bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical management of clavicle fractures in Australia: an analysis of Australian Medicare Benefits Schedule database from 2001 to 2020
Authors: Campbell Ryan J. , Handford Cameron , Donaldson Matthew J. , Sivakumar Brahman S. , Jiang Eric , Symes Michael 
Published: February 2023

AbstractBackgroundThere is no consensus on the optimal management of clavicle fractures, with advocates of both operative and non‐operative management. The objective of this study is to assess the trends in the management of clavicle fractures in Australia over the past two decades.MethodsThe incidence of surgical fixation of clavicle fractures from 2001 to 2020 was analysed using the Australian Medicare Benefits Schedule database, reflective of operations performed on privately insured patients, thus excluding public patients and compensable cases. An offset term was utilized with data from the Australian Bureau of Statistics to account for population changes over the study period.ResultsA total of 17 089 procedures for the management of clavicle fractures were performed from 2001 to 2020. The incidence of operative intervention increased from 1.87 per 100 000 in 2001 to a peak of 6.63 per 100 000 in 2016. An overall increase was seen in males (310%) and females (347%) over the study period, as well as across all age groups. A greater proportion of operative interventions was performed on males (n = 14 075, 82%) than females (n = 3014, 18%, P < 0.001). The greatest increase in intervention was noted in those aged 65 or older (14% increase per year, 95% CI 11%–17%, P < 0.05). In 2020, the incidence of operative intervention decreased to a level last seen in 2013.ConclusionsThe incidence of operative interventions for clavicle fractures has increased in Australia over the 20‐year study period. This increase is in keeping with recent evidence suggesting several advantages when displaced mid‐shaft clavicle fractures are operatively managed.
Weight loss by calorie restriction does not alter appetite‐regulating gut hormone responses from perfused rat small intestine
Authors: Gerstenberg Marina K. , Andersen Daniel B. , Torz Lola , Castorena Carlos M. , Bookout Angie L. , Hartmann Bolette , Rehfeld Jens F. , Petersen Natalia , Holst Jens J. , Kuhre Rune E. 
Published: February 2023

AbstractAimPostprandial secretion of the appetite‐inhibiting hormones, glucagon‐like peptide‐1 (GLP‐1), and peptide YY are reduced with obesity. It is unclear if the reduced secretion persists following weight loss (WL), if other appetite‐inhibiting hormones are also reduced, and if so whether reduced secretion results from intrinsic changes in the gut.MethodsTo address whether WL may restore secretion of GLP‐1 and other appetite‐inhibiting hormones, we performed a gut perfusion study of the small intestine in diet‐induced obese (DIO) rats after WL. A 20% weight loss (means ± SEM (g): 916 ± 53 vs. 703 ± 35, p < 0.01, n = 7) was induced by calorie restriction, and maintained stable for ≥7 days prior to gut perfusion to allow for complete renewal of enteroendocrine cells. Age‐matched DIO rats were used as comparator. Several gut hormones were analyzed from the venous effluent, and gene expression was performed on gut tissue along the entire length of the intestine.ResultsSecretion of cholecystokinin, gastrin, glucose‐dependent insulinotropic peptide, GLP‐1, neurotensin, and somatostatin was not affected by WL during basal conditions (p ≥ 0.25) or in response to macronutrients and bile acids (p ≥ 0.14). Glucose absorption was indistinguishable following WL. The expression of genes encoding the studied peptides, macronutrient transporters (glucose, fructose, and di‐/tripeptides) and bile acid receptors did also not differ between DIO and WL groups.ConclusionsThese data suggest that the attenuated postprandial responses of GLP‐1, as well as reduced responses of other appetite‐inhibiting gut hormones, in people living with obesity may persist after weight loss and may contribute to their susceptibility for weight regain.
Editorial: An international showcase
Authors: Nind Melanie 
Published: February 2023

Accessible summary

After the consultation with people with learning disabilities, the topic of health inequalities was chosen for the 2024 special issue.
The lives of people with learning disabilities around the world was also of interest to people so we have made this the theme of this issue. There are papers from the Czech Republic, Hong Kong, Belgium, Chile and Iceland.
We also have papers about life in the COVID‐19 pandemic.
Defining cases of asthma, eczema and allergic rhinitis using electronic health records in the Born in Bradford birth cohort
Authors: Souza da Cunha Sergio , Santorelli Gillian , Pembrey Lucy 
Published: February 2023

Key Messages• In electronic health records, the accuracy of diagnostic codes to define outcomes can be uncertain• The accuracy can vary in different settings, doctors and practices, even with validated codes• We recommend definitions combining codes previously described and other codes available in the records
miR‐26a‐5p alleviates CFA‐induced chronic inflammatory hyperalgesia through Wnt5a/CaMKII/NFAT signaling in mice
Authors: Lu Yitian , Liu Maozhu , Guo Xiangna , Wang Peng , Zeng Fanning , Wang Haitao , Tang Jing , Qin Zaisheng , Tao Tao 
Published: February 2023

AbstractBackgroundInflammation often leads to the occurrence of chronic pain, and many miRNAs have been shown to play a key role in the development of inflammatory pain. However, whether miR‐26a‐5p relieves pain induced by inflammation and its possible mechanism are still unclear.MethodsThe complete Freund's adjuvant (CFA)‐induced inflammatory pain mouse model was employed. Intrathecal or subcutaneous injection of miR‐26a‐5p agomir was performed after modeling to study its antinociceptive effect and the comparison of different administration methods. Bioinformatics analysis of miRNAs was performed to study the downstream mechanisms of miR‐26a‐5p. HE staining, RT‐qPCR, Western blotting, and immunofluorescence were used for further validation.ResultsA single intrathecal and subcutaneous injection of miR‐26a‐5p both reversed mechanical hypersensitivity and thermal latency in the left hind paw of mice with CFA‐induced inflammatory pain. HE staining and immunofluorescence studies found that both administrations of miR‐26a‐5p alleviated inflammation in the periphery and spinal cord. Bioinformatics analysis and dual‐luciferase reporter gene analysis identified Wnt5a as a direct downstream target gene of miR‐26a‐5p. Wnt5a was mainly expressed in neurons and microglia in the spinal cord of mice with inflammatory pain. Intrathecal injection of miR‐26a‐5p could significantly reduce the expression level of Wnt5a and inhibit the downstream molecules of noncanonical Wnt signaling Camk2/NFAT, inhibiting the release of spinal cord inflammatory factors and alleviating the activation of microglia. In addition, miR‐26a‐5p could also inhibit lipopolysaccharide (LPS)‐stimulated BV2 cell inflammation in vitro through a noncanonical Wnt signaling pathway.ConclusionsmiR‐26a‐5p is a promising therapy for CFA‐induced inflammatory pain. Both intrathecal and subcutaneous injections provide relief for inflammatory pain. miR‐26a‐5p regulated noncanonical Wnt signaling to be involved in analgesia partly through antineuroinflammation, suggesting a pain‐alleviating effect via noncanonical Wnt signaling pathway in the CFA‐induced inflammatory pain model in vivo.
Marsdenia tenacissima extract prevents the malignant progression of glioma through upregulating lncRNA MEG3 and SFRP1‐dependent inhibition of Wnt/β‐catenin pathway
Authors: Chen Lei , Gong Xin , Huang Mengyi 
Published: February 2023

AbstractBackground/AimRecent studies have highlighted the tumor‐suppressive effect of Marsdenia tenacissima extract (MTE) on human cancers. This research unveils the potential impact of MTE on glioma and ascertains the relevant molecular mechanisms.MethodsGlioma cells were treated with MTE, with normal human astrocytes (NHAs) as controls. A battery of function experiments, including the CCK‐8 viability test, colony formation assay, scratch migration assay, and Transwell invasion assay, was executed to address the responses of glioma cells to MTE treatment and gain or loss of function of lncMEG3, miR‐542‐3p, and SFRP1. FISH, RIP, and dual‐luciferase reporter assays were adopted for assessing gene interactions. U251‐GFP‐Luc cells were delivered into nude mice through intracranial injection to develop an orthotopic glioma model for in vivo validation.Results200 mg/mL MTE could suppress the proliferating, migrating, and invading properties of glioma cells but not affect those of NHAs. MTE treatment enhanced the expression of lncMEG3, which competes with SFRP1 for binding miR‐542‐3p. SFRP1 could inactivate the Wnt/β‐catenin pathway. Animal experimentation substantiated the antitumor activity and mechanism of MTE in nude mice.ConclusionsMTE suppresses glioma via the lncMEG3/miR‐542‐3p/SFRP1/Wnt/β‐catenin axis. These findings contribute to a theoretical basis for the use of MTE for glioma patients.
Dl‐3‐n‐butylphthalide promotes synaptic plasticity by activating the Akt/ERK signaling pathway and reduces the blood–brain barrier leakage by inhibiting the HIF‐1α/MMP signaling pathway in vascular dementia model mice
Authors: Che Ping , Zhang Juan , Yu Mingqian , Tang Ping , Wang Yanhui , Lin Aolei , Xu Jing , Zhang Nan 
Published: February 2023

AbstractAimsDL‐3‐n‐butylphthalide (NBP) exerts beneficial effects on global cognitive functions, but the underlying molecular mechanisms are still poorly understood. The present study aimed to investigate whether NBP mediates synaptic plasticity and blood–brain barrier (BBB) function, which play a pivotal role in the pathogenesis of vascular dementia (VaD), in a mouse model of bilateral common carotid artery stenosis (BCAS).MethodsNBP was administered to model mice at a dose of 80 mg/kg by gavage for 28 days after surgery. Cognitive function was evaluated by behavioral tests, and hippocampal synaptic plasticity was evaluated by in vivo electrophysiological recording. Cerebral blood flow (CBF), hippocampal volume, and white matter integrity were measured with laser speckle imaging (LSI) and MRI. In addition, BBB leakage and the expression of proteins related to the Akt/ERK and HIF‐1α/MMP signaling pathways were assessed by biochemical assays.ResultsNBP treatment alleviated cognitive impairment, hippocampal atrophy, and synaptic plasticity impairment induced by BCAS. In addition, NBP treatment increased CBF, promoted white matter integrity, and decreased BBB leakage. Regarding the molecular mechanisms, in mice with BCAS, NBP may activate the Akt/ERK signaling pathway, which upregulates the expression of synapse‐associated proteins, and it may also inhibit the HIF‐1α/MMP signaling pathway, thereby increasing the expression of tight junction (TJ) proteins.ConclusionIn conclusion, our results demonstrated the therapeutic effects of NBP in improving cognitive function via a wide range of targets in mice subjected to BCAS.
Exosomal miR‐128‐3p reversed fibrinogen‐mediated inhibition of oligodendrocyte progenitor cell differentiation and remyelination after cerebral ischemia
Authors: Hou Huiqing , Wang Yafei , Yang Lan , Wang Yongjun 
Published: February 2023

AbstractAimsTo investigate the role of exosomal miR‐128‐3p in promoting fibrinogen‐mediated inhibition of oligodendrocyte progenitor cell (OPC) differentiation and the therapeutic potential of exosomal miR‐128‐3p in cerebral ischemia.MethodsMouse models of middle cerebral artery occlusion (MCAO) were established as described previously. MCAO was treated with fibrinogen and exosomes by stereotactically injecting into the left stratum. Mouse cortical OPCs were used for mRNA and miRNA sequencing analysis. Exosomes were isolated from neural stem cells (NSCs) of mice.ResultsFibrinogen deposition suppressed remyelination after MCAO and inhibited OPC differentiation by activating ACVR1, the bone morphogenetic protein (BMP) signaling type I receptor. In vitro, miR‐sequencing and verification studies revealed that miR‐128‐3p is associated with BMP signaling mediated by ACVR1. Additionally, transfer of NSC‐derived exosomal miR‐128‐3p to OPCs significantly increased myelin basic protein expression and inhibited BMP signaling. Furthermore, NSC‐derived exosomal miR‐128‐3p protected against fibrinogen‐induced demyelination related to BMP signaling, reduced the infarct volume, and improved neurological function after MCAO.ConclusionsFibrinogen deposition inhibits remyelination after ischemic damage and NSC‐derived exosomal miR‐128‐3p promotes OPC differentiation into OLs by suppressing BMP signaling, indicating that NSC‐derived exosomal miR‐128‐3p represents a potential therapeutic target for ischemic stroke.
Nicotinamide mononucleotide restores oxidative stress‐related apoptosis of oocyte exposed to benzyl butyl phthalate in mice
Authors: Jiang Yi , Wang Di , Zhang Cheng , Jiao Yangyang , Pu Yanan , Cheng Rong , Li Chunyu , Chen Yan 
Published: February 2023

AbstractBenzyl butyl phthalate (BBP) is a chemical softener and plasticizer commonly used in toys, food packaging, wallpaper, detergents and shampoos. The estrogenic actions of BBP have detrimental effects on humans and animals. In this study, the specific influence of BBP on mouse oocyte maturation was investigated using in vivo and in vitro models. The experiment first verified that BBP exposure significantly affected the rate of oocyte exclusion of the first polar body, although it did not affect germinal vesicle breakdown (GVBD) through in vitro oocyte culture system. Results of in vitro fertilization show that BBP exposure affects blastocyst rate. Subsequently, the results obtained by immunofluorescence staining technology showed that oocyte spindle organization, chromosomal arrangement and the distribution of cortical actin were disrupted by BBP exposure, and led to the failure of oocyte meiotic maturation and the subsequent early embryo development. Singe‐cell transcriptome analysis found that BBP exposure altered the expression levels of 588 genes, most associated with mitochondria‐related oxidative stress. Further analysis demonstrated that the detrimental effects of BBP involved the disruption of mitochondrial function and oxidative stress‐induced early apoptosis. Nicotinamide mononucleotide (NMN) supplementation reduced the adverse effects of BBP. Collectively, these findings revealed a mechanism of BBP‐induced toxicity on female reproduction and showed that NMN provides an effective treatment for BBP actions.
The impact of geographic location versus center practice on center volume in liver transplantation after the acuity circle policy
Authors: Bekki Yuki , Myers Bryan , Tomiyama Koji , Melcher Marc L , Sasaki Kazunari 
Published: February 2023

AbstractBackgroundThe allocation system for livers used the acuity circles (AC) beginning in 2020. In this study, we sought to evaluate the effect of the AC policy on center transplant volumes, from geographic and center practice perspectives.MethodsUsing the US national registry data between 2018 and 2022, adult liver transplantations (LTs) were separated into two eras: before AC and after AC.ResultsThe number of LT for Model for End‐Stage Liver Disease (MELD) scores ≥29 have significantly increased by 10%, and waitlist times for those patients have been significantly shorter after AC. These benefits were not found in patients with MELD scores <29. The geographic distribution of transplant centers reveals that the majority of centers which increased their transplant volume (18 out of 25 centers) are located in high‐population states while there are seven transplant centers in nonhigh‐population states. The centers in the nonhigh‐population states utilized more marginal donation after brain death (DBD) and donation after circulatory death (DCD) donors by 27% and 155%, respectively. MELD scores were significantly lower in the nonhigh‐population states compared with those in the high‐population states (p < .01).ConclusionAC improved the LT access for patients with MELD scores ≥29, which benefited the high‐population states. However, aggressive center practices to utilize marginal DBD and DCD donors were able to increase transplant volume and lower median allocation MELD scores.
Two distinct pathogenic pathways of digital papillary adenocarcinoma — BRAF mutation or low‐risk HPV infection
Authors: Bui Chau M. , Pukhalskaya Tatsiana , Smoller Bruce R. , Zengin Hatice Betul , Heneidi Saleh , Vail Eric , Makhoul Elias , Balzer Bonnie 
Published: February 2023

AbstractDigital papillary adenocarcinoma (DPA) is a rare neoplasm that can exhibit local recurrence and distant metastasis. We present a series of eight cases of DPA showing two distinct clinical presentations, morphologies, immunophenotypes, and molecular features. Four cases were characterized by painless, slow‐growing nodules located on the digits. The lesions were small, well‐defined, and confined in the dermis. Histopathologically, these tumors were composed of glandular structures lined by cuboidal epithelium with luminal papillary infoldings. Only rare mitotic figures and minimal squamoid differentiation were present, and cellular necrosis was absent. All four cases were positive for the BRAF V600E immunohistochemistry but negative for p16, low‐risk and high‐risk HPV in situ hybridization (ISH). In contrast, the remaining four cases were characterized by painful, rapidly growing masses on the digits. These four lesions were located in the deep dermis and consisted of a solid, tightly packed papillary architecture lined by atypical epithelioid cells with inconspicuous nucleoli. Cellular necrosis, numerous mitotic figures, and prominent squamoid differentiation were seen. All cases were negative for the BRAF V600E IHC. However, they showed strong, patchy to diffuse reactivity for p16 and were positive for low‐risk HPV ISH and negative for high‐risk HPV ISH. Our findings suggest that the current classification of DPA encompasses tumors that show two discrete pathogenic pathways — BRAF mutation or low‐risk HPV infection. DPAs with low‐risk HPV infection exhibit aggressive clinical features, high‐grade morphology, marked squamoid differentiation, and wild‐type BRAF. DPAs with BRAF V600E have less aggressive clinical features, low‐grade morphologic findings, mild to absent squamoid differentiation, and negative HPV infection.
Standing genetic variation as a potential mechanism of novel cave phenotype evolution in the freshwater isopod, Asellus aquaticus
Authors: Rodas Lizet R. , Sarbu Serban M. , Bancila Raluca , Price Devon , Fišer Žiga , Protas Meredith 
Published: February 2023

AbstractNovel phenotypes can come about through a variety of mechanisms including standing genetic variation from a founding population. Cave animals are an excellent system in which to study the evolution of novel phenotypes such as loss of pigmentation and eyes. Asellus aquaticus is a freshwater isopod crustacean found in Europe and has both a surface and a cave ecomorph which vary in multiple phenotypic traits. An orange eye phenotype was previously revealed by F2 crosses and backcrosses to the cave parent within two examined Slovenian cave populations. Complete loss of pigmentation, both in eye and body, is epistatic to the orange eye phenotype and therefore the orange eye phenotype is hidden within the cave populations. Our goal was to investigate the origin of the orange eye alleles within the Slovenian cave populations by examining A. aquaticus individuals from Slovenian and Romanian surface populations and Asellus aquaticus infernus individuals from a Romanian cave population. We found orange eye individuals present in lab raised surface populations of A. aquaticus from both Slovenia and Romania. Using a mapping approach with crosses between individuals of two surface populations, we found that the region known to be responsible for the orange eye phenotype within the two previously examined Slovenian cave populations was also responsible within both the Slovenian and the Romanian surface populations. Complementation crosses between orange eye Slovenian and orange eye Romanian surface individuals suggest that the same gene is responsible for the orange eye phenotype in both surface populations. Additionally, we observed a low frequency phenotype of eye loss in crosses generated between the two surface populations and also in the Romanian surface population. Finally, in a cave population from Romania, A. aquaticus infernus, we found that the same region is also responsible for the orange eye phenotype as the Slovenian cave populations and the Slovenian and Romanian surface populations. Therefore, we present evidence that variation present in the cave populations could originate from standing variation present in the surface populations and/or transgressive hybridization of different surface phylogenetic lineages rather than de novo mutations.
Impact of decision and action outcomes on subsequent decision and action behaviours in humans
Authors: Saleri Lunazzi Clara , Thura David , Reynaud Amélie J. 
Published: February 2023

AbstractSpeed–accuracy trade‐off adjustments in decision‐making have been mainly studied separately from those in motor control. In the wild, however, animals coordinate their decision and action, often deciding while acting. Recent behavioural studies support this view, indicating that animals, including humans, trade decision time for movement time to maximize their global rate of reward during experimental sessions. Besides, it is well established that choice outcomes impact subsequent decisions. Crucially though, whether and how a decision outcome also influences the subsequent motor performance, and whether and how the outcome of a movement influences the next decision, is unclear. Here, we address these questions by analysing trial‐to‐trial changes of choice and motor behaviours in healthy human participants instructed to perform successive perceptual decisions expressed with reaching movements whose duration was either weakly or strongly constrained in separate tasks. Results indicate that after a wrong decision, subjects who were weakly constrained in their action duration decided more slowly and more accurately. Interestingly, they also shortened their subsequent movement duration by moving faster. Conversely, we found that errors of constrained movements influenced not only the speed and the amplitude of the following movement but those of the decision too. If the movement had to be slowed down, the decision that precedes that movement was accelerated and vice versa. Together, these results indicate that from one trial to the next, humans seek to determine a behavioural duration as a whole instead of optimizing each of the decision and action speed–accuracy trade‐offs independently of each other.
Evolutionary constraints mediate extinction risk under climate change
Authors: Garcia‐Costoya Guillermo , Williams Claire E. , Faske Trevor M. , Moorman Jacob D. , Logan Michael L. 
Published: February 2023

AbstractMounting evidence suggests that rapid evolutionary adaptation may rescue some organisms from the impacts of climate change. However, evolutionary constraints might hinder this process, especially when different aspects of environmental change generate antagonistic selection on genetically correlated traits. Here, we use individual‐based simulations to explore how genetic correlations underlying the thermal physiology of ectotherms might influence their responses to the two major components of climate change—increases in mean temperature and thermal variability. We found that genetic correlations can influence population dynamics under climate change, with declines in population size varying three‐fold depending on the type of correlation present. Surprisingly, populations whose thermal performance curves were constrained by genetic correlations often declined less rapidly than unconstrained populations. Our results suggest that accurate forecasts of the impact of climate change on ectotherms will require an understanding of the genetic architecture of the traits under selection.