bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Andersen’s model of health care utilization to assess factors associated with COVID-19 testing among adults in nine low-and middle-income countries: an online survey
Authors: Pengid Supa , Peltzer Karl , de Moura Villela Edlaine Faria , Fodjo Joseph Nelson Siewe , Siau Ching Sin , Chen Won Sun , Bono Suzanna A. , Jayasvasti Isareethika , Hasan M. Tasdik , Wanyenze Rhoda K. , Hosseinipour Mina C. , Dolo Housseini , Sessou Philippe , Ditekemena John D. , Colebunders Robert 
Published: February 2022

Abstract
Background
This study aimed to investigate, using Andersen’s model of health care utilization, factors associated with COVID-19 testing among adults in nine low- and middle- income countries.

Methods
In between 10 December 2020 and 9 February 2021, an online survey was organized in nine low- and middle-income countries. In total 10,183 adults (median age 45 years, interquartile range 33–57 years, range 18–93 years), including 6470 from Brazil, 1738 Malaysia, 1124 Thailand, 230 Bangladesh, 219 DR Congo, 159 Benin, 107 Uganda, 81 Malawi and 55 from Mali participated in the study. COVID-19 testing/infection status was assessed by self-report.

Results
Of the 10,183 participants, 40.3% had ever tested for COVID-19, 7.3% tested positive, and 33.0% tested negative. In an adjusted logistic regression model, predisposing factors (residing in Brazil, postgraduate education), enabling/disabling factors (urban residence, higher perceived economic status, being a student or worker in the health care sector, and moderate or severe psychological distress), and need factors (having at least one chronic condition) increased the odds of COVID-19 testing. Among those who were tested, participants residing in Bangladesh, those who had moderate to severe psychological distress were positively associated with COVID-19 positive diagnosis. Participants who are residing in Malaysia and Thailand, and those who had higher education were negatively associated with a COVID-19 positive diagnosis. Considering all participants, higher perceived economic status, being a student or worker in the health sector, and moderate or severe psychological distress were positively associated with a COVID-19 positive diagnosis, and residing in Malaysia, Thailand or five African countries was negatively associated with a COVID-19 positive diagnosis.

Conclusion
A high rate of COVID-19 testing among adults was reported in nine low-and middle-income countries. However, access to testing needs to be increased in Africa. Moreover, COVID-19 testing programmes need to target persons of lower economic status and education level who are less tested but most at risk for COVID-19 infection.
Development and validation of nomogram to predict very early recurrence of combined hepatocellular-cholangiocarcinoma after hepatic resection: a multi-institutional study
Authors: Wu Yijun , Liu Hongzhi , Zeng Jianxing , Chen Yifan , Fang Guoxu , Zhang Jinyu , Zhou Weiping , Zeng Yongyi , Liu Jingfeng 
Published: February 2022

Abstract
Background and objectives
Combined hepatocellular cholangiocarcinoma (cHCC) has a high incidence of early recurrence. The objective of this study is to construct a model predicting very early recurrence (VER) (i.e., recurrence within 6 months after surgery) of cHCC.

Methods
One hundred thirty-one consecutive patients from Eastern Hepatobiliary Surgery Hospital served as a development cohort to construct a nomogram predicting VER by using multi-variable logistic regression analysis. The model was internally and externally validated in a validation cohort of 90 patients from Mengchao Hepatobiliary Hospital using the C concordance statistic, calibration analysis, and decision curve analysis (DCA).

Results
The VER nomogram contains microvascular invasion (MiVI), macrovascular invasion (MaVI), and CA19-9 > 25 mAU/mL. The model shows good discrimination with C-indexes of 0.77 (95% CI: 0.69–0.85) and 0.76 (95% CI: 0.66–0.86) in the development cohort and validation cohort respectively. Decision curve analysis demonstrated that the model is clinically useful and the calibration of our model was favorable. Our model stratified patients into two different risk groups, which exhibited significantly different VER.

Conclusions
Our model demonstrated favorable performance in predicting VER in cHCC patients.
Heterozygous FMN2 missense variant found in a family case of premature ovarian insufficiency
Authors: Li Jie , Peng Tianliu , Wang Le , Long Panpan , Quan Ruping , Tan Hangjing , Zeng Minghua , Wu Xue , Yang Junting , Xiao Hongmei , Shi Xiaobo 
Published: February 2022

Abstract
Background
Premature ovarian insufficiency (POI) plagues 1% of women under 40, while quite a few remain an unknown cause. The development of sequencing has helped find pathogenic genes and reveal the relationship between DNA repair and ovarian reserve. Through the exome sequencing, our study targets screening out the possible POI pathogenic gene and variants in a Chinese family and 20 sporadic POI patients, preliminarily exploring the functional impact and finding out potential linkages between the gene and POI.

Results
The whole exome sequencing suggested a novel FMN2 heterozygous variant c.1949C > T (p.Ser650Leu) carried by all three patients in a Chinese family and another c.1967G > A(p.Arg656His) variant in a sporadic case. Since no FMN2 missense mutation is reported for causing human POI, we preliminarily assessed p.Ser650Leu variant via cross-species alignment and 3D modeling and found it possibly deleterious. A series of functional evidence was consistent with our hypothesis. We proved the expression of FMN2 in different stages of oocytes and observed a statistical difference of chromosomal breakages between the POI patient carrying p.Arg656His variant and the health control (p = 0.0013). Western Blot also suggested a decrease in FMN2 and P21 in the mutant type and an associated increase in H2AX. The p.Arg656His variant with an extremely low frequency also indicated that the gene FMN2 might play an essential role in the genetic etiology of POI. To the best of our knowledge, this is the first POI report on missense variants of FMN2.

Conclusion
This finding indicates a novel gene possibly related to POI and sheds lights on the study of FMN2.
Senescent skeletal cells cross-talk with synovial cells plays a key role in the pathogenesis of osteoarthritis
Authors: Wu Chong-Jie , Liu Ri-Xu , Huan Song-Wei , Tang Wang , Zeng Yu-Kai , Zhang Jun-Cheng , Yang Jie , Li Zhen-Yan , Zhou Ying , Zha Zhen-Gang , Zhang Huan-Tian , Liu Ning 
Published: February 2022

AbstractOsteoarthritis (OA) has been recognized as an age-related degenerative disease commonly seen in the elderly that affects the whole “organ” including cartilage, subchondral bone, synovium, and muscles. An increasing number of studies have suggested that the accumulation of senescent cells triggering by various stresses in the local joint contributes to the pathogenesis of age-related diseases including OA. In this review, we mainly focus on the role of the senescent skeletal cells (chondrocytes, osteoblasts, osteoclasts, osteocyte, and muscle cells) in initiating the development and progression of OA alone or through cross-talk with the macrophages/synovial cells. Accordingly, we summarize the current OA-targeted therapies based on the abovementioned theory, e.g., by eliminating senescent skeletal cells and/or inhibiting the senescence-associated secretory phenotype (SASP) that drives senescence. Furthermore, the existing animal models for the study of OA from the perspective of senescence are highlighted to fill the gap between basic research and clinical applications. Overall, in this review, we systematically assess the current understanding of cellular senescence in OA, which in turn might shed light on the stratified OA treatments.
PSnpBind: a database of mutated binding site protein–ligand complexes constructed using a multithreaded virtual screening workflow
Authors: Ammar Ammar , Cavill Rachel , Evelo Chris , Willighagen Egon 
Published: February 2022

AbstractA key concept in drug design is how natural variants, especially the ones occurring in the binding site of drug targets, affect the inter-individual drug response and efficacy by altering binding affinity. These effects have been studied on very limited and small datasets while, ideally, a large dataset of binding affinity changes due to binding site single-nucleotide polymorphisms (SNPs) is needed for evaluation. However, to the best of our knowledge, such a dataset does not exist. Thus, a reference dataset of ligands binding affinities to proteins with all their reported binding sites’ variants was constructed using a molecular docking approach. Having a large database of protein–ligand complexes covering a wide range of binding pocket mutations and a large small molecules’ landscape is of great importance for several types of studies. For example, developing machine learning algorithms to predict protein–ligand affinity or a SNP effect on it requires an extensive amount of data. In this work, we present PSnpBind: A large database of 0.6 million mutated binding site protein–ligand complexes constructed using a multithreaded virtual screening workflow. It provides a web interface to explore and visualize the protein–ligand complexes and a REST API to programmatically access the different aspects of the database contents. PSnpBind is open source and freely available at https://psnpbind.org.
A detailed time series of hourly circumference variations in Pinus pinea L. in Chile
Authors: Loewe-Muñoz Veronica , del Río Rodrigo , Delard Claudia , Balzarini Mónica 
Published: February 2022

Key messageThe dataset provides digital dendrometer measurements on stem circumference of irrigated and non-irrigated Pinus pinea trees. Data were obtained in a xeric non-native habitat of central Chile. Forest mensuration was hourly collected from six adult trees during a growth year. This data can be re-used to perform different studies, including growth and tree water status temporal correlations, climate-growth relationships, and to compare stone pine stands growing in native and non-native habitats. Such studies could facilitate decisions for the species management and contribute to the understanding of its growth dynamics in a climate change context, providing valuable information for a climate-smart forestry. Dataset access is at https://doi.org/10.5281/zenodo.6010567. Associated metadata are available at metadata-afs.nancy.inra.fr/geonetwork/srv/fre/catalog.search#/metadata/bcea7f69-2cf1-444b-8e5b-e9feb23683db
Incidence and predictors of fragility fracture in postmenopausal rheumatoid arthritis patients receiving oral bisphosphonates: a longitudinal observational study
Authors: Kishimoto Yuji , Kato Yoshihiro , Uemura Manami , Kuranobu Koji 
Published: February 2022

Abstract
Background
Although many studies have reported the predictors of fractures in patients with rheumatoid arthritis (RA) who are not receiving anti-osteoporotic treatments or who are receiving unspecified treatments, studies focusing on the predictors of fracture in patients with RA who are currently being treated with oral bisphosphonates (BP) are quite scarce. This study aims to investigate the incidence and predictors of fragility fracture in postmenopausal patients with RA receiving oral BP.

Methods
This retrospective longitudinal observational study comprised 98 postmenopausal RA patients receiving oral BP for a minimum of 6 months between April 2015 and December 2020. The cumulative incidence of fragility fractures including vertebral and nonvertebral fractures was investigated using the Kaplan–Meier method. Cox proportional hazards analysis was used to analyze baseline predictors of future fragility fractures. To determine a cutoff value of continuous predictors, the receiver-operating characteristic curve was applied.

Results
Twenty patients developed fractures during the study period, with a cumulative incidence of 6.1% at 12 months, 10.5% at a median follow-up of 28 months, and 14.4% at 36 months. Multivariable Cox hazards analysis showed a history of prior vertebral fracture (hazard ratio [HR] 6.26, 95% confidence interval [CI] 1.99‒19.68, P = 0.001) and dose of methotrexate (HR 0.87, 95% CI 0.76‒0.99, P = 0.041) to be independent predictors. The cutoff value for methotrexate dose was 4 mg/week.

Conclusions
We found a cumulative incidence of any fractures of 10.5% at 28 months in patients with RA currently being treated with oral BP. A history of prior vertebral fractures and methotrexate dose were positive and negative predictors for fractures, respectively. Practitioners should consider selecting another anti-osteoporotic drug in patients with RA who remain at risk despite receiving oral BP.
The impact of closed-loop intracortical stimulation on neural activity in brain-injured, anesthetized animals
Authors: Carè Marta , Averna Alberto , Barban Federico , Semprini Marianna , De Michieli Lorenzo , Nudo Randolph J. , Guggenmos David J. , Chiappalone Michela 
Published: February 2022

Abstract
Background
Acquired brain injuries, such as stroke, are a major cause of long-term disability worldwide. Intracortical microstimulation (ICMS) can be used successfully to assist in guiding appropriate connections to restore lost sensorimotor integration. Activity-Dependent Stimulation (ADS) is a specific type of closed-loop ICMS that aims at coupling the activity of two different brain regions by stimulating one in response to activity in the other. Recently, ADS was used to effectively promote behavioral recovery in rodent models following a unilateral traumatic brain injury in the primary motor cortex. While behavioral benefits have been described, the neurophysiological changes in spared areas in response to this type of stimulation have not been fully characterized. Here we explored how single-unit spiking activity is impacted by a focal ischemic lesion and, subsequently, by an ADS treatment.

Methods
Intracortical microelectrode arrays were implanted in the ipsilesional rostral forelimb area (RFA) to record spike activity and to trigger intracortical microstimulation in the primary somatosensory area (S1) of anaesthetized Long Evans rats. An ischemic injury was induced in the caudal forelimb area through microinjections of Endothelin-1. Activity from both RFA and S1 was recorded and analyzed off-line by evaluating possible changes, either induced by the lesion in the Control group or by stimulation in the ADS group.

Results
We found that the ischemic lesion in the motor area led to an overall increase in spike activity within RFA and a decrease in S1 with respect to the baseline condition. Subsequent treatment with ADS increased the firing rate in both RFA and S1. Post-stimulation spiking activity was significantly higher compared to pre-stimulation activity in the ADS animals versus non-stimulated controls. Moreover, stimulation promoted the generation of highly synchronized bursting patterns in both RFA and S1 only in the ADS group.

Conclusions
This study describes the impact on single-unit activity in ipsilesional areas immediately following a cortical infarct and demonstrates that application of ADS is effective in altering this activity.
Intra-arterial application of nimodipine in reversible cerebral vasoconstriction syndrome: a neuroradiological method to help differentiate from primary central nervous system vasculitis
Authors: Strunk Daniel , Veltkamp Roland , Meuth Sven G. , Chapot René , Kraemer Markus 
Published: February 2022

Abstract
Background
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by a prolonged, but self-limiting segmental cerebral vasoconstriction. Neurological outcomes vary, but can be severe. The clinical hallmark of RCVS is thunderclap headache, which might come along with further neurological symptoms. Distinguishing RCVS from other entities, such as primary angiitis of the central nervous system (PACNS), is of utmost importance for appropriate therapy. The angiographic response to intra-arterial nimodipine application has been suggested as an additional diagnostic criterion for RCVS but confirmatory studies are limited. We aimed to evaluate the angiographic nimodipine test.

Methods
We reviewed retrospectively the clinical and imaging data of 13 RCVS patients, who were admitted to a single German neurological department between January 2013 and December 2020.

Results
Out of 13 patients diagnosed with RCVS, 4 patients underwent an angiographic nimodipine test. In all 4 patients cerebral vasoconstriction completely resolved during nimodipine application. Among the four patients with a positive test, there was one individual, in whom a response was detected after a delay of 60 min. In all patients, we found a complete resolution of cerebral vasoconstriction within 12 weeks.

Conclusion
Our findings support the usefulness of the application of nimodipine in diagnosing RCVS. Prolonged angiographic observation of the vascular response after nimodipine injection is important.
Assessment of serum Talin-1 in liver cirrhosis and hepatocellular carcinoma
Authors: Ibrahim El Said H. , Naguib Hend , Emara Doaa M. , El Sayed Eman T. , Tawfik Marwa M. R. 
Published: February 2022

Abstract
Background
Early detection of hepatocellular carcinoma (HCC) is crucial for improving the survival rate for patients. Talin-1 is first identified as a cytoskeleton protein that is required for cell adhesion and motility and plays a role in tumor migration and metastasis. In the present work, we aimed to study the possible role of Talin1 compared to alpha fetoprotein (AFP) in the diagnosis and prognosis of HCC.

Methods
To achieve this goal, serum levels of Talin-1 were measured using enzyme-linked immunosorbent assay (ELISA) in 90 patients divided into four groups. Group I: 30 patients with early HCC. Group II: 30 patients with late HCC according to Modified Barcelona-Clinic Liver Cancer (BCLC). Group III: 15 patients with liver cirrhosis, and group IV: 15 healthy controls. Receiver operating characteristics (ROC) curve analysis was used to create a predictive model for Talin-1 relative to AFP in HCC diagnosis.

Results
It was found that serum Talin-1 in HCC patients was significantly higher compared to its level in cirrhotic patients and the healthy control group. Talin-1 was superior to AFP regarding sensitivity, specificity, positive, and negative predictive value in the diagnosis of HCC. We also found a significant positive correlation between serum Talin-1 and the degree of tumor burden of HCC (BCLC staging), tumor size, and vascular invasion.

Conclusion
Talin-1 holds a promise as a potential marker for HCC diagnosis and prognosis.
Risk of COVID-19 Infections and of Severe Complications Among Survivors of Childhood, Adolescent, and Young Adult Cancer: A Population-Based Study in Ontario, Canada
Authors: Gupta Sumit , Sutradhar Rinku , Alexander Sarah , Science Michelle , Lau Cindy , Nagamuthu Chenthila , Agha Mohammad , Nathan Paul C. , Hodgson David 
Published: February 2022

PURPOSESurvivors of childhood, adolescent, and young adult cancer are at risk of late effects, including pulmonary and infectious complications. Whether survivors are at increased risk of COVID-19 infection and severe complications is unknown.METHODSPopulation-based registries in Ontario, Canada, identified all 5-year survivors of childhood cancer diagnosed age 0-17 years between 1985 and 2014, and of six common adolescent and young adult cancers diagnosed age 15-21 years between 1992 and 2012. Each survivor alive on January 1, 2020, was randomly matched by birth year, sex, and residence to 10 cancer-free population controls. Individuals were linked to population-based laboratory and health care databases to identify COVID-19 tests, vaccinations, infections, and severe outcomes (emergency department [ED] visits, hospitalizations, intensive care unit admissions, and death within 60 days). Demographic, disease, and treatment-related variables were examined as possible predictors of outcomes.RESULTSTwelve thousand four hundred ten survivors were matched to 124,100 controls. Survivors were not at increased risk of receiving a positive COVID-19 test (386 [3.1%] v 3,946 [3.2%]; P = .68) and were more likely to be fully vaccinated (hazard ratio, 1.23; 95 CI, 1.20 to 1.37). No increase in risk among survivors was seen in emergency department visits (adjusted odds ratio, 1.2; 95 CI, 0.9 to 1.6; P = .19) or hospitalization (adjusted odds ratio, 1.8; 95 CI, 1.0 to 3.5; P = .07). No survivor experienced intensive care unit admission or died after COVID-19 infection. Pulmonary radiation or chemotherapies associated with pulmonary toxicity were not associated with increased risk.CONCLUSIONCancer survivors were not at increased risk of COVID-19 infections or severe sequelae. These results can inform risk-counseling of survivors and their caregivers. Further study is warranted to determine risk in older survivors, specific subsets of survivors, and that associated with novel COVID-19 variants.
Dynamic Changes of Reproductive Hormones in Male Minipuberty: Temporal Dissociation of Leydig and Sertoli Cell Activity
Authors: Busch Alexander Siegfried , Ljubicic Marie Lindhardt , Upners Emmie N , Fischer Margit Bistrup , Raket Lars Lau , Frederiksen Hanne , Albrethsen Jakob , Johannsen Trine Holm , Hagen Casper P , Juul Anders 
Published: February 2022

Abstract

Context
The male hypothalamic-pituitary-gonadal (HPG) axis is transiently active during the first months of life with surging serum concentrations of reproductive hormones. This period, termed minipuberty, appears to be essential for priming testicular function. Despite the central role for male reproductive function, longitudinal data on HPG axis activation in infancy is sparse.

Objective
To explore the dynamics of HPG hormone activity in healthy male infants, to assess the association of HPG axis activity and testicular volume, and to establish reference curves for serum levels of reproductive hormones.

Design
Prospective, longitudinal birth cohort (the COPENHAGEN Minipuberty Study, 2016-2018, 1-year follow-up).

Setting
Population-based.

Patients or Other Participants
Healthy, male, term, singleton newborns were followed from birth on with repeated clinical examinations including blood sampling during a 1-year follow-up. A total of 128 boys contributed to this study, while 119 participated in the postnatal follow-up.

Main Outcome Measures
Serum reproductive hormone concentrations and testicular volume.

Results
Reproductive hormone concentrations showed marked dynamics during the first 6 months of age. Gonadotropins, total testosterone, and insulin-like factor 3 peaked at around 1 month of age. Inhibin B, anti-Müllerian hormone, and testicular volume peaked at around 4 to 5 months. Correlations largely recapitulated typical HPG axis pathways but also differed significantly from adult men.

Conclusions
We demonstrate a temporal dissociation of Leydig and Sertoli cell activity during male minipuberty and provide reference curves for reproductive hormones.
Gynoecium and fruit development in Arabidopsis
Authors: Herrera-Ubaldo Humberto , de Folter Stefan 
Published: February 2022

ABSTRACT
Flowering plants produce flowers and one of the most complex floral structures is the pistil or the gynoecium. All the floral organs differentiate from the floral meristem. Various reviews exist on molecular mechanisms controlling reproductive development, but most focus on a short time window and there has been no recent review on the complete developmental time frame of gynoecium and fruit formation. Here, we highlight recent discoveries, including the players, interactions and mechanisms that govern gynoecium and fruit development in Arabidopsis. We also present the currently known gene regulatory networks from gynoecium initiation until fruit maturation.