Miracle-dz/UniFAR-FTUs huggingface dataset:
Lasting Effects of COVID-19 Pandemic on Prehospital Emergency Medical Service Missions

Purpose The COVID-19 pandemic confronted prehospital emergency medical services (PHEMS) with immense challenges. This study aimed to investigate the development of PHEMS mission numbers and times in the COVID-affected region of Southwest Saxony (SWS). Patients and Methods This was a retrospective analysis of PHEMS in SWS during lockdown periods and equal time spans in the previous and following years. Differences were tested for statistical significance using the chi-squared test and one-way analysis of variance (ANOVA). Results The total number of missions showed a substantial drop during the first (−16.6%) and the second (−4.5%) lockdown period compared with the previous year. Next-year periods showed a recovery that was nearly equivalent to the starting point. The first lockdown period was not associated with longer overall mission times. The minutes spent at the scene differed significantly between the first lockdown period (31.1 ± 3.52 min), previous year (28.4 ± 4.84 min), and follow-up period (31.8 ± 0.98 min). During the second lockdown, the overall mission times (71.6 ± 2.91 min), response times in minutes (8.9 ± 0.49 min), and minutes spent at the scene (31.4 ± 2.99 min) were significantly longer. The minutes spent at the scene (32.3 ± 18.68 min) and the overall mission time (69.6 ± 1.92 min) remained significantly longer during the control period. Conclusion Our data confirm the impact of the SARS-CoV-2 pandemic on German PHEMS. It can be concluded that nationwide lockdown measures led to lasting effects regarding a reduction in the total mission number, transport-on-site released-ratio, and emergency time intervals in the following year, without lockdown restrictions. The lasting effects on the transport-on-site released-ratio and emergency time intervals call for a re-evaluation of the delivery of emergency services during pandemics. These findings can inform future policy decisions and resource allocations to ensure optimal emergency medical services.
Cerebrovascular risk factors and their time-dependent effects on stroke survival in the EMMA cohort study

To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to <2.5 y). Worsening disability also impacted mortality in the period from ≥2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow-up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up.
Genetically determined thymic function affects strength and duration of immune response in COVID patients with pneumonia

Thymic activation improves the outcome of COVID-19 patients with severe pneumonia. The rs2204985 genetic polymorphism within the TCRA-TCRD locus, which affects thymic output in healthy individuals, was found here to modify SARS-CoV-2–specific immunity and disease severity in COVID-19 patients with severe pneumonia. Forty patients with severe COVID-19 pneumonia were investigated. The GG genotype at the rs2204985 locus was associated, independently of age and sex, with stronger and long-lasting anti–SARS-CoV-2 helper and cytotoxic T cell responses 6 months after recovery. The GG genotype was also associated with less severe lung involvement, higher thymic production, and higher counts of blood naïve T lymphocytes, including recent thymic emigrants, and a larger population of activated stem cell memory CD4+ T cells. Overall, GG patients developed a more robust and sustained immunity to SARS-CoV-2. Polymorphism at rs2204985 locus should be considered as an additional predictive marker of anti–SARS-CoV-2 immune response.
An antibody-based molecular switch for continuous small-molecule biosensing

We present a generalizable approach for designing biosensors that can continuously detect small-molecule biomarkers in real time and without sample preparation. This is achieved by converting existing antibodies into target-responsive “antibody-switches” that enable continuous optical biosensing. To engineer these switches, antibodies are linked to a molecular competitor through a DNA scaffold, such that competitive target binding induces scaffold switching and fluorescent signaling of changing target concentrations. As a demonstration, we designed antibody-switches that achieve rapid, sample preparation–free sensing of digoxigenin and cortisol in undiluted plasma. We showed that, by substituting the molecular competitor, we can further modulate the sensitivity of our cortisol switch to achieve detection at concentrations spanning 3.3 nanomolar to 3.3 millimolar. Last, we integrated this switch with a fiber optic sensor to achieve continuous sensing of cortisol in a buffer and blood with <5-min time resolution. We believe that this modular sensor design can enable continuous biosensor development for many biomarkers.
A Retrospective Review of 30-Day Hospital Readmission Risk After Open Heart Surgery in Patients With Atrial Fibrillation

Introduction Readmission rates after open heart surgery (OHS) remain an important clinical issue. The causes are varied, with identifying risk factors potentially providing valuable information to reduce healthcare costs and the rate of post-operative complications. This study aimed to characterize the reasons for 30-day hospital readmission rates of patients after open heart surgery. Methods All patients over 18 years of age undergoing OHS at a community hospital from January 2020 through December 2020 were identified. Demographic data, medical history, operative reports, post-operative complications, and telehealth interventions were obtained through chart review. Descriptive statistics and readmission rates were calculated, along with a logistic regression model, to understand the effects of medical history on readmission. Results A total of 357 OHS patients met the inclusion criteria for the study. Within the population, 8.68% of patients experienced readmission, 10.08% had an emergency department (ED) visit, and 95.80% had an outpatient office visit. A history of atrial fibrillation (AFib) significantly predicted 30-day hospital readmissions but not ED or outpatient office visits. Telehealth education was delivered to 66.11% of patients. Conclusion The study investigated factors associated with 30-day readmission following OHS. AFib patients were more likely to be readmitted than patients without atrial fibrillation. No other predictors of readmission, ED visits, or outpatient office visits were found. Patients reporting symptoms of tachycardia, pain, dyspnea, or "other" could be at increased risk for readmission.
Antioxidant and anti-inflammatory properties of ginsenoside Rg1 for hyperglycemia in type 2 diabetes mellitus: systematic reviews and meta-analyses of animal studies

Background: According to existing laboratory data, ginsenoside Rg1 may help cure diabetes and its complications by reducing oxidative stress (OS) and managing inflammation. However, this conclusion lacks reliability and is unclear. As a result, the purpose of this systematic review and meta-analysis was to evaluate the antioxidant and anti-inflammatory effects of ginsenoside Rg1 in the treatment of diabetes and its complications. Methods: We searched for relevant studies published through December 2022, including electronic bibliographic databases such as PubMed, EMBASE, Web of Science, CNKI, and Wanfang. The SYstematic Review Center for Laboratory Animal Experimentation Risk of Bias (SYRCLE RoB) tool was used to conduct a meta-analysis to assess the methodological quality of animal research. The meta-analysis was conducted using RevMan5.4 software, following the Cochrane Handbook for Systematic Reviews of Interventions. This study is registered in the International Systems Review Prospective Registry (PROSPERO) as CRD42023386830. Results: Eighteen eligible studies involving 401 animals were included. Ginsenoside Rg1 was significantly correlated with blood glucose (BG), insulin levels, body weight, superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels. In addition, according to subgroup analysis, the hypoglycemic, anti-inflammatory, and antioxidant effects of ginsenoside Rg1 in type 2 diabetic animals were not affected by experimental species, modeling, experimental drug dosage, or course of treatment. Conclusion: This meta-analysis presents a summary of the hypoglycemic effects of ginsenoside Rg1, which are achieved through anti-inflammatory and antioxidant mechanisms. These findings provide evidence-based support for the medical efficacy of ginsenoside Rg1. Specifically, ginsenoside Rg1 reduced MDA levels and restored SOD activity to exert its antioxidant activity. It had a positive effect on the reduction of IL-6 and TNF-α levels. However, the inclusion of studies with low methodological quality and the presence of publication bias may undermine the validity of the results. Further investigation with a more rigorous experimental design and comprehensive studies is necessary to fully understand the specific glycemic mechanisms of ginsenosides. Systematic Review Registration: https://www.crd. york.ac. uk/PROSPERO/, identifier https://CRD42023386830.
Diagnostic accuracy of a point‐of‐care urine tenofovir assay, and associations with HIV viraemia and drug resistance among people receiving dolutegravir and efavirenz‐based antiretroviral therapy

Novel point‐of‐care assays which measure urine tenofovir (TFV) concentrations may have a role in improving adherence monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). However, further studies of their diagnostic accuracy, and whether results are associated with viraemia and drug resistance, are needed to guide their use, particularly in the context of the global dolutegravir rollout.
Overview of approaches to estimate real-world disease progression in lung cancer

Abstract Background Randomized clinical trials of novel treatments for solid tumors normally measure disease progression using the Response Evaluation Criteria in Solid Tumors. However, novel, scalable approaches to estimate disease progression using real-world data are needed to advance cancer outcomes research. The purpose of this narrative review is to summarize examples from the existing literature on approaches to estimate real-world disease progression and their relative strengths and limitations, using lung cancer as a case study. Methods A narrative literature review was conducted in PubMed to identify articles that used approaches to estimate real-world disease progression in lung cancer patients. Data abstracted included data source, approach used to estimate real-world progression, and comparison to a selected gold standard (if applicable). Results A total of 40 articles were identified from 2008 to 2022. Five approaches to estimate real-world disease progression were identified including manual abstraction of medical records, natural language processing of clinical notes and/or radiology reports, treatment-based algorithms, changes in tumor volume, and delta radiomics–based approaches. The accuracy of these progression approaches were assessed using different methods, including correlations between real-world endpoints and overall survival for manual abstraction (Spearman rank ρ = 0.61-0.84) and area under the curve for natural language processing approaches (area under the curve = 0.86-0.96). Conclusions Real-world disease progression has been measured in several observational studies of lung cancer. However, comparing the accuracy of methods across studies is challenging, in part, because of the lack of a gold standard and the different methods used to evaluate accuracy. Concerted efforts are needed to define a gold standard and quality metrics for real-world data.
Lateralization and Time-Course of Cortical Phonological Representations during Syllable Production

Abstract Spoken language contains information at a broad range of timescales, from phonetic distinctions on the order of milliseconds to semantic contexts which shift over seconds to minutes. It is not well understood how the brain’s speech production systems combine features at these timescales into a coherent vocal output. We investigated the spatial and temporal representations in cerebral cortex of three phonological units with different durations: consonants, vowels, and syllables. Electrocorticography (ECoG) recordings were obtained from five participants while speaking single syllables. We developed a novel clustering and Kalman filter-based trend analysis procedure to sort electrodes into temporal response profiles. A linear discriminant classifier was used to determine how strongly each electrode’s response encoded phonological features. We found distinct time-courses of encoding phonological units depending on their duration: consonants were represented more during speech preparation, vowels were represented evenly throughout trials, and syllables during production. Locations of strongly speech-encoding electrodes (the top 30% of electrodes) likewise depended on phonological element duration, with consonant-encoding electrodes left-lateralized, vowel-encoding hemispherically balanced, and syllable-encoding right-lateralized. The lateralization of speech-encoding electrodes depended on onset time, with electrodes active before or after speech production favoring left hemisphere and those active during speech favoring the right. Single-electrode speech classification revealed cortical areas with preferential encoding of particular phonemic elements, including consonant encoding in the left precentral and postcentral gyri and syllable encoding in the right middle frontal gyrus. Our findings support neurolinguistic theories of left hemisphere specialization for processing short-timescale linguistic units and right hemisphere processing of longer-duration units.
A Dual-Band Electronic-Scanning Leaky-Wave Antenna Based on a Corrugated Microstrip Line

A dual-band fixed-frequency beam-scanning leaky-wave antenna (LWA) based on a corrugated microstrip line (CML) has been proposed. The proposed CML includes a series of uniform grooves that are alternately loaded by capacitors and varactors. The unit cell of the CML supports two kinds of modes in two different frequency bands. In each band, the dispersion characteristics of the CML can be electronically tuned by changing the capacitance loaded in the unit cell. Therefore, by simply changing the bias voltage of the loaded varactor diodes in the CML, the surface impedance of the LWA is dynamically reconfigured, and moreover, the radiation beams of the LWA are electronically steerable at a fixed frequency in each band. The experimental results show that at 4.25 and 5.75 GHz, the designed dual-band LWA can electronically steer the radiation beams in the maximum range of 80° and 22°, respectively, by changing the bias voltage from 0 to 10 V.
Mitochondrial DNA variation in Aedes aegypti (Diptera: Culicidae) mosquitoes from Jeddah, Saudi Arabia

Abstract Wolbachia (Hertig 1936) (Rickettsiales: Ehrlichiaceae) has emerged as a valuable biocontrol tool in the fight against dengue by suppressing the transmission of the virus through mosquitoes. Monitoring the dynamics of Wolbachia is crucial for evaluating the effectiveness of release programs. Mitochondrial (mtDNA) markers serve as important tools for molecular tracking of infected mitochondrial backgrounds over time but require an understanding of the variation in release sites. In this study, we investigated the mitochondrial lineages of Aedes aegypti (Linnaeus 1762) in Jeddah, Saudi Arabia, which is a prospective release site for the “wAlbBQ” Wolbachia-infected strain of this mosquito species. We employed a combination of comprehensive mitogenomic analysis (including all protein-coding genes) and mtDNA marker analysis (cox1 and nad5) using data collected from Jeddah. We combined our mitogenome and mtDNA marker data with those from previous studies to place mitochondrial variation in Saudi Arabia into a broader global context. Our findings revealed the presence of 4 subclades that can be broadly categorized into 2 major mitochondrial lineages. Ae. aegypti mosquitoes from Jeddah belonged to both major lineages. Whilst mitogenomic data offered a higher resolution for distinguishing Jeddah mosquitoes from the wAlbBQ strain, the combination of cox1 and nad5 mtDNA markers alone proved to be sufficient. This study provides the first important characterization of Ae. aegypti mitochondrial lineages in Saudi Arabia and offers essential baseline information for planning future molecular monitoring efforts during the release of Wolbachia-infected mosquitoes.
Seryl-tRNA synthetase promotes translational readthrough by mRNA binding and involvement of the selenocysteine incorporation machinery

Abstract Translational readthrough of UGA stop codons by selenocysteine-specific tRNA (tRNASec) enables the synthesis of selenoproteins. Seryl-tRNA synthetase (SerRS) charges tRNASec with serine, which is modified into selenocysteine and delivered to the ribosome by a designated elongation factor (eEFSec in eukaryotes). Here we found that components of the human selenocysteine incorporation machinery (SerRS, tRNASec, and eEFSec) also increased translational readthrough of non-selenocysteine genes, including VEGFA, to create C-terminally extended isoforms. SerRS recognizes target mRNAs through a stem-loop structure that resembles the variable loop of its cognate tRNAs. This function of SerRS depends on both its enzymatic activity and a vertebrate-specific domain. Through eCLIP-seq, we identified additional SerRS-interacting mRNAs as potential readthrough genes. Moreover, SerRS overexpression was sufficient to reverse premature termination caused by a pathogenic nonsense mutation. Our findings expand the repertoire of selenoprotein biosynthesis machinery and suggest an avenue for therapeutic targeting of nonsense mutations using endogenous factors.
Bi-directional nucleosome sliding by the Chd1 chromatin remodeler integrates intrinsic sequence-dependent and ATP-dependent nucleosome positioning

Abstract Chromatin remodelers use a helicase-type ATPase motor to shift DNA around the histone core. Although not directly reading out the DNA sequence, some chromatin remodelers exhibit a sequence-dependent bias in nucleosome positioning, which presumably reflects properties of the DNA duplex. Here, we show how nucleosome positioning by the Chd1 remodeler is influenced by local DNA perturbations throughout the nucleosome footprint. Using site-specific DNA cleavage coupled with next-generation sequencing, we show that nucleosomes shifted by Chd1 can preferentially localize DNA perturbations – poly(dA:dT) tracts, DNA mismatches, and single-nucleotide insertions – about a helical turn outside the Chd1 motor domain binding site, super helix location 2 (SHL2). This phenomenon occurs with both the Widom 601 positioning sequence and the natural +1 nucleosome sequence from the Saccharomyces cerevisiae SWH1 gene. Our modeling indicates that localization of DNA perturbations about a helical turn outward from SHL2 results from back-and-forth sliding due to remodeler action on both sides of the nucleosome. Our results also show that barrier effects from DNA perturbations can be extended by the strong phasing of nucleosome positioning sequences.
The arginine methyltransferase Prmt1 coordinates the germline arginine methylome essential for spermatogonial homeostasis and male fertility

Abstract Arginine methylation, catalyzed by the protein arginine methyltransferases (PRMTs), is a common post-translational protein modification (PTM) that is engaged in a plethora of biological events. However, little is known about how the methylarginine-directed signaling functions in germline development. In this study, we discover that Prmt1 is predominantly distributed in the nuclei of spermatogonia but weakly in the spermatocytes throughout mouse spermatogenesis. By exploiting a combination of three Cre-mediated Prmt1 knockout mouse lines, we unravel that Prmt1 is essential for spermatogonial establishment and maintenance, and that Prmt1-catalyzed asymmetric methylarginine coordinates inherent transcriptional homeostasis within spermatogonial cells. In conjunction with high-throughput CUT&Tag profiling and modified mini-bulk Smart-seq2 analyses, we unveil that the Prmt1-deposited H4R3me2a mark is permissively enriched at promoter and exon/intron regions, and sculpts a distinctive transcriptomic landscape as well as the alternative splicing pattern, in the mouse spermatogonia. Collectively, our study provides the genetic and mechanistic evidence that connects the Prmt1-deposited methylarginine signaling to the establishment and maintenance of a high-fidelity transcriptomic identity in orchestrating spermatogonial development in the mammalian germline.
Cardiorespiratory fitness in individuals with type 2 diabetes mellitus: a systematic review and meta-analysis

ABSTRACT Objective: To conduct a systematic review and meta-analysis assessing the cardiorespiratory fitness (CRF) among individuals with and without type 2 diabetes Materials and methods: The current review was registered in PROSPERO under the number CRD42018082718. MEDLINE, EMBASE, and Cochrane Library databases were searched from inception through February 2022. Eligibility criteria consisted of observational or interventional studies that evaluated CRF through cardiopulmonary exercise testing or six-minute walk test in individuals with type 2 diabetes compared with individuals without type 2 diabetes. For data extraction, we used baseline CRF assessments of randomized clinical trials or follow-up CRF assessments in observational studies. We performed a meta-analysis using maximal oxygen consumption (VO2max), and distance walked in the 6MWT as primary outcomes. They were extracted and expressed as mean differences (MDs) and 95% CIs between treatment and comparator groups. The meta-analysis was conducted using Review Manager (RevMan) software. Results: Out of 8,347 studies retrieved, 77 were included. Compared with individuals without type 2 diabetes, individuals with diabetes achieved a lower VO2max (−5.84 mL.kg−1.min−1, 95% CI −6.93, −4.76 mL.kg−1.min−1, p = <0.0001; I2 = 91%, p for heterogeneity < 0.0001), and a smaller distance walked in 6MWT (−93.30 meters, 95% CI −141.2, −45.4 meters, p > 0.0001; I2: 94%, p for heterogeneity < 0.0001). Conclusion: Type 2 diabetes was associated with lower cardiorespiratory fitness, as observed by lower VO2max on maximal tests, and smaller distance walked in 6MWT, however the quality of studies was low.