Miracle-dz/UniFAR-FTUs huggingface dataset:
Basophil Depletion Alters Host Immunity, Intestinal Permeability, and Mammalian Host-to-Mosquito Transmission in Malaria

Malaria-induced bacteremia has been shown to result from intestinal mast cell (MC) activation. The appearance of MCs in the ileum and increased intestinal permeability to enteric bacteria are preceded by an early Th2-biased host immune response to infection, characterized by the appearance of IL-4, IL-10, mast cell protease (Mcpt)1 and Mcpt4, and increased circulating basophils and eosinophils. Given the functional similarities of basophils and MCs in the context of allergic inflammation and the capacity of basophils to produce large amounts of IL-4, we sought to define the role of basophils in increased intestinal permeability, in MC influx, and in the development of bacteremia in the context of malaria. Upon infection with nonlethal Plasmodium yoelii yoelii 17XNL, Basoph8 × ROSA-DTα mice or baso (−) mice that lack basophils exhibited increased intestinal permeability and increased ileal MC numbers, without any increase in bacterial 16S ribosomal DNA copy numbers in the blood, relative to baso (+) mice. Analysis of cytokines, chemokines, and MC-associated factors in the ileum revealed significantly increased TNF-α and IL-13 at day 6 postinfection in baso (−) mice compared with baso (+) mice. Moreover, network analysis of significantly correlated host immune factors revealed profound differences between baso (−) and baso (+) mice following infection in both systemic and ileal responses to parasites and translocated bacteria. Finally, basophil depletion was associated with significantly increased gametocytemia and parasite transmission to Anopheles mosquitoes, suggesting that basophils play a previously undescribed role in controlling gametocytemia and, in turn, mammalian host-to-mosquito parasite transmission.
Equivalence Theorems and the Local-Global Property

OF DISSERTATION Equivalence Theorems and the Local-Global Property In this thesis we revisit some classical results about the MacWilliams equivalence theorems for codes over fields and rings. These theorems deal with the question whether, for a given weight function, weight-preserving isomorphisms between codes can be described explicitly. We will show that a condition, which was already known to be sufficient for the MacWilliams equivalence theorem, is also necessary. Furthermore we will study a local-global property that naturally generalizes the MacWilliams equivalence theorems. Making use of F-partitions, we will prove that for various subgroups of the group of invertible matrices the local-global extension principle is valid.
Platelet-to-lymphocyte ratio associated with the clinicopathological features and prognostic value of breast cancer: A meta-analysis

The association of platelet-to-lymphocyte ratio (PLR) with the clinicopathological features and prognosis in patients with breast cancer was evaluated. Related studies were searched from PubMed, Embase, Cochrane Library, and Web of Science up to July 1, 2021. Then, basic characteristic and prognostic data were extracted from the included studies. We synthesized and compared primary outcomes such as overall survival. Subgroups analyses in pathology, geographical area, follow-up time, and sample size were conducted. The pooled hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) served as measures to assess the relationship of PLR with prognosis and clinicopathological features of breast cancer patients. After literature retrieval and selection, 20 studies with 7484 patients were included in this meta-analysis. High PLR was significantly related to poor overall survival (HR = 1.88; 95% CI 1.61, 2.19; P < 0.001) in breast cancer patients. Also, high PLR was associated with lymph node metastasis (LNM) (OR = 1.82; 95% CI 1.32, 2.52; P < 0.001), advanced tumor-node-metastasis (TNM) stage (OR = 1.89; 95% CI 1.25, 2.87; P = 0.003), and distant metastasis (OR = 1.76; 95% CI 1.14, 2.72; P = 0.01) in breast cancer. The stability and reliability of results in this meta-analysis were confirmed by sensitivity analysis. Elevated PLR is related to a poor prognosis and a higher risk of LNM, advanced TNM stage, and distant metastasis in breast cancer patients. Therefore, PLR can be identified as a biomarker with potential prognostic value in breast cancer.
Understanding the effects of COVID-19 stigmatisation on job performance: a survey of frontline healthcare workers

Abstract The level of stigmatisation among health care providers has increased during the COVID-19 pandemic, and understanding the effect of COVID-19 stigmatisation on job performance has become increasingly important. The study explores the influence of COVID-19 stigmatisation on job performance among frontline health workers via the mediating role of anxiety. Furthermore, the moderating effect of resilience in the association between COVID-19 stigmatisation and anxiety is further examined. Participants were made up of 820 frontline health workers working in the epicentres of the Bono Ahafo, Western, Greater Accra, and Northern regions of Ghana. The hierarchical regression technique was employed in estimating the relationship between the variables. COVID-19 stigmatisation among frontline health workers directly affected anxiety and performance. In addition, the results showed that resilience moderated the relationship between COVID-19 stigmatisation and anxiety. The findings again demonstrated that anxiety partially mediated the association between concern for disclosure and public attitude and negative experience and job performance, whereas personalised stigma was insignificant. The study provides implications for establishing anti-stigma interventions and programs to enhance job performance among health workers. Key messages Many healthcare workers are subject to stigmatisation during the COVID-19 pandemic. The study employs hierarchical regression methods to examine the impacts of COVID-19 stigmatisation on job performance among frontline health workers. The health management team should strengthen interventions to control the stigma experienced by health workers during COVID-19 treatments.
App-Based Evaluation of Older People’s Fall Risk Using the mHealth App Lindera Mobility Analysis: Exploratory Study

Background Falls and the risk of falling in older people pose a high risk for losing independence. As the risk of falling progresses over time, it is often not adequately diagnosed due to the long intervals between contacts with health care professionals. This leads to the risk of falling being not properly detected until the first fall. App-based software able to screen fall risks of older adults and to monitor the progress and presence of fall risk factors could detect a developing fall risk at an early stage prior to the first fall. As smartphones become more common in the elderly population, this approach is easily available and feasible. Objective The aim of the study is to evaluate the app Lindera Mobility Analysis (LIN). The reference standards determined the risk of falling and validated functional assessments of mobility. Methods The LIN app was utilized in home- and community-dwelling older adults aged 65 years or more. The Berg Balance Scale (BBS), the Tinetti Test (TIN), and the Timed Up & Go Test (TUG) were used as reference standards. In addition to descriptive statistics, data correlation and the comparison of the mean difference of analog measures (reference standards) and digital measures were tested. Spearman rank correlation analysis was performed and Bland-Altman (B-A) plots drawn. Results Data of 42 participants could be obtained (n=25, 59.5%, women). There was a significant correlation between the LIN app and the BBS (r=–0.587, P<.001), TUG (r=0.474, P=.002), and TIN (r=–0.464, P=.002). B-A plots showed only few data points outside the predefined limits of agreement (LOA) when combining functional tests and results of LIN. Conclusions The digital app LIN has the potential to detect the risk of falling in older people. Further steps in establishing the validity of the LIN app should include its clinical applicability. Trial Registration German Clinical Trials Register DRKS00025352; https://tinyurl.com/65awrd6a
Bacterial Culture Underestimates Lung Pathogen Detection and Infection Status in Cystic Fibrosis

Chronic lung infection is the leading cause of morbidity and early mortality for people with cystic fibrosis (pwCF). Microbiological surveillance to detect lung pathogens is recommended as best practise in CF patient care. ABSTRACT Microbiological surveillance of airway secretions is central to clinical care in cystic fibrosis (CF). However, the efficacy of microbiological culture, the diagnostic gold standard for pathogen detection, has been increasingly questioned. Here we compared culture with targeted quantitative PCR (QPCR) for longitudinal detection of 2 key pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. Prospectively collected respiratory samples taken from 20 pediatric and 20 adult CF patients over a period of 3-years were analyzed. Patients were eligible if considered free of chronic Pseudomonas infection within 12-months prior to start of study. QPCR revealed high levels of infection with both pathogens not apparent from culture alone. Pseudomonas and Staphylococcus were detected by culture on at least one sampling occasion in 12 and 29 of the patients, respectively. Conversely, both pathogens were detected in all 40 patients by QPCR. Classification of infection status also significantly altered in both pediatric and adult patients, where the number of patients deemed chronically infected with Pseudomonas and Staphylococcus increased from 1 to 28 and 9 to 34, respectively. Overall, Pseudomonas and Staphylococcus infection status classification changed respectively for 36 and 27 of all patients. In no cases did molecular identification lead to a patient being in a less clinically serious infection category. Pathogen detection and infection status classification significantly increased when assessed by QPCR in comparison to culture. This could have implications for clinical care of CF patients, including accuracy of infection diagnosis, relevant and timely antibiotic selection, antimicrobial resistance development, establishment of chronic infection, and cross-infection control. IMPORTANCE Chronic lung infection is the leading cause of morbidity and early mortality for people with cystic fibrosis (pwCF). Microbiological surveillance to detect lung pathogens is recommended as best practise in CF patient care. Here we studied pathogen detection in 40 pwCF over several years. We found that microbiological culture, the diagnostic gold standard, was significantly disparate to targeted culture-independent approaches for detection and determination of chronic infection status of two important pathogens in CF. Pathogen detection was significantly lower by culture and consequently infection status was also misclassified in most cases. In particular, the extent of chronic infection by both P. aeruginosa and S. aureus not realized with culture was striking. Our findings have implications for the development of infection and clinical care of pwCF. Future longitudinal studies with greater patient numbers will be needed to establish the full extent of the clinical implications indicated from this study.
Transplantation of Astrocytic Mitochondria Modulates Neuronal Antioxidant Defense and Neuroplasticity and Promotes Functional Recovery after Intracerebral Hemorrhage

Astrocytes release functional mitochondria (Mt) that play regulatory and prosurvival functions on entering adjacent cells. We recently demonstrated that these released Mts could enter microglia to promote their reparative/prophagocytic phenotype that assists in hematoma cleanup and neurological recovery after intracerebral hemorrhage (ICH). However, the relevance of astrocytic Mt transfer into neurons in protecting brain after ICH is unclear. Here, we found that ICH causes a robust increase in superoxide generation and elevated oxidative damage that coincides with loss of the mitochondrial enzyme manganese superoxide dismutase (Mn-SOD). The damaging effect of ICH was reversed by intravenous transplantation of astrocytic Mt, which on entering the brain (and neurons), restored Mn-SOD levels and reduced neurological deficits in male mice subjected to ICH. Using an in vitro ICH-like injury model in cultured neurons, we established that astrocytic Mt on entering neurons prevented reactive oxygen species-induced oxidative stress and neuronal death by restoring neuronal Mn-SOD levels while at the same time promoted neurite extension and upregulation of synaptogenesis-related gene expression. Furthermore, we found that Mt genome-encoded small peptide humanin, which is normally abundant in Mt, could simulate Mt-transfer effect on neuronal Mn-SOD expression, oxidative stress, and neuroplasticity under ICH-like injury. This study demonstrates that adoptive astrocytic Mt transfer enhances neuronal Mn-SOD-mediated antioxidative defense and neuroplasticity in the brain, which potentiate functional recovery following ICH. SIGNIFICANCE STATEMENT Mitochondrial dysfunction and antioxidant defense play essential roles in brain damage after ICH. Astrocytes release functional Mt that enters adjacent cells to help brain homeostatic function. Here, we show that systemic transplantation of astrocytic Mt restores ICH-impaired neuronal antioxidative defense, enhances neurite outgrowth, and improves stroke recovery after ICH. Our study suggests that systemic transplantation of astrocytic Mt could be considered as a novel and potentially promising strategy for ICH treatment.
Identification and characterization of in vitro expanded hematopoietic stem cells

Hematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved > 200‐fold expansion of functional HSCs, but their molecular characterization has not been possible since the majority of cells are non‐HSCs and single cell‐initiated cultures have substantial clone‐to‐clone variability. Using the Fgd5 reporter mouse in combination with the EPCR surface marker, we report exclusive identification of HSCs from non‐HSCs in expansion cultures. By directly linking single‐clone functional transplantation data with single‐clone gene expression profiling, we show that the molecular profile of expanded HSCs is similar to proliferating fetal HSCs and reveals a gene expression signature, including Esam, Prdm16, Fstl1, and Palld, that can identify functional HSCs from multiple cellular states. This “repopulation signature” (RepopSig) also enriches for HSCs in human datasets. Together, these findings demonstrate the power of integrating functional and molecular datasets to better derive meaningful gene signatures and opens the opportunity for a wide range of functional screening and molecular experiments previously not possible due to limited HSC numbers.
Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Sodium–Glucose Cotransporter 2 Inhibitor Treatment: The FIDELITY Analysis

OBJECTIVE Finerenone reduced the risk of kidney and cardiovascular events in people with chronic kidney disease (CKD) and type 2 diabetes in the FIDELIO-DKD and FIGARO-DKD phase 3 studies. Effects of finerenone on outcomes in patients taking sodium–glucose cotransporter 2 inhibitors (SGLT2is) were evaluated in a prespecified pooled analysis of these studies. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes and urine albumin-to-creatinine ratio (UACR) ≥30 to ≤5,000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 were randomly assigned to finerenone or placebo; SGLT2is were permitted at any time. Outcomes included cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% eGFR decline, or renal death) end points, changes in UACR and eGFR, and safety outcomes. RESULTS Among 13,026 patients, 877 (6.7%) received an SGLT2i at baseline and 1,113 (8.5%) initiated one during the trial. For the cardiovascular composite, the hazard ratios (HRs) were 0.87 (95% CI 0.79–0.96) without SGLT2i and 0.67 (95% CI 0.42–1.07) with SGLT2i. For the kidney composite, the HRs were 0.80 (95% CI 0.69–0.92) without SGLT2i and 0.42 (95% CI 0.16–1.08) with SGLT2i. Baseline SGLT2i use did not affect risk reduction for the cardiovascular or kidney composites with finerenone (Pinteraction = 0.46 and 0.29, respectively); neither did SGLT2i use concomitant with study treatment. CONCLUSIONS Benefits of finerenone compared with placebo on cardiorenal outcomes in patients with CKD and type 2 diabetes were observed irrespective of SGLT2i use.
The marital relationship and health‐related quality of life of prostate cancer patients and their spouses: A prospective, longitudinal study

Abstract Aims This study aims to measure any changes in the marital relationship during the first year after a diagnosis of prostate cancer, identify the demographic characteristics that influenced such changes, and measure changes related to health‐related quality of life (HRQoL). Background Knowledge is limited on the impact of a diagnosis of prostate cancer on the marital relationship and HRQoL of patients and their spouses. Design A 1‐year longitudinal study. Methods Data were collected from five Finnish hospitals between October 2013 and January 2017. Of the 350 recruited couples (N = 700), 179 patients and 166 spouses completed the Marital Questionnaire and the RAND 36‐Item Health Survey 1 year after diagnosis. Results No major changes were found in the marital relationship during the follow‐up period. The spouses reported statistically significant changes in their marital relationships, but the patients did not. Furthermore, changes in the marital relationship were not associated with the patients' HRQoL. Among spouses, emotional well‐being was associated with changes in the marital relationship. Conclusion The marital relationship was relevant in terms of the spouses' HRQoL during the first year after a diagnosis of prostate cancer. Nurses and other healthcare providers should assess counselling and support provided to spouses individually.
Protein and Energy Intakes Are Skewed toward the Evening among Children and Adolescents in the United States: NHANES 2013–2014 1–4

Background: Emerging evidence suggests that the timing, amount at individual eating occasions, and distribution of protein and energy intakes throughout the day may affect health. Objective: We examined the timing, amounts, and distribution of protein and energy intakes throughout the day among participants aged 4–18 y in the United States in the context of chronobiology and nutrition. Methods: This cross-sectional analysis included 2532 participants aged 4–18 y who completed the ﬁrst interviewer-administered 24-h dietary recall in NHANES 2013–2014. Descriptive statistics for intakes across the day were provided as percentiles, means 6 SEMs, and percentages of nonconsumers. Statistical differences between intakes across the day were tested with the use of individual-level ﬁxed-effects regression models. Cumulative distribution functions were used to examine the timing of the ﬁrst and last caloric eating occasion. Results: Mean 6 SEM protein (grams) and energy (percentage of the day) intakes were signiﬁcantly higher ( P < 0.05) in the evening than in the morning among all age groups. The percentage of participants aged 4–8, 9–13, and 14–18 y who had their ﬁrst eating occasion at or after 1100 was 4%, 14%, and 20%, respectively, and the percentage who had their last eating occasion at or after 2100 was 8%, 19%, and 34%, respectively. Conclusions: Protein and energy intakes among participants aged 4–18 y in this study were largest in the evening and midday and smallest in the morning and afternoon. Clinical trials are needed to assess any potential impact such dietary behaviors may have on health outcomes related to metabolic dysfunction in children and adolescents. J Nutr 2017;147:1160–6.
Contrasting hydrodynamic regimes of submerged pinnacle and emergent coral reefs

Hydrodynamics on coral reefs vary with depth, reef morphology and seascape position. Differences in hydrodynamic regimes strongly influence the structure and function of coral reef ecosystems. Submerged coral reefs on steep-sided, conical bathymetric features like seamounts experience enhanced water circulation as a result of interactions between currents and the abrupt physical structure. There may also be similar interactions between smaller pinnacles and regional water currents in offshore locations (crests > 10 m), while shallow reefs (crests <10 m) may be more subject to surface currents driven by wind, waves and tide. Here we tested whether coral pinnacles experienced stronger and more variable currents compared to emergent reefs at the same depth in both nearshore and offshore positions. Current speeds and temperature were monitored for 12 months at 11 reefs, representing the three different reef categories: submerged offshore pinnacles, emergent offshore reefs and emergent nearshore reefs. We found different patterns in current speeds and temperature among reef types throughout the year and between seasons. Submerged pinnacles exhibited stronger, more variable current speeds compared to both near and offshore emergent reefs. We found seasonal changes in current speeds for pinnacle and nearshore reefs but no variation in current strength on offshore reefs. Whilst instantaneous current directions did reflect the seascape position of individual sites, there was no difference in the directional variability of current speeds between reef types. Annual daily average temperatures at all reef types were not strongly seasonal, changing by less than 2 °C throughout the year. Daily temperature ranges at specific sites however, exhibited considerable variability (annual range of up to 6.5 °C), particularly amongst offshore emergent reefs which experienced the highest temperatures despite greater exposure to regional-scale circulation patterns. Additionally, we found a consistent mismatch between satellite sea surface temperatures and in-situ temperature data, which was on average 2 °C cooler throughout the annual study period. Our results suggest that distinct hydrodynamic processes occur on smaller submerged structures that are physically analogous to seamounts. Our findings highlight important nuances in environmental processes that occur on morphologically distinct coral reef habitats and these are likely to be important drivers for the community dynamics of organisms that inhabit these reefs.
CMTr mediated 2′-O-ribose methylation status of cap-adjacent nucleotides across animals

Cap methyltransferases (CMTrs) O methylate the 2′ position of the ribose (cOMe) of cap-adjacent nucleotides of animal, protist, and viral mRNAs. Animals generally have two CMTrs, whereas trypanosomes have three, and many viruses encode one in their genome. In the splice leader of mRNAs in trypanosomes, the first four nucleotides contain cOMe, but little is known about the status of cOMe in animals. Here, we show that cOMe is prominently present on the first two cap-adjacent nucleotides with species- and tissue-specific variations in Caenorhabditis elegans, honeybees, zebrafish, mouse, and human cell lines. In contrast, Drosophila contains cOMe primarily on the first cap-adjacent nucleotide. De novo RoseTTA modeling of CMTrs reveals close similarities of the overall structure and near identity for the catalytic tetrad, and for cap and cofactor binding for human, Drosophila and C. elegans CMTrs. Although viral CMTrs maintain the overall structure and catalytic tetrad, they have diverged in cap and cofactor binding. Consistent with the structural similarity, both CMTrs from Drosophila and humans methylate the first cap-adjacent nucleotide of an AGU consensus start. Because the second nucleotide is also methylated upon heat stress in Drosophila, these findings argue for regulated cOMe important for gene expression regulation.