Miracle-dz/UniFAR-FTUs huggingface dataset:
Lethal Infectious Diseases as Inborn Errors of Immunity: Toward a Synthesis of the Germ and Genetic Theories.

It was first demonstrated in the late 19th century that human deaths from fever were typically due to infections. As the germ theory gained ground, it replaced the old, unproven theory that deaths from fever reflected a weak personal or even familial constitution. A new enigma emerged at the turn of the 20th century, when it became apparent that only a small proportion of infected individuals die from primary infections with almost any given microbe. Classical genetics studies gradually revealed that severe infectious diseases could be driven by human genetic predisposition. This idea gained ground with the support of molecular genetics, in three successive, overlapping steps. First, many rare inborn errors of immunity were shown, from 1985 onward, to underlie multiple, recurrent infections with Mendelian inheritance. Second, a handful of rare and familial infections also segregating as Mendelian traits but striking humans resistant to other infections were deciphered molecularly from 1996 onward. Third, a growing number of rare or common sporadic infections were shown to result from monogenic, but not Mendelian, inborn errors from 2007 onward. A synthesis of the hitherto mutually exclusive germ and genetic theories is now in view. This article has been accepted for publication on April 14, 2020. Changes may still occur before final publication. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 16 is January 24, 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
The viral protein U (Vpu)-interacting host protein ATP6V0C down-regulates cell-surface expression of tetherin and thereby contributes to HIV-1 release

Host proteins with antiviral activity have evolved as first-line defenses to suppress viral replication. The HIV-1 accessory protein viral protein U (Vpu) enhances release of the virus from host cells by down-regulating the cell-surface expression of the host restriction factor tetherin. However, the exact mechanism of Vpu-mediated suppression of antiviral host responses is unclear. To further understand the role of host proteins in Vpu's function, here we carried out yeast two-hybrid screening and identified the V0 subunit C of vacuolar ATPase (ATP6V0C) as a Vpu-binding protein. To examine the role of ATP6V0C in Vpu-mediated tetherin degradation and HIV-1 release, we knocked down ATP6V0C expression in HeLa cells and observed that ATP6V0C depletion impairs Vpu-mediated tetherin degradation, resulting in defective HIV-1 release. We also observed that ATP6V0C overexpression stabilizes tetherin expression. This stabilization effect was specific to ATP6V0C, as overexpression of another subunit of the vacuolar ATPase, ATP6V0C″, had no effect on tetherin expression. ATP6V0C overexpression did not stabilize CD4, another target of Vpu-mediated degradation. Immunofluorescence localization experiments revealed that the ATP6V0C-stabilized tetherin is sequestered in a CD63– and lysosome-associated membrane protein 1 (LAMP1)–positive intracellular compartment. These results indicate that the Vpu-interacting protein ATP6V0C plays a role in down-regulating cell-surface expression of tetherin and thereby contributes to HIV-1 assembly and release.
Screening and Treatment of Vitamin D Deficiency in UK Patients with Crohn’s Disease: Self-Reported Practice among Gastroenterologists

Currently, there is no UK national recommendation to measure vitamin D levels in patients with inflammatory bowel diseases (IBD). Patients with IBD are at risk of developing vitamin D deficiency with the highest prevalence frequently reported in those with Crohn’s disease (CD). Treating vitamin D deficiency as part of CD management continues to be of interest. Our aim was to identify influences on practice and self-reported practice among British Society of Gastroenterology (BSG)-IBD section members in the screening and the treatment of vitamin D deficiency in patients with CD. A web-based survey was distributed via email to members of the BSG-IBD section. Reported screening practice was generally annual in those with a history of previous surgery related to CD or small bowel CD. A total of 83% of respondents (n = 64) thought that vitamin D levels should be routinely monitored in patients with CD. Treatments for mild/moderate deficiency included increased sunlight exposure (mean frequency = 21, SD = 15) and dietary advice (mean frequency = 22, SD = 14); in moderate/severe deficiency, oral supplementation was recommended (mean frequency = 14, SD = 13). Respondents reported factors most likely to influence practice, including clearer evidence and guidance. Well conducted studies in CD patients with identified vitamin D deficiency are needed to inform national guidance and clinical practice.
High-Flow Nasal Cannula in Early Emergency Department Management of Acute Hypercapnic Respiratory Failure Due to Cardiogenic Pulmonary Edema

BACKGROUND: Noninvasive ventilation (NIV) is the recommended ventilatory support for acute cardiogenic pulmonary edema (CPE) associated with acute respiratory failure or hypercapnia. High-flow nasal cannula (HFNC) has emerged as an alternative to NIV in acute hypoxemic respiratory failure. We aimed to assess the efficacy of HFNC on early changes in PaCO2 and respiratory parameters in patients in the emergency department with acute hypercapnic CPE and to compare it to NIV. METHODS: We conducted a prospective observational study in consecutive emergency department patients with acute hypercapnic CPE. Subjects received either HFNC or NIV, according to the attending emergency physician's expertise in HFNC. The primary outcome was change in PaCO2 after treatment for 1 h. Secondary outcomes were change in pH, breathing frequency, signs of work of breathing, and comparisons to NIV. RESULTS: Twenty-seven subjects with a discharge diagnosis of hypercapnic CPE were analyzed. Subjects had a median age of 87 y (interquartile range [IQR] 78–93); 37% were male. Twelve (44%) received HFNC, and 15 (56%) received NIV. Median of changes in PaCO2 from baseline to after 1 h of treatment were 7 mm Hg (IQR 4–11, P = .002) for HFNC and 3 mm Hg (IQR 1–8, P = .02) for NIV, with no between-group difference. pH, breathing frequency and signs of work of breathing also improved after both HFNC and NIV. CONCLUSIONS: This preliminary study suggests that HFNC treatment for 1 h improves PaCO2 and respiratory parameters in subjects with hypercapnic acute CPE in a manner that is comparable to NIV. Further studies are needed to assess HFNC as a possible alternative to NIV in early management of acute hypercapnic respiratory failure of cardiogenic origin. (ClinicalTrials.gov registration NCT03883555.)
Use of Mental Health Apps by Patients With Breast Cancer in the United States: Pilot Pre-Post Study

Background Nearly half of the patients with breast cancer experience clinically significant mental distress within the first year of receiving their cancer diagnosis. There is an urgent need to identify scalable and cost-efficient ways of delivering empirically supported mental health interventions to patients with breast cancer. Objective The aim of this study was to evaluate the feasibility of in-clinic recruitment for a mobile phone app study and to evaluate the usability and preliminary impact of a suite of mental health apps (IntelliCare) with phone coaching on psychosocial distress symptoms in patients recently diagnosed with breast cancer. Methods This pilot study adopted a within-subject, 7-week pre-post study design. A total of 40 patients with breast cancer were recruited at a US National Cancer Institute–designated clinical cancer center. Self-reported distress (Patient Health Questionnaire-4) and mood symptoms (Patient-Reported Outcomes Measurement Information System depression and anxiety scales) were assessed at baseline and postintervention. App usability was assessed at postintervention. Results The minimum recruitment threshold was met. There was a significant decrease in general distress symptoms, as well as symptoms of depression and anxiety, from baseline to postintervention. Overall, participants reported high levels of ease of app use and learning. Scores for app usefulness and satisfaction were reinforced by some qualitative feedback suggesting that tailoring the apps more for patients with breast cancer could enhance engagement. Conclusions There is a dire need for scalable, supportive interventions in cancer. The results from this study inform how scalable mobile phone–delivered programs with additional phone support can be used to support patients with breast cancer. International Registered Report Identifier (IRRID) RR2-10.2196/11452
Do Work Engagement and Transformational Leadership Facilitate Knowledge Sharing? A Perspective of Conservation of Resources Theory

Based on the perspective of conservation of resources (COR) theory, this study adopts a multilevel approach to examine the influences of employees’ personal resources (i.e., work engagement and intrinsic motivation) and external resources (i.e., transformational leadership) on knowledge sharing. This study conducts a survey to explore the interrelationships among transformational leadership, work engagement, intrinsic motivation, and knowledge sharing. The sample includes 33 healthcare work groups consisting of 214 group members. The results show that an individual’s personal and external resources are positive and benefit the promotion of knowledge sharing. As for personal resources, work engagement has a positive impact on knowledge sharing by increasing intrinsic motivation. Regarding external resources, transformational leadership acts as a facilitator for knowledge sharing. Specifically, the conditional indirect effects of work engagement on knowledge sharing through intrinsic motivation are more positive under high levels of transformational leadership, rather than low levels of transformational leadership. Based on the COR theory, this is the first study to argue that knowledge sharing could be considered as an active activity and that individuals could be eager to perform knowledge sharing when they possess significant personal and external resources. The results of this study provide new insights into knowledge sharing.
The Clinical Role of Insulin Degludec/Insulin Aspart in Type 2 Diabetes: An Empirical Perspective from Experience in Australia

Treatment intensification in people with type 2 diabetes following failure of basal insulin commonly involves the addition of a rapid-acting insulin analogue (basal plus one or more prandial doses; multiple daily injections) or by a switch to premixed insulin. Insulin degludec/insulin aspart (IDegAsp), comprising rapid-acting insulin aspart and ultra-long-acting insulin degludec in solution, enables both fasting and post-prandial glucose control, with some advantages over other treatment intensification options. These include straightforward dose titration, flexibility in dose timing, low injection burden, simplicity of switching and a lower risk of hypoglycaemia. In Australia, where insulin degludec on its own is not available, IDegAsp enables patients to still benefit from its ultra-long-acting properties. This review aims to provide guidance on where and how to use IDegAsp. Specifically, guidance is included on the initiation of IDegAsp in insulin-naïve patients, treatment intensification from basal insulin, switching from premixed or basal-bolus insulin to IDegAsp, up-titration from once- to twice-daily IDegAsp and the use of IDegAsp in special populations or situations.
What do Firefighting Ability Tests Tell Us About Firefighter Physical Fitness? A Systematic Review of the Current Evidence.

Fyock-Martin, MB, Erickson, EK, Hautz, AH, Sell, KM, Turnbaugh, BL, Caswell, SV, and Martin, JR. What do firefighting ability tests tell us about firefighter physical fitness? A systematic review of the current evidence. J Strength Cond Res XX(X): 000-000, 2020-The firefighting profession is a physiologically demanding occupation. Currently, sudden cardiac deaths account for 40-50% of firefighter job-related deaths, for which, inadequate aerobic fitness (AF) and obesity are established as risk factors. Departments have instituted firefighting physical ability tests (FPATs) as a method of quantifying readiness for occupational-related demands. A systematic review of the current literature examining the correlation between field fitness test performance and FPAT completion times was performed. The search identified 5 studies that met the eligibility criteria. The total number of subjects in the 5 studies was 265 (259 men and 6 women), including 200 professional firefighters (75.5%), 40 volunteer (15.1%), 20 officers (7.5%), and 5 recruits (1.9%). Upper-body strength (UBs) and upper-body endurance (UBe) had the strongest correlation to FPATs (r = -0.31 to -0.66; R = 0.10 to 0.44 and r = -0.27 to -0.61; R = 0.07 to 0.37; p < 0.05, respectively). Two studies suggested that AF has a weak-to-moderate relationship with FPATs (r = 0.38 and r = -0.62). Two studies showed that anaerobic capacity had weak-to-strong correlations with FPATs (r = -0.40 and r = 0.79; R = 0.16 to 0.62; p < 0.05). No studies found a statistically significant correlation between lower-body strength and FPAT performance. Further research is needed to better understand the role of field-based fitness test results on FPAT performance. An annual department-driven multicomponent fitness assessment measuring UBs, UBe, anaerobic capacity, and AF is recommended based on the evidence reviewed.
Neural Learning-Based Fixed-Time Consensus Tracking Control for Nonlinear Multiagent Systems With Directed Communication Networks

This article investigates the problem of fixed-time consensus tracking for nonlinear multiagent systems. Different from the existing studies where the follower systems are linear or pure integrator-type systems, in this article, the follower systems have completely unknown nonlinear functions and time-varying disturbances. Within this framework, a fixed-time observer-based distributed control strategy is proposed to realize the consensus tracking. First, a distributed fixed-time observer is designed for each follower to estimate the leader’s state under directed networks. Then, based on the estimate, a fixed-time tracking control protocol is developed where novel approximation and estimation schemes are designed to tackle the nonlinear functions and disturbances. Furthermore, under the proposed control strategy, it is proved that the tracking errors converge into a small set near zero with a fixed-time convergence rate. Finally, the validity of the proposed method is verified by the simulation results.
Lung function in men with and without HIV: a nested cohort substudy.

OBJECTIVES Initial studies suggest HIV-positive persons may be at increased risk for chronic lung diseases such as chronic obstructive pulmonary disease, but have commonly relied on single-center designs, lacked HIV-negative controls, or assessed lung function with only spirometry. We tested differences in spirometry and single-breath diffusing capacity for carbon monoxide (DLCO) in persons with and without HIV. DESIGN Cross-sectional, observational study. METHODS Participants were enrolled from the Multicenter AIDS Cohort Study, a longitudinal cohort study of MSM (both HIV-positive and HIV-negative) at four sites in the United States. Standardized spirometry and DLCO testing were performed in all eligible, consenting participants at routine study visits. We tested associations between HIV status and spirometry and DLCO results, using linear and logistic regression. RESULTS Among 1067 men, median age was 57 years, prevalence of current marijuana (30%), and cigarette (24%) use was high, and another 45% were former cigarette smokers. Median forced expiratory volume in 1 s was 97% of predicted normal and DLCO was 85% of predicted normal. HIV-positive persons demonstrated no statistical difference in forced expiratory volume in 1 s compared with HIV-negative persons, but had worse DLCO (adjusted difference -2.6% of predicted; 95% confidence interval: -4.7 to -0.6%) and a higher risk of DLCO impairment (odds ratio for DLCO < 60% of predicted 2.97; 95% confidence interval: 1.36-6.47). Lower DLCO was associated with lower nadir CD4 cell counts. CONCLUSION HIV-positive men are at increased risk of abnormal gas exchange, indicated by low DLCO, compared with men without HIV.
Running Demands of Provincial Women's Rugby Union Matches in New Zealand

Abstract Busbridge, AR, Hamlin, MJ, Jowsey, JA, Vanner, MH, and Olsen, PD. Running demands of provincial women's rugby union matches in New Zealand. J Strength Cond Res 36(4): 1059–1063, 2022—There has been rapid growth in participation in women's rugby but there is minimal research on the sport. The aim of this study was to increase our knowledge of the running demands of high-level female players in the New Zealand Provincial Rugby Competition. Players (n = 20) wore 10-Hz Global Positioning System units during 7 matches to measure total distance covered, all running distance (≥6.4 km·h−1), high-intensity (HI) running (≥16.1 km·h−1), meters per minute (m·min−1), and maximum speed (km·h−1). Mean ± SD were calculated for forwards and backs. Forwards and backs covered a similar total distance (5,616 ± 809 m and 5,852 ± 1,022 m, respectively) and running distance (3,181 ± 583 m and 3,095 ± 805 m, respectively). However, when separated into specific playing positions, the half back recorded significantly higher running distances (4,292 ± 171 m), greater HI running distances (1,003 ± 58 m), and more distance overall (6,812 ± 277 m) than other positions (p ≤ 0.05). By contrast, outside backs did less running (2,456 ± 114 m) than other positions (p ≤ 0.05), and had the lowest distance for HI running (528 ± 39 m) in the backs. Running demands were similar for forwards and backs; however, within positions there was considerable variation, and the lower running measurements for outside backs maybe unique to women's rugby. Due to these findings and possible different tactical approaches, the development of training and speed zone bands specific to female players is advised because male research findings may lack transferability to women's rugby.
Asbestos Air Pollution: Description of a Mesothelioma Cluster Due to Residential Exposure from an Asbestos Cement Factory

The study describes a cluster of 71 malignant mesothelioma cases among Bari residents without asbestos exposure other than residential exposure. This small cohort, as expected, was composed of a majority of females (56.34%) with a M/F ratio of 0.8, ages ≤ 65 years old (52.11%) and the epithelioid morphological type (78.87%). Sixty-four subjects (90.14%) lived between 10 m and 1000 m from the asbestos cement factory (Fibronit), and the latency length was longer than 55 years for 25 subjects (35.21%). The adjusted risk (adjusted OR) of observing the epithelial form of mesothelioma among subjects living at small distances from Fibronit was high (OR = 1.870 (0.353–9.905)) for people living 550–1000 m from the site and for those living less than 550 m from the site (OR = 1.470 (0.262–8.248)). Additionally, the subjects with a high length of exposure showed a relevant risk of epithelioid mesothelioma both for 21–40 years of exposure (OR = 2.027 (0.521–7.890)) and more than 40 years of exposure (OR = 2.879 (0.651–12.736)). All of the estimates were high but not significant because this transitional study has a typically low power. The adjustment for latency showed the same trend. Using detailed information collected by the regional mesothelioma registry, this study provided evidence of a continuing health impact of the Fibronit asbestos cement factory in Bari on the resident population.
Multi‐arterial and total‐arterial coronary revascularization: Past, present, and future perspective

Although abundant biological, clinical, and scientific evidence exists on the superiority of multi‐arterial (MAR) and total‐arterial revascularization (TAR) over the conventional strategy with a single internal thoracic artery, only 10% of patients undergoing coronary artery bypass grafting (CABG) in the United States receives a second arterial conduit, and only 5% of patients receives TAR.
Visible Light as an Antimicrobial Strategy for Inactivation of Pseudomonas fluorescens and Staphylococcus epidermidis Biofilms

The increase of antimicrobial resistance is challenging the scientific community to find solutions to eradicate bacteria, specifically biofilms. Light-Emitting Diodes (LED) represent an alternative way to tackle this problem in the presence of endogenous or exogenous photosensitizers. This work adds to a growing body of research on photodynamic inactivation using visible light against biofilms. Violet (400 nm), blue (420 nm), green (570 nm), yellow (584 nm) and red (698 nm) LEDs were used against Pseudomonas fluorescens and Staphylococcus epidermidis. Biofilms, grown on a polystyrene surface, were irradiated for 4 h. Different irradiance levels were investigated (2.5%, 25%, 50% and 100% of the maximum irradiance). Surviving cells were quantified and the inactivation kinetic parameters were estimated. Violet light could successfully inactivate P. fluorescens and S. epidermidis (up to 6.80 and 3.69 log10 reduction, respectively), while blue light was effective only against P. fluorescens (100% of maximum irradiance). Green, yellow and red irradiation neither increased nor reduced the biofilm cell density. This is the first research to test five different wavelengths (each with three intensities) in the visible spectrum against Gram-positive and Gram-negative biofilms. It provides a detailed study of the potential of visible light against biofilms of a different Gram-nature.
Seroprevalence of Crimean‐Congo haemorrhagic fever among three selected risk human groups in disease‐endemic region of Pakistan

The occurrence of Crimean‐Congo haemorrhagic fever (CCHF) in humans is linked with animals living in close vicinity, and information on the incidence of CCHF at the human–animal interface is scarce. Therefore, the current study was designed to identify the high‐risk groups of individuals linked with animals in the Chakwal district of Pakistan having a history of CCHF cases in humans. In subject matter, coupled with risk factor analysis, we performed a sero‐based CCHF surveillance in three selected risk groups of humans including abattoir workers (n = 137), milkmen (n = 169) and animal handlers (n = 147). Sera samples and questionnaire‐based data were collected from each of the participants and screened for anti‐CCHFV IgG antibodies using enzyme‐linked immunosorbent assay. The highest seroprevalence was observed in animal handlers (n = 14, 9.52%, 95% CI: 4.68–13.99) followed by abattoir workers (n = 9, 6.57%, 95% CI: 2.42–10.72) and milkmen (n = 3, 1.78%, 95% CI: 0.24–4.24). The risk of seropositivity was significantly associated with humans linked with tick‐infested animals (OR: 11.0, 95% CI: 1.5–83.0, p = .002), old age >40 years (OR: 6.6, 95% CI: 2.7–16.0, p < .0001), illiteracy (OR: 4.3, 95% CI: 1.5–13.0, p = .004) and humans without knowledge about CCHF (OR: 7.6, 95% CI: 1.8–33.0, p = .0009). The findings of the current study highlighted the seroprevalence of CCHF in high‐risk groups of humans living in a disease‐endemic area of Pakistan and highlight the need for well‐integrated disease surveillance in the future to better comprehend disease control interventions.