Miracle-dz/UniFAR-FTUs huggingface dataset:
The Timing and Magnitude of the Type I Interferon Response Are Correlated with Disease Tolerance in Arbovirus Infection

The host immune response usually aims to inhibit virus replication in order to avoid cell damage and disease. In some cases, however, the infected host avoids the deleterious effects of infection despite high levels of viral replication. ABSTRACT Infected hosts possess two alternative strategies to protect themselves against the negative impact of virus infections: resistance, used to abrogate virus replication, and disease tolerance, used to avoid tissue damage without controlling viral burden. The principles governing pathogen resistance are well understood, while less is known about those involved in disease tolerance. Here, we studied bluetongue virus (BTV), the cause of bluetongue disease of ruminants, as a model system to investigate the mechanisms of virus-host interactions correlating with disease tolerance. BTV induces clinical disease mainly in sheep, while cattle are considered reservoirs of infection, rarely exhibiting clinical symptoms despite sustained viremia. Using primary cells from multiple donors, we show that BTV consistently reaches higher titers in ovine cells than cells from cattle. The variable replication kinetics of BTV in sheep and cow cells were mostly abolished by abrogating the cell type I interferon (IFN) response. We identified restriction factors blocking BTV replication, but both the sheep and cow orthologues of these antiviral genes possess anti-BTV properties. Importantly, we demonstrate that BTV induces a faster host cell protein synthesis shutoff in primary sheep cells than cow cells, which results in an earlier downregulation of antiviral proteins. Moreover, by using RNA sequencing (RNA-seq), we also show a more pronounced expression of interferon-stimulated genes (ISGs) in BTV-infected cow cells than sheep cells. Our data provide a new perspective on how the type I IFN response in reservoir species can have overall positive effects on both virus and host evolution. IMPORTANCE The host immune response usually aims to inhibit virus replication in order to avoid cell damage and disease. In some cases, however, the infected host avoids the deleterious effects of infection despite high levels of viral replication. This strategy is known as disease tolerance, and it is used by animal reservoirs of some zoonotic viruses. Here, using a virus of ruminants (bluetongue virus [BTV]) as an experimental system, we dissected virus-host interactions in cells collected from species that are susceptible (sheep) or tolerant (cow) to disease. We show that (i) virus modulation of the host antiviral type I interferon (IFN) responses, (ii) viral replication kinetics, and (iii) virus-induced cell damage differ in tolerant and susceptible BTV-infected cells. Understanding the complex virus-host interactions in disease tolerance can allow us to disentangle the critical balance between protective and damaging host immune responses.
Highly cited tropical medicine articles in the Web of Science from 1991 to 2020: A bibliometric analysis.

BACKGROUND An adequate response to health needs to include the identification of research patterns about the large number of people living in the tropics and subjected to tropical diseases. Studies have shown that research does not always match the real needs of those populations, and that citation reflects mostly the amount of money behind particular publications. Here we test the hypothesis that research from richer institutions is published in better-indexed journals, and thus has greater citation rates. METHODS The data in this study were extracted from the Science Citation Index Expanded database; the 2020 journal Impact Factor (IF2020) was updated to 30 June 2021. We considered places, subjects, institutions and journals. RESULTS We identified 1041 highly cited articles with ≥100 citations in the category of tropical medicine. About a decade is needed for an article to reach peak citation. Only two COVID-19-related articles were highly cited in the last 3 y. The most cited articles were published by the journals Memorias Do Instituto Oswaldo Cruz (Brazil), Acta Tropica (Switzerland) and PLoS Neglected Tropical Diseases (USA). The USA dominated five of the six publication indicators. International collaboration articles had more citations than single-country articles. The UK, South Africa and Switzerland had high citation rates, as did the London School of Hygiene and Tropical Medicine in the UK, the Centers for Disease Control and Prevention in the USA and the WHO in Switzerland. CONCLUSIONS About 10 y of accumulated citations is needed to achieve ≥100 citations as highly cited articles in the Web of Science category of tropical medicine. Six publication and citation indicators, including authors' publication potential and characteristics evaluated by Y-index, indicate that the currently available indexing system places tropical researchers at a disadvantage against their colleagues in temperate countries, and suggest that, to progress towards better control of tropical diseases, international collaboration should increase, and other tropical countries should follow the example of Brazil, which provides significant financing to its scientific community.
Performance Analysis of Mixed Nakagami-   $m$ and Gamma–Gamma Dual-Hop FSO Transmission Systems

In this paper, we carry out a unified performance analysis of a dual-hop relay system over the asymmetric links composed of both radio-frequency (RF) and unified free-space optical (FSO) links under the effect of pointing errors. Both fixed and variable gain relay systems are studied. The RF link is modeled by the Nakagami-m fading channel and the FSO link by the Gamma-Gamma fading channel subject to both types of detection techniques (i.e., heterodyne detection and intensity modulation with direct detection). In particular, we derive new unified closed-form expressions for the cumulative distribution function, the probability density function, the moment generating function (MGF), and the moments of the end-to-end signal-to-noise ratio (SNR) of these systems in terms of the Meijer's G function. Based on these formulas, we offer exact closed-form expressions for the outage probability (OP), the higher order amount of fading, and the average bit error rate (BER) of a variety of binary modulations in terms of the Meijer's G function. Furthermore, an exact closed-form expression of the end-to-end ergodic capacity is derived in terms of the bivariate G function. Additionally, by using the asymptotic expansion of the Meijer's G function at the high-SNR regime, we derive new asymptotic results for the OP, the MGF, and the average BER in terms of simple elementary functions.
Picturing asthma in Turkey: results from the Turkish adult asthma registry

Abstract Introduction National data on asthma characteristics and the factors associated with uncontrolled asthma seem to be necessary for every country. For this purpose, we developed the Turkish Adult Asthma Registry for patients with asthma aiming to take a snapshot of our patients, thereby assigning the unmet needs and niche areas of intervention. Methods Case entries were performed between March 2018 and March 2022. A web-based application was used to record data. Study outcomes were demographic features, disease characteristics, asthma control levels, and phenotypes. Results The registry included 2053 patients from 36 study centers in Turkey. Female subjects dominated the group (n = 1535, 74.8%). The majority of the patients had allergic (n = 1158, 65.3%) and eosinophilic (n = 1174, 57.2%) asthma. Six hundred nineteen (32.2%) of the patients had obese asthma. Severe asthma existed in 670 (32.6%) patients. Majority of cases were on step 3–5 treatment (n: 1525; 88.1%). Uncontrolled asthma was associated with low educational level, severe asthma attacks in the last year, low FEV1, existence of chronic rhinosinusitis and living in particular regions. Conclusion The picture of this registry showed a dominancy of middle-aged obese women with moderate-to-severe asthma. We also determined particular strategic targets such as low educational level, severe asthma attacks, low FEV1, and chronic rhinosinusitis to decrease uncontrolled asthma in our country. Moreover, some regional strategies may also be needed as uncontrolled asthma is higher in certain regions. We believe that these data will guide authorities to reestablish national asthma programs to improve asthma service delivery.
Saddlepoint approximations to score test statistics in logistic regression for analyzing genome‐wide association studies

We investigate saddlepoint approximations of tail probabilities of the score test statistic in logistic regression for genome‐wide association studies. The inaccuracy in the normal approximation of the score test statistic increases with increasing imbalance in the response and with decreasing minor allele counts. Applying saddlepoint approximation methods greatly improve the accuracy, even far out in the tails of the distribution. By using exact results for a simple logistic regression model, as well as simulations for models with nuisance parameters, we compare double saddlepoint methods for computing two‐sided P$$ P $$ ‐values and mid‐ P$$ P $$ ‐values. These methods are also compared to a recent single saddlepoint procedure. We investigate the methods further on data from UK Biobank with skin and soft tissue infections as phenotype, using both common and rare variants.
Minimally invasive management of pathologic fractures of the pelvis and sacrum: Tumor ablation and fracture stabilization

Pathologic fractures of the pelvis/sacrum due to metastatic bone disease (MBD) cause pain and dysfunction due to mechanical instability of the pelvic ring. This study presents our multi‐institutional experience with percutaneous stabilization of pathologic fractures and osteolytic lesions from MBD throughout the pelvic ring.
Structures of Vac8-containing protein complexes reveal the underlying mechanism by which Vac8 regulates multiple cellular processes

Significance Armadillo repeat-containing (ARM) proteins form an evolutionarily conserved protein family and participate in various cellular processes mainly by providing binding platforms for diverse proteins. However, it is unknown how a single ARM protein mediates its interactions with multiple binding partners so that one process does not hinder another. We used Vac8, the only ARM protein found in the budding yeast Saccharomyces cerevisiae, as a model to investigate the mode of action of ARM proteins. By performing X-ray crystallography of Vac8-containing protein complexes in combination with biochemical and microscopic analyses, this study provides a working model of how Vac8 differentially regulates three cellular processes (formation of an interorganellar contact site, an autophagy-like process, and organelle inheritance).
Payments for ecosystem services did not crowd out pro-environmental behavior: Long-term experimental evidence from Uganda

Significance Deforestation is a major driver of greenhouse gas emissions and biodiversity loss. Payments for ecosystem services (PES) are one prominent policy instrument to protect forests. However, concerns have been raised that the introduction of monetary incentives for land users to engage in environmentally friendly behavior can undermine their motivation to do so in the long term. Such a crowding-out effect may render economic incentives less effective and, in the worst case, even counterproductive. This poses a particular concern if economic incentives are terminated. We studied the long-term effects of a terminated PES program in Uganda using a rigorous experimental design, concluding that pro-environmental behavior and its underlying motives are not adversely affected in the long term by temporary economic incentives.
Artificial Intelligence–Based Ethical Hacking for Health Information Systems: Simulation Study

Background Health information systems (HISs) are continuously targeted by hackers, who aim to bring down critical health infrastructure. This study was motivated by recent attacks on health care organizations that have resulted in the compromise of sensitive data held in HISs. Existing research on cybersecurity in the health care domain places an imbalanced focus on protecting medical devices and data. There is a lack of a systematic way to investigate how attackers may breach an HIS and access health care records. Objective This study aimed to provide new insights into HIS cybersecurity protection. We propose a systematic, novel, and optimized (artificial intelligence–based) ethical hacking method tailored specifically for HISs, and we compared it with the traditional unoptimized ethical hacking method. This allows researchers and practitioners to identify the points and attack pathways of possible penetration attacks on the HIS more efficiently. Methods In this study, we propose a novel methodological approach to ethical hacking in HISs. We implemented ethical hacking using both optimized and unoptimized methods in an experimental setting. Specifically, we set up an HIS simulation environment by implementing the open-source electronic medical record (OpenEMR) system and followed the National Institute of Standards and Technology’s ethical hacking framework to launch the attacks. In the experiment, we launched 50 rounds of attacks using both unoptimized and optimized ethical hacking methods. Results Ethical hacking was successfully conducted using both optimized and unoptimized methods. The results show that the optimized ethical hacking method outperforms the unoptimized method in terms of average time used, the average success rate of exploit, the number of exploits launched, and the number of successful exploits. We were able to identify the successful attack paths and exploits that are related to remote code execution, cross-site request forgery, improper authentication, vulnerability in the Oracle Business Intelligence Publisher, an elevation of privilege vulnerability (in MediaTek), and remote access backdoor (in the web graphical user interface for the Linux Virtual Server). Conclusions This research demonstrates systematic ethical hacking against an HIS using optimized and unoptimized methods, together with a set of penetration testing tools to identify exploits and combining them to perform ethical hacking. The findings contribute to the HIS literature, ethical hacking methodology, and mainstream artificial intelligence–based ethical hacking methods because they address some key weaknesses of these research fields. These findings also have great significance for the health care sector, as OpenEMR is widely adopted by health care organizations. Our findings offer novel insights for the protection of HISs and allow researchers to conduct further research in the HIS cybersecurity domain.
Detectable Coloring of Graphs

Let G be a connected graph of order n > 3 and let c : E(G) —> {1, 2 , . , k} be a coloring of the edges of G (where adjacent edges may be colored the same). For each vertex v of G, the color code of v with respect to c is the fc-tuple c(v) — (oi, «2 , ■ ■ ■, ak)-, where at is the number of edges incident with v th a t are colored i (1 < i < k). The coloring c is detectable if distinct vertices have distinct color codes. The detection number det(G) of G is the minimum positive integer k for which G has a detectable fc-coloring.
The Effectiveness of Digital-Based Psychotherapy in Overcoming Psychological Problems in College Students During the COVID-19 Pandemic: A Scoping Review

Purpose: This review aims to determine the effectiveness of the application of digital-based psychotherapy in overcoming the psychological problems of college students during the COVID-19 pandemic. Methods: Several databases consisting of EBSCO-Host CINAHL, PubMed, Scopus, Sage Journal, and Taylor and Francis were used in the search process and resulted in experimental studies focusing on the effectiveness of the application of digital-based psychotherapy during the COVID-19 pandemic timeline (2019–2022). Descriptive and exploratory analyses were performed based on the data set from the study. Results: A total of 12 articles were included in the review. The digital psychotherapy interventions found are diverse including websites, smartphone applications, and video conferencing with the types of therapies provided in the form of, Cognitive Therapy, Cognitive-Behavioral Therapy, Psychodynamic Therapy, and Mindfulness Therapy. Each intervention has a diverse duration and frequency adjusting to the type of therapy given. Digital psychotherapeutic interventions are effective in reducing mental health problems among college students during the COVID-19 pandemic. Conclusions: The use of digital psychotherapy can be used as a prevention and support service for students who experience psychological problems during the COVID-19 pandemic. The combination of the use of digital media with video conferencing can be considered to increase the effectiveness of this service. Nurses need to understand how the procedure for implementing digital-based psychotherapy is to improve the quality of mental care services as an effort to prevent and support students. More research is needed to find out the effectiveness of the use of digital psychotherapy services and how they impact the psychological well-being of students holistically.
Postural control among individuals with and without chronic obstructive pulmonary disease: A cross-sectional study of motor and sensory systems

Background Chronic obstructive pulmonary disease (COPD) is considered a heterogenic syndrome with systemic effects, including muscle dysfunction. There is evidence of postural control impairments among individuals with COPD, partly related to muscle weakness. However, research is scarce regarding the other underlying systems of postural control, such as the visual, somatosensory and vestibular system. The aim was to compare postural control, as well as the motor and sensory systems, between individuals with and without COPD. Methods Twenty-two participants with COPD (mean age 74.0 ±6.2 years) and 34 non-obstructive references (mean age 74.9 ±4.9 years) participated in this cross-sectional study. Postural control was assessed with center of pressure trajectory of postural sway in quiet as well as a limits of stability test, calculating mediolateral and anteroposterior amplitudes for each test. Assessment of function in the motor system included maximum hand grip strength, as well as maximum strength in muscles around the hip, knee and ankle joints. Visual acuity, pressure sensibility, proprioception, vestibular screening, and reaction time were also included. Data was compared between groups, and significant differences in postural control were further analyzed with an orthogonal projection of latent structures regression model. Results There was a significantly increased sway amplitude in the mediolateral direction in quiet stance on soft surface with eyes open (p = 0.014) as well as a smaller anteroposterior amplitude in the limits of stability test (p = 0.019) in the COPD group. Regression models revealed that the mediolateral amplitude was related to visual acuity and the burden of tobacco smoking assessed as pack-years. Further, muscle strength associated with anteroposterior amplitude in limits of stability test in the COPD group, and with age and ankle dorsal flexion strength among the referents. Besides for lower ankle plantar flexion strength in the COPD group, there were however no significant differences in muscle strength. Conclusions Individuals with COPD had a decreased postural control and several factors were associated with the impairments. The findings imply that the burden of tobacco smoking and reduced visual acuity relate to increased postural sway in quiet stance, and that muscle weakness is related to decreased limits of stability, among individuals with COPD.
Combining Signal Peptidase and Lipoprotein Processing Inhibitors Overcomes Ayr Resistance in Staphylococcus aureus

Antibiotic resistance in bacterial pathogens is an ongoing public health concern. The arylomycins are a class of natural product antibiotics that target the type I signal peptidase, which carries out the terminal step in protein secretion. ABSTRACT Antibiotic resistance in bacterial pathogens is an ongoing public health concern. The arylomycins are a class of natural product antibiotics that target the type I signal peptidase, which carries out the terminal step in protein secretion. Here, we used transposon sequencing (Tn-Seq) to profile the effects of the optimized arylomycin derivative G0775 in Staphylococcus aureus. Our transposon libraries include both upregulation and inactivation mutants, allowing us to identify resistance mechanisms and targets for synergism. We identified several cell envelope pathways that, when inactivated, sensitize S. aureus to the arylomycin G0775. These pathways include the lipoprotein processing pathway, and we have shown that inhibitors of this pathway synergize with G0775 even though lipoprotein processing is nonessential in S. aureus. Moreover, we found that blocking this pathway completely reverses Ayr resistance, which is a major resistance mechanism to arylomycins, including G0775. Our Tn-Seq data also showed that upregulation of mprF and several other genes is protective against G0775. Because a subset of these genes was previously found in a Tn-Seq profile of the clinically important antibiotic daptomycin, we tested a set of daptomycin-nonsusceptible clinical isolates with gain-of-function mutations in mprF for susceptibility to arylomycin G0775. Despite structural and mechanistic differences between these antibiotics, we observed similar decreases in susceptibility. Taken together, our results highlight how Tn-Seq profiles that include both gene inactivation and upregulation can identify targets, antibiotic resistance mechanisms, and strategies to overcome resistance.
YAP/BRD4‐controlled ROR1 promotes tumor‐initiating cells and hyperproliferation in pancreatic cancer

Tumor‐initiating cells are major drivers of chemoresistance and attractive targets for cancer therapy, however, their identity in human pancreatic ductal adenocarcinoma (PDAC) and the key molecules underlying their traits remain poorly understood. Here, we show that a cellular subpopulation with partial epithelial‐mesenchymal transition (EMT)‐like signature marked by high expression of receptor tyrosine kinase‐like orphan receptor 1 (ROR1) is the origin of heterogeneous tumor cells in PDAC. We demonstrate that ROR1 depletion suppresses tumor growth, recurrence after chemotherapy, and metastasis. Mechanistically, ROR1 induces the expression of Aurora kinase B (AURKB) by activating E2F through c‐Myc to enhance PDAC proliferation. Furthermore, epigenomic analyses reveal that ROR1 is transcriptionally dependent on YAP/BRD4 binding at the enhancer region, and targeting this pathway reduces ROR1 expression and prevents PDAC growth. Collectively, our findings reveal a critical role for ROR1high cells as tumor‐initiating cells and the functional importance of ROR1 in PDAC progression, thereby highlighting its therapeutic targetability.