bluuebunny/crossref_metadata_2025_split huggingface dataset:
An imbalance of netrin‐1 and DCC during nigral degeneration in experimental models and patients with Parkinson's disease
Authors: Hua Ye , Han Wenjing , Zhou Linfeng , Gao Jing , Zhao Jifeng , Song Nanshan , Hu Bin , Yao Qingyu , Liu Yumin , Xu Deen , Lu Yunnan , Fan Yi 
Published: March 2023

AbstractAimsMultiple guidance cues, such as netrin‐1 (NTN‐1)/deleted in colorectal carcinoma (DCC), control the guidance of axons and help establish functional neural circuits during development. However, the function of these guidance molecules during the neurodegenerative process is unclear.MethodsTo access the alterations of NTN‐1 and DCC during the onset and progression of PD, we first established two subacute and one chronic PD model. Then, we investigated the relationship between the NTN‐1/DCC pathway and cell death in SH‐SY5Y cells. Finally, we conducted correlation studies between plasma NTN‐1 and parkinsonian symptoms in patients to understand how this pathway contributes to PD.ResultsWe found that the imbalance of NTN‐1 and DCC was a common feature of nigral DA neuron injury in PD mouse models. We investigated that MPP+ inhibited NTN‐1 expression and increased DCC expression in a concentration‐ and time‐dependent manner. We further discovered a significant decrease in plasma NTN‐1 levels and a positive correlation with UPDRS scores in PD patients.ConclusionOur findings confirmed the imbalance of NTN‐1/DCC signaling during nigral degeneration in experimental PD models and found for the first time a correlation of plasma NTN‐1 with PD symptoms in patients.
LncRNA INPP5F ameliorates stress‐induced hypertension via the miR‐335/Cttn axis in rostral ventrolateral medulla
Authors: Zhang Shuai , Chen Gaojun , Wang Xueping , Tong Lei , Wang Linping , Liu Tianfeng , Zhu Liucun , Zhou Shumin , Liu Haisheng , Du Dongshu 
Published: March 2023

AbstractAimsThe rostral ventrolateral medulla (RVLM) is an essential vasomotor center responsible for regulating the development of stress‐induced hypertension (SIH). Long non‐coding RNAs (lncRNAs) play critical roles in various physiopathology processes, but existing research on the functions of RVLM lncRNAs on SIH has been lacking. In this study, we investigated the roles of RVLM lncRNAs in SIH.MethodsGenome‐wide lncRNA profiles in RVLM were determined by RNA sequencing in a SIH rat model established using electric foot shocks plus noises. The hypotensive effect of lncRNA INPP5F and the underlying mechanisms of lncRNA INPP5F on SIH were explored through in vivo and in vitro experiments, such as intra‐RVLM microinjection and immunofluorescence.ResultsWe discovered 10,179 lncRNA transcripts, among which the lncRNA INPP5F expression level was significantly decreased in SIH rats. Overexpression of lncRNA INPP5F in RVLM dramatically reduced the blood pressure, sympathetic nerve activity, and neuronal excitability of SIH rats. LncRNA INPP5F overexpression markedly increased Cttn expression and reduced neural apoptosis by activating the PI3K‐AKT pathway, and its inhibition had opposite effects. Mechanistically, lncRNA INPP5F acted as a sponge of miR‐335, which further regulated the Cttn expression.ConclusionLncRNA INPP5F was a key factor that inhibited SIH progression, and the identified lncRNA INPP5F/miR‐335/Cttn/PI3K‐AKT/apoptosis axis represented one of the possible mechanisms. LncRNA INPP5F could serve as a therapeutic target for SIH.
Nature benefit hypothesis: Direct experiences of nature predict self‐reported pro‐biodiversity behaviors
Authors: Soga Masashi , Gaston Kevin J. 
Published: March 2023

AbstractHuman activities are damaging the world's ecosystems, posing a serious threat to life on Earth, including humanity. To address this situation, widespread and significant changes in human behavior are necessary. Direct experiences of nature can encourage individuals to adopt positive actions towards biodiversity (hereafter pro‐biodiversity behavior), but this relationship has not been well studied. Using a large sample of Japanese adults, we demonstrate that both recent and childhood frequencies of nature experiences are associated with an increased likelihood of exhibiting pro‐biodiversity behaviors. This association was found to be consistent across various forms of behaviors, including purchasing ecofriendly products, reducing pesticide use in domestic gardens, and donating to conservation organizations. However, our research also reveals a declining trend of childhood experiences of nature in Japan, resulting in an “extinction of experience.” Our results suggest that enhancing people's personal experiences with nature could help promote desired behavioral change to halt biodiversity loss.
Single‐cell transcriptomics implicates the FEZ1–DKK1 axis in the regulation of corneal epithelial cell proliferation and senescence
Authors: Zhu Liqiong , Wang Li , Liu Dongmei , Chen Chaoqun , Mo Kunlun , Lan Xihong , Liu Jiafeng , Huang Ying , Guo Dianlei , Huang Huaxing , Li Mingsen , Guo Huizhen , Tan Jieying , Zhang Kang , Ji Jianping , Yuan Jin , Ouyang Hong 
Published: March 2023

AbstractLimbal stem/progenitor cells (LSC) represent the source of corneal epithelium renewal. LSC proliferation and differentiation are essential for corneal homeostasis, however, the regulatory mechanism remains largely unexplored. Here, we performed single‐cell RNA sequencing and discovered proliferation heterogeneity as well as spontaneously differentiated and senescent cell subgroups in multiply passaged primary LSC. Fasciculation and elongation protein zeta 1 (FEZ1) and Dickkopf‐1 (DKK1) were identified as two significant regulators of LSC proliferation and senescence. These two factors were mainly expressed in undifferentiated corneal epithelial cells (CECs). Knocking down the expression of either FEZ1 or DKK1 reduced cell division and caused cell cycle arrest. We observed that DKK1 acted as a downstream target of FEZ1 in LSC and that exogenous DKK1 protein partially prevented growth arrest and senescence upon FEZ1 suppression in vitro. In a mouse model of corneal injury, DKK1 also rescued the corneal epithelium after recovery was inhibited by FEZ1 suppression. Hence, the FEZ1–DKK1 axis was required for CEC proliferation and the juvenile state and can potentially be targeted as a therapeutic strategy for promoting recovery after corneal injury.
Sleep loss impairs intestinal stem cell function and gut homeostasis through the modulation of the GABA signalling pathway in Drosophila
Authors: Zhou Juanyu , He Li , Liu Mengyou , Guo Xiaoxin , Du Gang , Yan La , Zhang Zehong , Zhong Zhendong , Chen Haiyang 
Published: March 2023

AbstractSleep is essential for maintaining health. Indeed, sleep loss is closely associated with multiple health problems, including gastrointestinal disorders. However, it is not yet clear whether sleep loss affects the function of intestinal stem cells (ISCs). Mechanical sleep deprivation and sss mutant flies were used to generate the sleep loss model. qRT‐PCR was used to measure the relative mRNA expression. Gene knock‐in flies were used to observe protein localization and expression patterns. Immunofluorescence staining was used to determine the intestinal phenotype. The shift in gut microbiota was observed using 16S rRNA sequencing and analysis. Sleep loss caused by mechanical sleep deprivation and sss mutants disturbs ISC proliferation and intestinal epithelial repair through the brain–gut axis. In addition, disruption of SSS causes gut microbiota dysbiosis in Drosophila. As regards the mechanism, gut microbiota and the GABA signalling pathway both partially played a role in the sss regulation of ISC proliferation and gut function. The research shows that sleep loss disturbed ISC proliferation, gut microbiota, and gut function. Therefore, our results offer a stem cell perspective on brain–gut communication, with details on the effect of the environment on ISCs.
Risk factors of anastomosis‐related difficult endoscopic retrograde cholangiopancreatography following endoscopic ultrasound‐guided gastro‐gastrostomy using a standardized protocol (with video)
Authors: Pérez‐Cuadrado‐Robles Enrique , Alric Hadrien , Quénéhervé Lucille , Monino Laurent , Poghosyan Tigran , Benosman Hedi , Vienne Ariane , Perrod Guillaume , Rebibo Lionel , Aidibi Ali , Tenorio‐González Elena , Ragot Emilia , Karoui Mehdi , Cellier Christophe , Rahmi Gabriel 
Published: March 2023

ObjectivesLittle is known about how to perform the endoscopic ultrasound (EUS)‐directed transgastric endoscopic retrograde cholangiopancreatography (ERCP; EDGE) in patients with gastric bypass using lumen‐apposing metal stents (LAMS). The aim was to assess the risk factors of anastomosis‐related difficult ERCP.MethodsObservational single‐center study. All patients who underwent an EDGE procedure in 2020–2022 following a standardized protocol were included. Risk factors for difficult ERCP, defined as the need of >5 min LAMS dilation or failure to pass a duodenoscope in the second duodenum, were assessed.ResultsForty‐five ERCPs were performed in 31 patients (57.4 ± 8.2 years old, 38.7% male). The EUS procedure was done using a wire‐guided technique (n = 28, 90.3%) for biliary stones (n = 22, 71%) in most cases. The location of the anastomosis was gastro‐gastric (n = 24, 77.4%) and mainly in the middle‐excluded stomach (n = 21, 67.7%) with an oblique axis (n = 22, 71%). The ERCP technical success was 96.8%. There were 10 difficult ERCPs (32.3%) due to timing (n = 8), anastomotic dilation (n = 8), or failure to pass (n = 3). By multivariable analysis adjusted by two‐stage procedures, the risk factors for a difficult ERCP were the jejuno‐gastric route (85.7% vs. 16.7%; odds ratio [ORa] 31.875; 95% confidence interval [CI] 1.649–616.155; P = 0.022), and the anastomosis to the proximal/distal excluded stomach (70% vs. 14.3%; ORa 22.667; 95% CI 1.676–306.570; P = 0.019). There was only one complication (3.2%) and one persistent gastro‐gastric fistula (3.2%) in a median follow‐up of 4 months (2–18 months), with no weight regain (P = 0.465).ConclusionsThe jejunogastric route and the anastomosis with the proximal/distal excluded stomach during the EDGE procedure increase the difficulty of ERCP.
Robustness of the cognitive gains in 7‐month‐old bilingual infants: A close multi‐center replication of Kovács and Mehler (2009)
Authors: Spit Sybren , Geambașu Andreea , Renswoude Daan van , Blom Elma , Fikkert Paula , Hunnius Sabine , Junge Caroline , Verhagen Josje , Visser Ingmar , Wijnen Frank , Levelt Clara C 
Published: March 2023

AbstractWe present an exact replication of Experiment 2 from Kovács and Mehler's 2009 study, which showed that 7‐month‐old infants who are raised bilingually exhibit a cognitive advantage. In the experiment, a sound cue, following an AAB or ABB pattern, predicted the appearance of a visual stimulus on the screen. The stimulus appeared on one side of the screen for nine trials and then switched to the other side. In the original experiment, both mono‐ and bilingual infants anticipated where the visual stimulus would appear during pre‐switch trials. However, during post‐switch trials, only bilingual children anticipated that the stimulus would appear on the other side of the screen. The authors took this as evidence of a cognitive advantage. Using the exact same materials in combination with novel analysis techniques (Bayesian analyses, mixed effects modeling and cluster based permutation analyses), we assessed the robustness of these findings in four babylabs (N = 98). Our results did not replicate the original findings: although anticipatory looks increased slightly during post‐switch trials for both groups, bilingual infants were not better switchers than monolingual infants. After the original experiment, we presented additional trials to examine whether infants associated sound patterns with cued locations, for which we did not find any evidence either. The results highlight the importance of multicenter replications and more fine‐grained statistical analyses to better understand child development.Highlights
We carried out an exact replication across four baby labs of the high‐impact study by Kovács and Mehler (2009).
We did not replicate the findings of the original study, calling into question the robustness of the claim that bilingual infants have enhanced cognitive abilities.
After the original experiment, we presented additional trials to examine whether infants correctly associated sound patterns with cued locations, for which we did not find any evidence.
The use of novel analysis techniques (Bayesian analyses, mixed effects modeling and cluster based permutation analyses) allowed us to draw better‐informed conclusions.
Stereotypes in the classroom's air: Classroom racial stereotype endorsement, classroom engagement, and STEM achievement among Black and White American adolescents
Authors: Del Toro Juan , Wang Ming‐Te 
Published: March 2023

AbstractInitiatives promoting diversity, equity, and inclusion in predominantly White contexts, including STEM fields, have primarily relied on approaches to increase the representation of minoritized individuals. However, an increase in the representation of minoritized individuals is only one step of the process, as the present study suggests that explicit beliefs about particular racial groups’ abilities also matter. The present article examined whether classroom racial stereotype endorsement about science and math disadvantaged Black American adolescents relative to their White American peers. Across two longitudinal studies with 533 and 1,189 adolescents (N‐adolescents = 1722; N‐classrooms = 86; 45% Black American, 55% White American; 51% females; M‐age = 13–14), classroom pro‐White/anti‐Black stereotype endorsement in the fall term predicted better science and math achievement scores for White American adolescents and lower science and math achievement scores for Black American adolescents at the end of the academic year. Student‐ and teacher‐reported student engagement in science and math classrooms mediated the longitudinal relations between classroom pro‐White/anti‐Black stereotype endorsement and students’ achievement scores. Results suggest that classrooms may be important conduits for communicating racial stereotypes that create racially hostile STEM learning environments.Research Highlights
Using a longitudinal sample of 1722 adolescents enrolled in 86 classrooms, the present study examined the consequences of classroom racial stereotype endorsement during adolescence.
White American adolescents demonstrated favorable achievement scores in science and math when their classmates endorsed traditional, or pro‐White/anti‐Black, stereotypes.
Black American adolescents showed worse achievement scores in science and math when their classmates endorsed pro‐White/anti‐Black stereotypes.
Classroom engagement mediated the longitudinal relations between classroom pro‐White/anti‐Black stereotype endorsement and achievement scores for both Black and White American adolescents.
Glucose‐dependent insulinotropic polypeptide counteracts diet‐induced obesity along with reduced feeding, elevated plasma leptin and activation of leptin‐responsive and proopiomelanocortin neurons in the arcuate nucleus
Authors: Han Wanxin , Wang Lei , Ohbayashi Kento , Takeuchi Masakazu , O'Farrell Libbey , Coskun Tamer , Rakhat Yermek , Yabe Daisuke , Iwasaki Yusaku , Seino Yutaka , Yada Toshihiko 
Published: March 2023

AbstractAimTo clarify the effects of glucose‐dependent insulinotropic polypeptide (GIP) receptor agonists (GIPRAs) on feeding and body weight.Materials and MethodsAcute and subchronic effects of subcutaneous GIPFA‐085, a long‐acting GIPRA, on blood glucose, food intake, body weight, respiratory exchange ratio and plasma leptin levels were measured in diet‐induced obese (DIO) mice and/or functional leptin‐deficient ob/ob mice. The effects of GIPFA‐085 on the hypothalamic arcuate nucleus (ARC) neurons from lean and DIO mice were studied by measuring cytosolic Ca2+ concentration ([Ca2+]i).ResultsSingle bolus GIPFA‐085 (30, 300 nmol/kg) dose‐dependently reduced blood glucose in glucose tolerance tests, elevated plasma leptin levels at 0.5‐6 hours and inhibited food intake at 2‐24 hours after injection in DIO mice. Daily GIPFA‐085 (300 nmol/kg) inhibited food intake and increased fat utilization on day 1, and reduced body weight gain on days 3‐12 of treatment in DIO, but not ob/ob, mice. GIPFA‐085 increased [Ca2+]i in the ARC leptin‐responsive and proopiomelanocortin (POMC) neurons. GIPFA‐085 and leptin cooperated to increase [Ca2+]i in ARC neurons and inhibit food intake.ConclusionsGIPFA‐085 acutely inhibits feeding and increases lipid utilization, and sustainedly lowers body weight in DIO mice via mechanisms involving rises in leptin and activation of ARC leptin‐responsive and POMC neurons. This study highlights the therapeutic potential of GIPRAs for treating obesity and diabetes.
Once‐weekly semaglutide use in patients with type 2 diabetes: Results from the SURE France multicentre, prospective, observational study
Authors: Mohammedi Kamel , Belhatem Narimene , Berentzen Tina Landsvig , Catarig Andrei‐Mircea , Potier Louis 
Published: March 2023

AbstractAimsReal‐world data are required to support glucagon‐like peptide‐1 receptor agonist use in type 2 diabetes (T2D). SURE France assessed once‐weekly semaglutide in adults with T2D in real‐world clinical practice.Materials and MethodsThis multicentre, prospective, open‐label, single‐arm study included adults with T2D and ≥1 documented glycated haemoglobin (HbA1c) value ≤12 weeks before semaglutide initiation. The primary endpoint was HbA1c change from baseline to end of study (EOS; ~30 weeks). Secondary endpoints included change from baseline to EOS in body weight (BW) and waist circumference (WC); and proportion achieving HbA1c targets. Baseline characteristics and safety were reported for the full analysis set (patients initiating semaglutide). Analysis of other endpoints was based on the effectiveness analysis set (study completers receiving semaglutide at EOS).ResultsOf 497 patients initiating semaglutide (41.6% female, mean age 58.3 years), 348 completed the study on treatment. Baseline HbA1c, diabetes duration, BW and WC, were 8.3%, 10.0 years, 98.2 kg and 114.2 cm, respectively. The most common reasons for initiating semaglutide were to improve glycaemic control (79.7%), reduce BW (69.8%) and address cardiovascular risk (24.1%). At EOS, mean changes were: HbA1c, –1.2% points [95% confidence interval (CI) –1.32; –1.10]; BW, –4.7 kg (95% CI –5.38; –4.07); and WC, –4.9 cm (95% CI –5.94; –3.88). At EOS, 81.7%, 67.7% and 51.6% of patients achieved an HbA1c target of <8.0%, <7.5% and <7.0%, respectively. No new safety concerns were identified.ConclusionsThese results support the benefits of semaglutide in a real‐world setting in adults with T2D in France showing a significant reduction in HbA1c and body weight.
Reasons for ineligibility for clinical trials of patients with medication‐resistant epilepsy
Authors: Kerr Wesley T. , Chen Hai , Figuera Losada Mariana , Cheng Christopher , Liu Tiffany , French Jaqueline 
Published: March 2023

AbstractSelection criteria for clinical trials for medication‐resistant epilepsy are used to limit variability and to ensure safety. However, it has become more challenging to recruit subjects for trials. This study investigated the impact of each inclusion and exclusion criterion on medication‐resistant epilepsy clinical trial recruitment at a large academic epilepsy center. We retrospectively identified all patients with medication‐resistant focal or generalized onset epilepsy who attended an outpatient clinic over a consecutive 3‐month period. We assessed each patient's eligibility for trials with commonly required inclusion and exclusion criteria to evaluate the proportion of eligible patients and the most common reasons for exclusion. Among 212 patients with medication‐resistant epilepsy, 144 and 28 patients met the criteria for focal or generalized onset epilepsy, respectively. Overall, 9.4% (n = 20) patients were eligible for trials (19 focal onset and one generalized onset). Most patients were excluded from the study due to insufficient seizure frequency (58% of focal onset, 55% of generalized onset). A small proportion of patients with medication‐resistant epilepsy were eligible for trials based on common selection criteria. These eligible patients may not be representative of the general population of patients with medication‐resistant epilepsy. Insufficient seizure frequency was the most common reason for exclusion.
Diagnostic and therapeutic approaches in refractory insular epilepsy
Authors: Feys Odile , Goldman Serge , Lolli Valentina , Depondt Chantal , Legros Benjamin , Gaspard Nicolas , Schuind Sophie , De Tiège Xavier , Rikir Estelle 
Published: March 2023

AbstractDue to heterogenous seizure semiology and poor contribution of scalp electroencephalography (EEG) signals, insular epilepsy requires use of the appropriate diagnostic tools for its diagnosis and characterization. The deep location of the insula also presents surgical challenges. The aim of this article is to review the current diagnostic and therapeutic tools and their contribution to the management of insular epilepsy. Magnetic resonance imaging (MRI), isotopic imaging, neurophysiological imaging, and genetic testing should be used and interpretated with caution. Isotopic imaging and scalp EEG have demonstrated a lower value in epilepsy from insular compared to temporal origin, which increases the interest of functional MRI and magnetoencephalography. Intracranial recording with stereo‐electroencephalography (SEEG) is often required. The insular cortex, being highly connected and deeply located under highly functional areas, is difficult to reach, and its ablative surgery raises functional issues. Tailored resection based on SEEG or alternative curative treatments, such as radiofrequency thermocoagulation, laser interstitial thermal therapy, or stereotactic radiosurgery, have produced encouraging results. The management of insular epilepsy has benefited from major advances in the last years. Perspectives for diagnostic and therapeutic procedures will contribute to better management of this complex form of epilepsy.
The dynamics of the diversity–energy relationship during the last 21,000 years
Authors: Šímová Irena , Ordonez Alejandro , Storch David 
Published: March 2023

AbstractAimSpatial diversity patterns are linked to energy availability, but how the diversity–energy relationship changes in space and time is unclear. There are three possible scenarios: (a) equilibrium dynamics, where diversity is always positively related to energy availability in both time and space; (b) out‐of‐equilibrium dynamics, where diversity is determined by energy availability in equilibrium, but diversity variation lags behind changes in energy availability, leading to a mismatch between temporal and spatial diversity–energy relationships; and (c) disequilibrium dynamics where the equilibrium does not exist or is irrelevant. We attempt to distinguish these scenarios using spatio‐temporal palaeoecological data.LocationUSA and Canada.Time period21,000–1,000 years before present.Major taxa studiedWoody plants.MethodsWe tested for the strength and direction of temporal and spatial relationships between pollen type diversity of woody species and energy availability (estimated from temperature and precipitation) in 1,000‐year time steps.ResultsWhereas the temporal diversity–energy relationship appears only when energy levels rapidly change, the spatial diversity–energy relationship is pronounced only when these levels stabilize.Main conclusionsOur findings are consistent with the out‐of‐equilibrium scenario – diversity equilibria do exist and act as attractors of diversity dynamics, but diversity is often out of equilibrium. Consequently, current rapid climate changes can disrupt spatially consistent diversity–energy relationships. To understand diversity dynamics, it is crucial to simultaneously consider both the spatial and temporal dimensions of diversity variation.