bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depletion of gut microbiota influents glucose metabolism and hyperandrogenism traits of mice with PCOS induced by letrozole
Authors: Li Yushan , Zhu Yuchen , Li Dan , Liu Wen , Zhang Yi , Liu Wei , Zhang Chenhong , Tao Tao 
Published: October 2023

BackgroundPolycystic ovary syndrome (PCOS) is a multifaceted disorder that impacts metabolism, reproduction, as well as endocrine function, characterized by excessive levels of androgen and insulin resistance. The gut microbiota has been implicated in the pathogenesis of PCOS. However, the precise mechanisms through which the gut microbiota influences PCOS still require further elucidation.MethodsThe PCOS mouse model was established through the administration of letrozole to both conventional and antibiotics-treated mice. The evaluation of glucose metabolism, sex hormone levels, and ovarian morphology was conducted. Furthermore, the fecal samples from each group of mice were subjected to 16S rRNA gene sequencing, and functional prediction of gut microbiota was proceeded using PICRUSt2 to explore potential mechanisms.ResultsBy using letrozole-induced PCOS mice model, we manifested that antibiotic intervention significantly reduced the serum total testosterone level and ameliorated glucose intolerance. Antibiotic treatment reduced the number of amplicon sequence variants (ASVs), as well as the Shannon and Simpson index. Meanwhile, letrozole induced a significant increase in the Shannon and Simpson index instead of ASVs. Through random forest model analysis, the results revealed significant alterations in three distinct groups of microbiota, namely Clostridia_vadinBB60_group, Enterorhabdus, and Muribaculaceae after letrozole treatment. Further correlation analysis revealed a positive association between alterations in these microbiota and both serum total testosterone levels and the area under the curve (AUC) of blood glucose in IPGTT. The administration of antibiotics led to a decrease in the absolute abundance of 5 ASVs belonging to unclassified Clostridia_vadinBB60_group, unclassified Enterorhabdus, and unclassified Muribaculaceae, which exhibited a positive correlation with the levels of total testosterone in mice serum, as well as the area under the curve of blood glucose in IPGTT. Moreover, 25 functional pathways of gut microbiome were significantly discrepant between the letrozole-treated mice with and without antibiotics.ConclusionThese results suggest that disturbance of the gut microbiota may take participate in the progression of PCOS and manipulating the composition of the gut microbiota may be a therapeutic approach for managing PCOS.
Understanding the role of youth in Indigenous territorial governance
Authors: Sarigumba Maria Paula , Soriano Marlene , Robson James P. , Quiviquivi Ignacio , Cabrera Olga Lidia 
Published: October 2023

Indigenous territories cover more than one-fourth of the world’s land surface, overlap with distinct ecological areas, and harbour significant cultural and biological diversity; their stewardship provides critical contributions to livelihood, food security, conservation, and climate action. How these territories are accessed, used, and managed is an important question for owner communities, state governments, development agencies, and researchers alike. This extends to how broad community memberships remain invested in territorial use and management, with young people comprising one sub-group often underrepresented in decision-making spaces. We know that internal community norms and structures–often dominated by older, adult males–can limit opportunities for youth to contribute their energy and ideas. We also know that youth can and do leave their home communities to pursue life, work, or education goals and aspirations. Drawing on insights from 5 years of collaborative research with the Indigenous Territory of Lomerío (ITL), Bolivia, we explore the roles that youth play in territorial governance, their perceptions of current structures and novel engagement strategies, and consider what lessons from this case could be applied more broadly. Our findings point to the ITL as an instructive example of how Indigenous (and other rural and remote) communities might enable young people to participate more fully in territorial governance, highlighting the importance of an enabling, underlying socio-cultural context. Based on our work in Bolivia, and lessons from other places, we discuss ways to enhance youth-community-territory linkages to support Indigenous land sovereignty and stewardship and reflect on how research co-design and knowledge co-production can help deliver more robust, inclusive, and useful (in an applied sense) empirical insights in support of such efforts.
Using enhanced vegetation index and land surface temperature to reconstruct the solar-induced chlorophyll fluorescence of forests and grasslands across latitude and phenology
Authors: Zhang Peipei , Liu Haiqiu , Li Hangzhou , Yao Jianen , Chen Xiu , Feng Jinying 
Published: October 2023

IntroductionForest and grassland are the two main carbon-collecting terrestrial ecosystems, and detecting their solar-induced chlorophyll fluorescence (SIF) enables evaluation of their photosynthetic intensity and carbon-collecting capacity. Since SIF that is retrieved directly from satellite observations suffers from low spatial resolution, discontinuity, or low temporal resolution, some vegetation indexes (VIs) and meteorological factors are used as predictors to reconstruct SIF products. Yet, unlike VIs, certain meteorological factors feature a relatively low space resolution and their observations are not always accessible. This study aimed to explore the potential of reconstructing SIF from fewer predictors whose high-resolution observations are easily accessible.MethodsA total of six forest and grassland regions across low, mid, and high latitudes were selected, and the commonly used predictors-normalized difference vegetation index (NDVI), enhanced vegetation index (EVI), and land surface temperature (LST)—were compared for their correlation with SIF. Results show that the combination of EVI and LST is more strongly correlated with SIF, but each contributed differently to SIF at differing growth stages of forest and grassland. Accordingly, we proposed the idea of a combined sampling approach that considers both location and phenological phase, to explore the extent to which time and space coverage samples' span could enlarge the disparity of EVI data in particular regions at specific growth stages. To do that, three kinds of sample combination methods were proposed: monthly regression at a global scale, seasonal regression at a regional scale, and monthly regression at a regional scale. Following this, Sentinel-3 EVI and MODIS LST data were used to reconstruct 500 m SIF in the six regions by implementing the proposed methodology.Results and discussionThese results showed that the R2 values were ≥0.90 between the reconstructed SIF and MODIS GPP (gross primary productivity), 0.70 with GOME-2 SIF and 0.77 with GOSIF, thus proving the proposed methodology could produce reliable results for reconstruction of 500 m SIF. This proposed approach, which bypasses dependence of traditional SIF reconstruction model on numerous predictors not easy to obtain, can serve as a better option for more efficient and accurate high-resolution SIF reconstructions in the future.
Real-world clinical effectiveness of Tixagevimab/Cilgavimab and Regdanvimab monoclonal antibodies for COVID-19 treatment in Omicron variant-dominant period
Authors: Fomina Daria S. , Lebedkina Marina S. , Iliukhina Anna A. , Kovyrshina Anna V. , Shelkov Artem Y. , Andreev Sergey S. , Chernov Anton A. , Dolzhikova Inna V. , Kruglova Tatyana S. , Andrenova Gerelma V. , Tukhvatulin Amir I. , Shcheblyakov Dmitry V. , Karaulov Alexander V. , Lysenko Maryana A. , Logunov Denis Y. , Gintsburg Alexander L. 
Published: October 2023

Several virus-neutralizing monoclonal antibodies (mAbs) have become new tools in the treatment of the coronavirus disease (COVID-19), but their effectiveness against the rapidly mutating virus is questionable. The present study investigated the effectiveness of Tixagevimab/Cilgavimab and Regdanvimab for mild and moderate COVID-19 treatment in real-world clinical practice during the Omicron variant-dominant period. Patients with known risk factors for disease progression and increasing disease severity were enrolled in the study within the first 7 days of symptom onset. Seventy-seven patients were divided into four groups: first 15 patients received 300 mg Tixagevimab/Cilgavimab intravenously (IV) and 23 patients got the same drug 300 mg intramuscularly (IM), the next 15 patients was on the same combination in dose of 600 mg IV, and 24 patients were on Regdanvimab at a dose of 40 mg/kg IV. By Day 4, 100% of Tixagevimab/Cilgavimab IV patients showed negative polymerase chain reaction results for SARS-CoV-2 Ribonucleic acid (RNA) regardless of the mAbs dose while in the Regdanvimab group 29% of the patients were positive for SARS-CoV-2 virus RNA. The testing for virus neutralizing antibodies (nAbs) to various Omicron sublineages (BA.1, BA.2, and BA.5) showed that an increase in nAb levels was detected in blood serum immediately after the drug administration only in Tixagevimab/Cilgavimab 300 mg and 600 mg IV groups. In the group of intravenous Regdanvimab, a significant increase in the level of nAbs to the Wuhan variant was detected immediately after the drug administration, while no increase in nAbs to different Omicron sublineages was observed.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT05982704.
Integrated Immunopeptidomic and Proteomic Analysis of COVID-19 lung biopsies
Authors: Yin Shanye , Klaeger Susan , Chea Vipheaviny A. , Carulli Isabel P. , Rachimi Suzanna , Black Katharine E. , Filbin Michael , Hariri Lida P. , Knipe Rachel S. , Padera Robert F. , Stevens Jonathan D. , Lane William J. , Carr Steven A. , Wu Catherine J. , Kim Edy Yong , Keskin Derin B. 
Published: October 2023

IntroductionSevere respiratory illness is the most prominent manifestation of patients infected with SARS-CoV-2, and yet the molecular mechanisms underlying severe lung disease in COVID-19 affected patients still require elucidation. Human leukocyte antigen class I (HLA-I) expression is crucial for antigen presentation and the host’s response to SARS-CoV-2.MethodsTo gain insights into the immune response and molecular pathways involved in severe lung disease, we performed immunopeptidomic and proteomic analyses of lung tissues recovered at four COVID-19 autopsy and six non-COVID-19 transplants.ResultsWe found signals of tissue injury and regeneration in lung fibroblast and alveolar type I/II cells, resulting in the production of highly immunogenic self-antigens within the lungs of COVID-19 patients. We also identified immune activation of the M2c macrophage as the primary source of HLA-I presentation and immunogenicity in this context. Additionally, we identified 28 lung signatures that can serve as early plasma markers for predicting infection and severe COVID-19 disease. These protein signatures were predominantly expressed in macrophages and epithelial cells and were associated with complement and coagulation cascades.DiscussionOur findings emphasize the significant role of macrophage-mediated immunity in the development of severe lung disease in COVID-19 patients.
Mortality rate and predictors of COVID-19 inpatients in Ethiopia: a systematic review and meta-analysis
Authors: Birhanu Molla Yigzaw , Jemberie Selamawit Shita 
Published: October 2023

IntroductionThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an extremely rare virus that devastates the economy and claims human lives. Despite countries' urgent and tenacious public health responses to the COVID-19 pandemic, the disease is killing a large number of people. The results of prior studies have not been used by policymakers and programmers due to the presence of conflicting results. As a result, this study was conducted to fill the knowledge gap and develop a research agenda.ObjectiveThis study aimed to assess the mortality rate and predictors of COVID-19 hospitalized patients in Ethiopia.MethodsElectronic databases were searched to find articles that were conducted using a retrospective cohort study design and published in English up to 2022. The data were extracted using a Microsoft Excel spreadsheet and exported to StataTM version 17.0 for further analysis. The presence of heterogeneity was assessed and presented using a forest plot. The subgroup analysis, meta-regression, and publication bias were computed to identify the source of heterogeneity. The pool COVID-19 mortality rate and its predictors were calculated and identified using the random effects meta-analysis model, respectively. The significant predictors identified were reported using a relative risk ratio and 95% confidence interval (CI).ResultsSeven studies with 31,498 participants were included. The pooled mortality rate of COVID-19 was 9.13 (95% CI: 5.38, 12.88) per 1,000 person-days of mortality-free observation. Those study participants who had chronic kidney disease had 2.29 (95% CI: 1.14, 4.60) times higher chance of experiencing mortality than their corresponding counterparts, diabetics had 2.14 (95% CI: 1.22, 3.76), HIV patients had 2.98 (95% CI: 1.26, 7.03), hypertensive patients had 1.63 (95% CI: 1.43, 1.85), and smoker had 2.35 (95% CI: 1.48, 3.73).ConclusionCOVID-19 mortality rate was high to tackle the epidemic of the disease in Ethiopia. COVID-19 patients with chronic renal disease, diabetes, hypertension, smoking, and HIV were the significant predictors of mortality among COVID-19 patients in Ethiopia. COVID-19 patients with chronic diseases and comorbidities need special attention, close follow-up, and care from all stakeholders.
Choroidal thickness in relation to diopter and axial length among myopic children
Authors: Zhu Huailin , Liu Changyang , Gao Mingjun , Zhang Siqi , Zhang Lan , Zhao Qi 
Published: October 2023

PurposeThe aim of this study was to analyze the relationship between diopter (D) and choroidal thickness in myopic children by describing the values of choroidal thickness, and explore choroidal thickness as an important indicator for evaluating the progression of myopia.MethodsThe study included myopic and emmetropic children aged 6–14 years (156 eyes) from the Second Hospital of Dalian Medical University. The participants were divided into four groups according to the spherical equivalent refraction (SER): low myopes, moderate myopes, high myopes, and emmetropes. Choroidal thickness was measured in nine areas using the Early Treatment Diabetic Retinopathy Study (ETDRS) grid layout, which divided the areas into concentric circles of 0 × 0 mm, 3 × 3 mm, and 5 × 5 mm from the Sub Fovea. The images were obtained manually with spectral-domain optical coherence tomography scanner.ResultsThere were significant differences of choroidal thickness in the nine areas of the ETDRS grid for all myopes. The distribution of choroidal thickness in low and moderate myopes were different from that in high myopes. In the horizontal direction, choroidal thickness decreased from the temporal to nasal areas for all myopes. In the vertical direction, the choroidal thickness in the perifovea was smaller than that in the parafovea (SER ≥ −2.75D), and the choroidal thickness in the perifovea was greater than that in the parafovea (SER &lt; −2.75D). When comparing emmetropes with myopes, the closer the choroidal thickness was to the central fovea, the more significant the differences were, while the differences were smaller to the perifovea. Among all children, choroidal thickness was positive to SER and negative to axial length (AL) in all areas. For every 1D increase in myopia, the subfoveal choroidal thickness decreased by 13 μm, and for every 1 mm increase in AL, the subfoveal choroidal thickness decreased by 23 μm. Furthermore, SER and AL showed the strongest correlation with choroidal thickness in the inferior area.ConclusionOptical coherence tomography results revealed choroidal thickness was thinner in myopic children. Choroidal thickness was positive to SER and negative to AL. Therefore, we consider choroidal thickness to be an important indicator for evaluating the myopia progress.
Case report: JC polyomavirus nephropathy in simultaneous heart–kidney transplantation: the role of viral-specific in situ hybridization staining
Authors: Abu Jawdeh Bassam G. , Smith Maxwell L. , Hudson Madeline R. , Mour Girish K. , Budhiraja Pooja , Rosenthal Julie L. 
Published: October 2023

IntroductionJC polyomavirus (JCPyV) is a ubiquitous virus that can be latent in the brain and the kidney. It is the etiologic agent responsible for progressive multifocal leukoencephalopathy, a fatal, demyelinating disease of the central nervous system, and rarely causes polyomavirus nephropathy in immunocompromised kidney transplant recipients.Case descriptionWe present the first case of JCPyV nephropathy in a simultaneous heart–kidney transplant patient, where viral-specific in situ hybridization staining of the kidney tissue was utilized to confirm the diagnosis. The patient was diagnosed 6 years after simultaneous heart–kidney transplantation and was treated with immunosuppression reduction and intravenous immunoglobulin.DiscussionJCPyV nephropathy should be considered in the differential diagnosis of kidney allograft injury, particularly, with suggestive light microscopy histologic features in the absence of BK polyomavirus viremia and/or viruria. In addition to obtaining JCPyV PCR in the blood, in situ hybridization staining may have a utility in confirming the diagnosis. To date, we lack effective JCPyV-specific therapies, and prompt initiation of immunosuppression reduction remains the mainstay of treatment.
Prevalence of dementia in a level 4 university epilepsy center: how big is the problem?
Authors: Helmstaedter Christoph , Lutz Teresa , Wolf Vinzent , Witt Juri-Alexander 
Published: October 2023

BackgroundThe relationship between epilepsy and dementia is currently a topic of great interest. Our study aimed to determine the prevalence of dementia diagnoses among patients of a large level 4 university epilepsy center.MethodsIn this retrospective monocentric study conducted at the Department of Epileptology of the University Hospital Bonn, we searched for dementia-related terms in a total of 145,501 medical letters from 40,360 adult patients who were seen between 2003 and 2021. Files with at least one hit were selected and analyzed with regard to diagnoses, age, age at epilepsy onset, and the question as to whether epilepsy preceded or followed the dementia diagnosis.ResultsAmong the medical letters of 513 patients, dementia-related terms were found. The letters of 12.7% of these patients stated a dementia diagnosis, 6.6% were suspected of having dementia, 4.9% had mild cognitive impairment, and 6.6% had other neurodegenerative diseases without dementia. Taking all 40,360 patients into account, the prevalence of diagnosed or suspected dementia was 0.25%. An older age (≥60 years) and late-onset epilepsy (≥60 years), but not a longer epilepsy duration, increased the odds of dementia by 6.1 (CI 3.5–10.7) and 2.9 (CI 1.7–4.7), respectively. Additionally, vascular, metabolic, inflammatory, and behavioral mood-related comorbidities were commonly observed. Epilepsy tended to precede (23.2%) rather than follow (8.1%) the dementia diagnosis.ConclusionDespite the clear limitations of a selection bias and the potential underdiagnosis of dementia and underestimation of its prevalence when relying on the medical letters from a specialized center which rather focuses on epilepsy-related issues, the findings of this study offer valuable insights from the perspective of an epilepsy center. In this setting, the prevalence of dementia in epilepsy is rather low. However, physicians should be aware that the risk of dementia is higher in the elderly, in late-onset epilepsies, and when comorbid risk factors exist. Seizures can also be an early sign of a neurodegenerative disease. Future research should explicitly screen for dementia in patients with epilepsy and stratify them according to their underlying pathologies and comorbidities.
Machine learning-based prediction of symptomatic intracerebral hemorrhage after intravenous thrombolysis for stroke: a large multicenter study
Authors: Wen Rui , Wang Miaoran , Bian Wei , Zhu Haoyue , Xiao Ying , He Qian , Wang Yu , Liu Xiaoqing , Shi Yangdi , Hong Zhe , Xu Bing 
Published: October 2023

BackgroundThis study aimed to compare the performance of different machine learning models in predicting symptomatic intracranial hemorrhage (sICH) after thrombolysis treatment for ischemic stroke.MethodsThis multicenter study utilized the Shenyang Stroke Emergency Map database, comprising 8,924 acute ischemic stroke patients from 29 comprehensive hospitals who underwent thrombolysis between January 2019 and December 2021. An independent testing cohort was further established, including 1,921 patients from the First People’s Hospital of Shenyang. The structured dataset encompassed 15 variables, including clinical and therapeutic metrics. The primary outcome was the sICH occurrence post-thrombolysis. Models were developed using an 80/20 split for training and internal validation. Performance was assessed using machine learning classifiers, including logistic regression with lasso regularization, support vector machine (SVM), random forest, gradient-boosted decision tree (GBDT), and multilayer perceptron (MLP). The model boasting the highest area under the curve (AUC) was specifically employed to highlight feature importance.ResultsBaseline characteristics were compared between the training cohort (n = 6,369) and the external validation cohort (n = 1,921), with the sICH incidence being slightly higher in the training cohort (1.6%) compared to the validation cohort (1.1%). Among the evaluated models, the logistic regression with lasso regularization achieved the highest AUC of 0.87 (95% confidence interval [CI]: 0.79–0.95; p &lt; 0.001), followed by the MLP model with an AUC of 0.766 (95% CI: 0.637–0.894; p = 0.04). The reference model and SVM showed AUCs of 0.575 and 0.582, respectively, while the random forest and GBDT models performed less optimally with AUCs of 0.536 and 0.436, respectively. Decision curve analysis revealed net benefits primarily for the SVM and MLP models. Feature importance from the logistic regression model emphasized anticoagulation therapy as the most significant negative predictor (coefficient: −2.0833) and recombinant tissue plasminogen activator as the principal positive predictor (coefficient: 0.5082).ConclusionAfter a comprehensive evaluation, the MLP model is recommended due to its superior ability to predict the risk of symptomatic hemorrhage post-thrombolysis in ischemic stroke patients. Based on decision curve analysis, the MLP-based model was chosen and demonstrated enhanced discriminative ability compared to the reference. This model serves as a valuable tool for clinicians, aiding in treatment planning and ensuring more precise forecasting of patient outcomes.