bluuebunny/crossref_metadata_2025 huggingface dataset:
A cultural adaptation and testing on the reliability and validity of the Chinese version of the Menopause Symptom Assessment Scale
Authors: Hou Jie , Wang Diya , Su Jing
Published: December 2024

Objective

The aim of this study was to modify the Chinese version of the Menopause Symptom Assessment Scale (MSAS) and evaluate its validity and reliability.

Methods

An expert panel from the gynecology and nursing domain determined items that should remain or be revised, and 30 participants were selected for the pilot study. A total of 255 women who met the criteria for inclusion were enrolled in the investigation. SPSS 25.0 and AMOS 25.0 were used to analyze data. The internal and external reliability of the scale was evaluated using Cronbach's α coefficient, split-half reliability, and test-retest reliability, respectively. Expert review, exploratory factor analysis, and confirmatory factor analysis were used to evaluate the scale's validity, which encompasses both its content validity and structural validity.

Results

The Chinese version of the MSAS contains 43 items with 5 dimensions, including sexual function, psychological status, interpersonal anxiety, autonomic balance, and other subjective symptoms. The correlation coefficient (r value) between individual items and the total scale ranged from 0.49 to 0.67 (P < 0.05); the Item-Content Validity Index range from 0.80 to 1.00, and Scale-Content Validity Index was 0.91; the Cronbach's α coefficient was 0.85, and the test-retest reliability was 0.93; exploratory factor analysis revealed a cumulative variance contribution of 76.98%; the fitting index of the scale structure model was good.

Conclusions

The updated Chinese version of the MSAS presented good reliability and validity and could be applied in assessing menopausal symptoms in Chinese women.
Comparison between virtual reality and traditional lecture methods in educating respiratory therapy students on pediatric difficult airway diseases
Authors: Hsu Wen-Jing , Tang Yi-Hsuan , Chen Wei-Chih , Lee Yu-Sheng , Tsao Pei-Chen , Chen Wei-Yu , Yang Ying-Ying , Ko Hsin-Kuo , Pan Sheng-Wei , Ting Yu-Fen , Yang Shih-Hsing , Jeng Mei-Jy
Published: December 2024

Background:

Pediatric airway diseases are associated with complex challenges because of smaller and more dynamic airway structures in children. These conditions, along with specialized management by medical care staff, should be immediately and precisely recognized to prevent life-threatening obstructions and long-term respiratory complications. Recently, virtual reality (VR) has emerged as an innovative approach to clinical medical education. To evaluate and compare the effectiveness of VR-based education and traditional lectures in enhancing knowledge retention, clinical reasoning, and motivation among senior respiratory therapy students.

Methods:

This experimental research was conducted between November 2020 and September 2022, involving 54 students from a School of Respiratory Therapy, with 43 completing a pre-test and undergoing random assignment into either a VR or a traditional education (non-VR) group. Samsung Gear VR Oculus headsets were used by the VR group for instructions on conditions such as laryngeal malacia, subglottic stenosis, and tracheomalacia. Theoretical exams, objective structured clinical examinations (OSCE), and instructional material motivation survey (IMMS) were used to evaluate participants’ knowledge retention, clinical reasoning, and application capabilities, followed by statistical analysis comparing both study groups.

Results:

No significant differences in pre-test scores were observed between the two groups. However, the VR group outperformed the non-VR group in OSCE scores significantly (p = 0.003) and demonstrated greater learning motivation and satisfaction based on IMMS scores. No notable difference in immediate post-education theoretical examination scores was observed between the groups.

Conclusion:

VR-based education markedly improved the clinical reasoning and application skills of respiratory therapy students over traditional lecture methods. VR learning also increased students’ motivation and satisfaction, indicating a more immersive and effective educational experience. These findings reveal that VR may be best utilized as a supplemental educational tool in clinical training programs. Future studies with larger samples and longer follow-up are warranted to further explore the optimal integration of VR in education.
Iron deficiency promotes intra-leaflet hemorrhage-induced aortic valve calcification: an experimental study
Authors: Liu Huiruo , Yang Zeyu , Sun Hourong , Wang Zerui , Xu Feng , Chen Yuguo , Li Chuanbao
Published: December 2024

Background:

Intra-leaflet hemorrhage (IH) plays a well-recognized detrimental role in calcified aortic valve disease (CAVD). However, IH-induced fibro-osteogenic responses in valvular interstitial cells (VICs) appear to be triggered under specific pathological conditions. Iron deficiency (ID), a common co-morbidity in CAVD, may influence these responses. This study investigated the relationship between ID and pathological changes associated with CAVD, and its effects on IH-mediated fibro-osteogenic differentiation of VICs.

Methods and results:

Two independent studies were conducted, including 2495 patients in the discovery study and 34 in the validation study. Our data demonstrated that ID was associated with CAVD severity and progression, particularly in an age-dependent manner. Based on these clinical findings, immunofluorescence and Western blot analyses revealed that TFR1, a key iron import transporter, was significantly upregulated in human calcified aortic valves. Concurrently, iron accumulation was detected by Perl’s staining in both calcific and non-calcific valve sections. In vitro, VICs cultured with human serum from ID patients showed red blood cell lysis-induced iron overload and fibro-calcific differentiation.

Conclusions:

ID triggers TFR1-mediated intracellular iron overload, leading to fibrosis and calcification in human VICs, thereby contributing to IH-mediated valve remodeling and calcification. These findings supported the potential role of monitoring and correcting ID to slow or prevent the progression of valvular calcification.
Chinese guidelines for ultrasound-guided thermal ablation of thyroid nodules (2024 edition)
Authors: Han Zhi-Yu , Dou Jian-Ping , Zheng Lin , Xu Min , Ren Jie , Wang Hui , Wang Shu-Rong , Zhan Wei-Wei , Zhou Jian-Qiao , Xu Shu-Hang , Cheng Wen , Lu Man , Xu Dong , Yu Jie , Jing Fei , Yu Ming-an , Yu Song-Yuan , Cheng Zhi-Gang , Peng Cheng-Zhong , Che Ying , Dai Wei-de , Zhou Zu-Bang , Yang Hong , Leng Xiao-Ping , Sun Li-Ping , He Guang-Bin , He Guang-Zhi , Cong Zhi-Bin , Li Qin-Ying , Zhao Qi-Yu , Nan Bai , Liu Cun , Guo Jia , Li Qian , Wei Qiang , Wang Gang , Huang Ying , Sun De-Sheng , Jiang Tian-an , Liang Ping
Published: December 2024

The Chinese guidelines for ultrasound-guided thermal ablation of thyroid nodules (2024 edition) were jointly initiated by the Ultrasound Committee of Chinese Medical Association, the Interventional Ultrasound Committee of Chinese Association of Ultrasound in Medicine and Engineering, the Ultrasonic Intervention Committee of Chinese Colleges of Interventionalists, and the Oncological Intervention Committee of Chinese Research Hospital Association; 37 multidisciplinary experts in interventional ultrasound, ultrasound medicine, endocrinology, and thyroid surgery participated in the compilation of this guide, which expanded the depth and breadth of the perspective and enhanced the authority of the guide. Based on the systematic review of literature related to ultrasound-guided thermal ablation of thyroid nodules and the professional opinions of experts, the guidelines define the indications and contraindications of thermal ablation, including pre-ablation evaluation and preparation, thermal ablation techniques and operational procedures, post-ablation follow-up, therapeutic effect evaluation, complication prevention and treatment, and the writing of medical documents for ablation. According to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), a total of 17 objective and comprehensive recommendations were given. The publication and promotion of this guideline will play a positive role in promoting the standardization of ultrasound-guided thermal ablation of thyroid nodules.
A bibliotherapy intervention to improve emotional wellbeing during cancer treatment: a pilot study
Authors: Wells Elizabeth , Gunn Kate , Velasquez Diane , Kaeding Jo , Hutchinson Amanda
Published: December 2024

Background:

Bibliotherapy, or reading for therapy, has been shown to help with a variety of mental health conditions, yet reading can be difficult for those undergoing treatment due to cancer-related cognitive impairment (CRCI). Listening is likely to be easier than reading when experiencing CRCI and fatigue. Currently, no studies examine the potential impact of read-aloud programs on the emotional wellbeing of people undergoing cancer treatment.

Methods:

To explore a way to introduce or reinstate reading and the benefits it can bring, a new bibliotherapy model was developed and delivered to 38 people who were undergoing or had recently completed treatment. Most participants (97%) were older than 45 years, 34% were palliative, and 13% had incurable but treatable cancer, while 95% self-reported symptoms of CRCI. The bibliotherapy model was personalized in its approach to book selection and delivery (one-on-one in-person or via Zoom). Using a pragmatic, mixed-methods framework, participant wellbeing was measured preintervention to postintervention and qualitative interviews were conducted to explore psychosocial effects from participants' (n = 35) and family members' (n = 17) perspectives and were analyzed using reflexive thematic analysis.

Results:

Stress, anxiety, and depression decreased (as measured by DASS-21, P = .004, P = .000 and P = .015, respectively), and wellbeing increased (as measured by Warwick-Edinburgh Mental Wellbeing Scale [WEMWBS], P = .001) preintervention to postintervention. Qualitative analyses highlighted the aspects of the program participants valued: relaxation, mood lift, increased self-efficacy, time out, and feelings of warmth/nurturing. Distraction/escapism was viewed by participants as having benefits to their mood, pain, and nausea. Human interaction was also highly valued: the sense of connection with the reader was important. Family members expressed feelings of comfort and respite.

Conclusions:

Findings suggest a tailored bibliotherapy program may be associated with increases in the emotional wellbeing of people undergoing or recently completed cancer treatment, and comfort and respite for their family members. While further research using a randomized controlled trial design is needed, these findings suggest this model is eminently suitable as an offering in integrative cancer centers and palliative settings, with no negative unintended consequences being observed.
Renal Juxtaglomerular Cell Tumors Exhibit Distinct Genomic and Epigenomic Features and Lack Recurrent Gene Fusions
Authors: Michalova Kvetoslava , Martinek Petr , Mezencev Roman , Gupta Sounak , Williamson Sean , Wasco Matthew , Mohanty Sambit , Magi-Galluzzi Cristina , Cañete-Portillo Sofia , Aron Manju , Kandukuri Shivani , Lobo João , Barkan Güliz A. , Kilic Irem , Strakova-Peterikova Andrea , Pivovarcikova Kristyna , Michal Michael , Michal Michal , Ulbright Thomas M. , Acosta Andres M.
Published: December 2024

Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent. Recently, whole-genome analysis identified alterations involving genes of MAPK-RAS pathway in a subset, but no major pathogenic alterations have been discovered in prior whole transcriptome analyses. Considering the limited understanding of the molecular features of JxGCTs, we sought to assess a collaborative series with a multiomic approach to further define the molecular characteristics of this entity. Fifteen tumors morphologically compatible with JxGCTs were evaluated using immunohistochemistry for renin, single-nucleotide polymorphism array (SNP), low-pass whole-genome sequencing, and RNA sequencing (fusion assay). In addition, methylation analysis comparing JxGCT, GT, and SFT was performed. All cases tested with renin (n=11) showed positive staining. Multiple chromosomal abnormalities were identified in all cases analyzed (n=8), with gains of chromosomes 1p, 10, 17, and 19 and losses of chromosomes 9, 11, and 21 being recurrent. A pathogenic HRAS mutation was identified in one case as part of the SNP array analysis. Thirteen tumors were analyzed by RNA sequencing, with 2 revealing in-frame gene fusions: TFG::GPR128 (interpreted as stochastic) and NAB2::STAT6. The latter, originally diagnosed as JxGCT, was reclassified as SFT and excluded from the series. No fusions were detected in the remaining 11 cases; of note, no case harbored NOTCH fusions previously described in GT. Genomic methylation analysis showed that JxGCT, GT, and SFT form separate clusters, confirming that JxGCT represents a distinct entity (ie, different from GT). The results of our study show that JxGCTs are a distinct tumor type with a recurrent pattern of chromosomal imbalances that may play a role in oncogenesis, with MAPK-RAS pathway activation being likely a driver in a relatively small subset.
A Case of NTRK Fusion Corpus Sarcoma With Pseudobiphasic Growth Pattern and Literature Review
Authors: Zhang Xiao-Ying , Jiang Han-Wen , Wen Xiao-Bo , Yu Qian , Li Ying , Wang Hao , Han Jing , Yang Shi-Cong
Published: December 2024

The incidence of neurotrophic tyrosine kinase receptor (NTRK) fusion uterine sarcoma is extremely low, and reports have been mostly focused on cases localized to the cervix. So far, only 4 cases have been reported of the uterine corpus. In this study, we reported a case of NTRK fusion corpus sarcoma. This study aimed to expand the morphologic spectrum of this tumor, which showed adenosarcoma-like features not previously described. The tumor was confined to the uterine corpus, polypoid growth, comprised predominantly of a fascicular proliferation of spindle cells, entrapping benign endometrial glands, and exhibited a pseudo-biphasic growth pattern. The tumor showed coexpression of S-100, CD34, and pan-Trk by immunohistochemistry, DNA-sequencing identified TPR-NTRK1 gene fusion and AKT1(E17K) mutation. Four cases of NTRK fusion corpus sarcoma were reviewed. The clinicopathologic features, immunohistochemical phenotype, molecular testing, and prognosis of 5 cases including this one were summarized and analyzed. Most cases exhibited an infiltrative g rowth pattern and showed mild or moderate cytologic atypia. The potential for these tumors to be misclassified as uterine adenosarcoma or other uterine mesenchymal tumors. The diagnosis relies on pan-Trk, S-100, CD34 immunohistochemistry, and molecular testing. Surgical resection is the mainstay of treatment for most patients. Distinguishing these tumors from morphologic mimics is significant because patients with advanced-stage disease may be treated with TRK inhibitors.
A genetic safeguard for eliminating target genes in synthetic probiotics in response to a loss of the permissive signal in a gut environment
Authors: Nguyen Nhu , Wang Miaomiao , Li Lin , Chan Clement T. Y.
Published: December 2024

Following the development of therapeutic probiotics, there is an emerging demand for constraining engineered microbial activities to ensure biosafety. Many biocontainment studies developed genetic devices that involve cell death and growth inhibition on the engineered microbes, which often create basal levels of cytotoxicity that hamper cell fitness and performance on therapeutic functions; furthermore, these toxic pathways may promote genetic instability that leads to mutations and breakdown of biocontainment circuit. To address this issue, here we explore a circuit design that destroys the engineered genetic materials in a probiotic strain, instead of killing these cells, under non-permissive conditions. Our safeguard circuit involves a two-layered transcriptional regulatory circuit to control the expression of a CRISPR system that targets the engineered genes for degradation. InEscherichia coli Nissle 1917(EcN), the biocontainment system continuously scavenged and destroyed the target until no engineered cellular function could be detected, suggesting this strategy has the potential to avoid escapee formation. Additionally, this safeguard circuit did not affectEcNcell fitness. We further demonstrated that the engineered probiotics inhabited in mouse guts and continued the engineered activities for at least 7 days when the permissive signal was supplied constantly; when the permissive signal was not provided, the engineered activities became undetectable within two days. Together, these studies support that our safeguard design is feasible for synthetic probiotic applications.

HIGHLIGHTS

Our safeguard system only destroys target genes and does not kill the host microbes

It terminated engineered activities in guts in response to a loss of a signal

This safeguard allowed synthetic probiotics to inhabit in guts for at least a week

Cellobiose has great potential to serve as a continuous genetic signal in guts
Perinatal and maternal factors associated with Autism Spectrum Disorder
Authors: Edlund Susanna , Haglund Nils , Bornehag Carl-Gustaf , Gennings Chris , Kiviranta Hannu , Kolevzon Alexander , Lindh Christian , Rantakokko Panu , Reichenberg Abraham , Swan Shanna , Källén Karin
Published: December 2024

This study comprehensively examines maternal and perinatal conditions associated with autism spectrum disorder (ASD) in a total population sample with individually confirmed diagnoses from South Sweden. Following thorough review of medical records, 996 cases were ascertained and classified based on level of intellectual disability, ASD severity and family-history of ASD. 10 controls per case were randomly selected from the population (N=9,960). Multiple maternal and perinatal conditions were associated with increased risk for ASD, but associations varied by ASD comorbid conditions. Only high maternal BMI was associated with ASD risk across all ASD sub-groups. Results suggest differences in ASD etiology by comorbid subgroups and highlight potential modifiable risk factors.
Geometry-based BERT: an experimentally validated deep learning model for molecular property prediction in drug discovery
Authors: Zhang Xiang , Qian Chenliang , Yang Bochao , Jin Hongwei , Wu Song , Xia Jie , Yang Fan , Zhang Liangren
Published: December 2024

Various deep learning based methods have significantly impacted the realm of drug discovery. The development of deep learning methods for identifying novel structural types of active compounds has become an urgent challenge. In this paper, we introduce a self-supervised representation learning framework, i.e., GEO-BERT. GEO-BERT considers the information of atoms and chemical bonds in chemical structures as the input, and integrates the positional information of the three-dimensional conformation of the molecule for training. Specifically, GEO-BERT enhances its ability to characterize molecular structures by introducing three different positional relationships: atom-atom, bond-bond, and atom-bond. By benchmarking study, GEO-BERT has demonstrated optimal performance on multiple benchmarks. We also performed prospective study to validate the GEO-BERT model, with screening for DYRK1A inhibitors as a case. Two potent and novel DYRK1A inhibitors (IC50: <1 μM) were ultimately discovered at a hit rate of 10%. Taken together, we have developed the Geometry-based BERT model for molecular property prediction and proved its practical utility in early-stage drug discovery.

Graphical Abstract

GEO-BERT is a model pretrained on large-scale drug molecule data, while improving the accuracy of property prediction by using three-dimensional structural information within the molecule.
Mapping eukaryotic chromatin accessibility and histone modifications with DNA deaminase
Authors: Dong Wenyang , Zhang Jiankun , Dai Leyi , Chen Jinxin Phaedo , Wu Honggui , He Runsheng , Pang Yuxuan , Wang Zhi , Jian Fanchong , Ren Jun , Liu Yijun , Tian Yu , Liu Shuang , Zhao Xuechen , Xie Xiaoliang Sunney
Published: December 2024

A variety of methods such as ATAC-seq and CUT&Tag have been developed for probing chromatin states. However, enzymatic cleavage of DNA in these methods hinders their multi-omics integration with other DNA profiling techniques. Here, by extending our use of dsDNA deaminase (FOOtprinting with DeamInasE, FOODIE), we introduce two new methods for mapping Chromatin Open region by DeamInasE (ChrODIE) and histone modification by ANtibody-associated DeamInasE (ANDIE), respectively. Unlike cleavage-based methods, both ChrODIE and ANDIE leave genomic DNA after deamination unfragmented and amplifiable. This offers the potential for simultaneous or downstream integration with other genomic profiling methods, such as mapping 3D genome interactions.
Experimental data supporting a novel hypothesis for the rhythmic initiation of proximal colon motor complexes
Authors: Morales-Soto Wilmarie , Stiglitz Emma S. , Edwards Brian S. , Smith-Edwards Kristen M.
Published: December 2024

Current models of colon motility are largely based on studies of distal regions where distension-induced neural peristalsis predominates, but the proximal colon significantly differs in terms of cellular organization and its rhythmic motor activity that continues without external sensory input, emphasizing the need to define the unique mechanisms utilized by the proximal colon. With the long-term goal of developing a new model for the rhythmic initiation of proximal colon motor complexes (CMCs), we usedin situcalcium imaging to define activity patterns in key players for colon motility [i.e., submucosal interstitial cells of Cajal (ICC-SM) and myenteric neurons of the enteric nervous system (ENS)], while simultaneously monitoring motor output in the proximal mouse colon. We observed repeated patterns of activity in ICC-SM and ENS myenteric neurons during the intervals between CMCs that could be used to predict the timing of subsequent CMC events. Based on our findings, we propose a novel hypothesis that cyclical interactions between the ENS and ICC-SM act as an intrinsic pattern generator for the rhythmic initiation of proximal CMCs.
Morphological Plasticity and Reproductive Strategies ofKalanchoeSpecies in Invasive Spread
Authors: Zhang Zhe , Sugiura Daisuke , Yamori Wataru , Tang Yanhong
Published: December 2024

Kalanchoespecies, originally introduced worldwide as ornamentals, are now reported to be spreading in many regions, including China. It is hypothesized that morphological plasticity and the production of asexual plantlets contribute to their successful invasion. To address the hypothesis, four species -Kalanchoe delagoensisEckl. & Zeyh.,Kalanchoe × houghtoniiD. B. Ward,Kalanchoe laetivirensDesc. andKalanchoe daigremontianaRaym. - Hamet & H. Perrier - were cultivated under contrasting light and water conditions, and their reproductive and vegetative traits were examined. The plants subjected to high light tended to prioritize plantlet production, accompanied by a reduction in vegetative growth. Two distinct reproductive strategies were observed:K. delagoensisandK. × houghtoniisignificantly increased plantlet production under high light conditions, whereasK. daigremontianaandK. laetivirensenhanced the fresh weight of individual plantlets without altering the total number produced. These results highlight the high plasticity of vegetative and reproductive growth in response to light and water availability. The increased production of plantlets may contribute to the widespread occurrence ofKalanchoespecies in open fields.
A novel method for in vivo assessment of soft tissue weight in bivalves
Authors: Duan Shiyun , Gao Yunlong , Hu Xiaoli , Yin Xiaoshen
Published: December 2024

Aquaculture has been playing an increasingly important role in supplying proteins. To satisfy the rapidly growing demands for quality aquatic foods, the efficiency of aquaculture production needs to be improved. One strategy to achieve more efficient aquaculture production is to produce high-yielding seeds through breeding programs, for which in vivo assessment of target traits is indispensable to prevent candidate parents from being sacrificed for measurement and to track dynamically changing yield-related traits. Farmed mollusks, most of which are bivalves, rank the second among all aquatic animals in aquaculture production. Bivalves with heavier soft tissue, the major edible part, are preferable, target species for breeding and farming. A prerequisite for obtaining such species is to make accurate but nondestructive assessments of soft tissue weight, which cannot be accomplished using traditional dissection- or imaging-based methods. To resolve this issue, we take advantage of the complex relationships among shell dimension- and weight-related traits to construct classical, shell dimension- or wet weight-based models and novel, shell surface area-based models for in vivo assessment of soft tissue weight in Zhikong scallop (Chlamys farreri) and yesso scallop (Patinopecten yessoensis). Overall, soft tissue weight estimated by wet weight-involving models are highly correlated with observed values, indicating wet weight as a key proxy for soft tissue weight. While some models incorporating wet weight tend to systematically over- or under-estimate soft tissue weight despite the strong association between actual and estimated values, the novel, shell surface area-based model, MLR-log10Sshell-RR, generates accurate estimates free of systematic biases across populations of different ages for both species, suggesting it as a promising approach for in vivo assessment of soft tissue weight for scallops and other bivalves with bilaterally symmetrical shells.
An Expanded Registry of Candidate cis-Regulatory Elements for Studying Transcriptional Regulation
Authors: Moore Jill E. , Pratt Henry E. , Fan Kaili , Phalke Nishigandha , Fisher Jonathan , Elhajjajy Shaimae I. , Andrews Gregory , Gao Mingshi , Shedd Nicole , Fu Yu , Lacadie Matthew C , Meza Jair , Ganna Mohit , Choudhury Eva , Swofford Ross , Farrell Nina P. , Pampari Anusri , Ramalingam Vivekanandan , Reese Fairlie , Borsari Beatrice , Yu Michelle , Wattenberg Eve , Ruiz-Romero Marina , Razavi-Mohseni Milad , Xu Jinrui , Galeev Timur , Beer Michael A. , Guigó Roderic , Gerstein Mark , Engreitz Jesse , Ljungman Mats , Reddy Timothy E. , Snyder Michael P. , Epstein Charles B , Gaskell Elizabeth , Bernstein Bradley E , Dickel Diane E. , Visel Axel , Pennacchio Len A. , Mortazavi Ali , Kundaje Anshul , Weng Zhiping
Published: December 2024

Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression. Previously, The ENCODE consortium mapped biochemical signals across many cell types and tissues and integrated these data to develop a Registry of 0.9 million human and 300 thousand mouse candidate cis-Regulatory Elements (cCREs) annotated with potential functions1. We have expanded the Registry to include 2.35 million human and 927 thousand mouse cCREs, leveraging new ENCODE datasets and enhanced computational methods. This expanded Registry covers hundreds of unique cell and tissue types, providing a comprehensive understanding of gene regulation. Functional characterization data from assays like STARR-seq, MPRA, CRISPR perturbation, and transgenic mouse assays now cover over 90% of human cCREs, revealing complex regulatory functions. We identified thousands of novel silencer cCREs and demonstrated their dual enhancer/silencer roles in different cellular contexts. Integrating the Registry with other ENCODE annotations facilitates genetic variation interpretation and trait-associated gene identification, exemplified by discoveringKLF1as a novel causal gene for red blood cell traits. This expanded Registry is a valuable resource for studying the regulatory genome and its impact on health and disease.
Fast Myosin Binding Protein-C is a Vital Regulator in Young and Aged Fast Skeletal Muscle Homeostasis
Authors: Baby Akhil , Ananthamohan Kalyani , Song Taejeong
Published: December 2024

Background

Skeletal muscle plays a vital role in voluntary motion and locomotion. Fast-twitch muscle fibers are characterized by their rapid contraction kinetics, high force generation capacity, and a distinct gene expression profile compared to slow-twitch fibers. Skeletal myosin binding protein-C (MyBP-C) paralogs, slow (sMyBP-C) and fast (fMyBP-C), interact with myosin and actin filaments within sarcomeres to modulate force development during contraction. These paralogs are differentially expressed in muscle fibers, with fMyBP-C predominantly expressed in the fast-twitch fibers. However, the role of fMyBP-C in skeletal muscle disease states and aging remains poorly understood. This study employs mouse models with fMyBP-C ablation to investigate its significance in skeletal muscle physiology.

Methods

Adult skeletal muscle samples aged 2∼7 months from male and female wild-type, db/db, MDX, ECC injury model, were used to determine the differential expression of fMyBP-C. Next,Mybpc2knockout (C2-/-) young (3∼5 months) and old (22 months) male mice were used to define the role of fMyBP-C in aging. Western immunoblotting was employed to analyze the expression of fMyBP-C and sMyBP-C and the phosphorylation status of sMyBP-C. The impact of C2-/-and aging on the fiber type, size, and number as well as general muscle structure was assessed by immunohistochemistry and electron microscopy. The functional effect of C2-/-and aging was measured in terms of in vivo and ex vivo muscle force generation. Lastly, RNA sequencing was performed to identify the molecular pathways dysregulated in the C2-/-mediated muscle dysfunction in young and old mice.

Results

fMyBP-C was significantly reduced with a modest compensatory upregulation of sMyBP-C in the diseased fast-twitch muscles. fMyBP-C has a significantly higher expression in the male skeletal muscles compared to females. Further studies using young male C2-/-mice showed a significant reduction in isometric tetanic force generation and relaxation rate, fiber type switching, atrophy, and altered gene expressions related to muscle function and metabolism compared to wild-type mice. Similarly, compared to their wild-type counterparts, aged male C2-/-mice display significant deficits in muscle strength, endurance, and survival rate, accompanied by changes in muscle fiber size and molecular signaling pathways critical for muscle homeostasis.

Conclusion

fMyBP-C is an important regulator of muscle function and homeostasis in young and aged male fast-twitch muscle fibers. The absence of fMyBP-C aggravates the effect of aging on muscle structure and function. fMyBP-C has the potential to be a therapeutic target to modulate muscle wasting caused by aging and disease.
Longitudinal assessment of DREADD expression and efficacy in the monkey brain
Authors: Nagai Yuji , Hori Yukiko , Inoue Ken-ichi , Hirabayashi Toshiyuki , Mimura Koki , Oyama Kei , Miyakawa Naohisa , Hori Yuki , Iwaoki Haruhiko , Kumata Katsushi , Zhang Ming-Rong , Takada Masahiko , Higuchi Makoto , Minamimoto Takafumi
Published: December 2024

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) offer a powerful means for reversible control of neuronal activity through systemic administration of inert actuators. Because chemogenetic control relies on DREADD expression levels, understanding and quantifying the temporal dynamics of their expression is crucial for planning long-term experiments in monkeys. In this study, we longitudinally quantifiedin vivoDREADD expression in macaque monkeys using positron emission tomography with the DREADD-selective tracer [11C]deschloroclozapine (DCZ), complemented by functional studies. Twenty macaque monkeys were evaluated after being injected with adeno-associated virus vectors expressing the DREADDs hM4Di or hM3Dq, whose expression was quantified as changes in [11C]DCZ binding potential from baseline levels. Expression levels of both hM4Di and hM3Dq peaked around 60 days post-injection, remained stable for about 1.5 years, and declined gradually after two years. Significant chemogenetic control of neural activity and behavior persisted for about two years. Virus titer and the presence of protein tags significantly influenced expression levels, with co-expressed protein tags reducing overall expression levels. These findings provide valuable insights and guidelines for optimizing the use of DREADDs in long-term primate studies and potential therapeutic applications.
Dynamics of postnatal bone development and epiphyseal synostosis in the caprine autopod
Authors: Panebianco Christopher J. , Essaidi Maha , Barnes Elijah , Williams Ashley , Vancíková Karin , Labberté Margot C. , Brama Pieter , Nowlan Niamh C. , Boerckel Joel D.
Published: December 2024

Bones develop to structurally balance strength and mobility. Bone developmental dynamics are influenced by whether an animal is ambulatory at birth (i.e.,precocial). Precocial species, such as goats, develop advanced skeletal maturity in utero, making them useful models for studying the dynamics of bone formation under mechanical load. Here, we used microcomputed tomography and histology to characterize postnatal bone development in the autopod of the caprine lower forelimb. The caprine autopod features two toes, fused by metacarpal synostosis (i.e., bone fusion) prior to birth. Our analysis focused on the phalanges 1 (P1) and metacarpals of the goat autopod from birth through adulthood (3.5 years). P1 cortical bone densified rapidly after birth (half-life using one-phase exponential decay model (τ1/2= 1.6 ± 0.4 months), but the P1 cortical thickness increased continually through adulthood (τ1/2= 7.2 ± 2.7 mo). Upon normalization by body mass, the normalized polar moment of inertia of P1 cortical bone was constant over time, suggestive of structural load adaptation. P1 trabecular bone increased in trabecular number (τ1/2= 6.7 ± 2.8 mo) and thickness (τ1/2= 6.6 ± 2.0 mo) until skeletal maturity, while metacarpal trabeculae grew primarily through trabecular thickening (τ1/2= 7.9 ± 2.2 mo). Unlike prenatal fusion of the metacarpal diaphysis, synostosis of the epiphyses occurred postnatally, prior to growth plate closure, through a unique fibrocartilaginous endochondral ossification. These findings implicate ambulatory loading in postnatal bone development of precocial goats and identify a novel postnatal synostosis event in the caprine metacarpal epiphysis.
A practical DNA data storage using expanded alphabet introducing 5-methylcytosine
Authors: Liu Deruilin , Xu Demin , Shi Liuxin , Zhang Jiayuan , Bi Kewei , Luo Bei , Liu Chen , Li Yuxiang , Fan Guangyi , Wang Wen , Ping Zhi
Published: December 2024

DNA molecular is a promising next-generation data storage medium. Recently, it has been theoretically proposed that non-natural or modified bases can serve as extra molecular letters to increase the information density. However, the feasibility of the strategy is challenging due to the difficulty in synthesizing and the complex structure of non-natural DNA sequences. Here, we described a practical DNA data storage transcoding scheme named R+ based on expanded molecular alphabet by introducing 5-methlcytosine(5mC). We also demonstrated the experimental validation by encoding one representative file into several 1.3~1.6 kbpsin vitroDNA fragments for nanopore sequencing. The results show an average data recovery rate of 98.97% and 86.91% with and without reference respectively. This work validates the practicability of 5mC in DNA storage systems, with a potentially wide range of applications.

Availability & Implementation

R+ is implemented in Python and the code is available under the MIT license athttps://github.com/Incpink-Liu/DNA-storage-R_plus
GP-ML-DC: An Ensemble Machine Learning-Based Genomic Prediction Approach with Automated Two-Phase Dimensionality Reduction via Divide-and-Conquer Techniques
Authors: Liu Quanzhong , Ma Haofeng , Zhang Zhuangbiao , Hu Zhunhao , Wang Xihong , Li Ran , Cai Yudong , Jiang Yu
Published: December 2024

Traditional machine learning (ML) and deep learning (DL) methods for genome prediction often face challenges due to the imbalance between the limited number of samples (n) and the large number of single nucleotide polymorphisms (SNPs) (p), wherenis much smaller thanp. To address this, we propose GP-ML-DC, an innovative genome predictor that combines traditional ML and DL models with a unique two-phase, parameter-free dimensionality reduction technique. Initially, GP-ML-DC reduces feature dimensionality by characterizing genes as features. Building on big data methodologies, it employs a divide-and-conquer approach to segment gene regions into multiple haplotypes, further decreasing dimensionality. Each haplotype segment is processed by a sub-task based on traditional ML, followed by integration via a neural network that synthesizes the results of all sub-tasks. Our experiments, conducted on four cattle milk-related traits using ten-fold cross-validation and independent testing, show that GP-ML-DC significantly surpasses current state-of-the-art genome predictors in prediction performance.
Chromosome-level genome assembly of the Asian tramp snailBradybaena similaris(Stylommatophora: Camaenidae)
Authors: Ishii Yasuto , Toyoda Atsushi , Lewis Alec , Davison Angus , Miura Osamu , Kimura Kazuki , Chiba Satoshi
Published: December 2024

While terrestrial land snails have long been subjected to evolutionary research, a lack of high-quality genomic resources has impeded recent progress.Bradybaenasnails in particular have numerous intriguing traits that make them a good model for studying evolution, including shell pattern polymorphism and convergent evolution. They are also introduced and invasive across the world. In this study, we present a chromosome-level genome assembly of the Asian tramp snailBradybaena similarisutilizing 88-fold Illumina short-read sequences, 125-fold Nanopore long-read sequences, 63-fold PacBio HiFi sequences, and 47-fold Hi-C sequences. The assembled genome of 2.18 Gb is anchored to 28 chromosomes, and exhibits high completeness (98.8% metazoan BUSCO completeness) and contiguity (N50 of 75.6 Mb). Additionally, we also obtained a high-quality transcriptome for annotation. This resource represents the first chromosome-level assembly for snails in the superfamily Helicoidea, which includes more than 5,000 species of terrestrial snails, and will facilitate genomic study inBradybaenaand, more broadly, in the superfamily Helicoidea.

SIGNIFICANCE STATEMENT

While the Helicoidea is the largest land snail superfamily, consisting of more than 5,000 species, many of interest to evolutionary studies, no chromosome-level assembly has been available for any species. Previously, the genusBradybaenain the Helicoidea has been studied in the context of speciation, adaptation and invasive biology, and thereby has high potential for further research. In this study, we present a chromosome-level assembly and transcriptome of the Asian tramp snailBradybaena similaris. These high-quality genomic resources will facilitate research on related species, and eventually enhance our understanding of many areas of evolutionary biology.
Prelimbic Cortex Activity Predicts Anxiety-Like Behavior in the Elevated Plus Maze
Authors: Smoak Marina A. , Galvan Karla J. , Calvo Daniel E. , Powers Rosalie E. , Moschak Travis M.
Published: December 2024

The medial prefrontal cortex (mPFC) plays a critical role in emotional regulation, and its dysregulation is linked to anxiety disorders. In particular, the prelimbic cortex (PrL) of the mPFC is thought to modulate anxiety-related behaviors, though its precise role remains debated. Here, we used endoscopic in vivo calcium imaging to assess PrL neuronal activity in male and female Sprague-Dawley rats performing in the Elevated Plus Maze (EPM), a widely used task to measure anxiety-like behavior. We found that animals that spent less time in the open arms exhibited higher PrL activity in the open arms, suggesting that heightened PrL activity may reflect greater anxiety or increased avoidance behavior. These results suggest that the PrL may play a role in regulating the emotional response to anxiety-provoking situations, potentially influencing the tolerance for exposure to threatening environments.
Natural anomaly matching
Authors: Bolognesi Stefano , Konishi Kenichi , Luzio Andrea , Orso Matteo
Published: December 2024

In a large class of chiral gauge theories in four dimensions it was found that certain natural assumption about the bifermion condensates leads to the infrared effective theory where the ’t Hooft anomaly matching conditions are satisfied in an entirely evident fashion, without need of verifying arithmetic equations. This is due to the fact that in these systems, characterized by dynamical color (and flavor) symmetry breaking, the quantum numbers and multiplicities of the low-energy massless fermions match exactly those of the fermions in the UV theory which do not condense and remain massless, with respect to the unbroken symmetries. This means also that the stronger constraints following from the matching request of mixed anomalies involving certain generalized 1-form center symmetries, as well as some global anomalies such as Witten’s SU(2) anomaly, are all fully satisfied. It is the aim of this note to clarify better the working of this phenomenon (which we call natural anomaly matching), correct some earlier statements made about it, and illustrate it further with a few new examples.

Published by the American Physical Society
2024
Rare
Λc
decays and new physics effects
Authors: Zhang Sheng-Qi , Qiao Cong-Feng
Published: December 2024

Recent experimental progress on baryonic rare decays has spurred a deeper investigation on flavor-changing neutral current transitions in the baryon sector. Within the framework of QCD sum rules, we derive a complete set of form factors for the Λc→p process in the large recoil region and use the z-series parametrization to extrapolate them across the full physical range. Employing these form factors and flavor symmetries, we compute branching fractions for the decays Λc→pe+e− and Λc→pμ+μ−, as well as for rare Ξc decay modes. We examine as well the new physics effects through specific angular observables such as the lepton forward-backward asymmetry and the fraction of longitudinally polarized dileptons. Results indicate that new physics models may be testified in baryonic rare decays, with immense data collected in running and future colliders.

Published by the American Physical Society
2024
q
-deformed evolutionary dynamics in simple matrix games
Authors: Kitching Christopher R. , Galla Tobias
Published: December 2024

We consider evolutionary games in which the agent selected for update compares strategies with q neighbors, rather than a single neighbor as in standard evolutionary game theory. If all q sampled neighbors agree, then agents update their strategy using a smoothed best-response rule. Following ideas from social impact theory, we also study mathematical generalizations of the dynamics to noninteger q>0. Looking at fixed point stability and fixation times for 2×2 games with all-to-all interactions, we find that the flow changes significantly as a function of q. Further, we develop the pair approximation for the q-deformed dynamics on uncorrelated graphs. We also study games with more than two strategies, such as the rock-paper-scissors game where we show that changing q leads to the emergence of new types of flow within the simplex.

Published by the American Physical Society
2024
Change-driven process management: exploring a new process paradigm adaptable to societal changes
Authors: Cronemyr Peter , Fundin Anders , Wemme Lars
Published: December 2024

Purpose

Process management principles are challenging owing to the increasing need for sustainable operations. The demand for rapid deliveries implies accelerated changes and increased flexibility. Therefore, this study aims to facilitate process improvements based on change-driven needs.

Design/methodology/approach

The research is conducted using holistic multiple case studies of eight Swedish organisations (with employees from Sweden, France and Germany), representing the automotive, energy, medical technology, healthcare, telecom and social services sectors.

Findings

A process management model with four change-driven phases is presented. The model fulfils demands for both speed and quality in process changes, providing specific guidance on working methods for (1) control and stability, (2) creativity and stability, (3) creativity and change and (4) control and change.

Research limitations/implications

This research is limited to eight organisations in Sweden, France, and Germany that participate in the automotive, energy, medical technology, healthcare, telecom and social services sectors. Future research should explore broader international contexts.

Practical implications

The proposed model helps decision-makers adapt process management to evolving business and operational needs; thus, leaders can make grounded decisions on when and how to change operations based on changing internal and external requirements.

Originality/value

This study challenges the current process management paradigm with new knowledge of how process management can be adapted to new business opportunities.
Shadow of a doubt: a network analysis of mentoring as a screen industry equity intervention
Authors: Jones Pete , Verhoeven Deb , Dadlani Aresh
Published: December 2024

Purpose

Policies intended to encourage gender equity in the film industry are ramifying and take many forms. This paper uses social network analysis to assess the effectiveness of one popular equity policy, shadowing, a form of mentoring. In shadowing programs, women and gender minorities (WGM) are connected to more experienced members of the industry through attachment to their productions.

Design/methodology/approach

We constructed real collaboration networks based on film releases from 2005 to 2020 in three countries and simulated the effects that hypothetical shadowing interventions would have on the distribution of social capital in these networks. We implement different versions of the intervention, including different eligibility criteria for shadows and shadowees as well as isolating the additive effects on participants’ project portfolios.

Findings

We find that shadowing is effective in enabling WGM to access the strongest network positions, which are currently disproportionately occupied by men. However, we show that the primary reason that shadowing is effective in doing this is because it provides a second project affiliation to WGM in an industry where it is difficult to get past one’s first project.

Originality/value

Our study contributes to the literature on how mentoring policies affect people’s professional networks as well as scholarship on mentoring as a gender equity policy. We contribute novel evidence to debates about the efficacy of shadowing programs for WGM in the film industry. We suggest that shadowing can be effective as a tool for not only helping individual WGM advance their careers but also for structurally reconfiguring the distribution of power in project-based collaboration networks.