bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytes in CA1 modulate schema establishment in the hippocampal-cortical neuron network
Authors: Liu Shu , Wong Heung Yan , Xie Li , Iqbal Zafar , Lei Zhuogui , Fu Zhongqi , Lam Yuk Yan , Ramkrishnan Aruna Surendran , Li Ying 
Published: November 2022

Abstract
Background
Schema, a concept from cognitive psychology used to explain how new information is integrated with previous experience, is a framework of acquired knowledge within associative network structures as biological correlate, which allows new relevant information to be quickly assimilated by parallel cortical encoding in the hippocampus (HPC) and cortex. Previous work demonstrated that myelin generation in the anterior cingulate cortex (ACC) plays a critical role for dynamic paired association (PA) learning and consolidation, while astrocytes in ACC play a vital role in cognitive decision-making. However, circuit components and mechanism involving HPC-anterior cingulate cortex (ACC) during schema formation remain uncertain. Moreover, the correlation between HPC-ACC circuit and HPC astrocytic activity is unclear.

Results
Utilizing a paired association (PA) behavioral paradigm, we dynamically recorded calcium signals of CA1-ACC projection neurons and ACC neurons during schema formation. Depending on the characteristics of the calcium signals, three distinct stages of schema establishment process were identified. The recruitment of CA1-ACC network was investigated in each stage under CA1 astrocytes Gi pathway chemogenetic activation. Results showed that CA1-ACC projecting neurons excitation gradually decreased along with schema development, while ACC neurons revealed an excitation peak in the middle stage. CA1 astrocytic Gi pathway activation will disrupt memory schema development by reducing CA1-ACC projection neuron recruitment in the initial stage and prevent both CA1-ACC projection neurons and ACC neuron excitation in the middle stage. CA1 astrocytes Gi markedly suppress new PA assimilation into the established memory schema.

Conclusions
These results not only reveal the dynamic feature of CA1-ACC network during schema establishment, but also suggest CA1 astrocyte contribution in different stages of schema establishment.
ERF49 mediates brassinosteroid regulation of heat stress tolerance in Arabidopsis thaliana
Authors: Chen Xia , Xue Huidan , Zhu Liping , Wang Huiqin , Long Hao , Zhao Jun , Meng Funing , Liu Yunfei , Ye Yuan , Luo Xiaomin , Liu Zhi , Xiao Guanghui , Zhu Shengwei 
Published: November 2022

Abstract
Background
Heat stress is a major abiotic stress affecting the growth and development of plants, including crop species. Plants have evolved various adaptive strategies to help them survive heat stress, including maintaining membrane stability, encoding heat shock proteins (HSPs) and ROS-scavenging enzymes, and inducing molecular chaperone signaling. Brassinosteroids (BRs) are phytohormones that regulate various aspects of plant development, which have been implicated also in plant responses to heat stress, and resistance to heat in Arabidopsis thaliana is enhanced by adding exogenous BR. Brassinazole resistant 1 (BZR1), a transcription factor and positive regulator of BR signal, controls plant growth and development by directly regulating downstream target genes. However, the molecular mechanism at the basis of BR-mediated heat stress response is poorly understood. Here, we report the identification of a new factor critical for BR-regulated heat stress tolerance.

Results
We identified ERF49 in a genetic screen for proteins required for BR-regulated gene expression. We found that ERF49 is the direct target gene of BZR1 and that overexpressing ERF49 enhanced sensitivity of transgenic plants to heat stress. The transcription levels of heat shock factor HSFA2, heat stress-inducible gene DREB2A, and three heat shock protein (HSP) were significantly reduced under heat stress in ERF49-overexpressed transgenic plants. Transcriptional activity analysis in protoplast revealed that BZR1 inhibits ERF49 expression by binding to the promoter of ERF49. Our genetic analysis showed that dominant gain-of-function brassinazole resistant 1-1D mutant (bzr1-1D) exhibited lower sensitivity to heat stress compared with wild-type. Expressing ERF49-SRDX (a dominant repressor reporter of ERF49) in bzr1-1D significantly decreased the sensitivity of ERF49-SRDX/bzr1-1D transgenic plants to heat stress compared to bzr1-1D.

Conclusions
Our data provide clear evidence that BR increases thermotolerance of plants by repressing the expression of ERF49 through BZR1, and this process is dependent on the expression of downstream heat stress-inducible genes. Taken together, our work reveals a novel molecular mechanism mediating plant response to high temperature stress.
Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood
Authors: van Cruchten Remco T. P. , van As Daniël , Glennon Jeffrey C. , van Engelen Baziel G. M. , ‘t Hoen Peter A. C. ,   the OPTIMISTIC consortium,   the ReCognitION consortium, Okkersen K , Jimenez-Moreno C , Wenninger S , Daidj F , Cumming S , Littleford R , Monckton D G , Lochmüller H , Catt M , Faber C G , Hapca A , Donnan P T , Gorman G , Bassez G , Schoser B , Knoop H , Treweek S , Wansink Derick G. , Impens Francis , Gabriels Ralf , Claeys Tine , Ravel-Chapuis Aymeric , Jasmin Bernard J. , Mahon Niamh , Nieuwenhuis Sylvia , Martens Lennart , Novak Petr , Furling Denis , Baak Arie , Gourdon Genevieve , MacKenzie Alex , Martinat Cecile , Neault Nafisa , Roos Andreas , Duchesne Elise , Salz Renee , Thompson Rachel , Baghdoyan Sandrine , Varghese Anu Mary , Blom Paul , Spendiff Sally , Manta Alexander 
Published: November 2022

AbstractBackgroundMyotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (DMPK) gene. The OPTIMISTIC clinical trial demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Through a process of reverse engineering, this study aims to identify druggable molecular biomarkers associated with the clinical improvement in the OPTIMISTIC cohort.MethodsBased on full blood samples collected during OPTIMISTIC, we performed paired mRNA sequencing for 27 patients before and after the CBT intervention. Linear mixed effect models were used to identify biomarkers associated with the disease-causing CTG expansion and the mean clinical improvement across all clinical outcome measures.ResultsWe identified 608 genes for which their expression was significantly associated with the CTG-repeat expansion, as well as 1176 genes significantly associated with the average clinical response towards the intervention. Remarkably, all 97 genes associated with both returned to more normal levels in patients who benefited the most from CBT. This main finding has been replicated based on an external dataset of mRNA data of DM1 patients and controls, singling these genes out as candidate biomarkers for therapy response. Among these candidate genes wereDNAJB12,HDAC5, andTRIM8, each belonging to a protein family that is being studied in the context of neurological disorders or muscular dystrophies. Across the different gene sets, gene pathway enrichment analysis revealed disease-relevant impaired signaling in, among others, insulin-, metabolism-, and immune-related pathways. Furthermore, evidence for shared dysregulations with another neuromuscular disease, Duchenne muscular dystrophy, was found, suggesting a partial overlap in blood-based gene dysregulation.ConclusionsDM1-relevant disease signatures can be identified on a molecular level in peripheral blood, opening new avenues for drug discovery and therapy efficacy assessments.
Putative juvenile terrorists: the relationship between multiple traumatization, mental health, and expectations for reintegration among Islamic State recruited adolescent and young adult fighters
Authors: Mohammed Rezhna , Neuner Frank 
Published: November 2022

Abstract
Background
In several conflicts worldwide children are recruited as fighters in irregular forces. These children need to be reintegrated into the society after the conflict. However, concurrent to various reservations in the communities, the reintegration of former child soldiers is challenged by the fact that many of the affected children were indoctrinated by the armed group and traumatized through war events. Even several years after the defeat of the terrorist organization ISIS in Iraq, systematic efforts towards the reintegration of children who had been recruited by ISIS are notably absent.

Methods
we conducted clinical interviews with a sample of N = 59 adolescents and young adults who were incarcerated for terrorism in the prisons of the Kurdistan Region of Iraq to assess levels and types of trauma exposure, PTSD, depression, readiness to reintegrate and ongoing identification with ISIS.

Results
We found high levels of PTSD and depression that were associated with trauma exposure. The subjective readiness to reintegrate into the communities was associated with trauma exposure and was mediated by depression, even after controlling for the influence of ongoing identification with the armed group.

Conclusion
The study indicates that trauma-related mental ill-health should be considered in efforts to reintegrate young former terrorists.
Tuning gradient boosting for imbalanced bioassay modelling with custom loss functions
Authors: Boldini Davide , Friedrich Lukas , Kuhn Daniel , Sieber Stephan A. 
Published: November 2022

AbstractWhile in the last years there has been a dramatic increase in the number of available bioassay datasets, many of them suffer from extremely imbalanced distribution between active and inactive compounds. Thus, there is an urgent need for novel approaches to tackle class imbalance in drug discovery. Inspired by recent advances in computer vision, we investigated a panel of alternative loss functions for imbalanced classification in the context of Gradient Boosting and benchmarked them on six datasets from public and proprietary sources, for a total of 42 tasks and 2 million compounds. Our findings show that with these modifications, we achieve statistically significant improvements over the conventional cross-entropy loss function on five out of six datasets. Furthermore, by employing these bespoke loss functions we are able to push Gradient Boosting to match or outperform a wide variety of previously reported classifiers and neural networks. We also investigate the impact of changing the loss function on training time and find that it increases convergence speed up to 8 times faster. As such, these results show that tuning the loss function for Gradient Boosting is a straightforward and computationally efficient method to achieve state-of-the-art performance on imbalanced bioassay datasets without compromising on interpretability and scalability.
Graphical Abstract
De novo and inherited variants in coding and regulatory regions in genetic cardiomyopathies
Authors: Vadgama Nirmal , Ameen Mohamed , Sundaram Laksshman , Gaddam Sadhana ,   Genomics England Research Consortium, Gifford Casey , Nasir Jamal , Karakikes Ioannis 
Published: November 2022

Abstract
Background
Cardiomyopathies are a leading cause of progressive heart failure and sudden cardiac death; however, their genetic aetiology remains poorly understood. We hypothesised that variants in noncoding regulatory regions and oligogenic inheritance mechanisms may help close the diagnostic gap.

Methods
We first analysed whole-genome sequencing data of 143 parent–offspring trios from Genomics England 100,000 Genomes Project. We used gene panel testing and a phenotype-based, variant prioritisation framework called Exomiser to identify candidate genes in trios. To assess the contribution of noncoding DNVs to cardiomyopathies, we intersected DNVs with open chromatin sequences from single-cell ATAC-seq data of cardiomyocytes. We also performed a case–control analysis in an exome-negative cohort, including 843 probands and 19,467 controls, to assess the association between noncoding variants in known cardiomyopathy genes and disease.

Results
In the trio analysis, a definite or probable genetic diagnosis was identified in 21 probands according to the American College of Medical Genetics guidelines. We identified novel DNVs in diagnostic-grade genes (RYR2, TNNT2, PTPN11, MYH7, LZR1, NKX2-5), and five cases harbouring a combination of prioritised variants, suggesting that oligogenic inheritance and genetic modifiers contribute to cardiomyopathies. Phenotype-based ranking of candidate genes identified in noncoding DNV analysis revealed JPH2 as the top candidate. Moreover, a case–control analysis revealed an enrichment of rare noncoding variants in regulatory elements of cardiomyopathy genes (p = .035, OR = 1.43, 95% Cl = 1.095–1.767) versus controls. Of the 25 variants associated with disease (p< 0.5), 23 are novel and nine are predicted to disrupt transcription factor binding motifs.

Conclusion
Our results highlight complex genetic mechanisms in cardiomyopathies and reveal novel genes for future investigations.
Psychometric assessment of Persian translation of Yale Food Addiction Scale Version 2.0 (YFAS 2.0) in Iranian college students
Authors: Ghanbari Nikzad , Nooripour Roghieh , Firoozabadi Abbas , Var Tabassom Saeid Par , Wisniewski Pamela , Hosseini Seyed Ruhollah 
Published: November 2022

Abstract
Background
Food addiction at the individual level causes physical and mental health problems, impairs individuals' social functioning, and causes dysfunction in the family system. Therefore, a tool to identify this behavioral disorder is one of the health requirements of communities. This research aimed to investigate the psychometric assessment of the Persian translation of Yale Food Addiction Scale Version 2.0 (YFAS 2.0) in Iranian college students.

Method
This research was cross-sectional descriptive, and 451 students were selected by convenience sampling method. Yale Food Addiction Scale Version 2.0 (YFAS 2.0), Depression, Anxiety, and Stress Scale-21 (DASS-21), and Food Craving Questionnaire-Trait, reduced (FCQ-T-r) were used to collect data.

Results
The confirmatory factor analysis indicated that single-factor model provides a good fit to data (SRMR = 0.078; CFI = 0.94; NFI = 0.92; IFI = 0.94; RFI = 0.91; GFI = 0.90; RMSEA = 0.078). The YFAS's 2.0 positive correlations with three DASS-21 subscales ranged from 0.30 to 0.39, and Food Craving Questionnaire-Trait, reduced (FCQ-T-r) ranged from 0.58 to 0.72. All correlations were statistically significant, indicating acceptable convergent validity (P < 0.01).

Conclusion
The validity of the Persian questionnaire translation has been confirmed. Researchers and specialists can use this scale to diagnose food addiction for research or diagnostic purposes in Iranian society.
Bone scintigraphy outperformed anatomic images in frostbite injuries: a case report
Authors: Ronchi Brunela , Peña Gustavo Agustin , Carla Albertti 
Published: November 2022

AbstractFrostbite is a localized cold thermal injury, as a result of tissue exposure to temperatures below freezing point for a prolonged period of time. The spectrum of injury is broad; thus, frostbite injuries may have deleterious effects with the possibility of losing part or whole extremities. We aim to present the case of a 38-year-old male patient evaluated with multiphase technetium-99m-methylene diphosphonate bone scintigraphy. This methodology may accelerate clinical management of frostbite injuries because it provides precise clinical-imaging correlation by determining the extent of injury and can accurately predict the level of amputation if required.
Epilepsy, intellectual disability and the epilepsy care pathway: improving outcomes
Authors: Kerr Michael , Goodwin Geraldine , Hanna Jane 
Published: November 2022

SUMMARYThe strong, life-long association between epilepsy and intellectual disability means that psychiatric teams, and the services they exist in, have a need for significant competencies in the field of epilepsy. This article addresses these competencies through the pathway of care. It will focus on those areas most relevant to psychiatric care and, when possible, explore where technology has begun to influence practice. The pathway leads from diagnosis through, in some cases, to mortality and support of the bereaved in psychiatric care. We will approach the topic through showing how the intertwining themes of information, empowerment, access to care, assessment of risk and psychological support are important. Technological advances are supporting changes in most of these areas, and psychological support, a knowledge of the needs of people with epilepsy and intellectual disability and epilepsy skills remain the foundation in the application of these advances.
Approach to the Patient With Short Stature: Genetic Testing
Authors: Perchard Reena , Murray Philip George , Clayton Peter Ellis 
Published: November 2022

AbstractThe first step in the evaluation of the short child is to decide whether growth parameters in the context of the history are abnormal or a variant of normal. If growth is considered abnormal, system and hormonal tests are likely to be required, followed by more directed testing, such as skeletal survey and/or genetic screening with karyotype or microarray. In a small percentage of short children in whom a diagnosis has not been reached, this will need to be followed by detailed genetic analysis; currently, exome sequencing using targeted panels relevant to the phenotype is the commonly used test. Clinical scenarios are presented that illustrate how such genetic testing can be used to establish a molecular diagnosis, and how that diagnosis contributes to the management of the short child. New genetic causes for short stature are being recognized on a frequent basis, while the clinical spectrum for known genes is being extended. We recommend that an international repository for short stature conditions is established for new findings to aid dissemination of knowledge, but also to help in the definition of the clinical spectrum both for new and established conditions.
ACROBAT Edge: Safety and Efficacy of Switching Injected SRLs to Oral Paltusotine in Patients With Acromegaly
Authors: Gadelha Monica R , Gordon Murray B , Doknic Mirjana , Mezősi Emese , Tóth Miklós , Randeva Harpal , Marmon Tonya , Jochelson Theresa , Luo Rosa , Monahan Michael , Madan Ajay , Ferrara-Cook Christine , Struthers R Scott , Krasner Alan 
Published: November 2022

AbstractContextPaltusotine is a once-daily, oral, nonpeptide small-molecule somatostatin receptor type 2 (SST2) agonist in clinical development for treatment of acromegaly.ObjectiveThis work aimed to evaluate change in insulin-like growth factor I (IGF-I) levels in patients switched from octreotide long-acting release or lanreotide depot monotherapy to paltusotine.MethodsA phase 2, open-label, prospective, multicenter, multinational, nonrandomized, single-arm exploratory study was conducted in which dosage uptitrations were performed in a double-blinded manner. At 26 global sites, patients with acromegaly switched to paltusotine from injected somatostatin receptor ligand (SRL)-based therapy. Patients received 13-week treatment with once-daily oral paltusotine (10-40 mg/d). The primary end point was change from baseline to week 13 in IGF-I for patients who switched from long-acting octreotide or lanreotide depot monotherapy to paltusotine (group 1). All patients underwent a 4-week paltusotine washout at end of treatment period (wk 13-17). IGF-I, growth hormone (GH), patient-reported outcome, and safety data were collected.ResultsForty-seven patients enrolled. In group 1 (n = 25), IGF-I and GH showed no significant change between SRL baseline and end of paltusotine treatment at week 13 (median change in IGF-I = −0.03×upper limit of normal [ULN]; P = .6285; GH = −0.05 ng/mL; P = .6285). IGF-I and GH rose significantly in the 4 weeks after withdrawing paltusotine (median change in IGF-I = 0.55×ULN; P &lt; .0001 [median increase 39%]; GH = 0.72 ng/mL; P &lt; .0001 [109.1% increase]). No patients discontinued because of adverse events (AE); no treatment-related serious AEs were reported.ConclusionThese results suggest once-daily oral paltusotine was effective in maintaining IGF-I values in patients with acromegaly who switched from injected SRLs. Paltusotine was well tolerated with a safety profile consistent with other SRLs.
Discoidin domain receptor regulates ensheathment, survival and caliber of peripheral axons
Authors: Corty Megan M. , Hulegaard Alexandria L. , Hill Jo Q. , Sheehan Amy E. , Aicher Sue A. , Freeman Marc R. 
Published: November 2022

ABSTRACT
Most invertebrate axons and small-caliber axons in mammalian peripheral nerves are unmyelinated but still ensheathed by glia. Here, we use Drosophila wrapping glia to study the development and function of non-myelinating axon ensheathment, which is poorly understood. Selective ablation of these glia from peripheral nerves severely impaired larval locomotor behavior. In an in vivo RNA interference screen to identify glial genes required for axon ensheathment, we identified the conserved receptor tyrosine kinase Discoidin domain receptor (Ddr). In larval peripheral nerves, loss of Ddr resulted in severely reduced ensheathment of axons and reduced axon caliber, and we found a strong dominant genetic interaction between Ddr and the type XV/XVIII collagen Multiplexin (Mp), suggesting that Ddr functions as a collagen receptor to drive axon wrapping. In adult nerves, loss of Ddr decreased long-term survival of sensory neurons and significantly reduced axon caliber without overtly affecting ensheathment. Our data establish essential roles for non-myelinating glia in nerve development, maintenance and function, and identify Ddr as a key regulator of axon–glia interactions during ensheathment and establishment of axon caliber.
A new CUT&RUN low volume-urea (LoV-U) protocol optimized for transcriptional co-factors uncovers Wnt/β-catenin tissue-specific genomic targets
Authors: Zambanini Gianluca , Nordin Anna , Jonasson Mattias , Pagella Pierfrancesco , Cantù Claudio 
Published: November 2022

ABSTRACT
Upon WNT/β-catenin pathway activation, stabilized β-catenin travels to the nucleus where it associates with the TCF/LEF transcription factors, constitutively bound to genomic Wnt-responsive elements (WREs), to activate target gene transcription. Discovering the binding profile of β-catenin is therefore required to unambiguously assign direct targets of WNT signaling. Cleavage under targets and release using nuclease (CUT&RUN) has emerged as prime technique for mapping the binding profile of DNA-interacting proteins. Here, we present a modified version of CUT&RUN, named LoV-U (low volume and urea), that enables the robust and reproducible generation of β-catenin binding profiles, uncovering direct WNT/β-catenin target genes in human cells, as well as in cells isolated from developing mouse tissues. CUT&RUN-LoV-U outperforms original CUT&RUN when targeting co-factors that do not bind the DNA, can profile all classes of chromatin regulators and is well suited for simultaneous processing of several samples. We believe that the application of our protocol will allow the detection of the complex system of tissue-specific WNT/β-catenin target genes, together with other non-DNA-binding transcriptional regulators that act downstream of ontogenetically fundamental signaling cascades.