Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential screen and treatment of vestibular dysfunction in an elderly patient: A case report

ABSTRACT Background/Purpose Concussion sequelae in the elderly is under recognized and negatively impacts quality of life. Labyrinthine concussion (LC) is an uncommon diagnosis, as is multiple canal (MC) benign paroxysmal positional vertigo (BPPV). This case report highlights physical therapist (PT) evaluation and treatment of an elderly male misdiagnosed with LC and successfully treated for MC BPPV. Case Description A 72 year old male presented to his PT 23 days after falling off a ladder, resulting in a mild traumatic brain injury (mTBI). Diagnosed with LC, he was referred to PT due to ongoing symptoms of “falling backwards,” poor gait, and diminished mobility. PT examination revealed an atypical BPPV. Thus, the patient was treated in two PT visits, which included canalith repositioning techniques and neuromuscular reeducation. Outcomes The PT diagnosis was MC BPPV, including the right lateral and left posterior semicircular canals. Initial positive findings of Head Impulse Test, Bow and Lean Test, Dix-Hallpike, and Roll Test were negative on the last visit. Patient-Specific Functional Scale improved from 0 to 9.9 (10 being no limitations). The patient progressed from minimum assistance to independence in bed mobility, transfers, gait, and previous activities. Discussion The patient’s presentation was atypical in signs and symptoms with a diagnosis of LC. PT examination and intervention successfully resolved the patient’s signs and symptoms within two visits. Further research is needed regarding identification and treatment of elderly individuals with head injuries, such as MC BPPV, as well as the efficacy of a PT seeing patients shortly after mTBI.
Associations of conscientiousness with cardiac troponin T and stress coping responses in a teacher cohort: the SABPA prospective cohort study.

BACKGROUND In a South African bi-ethnic cohort, defensive (DefS)/social support/avoidance coping strategies have been shown to influence cardiac troponin T (cTnT) levels through different stress signalling pathways. Personality traits (extraversion, neuroticism, conscientiousness, openness to experience, agreeableness) partially control stress coping responses and may affect prospective cardiac responses. Hence in this cohort, we aimed to examine relationships between personality traits and coping strategies, and to assess associations between cTnT changes over time, personality traits and coping strategies. METHODS A cohort of African and Caucasian male and female teachers (n = 359) participating in both phases of the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study, was prospectively followed for three years. Personality traits (Basic Traits Inventory) and coping (Coping Strategy Indicator) scores were determined. Fasting serum samples for cTnT determination were collected. Established hypertension-related cTnT cut-off points of 4.2 pg/ml (Africans) and 5.6 pg/ml (Caucasians) were applied. RESULTS Higher neuroticism and lower conscientiousness scores were found in the Africans than in the Caucasians (p < 0.05). Both traits correlated with all three coping strategies in Caucasians, but only with DefS and avoidance coping in Africans. Over a period of three years, cTnT levels decreased in both races. Compared to Africans, Caucasians showed a greater recovery from the ethnic-specific cTnT cut-off point over time. In the Africans with high DefS scores, cTnT level changes were inversely associated with conscientiousness (adjusted R2 = 0.14; β = -0.26). In Caucasians scoring high in avoidance coping, conscientiousness (odds ratio 0.84) and neuroticism (odds ratio 0.90) showed a lower likelihood of predicting the cTnT cut-off point. CONCLUSION In both races, conscientiousness may contribute to healthier stress coping responses and protect against cardiac ischaemia and risk of hypertension.
Pathways for avian influenza virus spread: GPS reveals wild waterfowl in commercial livestock facilities and connectivity with the natural wetland landscape

Abstract Zoonotic diseases are of considerable concern to the human population and viruses such as avian influenza (AIV) threaten food security, wildlife conservation and human health. Wild waterfowl and the natural wetlands they use are known AIV reservoirs, with birds capable of virus transmission to domestic poultry populations. While infection risk models have linked migration routes and AIV outbreaks, there is a limited understanding of wild waterfowl presence on commercial livestock facilities, and movement patterns linked to natural wetlands. We documented 11 wild waterfowl (three Anatidae species) in or near eight commercial livestock facilities in Washington and California with GPS telemetry data. Wild ducks used dairy and beef cattle feed lots and facility retention ponds during both day and night suggesting use for roosting and foraging. Two individuals (single locations) were observed inside poultry facility boundaries while using nearby wetlands. Ducks demonstrated high site fidelity, returning to the same areas of habitats (at livestock facilities and nearby wetlands), across months or years, showed strong connectivity with surrounding wetlands, and arrived from wetlands up to 1251 km away in the week prior. Telemetry data provides substantial advantages over observational data, allowing assessment of individual movement behaviour and wetland connectivity that has significant implications for outbreak management. Telemetry improves our understanding of risk factors for waterfowl–livestock virus transmission and helps identify factors associated with coincident space use at the wild waterfowl–domestic livestock interface. Our research suggests that even relatively small or isolated natural and artificial water or food sources in/near facilities increases the likelihood of attracting waterfowl, which has important consequences for managers attempting to minimize or prevent AIV outbreaks. Use and interpretation of telemetry data, especially in near‐real‐time, could provide key information for reducing virus transmission risk between waterfowl and livestock, improving protective barriers between wild and domestic species, and abating outbreaks.
Contamination Rates in Duodenoscopes Reprocessed Using Enhanced Surveillance and Reprocessing Techniques: A Systematic Review and Meta-Analysis

Background/Aims Multiple outbreaks of multidrug-resistant organisms have been reported worldwide due to contaminated duodenoscopes. In 2015, the United States Food and Drug Administration recommended the following supplemental enhanced surveillance and reprocessing techniques (ESRT) to improve duodenoscope disinfection: (1) microbiological culture, (2) ethylene oxide sterilization, (3) liquid chemical sterilant processing system, and (4) double high-level disinfection. A systematic review and meta-analysis was performed to assess the impact of ESRT on the contamination rates. Methods A thorough and systematic search was performed across several databases and conference proceedings from inception until January 2021, and all studies reporting the effectiveness of various ESRTs were identified. The pooled contamination rates of post-ESRT duodenoscopes were estimated using the random effects model. Results A total of seven studies using various ESRTs were incorporated in the analysis, which included a total of 9,084 post-ESRT duodenoscope cultures. The pooled contamination rate of the post-ESRT duodenoscope was 5% (95% confidence interval [CI]: 2.3%–10.8%, inconsistency index [I2]=97.97%). Pooled contamination rates for high-risk organisms were 0.8% (95% CI: 0.2%–2.7%, I2=94.96). Conclusions While ESRT may improve the disinfection process, a post-ESRT contamination rate of 5% is not negligible. Ongoing efforts to mitigate the rate of contamination by improving disinfection techniques and innovations in duodenoscope design to improve safety are warranted.
A Pilot Randomized Controlled Trial of Virtual Reality Distraction to Reduce Procedural Pain During Subcutaneous Port Access in Children and Adolescents With Cancer

Objectives: We aimed to determine the feasibility of virtual reality (VR) distraction for children with cancer undergoing subcutaneous port (SCP) access. We also aimed to estimate preliminary treatment effects of VR compared with an active distraction control (iPad). Materials and Methods: A single-site pilot randomized controlled trial comparing VR to iPad distraction was conducted. Eligible children and adolescents were aged 8 to 18 years undergoing treatment for cancer with upcoming SCP needle insertions. Intervention acceptability was evaluated by child, parent, and nurse self-report. Preliminary effectiveness outcomes included child-reported pain intensity, distress, and fear. Preliminary effectiveness was determined using logistic regression models with outcomes compared between groups using preprocedure scores as covariates. Results: Twenty participants (mean age 12 y) were randomized to each group. The most common diagnosis was acute lymphocytic leukemia (n=23, 58%). Most eligible children and adolescents (62%) participated, and 1 withdrew after randomization to the iPad group. Nurses, parents, and children reported the interventions in both groups to be acceptable, with the VR participants reporting significantly higher immersion in the distraction environment (P=0.0318). Although not statistically significant, more VR group participants indicated no pain (65% vs. 45%) and no distress (80% vs. 47%) during the procedure compared with the iPad group. Fear was similar across groups, with ~60% of the sample indicating no fear. Discussion: VR was feasible and acceptable to implement as an intervention during SCP access. Preliminary effectiveness results indicate that VR may reduce distress and distress compared with iPad distraction. These data will inform design of a future full-scale randomized controlled trial.
Cytogenetic risk classification maintains its prognostic significance in transplanted FLT3‐ITD mutated acute myeloid leukemia patients: On behalf of the acute leukemia working party/European society of blood and marrow transplantation

FMS‐like tyrosine kinase 3 internal tandem duplication (FLT3‐ITD) mutational status is a pivotal prognosticator in acute myeloid leukemia (AML) patients and significantly increases the risk of disease relapse. However, it remains unclear whether in FLT3‐ITD patients referred for allogeneic stem cell transplantation (allo‐SCT), baseline cytogenetics significantly impacts clinical outcome. Using the European Society of Blood and Marrow Transplantation registry, we performed a retrospective analysis of 1631 FLT3‐ITD AML patients who underwent allo‐SCT with the aim of determining the influence of cytogenetic risk category on patient outcomes. Median patient age was 49 years and median follow‐up duration was 36 months. Two‐year leukemia‐free survival (LFS) and incidence of relapse were 54% and 31.6%, respectively. Non‐relapse mortality was experienced by 14.4% with a 2‐year overall survival (OS) of 60.1%. On multivariate analysis, LFS was significantly lower in patients with intermediate and adverse risk cytogenetics compared with those with favorable risk cytogenetics, (hazard ratio [HR] = 1.48, 95% confidence interval [CI], 1.06–2.06; p = .02), and (HR = 01.65, 95% CI, 1.13–2.40; p = .009), respectively. OS was significantly lower in patients with adverse risk cytogenetics compared with patients with favorable risk cytogenetics (HR = 1.74, 95% CI, 1.16–2.61; p = .008) with a trend toward lower OS in patients with intermediate risk cytogenetics compared to those with favorable risk cytogenetics (HR = 1.43, 95% CI, 1.00–2.05; p = .052). In addition, adverse risk patients and intermediate risk patients experienced higher relapse rates compared with favorable risk patients (HR = 1.83, 95% CI, 1.13–2.94; p = .013 and HR = 1.82, 95% CI, 1.19–2.77; p = .005). Overall, cytogenetic studies aid in refinement of risk stratification in transplanted FLT3‐ITD AML patients.
Dexmedetomidine attenuates ischemia and reperfusion-induced cardiomyocyte injury through p53 and forkhead box O3a (FOXO3a)/p53-upregulated modulator of apoptosis (PUMA) signaling signaling

ABSTRACT Dexmedetomidine (DEX) has been reported to attenuate the ischemia and reperfusion (I/R) induced cardiomyocyte apoptosis. However, mechanisms underlying these protective effect remain to be fully elucidated. Cardiomyocyte apoptosis is associated with ischemic heart disease. Here we investigated the role of DEX in I/R -induced cardiomyocyte apoptosis. Mice and H9c2 cardiomyocyte cells were subjected to cardiomyocyte I/R injury and hypoxia/reoxygenation (H/R) injury, respectively. The roles and mechanisms of DEX on H9c2 cardiomyocyte cells and mice cardiomyocyte cells exposured to H/R or I/R injury were explored. The results showed that DEX attenuates H/R injury-induced H9c2 cell apoptosis and alleviated mitochondrial oxidative stress; it also reduced myocardial infarct size and protected the cardiac function following cardiomyocyte I/R injury. In addition, H/R and I/R injury increased p53 expression and forkhead box O3a (FOXO3a)/p53-upregulated modulator of apoptosis (PUMA) signaling in H9c2 cardiomyocyte cells and cardiomyocytes. Targeting p53 expression or FOXO3a/PUMA signaling inhibited cell apoptosis and protected against H/R injury in H9c2 cardiomyocyte cells and cardiomyocytes. Pretreatment with DEX reduced the H/R or I/R injury-induced activation of p53 expression and FOXO3a/PUMA signaling, and alleviated H/R or I/R injury-induced apoptosis and mitochondrial oxidative stress. Therefore, DEX could alleviate H/R- or I/R-induced cardiomyocytes injury by reducing cell apoptosis and blocking p53 expression and FOXO3a/PUMA signaling. Targeting p53 or/and FOXO3a/PUMA signaling could alleviate cardiomyocyte I/R injury.
Protein‐enabled detection of ibuprofen and sulfamethoxazole using solid‐state nanopores

Enabled by proteins, we present an all‐electrical method for rapid detection of small pharmaceuticals (ibuprofen and sulfamethoxazole [SMZ]) in aqueous media using silicon nitride pores. Specifically, we use carrier proteins, bovine serum albumin (BSA), and take advantage of their interactions with two small drug molecules to form BSA–drug complexes which can be detected by nm‐diameter pores, thereby confirming the presence of small pharmaceuticals. We demonstrate detection of ibuprofen and SMZ at concentrations down to 100 nM (∼21 μg/L) and 48.5 nM (12 μg/L), respectively. We observe changes in electrical signal characteristics (reflected in event durations, rates, current magnitudes, and estimated particle diameters) of BSA–drug complexes compared to BSA‐only, and differences between these two small pharmaceuticals, possibly paving a path toward developing selective sensors by identifying “electrical fingerprints” of these molecules in the future. These distinct electrical signals are likely a combined result of diffusion, electrophoretic and electroosmotic effects, interactions between the pore and particles, which depend on pore diameters, pH, and the resulting surface charges. The use of single‐molecule‐counting nanopores allows sensing of small pharmaceuticals, studies of protein conformational changes, and may aid in efforts to evaluate the impact of small drug molecules on aquatic and human life.
Spinal malformation − A biochemical analysis using congenital kyphosis rats

Spinal kyphosis involves the vertebrae curving excessively backward, beyond their physiological curvature. Although the normal structure of the spinal vertebrae is extremely important for maintaining posture, the normal function of the thoracic and abdominal organs, and cosmetics, our knowledge concerning the pathogenesis of this disease is lacking. Furthermore, the responsible gene has not yet been identified. In this short review, we summarize the current state of kyphosis research and introduce the molecular and cellular mechanisms associated with the pathogenesis of this disease, based on findings obtained using rats that develop kyphosis.
The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources

PURPOSE: Several groups and resources provide information that pertains to the validity of gene-disease relationships used in genomic medicine and research; however, universal standards and terminologies to define the evidence base for the role of a gene in disease, and a single harmonized resource were lacking. To tackle this issue, the Gene Curation Coalition (GenCC) was formed. METHODS: The GenCC drafted harmonized definitions for differing levels of gene-disease validity based on existing resources, and performed a modified Delphi survey with three rounds to narrow the list of terms. The GenCC also developed a unified database to display curated gene-disease validity assertions from its members. RESULTS: Based on 241 survey responses from the genetics community, a consensus term set was chosen for grading gene-disease validity and database submissions. As of December 2021, the database contains 15,241 gene-disease assertions on 4,569 unique genes from 12 submitters. When comparing submissions to the database from distinct sources, conflicts in assertions of gene-disease validity ranged from 5.3% to 13.4%. CONCLUSION: Terminology standardization, sharing of gene-disease validity classifications, and resolution of curation conflicts will facilitate collaborations across international curation efforts and in turn, improve consistency in genetic testing and variant interpretation.
Needle in a Whey-Stack: PhRACS as a Discovery Tool for Unknown Phage-Host Combinations

PhRACS aims to bridge the current divide between in silico genetic analyses (i.e., phageomic studies) and traditional culture-based methodology. Through the labeling of specific bacterial hosts with fluorescently tagged recombinant phage receptor binding proteins and the isolation of tagged cells using flow cytometry, PhRACS allows the full potential of phageomic data to be realized in the wet laboratory. ABSTRACT The field of metagenomics has rapidly expanded to become the go-to method for complex microbial community analyses. However, there is currently no straightforward route from metagenomics to traditional culture-based methods of strain isolation, particularly in (bacterio)phage biology, leading to an investigative bottleneck. Here, we describe a method that exploits specific phage receptor binding protein (RBP)-host cell surface receptor interaction enabling isolation of phage-host combinations from an environmental sample. The method was successfully applied to two complex sample types—a dairy-derived whey sample and an infant fecal sample, enabling retrieval of specific and culturable phage hosts. IMPORTANCE PhRACS aims to bridge the current divide between in silico genetic analyses (i.e., phageomic studies) and traditional culture-based methodology. Through the labeling of specific bacterial hosts with fluorescently tagged recombinant phage receptor binding proteins and the isolation of tagged cells using flow cytometry, PhRACS allows the full potential of phageomic data to be realized in the wet laboratory.
Development of a Spontaneous HPV16 E6/E7-Expressing Head and Neck Squamous Cell Carcinoma in HLA-A2 Transgenic Mice

Our data indicate that mutated HPV16 E6(R55K)(delK75) and mutated HPV16 E7(N53S) DNA abolishes the presentation of HPV16 E6 and E7 through murine MHC-I and results in their presentation through human HLA-A2 molecules. Additionally, the mutated HPV16 E6 and E7 remain oncogenic. ABSTRACT Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is a growing global health problem. HPV16 has been attributed to a majority of HPV-associated HNSCCs. In order to test candidate immunotherapies, we developed a spontaneous HPV16-driven HNSCC model in HLA-A2 (AAD) transgenic mice. We sought to eliminate the confounding effects of dominant HPV antigen presentation through murine major histocompatibility complex class I (MHC-I) via epitope mutagenesis (without compromising tumorigenicity). We generated HPV16 E6(R55K)(delK75) and E7(N53S) expression constructs with mutations in known dominant H-2Db epitopes and characterized their presentation through murine and human MHC-I molecules using in vitro and in vivo activation of HPV16 E6/E7 antigen-specific CD8+ T cells. In addition, we tested the ability of E6(R55K)(delK75) and E7(N53S) for oncogenicity. The mutated E7(N53S) abolished the presentation of murine H-2Db-restricted HPV16 E7 peptide (i.e., amino acids [aa] 49 to 57) cytotoxic T lymphocyte (CTL) epitope and resulted in HLA-A2-restricted presentation of the HPV16 E7 (aa 11 to 20)-specific CTL epitope. The mutated E6(R55K)(delK75) abolished the activation of murine MHC-I-restricted E6-specific CD8+ T cell-mediated immune responses in C57BL/6 mice. In addition, the vaccination led to the activation of human HLA-A2-restricted E6-specific CD8+ T cell-mediated immune responses in HLA-A2 (AAD) transgenic mice. Injection of DNA plasmids encoding LucE7(N53S)E6(R55K)(delK75), AKT, c-Myc, and SB100 followed by electroporation results in development of squamous cell carcinoma in the oral/pharyngeal cavity of all of the HLA-A2 (AAD) transgenic mice (5/5), with 2/5 tumor-bearing mice developing metastatic carcinoma in the neck lymph nodes. IMPORTANCE Our data indicate that mutated HPV16 E6(R55K)(delK75) and mutated HPV16 E7(N53S) DNA abolishes the presentation of HPV16 E6 and E7 through murine MHC-I and results in their presentation through human HLA-A2 molecules. Additionally, the mutated HPV16 E6 and E7 remain oncogenic. Our approach is potentially applicable to different human MHC-I transgenic mice for the identification of human MHC-I restricted HPV16 E6/E7-specific CTL epitopes as well as the generation of spontaneous HPV E6/E7-expressing oral/pharyngeal carcinoma.