resources to buffer stress in confinement situations.
Parthenolide reveals an allosteric mode to inhibit the deISGylation activity of SARS-CoV‑2 papain-like protease

The coronavirus papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for viral polypeptide cleavage and the deISGylation of interferon-stimulated gene 15 (ISG15), which enable it to participate in virus replication and host innate immune pathways. Therefore, PLpro is considered an attractive antiviral drug target. Here, we show that parthenolide, a germacrane sesquiterpene lactone, has SARS-CoV-2 PLpro inhibitory activity. Parthenolide covalently binds to Cys-191 or Cys-194 of the PLpro protein, but not the Cys-111 at the PLpro catalytic site. Mutation of Cys-191 or Cys-194 reduces the activity of PLpro. Molecular docking studies show that parthenolide may also form hydrogen bonds with Lys-192, Thr-193, and Gln-231. Furthermore, parthenolide inhibits the deISGylation but not the deubiquitinating activity of PLpro in vitro. These results reveal that parthenolide inhibits PLpro activity by allosteric regulation.
Developmental effects of siloxane exposure in zebrafish: A comparison study using laboratory‐mixed and environmental water samples

Siloxanes are used in personal care, biomedical, and industrial products. Their worldwide use and persistence in the environment cause consistent exposure for both humans and aquatic animals. Two siloxane congeners, decamethylcyclopentasiloxane (D5; CAS 541‐02‐6) and octamethylcyclotetrasiloxane (D4; CAS 556‐67‐2), are among the most prevalent, with measurable levels in air, sediment, water, and biological samples. However, few studies have examined the impact of developmental (embryo/larva) exposure. To address this gap, we performed parallel experiments using wildtype zebrafish (Danio rerio). One set of experiments used laboratory‐mixed individual solutions containing either D4, D5, or 2,4,6,8‐tetramethylcyclotetrasiloxane (D4H; CAS 2370‐88‐9); the other used environmental water samples containing a mixture of siloxanes, including D4 and D5. These samples were collected from Bladensburg Waterfront Park (BWP) a site along the Anacostia River, Washington, DC. In both experiments, zebrafish (24–48 h postfertilization, hpf) were exposed until 7 or 14 days (d)pf. Chronic exposure to D4, D5, or BWP water until 7 dpf caused stress‐like behaviors and reduced swim velocities; anatomical differences were noted only in BWP‐exposed larvae. At 14 dpf, BWP‐treated larvae still showed slower swimming velocities and increased immobility; anatomical differences were no longer evident and thigmotactic behavior was reduced. D4 and D5‐exposed larvae did not survive after 10 dpf. Larvae exposed to D4H showed no decreases in behavior or growth at either age. These results suggest early developmental sensitivity to siloxane exposure and point to the need to consider embryonic/larval endpoints when assessing aquatic contaminants.
Predicting Perceived Vocal Roughness Using a Bio-Inspired Computational Model of Auditory Temporal Envelope Processing.

PURPOSE Vocal roughness is often present in many voice disorders but the assessment of roughness mainly depends on the subjective auditory-perceptual evaluation and lacks acoustic correlates. This study aimed to apply the concept of roughness in general sound quality perception to vocal roughness assessment and to characterize the relationship between vocal roughness and temporal envelop fluctuation measures obtained from an auditory model. METHOD Ten /ɑ/ recordings with a wide range of roughness were selected from an existing database. Ten listeners rated the roughness of the recordings in a single-variable matching task. Temporal envelope fluctuations of the recordings were analyzed with an auditory processing model of amplitude modulation that utilizes a modulation filterbank of different modulation frequencies. Pitch strength and the smoothed cepstral peak prominence were also obtained for comparison. RESULTS Individual simple regression models yielded envelope standard deviation from a modulation filter with a low center frequency (64.3 Hz) as a statistically significant predictor of vocal roughness with a strong coefficient of determination (r 2 = .80). Pitch strength and CPPS were not significant predictors of roughness. CONCLUSION This result supports the possible utility of envelope fluctuation measures from an auditory model as objective correlates of vocal roughness.
The experience of staff utilizing data to evaluate and improve person‐centred practice: An action research study

Abstract Aim Explore how nurses and midwives use patient experience data collected from a mobile health app to influence the development of person‐centred practice. Design Participatory action research, underpinned by the Person‐Centred Nursing Framework and Practice Development principles. Methods Six clinical units in a large health district engaged in three action cycles from 2018 to 2020 using a mobile health app. Nursing/midwifery staff on the units (N = 177) utilized data collected via the app to evaluate and improve person‐centred practice. A pre–post survey using the PCPI‐S was conducted to evaluate staff perceptions of person‐centredness. Data from the surveys (n = 101 in 2018 and n = 102 in 2020) and 17 semi‐structured interviews were used to understand the influence working with these data had on person‐centred practice. The Guidelines for Best Practices in the Reporting of Participatory Action Research have been used to report this study. Results Improvements in person‐centred practice were noted across both data sets. There was a statistically significant increase in two domains of the PCPI‐S in the independent t‐test and across all three domains in the paired t‐test results. Thematic analysis resulted in the identification of six themes: Getting everyone on board, once we understood, keeping on track, there's a person in the bed, knowing you're doing a good job and improving over time. Conclusion Engaging with the data collected from the app in a facilitated and collaborative way results in increases in person‐centredness. Impact This study provides insight into how nurses and midwives used data from a mHealth app to evaluate and improve person‐centred practice. Utilizing the data generated by the app resulted in increased person‐centredness amongst staff and changes to practice and culture. Nursing and midwifery teams who are supported to engage with patient experience data in an action‐oriented way will see person‐centred practice improvements, affecting patients and staff.
Physical stress and physical exercise dependence

ABSTRACT The aim of this study was to verify the referring scores of exer-cise dependence, quality of life as well as the mood indicators inadventure race (AR) athletes. 17 athletes of both sexes participa-ted in the study and all had a history of three years in this modality,with national and international experience, and figured in the firstpositions in the Brazilian ranking. The age, height, weight, bodymass index (BMI) and oxygen uptake averages ± standard deviati-ons were: 31.11 ± 6.30 years; 1.73 ± 0.07 cm; 70.75 ± 7.96 kg;23.48 ± 1.48 wt/ht 2 and 58.70 ± 6.63 ml.min -1 . kg , respectively.The volunteers were given the following questionnaires: ExerciseDependency Scale (EDE), Idate Trait and State, Profile of MoodStates (POMS), SF-36 Health Research and Social Patterns Ques-tionnaire. The results showed that scores in EDE indicated exerci-se dependence, and the mood questionnaires revealed moderateanxiety, while the POMS did not detect any indicative scores ofmood disorders. Concerning the quality of life, the average of 8dimensions of the SF-36 was higher than 85%, suggesting thatalthough there was exercise dependence, this fact alone did notpromote significant alterations in mood and quality of life. Thus,our data suggested that athletes of AR have exercise dependencenot associated to mood disorders.
Evaluating the Efficacy of a Guided and Unguided Internet-Based Self-help Intervention for Chronic Loneliness: Protocol for a 3-Arm Randomized Controlled Trial

Background Loneliness, or perceived social isolation, is prevalent in both the general population and clinical practice. Although loneliness has repeatedly been associated with mental and physical health, research on interventions that reduce loneliness effectively is still rather scarce. Objective This study aims to evaluate the efficacy of a guided and an unguided version of the same internet-based cognitive behavioral self-help program for loneliness (SOLUS-D) for adults. Methods A total of 250 participants will be randomly assigned to 1 of 2 intervention groups (SOLUS-D with guidance or SOLUS-D without guidance) or a wait-list control group (2:2:1 allocation ratio). Adult participants experiencing high levels of loneliness will be recruited from the general population. Individuals currently experiencing at least moderately severe depressive symptoms, an ongoing severe substance use disorder, previous or current bipolar or psychotic disorder, or acute suicidality will be excluded from the trial. Assessments will take place at baseline, 5 weeks (midassessment), and 10 weeks (postassessment). The primary outcome is loneliness assessed using the 9-item University of California, Los Angeles Loneliness Scale at the posttreatment time point. Secondary outcomes include depressive symptoms, symptoms of social anxiety, satisfaction with life, social network size, and variables assessing cognitive bias and social behavior. The maintenance of potentially achieved gains will be assessed and compared at 6 and 12 months after randomization in the 2 active conditions. Potential moderators and mediators will be tested exploratorily. Data will be analyzed on an intention-to-treat basis. Results Recruitment and data collection started in May 2021 and are expected to be completed by 2022, with the 12-month follow-up to be completed by 2023. As of the time of submission of the manuscript, 134 participants were randomized. Conclusions This 3-arm randomized controlled trial will add to the existing research on the efficacy of loneliness interventions. Furthermore, it will shed light on the role of human guidance in internet-based treatments for individuals with increased levels of loneliness and the possible mechanisms of change. If SOLUS-D proves effective, it could provide a low-threshold, cost-efficient method of helping and supporting individuals with increased levels of loneliness. Trial Registration ClinicalTrials.gov NCT04655196; https://clinicaltrials.gov/ct2/show/NCT04655196 International Registered Report Identifier (IRRID) DERR1-10.2196/36358
Deep Spike Learning With Local Classifiers

Backpropagation has been successfully generalized to optimize deep spiking neural networks (SNNs), where, nevertheless, gradients need to be propagated back through all layers, resulting in a massive consumption of computing resources and an obstacle to the parallelization of training. A biologically motivated scheme of local learning provides an alternative to efficiently train deep networks but often suffers a low performance of accuracy on practical tasks. Thus, how to train deep SNNs with the local learning scheme to achieve both efficient and accurate performance still remains an important challenge. In this study, we focus on a supervised local learning scheme where each layer is independently optimized with an auxiliary classifier. Accordingly, we first propose a spike-based efficient local learning rule by only considering the direct dependencies in the current time. We then propose two variants that additionally incorporate temporal dependencies through a backward and forward process, respectively. The effectiveness and performance of our proposed methods are extensively evaluated with six mainstream datasets. Experimental results show that our methods can successfully scale up to large networks and substantially outperform the spike-based local learning baselines on all studied benchmarks. Our results also reveal that gradients with temporal dependencies are essential for high performance on temporal tasks, while they have negligible effects on rate-based tasks. Our work is significant as it brings the performance of spike-based local learning to a new level with the computational benefits being retained.