Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of occupational respiratory symptoms and associated factors among industry workers in Ethiopia: A systematic review and meta-analysis

Background Occupational respiratory diseases are major global public health problems, particularly for industry workers. Several studies have investigated occupational respiratory symptoms in various parts of Ethiopia. The findings have been inconsistent and inconclusive, and there is no nationally representative data on the subject. Therefore, this study aimed to estimate the pooled prevalence and factors associated with occupational respiratory symptoms among industry workers in Ethiopia (2010–2022). Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis framework Guidelines, search was conducted on several international databases including PubMed, CINAHL, African Journals Online, Hinari, Global Health, and Google scholar. The extracted data was analyzed using STATA 14. Random effect model was used to estimate the effect size. Egger regression test and I2 statistics were used to determine potential publication bias and heterogeneity, respectively among the reviewed articles. Results The meta-analysis included a total of 15 studies with 5,135 participants, revealing a pooled prevalence of 51.6% (95% CI: 43.6–59.6) for occupational respiratory symptoms among industry workers in Ethiopia. The absence of personal protective equipment (OR = 1.97, 95% CI: [1.17–3.32]), lack of occupational health and safety training (OR = 3.04, 95% CI: [2.36–3.93]), previous dust exposure (OR = 3.17, 95% CI: [2.3–4.37]), poor working environment (OR = 2.4, 95% CI: [1.7–3.2]), work experience greater than five years (OR = 4.04, 95% CI: [1.61–10.16]), smoking (OR = 6.91, 95% CI: [2.94–16.2]), and previous respiratory illness (OR = 4.25, 95% CI: [2.44–7.42]) were found to associate with the symptoms. Conclusions The high prevalence of occupational respiratory symptoms among industry workers in Ethiopia underscores the urgent need for effective interventions. The provision of personal protective equipment and improvement of working environments by the government, industry owners, and other stakeholders are crucial in reducing occupational respiratory symptoms. Additionally, prioritizing occupational health and safety training for industry workers can help prevent and mitigate the impact of occupational respiratory diseases. Registration This systematic review has been registered in the International Prospective Registry of Systematic Review (PROSPERO) with a specific registration number CRD42022383745.
Sex differences in pediatric caudal epidural anesthesia under sedation without primary airway instrumentation

Study objective To identify sex differences associated with caudal epidurals, the most commonly used technique of pediatric regional anesthesia, based on individually validated data of ultrasound-guided blocks performed between 04/2014 and 12/2020. Methods Prospectively collected and individually validated data of a cohort of children aged between 0–15 years was analyzed in a retrospective observational study. We included pediatric surgeries involving a primary plan of caudal epidural anesthesia under sedation (without airway instrumentation) and a contingency plan of general anesthesia. Sex-specific rates were analyzed for overall failure of the primary anesthesia plan, for residual pain, for block-related technical complications and for critical respiratory events. We used Fisher´s exact tests and multivariable logistic regressions were used to evaluate sex-specific associations. Results Data from 487 girls and 2060 boys ≤15 years old (ASA status 1 to 4) were analyzed. The primary-anesthesia-plan failure rate was 5.5% (95%CI 3.8%-7.8%) (N = 27/487) among girls and 4.7% (95%CI 3.9%-5.7%) (N = 97/2060) among boys (p = 0.41). Residual pain was the main cause of failure, with rates of 4.5% (95%CI 2.9–6.6%) (N = 22/487) among girls and 3.0% (95%CI 2.3–3.8%) (N = 61/2060) among boys (p = 0.089). Block-related technical complications were seen at rates of 0.8% (95%CI 0.3%-1.9%) (N = 4/487) among girls vs 2.5% (95%CI 0.5–2.7%) (N = 51/2060) among boys and, hence, significantly more often among male patients (p = 0.023). Male sex was significantly associated with higher odds (adjusted OR: 3.18; 95% CI: 1.12–9; p = 0.029) for such technical complications regardless of age, ASA status, gestational week at birth or puncture attempts. Critical respiratory events occurred at a 1.7% (95%CI 1.2%-2.3%) rate (N = 35/2060) twice as high among boys as 0.8% (95%CI 0.3%-1.9%) (N = 4/487) among girls (p = 0.21). Conclusions While the the primary-anesthesia-plan failure rate was equal for girls and boys, technical complications and respiratory events are more likely to occur in boys.
An engineered T-cell engager with selectivity for high mesothelin-expressing cells and activity in the presence of soluble mesothelin

ABSTRACT Mesothelin (MSLN) is an attractive immuno-oncology target, but the development of MSLN-targeting therapies has been impeded by tumor shedding of soluble MSLN (sMSLN), on-target off-tumor activity, and an immunosuppressive tumor microenvironment. We sought to engineer an antibody-based, MSLN-targeted T-cell engager (αMSLN/αCD3) with enhanced ability to discriminate high MSLN-expressing tumors from normal tissue, and activity in the presence of sMSLN. We also studied the in vivo antitumor efficacy of this molecule (NM28-2746) alone and in combination with the multifunctional checkpoint inhibitor/T-cell co-activator NM21-1480 (αPD-L1/α4-1BB). Cytotoxicity and T-cell activation induced by NM28-2746 were studied in co-cultures of peripheral blood mononuclear cells and cell lines exhibiting different levels of MSLN expression, including in the presence of soluble MSLN. Xenotransplant models of human pancreatic cancer were used to study the inhibition of tumor growth and stimulation of T-cell infiltration into tumors induced by NM28-2746 alone and in combination with NM21-1480. The bivalent αMSLN T-cell engager NM28-2746 potently induced T-cell activation and T-cell mediated cytotoxicity of high MSLN-expressing cells but had much lower potency against low MSLN-expressing cells. A monovalent counterpart of NM28-2746 had much lower ability to discriminate high MSLN-expressing from low MSLN-expressing cells. The bivalent molecule retained this discriminant ability in the presence of high concentrations of sMSLN. In xenograft models, NM28-2746 exhibited significant tumor suppressing activity, which was significantly enhanced by combination therapy with NM21-1480. NM28-2746, alone or in combination with NM21-1480, may overcome shortcomings of previous MSLN-targeted immuno-oncology drugs, exhibiting enhanced discrimination of high MSLN-expressing cell activity in the presence of sMSLN.
Life expectancy and end-of-life communication in adult patients with congenital heart disease, 40–53 years after surgery

Abstract Aims Although survival of patients with congenital heart disease (CHD) improved significantly over time, life expectancy is still not normal. We aimed to investigate how adult patients, their partners, and treating cardiologists estimated the individual life expectancy of CHD patients. Furthermore, preferences regarding end-of-life (EOL) communication were investigated. Methods and results In this study, we included 202 patients (age: 50 ± 5) who were operated in childhood (<15 years old) between 1968 and 1980 for one of the following diagnoses: atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot, or transposition of the great arteries. A specific questionnaire was administered to both the patients and their partners, exploring their perceived life expectancy and EOL wishes. Two cardiologists independently assessed the life expectancy of each patient. Most adults with CHD believed their life expectancy to be normal. However, significant differences were found between estimated life expectancy by the cardiologist and patients (female: P = 0.001, male: P = 0.002) with moderate/severe defects, as well as for males with mild defects (P = 0.011). Regarding EOL communication, 85.1% of the patients reported that they never discussed EOL with a healthcare professional. Compared with patients with mild CHD, significantly more patients with moderate/severe defect discussed EOL with a physician (P = 0.011). The wish to discuss EOL with the cardiologist was reported by 49.3% of the patients and 41.7% of their partners. Conclusion Adult patients, especially with moderate/severe CHD, perceived their life expectancy as normal, whereas cardiologists had a more pessimistic view than their patients. Increased attention is warranted for discussions on life expectancy and EOL to improve patient-tailored care.
Menopause and stress urinary incontinence: The risk factors of stress urinary incontinence in perimenopausal and postmenopausal women

The prevalence of stress urinary incontinence (SUI) increases around menopause. The quality of life of perimenopausal and postmenopausal women with SUI is significantly affected. This study aimed to investigate the prevalence of SUI and the associated risk factors in a population of Chinese perimenopausal and postmenopausal women.
Cooperative Learning for Personalized Context-Aware Pain Assessment From Wearable Data

Despite the promising performance of automated pain assessment methods, current methods suffer from performance generalization due to the lack of relatively large, diverse, and annotated pain datasets. Further, the majority of current methods do not allow responsible interaction between the model and user, and do not take different internal and external factors into consideration during the model's design and development. This article aims to provide an efficient cooperative learning framework for the lack of annotated data while facilitating responsible user communication and taking individual differences into consideration during the development of pain assessment models. Our results using body and muscle movement data, collected from wearable devices, demonstrate that the proposed framework is effective in leveraging both the human and the machine to efficiently learn and predict pain.
The course of patients with hairy cell leukemia during the omicron surge of the Covid‐19 pandemic

In this study, we aim to explore the outcomes of Covid‐19 infection in patients with Hairy cell leukemia (HCL). The cohort is based on data obtained from electronic medical records. It includes 218 consecutive patients diagnosed with HCL between 16 June 1998, and 20 September 2022, out of which the coronavirus has infected 85 patients during the Omicron surge. Out of 85 patients with HCL who were infected by Covid‐19; 7 patients (8.2%) have been hospitalized, and the mortality rate was 2.3% (two patients). Thirteen of the 85 patients had been infected by Covid‐19 in previous waves, including 9/13 after vaccination, and none of them developed a severe disease. Humoral immune response after three doses of the BNT162b2 mRNA vaccination regimen was evaluated in 40 patients and was attained in 67.5%. Based on multivariate analysis: unfavorable outcome was significantly more common in patients with HCL above 65 years old, who had at least one cytopenia, and with comorbidity of cardiovascular disease or asplenia. Our results indicates that the course of COVID‐19 in patients with HCL during the Omicron wave has been improved relatively favorable.
Pediatric reference intervals for hematology parameters in healthy infants and young children in Iran

Defining accurate age‐ and sex‐specific reference intervals (RIs) for hematology parameters, especially for the pediatric population, is important for making an appropriate clinical diagnosis. To address gaps, we established age‐specific RIs for 11 hematologic parameters in Iranian children younger than 30 months for the first time.
Recursive Computation for Block‐Nested Covariance Matrices

Covariance matrices corresponding to samples of multivariate time series or spatial random fields have a block‐Toeplitz structure that has a nested pattern. Also, non‐lattice data samples yield nested covariance matrices, although they are no longer block‐Toeplitz. The nested structure of such matrices facilitates the computation of their inverses, among other related quantities. Recursive algorithms, based upon this nested structure, are presented, yielding applications such as the simulation of vector time series, the evaluation of Gaussian likelihoods and Whittle likelihoods, the computation of spectral factorization, and the calculation of projections. Both multivariate time series applications and two‐dimensional random fields applications are discussed, as well as applications to non‐lattice data.
GSK-3 Inhibitor Elraglusib Enhances Tumor-Infiltrating Immune Cell Activation in Tumor Biopsies and Synergizes with Anti-PD-L1 in a Murine Model of Colorectal Cancer

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that has been implicated in numerous oncogenic processes. GSK-3 inhibitor elraglusib (9-ING-41) has shown promising preclinical and clinical antitumor activity across multiple tumor types. Despite promising early-phase clinical trial results, there have been limited efforts to characterize the potential immunomodulatory properties of elraglusib. We report that elraglusib promotes immune cell-mediated tumor cell killing of microsatellite stable colorectal cancer (CRC) cells. Mechanistically, elraglusib sensitized CRC cells to immune-mediated cytotoxicity and enhanced immune cell effector function. Using western blots, we found that elraglusib decreased CRC cell expression of NF-κB p65 and several survival proteins. Using microarrays, we discovered that elraglusib upregulated the expression of proapoptotic and antiproliferative genes and downregulated the expression of cell proliferation, cell cycle progression, metastasis, TGFβ signaling, and anti-apoptotic genes in CRC cells. Elraglusib reduced CRC cell production of immunosuppressive molecules such as VEGF, GDF-15, and sPD-L1. Elraglusib increased immune cell IFN-γ secretion, which upregulated CRC cell gasdermin B expression to potentially enhance pyroptosis. Elraglusib enhanced immune effector function resulting in augmented granzyme B, IFN-γ, TNF-α, and TRAIL production. Using a syngeneic, immunocompetent murine model of microsatellite stable CRC, we evaluated elraglusib as a single agent or combined with immune checkpoint blockade (anti-PD-1/L1) and observed improved survival in the elraglusib and anti-PD-L1 group. Murine responders had increased tumor-infiltrating T cells, augmented granzyme B expression, and fewer regulatory T cells. Murine responders had reduced immunosuppressive (VEGF, VEGFR2) and elevated immunostimulatory (GM-CSF, IL-12p70) cytokine plasma concentrations. To determine the clinical significance, we then utilized elraglusib-treated patient plasma samples and found that reduced VEGF and BAFF and elevated IL-1 beta, CCL22, and CCL4 concentrations correlated with improved survival. Using paired tumor biopsies, we found that tumor-infiltrating immune cells had a reduced expression of inhibitory immune checkpoints (VISTA, PD-1, PD-L2) and an elevated expression of T-cell activation markers (CTLA-4, OX40L) after elraglusib treatment. These results address a significant gap in knowledge concerning the immunomodulatory mechanisms of GSK-3 inhibitor elraglusib, provide a rationale for the clinical evaluation of elraglusib in combination with immune checkpoint blockade, and are expected to have an impact on additional tumor types, besides CRC.
Head movement direction in football - a field study on visual scanning activity during the UEFA-U17 and -U21 European Championship 2019

ABSTRACT Visual exploration (scanning) of one’s environment is a key aspect in team sports. Based on Gibson’s (1979) ecological approach of visual perception, this study aims to advance the understanding of scanning by focusing on the direction of head movements in football and its implications for subsequent on-ball actions. The video-based data analysis consisted of nine selected matches and 162 players of the Union of European Football Associations (UEFA) U17 and U21 European Championship 2019. The results indicate that the direction of the last scan prior to receiving the ball is related to the foot used for the first ball contact. This relationship was further analysed in view of the game context (direction of play and opponent pressure) and with information about the player’s dominant foot. The findings reveal a relationship between the direction of the last scan before receiving the ball and the direction the game is proceeded in. Further, when a player performs the last scan to the side of their dominant foot, the probability increases that their dominant foot is used for the subsequent first ball contact. Depending on the direction of the last scan, opponent pressure had various effects on the foot used for the first contact.
Various Correlations between the H-Index and Citation Rate (CPP) in Neuroscience and Quantum Physics: New Findings

Traditional bibliometric indicators are only partially suitable for evaluating the scientific achievements of individual people. They are either not definitive or they are too complicated to use due to technical and methodological difficulties. There is still no definite evidence for the correlation between the citation rate (CPP) and the H-Index. In order to obtain a reliable assessment of what the relation is between the H-Index and the citation rate, we performed a study on 30 relevant scientists from the disciplines of "particle physics" and "neurology". The foregoing discussions on the different correlations revealed that the form and degree of correlation do not just vary considerably between the individual comparisons but also amongst the disciplines. In both disciplines, the correlation between the citation rate CPP and the H-Index was relatively low. We also found varying degrees of correlation here.
Corticomuscular Coherence in Children with Unilateral Cerebral Palsy: A Feasibility and Preliminary Protocol Study

Objective This study assessed the feasibility of corticomuscular coherence measurement during a goal-directed task in children with unilateral cerebral palsy while establishing optimal experimental parameters. Methods Participants (Manual Ability Classification System levels I-III) completed a submaximal isometric goal-directed grip task during simultaneous electroencephalography and electromyography (EMG) acquisition. Results All participants (n = 11, 6 females, mean age 11.3 ±2.4 years) completed corticomuscular coherence procedures. Of the 40 trials obtained per extremity, an average of 29 (n = 9) and 27 (n = 10) trials were retained from the more- and less-affected extremities, respectively. Obtaining measurement stability required an average of 28 trials per extremity. Conclusion Findings from this work support the feasibility of corticomuscular coherence measurement in children with unilateral cerebral palsy. Acquiring 28 to 40 corticomuscular coherence trials per extremity is ideal. The experimental parameters established in this work will inform future corticomuscular coherence application in pediatric unilateral cerebral palsy.
Testing for normality in truncated anthropometric samples

Anthropometric historical analysis depends on the assumption that human characteristics—such as height—are normally distributed. I propose and evaluate a metric entropy, based on nonparametrically estimated densities, as a statistic for a consistent test of normality. My first test applies to full distributions for which other tests already exist and performs similarly. A modified version applies to truncated samples for which no test has been previously devised. This second test exhibits correct size and high power against standard alternatives. In contrast to the distributional prior of Floud et al. (1990), the test rejects normality in large parts of their sample; the remaining data reveal a downward trend in height, not upward as they argue.
Impact of the pentose phosphate pathway on metabolism and pathogenesis of Staphylococcus aureus

Staphylococcus aureus is an important pathogen that leads to significant disease through multiple routes of infection. We recently published a transposon sequencing (Tn-seq) screen in a mouse acute pneumonia model and identified a hypothetical gene (SAUSA300_1902, pgl) with similarity to a lactonase of Escherichia coli involved in the pentose phosphate pathway (PPP) that was conditionally essential. Limited studies have investigated the role of the PPP in physiology and pathogenesis of S. aureus. We show here that mutation of pgl significantly impacts ATP levels and respiration. RNA-seq analysis of the pgl mutant and parent strains identified compensatory changes in gene expression for glucose and gluconate as well as reductions in the pyrimidine biosynthesis locus. These differences were also evident through unbiased metabolomics studies and 13C labeling experiments that showed mutation of pgl led to reductions in pyrimidine metabolism including decreases in ribose-5P, UMP and GMP. These nucleotide reductions impacted the amount of extracellular DNA in biofilms and reduced biofilm formation. Mutation also limited the capacity of the strain to resist oxidant damage induced by hydrogen peroxide and paraquat and subsequent intracellular survival inside macrophages. Changes in wall teichoic acid impacted susceptibility to hydrogen peroxide. We demonstrated the importance of these changes on virulence in three different models of infection, covering respiratory, skin and septicemia, demonstrating the need for proper PPP function in all models. This work demonstrates the multifaceted role metabolism can play in multiple aspects of S. aureus pathogenesis.
Sodium Oxybate in Alcohol‐Responsive Essential Tremor of Voice: An Open‐Label Phase II Study

Essential tremor of voice (ETv) is characterized by involuntary oscillations of laryngeal and upper airway muscles, causing rhythmic alterations in pitch and loudness during both passive breathing and active laryngeal tasks, such as speaking and singing. Treatment of ETv is challenging and typically less effective compared with treatment of ET affecting extremities.
Population genomics reveals mechanisms and dynamics of de novo expressed open reading frame emergence in Drosophila melanogaster

Novel genes are essential for evolutionary innovations and differ substantially even between closely related species. Recently, multiple studies across many taxa showed that some novel genes arise de novo, that is, from previously noncoding DNA. To characterize the underlying mutations that allowed de novo gene emergence and their order of occurrence, homologous regions must be detected within noncoding sequences in closely related sister genomes. So far, most studies do not detect noncoding homologs of de novo genes because of incomplete assemblies and annotations, and long evolutionary distances separating genomes. Here, we overcome these issues by searching for de novo expressed open reading frames (neORFs), the not-yet fixed precursors of de novo genes that emerged within a single species. We sequenced and assembled genomes with long-read technology and the corresponding transcriptomes from inbred lines of Drosophila melanogaster, derived from seven geographically diverse populations. We found line-specific neORFs in abundance but few neORFs shared by lines, suggesting a rapid turnover. Gain and loss of transcription is more frequent than the creation of ORFs, for example, by forming new start and stop codons. Consequently, the gain of ORFs becomes rate limiting and is frequently the initial step in neORFs emergence. Furthermore, transposable elements (TEs) are major drivers for intragenomic duplications of neORFs, yet TE insertions are less important for the emergence of neORFs. However, highly mutable genomic regions around TEs provide new features that enable gene birth. In conclusion, neORFs have a high birth-death rate, are rapidly purged, but surviving neORFs spread neutrally through populations and within genomes.