bluuebunny/crossref_metadata_2025_split huggingface dataset:
Segmented Correspondence Curve Regression for Quantifying Covariate Effects on the Reproducibility of High-Throughput Experiments
Authors: Zhang Feipeng , Li Qunhua 
Published: September 2022

Abstract
High-throughput biological experiments are essential tools for identifying biologically interesting candidates in large-scale omics studies. The results of a high-throughput biological experiment rely heavily on the operational factors chosen in its experimental and data-analytic procedures. Understanding how these operational factors influence the reproducibility of the experimental outcome is critical for selecting the optimal parameter settings and designing reliable high-throughput workflows. However, the influence of an operational factor may differ between strong and weak candidates in a high-throughput experiment, complicating the selection of parameter settings. To address this issue, we propose a novel segmented regression model, called segmented correspondence curve regression, to assess the influence of operational factors on the reproducibility of high-throughput experiments. Our model dissects the heterogeneous effects of operational factors on strong and weak candidates, providing a principled way to select operational parameters. Based on this framework, we also develop a sup-likelihood ratio test for the existence of heterogeneity. Simulation studies show that our estimation and testing procedures yield well-calibrated type I errors and are substantially more powerful in detecting and locating the differences in reproducibility across workflows than the existing method. Using this model, we investigated an important design question for ChIP-seq experiments: How many reads should one sequence to obtain reliable results in a cost-effective way? Our results reveal new insights into the impact of sequencing depth on the binding-site identification reproducibility, helping biologists determine the most cost-effective sequencing depth to achieve sufficient reproducibility for their study goals.
LAMP‐2A ablation in hippocampal CA1 astrocytes confers cerebroprotection and ameliorates neuronal injury after global brain ischemia
Authors: Fu Han‐Yu , Cui Yang , Li Qiao , Wang Ding , Li Hui , Yang Long , Wang De‐Juan , Zhou Jing‐Wei 
Published: September 2022

AbstractReactive astrogliosis and neuronal death are major features of brain tissue damage after transient global cerebral ischemia/reperfusion (I/R). The CA1 subfield in the hippocampus is particularly susceptible to cell death after I/R. Recently, attention has focused on the relationship between the autophagy–lysosomal pathway and cerebral ischemia. Lysosomal‐associated membrane protein type‐2A (LAMP‐2A) is a key protein in chaperone‐mediated autophagy (CMA). However, LAMP‐2A expression in astrocytes of the hippocampus and its influence on brain injury following I/R remain unknown. Here, we show that LAMP‐2A is elevated in astrocytes of the CA1 hippocampal subfield after I/R and in primary cultured astrocytes after transient oxygen–glucose deprivation (OGD). Conditional LAMP‐2A knockdown in CA1 astrocytes inhibited astrocyte activation and prevented neuronal death by inhibiting the mitochondrial pathway of apoptosis after I/R, suggesting that elevated astrocytic LAMP‐2A contributes to regional ischemic vulnerability. Furthermore, astrocytic LAMP‐2A ablation ameliorated the spatial learning and memory deficits caused by I/R. Conditional astrocytic LAMP‐2A knockdown also prevented the loss of hippocampal synapses and dendritic spines, improved the synaptic ultrastructure, and inhibited the reduced expression of synaptic proteins after ischemia. Thus, our findings demonstrate that astrocytic LAMP‐2A expression increases upon I/R and that LAMP‐2A ablation specifically in hippocampal astrocytes contributes to cerebroprotection, suggesting a novel neuroprotective strategy for patients with global ischemia.
Combination therapy of lymphatic drug delivery and total body irradiation in a metastatic lymph node and lung mouse model
Authors: Sora Shota , Sukhbaatar Ariunbuyan , Fukushige Shinichi , Mori Shiro , Sakamoto Maya , Kodama Tetsuya 
Published: September 2022

AbstractChemotherapy using a lymphatic drug delivery system (LDDS) targeting lymph nodes (LNs) in the early stage of metastasis has a superior antitumor effect to systemic chemotherapy. An LDDS produces a higher drug retention rate and tissue selectivity in LNs. To expand the therapeutic coverage of LDDS from local treatment of metastatic LNs to prevention of distant metastases, the combination of treatment with therapies that enhance systemic tumor immune effects is an important therapeutic strategy. Recently, total body irradiation (TBI) has been shown to activate immune responses and alter the tumor microenvironment. Here we show that combination therapy with TBI and LDDS improves the antitumor effect of metastatic LNs and lung metastasis. Tumor cells were inoculated into the subiliac LN (SiLN) to induce metastasis into the proper axillary LN (PALN) and lung in a mouse model. TBI was carried out on day 4 after inoculation using a gamma irradiator. Lymphatic drug delivery into the accessory axillary LN was used to treat PALN. In vivo bioluminescence imaging, high‐frequency ultrasound, and histology showed that combination therapy using TBI (total dose 1.0 Gy once) and the LDDS suppressed tumor growth in LNs and lung metastases and was more effective than using LDDS or TBI alone. Quantitative RT‐PCR of spleens after combination therapy revealed increased expression of CD4, CD8, and IL‐12b, indicating an activated immune response. The results show that combination therapy with TBI and LDDS is a method to improve the efficacy of LN metastases and distant metastases therapy and is a promising novel approach to treat cancer patients.
Adjuvant atezolizumab in Japanese patients with resected stage IB‐IIIA non‐small cell lung cancer (IMpower010)
Authors: Kenmotsu Hirotsugu , Sugawara Shunichi , Watanabe Yasutaka , Saito Haruhiro , Okada Morihito , Chen‐Yoshikawa Toyofumi Fengshi , Ohe Yuichiro , Nishio Wataru , Nakagawa Shizuka , Nagao Haruka 
Published: September 2022

AbstractThe global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum‐based chemotherapy in patients with resected stage IB–IIIA non‐small cell lung cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)–IIIA NSCLC. Upon completing 1–4 cycles of adjuvant cisplatin‐based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator‐assessed disease‐free survival, tested hierarchically first in patients with stage II–IIIA NSCLC whose tumors expressed programmed death‐ligand 1 (PD‐L1) on ≥1% of tumor cells, then in all randomized patients with stage II–IIIA NSCLC, and finally in the intention‐to‐treat (ITT) population (stage IB–IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all‐randomized stage II–IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD‐L1 tumor cells ≥1% stage II–IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease‐free survival improvement with atezolizumab vs BSC was observed in the PD‐L1 tumor cells ≥1% stage II–IIIA (unstratified hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.25–1.08), all‐randomized stage II–IIIA (unstratified HR, 0.62; 95% CI, 0.35–1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34–1.10) populations. Atezolizumab‐related grade 3/4 adverse events occurred in 16% of patients; no treatment‐related grade 5 events occurred. Adjuvant atezolizumab showed disease‐free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.
MiR‐22‐3p in exosomes increases the risk of heart failure after down‐regulation of FURIN
Authors: Lu Wenlin , Liu Xuhui , Zhao Linghui , Yan Shirong , Song Qingyun , Zou Cao , Li Xun 
Published: September 2022

AbstractHeart failure (HF) is often the inevitable manifestation of myocardial ischemia. Hypoxia can induce cardiomyocytes to express many microRNAs (miRNAs), which are highly expressed in exosomes. In addition, miR‐22‐3p is a marker in heart failure. Therefore, miR‐22‐3p was taken as the research object to explore its role and mechanism in HF. HF differentially expressed miRNAs were screened by bioinformatic analysis. The HF rats model was constructed and identified by detecting serum brain natriuretic peptide (BNP) and ultrasound analysis [left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS)]. The extracted exosomes were identified by transmission electron microscopy, and Western blot was used to detect the expressions of Tsg101 and CD63. Quantitative real‐time polymerase chain reaction detected miR‐22‐3p expression in serum, exosomes, and serum without exosomes, while the cardiomyocytes cytotoxicity was detected by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and PKH26 staining. After overexpressing/silencing miR‐22‐3p in cells, cell viability, apoptosis, and apoptosis‐associated markers were detected. Bioinformatic analysis screened the target gene of miR‐22‐3p, which was verified by dual‐luciferase assay. Regulation of miR‐22‐3p on FURIN was measured by rescue tests. In vivo experiments were verified the above results. MiR‐22‐3p was identified as the research object. BNP was increased in the model group, while LVEF and LVFS were decreased. MiR‐22‐3p was overexpressed in HF‐treated serum and exosomes. Normal exosomes did not affect cardiomyocyte function, while high concentrations of HF‐treated exosomes were cytotoxic. By regulating apoptosis‐related genes, overexpressed miR‐22‐3p inhibited cell activity and promoted cell apoptosis. Silenced miR‐22‐3p with opposite effects counteracted effects of HF‐treated exosomes. FURIN, target gene of miR‐22‐3p, was negatively regulated by miR‐22‐3p, while overexpressed FURIN promoted cell activity and inhibited apoptosis. In vivo research was consistent with the results of cell experiments. By regulating FURIN, miR‐22‐3p in exosomes increases the risk of HF damage.
Variation in caregivers' references to their toddlers: Child‐directed speech in Vanuatu and Canada
Authors: Cebioğlu Senay , Marin Kelly A. , Broesch Tanya 
Published: September 2022

AbstractThe authors examined similarities and differences in Canadian and ni‐Vanuatu caregivers' child‐directed speech to their toddlers (N = 35, Mage: 21 months, 20 girls). Speech samples were collected (2013–2016) during free play and analyzed with a focus on describing parents' references to their toddlers. Canadian caregivers referred significantly more to toddlers' tangible characteristics (relative risk, RR = 2.12) and internal states (RR = 2.31), whereas ni‐Vanuatu caregivers referred more to actions (RR = 2.04). When referring to internal states, Canadian mothers referred significantly more to mind‐minded states, whereas ni‐Vanuatu caregivers referred more to body‐minded states (RR = 7.98). These findings are interpreted as capturing meaningful differences in toddlers' opportunities to attend to themselves. Implications for self‐concept development are discussed.
Finding methods for the inclusion of all children: Advancing participatory research with children with disabilities
Authors: Tiefenbacher Rebecka 
Published: September 2022

AbstractThis method‐focused article continues the discussion of how methodological challenges in research with children with disabilities can be overcome. By examining the difficulties in introducing walk‐and‐talk conversations in an ethnographic study with young children (3–11 years) with disabilities, it asks what doing research ‘with’ means and on whose terms research should take place. The article argues for a shift in the understanding of doing ‘with’, from a researcher‐controlled research encounter to the focusing of children's own activities. This ensures the participation of all children in research, by recognizing and listening to the many different ways in which children communicate.
Lung function in Lolland‐Falster Health Study (LOFUS)
Authors: Jacobsen Katja Kemp , Jepsen Randi , Bodtger Uffe , Rasmussen Knud , St‐Martin Gry 
Published: September 2022

AbstractBackgroundCOPD prevalence in Denmark is estimated at 18% based on data from urban populations. However, studies suggest that using the clinical cut‐off for airway obstruction in population studies may overestimate prevalence. The present study aims to compare estimated prevalence of airway obstruction using different cut‐offs and to present lung function data from the Lolland‐Falster Health Study, set in a rural‐provincial area.MethodsDescriptive analysis of participant characteristics and self‐reported respiratory disease and of spirometry results in the total population and in subgroups defined by these characteristics. Airway obstruction was assessed using previously published Danish reference values and defined according to either FEV1/FVC below lower limit of normal (LLN) 5% (as in clinical diagnosis) or 2.5% (suggested for population studies), or as FEV1/FVC < 70%.ResultsUsing either FEV1/FVC < 70% or LLN 5% cut‐off, 19.0% of LOFUS participants aged 35 years or older had spirometry, suggesting airway obstruction. By the LLN 2.5% criterion, the proportion was considerably lower, 12.2%. The prevalence of airway obstruction was higher among current smokers, in participants with short education or reporting low leisure‐time physical activity and in those with known respiratory disease. Approximately 40% of participants reporting known respiratory disease had normal spirometry, and 8.7% without known respiratory disease had airway obstruction.ConclusionPrevalence of airway obstruction in this rural population was comparable to previous estimates from urban Danish population studies. The choice of cut‐off impacts the estimated prevalence, and using the FEV1/FVC cut‐off may overestimate prevalence. However, many participants with known respiratory disease had normal spirometry in this health study.
Clinical significance of prediabetes, undiagnosed diabetes and diagnosed diabetes on critical outcomes in COVID‐19: Integrative analysis from the JapanCOVID‐19 task force
Authors: Fukushima Takahiro , Chubachi Shotaro , Namkoong Ho , Asakura Takanori , Tanaka Hiromu , Lee Ho , Azekawa Shuhei , Okada Yukinori , Koike Ryuji , Kimura Akinori , Imoto Seiya , Miyano Satoru , Ogawa Seishi , Kanai Takanori , Fukunaga Koichi ,   The Japan COVID‐19 Task Force
Published: September 2022

AbstractAimDiabetes mellitus (DM) is a known risk factor for severe coronavirus disease 2019 (COVID‐19), but the clinical impact of undiagnosed diabetes and prediabetes in COVID‐19 are unclear particularly in Japan. We clarify the difference in clinical characteristics, including age, sex, body mass index and co‐morbidities, laboratory findings and critical outcomes, in a large Japanese COVID‐19 cohort without diabetes, with prediabetes, undiagnosed diabetes and diagnosed diabetes, and to identify associated risk factors.Materials and MethodsThis multicentre, retrospective cohort study used the Japan COVID‐19 Task Force database, which included data on 2430 hospitalized COVID‐19 patients from over 70 hospitals from February 2020 to October 2021. The prevalence of prediabetes, undiagnosed diabetes and diagnosed diabetes were estimated based on HbA1c levels or a clinical diabetes history. Critical outcomes were defined as the use of high‐flow oxygen, invasive positive‐pressure ventilation or extracorporeal membrane oxygenation, or death during hospitalization.ResultsPrediabetes, undiagnosed diabetes and diagnosed diabetes were observed in 40.9%, 10.0% and 23.0%, respectively. Similar to diagnosed diabetes, prediabetes and undiagnosed diabetes were risk factors for critical COVID‐19 outcomes (adjusted odds ratio [aOR] [95% CI]: 2.13 [1.31‐3.48] and 4.00 [2.19‐7.28], respectively). HbA1c was associated with COVID‐19 severity in prediabetes patients (aOR [95% CI]: 11.2 [3.49‐36.3]), but not other groups.ConclusionsWe documented the clinical characteristics and outcomes of Japanese COVID‐19 patients according to HbA1c levels or diabetes co‐morbidity. As well as undiagnosed and diagnosed diabetes, physicians should be aware of prediabetes related to COVID‐19 severity.
From dogmatic slumber to rationalist nightmares: Kant among the dreamers of reason
Authors: Stratmann Joe 
Published: September 2022

AbstractWhat awakened Kant from his dogmatic slumber? On the traditional narrative, he was awakened by Hume's challenge to our cognition of causal connections. A more recent narrative claims that he was awakened by Hume's challenge to our cognition of non‐logical connections more generally. In this paper, I argue that a key part of Kant's awakening was far wider‐reaching: he came to realize that all dogmas must be abandoned. An oft‐overlooked technical notion, dogmas are non‐logical principles cognizable to unaided human reason. I detail how Kant repudiated dogmas by the mid‐1760's in engaging with his German predecessor, Christian Crusius. This repudiation lays the foundation for his critical project. For once liberated of dogmas, reason must look beyond itself for the principles that would enable rational cognitionof non‐logical connections.
Risk of future stroke in patients with a diagnosis of peripheral vertigo in the emergency department
Authors: Choi Jeong‐Yoon , Kim Seok , Boo Dachung , Yoo Sooyoung , Kim Hyo‐Jung , Kim Jun Yup , Lee Keon‐Joo , Kang Jihoon , Kim Beom Joon , Han Moon‐Ku , Bae Hee‐Joon , Kim Ji‐Soo 
Published: September 2022

AbstractBackground and purposeThe temporal characteristics of stroke risks were evaluated in emergency department patients who had a diagnosis of peripheral vertigo. It was also attempted to reveal the stroke risk factor amongst those with peripheral vertigo.MethodsThis is a parallel‐group cohort study in a tertiary referral hospital. After assigning each of 4367 matched patients to the comparative set of peripheral vertigo and appendicitis‐ureterolithiasis groups and each of 4911 matched patients to the comparative set of peripheral vertigo and ischaemic stroke groups, the relative stroke risk was evaluated. In addition, to predict the individual stroke risk in patients with peripheral vertigo, any association between the demographic factors and stroke events was evaluated in the peripheral vertigo group.ResultsThe peripheral vertigo group had a higher stroke risk than the appendicitis‐ureterolithiasis group (hazard ratio 1.73, 95% confidence interval 1.18–2.55) but a lower risk than the ischaemic stroke group (hazard ratio 0.30, 95% confidence interval 0.24–0.37). The stroke risk of the peripheral vertigo group was just below that of small vessel stroke. The stroke risk of the peripheral vertigo group differed markedly by time: higher within 7 days, moderate between 7 days and 1 year, and diminished thereafter. Old age (>65 years), male gender and diabetes mellitus were the risk factors for stroke in the peripheral vertigo group.ConclusionPatients with a diagnosis of peripheral vertigo in the emergency department showed a moderate future stroke risk and so a stroke preventive strategy tailored to the timing of symptom onset and individual risk is required.
Cutting edge technologies in chronic inflammation research
Authors: Laman Jon D. 
Published: September 2022

AbstractThis concise review provides the broad background and selection from the literature for a Keynote lecture at EHSF 2022 on state of the art technologies in inflammation research, with an emphasis on disease of the skin and the nervous system. The value of ex vivo skin explant models is discussed, as well as the innovative use of animal models, wherein the crucial roles of antigen experience and “wild” microbiota are emphasized. Spectral flow cytometry allowing large surface marker panels to be explored is touched upon, as well as multiplex technology for cytokines and other analytes important for inflammation and tissue damage. Single‐cell sequencing and in situ transcriptomics (spatial profiling) now provide exciting granular information on functional cell subsets, interactions and plasticity. A selection of novel research and diagnostic tools for antibodies against linear peptides or gangliosides is presented. Finally, the review discusses a new anti‐inflammatory strategy against skin inflammation with a panel of protease inhibitors derived from the protein fraction of industrial starch potatoes.
Climate drives the spatiotemporal dynamics of scrub typhus in China
Authors: Ding Fangyu , Wang Qian , Hao Mengmeng , Maude Richard James , John Day Nicholas Philip , Lai Shengjie , Chen Shuai , Fang Liqun , Ma Tian , Zheng Canjun , Jiang Dong 
Published: September 2022

AbstractScrub typhus is a climate‐sensitive and life‐threatening vector‐borne disease that poses a growing public health threat. Although the climate‐epidemic associations of many vector‐borne diseases have been studied for decades, the impacts of climate on scrub typhus remain poorly understood, especially in the context of global warming. Here we incorporate Chinese national surveillance data on scrub typhus from 2010 to 2019 into a climate‐driven generalized additive mixed model to explain the spatiotemporal dynamics of this disease and predict how it may be affected by climate change under various representative concentration pathways (RCPs) for three future time periods (the 2030s, 2050s, and 2080s). Our results demonstrate that temperature, precipitation, and relative humidity play key roles in driving the seasonal epidemic of scrub typhus in mainland China with a 2‐month lag. Our findings show that the change of projected spatiotemporal dynamics of scrub typhus will be heterogeneous and will depend on specific combinations of regional climate conditions in future climate scenarios. Our results contribute to a better understanding of spatiotemporal dynamics of scrub typhus, which can help public health authorities refine their prevention and control measures to reduce the risks resulting from climate change.