bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional characterization of novel F7 mutations identified in Chinese factor VII‐deficient patients
Authors: Lou Can , Jiang Jiali , Chen Weizhi , Zhang Zhili , Xu Guanqun , Liu Yu , Dai Jing , Ding Qiulan , Wang Xuefeng , Wei Hongying , Wu Youwei , Xu Qin , Wu Wenman 
Published: March 2023

SummaryHereditary factor VII (FVII) deficiency is a rare recessive bleeding disorder with an estimated prevalence of 1/500 000. We had investigated 50 unrelated Chinese patients with FVII deficiency and identified, in total, 25 mutations, including 18 missense mutations and 5 splicing mutations, on the F7 gene. The nucleotide transition c.1224T>G (p.His408Gln) in exon 9 constitutes a hotspot of mutation, with 19 patients harbouring this genetic variance. Few patients were homozygous or compound heterozygous for deleterious mutations, such as non‐sense mutations, large insertion or deletions, indicating that complete deficiency of FVII may not be compatible with life. The eight novel mutations identified in the study, including one small deletion (p.Glu49GlyfsTer101), three type I missense mutations, p.Cys238Phe, p.Gly420Asp, p.Ala252Val and four type II missense mutations, p.Val336Met, p.Ser342Gly, p.Gly432Ser and p.Ile213Asn, were further analysed by in vitro expression and functional studies. The laboratory phenotype and structural analysis confirmed the functional consequence of p.Ile213Asn mutation involving cleavage and activation site. The molecular dynamic simulations and binding energy calculations along with functional probing of p.Gly432Ser mutation revealed the critical role of residue Gly432 in the binding between activated factor VII (factor VIIa) and tissue factor.
Annexin‐A5 and annexin‐A6 silencing prevents metastasis of breast cancer cells in zebrafish
Authors: Gounou Céline , Bouvet Flora , Liet Benjamin , Prouzet‐Mauléon Valérie , d'Agata Léna , Harté Etienne , Argoul Françoise , Siegfried Géraldine , Iggo Richard , Khatib Abdel‐Majid , Bouter Anthony 
Published: March 2023

AbstractBackground InformationDuring tumor invasion and metastasis processes, cancer cells are exposed to major compressive and shearing forces, due to their migration through extracellular matrix, dense cell areas, and complex fluids, which may lead to numerous plasma membrane damages. Cancer cells may survive to these mechanical stresses thanks to an efficient membrane repair machinery. Consequently, this machinery may constitute a relevant target to inhibit cancer cell dissemination.ResultsWe show here that annexin‐A5 (ANXA5) and ANXA6 participate in membrane repair of MDA‐MB‐231 cells, a highly invasive triple‐negative breast cancer cell line. These crucial components of the membrane repair machinery are substantially expressed in breast cancer cells in correlation with their invasive properties. In addition, high expression of ANXA5 and ANXA6 predict poor prognosis in high‐grade lung, gastric, and breast cancers. In zebrafish, the genetic inhibition of ANXA5 and ANXA6 leads to drastic reduction of tumor cell dissemination.ConclusionWe conclude that the inhibition of ANXA5 and ANXA6 prevents membrane repair in cancer cells, which are thus unable to survive to membrane damage during metastasis.SignificanceThis result opens a new therapeutic strategy based on targeting membrane repair machinery to inhibit tumor invasion and metastasis.
Justification for the 2017 periodontitis classification in the light of the Checklist for Modifying Disease Definitions: A narrative review
Authors: Raittio Eero , Baelum Vibeke 
Published: March 2023

AbstractOnce a while, disease classifications have needed revision because new knowledge has accumulated, and new technologies and better treatments have emerged. Changes made to disease classifications should be trustworthy and openly justified. The periodontitis definition and classification system was changed in 2017 by the ‘World Workshop on the Classification of Periodontal and Peri‐Implant Diseases and Conditions’. The workshop, comprising clinicians and researchers, resulted in the production of a 23‐article special issue that introduced the new definitions and classifications of periodontitis. In this narrative review, we critically review how the changes made to the periodontitis definition and classification were justified in the light of the Checklist for Modifying Disease Definitions. Under each of the eight items of the checklist, we have discussed how the item was or could have been considered in the light of the checklist and its guidance. In our view, the new definition and classification of periodontitis was presented in an understandable way, even though the changes from the previous definition were not made visible. However, the issues of (1) estimated changes in prevalence or incidence, (2) triggers for the change, (3) prognostic ability, (4) repeatability or reproducibility, (5) incremental benefits, (6) incremental harms or (7) net benefits and harms related to the introduction of new classification were not considered in the way suggested in the checklist. Thereby, a balanced assessment of potential benefits and harms associated with the new periodontitis classification system was not presented, and to a large extent it remains unknown if the use of the new classification system will provide more net benefits to patients and to the community than previous systems. It is our view that patients and societies deserve transparent and balanced assessments of the potential benefits and harms associated with the periodontitis classification. Importantly, these should reflect the values and preferences also of the patients and the wider community and consider the impact on resource usage.
The Hospital Frailty Risk Score and outcomes in head and neck cancer surgery
Authors: Imam Towhid , Konstant‐Hambling Rob , Flint Helene , Brooks Tracey‐Ann , Patel Nimesh N. , Conroy Simon 
Published: March 2023

AbstractObjectiveThis study aimed to assess if the Hospital Frailty Risk Score (HFRS) could predict outcomes for older people undergoing head and neck procedures.DesignA retrospective cohort study of patients admitted between April 2008 and February 2020, undergoing head and neck procedures defined as major resections using procedural codes.SettingThe analysis was performed using data from the NHS Secondary Uses Service (SUS) electronic database.ParticipantsA number of 7479 patients were selected based on an age of 75 years and above and an admission associated with a diagnostic code associated with a head and neck cancer. Based on HFRS, 5153 patients were risk‐stratified into mild, moderate, and severe frailty risk.Main Outcome MeasuresThe relationships between frailty risk and length of stay, readmission rate, and mortality were quantified using descriptive statistics.ResultsSeverely frail patients had a median length of stay of 9 days compared to 3 for mildly frail patients. Twenty‐seven percentage of severely frail patients were readmitted within 30 days of surgery. Rising levels of frailty correlate with a higher risk of death following surgery which is maintained in longer term mortality at 1 year and until the data were extracted in March 2022. Fifty percentage of moderately frail patients and 66% of severely frail patients had died in hospital by the end of the study period.ConclusionThe results quantify the relationship between frailty and adverse health outcomes. This information could be used to identify those that might benefit from holistic assessment, aid prognostication, commissioning, and service planning.
A randomized, single‐dose, crossover study of the effects of ulotaront on electrocardiogram intervals in subjects with schizophrenia
Authors: Tsukada Hironobu , Milanovic Snezana M. , Darpo Borje , Xue Hongqi , Xiong Kuangnan , Tripp Emily , Lennek Lisa , Worden MaryAlice , Hopkins Seth C. , Galluppi Gerald R. 
Published: March 2023

AbstractThis study (NCT04369391) evaluated the effects of ulotaront (SEP‐363856), a novel trace amine‐associated receptor 1 (TAAR1) agonist in development for schizophrenia, on electrocardiogram parameters. Study design was a randomized, single‐dose, three‐period crossover (ulotaront 150 mg, placebo, moxifloxacin 400 mg). Sixty subjects with schizophrenia completed all periods. Ulotaront had no clinically relevant effect on heart rate, PR interval, or QRS duration. In by‐time‐point analysis (secondary analysis), the upper bound of the two‐sided 90% confidence interval for ΔΔQTcF (QT interval corrected for heart rate using Fridericia's formula) was below 10 ms at all time points for ulotaront. In concentration‐QTc analysis (primary analysis), a linear mixed‐effects model with ulotaront and its major metabolite SEP‐383103 was selected as the primary model based on prespecified criteria. Effect on ∆∆QTcF exceeding 10 ms can be excluded within observed ranges of ulotaront and SEP‐383103 plasma concentrations up to ~574 and ~272 ng/mL, respectively. The upper bound of 90% CI for ΔΔQTcF can be predicted to be below 10 ms at the highest anticipated clinical exposure, currently defined as steady‐state mean Cmax at ulotaront 100 mg/day in CYP2D6 poor metabolizers, ~416 and ~211 ng/mL for ulotaront and SEP‐383103, respectively. Assay sensitivity was demonstrated by the QTc effect caused by moxifloxacin. In conclusion, ulotaront is unlikely to cause clinically relevant QTc prolongation in patients with schizophrenia at the anticipated maximum therapeutic dose.
Triangulating causality between childhood obesity and neurobehavior: Behavioral genetic and longitudinal evidence
Authors: Kulisch Leonard Konstantin , Arumäe Kadri , Briley Daniel A , Vainik Uku 
Published: March 2023

AbstractChildhood obesity is a serious health concern that is not yet fully understood. Previous research has linked obesity with neurobehavioral factors such as behavior, cognition, and brain morphology. The causal directions of these relationships remain mostly untested. We filled this gap by using the Adolescent Brain Cognitive Development study cohort comprising 11,875 children aged 9–10. First, correlations between the age‐ and sex‐specific 95th BMI percentile (%BMIp95) and neurobehavioral measures were cross‐sectionally analyzed. Effects were then aggregated by neurobehavioral domain for causal analyses. Behavioral genetic Direction of Causation modeling was used to test the direction of each relationship. Findings were validated by longitudinal cross‐lagged panel modeling. %BMIp95 correlated with impulsivity, motivation, psychopathology, eating behavior, and cognitive tests (executive functioning, language, memory, perception, working memory). Greater %BMIp95 was also associated with reduced cortical thickness in frontal and temporal brain areas but with increased thickness in parietal and occipital areas. Similar although weaker patterns emerged for cortical surface area and volume. Behavioral genetic modeling suggested causal effects of %BMIp95 on eating behavior (β = 0.26), cognition (β = 0.05), cortical thickness (β = 0.15), and cortical surface area (β = 0.07). Personality/psychopathology (β = 0.09) and eating behavior (β = 0.16) appeared to influence %BMIp95. Longitudinal evidence broadly supported these findings. Results regarding cortical volume were inconsistent. Results supported causal effects of obesity on brain functioning and morphology. The present study highlights the importance of physical health for brain development and may inform interventions aimed at preventing or reducing pediatric obesity.Research Highlights
A continuous measure related to obesity, %BMIp95, has correlations with various measures of brain functioning and structure
Behavioral genetic and longitudinal modeling suggest causal links from personality, psychopathology, and eating behavior to %BMIp95
Results also indicate directional links from %BMIp95 to eating behavior, cognition, cortical thickness, and cortical surface area
Obesity may play a role for healthy brain development during childhood
Heart failure and diabetes: Clinical significance and epidemiology of this two‐way association
Authors: Jerkins Terri , McGill Janet B. , Bell David S. H. 
Published: March 2023

AbstractPeople with type 2 diabetes (T2DM) and those with prediabetes have an increased risk of heart failure (HF). Longer duration of T2DM correlates with a greater risk of HF, but HF is also seen in patients with recent‐onset diabetes. Insulin resistance is more likely to be present in patients with HF. The risk of HF persists even in the face of standard‐of‐care preventive treatments for atherosclerotic cardiovascular (CV) disease. HF is commonly the presenting symptom of CV disease in people with diabetes and is the most expensive complication of diabetes because of the high cost of hospitalizations. Recently hospitalization for HF has been included in CV outcome trials (CVOTs), including for medications that are used to treat T2DM, which has led to new therapies for all HF patients. In addition, these CVOTs have shown that many drugs used in the therapy of diabetes are either neutral or detrimental in the HF patient and should be used with caution in patients with existing HF or those at high risk of HF. Most recently, sodium‐glucose cotransporter‐2 receptor blockers have shown efficacy in both HF with reduced ejection fraction (EF) and HF with preserved EF. The only other oral or injectable diabetes agent shown to improve outcomes in both is metformin.
Rethinking human capital: Perspectives from women working in the informal economy
Authors: Ghore Yogesh , Long Brad , Ozkok Zeynep , Derici Derin 
Published: March 2023

AbstractMotivationThe development of human capital is a priority for most nation states, accelerated by the COVID‐19 global pandemic. In the context of reimagining a “new normal” post‐COVID, we reconsider the concept of human capital, and focus on knowledge, skills, and training of individuals in order to capture aspects of inclusive development.PurposeThis paper shows how the perspective of women, informal sector workers, representing some of the most marginalized workers in society, informs and improves our understanding of human capital and its development and utilization.Methods and approachOur findings are derived from field‐based research conducted over the summer of 2021 in which multiple (virtual) focus group discussions (FGDs) were held with selected members of the Self‐Employed Women's Association (SEWA) in India.FindingsThrough our FGDs, the participants provided new perspectives and insights into our knowledge of human capital, emphasizing the importance of social protection programmes, gender equity, ongoing training opportunities, decentralized supply chains, and income security. Perhaps most significantly, the benefits accrued to women through being organized have been key to unlocking their human capital potential.Policy implicationsOur research highlights themes that are often overlooked in the literature or are beyond the scope of more narrow conceptualizations of human capital. We show that human capital is tightly interwoven with other forms of capital (community assets), and hence efforts to build the former cannot be achieved in isolation from attending to the latter.
Occurrence of brown root rot in Ocean Expo Park, Okinawa, Japan: Infection route and preventive control measures
Authors: Tsujimoto Satoshi , Akiba Mitsuteru , Kameyama Norikazu , Sahashi Norio 
Published: March 2023

AbstractOcean Expo Park, established in 1976 on subtropical Okinawa Island, Japan, has approximately 8000 planted or naturally grown trees in an area of 77.2 ha. Windfall of these trees occurs mainly due to typhoons; wood chips made from the trunks and roots of windfall trees are commonly used as mulching material throughout the park areas, despite possible infection by pathogenic fungi such as Phellinus noxius, the pathogen causing brown root rot. P. noxius is distributed in tropical and subtropical areas worldwide and has a broad host range. The fungus can infect host plants with mycelia via root‐to‐root contact or with basidiospores. Here, we report the current status of tree damage caused by brown root rot in the park and infer the infection routes of P. noxius based on microsatellite markers. Among a total of 294 trees surveyed in the park, P. noxius was isolated from 13 trees of five species. P. noxius was observed more frequently on Ficus microcarpa than on other tree species. Ficus superba var. japonica was identified as a new host species, and Bombax ceiba was first recorded as a host plant of P. noxius in Japan. Among the 13 P. noxius isolates from the diseased trees, 2 isolates from adjacent diseased trees were considered to be of the same genet, while the other 11 isolates were different genets, indicating that infection by basidiospores occurred frequently among trees in the entire park, although spread via root systems also occurred between at least two adjacent trees. An identical genet was not detected at distant locations, which suggests that the disease does not spread via chips. However, mulching with chips can lead to wood decay due to decaying fungi other than P. noxius. Therefore, in accordance with the precautionary principle, the park currently prohibits the chipping and mulching of windfall or damaged trees and is considering disposal methods such as burning.
Safety, feasibility, and neuromuscular activity of acute low‐load resistance exercise with or without blood flow restriction in patients with severe hemophilia
Authors: Calatayud Joaquín , Ogrezeanu Daniel C. , Carrasco Juan J. , Martinez‐Valdes Eduardo , Pérez‐Alenda Sofía , Cruz‐Montecinos Carlos , Andersen Lars L. , Aagaard Per , Suso‐Martí Luís , Casaña José 
Published: March 2023

AbstractObjectiveTo compare the safety, feasibility, and neuromuscular activity of acute low‐load resistance exercise with/without blood flow restriction (BFR) in people with severe hemophilia (PwH).MethodsEight PwH under prophylaxis (5 with resistance training experience) performed 6 randomly ordered conditions of 3 intensity‐matched knee extensions: no external load and no BFR, no external load and light BFR (20% of arterial occlusion pressure [AOP]), no external load and moderate BFR (40% AOP), external low load and no BFR, external low load with light BFR, and external low load with moderate BFR. Rated perceived exertion, pain, exercise tolerability, and adverse effects were assessed. Normalized root‐mean‐square (nRMS), nRMS spatial distribution, and muscle fiber‐conduction velocity (MFCV) were determined using high‐density surface electromyography for the vastus medialis and lateralis.ResultsExercises were tolerated, without pain increases or adverse events. Externally resisted conditions with/without BFR provided greater nRMS than nonexternally resisted conditions (p < 0.05). Spatial distribution and MFCV did not vary between conditions.ConclusionsIn these patients, knee extensions with low external resistance and BFR at 20% or 40% AOP appear safe, feasible and do not cause acute/delayed pain. However, BFR during three consecutive repetitions does not increase nRMS nor changes nRMS spatial distribution or MFCV.
Impact of the source of hematopoietic stem cells on immune reconstitution after transplantation: A systematic review
Authors: Sugiyanto Michael , Gosal Stephanie , Kosim Agatha , Tahapary Dicky Levenus , Sianipar Imelda Rosalyn 
Published: March 2023

AbstractHematopoietic stem cell (HSC) transplantation's success lies in its ability to induce immune reconstitution. To date, there is no review published to compare the immune reconstitution among the three sources of HSC: umbilical cord blood (UCB), bone marrow (BM), and peripheral blood (PB). The review aims to analyze the kinetic of immune reconstitution among UCB, PB, and BM in HSC transplant patients by focusing on natural killer (NK) cells, B and T lymphocytes, and neutrophils. A systematic review was conducted through five databases, searching for clinical trials and randomized control trials (RCTs) which analyze the kinetics of immune reconstitution in at least two sources. Selected studies were assessed with Cochrane RoB 2.0. This review included 14 studies, with a total of 2539 subjects. The PB group achieved the fastest time to neutrophil recovery, while the B‐cell count was the highest in the UCB group. The T‐cell count is the lowest in the BM group, and the NK‐cell count does not differ significantly among the three HSC sources. Among the three sources of HSC, there is no superior HSC source for any immune reconstitution parameter. More studies must be conducted to compare the immune reconstitution and clinical outcomes of all HSC sources in specific diseases.
Effects of constant darkness on behaviour and physiology of male and female mice
Authors: Singh Dhyanendra , Pandey Shalini , Ghosh Arindam , Aich Palok 
Published: March 2023

AbstractA healthy state of life suggests not only a disease‐free condition but also normal psychological functioning and behaviour. To maintain a healthy life, the duration of light exposure is a crucial factor. Perturbation of the standard light–dark cycle (LD: 12 h light‐12 h dark in mice) may result in brain, behavioural and physiological abnormalities. The current study determined the effects of 3 and 5 weeks of constant darkness (DD: 00 h light‐24 h dark) on the behaviour, hormones, prefrontal cortex (PFC) and metabolome of male and female C57BL/6 J mice. We also studied 3 weeks of restoration in LD following 5 weeks of DD exposure. The results revealed that 3 weeks of DD affected male mice more than females, and 5 weeks of DD had a comparable impact on behaviour, hormones and the PFC of male and female mice. After restoration in LD, the DD‐induced changes reverted to time‐matched LD conditions in male and female mice. Furthermore, metabolome analysis corroborated male and female mice's behavioural and molecular kinetics. The present study laid the foundation for understanding how DD affects behaviour and the PFC as a function of (a) time and (b) sex and described the roles of stress and sex hormones, cytokines, neurotrophins and metabolic pathways.