bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on biomechanical compatibility for a novel artificial anal sphincter with constant force
Authors: Wang Minghui , Liu Yunlong , Liao Yucheng , Yu Hongliu
Published: March 2023

Background

Existing artificial anal sphincter studies have shown that biomechanical compatibility problem between artificial anal sphincter and rectum caused by long‐term morphological changes of the tissue surrounding the implanted prosthesis can lead to device failure or tissue ischemic necrosis. In this article, a mechanical artificial anal sphincter with constant force clamping is designed based on the superelasticity of shape memory alloys, which improved the biomechanical compatibility of implantable artificial anal sphincter.

Methods

Firstly, the anatomical structure and the biomechanical properties of the rectum are analyzed to obtain the size parameters and material parameters of the rectal model. Secondly, a novel artificial anal sphincter with constant force is designed to improve the biomechanical compatibility between the artificial sphincter and the rectum. Thirdly, the static analysis of artificial anal sphincter is carried out by finite element analysis.

Results

The simulation results show that the artificial anal sphincter can maintain a constant clamping force of 4 N within a certain variation range of intestinal tissue thickness, which verifies the constant force characteristic of the artificial anal sphincter. The constant clamping force of the artificial anal sphincter to the rectum is 4 N that is greater than the clamping force 3.99 N required to close the rectum, which verifies the effectiveness the artificial anal sphincter. The surface contact stress and the minimum principal stress of the rectum in the clamping state are less than the pressure threshold, which verifies the safety of the artificial anal sphincter.

Conclusions

The novel artificial anal sphincter has better biomechanical compatibility and improves the mechanical match between artificial sphincter and intestinal tissue. This study may provide more reasonable and effective simulation data for in vivo experiments of artificial anal sphincter in future, which may provide theoretical and technical support for further research about clinical application of artificial anal sphincter.
Phoenician–Punic amphorae in northern coastal Etruria: New evidence from Pisa (Italy)
Authors: Taccola Emanuele , Miriello Domenico , De Luca Raffaella , Cicogna Francesca , Coiai Serena , Girimonte Genea , Raneri Simona
Published: March 2023

This study outlines the circulation of Phoenician–Punic amphorae in northern coastal Etruria, with a particular focus on Pisa (Italy), where their presence has been attested since the mid‐eighth century BCE. A set of specimens from Piazza del Duomo was analysed by minero‐petrographic and geochemical techniques. The results were compared with literature data from Mediterranean production areas. The research allowed a better definition of the role of Etruscan Pisa in the frame of commercial and cultural routes in the Mediterranean, specifically in the Tyrrhenian area, also providing the opportunity to review the attestations of Phoenician–Punic amphora on a regional scale.
Serum angioneurin levels following electroconvulsive therapy for mood disorders
Authors: Zhang TianHong , Tang XiaoChen , Wei YanYan , Xu LiHua , Hu YeGang , Cui HuiRu , Zeng JiaHui , Ye JiaYi , Xie YuOu , Tang YingYing , Liu HaiChun , Chen Tao , Li ChunBo , Liu XiaoHua , Wang JiJun
Published: March 2023

Objectives

The efficacy of electroconvulsive therapy (ECT) in treating mood disorders (MDs) is hypothesized to be mediated by the induction of neurotrophic factors (denoted “angioneurins”) that trigger neuronal plasticity. This study aimed to assess the effects of ECT on serum angioneurin levels in patients with MD.

Methods

A total of 110 patients with MDs including 30 with unipolar depression, 25 with bipolar depression (BD), 55 with bipolar mania (BM), and 50 healthy controls were included in the study. Patients were subdivided into two groups: those who received ECT + medication (12 ECT sessions) and those who received only medication (no‐ECT). Depressive and manic symptom assessments and measurements of vascular endothelial growth factor (VEGF), fibroblast growth factor‐2, nerve growth factor (NGF), and insulin‐like growth factor‐1 levels in blood samples were performed at baseline and week 8.

Results

Patients in the ECT group, specifically those with BD and BM, had significantly increased levels of VEGF compared to their baseline VEGF levels (p = 0.002). No significant changes in angioneurin levels were observed in the no‐ECT group. Serum NGF levels were significantly associated with a reduction in depressive symptoms. Angioneurin levels were not associated with manic symptom reduction.

Conclusions

This study hints that ECT may increase VEGF levels with angiogenic mechanisms that amplify NGF signaling to promote neurogenesis. It may also contribute to changes in brain function and emotional regulation. However, further animal experiments and clinical validation are needed.
The philosophical and historical context of Bion's concept of reverie and its use as a rhetorical act in his theory of psychoanalysis
Authors: Sampolahti Timo , Laitila Aarno
Published: March 2023

In this article, we seek to clarify the historical and philosophical roots of Bion's somewhat enigmatic concept of reverie. We also reflect on the rhetorical reasons for Bion's decision to introduce the concept into psychotherapeutic discourse. Although Josef Breuer and Sigmund Freud (1894) had used the term in their Studies on Hysteria, prior to Bion it had lost its independent significance and role in psychotherapeutic theories. We would contend that even if the concept reverie has become increasingly popular in recent psychotherapeutic discourse, the relative neglect of its history and philosophy have led to problematic ways of implementing the concept in both the theory and practice of psychotherapy. We start from Jean‐Jacques Rousseau, moving on to Freud, William James, Henri Bergson and Gaston Bachelard. We present our view of why Bion considered reverie to be an indispensable tool in explicating certain psychoanalytic dimensions. We also reveal the kinds of historical and philosophical commitments that are embedded in the concept of reverie and append brief comments on the relevance of our analysis to the present state of psychotherapy and psychotherapy research.
Inhibition of protein kinase C delta leads to cellular senescence to induce anti‐tumor effects in colorectal cancer
Authors: Shimoyama Yuya , Yamada Kohji , Yoshida Saishu , Kawamura Akira , Hannya Yoshito , Imaizumi Yuta , Kumamoto Tomotaka , Takeda Yasuhiro , Shimoda Masayuki , Eto Ken , Yoshida Kiyotsugu
Published: March 2023

Protein kinase C delta (PKCδ) is a multifunctional serine–threonine kinase implicated in cell proliferation, differentiation, tumorigenesis, and therapeutic resistance. However, the molecular mechanism of PKCδ in colorectal cancer (CRC) remains unclear. In this study, we showed that PKCδ acts as a negative regulator of cellular senescence in p53 wild‐type (wt‐p53) CRC. Immunohistochemical analysis revealed that PKCδ levels in human CRC tissues were higher than those in the surrounding normal tissues. Deletion studies have shown that cell proliferation and tumorigenesis in wt‐p53 CRC is sensitive to PKCδ expression. We found that PKCδ activates p21 via a p53‐independent pathway and that PKCδ‐kinase activity is essential for p21 activity. In addition, both repression of PKCδ expression and inhibition of PKCδ activity induced cellular senescence‐like phenotypes, including increased senescence‐associated β‐galactosidase (SA‐β‐gal) staining, low LaminB1 expression, large nucleus size, and senescence‐associated secretory phenotype (SASP) detection. Finally, a kinase inhibitor of PKCδ suppressed senescence‐dependent tumorigenicity in a dose‐dependent manner. These results offer a mechanistic insight into CRC survival and tumorigenesis. In addition, a novel therapeutic strategy for wt‐p53 CRC is proposed.
Recent advances in extracellular vesicles in gastrointestinal cancer and lymphoma
Authors: Otsuka Motoyuki , Kotani Ai
Published: March 2023

Extracellular vesicles (EVs) are intercellular communication agents that transfer microRNAs (miRNAs), other non‐coding RNAs (ncRNAs), messenger RNAs (mRNAs), proteins, lipids, metabolites, and other molecules from donor cells (e.g., cancer cells) to recipient cells (e.g., stromal cells). In 2007, miRNAs were reported to be abundant among the ncRNAs present in EVs. Since then, many studies have investigated the functions of miRNAs and have attempted to apply these molecules to aid in the diagnosis and treatment of cancer. Research on EVs has expanded, particularly in the field of cancer, because cancer cells heavily secrete EVs. The cargo of these EVs, especially those in small EVs, such as exosomes, is assumed to work cooperatively and significantly in the tumor microenvironment and to promote metastasis. In this review, we first summarize recent studies on EVs in gastrointestinal cancer and highlight studies on human satellite II RNAs, which are a type of ncRNA found in EVs that possess repetitive sequences. Second, since several recent studies have revealed that phospholipids, which are components of EV membranes, play important roles in intercellular communication and the generation of lipid mediators in the tumor microenvironment, we review the reported roles of these molecules and discuss their potential use in the design of new cancer treatments.
ALKBH5‐induced circular RNA NRIP1 promotes glycolysis in thyroid cancer cells by targeting PKM2
Authors: Ji Xiaoyu , Lv Chengzhou , Huang Jiapeng , Dong Wenwu , Sun Wei , Zhang Hao
Published: March 2023

Although circular RNAs (circRNAs) are involved in cell proliferation, differentiation, apoptosis, and invasion, the underlying regulatory mechanisms of circRNAs in thyroid cancer have not been fully elucidated. This article aimed to study the role of circRNA regulated by N6‐methyladenosine modification in papillary thyroid cancer (PTC). Quantitative real‐time PCR, western blotting, and immunohistochemistry were used to investigate the expressions of circRNA nuclear receptor‐interacting protein 1 (circNRIP1) in PTC tissues and adjacent noncancerous thyroid tissues. In vitro and in vivo assays were carried out to assess the effects of circNRIP1 on PTC glycolysis and growth. The N6‐methyladenosine mechanisms of circNRIP1 were evaluated by methylated RNA immunoprecipitation sequencing, luciferase reporter gene, and RNA stability assays. Results showed that circNRIP1 levels were significantly upregulated in PTC tissues. Furthermore, elevated circNRIP1 levels in PTC patients were correlated with high tumor lymph node metastasis stage and larger tumor sizes. Functionally, circNRIP1 significantly promoted glycolysis, PTC cell proliferation in vitro, and tumorigenesis in vivo. Mechanistically, circNRIP1 acted as a sponge for microRNA (miR)‐541‐5p and miR‐3064‐5p and jointly upregulated pyruvate kinase M2 (PKM2) expression. Knockdown of m6A demethylase α‐ketoglutarate‐dependent dioxygenase alkB homolog 5 (ALKBH5) significantly enhanced circNRIP1 m6A modification and upregulated its expression. These results show that ALKBH5 knockdown upregulates circNRIP1, thus promoting glycolysis in PTC cells. Therefore, circNRIP1 can be a prognostic biomarker and therapeutic target for PTC by acting as a sponge for oncogenic miR‐541‐5p and miR‐3064‐5p to upregulate PKM2 expression.
A survey study on early detection of young children with disabilities in urban and rural areas of China
Authors: Su Xueyun , Peng Xiaomei , Liang Lelin , Li Yinhua , Xie Huichao
Published: March 2023

Aim

This study aimed to understand how children and families access early intervention in China.

Background

Timely identification and high‐quality intervention is expected to prevent and reduce the occurrence and severity of chronic functional impairment for children with disability and is of great significance to individuals and the society. The current study recruited 1129 caregivers of children with disabilities from rural and urban areas of China were recruited to participate in a survey.

Results

(a) The first concern about development was raised, usually by the parents, when a child with disabilities was 26 months of age, (b) developmental screening took place 4 months after the first concern and diagnostic evaluation happened 7 months after, (c) the types of early intervention programme varied across urban and rural areas and (d) child and family factors were found associating with age of detection.

Conclusions

Findings highlight the concerningly late age of children being identified for early intervention and disparities in services between urban and rural areas in China. Implications are provided for practitioners, policy makers and future research.
Srs11‐92, a ferrostatin‐1 analog, improves oxidative stress and neuroinflammation via Nrf2 signal following cerebral ischemia/reperfusion injury
Authors: Chen Yuhua , He Wei , Wei Hong , Chang Cuicui , Yang Lingjian , Meng Jiao , Long Tianlin , Xu Quanhua , Zhang Chi
Published: March 2023

Aim

Ferroptosis is increasingly becoming to be considered as an important mechanism of pathological cell death during stroke, and specific exogenous ferroptosis inhibitors have the ability to reverse cerebral ischemia/reperfusion injury. However, research on Srs11‐92 (AA9), a ferrostatin‐1 (Fer‐1) analog, in preclinical studies is limited.

Methods

In the middle cerebral artery occlusion‐reperfusion (MCAO/R) mice model or oxygen–glucose deprivation/reperfusion (OGD/R) cell model, Fer‐1, AA9, and/or ML385 were administered, and brain infarct size, neurological deficits, neuronal damage, oxidative stress, and neuroinflammation were determined after the damage, in vitro and in vivo.

Results

Fer‐1 and AA9 improved brain infarct size, neuronal damage, and neurological deficits in mice model of MCAO/R, and inhibited the overloaded iron deposition, ROS accumulation, and neuroinflammation response: it also increased the expression of GPx4, Nrf2, and HO‐1 and suppressed the expression of HMGB1 and NF‐κB p65 in the epicenter of injured hippocampal formation. However, Nrf2 inhibitor ML385 reversed the neuroprotective effect of AA9, including the oxidative stress and neuroinflammation. In vitro studies showed that AA9 relieved OGD/R‐induced neuronal oxidative stress and neuroinflammation via the Nrf2 pathway, which was impaired by ML385 in primary neurons.

Conclusion

The findings imply that Fer‐1 analog AA9 may be suitable for further translational studies for the protection of neuronal damage via Nrf2 signal pathway‐mediated oxidative stress and neuroinflammation in stroke and others neurological diseases.
Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study
Authors: Wu Jingjing , Guo Tao , Zhou Cheng , Bai Xueqin , Liu Xiaocao , Gu Luyan , Xuan Min , Gu Quanquan , Huang Peiyu , Song Zhe , Zhang Baorong , Xu Xiaojun , Zhang Minming , Guan Xiaojun
Published: March 2023

Background

Dysfunction of iron metabolism, especially in substantia nigra (SN), is widely acknowledged in Parkinson's disease (PD), but the genetic influence on iron deposition remains largely unknown. Thus, in this study, we aimed to investigate potential genetic impacts on iron deposition in PD.

Methods

Seventy‐four subjects, including 38 patients with PD and 36 age‐matched normal controls, participated in this study. Imaging genetic association analysis was used to identify the specific influence of single nucleotide polymorphism (SNP) on iron‐related quantitative traits (QT). Genetic effects on iron deposition at the disease level, SNP level, and their interactive effect were highlighted.

Results

Four strong SNP–QT associations were detected: rs602201‐susceptibility of bilateral SN, rs198440‐susceptibility of left SN, and rs7895403‐susceptibility of left caudate head. Detailed analyses showed that: (1) significant iron deposition was exclusively found in bilateral SN in PD; (2) altered polymorphisms of the A allele/A− genotype of rs602201 and G allele/G− genotype of rs198440 and rs7895403 were more frequently observed in PD; (3) for rs602201, among all subjects, A− genotype carriers showed significantly increased iron content than TT genotype in bilateral SN; for rs198440 and rs7895403, G− carriers showed increased iron content than AA genotype in left SN and left caudate head, respectively; and (4) rs602201 exhibited significant SNP‐by‐disease interaction in bilateral SN.

Conclusions

This study shows that rs602201 and rs198440 have a stimulative impact on nigral iron deposition in PD, which provides improved understanding of iron‐related pathogenesis in PD, and specifically, that vulnerability to iron deposition in SN is genetic‐based.
Upregulation of Wnt2b exerts neuroprotective effect by alleviating mitochondrial dysfunction in Alzheimer's disease
Authors: Xu Ling‐Zhi , Li Bing‐Qiu , Li Fang‐Yu , Quan Mei‐Na , Qin Wei , Li Ying , Li Wen‐Wen , Zhao Yu , Wei Yi‐Ping , Jia Jian‐Ping
Published: March 2023

Aims

This study investigated the relationship between plasma Wnt2b levels and Alzheimer's disease (AD), and explored the effect of Wnt2b on mitochondrial dysfunction in AD.

Methods

Healthy and AD subjects, AD transgenic mice, and in vitro models were used to investigate the roles of Wnt2b in abnormalities in canonical Wnt signaling and mitochondria in AD. RT‐qPCR, immunoblotting, and immunofluorescence analysis were performed to assay canonical Wnt signaling. Mitochondrial structure was analyzed by electron microscopy. Flow cytometry was used to examine the intracellular calcium and neuronal apoptosis.

Results

Plasma Wnt2b levels were lower in AD patients and positively correlated with cognitive performance. Similarly, Wnt2b was reduced in the hippocampus of AD mice and in vitro models. Next, Wnt2b overexpression and recombinant Wnt2b were used to endogenously and exogenously upregulate Wnt2b levels. Upregulation of Wnt2b could effectively prevent downregulation of canonical Wnt signaling, mitochondrial dysfunction in in vitro AD models. Subsequently, intracellular calcium overload and neuronal damage were ameliorated.

Conclusions

Our study highlights that Wnt2b decline is associated with cognitive impairment in AD, and upregulation of Wnt2b can exert neuroprotective effects in AD, particularly in ameliorating mitochondrial dysfunction.
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

Aims

Multiple 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.

Methods

To 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.

Results

We 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.

Conclusion

Our 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

Aims

The 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.

Methods

Genome‐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.

Results

We 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.

Conclusion

LncRNA 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

Human 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

Limbal 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

Sleep 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

Objectives

Little 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.

Methods

Observational 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.

Results

Forty‐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).

Conclusions

The 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

We 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

Initiatives 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

Aim

To clarify the effects of glucose‐dependent insulinotropic polypeptide (GIP) receptor agonists (GIPRAs) on feeding and body weight.

Materials and Methods

Acute 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).

Results

Single 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.

Conclusions

GIPFA‐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

Aims

Real‐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 Methods

This 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).

Results

Of 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.

Conclusions

These 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

Selection 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

Due 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.
Radiation resistance of cancer cells caused by mitochondrial dysfunction depends on SIRT3‐mediated mitophagy
Authors: Wei Yan , Xiao Guohui , Xu Hui , Sun Xuehua , Shi Yingying , Wang Fen , Kang Jinlin , Peng Jin , Zhou Fuxiang
Published: March 2023

Radiation resistance is the leading cause of radiotherapy failure in patients with cancer. Enhanced DNA damage repair is the main reason for cancer cells to develop resistance to radiation. Autophagy has been widely reported to be linked to increased genome stability and radiation resistance. Mitochondria are highly involved in the cell response to radiotherapy. However, the autophagy subtype mitophagy has not been studied in terms of genome stability. We have previously demonstrated that mitochondrial dysfunction is the cause of radiation resistance in tumour cells. In the present study, we found that SIRT3 was highly expressed in colorectal cancer cells with mitochondrial dysfunction, leading to PINK1/Parkin‐mediated mitophagy. Excessive activation of mitophagy enhanced DNA damage repair, therefore promoting the resistance of tumour cells to radiation. Mechanistically, mitophagy resulted in decreased RING1b expression, which led to a reduction in the ubiquitination of histone H2A at K119, thereby enhancing the repair of DNA damage caused by radiation. Additionally, high expression of SIRT3 was related to a poor tumour regression grade in rectal cancer patients treated with neoadjuvant radiotherapy. These findings suggest that restoring mitochondrial function could be an effective method for increasing the radiosensitivity of patients with colorectal cancer.
The dynamics of the diversity–energy relationship during the last 21,000 years
Authors: Šímová Irena , Ordonez Alejandro , Storch David
Published: March 2023

Aim

Spatial 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.

Location

USA and Canada.

Time period

21,000–1,000 years before present.

Major taxa studied

Woody plants.

Methods

We 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.

Results

Whereas 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 conclusions

Our 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.
Domain analysis of Drosophila Blimp‐1 reveals the importance of its repression function and instability in determining pupation timing
Authors: Sarhan Moustafa , Miyagawa Koichi , Ueda Hitoshi
Published: March 2023

The PRDM family transcription repressor Blimp‐1 is present in almost all multicellular organisms and plays important roles in various developmental processes. This factor has several conserved motifs among different species, but the function of each motif is unclear. Drosophila Blimp‐1 plays an important role in determining pupation timing by acting as an unstable transcriptional repressor of the βftz‐f1 gene. Thus, Drosophila provides a good system for analyzing the molecular and biological functions of each region in Blimp‐1. Various Blimp‐1 mutants carrying deletions at the conserved motifs were induced under the control of the heat shock promoter in prepupae, and the expression patterns of βFTZ‐F1 and Blimp‐1 and pupation timing were observed. The results showed that the regions with strong and weak repressor functions exist within the proline‐rich middle section of the factor and near the N‐terminal conserved motif, respectively. Rapid degradation was supported by multiple regions that were mainly located in a large proline‐rich region. Results revealed that pupation timing was affected by the repression ability and stability of Blimp‐1. This suggests that both the repression function and instability of Blimp‐1 are indispensable for the precise determination of pupation timing.
Mothering load: Underlying realities of professionally engaged Indian mothers during a global crisis
Authors: Mazumdar Ketoki , Parekh Sneha , Sen Isha
Published: March 2023

The current global crisis has had a significant impact on professionally engaged mothers and the proliferation of the invisible nature of the work that they are engaged in on a daily basis. Several research studies have indicated how mothers seem to have been particularly affected. Mothers experienced an exacerbation in their domestic household and child‐care responsibilities due to the absence of househelp and other child care arrangements while balancing their professional careers. These challenges crystallized the existing gender inequalities and the gendered nature of parenting. Using a feminist lens, this study explores the experiences of mothering load during COVID‐19 against the backdrop of urban India. A total of two themes and six sub‐themes were identified through the process of thematic analysis—Triad of work included increased care work, increased formal work, and increased worry work and Mothering experiences: Burdens and Biases included the lack of support, parental role overload, and gendered nature of parenting. This study adds to the limited empirical evidence of working mothers in India while straddling the worlds of feminism and mental health activism. Findings indicate the need to explicitly highlight the invisibilized phenomena of unpaid care work, worry work, and the gendered nature of parenting that contribute to the larger experience of mothering load. The findings also point toward acknowledging the importance of maternal mental health and the United Nations Sustainable Development Goal 5 to establish and enforce stronger policies around recognizing and appreciating unpaid care and domestic work to promote gender equality and empowering women at all levels. This may be enacted through the encouragement of shared responsibilities within the household and family units as contextually feasible and through the development of appropriate infrastructure, social protection policies, and the delivery of public services.