bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy
Authors: Cronin Shane J. F. , Andrews Nick A. , Latremoliere Alban 
Published: May 2023

The development of novel analgesics for chronic pain in the last 2 decades has proven virtually intractable, typically failing due to lack of efficacy and dose-limiting side effects. Identified through unbiased gene expression profiling experiments in rats and confirmed by human genome-wide association studies, the role of excessive tetrahydrobiopterin (BH4) in chronic pain has been validated by numerous clinical and preclinical studies. BH4 is an essential cofactor for aromatic amino acid hydroxylases, nitric oxide synthases, and alkylglycerol monooxygenase so a lack of BH4 leads to a range of symptoms in the periphery and central nervous system (CNS). An ideal therapeutic goal therefore would be to block excessive BH4 production, while preventing potential BH4 rundown. In this review, we make the case that sepiapterin reductase (SPR) inhibition restricted to the periphery (i.e., excluded from the spinal cord and brain), is an efficacious and safe target to alleviate chronic pain. First, we describe how different cell types that engage in BH4 overproduction and contribute to pain hypersensitivity, are themselves restricted to peripheral tissues and show their blockade is sufficient to alleviate pain. We discuss the likely safety profile of peripherally restricted SPR inhibition based on human genetic data, the biochemical alternate routes of BH4 production in various tissues and species, and the potential pitfalls to predictive translation when using rodents. Finally, we propose and discuss possible formulation and molecular strategies to achieve peripherally restricted, potent SPR inhibition to treat not only chronic pain but other conditions where excessive BH4 has been demonstrated to be pathological.
Sympathetic neuropathology is revealed in muscles affected by amyotrophic lateral sclerosis
Authors: Mazzaro Antonio , Vita Veronica , Ronfini Marco , Casola Irene , Klein Arianna , Dobrowolny Gabriella , Sorarù Gianni , Musarò Antonio , Mongillo Marco , Zaglia Tania 
Published: May 2023

Rationale: The anatomical substrate of skeletal muscle autonomic innervation has remained underappreciated since it was described many decades ago. As such, the structural and functional features of muscle sympathetic innervation are largely undetermined in both physiology and pathology, mainly due to methodological limitations in the histopathological analysis of small neuronal fibers in tissue samples. Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease which mainly targets motor neurons, and despite autonomic symptoms occurring in a significant fraction of patients, peripheral sympathetic neurons (SNs) are generally considered unaffected and, as such, poorly studied.Purpose: In this research, we compared sympathetic innervation of normal and ALS muscles, through structural analysis of the sympathetic network in human and murine tissue samples.Methods and Results: We first refined tissue processing to circumvent methodological limitations interfering with the detection of muscle sympathetic innervation. The optimized “Neuro Detection Protocol” (NDP) was validated in human muscle biopsies, demonstrating that SNs innervate, at high density, both blood vessels and skeletal myofibers, independent of the fiber metabolic type. Subsequently, NDP was exploited to analyze sympathetic innervation in muscles of SOD1G93A mice, a preclinical ALS model. Our data show that ALS murine muscles display SN denervation, which has already initiated at the early disease stage and worsened during aging. SN degeneration was also observed in muscles of MLC/SOD1G93A mice, with muscle specific expression of the SOD1G93A mutant gene. Notably, similar alterations in SNs were observed in muscle biopsies from an ALS patient, carrying the SOD1G93A mutation.Conclusion: We set up a protocol for the analysis of murine and, more importantly, human muscle sympathetic innervation. Our results indicate that SNs are additional cell types compromised in ALS and suggest that dysfunctional SOD1G93A muscles affect their sympathetic innervation.
The design and evaluation of the outflow structures of an interventional microaxial blood pump
Authors: Yun Zhong , Yao Jinfu , Wang Liang , Tang Xiaoyan , Feng Yunhao 
Published: May 2023

Blood pump design efforts are focused on enhancing hydraulic effectiveness and minimizing shear stress. Unlike conventional blood pumps, interventional microaxial blood pumps have a unique outflow structure due to minimally invasive technology. The outflow structure, composed of the diffuser and cage bridges, is crucial in minimizing the pump size to provide adequate hemodynamic support. This study proposed four outflow structures of an interventional microaxial blood pump depending on whether the diffuser with or without blades and cage bridges were straight or curved. The outflow flow structure’s effect on the blood pump’s hydraulic performance and shear stress distribution was evaluated by computational fluid dynamics and hydraulic experiments. The results showed that all four outflow structures could achieve the pressure and flow requirements specified at the design point but with significant differences in shear stress distribution. Among them, the outflow structure with curved bridges would make the blood dispersed more evenly when flowing out of the pump, which could effectively reduce the shear stress at the cage bridges. The outflow structure with blades would aggravate the secondary flow at the leading edge of the impeller, increasing the risk of flow stagnation. The combination of curved bridges and the bladeless diffuser had a relatively better shear stress distribution, with the proportion of fluid exposed to low scalar shear stress (&lt;50 Pa) and high scalar shear stress (&gt;150 Pa) in the blood pump being 97.92% and 0.26%, respectively. It could be concluded that the outflow structure with curved bridges and bladeless diffuser exhibited relatively better shear stress distribution and a lower hemolysis index of 0.00648%, which could support continued research on optimizing the microaxial blood pumps.
The associations of early specialization, sports volume, and maturity status with musculoskeletal injury in elite youth football players
Authors: Li Xiang , Feng Runze , Luo Shiyi , Li Chunman , Gómez-Ruano Miguel A. 
Published: May 2023

Background: Youth football in schools has experienced rapid growth in China. Despite the increase of players engaging in more frequent, intensive, and organized sports training at their early ages, the controversy over early specialization (ES) still exists. This study aims to: a) investigate the training situation of players in the Chinese School Football Programme and b) examine the associations of early specialization, sports volume, and maturity status with musculoskeletal injury.Methods: A cross-sectional survey was used. Players who participated in the National School Football Winter Camp were invited to fill out a questionnaire that included the data of maturity, ES, sports volume, and injury history (n = 88 boys and n = 90 girls).Results: The results have shown that 80.3% of the athletes were classified as ES, while 19.7% of them were classified as non-ES. Almost all athletes (96%) participated in a sport for more than 8 months in a year. Most athletes (75.8%) spent more than twice of the time on organized sports than leisure activities. 30.3% of the athletes trained on average more hours per week than the number of their ages. Binomial logistic regression models reflected the significant differences in the odds ratios (OR) of reporting a history of injury among athletes with different levels of specialization (p = 0.024) and the OR of reporting a history of leg injury among players with different weekly sports volumes (p = 0.038). Significant differences were also shown in the OR of players reporting foot injuries between players with different maturity states (p = 0.046), and the Chi-squared test showed significant differences in the OR of reporting acute injuries between players with different levels of specialization (p = 0.048) and weekly activity (p = 0.022). No significant differences were found between the remaining variables.Conclusion: Most school football elite players follow the ES pathway even though ES increases the risk of injury, especially acute injury. Pre-pubertal and early pubertal players have a higher incidence of foot injuries. Players who train more hours per week than their ages have more leg injuries and acute injuries. Therefore, priority protection and intervention should be carried out for populations with a high risk of injury.
3D cellular morphometrics of ovule primordium development in Zea mays reveal differential division and growth dynamics specifying megaspore mother cell singleness
Authors: Ouedraogo Inès , Lartaud Marc , Baroux Célia , Mosca Gabriella , Delgado Luciana , Leblanc Oliver , Verdeil Jean-Luc , Conéjéro Geneviève , Autran Daphné 
Published: May 2023

IntroductionDifferentiation of spore mother cells marks the somatic-to-reproductive transition in higher plants. Spore mother cells are critical for fitness because they differentiate into gametes, leading to fertilization and seed formation. The female spore mother cell is called the megaspore mother cell (MMC) and is specified in the ovule primordium. The number of MMCs varies by species and genetic background, but in most cases, only a single mature MMC enters meiosis to form the embryo sac. Multiple candidate MMC precursor cells have been identified in both rice and Arabidopsis, so variability in MMC number is likely due to conserved early morphogenetic events. In Arabidopsis, the restriction of a single MMC per ovule, or MMC singleness, is determined by ovule geometry. To look for potential conservation of MMC ontogeny and specification mechanisms, we undertook a morphogenetic description of ovule primordium growth at cellular resolution in the model crop maize.MethodsWe generated a collection of 48 three-dimensional (3D) ovule primordium images for five developmental stages, annotated for 11 cell types. Quantitative analysis of ovule and cell morphological descriptors allowed the reconstruction of a plausible developmental trajectory of the MMC and its neighbors.ResultsThe MMC is specified within a niche of enlarged, homogenous L2 cells, forming a pool of candidate archesporial (MMC progenitor) cells. A prevalent periclinal division of the uppermost central archesporial cell formed the apical MMC and the underlying cell, a presumptive stack cell. The MMC stopped dividing and expanded, acquiring an anisotropic, trapezoidal shape. By contrast, periclinal divisions continued in L2 neighbor cells, resulting in a single central MMC.DiscussionWe propose a model where anisotropic ovule growth in maize drives L2 divisions and MMC elongation, coupling ovule geometry with MMC fate.
Male and female Asians living with HIV: a text-mining analysis comparing their concerns
Authors: Chen Wei-Ti , Barbour Russell 
Published: May 2023

IntroductionAsians are “a forgotten population” whose HIV prevention and treatment needs have long been ignored. Studies on people living with HIV/AIDS (PLWHA) have primarily reported on physical and psychological conditions among men and gender minorities.MethodsWe used data-mining to select words and word patterns from pooled in-depth interviews conducted with 33 women and 12 men (n = 45) who were HIV positive and residing in San Francisco, United States, Shanghai, Beijing, or Taipei, China. We analyzed gender-based data (male vs. female) within the participant responses.ResultsDisclosure of HIV serostatus was discussed by both genders of PLWHA. Participants were concerned whether they should disclose their diagnosis and how to disclose it to their family members. Specifically, for women, family relationships and financial burdens were discussed most often. In terms of men, HIV disclosure was the key concern followed by disclosure of their sexual preference and concerns over what people were saying about them in the community.ConclusionThis project compared and contrasted concerns of Asian HIV-positive men and women. As healthcare providers promoting self-management by HIV-positive individuals of both genders, it is important to consider that there may be significant differences between them. Future interventions should consider how gender role influences self-management strategies in PLWHA and how support can be targeted to achieve a better quality of life for PLWHA.
Emergence of verb-pattern morphology in young Arabic speakers: morphological and semantic features
Authors: Tallas-Mahajna Naila , Armon-Lotem Sharon , Saiegh-Haddad Elinor 
Published: May 2023

IntroductionArabic, a Semitic language, displays a particularly rich derivational morphological system with all verb stems consisting of a semantic root and a prosodic verb-pattern. Such regular and frequently encountered knowledge is expected to be acquired early. The present study presents a developmental perspective on the relative contribution of morphological and semantic complexity to the acquisition of verbs in Spoken Arabic.MethodVerbs in a spontaneous corpus from 133 typically developing children, 2; 6–6; 0-year-old, were coded for type and token frequency of verbal patterns and root type, and classified according to semantic complexity.ResultsResults support an item-based emergence driven by semantic complexity at the earliest stages of acquisition. A developmental expansion in the diversity of verbal patterns and morphological complexity was observed with age. Morphological complexity is only identified when the same root appears in different verb patterns.DiscussionThe late emergence of the same root in different verb patterns indicates that the perception of verb patterns as abstract linguistic entities beyond the actual verbs is attained later than the semantically-constrained verbs in earlier childhood. We conclude that whereas semantic complexity obstructs verbs from emerging in the lexicon in younger age groups, morphological complexity constitutes no such obstruction, since their perception as morphological devices is attained later in acquisition.
ERP evidence for emotion-specific congruency effects between sentences and new words with disgust and sadness connotations
Authors: Gu Beixian , Liu Bo , Beltrán David , de Vega Manuel 
Published: May 2023

Introduction:The present study investigated how new words with acquired connotations of disgust and sadness, both negatively valenced but distinctive emotions, modulate the brain dynamics in the context of emotional sentences.Methods:Participants completed a learning session in which pseudowords were repeatedly paired with faces expressing disgust and sadness. An event-related potential (ERP) session followed the next day, in which participants received the learned pseudowords (herein, new words) combined with sentences and were asked to make emotional congruency judgment.Results:Sad new words elicited larger negative waveform than disgusting new words in the 146–228 ms time window, and emotionally congruent trials showed larger positive waveform than emotionally incongruent trials in the 304–462 ms time window. Moreover, the source localization in the latter suggested that congruent trials elicited larger current densities than incongruent trials in a number of emotion-related brain structures (e.g., the orbitofrontal cortex and cingulate gyrus) and language-related brain structures (e.g., the temporal lobe and the lingual gyrus).Discussion:These results suggested that faces are an effective source for the acquisition of words’ emotional connotations, and such acquired connotations can generate semantic and emotional congruency effects in sentential contexts.
Detecting delirium: a systematic review of ultrabrief identification instruments for hospital patients
Authors: Liu Yadong , Li Zhenzhen , Li Ying , Ge Ning , Yue Jirong 
Published: May 2023

ObjectiveEarly identification of delirium, which often occurs in older patients, can effectively reduce adverse prognoses. One way to increase the detection rate of delirium is to use an effective ultrabrief instrument for higher-frequency screening. The purpose of this review is to evaluate the diagnostic accuracy of ultrabrief screening tools for delirium.MethodsThe Cochrane Library, PubMed and EMBASE were searched from January 1, 1974, to November 31, 2022. We assessed the measurement properties of screening instruments using the consensus-based standards for selecting health measurement instruments (COSMIN) checklist and evaluated the risk bias of the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The diagnostic test accuracy of instruments for delirium was reported using sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR).ResultOf the 4,914 items identified, 26 met the eligibility criteria, resulting in 5 different delirium identification tools. The overall study quality assessed by the QUADAS-2 tool was moderate to good. Of the five screening tools, two instruments had sensitivity ≥80% and specificities ≥80%: 4AT and UB-2. The most comprehensive is the 4AT scale, which has a sensitivity of 0.80 [95% confidence interval (CI):0.68, 0.88] and a specificity of 0.89 (95%CI: 0.83, 0.93) and contains 4 items. UB-2 has a sensitivity of 0.88 (95%CI: 0.72, 0.96) and a specificity of 0.64 (95%CI: 0.56, 0.70).ConclusionUB-2 and MOTYB had excellent sensitivity for delirium screening at an early stage. In terms of sensitivity and intentionality, the 4AT is the best recommended scale.
What spelling errors can tell us about the development of processes involved in children’s spelling
Authors: Niolaki Georgia Z. , Negoita Alexandra , Vousden Janet I. , Terzopoulos Aris R. , Taylor Laura , Masterson Jackie 
Published: May 2023

IntroductionSpelling is an essential foundation for reading and writing. However, many children leave school with spelling difficulties. By understanding the processes children use when they spell, we can intervene with appropriate instruction tailored to their needs.MethodsOur study aimed to identify key processes (lexical-semantic and phonological) by using a spelling assessment that distinguishes different printed letter strings/word types (regular and irregular words, and pseudowords). Misspellings in the test from 641 pupils in Reception Year to Year 6 were scored using alternatives to binary correct versus incorrect scoring systems. The measures looked at phonological plausibility, phoneme representations and letter distance. These have been used successfully in the past but not with a spelling test that distinguishes irregularly spelled words from regular words and pseudowords.ResultsThe findings suggest that children in primary school rely on both lexical-semantic and phonological processes to spell all types of letter string, but this varies depending on the level of spelling experience (younger Foundation/Key stage 1 and older Key stage 2). Although children in younger year groups seemed to rely more on phonics, based on the strongest correlation coefficients for all word types, with further spelling experience, lexical processes seemed to be more evident, depending on the type of word examined.DiscussionThe findings have implications for the way we teach and assess spelling and could prove to be valuable for educators.
Clinician and patient perspectives on the ontology of mental disorder: a qualitative study
Authors: Kohne Annemarie Catharina Johanna , de Graauw Lukas Peter , Leenhouts-van der Maas Reina , Van Os Jim 
Published: May 2023

BackgroundPsychiatry may face an “identity crisis” regarding its very foundations. The lack of consensus regarding the theoretical grounds of psychiatry as a discipline has its epicenter in the discussion about the Diagnostic and Statistical Manual (DSM). A growing number of academics considers the manual broken and a growing number of patients voice concern. Despite the huge body of critique, 90% of Randomized Trials are based on DSM definitions of mental disorder. Therefore, the question regarding the ontology of mental disorder remains: what is a mental disorder, exactly?AimsWe aim to identify ontologies that live among patients and clinicians, evaluate the degree of consistency and coherence between clinician and patient views and contribute to the establishment of a novel ontological paradigm of mental disorder that is aligned with patients’ and clinicians’ perspectives.MethodEighty participants (clinicians/patients/clinicians with lived experience) were interviewed using a semi-structured interview, exploring their ideas on the ontology of mental disorder. This question was approached from different angles which led to comprising the interview schedule into different topics: “concept of disorder,” “representation by DSM,” “what is treated,” “what is recovered,” and “the right outcome measure.” Interviews were transcribed and analyzed using inductive Thematic Analysis.ResultsFrom all subthemes and main themes, a typology was constructed in which six, not necessarily mutually exclusive, ontological domains were identified: mental disorder as (1) disease, (2) functional impairment, (3) loss of adaptation, (4) existential problem, (5) highly subjective phenomenon, and (6) deviation from social norms. Common ground for the sample groups was that mental disorder is about functional impairment. Although about a fourth of sample clinicians holds an ontological concept of disease, only a small percentage of patients and none of the clinicians with lived experience adhered to an ontological concept of disease. The sample clinicians most often understand mental disorder to be a highly subjective phenomenon, and individuals with lived experience (patients and clinicians) most often understand mental (dis)order to be adaptational in nature: an (im)balance of burden in relation to strengths, skills, and recourses.ConclusionThe ontological palette is more diverse than what is taught about mental disorder in dominant scientific and educational discourse. There is a need to diversify the current, dominant ontology and make room for other ontologies. Investment is required in the development, elaboration and coming of age of these alternative ontologies, allowing them to reach their full potential and act as drivers of a landscape of promising novel scientific and clinical approaches.