bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive reprogramming of protein isoforms and histopathological alterations in the midgut of Anticarsia gemmatalis fed with protease inhibitors
Authors: Coura Roberta Ribeiro , da Silva Junior Neilier Rodrigues , Meriño‐Cabrera Yaremis , Díez Juan Diego Rios , Barros Rafael Almeida , Barbosa Samuel Lessa , de Oliveira João Vitor Aguilar , da Rocha Gabriele Corrêa , Serrão José Eduardo , de Oliveira Ramos Humberto Josué , de Almeida Oliveira Maria Goreti 
Published: October 2021

AbstractProtease inhibitors (PIs) interfere with digestion, leading to poor nutrient absorption and decreasing amino acid availability in insects. Ingestion of PIs can delay development, cause anatomical malformations, reduce fertility and change the set of proteases in the insect gut. This study evaluated the proteomic profile in the midgut of Anticarsia gemmatalis fed on synthetic (Berenil® with a bis‐benzamidine as active ingredient) and natural (SKTI) protease inhibitors and their effect on the gut physiology, proteolytic activity and the structural characteristics of the trypsin‐inhibitor binding. Larger numbers of protein isoforms were identified specially related to protease activity and stress processes, being that the synthetic PI triggered a lower reprogramming than SKTI. Furthermore, Berenil also promoted higher reduction on midgut protease activity at first times of PI treatment. Molecular modelling of the interactions between the identified proteases and PIs indicated that Berenil can interact with the trypsin enzymes and access to a more hydrophobic site promoting the inhibitory effect on serine proteases. Besides, its inhibitory capacity and structural damage on the midgut cells was sped up possibly by the delay in the expression of proteases, the reprogramming less extensive and the lower expression of upregulated isoforms. Thus, the integration of our results shows that the use of synthetic PIs, such as Berenil, can be efficient for the management of A. gemmatalis.
Low hatching success in the critically endangered kākāpō is driven by early embryo mortality not infertility
Authors: Savage J. L. , Crane J. M. S. ,   Kākāpō Recovery Team, Hemmings N. 
Published: October 2021

AbstractIn many endangered species, reproductive failure is a major barrier to recovery. The critically endangered kākāpō Strigops habroptilus exemplifies this challenge: 61% of their eggs fail to hatch, and of these 73% show no sign of development. Undeveloped eggs have previously been attributed to male infertility, but recent studies of non‐threatened bird species suggest fertilisation failure is rare in the wild. The underlying causes of fertilisation failure and embryo death differ, so distinguishing between them is essential for effective conservation management. Here we show that the majority (72%, n = 124) of undeveloped kākāpō eggs are fertilised, and combine this with conservation programme data on natural copulations, artificial inseminations, and paternity of developed eggs, to generate the most precise estimate to date of fertility in a wild population. We also demonstrate, for the first time in a wild bird, that artificial insemination results in greater numbers of sperm reaching the egg.
A novel statistical test for treatment differences in clinical trials using a response‐adaptive forward‐looking Gittins Index Rule
Authors: Barnett Helen Yvette , Villar Sofía S. , Geys Helena , Jaki Thomas 
Published: October 2021

AbstractThe most common objective for response‐adaptive clinical trials is to seek to ensure that patients within a trial have a high chance of receiving the best treatment available by altering the chance of allocation on the basis of accumulating data. Approaches that yield good patient benefit properties suffer from low power from a frequentist perspective when testing for a treatment difference at the end of the study due to the high imbalance in treatment allocations. In this work we develop an alternative pairwise test for treatment difference on the basis of allocation probabilities of the covariate‐adjusted response‐adaptive randomization with forward‐looking Gittins Index (CARA‐FLGI) Rule for binary responses. The performance of the novel test is evaluated in simulations for two‐armed studies and then its applications to multiarmed studies are illustrated. The proposed test has markedly improved power over the traditional Fisher exact test when this class of nonmyopic response adaptation is used. We also find that the test's power is close to the power of a Fisher exact test under equal randomization.
“How am I going to make it through pregnancy?” A qualitative examination of prenatal maternal stress
Authors: Mahaffey Brittain L , Tilley Jacqueline L , Molina Lucero K , Gonzalez Adam , Park Elyse , Lobel Marci 
Published: October 2021

AbstractBackgroundPrenatal maternal stress (PNMS) is common among childbearing women, and there is substantial evidence that persistent high levels of stress during pregnancy are associated with adverse birth outcomes and poorer postpartum mental health. Therefore, the purpose of this study was to examine the idiographic experiences of women who experienced elevated PNMS during their current or most recent pregnancy.MethodsSix focus groups were conducted, and data were collected from 26 women (n = 16 pregnant and n = 10 postpartum) at a large medical center in the United States (US). Data from the semi‐structured focus group prompts were analyzed by two independent raters using conventional content analysis21.ResultsThree key themes emerged from the data: (1) Navigating Changing Circumstances, (2) Being a “Good” Mother, and (3) Loss of Control and Autonomy.DiscussionThe current study offers one of the first in‐depth examinations of the experiences of highly stressed pregnant women using a qualitative approach and identifies stressors rarely described in quantitative research. These findings suggest that women's ability to prioritize their self‐care, and receive structural/institutional supports in the workplace and instrumental support at home, and overall health literacy promote successful coping with stress and highlight important future directions for intervention.
Uncovering mechanisms of seed predation by fish
Authors: Carvalho Lucélia Nobre , dos Santos Júnior João Batista , Correa Sandra Bibiana 
Published: October 2021

AbstractOur experiment revealed unexpected behavioral strategies involved in seed predation of Mabea fistulifera by fish (Brycon cephalus), including temporal storage of seeds in the stomach followed by regurgitation and reingestion of individual seeds. Larger fish were faster at removing the seed coat and exposing the endosperm, due to precise oral manipulation of seeds.Abstract in Portuguese is available with online material
Valence bias in metacontrol of decision making in adolescents and young adults
Authors: Bolenz Florian , Eppinger Ben 
Published: October 2021

AbstractThe development of metacontrol of decision making and its susceptibility to framing effects were investigated in a sample of 201 adolescents and adults in Germany (12–25 years, 111 female, ethnicity not recorded). In a task that dissociates model‐free and model‐based decision making, outcome magnitude and outcome valence were manipulated. Both adolescents and adults showed metacontrol and metacontrol tended to increase across adolescence. Furthermore, model‐based decision making was more pronounced for loss compared to gain frames but there was no evidence that this framing effect differed with age. Thus, the strategic adaptation of decision making continues to develop into young adulthood and for both adolescents and adults, losses increase the motivation to invest cognitive resources into an effortful decision‐making strategy.
Anti‐B cell therapies in multiple sclerosis
Authors: Kufukihara Kenji 
Published: October 2021

AbstractMultiple sclerosis (MS) has long been considered a T‐cell‐mediated autoimmune disease of the central nervous system. However, newer evidence shows that B cells play a crucial role in the pathogenesis of MS via antibody production, antigen presentation, T cell stimulation and activation, and production of pro‐inflammatory cytokines. Developing B cells express the CD20 molecule from the pre‐B cell to the plasmablast stage, and the anti‐CD20 monoclonal antibodies rituximab, ocrelizumab, ofatumumab and ublituximab are either in use or are being developed for treatment of MS as B cell‐depleting therapies. They have shown profound efficacy in strongly suppressing relapse and radiological disease activity. Another promising approach is the inhibition of Bruton’s tyrosine kinase (BTK), a key enzyme that is intricately involved in signaling from the B cell antigen receptor and the Fc receptors in B cells and myeloid cells. BTK is considered to play an essential role for differentiation and survival of B‐lineage cells, and BTK inhibition may dampen not only B cell activation but also innate immune activation in MS. Trials of BTK inhibitors are ongoing to establish their efficacy and safety in relapsing and progressive MS. The main safety issue with persistent B cell depletion is an increased risk of infection, possibly including an increased risk of severe COVID‐19; unfortunately, vaccine responses against COVID‐19 may also be blunted by anti‐CD20 monoclonal antibodies.
Patent landscape report on dental implants: A technical analysis
Authors: Cho Young‐Dan , Kim Woo‐Jin , Ryoo Hyun‐Mo , Ku Young 
Published: October 2021

AbstractBackground and purposeSignificant research and development (R&D) has been conducted to make the best dental implants while developing various patent applications and registrations. In this study, we evaluated the current status of patents on dental implants and identified the future direction of R&D progress.Materials and methodsA total of 29 711 patents related to dental implants were reviewed. These were published between 1909 and 2020 and retrieved from the Derwent Innovation patent database. The patents were grouped into three categories depending on the implant components: fixture, abutment, and artificial teeth.ResultsThe category with most patents was “abutment,” and the most cited patent was “screw‐type dental implant anchor.” Global patenting trends over the past 20 years showed that both applicants and applications increased in the early 2010s; however, these have since been on the decline. Currently, the United States holds the largest number of patents, and Nobel Biocare Holding AG is the top assignee. Technic maturation prediction analysis showed that the current dental implant technology is in the “decline stage.”ConclusionTrend analysis of the dental implant patent indicates the main contributors of development are profit‐oriented companies. Recent reduction in the number of new patent applications suggests the technology is in the mature declining stage. The emergence of new materials or technologies that may close the gap in clinical unmet needs would reverse the trend.
A modified conditioning regimen based on low‐dose cyclophosphamide and fludarabine for haploidentical hematopoietic stem cell transplant in severe aplastic anemia patients at risk of severe cardiotoxicity
Authors: Lin Fan , Zhang Yuanyuan , Han Tingting , Cheng Yifei , Mo Xiaodong , Wang Jingzhi , Chen Yuhong , Wang Fengrong , Tang Feifei , Han Wei , Yan Chenhua , Xu Zhengli , Zhang Xiaohui , Wang Yu , Huang Xiaojun , Xu Lanping 
Published: October 2021

AbstractSevere cardiotoxicity is a fatal complication during high‐dose cyclophosphamide (Cy)‐based conditioning in hematopoietic stem cell transplant (HSCT) for severe aplastic anemia (SAA). This study aimed to evaluate the feasibility and efficacy of a modified conditioning regimen in haploidentical HSCT (haplo‐HSCT) for severe‐cardiotoxic‐risk SAA patients. This BuCylowFlu conditioning utilized busulfan (Bu, 3.2 mg/kg for 2 days), low‐dose Cy (100 mg/kg), fludarabine (150 mg/m2), and rabbit antithymocyte globulin (rATG, 10 mg/kg). Compared to BuCy conditioning using high‐dose Cy of 200 mg/kg, Bu of 3.2 mg/kg for 2 days, and rATG of 10 mg/kg, the incidence of severe cardiotoxicity of BuCylowFlu conditioning was significantly decreased (2.17% vs 12.80%, p = .032). The engraftment rates (100% for neutrophil and 84.44% for platelet) were favorable. The probabilities of 100‐day transplant‐related mortality were similar in the BuCylowFlu and the BuCy group (8.75% vs 10.53%, p = .671). Both 1‐year overall survival (88.79% vs 84.66%, p = .357) and 1‐year failure‐free survival (84.78% vs 81.70%, p = .535) were comparable. The BuCylowFlu group had higher rates of cytomegalovirus and Epstein–Barr virus reactivation. In conclusion, the BuCylowFlu provided reduced severe cardiotoxicity, and achieved favorable engraftment and survival. Our results suggest BuCylowFlu conditioning can be a feasible alternative for haplo‐HSCT recipients at risk of severe cardiotoxicity.
Ceramide modulates electrophysiological characteristics and oxidative stress of pulmonary vein cardiomyocytes
Authors: Huang Shih‐Yu , Lu Yen‐Yu , Lin Yung‐Kuo , Chen Yao‐Chang , Chen Yi‐Ann , Chung Cheng‐Chih , Lin Wei‐Shiang , Chen Shih‐Ann , Chen Yi‐Jen 
Published: October 2021

AbstractBackgroundCeramide is involved in regulating metabolism and energy expenditure, and its abnormal myocardial accumulation may contribute to heart injury or lipotoxic cardiomyopathy. Whether ceramide can modulate the electrophysiology of pulmonary veins (PVs) remains unknown.Materials and methodsWe used conventional microelectrodes to measure the electrical activity of isolated rabbit PV tissue preparations before and after treatment with various concentrations of ceramide with or without H2O2 (2 mM), MitoQ, wortmannin or 740 YP. A whole‐cell patch clamp and fluorescence imaging were used to record the ionic currents, calcium (Ca2+) transients, and intracellular reactive oxygen species (ROS) and sodium (Na+) in isolated single PV cardiomyocytes before and after ceramide (1 μM) treatment.ResultsCeramide (0.1, 0.3, 1 and 3 μM) reduced the beating rate of PV tissues. Furthermore, ceramide (1 μM) suppressed the 2 mM H2O2‐induced faster PV beating rate, triggered activities and burst firings, which were further reduced by MitoQ. In the presence of wortmannin, ceramide did not change the PV beating rate. The H2O2‐induced faster PV beating rate could be counteracted by MitoQ or wortmannin with no additive effect from the ceramide. Ceramide inhibited pPI3K. Ceramide reduced Ca2+ transients, sarcoplasmic reticulum Ca2+ contents, L‐type Ca2+ currents, Na+ currents, late Na+ currents, Na+‐hydrogen exchange currents, and intracellular ROS and Na+ in PV cardiomyocytes, but did not change Na+‐Ca2+ exchange currents.ConclusionC2 ceramide may exert the distinctive electrophysiological effect of modulating PV activities, which may be affected by PI3K pathway–mediated oxidative stress, and might play a role in the pathogenesis of PV arrhythmogenesis.
Distinct representation of ipsilateral hand movements in sensorimotor areas
Authors: Bruurmijn Mark L. C. M. , Raemaekers Mathijs , Branco Mariana P. , Ramsey Nick F. , Vansteensel Mariska J. 
Published: October 2021

AbstractThere is ample evidence that the contralateral sensorimotor areas play an important role in movement generation, with the primary motor cortex and the primary somatosensory cortex showing a detailed spatial organization of the representation of contralateral body parts. Interestingly, there are also indications for a role of the motor cortex in controlling the ipsilateral side of the body. However, the precise function of ipsilateral sensorimotor cortex in unilateral movement control is still unclear. Here, we show hand movement representation in the ipsilateral sensorimotor hand area, in which hand gestures can be distinguished from each other and from contralateral hand gestures. High‐field functional magnetic resonance imaging (fMRI) data acquired during the execution of six left‐ and six right‐hand gestures by healthy volunteers showed ipsilateral activation mainly in the anterior section of precentral gyrus and the posterior section of the postcentral gyrus. Despite the lower activation in ipsilateral areas closer to the central sulcus, activity patterns for the 12 hand gestures could be mutually distinguished in these areas. The existence of a unique representation of ipsilateral hand movements in the human sensorimotor cortex favours the notion of transcallosal integrative processes that support optimal coordination of hand movements.
Hereditary cerebral amyloid angiopathy mimicking CADASIL syndrome
Authors: Psychogios Klearchos , Xiromerisiou Georgia , Kargiotis Odysseas , Safouris Apostolos , Fiolaki Aidonio , Bonakis Anastasios , Paraskevas Georgios P. , Giannopoulos Sotirios , Tsivgoulis Georgios 
Published: October 2021

AbstractBackgroundSmall vessel disease (SVD), and most specifically hereditary forms like CADASIL and cerebral amyloid angiopathy (hCAA), are conditions of increasing clinical importance. We report a rare case of hCAA in a Greek family that presented with a CADASIL clinical and neuroimaging phenotype.MethodsA 65‐year‐old man was admitted with recurrent transient episodes of right leg numbness. The patient's medical history started at the age of 50 years with depression and behavioral disorders. His family history was positive for stroke (father), dementia (father and brother), migraine (daughter) and depression (father and daughter).ResultsNeurological examination disclosed anomic aphasia with severely impaired cognitive status, and brisk reflexes. Brain computed tomography and magnetic resonance imaging showed CADASIL‐like leukoencephalopathy (hyperintense lesions in bilateral temporopolar area, external capsule, thalami, centrum semiovale and superior frontal regions) with occipital calcifications and cerebral microbleeds. Screen for variants in NOTCH3 gene was negative. Exome sequencing revealed a novel pathogenic mutation for hCAA.ConclusionsWe report a novel amyloid precursor protein mutation which results in a CADASIL‐like clinical phenotype (progressive cognitive and motor decline, stroke, migraine and behavioral disorders) and CADASIL‐leukoencephalopathy coupled with occipital calcifications. Earlier recognition and swift hCAA diagnosis may prompt rational preventive and potential disease‐modifying interventions.
The adhesive heterogeneity of different compartments of oral mucosal rete ridges
Authors: Li Lin , Chen Heng , He Sangang , Sa Guoliang 
Published: October 2021

AbstractRete ridges play a critical role in maintaining epidermal structure and mechanical properties. Notably, rete ridges can be divided into three compartments: the base, slope and tip. The present study aims to explore whether these three compartments have distinct adhesive functions. We collected 28 normal masticatory mucosae to prepare paraffin‐embedded sections. Immunohistochemistry and immunofluorescent staining were used to analyse the expression pattern of integrin α6 and β4 in different compartments of the rete ridges. To observe whether the different compartments had distinct adhesive forces, dermal‐epidermal junction separation experiments were performed by peeling the oral epithelium from the lamina propria after treatment with cold saline for 72 h. The results showed that integrin α6 and β4 prefer the basal layer keratinocytes closely adjacent to the base compartment of the rete ridges. The oral mucosal epithelium separated from the underlying lamina propria at the tip of rete ridges when they were peeled after the cold saline treatment. In conclusion, the adhesive force of the basal layer keratinocytes at the base of the rete ridges is stronger than at the tip.
Tofacitinib improved peripheral endothelial dysfunction and brain‐derived neurotrophic factor levels in the rat adjuvant‐induced arthritis model
Authors: Totoson Perle , Peyronnel Célian , Quirié Aurore , Pédard Martin , Cefis Marina , Bermont Laurent , Prigent‐Tessier Anne , Prati Clément , Tournier Maude , Wendling Daniel , Marie Christine , Demougeot Céline 
Published: October 2021

AbstractThis study aimed to explore the effect of Tofacitinib on endothelial dysfunction and cerebral levels of brain‐derived neurotrophic factor (BDNF) in the adjuvant‐induced arthritis (AIA) rat model. Tofacitinib (10 mg/kg twice a day) or vehicle was administered from the first signs of inflammation. Arthritis scores were daily monitored while other parameters including endothelial function assessed from aortic rings, radiographic scores, blood pressure, heart rate, circulating levels of triglycerides, cholesterol, and interleukin (IL)‐1β, tumor necrosis factor‐α (TNF‐α), IL‐17A, and cerebral BDNF levels were determined after 3 weeks of treatment. A group of non‐AIA rats served as controls. In AIA rats, as compared with vehicle, Tofacitinib significantly reduced arthritis and radiographic scores, decreased total cholesterol and low‐density lipoprotein cholesterol (LDL‐C), but changed neither blood pressure nor heart rate and proinflammatory cytokines levels. It also fully restored acetylcholine (Ach)‐induced relaxation (p < 0.05) through increased nitric oxide (NO) synthase activity, reduced BH4 deficiency and O2−° production, decreased cyclo‐oxygenase‐2 (COX‐2)/arginase activities, and enhanced endothelium‐derived hyperpolarizing factor (EDHF) production. These effects translated into a decrease in atherogenic index and an elevation of BDNF levels in the prefrontal cortex (p < 0.05) and hippocampus (p < 0.001). The present study identified Tofacitinib as an efficient therapeutic option to reduce cardiovascular risk and improve BDNF‐dependent cognition in arthritis.