Miracle-dz/UniFAR-FTUs huggingface dataset:
RAC1 controls progressive movement and competitiveness of mammalian spermatozoa

Mammalian spermatozoa employ calcium (Ca2+) and cyclic adenosine monophosphate (cAMP) signaling in generating flagellar beat. However, how sperm direct their movement towards the egg cells has remained elusive. Here we show that the Rho small G protein RAC1 plays an important role in controlling progressive motility, in particular average path velocity and linearity. Upon RAC1 inhibition of wild type sperm with the drug NSC23766, progressive movement is impaired. Moreover, sperm from mice homozygous for the genetically variant t-haplotype region (tw5/tw32), which are sterile, show strongly enhanced RAC1 activity in comparison to wild type (+/+) controls, and quickly become immotile in vitro. Sperm from heterozygous (t/+) males, on the other hand, display intermediate RAC1 activity, impaired progressive motility and transmission ratio distortion (TRD) in favor of t-sperm. We show that t/+-derived sperm consist of two subpopulations, highly progressive and less progressive. The majority of highly progressive sperm carry the t-haplotype, while most less progressive sperm contain the wild type (+) chromosome. Dosage-controlled RAC1 inhibition in t/+ sperm by NSC23766 rescues progressive movement of (+)-sperm in vitro, directly demonstrating that impairment of progressive motility in the latter is caused by enhanced RAC1 activity. The combined data show that RAC1 plays a pivotal role in controlling progressive motility in sperm, and that inappropriate, enhanced or reduced RAC1 activity interferes with sperm progressive movement. Differential RAC1 activity within a sperm population impairs the competitiveness of sperm cells expressing suboptimal RAC1 activity and thus their fertilization success, as demonstrated by t/+-derived sperm. In conjunction with t-haplotype triggered TRD, we propose that Rho GTPase signaling is essential for directing sperm towards the egg cells.
Autophagy‐inducing peptide increases CHO cell monoclonal antibody production in batch and fed‐batch cultures

The development of generic biopharmaceuticals is increasing the pressures for enhanced bioprocess productivity and yields. Autophagy (“self‐eating”) is a cellular process that allows cells to mitigate stresses such as nutrient deprivation. Reputed autophagy inhibitors have also been shown to increase autophagic flux under certain conditions, and enhance recombinant protein productivity in Chinese Hamster Ovary (CHO) cultures. Since peptides are commonly added to bioprocess culture media in hydrolysates, we evaluated the impact on productivity of an autophagy‐inducing peptide (AIP), derived from the cellular autophagy protein Beclin 1. This was analyzed in CHO cell batch and fed‐batch serum‐free cultures producing a human Immunoglobulin G1 (IgG1). Interestingly, the addition of 1–4 µM AIP enhanced productivity in a concentration‐dependent manner. Cell‐specific productivity increased up to 1.8‐fold in batch cultures, while in fed‐batch cultures a maximum twofold increase in IgG concentration was observed. An initial drop in cell viability also occurred before cultures recovered normal growth. Overall, these findings strongly support the value of investigating the effects of autophagy pathway modulation, and in particular, the use of this AIP medium additive to increase CHO cell biotherapeutic protein production and yields.
SARS-CoV-2 Seropositivity among Dental Staff and the Role of Aspirating Systems

Introduction: Health care workers (HCWs) are at a high risk of infection owing to occupational exposure to patients and virus-contaminated surfaces. Objectives: The study was aimed to reveal and compare the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patient-facing HCWs across 3 dental clinics equipped with different types of aspirating systems. Methods: This retrospective cohort study included 157 HCWs (43.58 ± 1.66 y) from 3 dental clinics in Ekaterinburg (Russian Federation) who reported to work during the coronavirus disease pandemic. All HCWs underwent serological testing once a week to detect immunoglobulin G and M antibodies against the SARS-CoV-2. The V6000 aspirating system with a vacuum controller (dry or semidry mode) and high-efficiency particulate air (HEPA) filters was used at clinics A and B, and the aspirated aerosol and air were evacuated and dissipated into the atmosphere. The VS900 aspirating vacuum pump without HEPA filters was used at clinic C. The aspirated aerosol and air were evacuated and dissipated into the operatories. All dental clinics followed the same recommendations for dental patient management and types of personal protective equipment used. Results: The estimated prevalence of SARS-CoV-2 infection was 11.5% (19 HCWs) over a 5-mo follow-up (May to August 2020). The prevalence of infection was unaffected by sex or the role of the member in the dental team (dentist/dental assistant). The prevalence of SARS-CoV-2 infection (+) was significantly higher at clinic C (equipped with an aspirating vacuum pump without HEPA filters) than at other clinics. Conclusion: The type of aspirating system used and the presence of HEPA filters could affect the prevalence of SARS-CoV-2 infection across dental clinics. Therefore, we recommend the use of aspirating systems installed with HEPA filters, which evacuate and dissipate aerosols into specialized areas. Knowledge Transfer Statement: This report confirms that dentists, being patient-facing HCWs, are at a high risk of acquiring the SARS-CoV-2 infection and identifies gaps in the protection of patients and staff in dental settings.
Chemical Reaction and Ion Bombardment Effects of Plasma Radicals on Optoelectrical Properties of SnO2 Thin Films via Atomic Layer Deposition

In this study, the effect of radical intensity on the deposition mechanism, optical, and electrical properties of tin oxide (SnO2) thin films is investigated. The SnO2 thin films are prepared by plasma-enhanced atomic layer deposition with different plasma power from 1000 to 3000 W. The experimental results show that plasma contains different amount of argon radicals (Ar*) and oxygen radicals (O*) with the increased power. The three deposition mechanisms are indicated by the variation of Ar* and O* intensities evidenced by optical emission spectroscopy. The adequate intensities of Ar* and O* are obtained by the power of 1500 W, inducing the highest oxygen vacancies (OV) ratio, the narrowest band gap, and the densest film structure. The refractive index and optical loss increase with the plasma power, possibly owing to the increased film density. According to the Hall effect measurement results, the improved plasma power from 1000 to 1500 W enhances the carrier concentration due to the enlargement of OV ratio, while the plasma powers higher than 1500 W further cause the removal of OV and the significant bombardment from Ar*, leading to the increase of resistivity.
Prevalence of SARS-CoV-2 Antibodies in Children and Adults with Type 1 Diabetes.

OBJECTIVE As diabetes is a risk factor for severe symptoms, hospitalization, and death with COVID-19 disease, we aimed to assess the prevalence of SARS-CoV-2 antibodies in children and adults people with and without type 1 diabetes in Colorado during 2020. RESEARCH DESIGN AND METHODS We developed a highly sensitive and specific test for antibodies against SARS-CoV-2 and measured the antibodies in people children and adults with new-onset (n=129) and established type 1 diabetes (n=94) seen for routine diabetes care at our Center between January and October, 2020. The antibodies were also measured in 562 children and 102 adults from the general population of Colorado. RESULTS The prevalence of SARS-CoV-2 antibodies in persons with new-onset type 1 diabetes (0.8%; 95% CI 0.1-4.2%) or those with established disease (4.3%; 1.7-10.4%) did not differ from that in the general population children (2.8%; 1.8-4.6%) or adults (3.9%; 1.5-9.7%). In a subset of individuals with positive antibodies (n=31), antibodies remained positive for up to 9 months, although the levels decreased starting 3 months after the infection (p=0.007). CONCLUSIONS From January to October 2020, the prevalence of SARS-CoV-2 antibodies were not different in persons children and adults with and without type 1 diabetes in Colorado. We found no evidence for increased prevalence of COVID-19 infections among youth with newly diagnosed type 1 diabetes.
Bleeding Risk of Direct Oral Anticoagulants in Patients With Heart Failure And Atrial Fibrillation.

BACKGROUND Patients with heart failure and atrial fibrillation are an important atrial fibrillation subgroup in which direct oral anticoagulants (DOACs) have not been adequately studied in real-world settings. Since DOACs rely on renal elimination and renal dysfunction is prevalent in patients with heart failure, their use may increase bleeding risk, negating some of their advantage over warfarin. METHODS We conducted a retrospective cohort study using linked Veterans Administration databases of patients with heart failure newly started on warfarin or DOACs for atrial fibrillation from October 2010 to August 2017 (23 635 warfarin, 25 823 DOAC). Outcomes included time to first bleeding, stroke, and death using Cox proportional hazards models with inverse probability of treatment weighting. RESULTS Total bleeding (hazard ratio, 0.62 [95% CI, 0.56-0.68]), major bleeding (hazard ratio, 0.49 [95% CI, 0.40-0.61]), and death (hazard ratio, 0.74 [95% CI, 0.71-0.78]) were lower with DOAC than warfarin, and with apixaban and dabigatran, but not rivaroxaban. Moderate/severe chronic kidney disease was common (48.7%); moderate chronic kidney disease was associated with increased bleeding with DOACs but not warfarin. However, death and bleeding remained lower with DOACs than warfarin across all renal function levels and clinical subgroups. A >20% transient/persistent decline in renal function occurred in 53% of DOAC-treated patients at some point during follow-up, would have required dose reduction in 10.5% of patients, and was associated with increased bleeding. Dose adjustments were made more often, and bleeding and death were lower in patients seen by pharmacists or anticoagulation clinics. There were significant between-site variations in DOAC dosing. CONCLUSIONS DOACs overall, apixaban and dabigatran, but not rivaroxaban, were associated with less total bleeding and death than warfarin in patients with heart failure and atrial fibrillation at all levels of renal function. Renal function decline resulted in increased bleeding in patients with DOACs. DOAC dose adjustment was often indicated, associated with increased bleeding when not adjusted, emphasizing the need for closer monitoring in these patients.
Topical and Systemic Formulation Options for Cutaneous T Cell Lymphomas

Although various anti-cutaneous T-cell lymphoma (CTCL) therapies are available for clinical use, appropriate chemotherapy lines for the treatment of CTCLs have yet to be established. Therefore, to date, various clinical trials for the treatment of advanced CTCLs are ongoing. In this review, we evaluate the therapeutic options that are available in clinical practice for treatment of early- and advanced-stage CTCLs (targeted therapies, histone deacetylase (HDAC) inhibitors, retinoids, interferons, cytotoxic drugs, etc.). We also examine clinical trials of novel regimens for the treatment of CTCLs.
Increased Expression of AKT3 in Neuroendocrine Differentiated Prostate Cancer Cells Alters the Response Towards Anti-Androgen Treatment

Simple Summary Metastatic castration-resistant prostate cancer is still untreatable, and patients have a very short life expectancy after diagnosis. One factor that makes metastatic castration-resistant prostate cancer so aggressive and difficult to treat is neuroendocrine differentiation of prostate carcinoma cells. We already showed that neuroendocrine differentiation of LNCaP cells results in increased AKT3 expression. The aim of this study was to demonstrate the role of AKT3 in neuroendocrine differentiation. Therefore, the previously obtained in vitro data were validated and extended to tissue from patient with neuroendocrine prostate cancer, where we show the presence of AKT3 in neuroendocrine cells. Furthermore, we demonstrate the oncogenic consequences of an increased AKT3 expression including inactivation of apoptotic proteins and a potential role of some miR-17 family members, negatively regulating AKT3, in neuroendocrine differentiation. Abstract Patients with advanced prostate carcinoma are often treated with an androgen deprivation therapy but long-term treatment can result in a metastatic castration-resistant prostate cancer. This is a more aggressive, untreatable tumor recurrence often containing areas of neuroendocrine differentiated prostate cancer cells. Using an in vitro model of NE-like cancer cells, it could previously be shown that neuroendocrine differentiation of LNCaP cells leads to a strong deregulation of mRNA and miRNA expression. We observe elevated RNA and protein levels of AKT Serine/Threonine Kinase 3 (AKT3) in neuroendocrine-like LNCaP cells. We used prostate resections from patients with neuroendocrine prostate cancer to validate these results and detect a co-localization of neuroendocrine marker genes with AKT3. Analysis of downstream target genes FOXO3A and GSK3 strengthens the assumption AKT3 may play a role in neuroendocrine differentiation. Overexpression of AKT3 shows an increased survival rate of LNCaP cells after apoptosis induction, which in turn reflects the significance in vivo or for treatment. Furthermore, miR-17, −20b and −106b, which are decreased in neuroendocrine-like LNCaP cells, negatively regulate AKT3 biosynthesis. Our findings demonstrate AKT3 as a potential therapeutic target and diagnostic tool in advanced neuroendocrine prostate cancer and a new mRNA–miRNA interaction with a potential role in neuroendocrine differentiation of prostate cancer.
Tai Chi practitioners have lower fall risks under dual-task conditions during stair descending

Stairs are among the most hazardous locations, and stair descending contributes to a high risk of falls among the elderly under dual-task (DT) conditions. The purpose of this study was to determine whether the practitioners of Tai Chi (TC), one type of mind-body exercise, have lower fall risks under DT conditions during stair descending, compared with their no-exercise (NE) counterparts. Fifteen TC practitioners with at least 10 years of experience in TC and fifteen NE participants were recruited in this study. They were asked to descend a six-step staircase under single-task (ST) and DT conditions. An eight-camera motion analysis system and two force plates were used for data collection. Results showed group by DT interactions in walking velocity (p = 0.016) and center of mass–center of pressure inclination angle (COM–COP IA) in the anteroposterior directions (p = 0.026). Group effects observed with foot clearance (p = 0.031), trunk (p = 0.041) and head (p = 0.002) tilt angles, and COM–COP IA in the mediolateral (p = 0.006) directions. Significant DT effects only detected in foot clearance (p = 0.004). Although both groups of participants adopted a more cautious gait strategy under the dual-task condition, the TC practitioners were less influenced by the DT paradigm than their NE counterparts. Our observations indicated that TC practitioners have lower fall risks under DT conditions during stair descending.
Hypersensitivity reactions to multiple anti-tuberculosis drugs

Objective This study aimed to evaluate hypersensitivity reactions to anti-tuberculosis (TB) drugs. Methods We retrospectively compared the clinical manifestations and treatment outcomes of single and multiple drug hypersensitivity reactions (DHRs). Results Twenty-eight patients were diagnosed with anti-TB DHRs using oral drug provocation tests. Of these 28 patients, 17 patients (60.7%) had DHRs to a single drug and 11 (39.3%) had multiple DHRs. The median age of patients was 57.5 years (interquartile range [IQR], 39.2–73.2). Of the total patients, 18 patients (64.3%) were men. The median number of anti-TB drugs causing multiple DHRs was 2.0 (IQR 2.0–3.0). Rifampin was the most common drug that caused DHRs in both the single and multiple DHR groups (n = 8 [47.1%] and n = 9 [52.9%], respectively). The treatment success rate was lower in the multiple DHR group than in the single DHR group; however, the difference was not statistically significant (81.8% vs. 94.1%; P = 0.543). Conclusions Multiple anti-TB DHRs were common in all patients who experienced DHRs, and rifampin was the most common causative drug. The treatment outcomes appeared to be poorer in patients with multiple DHRs than in those with single DHRs.
Suicidal ideation in older Ghanaian women: The roles of bodily pain, functional limitation, and chronic health conditions

Background: Although approximately 79% of the world’s suicides occur in low- and middle-income countries (LMICs), the limited research in these regions has primarily focused on the rates of suicide attempts (SA) and ideation among men and younger members of the population. Aim: This study investigated the associations between bodily pain, functional limitation, chronic health conditions, and suicidal ideation among older Ghanaian women with a positive screen for depression. Methods: Data was obtained from the World Health Organization’s Study on global AGEing and adult health (SAGE) Ghana Wave 1, a nationally representative sample. Based on the interpersonal theory of suicide, we used logistic regression analysis to investigate the associations between the variables. Results: Functional limitation, bodily pain, hopelessness, and hypertension were significantly associated with a higher risk of suicidal ideation after accounting for sociodemographic and other confounding factors. Conclusions: Early interventions designed to decrease hopelessness, hypertension, and functional limitations may lead to reduced suicide ideation among older Ghanaian women who screen positive for depression.
Effect of Straw Provision in Racks on Tail Lesions, Straw Availability, and Pen Hygiene in Finishing Pigs

Simple Summary Pigs spend the majority of their time exploring their surroundings. Unfulfilled exploratory behavior has been linked to tail biting in pigs, leading to decreased welfare and production. Straw provision enables exploratory behavior and reduces tail biting, but large amounts of straw may be difficult to incorporate into current production systems, causing e.g., poor hygiene. This study examined whether provision of straw in racks, rather than on the floor, can enable larger straw rations without compromising hygiene. The study was conducted on a commercial farm with 458 undocked pigs in 42 pens provided with straw in racks or on the floor. Available straw and manual cleaning requirement were assessed daily, and presence of tail lesions was assessed weekly. Compared with pigs in the floor treatment, pigs in the rack treatment had more lesions in the beginning of the production period, but fewer tail lesions at the end. This could be because pigs in the rack treatment initially did not consume straw from the rack, leading to low straw access early in the production period. Abstract Unfulfilled exploratory behavior in pigs has been linked to tail biting, which causes reduced performance and welfare. Provision of straw can reduce tail biting, but large straw rations can cause poor hygiene in pens. This study examined whether provision of straw in racks, rather than on the pen floor, can enable larger straw rations without compromising hygiene. The study was conducted on a commercial farm with 458 undocked pigs in 42 pens provided with straw in racks or on the floor. Available straw and manual cleaning requirement were assessed daily, and presence of tail lesions was assessed weekly. Both treatments had a low requirement for manual cleaning (Floor: 1.7%, Rack: 1.8%). Pigs in the rack treatment had a higher incidence of lesions early in the production period, which coincided with these pigs initially not consuming straw from the rack, leading to low straw access. Late in the production period, these pigs had learned how to use the rack and had a lower incidence of lesions than pigs in the floor treatment. Delayed use of the rack may have been linked to undeveloped spatial skills in the pigs, which needs further research.
Cutibacterium acnes as an Opportunistic Pathogen: An Update of Its Virulence-Associated Factors

Cutibacterium acnes is a member of the skin microbiota found predominantly in regions rich in sebaceous glands. It is involved in maintaining healthy skin and has long been considered a commensal bacterium. Its involvement in various infections has led to its emergence as an opportunist pathogen. Interactions between C. acnes and the human host, including the human skin microbiota, promote the selection of C. acnes strains capable of producing several virulence factors that increase inflammatory capability. This pathogenic property may be related to many infectious mechanisms, such as an ability to form biofilms and the expression of putative virulence factors capable of triggering host immune responses or enabling C. acnes to adapt to its environment. During the past decade, many studies have identified and characterized several putative virulence factors potentially involved in the pathogenicity of this bacterium. These virulence factors are involved in bacterial attachment to target cells, polysaccharide-based biofilm synthesis, molecular structures mediating inflammation, and the enzymatic degradation of host tissues. C. acnes, like other skin-associated bacteria, can colonize various ecological niches other than skin. It produces several proteins or glycoproteins that could be considered to be active virulence factors, enabling the bacterium to adapt to the lipophilic environment of the pilosebaceous unit of the skin, but also to the various organs it colonizes. In this review, we summarize current knowledge concerning characterized C. acnes virulence factors and their possible implication in the pathogenicity of C. acnes.
Injuries following accidents with electric scooters.

INTRODUCTION Since the introduction of electric scooter (e-scooter) rental services in Denmark in January 2019, injuries following accidents involving e-scooters have increased. Internationally, a few studies have been published examining patient and injury characteristics following accidents involving e-scooters. However, data are limited. The purpose of this study was to describe the injuries, treatment and hospital course following accidents involving e-scooters. METHODS Prospective collection of data on all persons involved in accidents related to e-scooters who were examined and treated at the Emergency Department of Bispebjerg and Frederiksberg, Denmark, during the period from 30 June 2019 to 30 September 2019. RESULTS A total of 49 patients, 37 (75.5%) male, 46 riders and three non-riders, with a median age of 26 years (range: 8-56 years) were admitted to the emergency department. Common injuries were head injuries (46.9%) and fractures (26.5%). Most patients (79.6%) were discharged to their home from the emergency department after treatment without further hospital follow-up. CONCLUSIONS The majority of persons involved in e-scooter accidents are young men. Our results revealed a high frequency of head injuries and fractures. Most patients were discharged to their home after treatment in the emergency department. FUNDING none. TRIAL REGISTRATION The study was approved as a quality control project by the Head of the Department of Emergency Medicine and the Head of the Hospital Administration.