Miracle-dz/UniFAR-FTUs huggingface dataset:
Preoperative optimization to prevent periprosthetic joint infection in at-risk patients

Periprosthetic joint infection (PJI) remains an important complication with devastating consequences after total joint arthroplasties. With the increasing number of arthroplasties worldwide, the number of PJI will increase correspondingly with a significant economic burden to our healthcare system. It is likely impossible to completely eradicate PJI; hence, assessment and optimization of its risk factors to preventing such a disastrous complication will be the key. There are many strategies to prevent PJI in the preoperative, intraoperative, or postoperative phases. The preoperative assessment provides a unique opportunity to screen and diagnose underlying comorbidities and optimize modifiable risk factors before elective surgeries. In this review, we will focus on current literature in preoperative assessment of various modifiable risk factors and share the experience and practical approach in our institution in preoperative optimization to reduce PJI in total joint arthroplasties.
Targeting HER3, a Catalytically Defective Receptor Tyrosine Kinase, Prevents Resistance of Lung Cancer to a Third-Generation EGFR Kinase Inhibitor

Although two growth factor receptors, EGFR and HER2, are amongst the best targets for cancer treatment, no agents targeting HER3, their kinase-defective family member, have so far been approved. Because emergence of resistance of lung tumors to EGFR kinase inhibitors (EGFRi) associates with compensatory up-regulation of HER3 and several secreted forms, we anticipated that blocking HER3 would prevent resistance. As demonstrated herein, a neutralizing anti-HER3 antibody we generated can clear HER3 from the cell surface, as well as reduce HER3 cleavage by ADAM10, a surface metalloproteinase. When combined with a kinase inhibitor and an anti-EGFR antibody, the antibody completely blocked patient-derived xenograft models that acquired resistance to EGFRi. We found that the underlying mechanism involves posttranslational downregulation of HER3, suppression of MET and AXL upregulation, as well as concomitant inhibition of AKT signaling and upregulation of BIM, which mediates apoptosis. Thus, although HER3 is nearly devoid of kinase activity, it can still serve as an effective drug target in the context of acquired resistance. Because this study simulated in animals the situation of patients who develop resistance to EGFRi and remain with no obvious treatment options, the observations presented herein may warrant clinical testing.
The Nutritional Status of Adult Antiretroviral Therapy Recipients with a Recent HIV Diagnosis; A Cross-Sectional Study in Primary Health Facilities in Gauteng, South Africa

The study determined the nutritional status of adult antiretroviral therapy (ART) recipients, and investigated the association between the duration on ART and the nutritional status. This study was based in primary health facilities in Gauteng, South Africa. The data collected included sociodemographic variables; the duration of the treatment; and the body mass index (BMI), classified as undernutrition (<18.5 kg/m2), normal (18.5–24.9 kg/m2), or overweight/obesity (≥25 kg/m2). ART recipients (n = 480) had a mean age of 35 (± 8.4SD) years. All had taken ART for six months or more (range 6–48 months). The data were analyzed using STATA 13.0. The overall prevalence of overweight/obesity was 39%, it was higher in females (46%) than in males (30%), 26% were overweight, and 13% were obese. Underweight was 13%, and was higher in males (18%) than females (9%). Being overweight was more likely in those aged ≥35 years and those in smaller households. Being obese was less likely in males, in the employed, and in those with a higher income, but was more likely in those with a longer duration on ART. Abdominal obesity was high, but less likely in males. Interventions to prevent overweight/obesity should be integrated into routine HIV care, while at the same time addressing the burden of undernutrition among ART recipients.
Association between response rates and monetary incentives in sample study: a systematic review and meta-analysis

Objective To investigate the effect of monetary incentive and the dose–response relationship of participants’ response rates in surveys. Methods Three databases were searched for randomised controlled trials (RCTs) that investigated the effect of monetary incentives on participants’ first and final response rates. First response is defined as the responses after the participant was initially contacted and final response is defined as the responses after several reminders were sent. The potential dose–response relationship of the amount of monetary incentive on the relative response rate (RRR) was established by fitting a restricted cubic spline function based on the robust-error meta-regression model. Results 105 RCTs were identified. The first RRR increased by 49% (RRR=1.49; 95% CI 1.29 to 1.72) when monetary incentives were provided. Dose–response analysis revealed that an amount between US$6.25 and US$8 had the maximum effect on increasing the first response rate. On average, the final RRR increased almost by 20% (RRR=1.18; 95% CI 1.11 to 1.25) with monetary incentive compared to no-monetary incentive. An amount between US$10 and US$15 had the maximum effect on the final response rate, with an increase in the final RRR of 34% (RRR=1.34; 95% CI 1.19 to 1.51). There was a significant increase in the response rate when two or more reminders were sent. Conclusion Monetary incentives and reminders improve the response rates. Future studies need to consider providing monetary incentives and sending at least two reminders to increase the response rate and reduce the chances of non-response bias.
Safety concerns reported by consumers, manufacturers and healthcare professionals: A detailed evaluation of opioid‐related adverse drug reactions in the FDA database over 15 years

To perform an in‐depth analysis of opioid‐related ADRs reported by consumers, manufacturers and healthcare professionals. Delving into the depth and breadth of reported opioid‐related adverse drug reactions (ADRs) provides an opportunity to strategize better clinical management and alleviate safety concerns. Retrospective pharmacovigilance disproportionality analysis for opioid‐related ADRs in the FDA Adverse Event Reporting System (FAERS) database was performed. Detailed analysis of patient (sex, age) and report (year of report; reporter: healthcare worker vs consumer) characteristics were conducted using reports from 2004 quarter 1 to 2018 quarter 4. Reporting odds ratios and confidence intervals (RORs,CI) were calculated. Of the 1 916 674 ADR reports, 300 985 indicated opioids as the primary medication. There was a surge in opioid‐related ADRs reported in 2018 with six times more reports compared to 2004 and twice the number of reports compared to 2017. The largest ROR among the 20 common ADRs was depression and suicide‐self‐injury (ROR 3.12, 95% CI 3.01‐3.22) for reports in age group ≥65 compared to age group 18 to 64, and lack of efficacy (ROR 6.80, 95% CI 6.61‐7.00) for males compared to females. ADRs with the largest RORs for consumers included lack of efficacy/effect (ROR 3.37, 95% CI 3.28‐3.46), administration site reactions (ROR 3.21, 95% CI 3.11‐3.32), depression and suicide self‐injury (ROR 2.26, 95% CI 2.14‐2.38) compared to healthcare professionals. Important aspects of opioid ADR voluntary reporting included suicidal ideation in elderly patients and lack of efficacy, especially in male patients. This examination provides insight to better manage safety concerns of opioids.
Are you sure? The relationship between response certainty and performance in visual detection using a perimetry-style task

Conventional psychophysical methods ignore the degree of confidence associated with each response. We compared the psychometric function for detection with that for “absolute certainty” in a perimetry-style task, to explore how knowledge of response certainty might aid the estimation of detection thresholds. Five healthy subjects performed a temporal 2-AFC detection task, indicating on each trial whether they were “absolutely certain. ” The method of constant stimuli was used to characterize the shape of the two psychometric functions. Four eccentricities spanning central and peripheral vision were tested. Where possible, conditions approximated those of the Humphrey Field Analyzer (spot size, duration, background luminance, test locations). Based on the empirical data, adaptive runs (ZEST) were simulated to predict the likely improvement in efficiency obtained by collecting certainty information. Compared to detection, threshold for certainty was 0.5 to 1.0 dB worse, and slope was indistinguishable across all eccentricities tested. A simple two-stage model explained the threshold difference; under this model, psychometric functions for detection and for certainty-given-detection are the same. Exploiting this equivalence is predicted to reduce the number of trials required to achieve a given level of accuracy by approximately 30% to 40%. The chances of detecting a spot and the chances of certainty-given-detection were approximately the same in young, healthy subjects. This means, for example, that a spot detected at threshold was labeled as “certainly” detected approximately half the time. The collection of certainty information could be used to improve the efficiency of estimation of detection thresholds.
The P Value Line Dance: When Does the Music Stop?

When should a trial stop? Such a seemingly innocent question evokes concerns of type I and II errors among those who believe that certainty can be the product of uncertainty and among researchers who have been told that they need to carefully calculate sample sizes, consider multiplicity, and not spend P values on interim analyses. However, the endeavor to dichotomize evidence into significant and nonsignificant has led to the basic driving force of science, namely uncertainty, to take a back seat. In this viewpoint we discuss that if testing the null hypothesis is the ultimate goal of science, then we need not worry about writing protocols, consider ethics, apply for funding, or run any experiments at all—all null hypotheses will be rejected at some point—everything has an effect. The job of science should be to unearth the uncertainties of the effects of treatments, not to test their difference from zero. We also show the fickleness of P values, how they may one day point to statistically significant results; and after a few more participants have been recruited, the once statistically significant effect suddenly disappears. We show plots which we hope would intuitively highlight that all assessments of evidence will fluctuate over time. Finally, we discuss the remedy in the form of Bayesian methods, where uncertainty leads; and which allows for continuous decision making to stop or continue recruitment, as new data from a trial is accumulated.
Assessment of type I interferons, clinical signs and virus shedding in broiler chickens with pre and post challenge Newcastle disease vaccination.

Background Newcastle disease (ND) causes devastating economic losses in poultry industry. Aims This study evaluates the plausible effect of prior or post challenge vaccination with a live commercial vaccine on some pathogenic aspects of velogenic Newcastle disease virus (vNDV) infection in broilers with an emphasis on elucidating type I interferons (IFNs) response trends. Methods Chicks (n=250) were randomly allocated into 5 equal groups including negative control (NC), positive control (PC) (challenged with vNDV), and treatment (T1-T3) groups: (T1) only received Villegas-Glisson/University of Georgia (VG/GA) strain of NDV vaccine, (T2) vaccinated 24 h prior to vNDV challenge, and (T3) vaccinated 24 h post vNDV challenge. Samples from trachea, cloacal content, and serum were collected at different time points to evaluate virus shedding or IFNs levels. Results Although clinical signs and lesions were not completely blocked by administration of vaccine prior to or post vNDV inoculation, the disease severity diminished as demonstrated by an increase in bird's survival rate and median survival days (MSDs). Moreover, prior to or post challenge VG/GA live vaccine administration, modified viral shedding patterns by decreasing the vNDV shedding period especially from the gastrointestinal (GI) system. Strong early type I IFNs response was observed in the trachea and sera of chickens vaccinated prior to or post-infection (pi) as compared to birds that received vaccine or vNDV alone. In trachea, IFN-α response was more pronounced than IFN-β, while both IFNs showed a considerable change in serum. Conclusion It seems that vaccination after challenge with vNDV can improve bird's health similar to prior administration and reduces virus shedding which may be due to type I IFNs production.
Progresses in Synthesis and Application of SiC Films: From CVD to ALD and from MEMS to NEMS

A search of the recent literature reveals that there is a continuous growth of scientific publications on the development of chemical vapor deposition (CVD) processes for silicon carbide (SiC) films and their promising applications in micro- and nanoelectromechanical systems (MEMS/NEMS) devices. In recent years, considerable effort has been devoted to deposit high-quality SiC films on large areas enabling the low-cost fabrication methods of MEMS/NEMS sensors. The relatively high temperatures involved in CVD SiC growth are a drawback and studies have been made to develop low-temperature CVD processes. In this respect, atomic layer deposition (ALD), a modified CVD process promising for nanotechnology fabrication techniques, has attracted attention due to the deposition of thin films at low temperatures and additional benefits, such as excellent uniformity, conformability, good reproducibility, large area, and batch capability. This review article focuses on the recent advances in the strategies for the CVD of SiC films, with a special emphasis on low-temperature processes, as well as ALD. In addition, we summarize the applications of CVD SiC films in MEMS/NEMS devices and prospects for advancement of the CVD SiC technology.
Spin cascade and doming in ferric hemes: Femtosecond X-ray absorption and X-ray emission studies

Significance The structure–function relationship in central to biology, while the structural dynamics are driven by electronic changes. Doming of ferrous heme proteins, which is central to the respiratory function of hemoglobin, ensues from populating high-spin states. However, for ferric heme proteins, doming was excluded. Here, we show that high-spin states are populated in photoexcited ferric cytochrome c, and we present evidence for doming. We also conclude that photo- or thermally activated doming occurs in a wide variety of ferric heme proteins, calling for a deeper understanding of its role in their respective functions. The structure–function relationship is at the heart of biology, and major protein deformations are correlated to specific functions. For ferrous heme proteins, doming is associated with the respiratory function in hemoglobin and myoglobins. Cytochrome c (Cyt c) has evolved to become an important electron-transfer protein in humans. In its ferrous form, it undergoes ligand release and doming upon photoexcitation, but its ferric form does not release the distal ligand, while the return to the ground state has been attributed to thermal relaxation. Here, by combining femtosecond Fe Kα and Kβ X-ray emission spectroscopy (XES) with Fe K-edge X-ray absorption near-edge structure (XANES), we demonstrate that the photocycle of ferric Cyt c is entirely due to a cascade among excited spin states of the iron ion, causing the ferric heme to undergo doming, which we identify. We also argue that this pattern is common to a wide diversity of ferric heme proteins, raising the question of the biological relevance of doming in such proteins.
Time Series Gene Expression Profiles Analysis Identified Several Potential Biomarkers for Sepsis.

Sepsis is a life-threatening disorder and leads to organ dysfunction and death. Therefore, searching for more alternative biomarkers is of great significance for sepsis assessment and surveillance. In our study, the gene expression profiles of 163 samples from healthy controls and septic patients were analyzed and 8 gene co-expression modules were identified by constructing weighted gene co-expression network. The blue and yellow modules showed close correlations with the phenotypic trait "days postsepsis. " Besides, differentially expressed genes (DEGs) over time in septic patients were screened using Short Time-series Expression Miner (STEM) program. The intersection of genes in the blue and yellow modules and DEGs, which were significantly enriched in "HTLV-1 infection" pathway, was analyzed with protein-protein interaction network. The logistic regression model based on these eight mRNAs was constructed to determine the type of the sample reliably. Eight vital genes CECR1, ANXA2, ELANE, CTSG, AZU1, PRTN3, LYZ, and DEFA4 presented high scores and may be associated with sepsis, which provided candidate biomarkers for sepsis.
Single-Task and Dual-Task Tandem Gait Performance Across Clinical Concussion Milestones in Collegiate Student-Athletes

Objective: To determine the length of time after concussion that impaired tandem gait performance is observed. Design: Clinical measurement, prospective longitudinal. Setting: NCAA collegiate athletic facility. Participants: Eighty-eight concussed NCAA Division I student-athletes and 30 healthy controls. Independent Variables: Group (concussion/control) and time (Baseline, Acute, Asymptomatic, and RTP). Main Outcome Measures: Participants completed 4 single-task and dual-task tandem gait trials. The concussion group completed tests at the following time points: preseason (Baseline), within 48 hours after concussion (Acute), on the day symptoms were no longer reported (Asymptomatic), and when cleared to return to sports (RTP). Controls completed the same protocol at similar intervals. The dual-task trials involved minimental style cognitive questions answered simultaneously during tandem gait. We analyzed the best time of the 4 trials, comparing groups with a linear mixed model. Results: Acutely after concussion, the concussion group performed single-task tandem gait slower (worse) than controls (concussion: 11.36 ± 2.43 seconds, controls: 9.07 ± 1.78 seconds, P < 0.001). The concussion group remained significantly slower than controls (9.95 ± 2.21 vs 8.89 ± 1.65 seconds, P = 0.03) at Asymptomatic day but not RTP. There were significant group (P < 0.001) and time (P < 0.001) effects for dual-task tandem gait. The groups were not significantly different at baseline for single-task (P = 0.95) or dual-task (P = 0.22) tandem gait. Conclusions: Our results indicate that tandem gait performance is significantly impaired acutely after concussion, compared with both preseason measures and controls. Postural control impairments were not present when the student-athletes were cleared for RTP. This information can assist clinicians when assessing postural control and determining recovery after a concussive injury.
Dengue Virus Degrades USP33–ATF3 Axis via Extracellular Vesicles to Activate Human Microglial Cells

Key Points DENV infection modulates EV cargo to influence neighboring and distant cells. miR-148a transferred via EVs suppresses USP33/ATF3 axis in human microglia. Dengue virus (DENV) infection disrupts host innate immune signaling at various checkpoints. Cellular levels and stability of intermediate signaling molecules are a crucial hijacking point for a successful viral pathogenesis. Stability and turnover of all the cellular proteins including intermediate signaling molecules are principally regulated by proteasomal degradation pathway. In this study, we show that how DENV infection and particularly DENV-NS1 can modulate the host extracellular vesicle (EV) cargo to manipulate the deubiquitination machinery of the human microglial cell (CHME3). We have performed EV harvesting, size analysis by nanoparticle tracking analysis, identification of cargo microRNA via quantitative PCR, microRNA target validation by overexpression, and knockdown via mimics and anti-miRs, immunoblotting, dual luciferase reporter assay, in vivo ubiquitination assay, chase assay, and promoter activity assay to reach the conclusion. In this study, we show that DENV-infected monocytes and DENV-NS1–transfected cells release high amounts of EVs loaded with miR-148a. These EVs get internalized by human microglial cells, and miR-148a suppresses the ubiquitin-specific peptidase 33 (USP33) protein expression levels via binding to its 3′ untranslated region. Reduced USP33 in turn decreases the stability of cellular ATF3 protein via deubiquitylation. ATF3 acts as a suppressor of major proinflammatory gene expression pathways of TNF-α, NF-κB, and IFN-β. Our mechanistic model explains how DENV uses the EV pathway to transfer miR-148a for modulating USP33 and downstream ATF3 levels in human microglial cells and contributes in neuroinflammation within the CNS.
Autophagy Augmentation to Alleviate Immune Response Dysfunction, and Resolve Respiratory and COVID-19 Exacerbations

The preservation of cellular homeostasis requires the synthesis of new proteins (proteostasis) and organelles, and the effective removal of misfolded or impaired proteins and cellular debris. This cellular homeostasis involves two key proteostasis mechanisms, the ubiquitin proteasome system and the autophagy–lysosome pathway. These catabolic pathways have been known to be involved in respiratory exacerbations and the pathogenesis of various lung diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and coronavirus disease-2019 (COVID-19). Briefly, proteostasis and autophagy processes are known to decline over time with age, cigarette or biomass smoke exposure, and/or influenced by underlying genetic factors, resulting in the accumulation of misfolded proteins and cellular debris, elevating apoptosis and cellular senescence, and initiating the pathogenesis of acute or chronic lung disease. Moreover, autophagic dysfunction results in an impaired microbial clearance, post-bacterial and/or viral infection(s) which contribute to the initiation of acute and recurrent respiratory exacerbations as well as the progression of chronic obstructive and restrictive lung diseases. In addition, the autophagic dysfunction-mediated cystic fibrosis transmembrane conductance regulator (CFTR) immune response impairment further exacerbates the lung disease. Recent studies demonstrate the therapeutic potential of novel autophagy augmentation strategies, in alleviating the pathogenesis of chronic obstructive or restrictive lung diseases and exacerbations such as those commonly seen in COPD, CF, ALI/ARDS and COVID-19.