bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Functional Roles of Narrow and Broadband High-Gamma Activities in Human Primary Somatosensory Cortex
Authors: Ryun Seokyun , Chung Chun Kee 
Published: March 2024

ABSTRACTIn previous studies, higher (broadband) and lower (narrowband) components of high-gamma (HG) activity (approximately from 50 to 150 Hz) have different functions and origins in the primary visual cortex (V1). However, in the primary somatosensory cortex (S1), it is unknown whether those are similarly segregated. Furthermore, the origin and functional role of S1 HG activity still remain unclear. Here, we investigate their roles by measuring neural activity during vibrotactile and texture stimuli in humans. Also, to estimate their origins, S1 layer-specific HG activity was measured in rats during somatosensory stimulation. In the human experiment, with texture stimulation, the lower HG activity (LHG, 50-70 Hz) in S1 represents the intensity of the sustained mechanical stimulus. In the vibrotactile experiment, the higher HG (HHG, 70 -150 Hz) activity in S1 depended on the ratio of low and high mechanical frequencies with its pattern being a mixture of neural activity for low and high mechanical frequencies. Furthermore, 8 texture types could be classified using power values of HHG activity, while the classification using LHG activity showed poor performance. In the rat experiment, we found that both HHG and LHG activities are highest in the somatosensory input layer (layer IV), similar to previous visual cortex studies. Interestingly, analysis of spike-triggered LFP (stLFP) revealed significant HG oscillations during pressure stimulation with the stLFP HG power most significant in layer IV, suggesting that both LHG and HHG activities are closely related to the neuronal firing in layer IV. In summary, LHG activity represents the intensity of tactile sensation, while HHG activity represents the detail of the surface geometry of objects interacting with skin. Additionally, low and high mechanical frequencies are processed in parallel in S1. Finally, both HHG and LHG originated in layer IV of S1.
Multi-omics Identify Serotonin Transporter as a Promising Therapeutic Target for Essential Tremor
Authors: Wang Lingbing , Li Yanjing , Lin Suzhen , Zhou Zhuofan , Zhang Shaoyi , Xu Tian-Le , Song Xing-Lei , Wu Yiwen 
Published: March 2024

AbstractEssential tremor (ET) stands as one of the most prevalent cerebellar movement disorders. However, effective treatment remains elusive, largely due to a limited understanding of its molecular pathology. Harmaline-induced tremor in mouse is a well-established animal model for ET, while with enigmatic mechanism. The aim of this study was to get insight into the molecular intricacies underlying cerebellar dysfunction in harmaline-induced tremor. Combining LC-MS/MS and RNA-Seq analysis, we delved into the variation of the cerebellum between harmaline-induced tremor and the control ones. This comprehensive investigation revealed a profile of this mouse model from mRNA and protein level, highlighting 5194 correlated coding molecules, with 19 proving to be significant. Further KEGG enrichment analysis identified cerebellar serotonin transporter (SERT) as the key molecule in harmaline-induced tremor. The implications of this transcriptomic and proteomic exploration underscore the potential therapeutic value of targeting SERT as a novel treatment approach for ET. In general, our study unveils crucial insights that could pave the way for molecular target identification and effective therapeutic interventions for ET.
A Systematic Examination of Generative Artificial Intelligence (GAI) Usage Guidelines for Scholarly Publishing in Medical Journals
Authors: Yin Shuhui , Lu Peiyi , Xu Zhuoran , Lian Zi , Ye Chenfei , Li Chihua 
Published: March 2024

AbstractBackgroundA thorough and in-depth examination of generative artificial intelligence (GAI) usage guidelines in medical journals will inform potential gaps and promote proper GAI usage in scholarly publishing. This study aims to examine the provision and specificity of GAI usage guidelines and their relationships with journal characteristics.MethodsFrom the SCImago Journal Rank (SJR) list for medicine in 2022, we selected 98 journals as top journals to represent highly indexed journals and 144 as whole-spectrum sample journals to represent all medical journals. We examined their GAI usage guidelines for scholarly publishing between December 2023 and January 2024.ResultsCompared to whole-spectrum sample journals, the top journals were more likely to provide author guidelines (64.3% vs. 27.8%) and reviewer guidelines (11.2% vs. 0.0%) as well as refer to external guidelines (85.7% vs 74.3%). Probit models showed that SJR score or region was not associated with the provision of these guidelines among top journals. However, among whole-spectrum sample journals, SJR score was positively associated with the provision of author guidelines (0.85, 95% CI 0.49 to 1.25) and references to external guidelines (2.01, 95% CI 1.24 to 3.65). Liner models showed that SJR score was positively associated with the specificity level of author and reviewer guidelines among whole-spectrum sample journals (1.21, 95% CI 0.72 to 1.70), and no such pattern was observed among top journals.ConclusionsThe provision of GAI usage guidelines is limited across medical journals, especially for reviewer guidelines. The lack of specificity and consistency in existing guidelines highlights areas deserving improvement. These findings suggest that immediate attention is needed to guide GAI usage in scholarly publishing in medical journals.Key pointsQuestionWhat are the provision and specificity of generative artificial intelligence (GAI) usage guidelines for scholarly publishing in top and whole-spectrum medical journals and their relationships with journal characteristics?FindingsAuthor guidelines were more abundant and specific in top journals than in whole-spectrum journals. However, reviewer guidelines were extremely scarce in both groups of journals. Journal ranking score was associated with both provision and specificity of GAI usage guidelines in whole-spectrum journals while no significant relationship was found in top journals.MeaningThe lack of provision and specificity as well as the inconsistencies in existing guidelines suggest that immediate attention is needed to guide GAI usage in scholarly publishing and safeguard integrity and trust in medical research.
CHARACTERIZATION OF ACROMEGALY ACCORDING TO TUMOR SIZE AT DIAGNOSIS
Authors: Del Corso Leticia Marinho , Andrade Vicente Florentino Castaldo , Fidalski Solena Ziemer Kusma , Boguszewski Cesar Luiz 
Published: March 2024

ABSTRACTPurposeTo evaluate the clinical, laboratory, radiological, therapeutic, and prognostic characteristics of patients with acromegaly according to the size of the growth hormone (GH)-secreting pituitary adenoma at diagnosis.Patients and MethodsObservational, retrospective, single-center study of patients with acromegaly followed at a tertiary center. Data from medical records were evaluated regarding age, symptoms, presence of arterial hypertension, type 2 diabetes mellitus, hypopituitarism, size of the initial lesion, invasiveness (cavernous sinus invasion), T2-weighted magnetic resonance imaging signal intensity, GH and insulin-like growth factor type 1 (IGF-1) levels, treatment performed [surgery, use of somatostatin receptor ligands (SRL), pegvisomant, cabergoline and bromocriptine and radiotherapy] and response to surgical or adjuvant treatment (normal levels of GH and/or IGF-1 after each treatment instituted).Patients were divided into groups according to the size of the adenoma at diagnosis (group I = ≤ 10 mm, II = 10-19 mm, III = 20-29 mm, IV = 30-39 mm and V = ≥ 40 mm), and comparisons were made between the 5 groups and two-by-two comparisons.Results117 patients were studied (59 women, age at diagnosis 43 ± 13 years). Group I consisted of 11 patients (9%), group II of 54 (46%), group III of 34 (29%), group IV of 10 (9%) and group V of 8 patients (7%). The prevalence of hypertension, diabetes mellitus and hypopituitarism were 49%, 25% and 28%, respectively. Hypopituitarism, invasiveness, and the use of SRL had their prevalence increased according to the size of the adenoma, as well as GH levels. Age, on the other hand, showed a negative correlation with tumor size, and group I was older when compared to the group with macroadenoma. The ROC curves showed that in relation to the size of the adenoma at diagnosis, most of the outcomes evaluated (hypopituitarism, invasiveness, radiotherapy, use of SRL, use of medications other than SRL, disease control after surgery) occurred with a tumor diameter of around 20 mm.ConclusionOur study demonstrated that microadenomas and macroadenomas < 20 mm are associated with lower morbidity and better therapeutic response in acromegaly. From a tumor diameter of 20 mm, there was no significant difference in the clinical, therapeutic and prognostic behavior of GH-secreting pituitary adenomas.Trial Registration number (Plataforma Brasil)CAAE 30066220.2.0000.0096 (April 02, 2020)
Machine Learning-Based Prediction of Coronary Care Unit Readmission: A Multi-Hospital Validation Study
Authors: Yau Fei-Fei Flora , Chiu I-Min , Wu Kuan-Han , Cheng Chi-Yung , Lee Wei-Chieh , Chen Huang-Chung , Cheng Cheng-I , Chen Tien-Yu 
Published: March 2024

AbstractReadmission to the Coronary Care Unit (CCU) has significant implications for patient outcomes and healthcare expenditure, emphasizing the urgency to accurately identify patients at high readmission risk. This study aims to construct and externally validate a predictive model for CCU readmission using machine learning (ML) algorithms across multiple hospitals. Patient information, including demographics, medical history, and laboratory test results were collected from electronic health record system and contributed to a total of 40 features. Three ML models, Logistic Regression, Random Forest, and Gradient Boosting were employed to estimate the readmission risk. The gradient boosting model was selected demonstrated superior performance with an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.887 in the internal validation set. Further external validation in hold-out test set and three other medical centers upheld the model’s robustness with consistent high AUCs, ranging from 0.852 to 0.879. The results endorse the integration of ML algorithms in healthcare to enhance patient risk stratification, potentially optimizing clinical interventions and diminishing the burden of CCU readmissions.Key learning pointsWhat is already known:Readmission to the CCU has significant implications for both patient outcomes and healthcare costs.Accurately distinguishing patients at high or low risk for CCU readmission is essential for clinicians to allocate resources effectivelyWhat this study adds:A predictive model for CCU readmission was constructed using machine learning algorithms trained from one medical center and validated externally in three major medical centers.Among the ML models evaluated, the Gradient Boosting model showed the highest performance with an AUC of 0.879 in hold-out test set, and its robustness was further confirmed in external validation across three medical centers with an AUC range from 0.848-0.863.By using different cut-off thresholds to prioritize the model’s sensitivity or specificity, clinicians can distinguish between high-risk and low-risk patients, enabling them to determine the appropriate level of monitoring and treatment planning for those at high risk.
Spatial Interaction Analysis of Infectious Disease Import and Export Between Regions
Authors: Lyu Mingdong , Liu Kuofu , Hall Randolph W. 
Published: March 2024

AbstractHuman travel plays a crucial role in the spread of infectious disease between regions. Travel of infected individuals from one region to another can transport a virus to places that were previously unaffected or may accelerate the spread of disease in places where the disease is not yet well established. We develop and apply models and metrics to analyze the role of inter-regional travel relative to the spread of disease, drawing from data on Covid-19 in the United States. To better understand how transportation affects disease transmission, we established a multi-regional time-varying compartmental disease model with spatial interaction. The compartmental model was integrated with statistical estimates of travel between regions. From the integrated model, we derived a transmission import index to assess the risk of Covid-19 transmission between states. Based on the index, we determined states with high risk for disease spreading to other states at months scale, and we analyzed how the index changed over time during 2020. Our model provides a tool for policymakers to evaluate the influence of travel between regions on disease transmission in support of strategies for epidemic control.
Multi-Site Investigation of Gut Microbiota in CDKL5 Deficiency Disorder Mouse Models: Targeting Dysbiosis to Improve Neurological Outcomes
Authors: Damiani Francesca , Giuliano Maria Grazia , Cornuti Sara , Putignano Elena , Tognozzi Andrea , Suckow Vanessa , Kalscheuer Vera M. , Tognini Paola 
Published: March 2024

ABSTRACTBackgroundCyclin-Dependent Kinase-Like 5 (CDKL5) deficiency disorder (CDD) is a rare X-linked developmental encephalopathy caused by pathogenic variants of the CDKL5 gene. In addition to a diverse range of neurological symptoms, CDD patients frequently manifest gastrointestinal (GI) issues and subclinical immune dysregulation. This comorbidity suggests a potential association with the intestinal microbiota, prompting an investigation into whether gut dysbiosis contributes to the severity of both GI and neurological symptoms.MethodsWe examined the gut microbiota composition in two CDKL5 null (KO) mouse models in males at three different developmental stages: postnatal day (P) 25 and P32 during youth, and P70 during adulthood.ResultsChanges in diversity and composition were observed, particularly during juvenile ages, suggesting a potential gut microbiota dysbiosis in the CDD mouse models. To further understand the role of the gut microbiota in CDD, we administered an antibiotic cocktail to the mice and conducted functional and behavioral assessments. Remarkably, significant improvement in visual cortical responses and reductions in hyperactive behavior were observed. To shed light on the cellular mechanisms we focused on microglia. Alterations in specific aspects of microglia morphology, indicative of activation state and surveillance of the microenvironment, were observed in the CDKL5 KO mice and ameliorated by antibiotic administration.ConclusionsOur findings highlight the potential impact of modifications in the intestinal microbiota on the severity of CDD symptoms, expanding our understanding beyond GI disturbances to encompass influences on neurological outcomes. This cross-border study provides valuable insights into the intricate interplay between gut microbiota and neurodevelopmental disorders.
Generation of human-pig chimeric renal organoids using iPSC technology
Authors: Fujimori Koki , Yamanaka Shuichiro , Shimada Kentaro , Matsui Kenji , Kawagoe Shiho , Kuroda Takao , Ikeda Atsushi , Inoue Makoto , Kobayashi Eiji , Yokoo Takashi 
Published: March 2024

AbstractThe potential of using porcine organs and human induced pluripotent stem cell (iPSC)-derived organoids as alternative organs for human transplantation has garnered growing attention. However, both approaches still face technological challenges. Interspecies chimeric organ production using human iPSCs is expected to be another promising approach that addresses the challenges associated with organ production. Our research group successfully generated human-mouse chimeric renal organoids by utilizing human iPSC-derived nephron progenitor cells (NPCs) and fetal mouse kidneys. However, the current technology has limited engraftment and development capabilities for human NPCs, and there have been no reports of generating interspecies chimeric renal organoids in larger animals, limited only to rodents. Therefore, in this study, we embarked on the production of human-pig chimeric renal organoids using the pig kidney, which is considered the most promising source of organs for interspecies transplantation to humans. To construct a human-pig chimeric renal organoid culture system, we first modified the existing human-mouse chimeric renal organoid culture system and developed a method that enables the survival and continued renal development of both species. This method was found to be applicable to porcine fetal kidney cells, and ultimately, we successfully produced human-pig chimeric renal organoids. Furthermore, this culture method can also be applied to the generation of human interspecies chimeric kidneys for future clinical applications.The findings of this study serve as a foundational technology that will greatly accelerate future research in humanized pig kidney production for clinical purposes, and are also expected to be used as an evaluation technique to ensure the quality of human NPCs for xenotransplantation.
CRISPR-Cas9-assisted genome editing inE. colielevates the frequency of unintended mutations
Authors: Widney Karl A. , Yang Dong-Dong , Rusch Leo M. , Copley Shelley D. 
Published: March 2024

ABSTRACTCas-assisted lambda Red recombineering techniques have rapidly become a mainstay of bacterial genome editing. Such techniques have been used to construct both individual mutants and massive libraries to assess the effects of genomic changes. We have found that a commonly used Cas9-assisted editing method results in unintended mutations elsewhere in the genome in 26% of edited clones. The unintended mutations are frequently found over 200 kb from the intended edit site and even over 10 kb from potential off-target sites. We attribute the high frequency of unintended mutations to error-prone polymerases expressed in response to dsDNA breaks introduced at the edit site. Most unintended mutations occur in regulatory or coding regions and thus may have phenotypic effects. Our findings highlight the risks associated with genome editing techniques involving dsDNA breaks inE. coliand likely other bacteria and emphasize the importance of sequencing the genomes of edited cells to ensure the absence of unintended mutations.GRAPHICAL ABSTRACT
Long read sequencing provides an insight into plasmids found among carbapenemase producingEnterobacteralesfrom hospitals in the United Kingdom during 2021 to 2023
Authors: Turton Jane F , Turton Jack A 
Published: March 2024

Abstract107 isolates ofEnterobacteralesconsisting ofKlebsiella pneumoniae(n=90),Escherichia coli(n=7),Enterobacter cloacaecomplex (n=6),Klebsiella oxytocacomplex (n=3) andCitrobacter freundi(n=1) and additionally an isolate ofAcinetobacter baumanniicarrying genes encoding NDM (NDM-1, NDM-5 and NDM-14), KPC (KPC-2 and KPC-3), OXA-48-like (OXA-48, OXA-181 and OXA-232) and IMP (IMP-1 and IMP-4) carbapenemases were sequenced using q20 nanopore chemistry to provide complete/near-complete assemblies and relevant plasmids compared. Investigation of potential ‘plasmid outbreaks’ in individual hospitals among isolates of different types and species revealed a mixed situation with some isolates carrying similar plasmids, but with segments missing/added and some plasmids that were clearly distinct.While most plasmids carryingblaOXA-48were typical IncL plasmids of approximately 60 kb that are widely described, there was some variation among these. One isolate carried an IncR plasmid that had only limited homology with the others. Identical 51,479 bp ColKP3/IncX3 plasmids carryingblaOXA-181were found from isolates from different hospitals that exactly matched those on GenBank from other countries. In other isolatesblaOXA-181was carried on IncFII plasmids.blaOXA-232was found in highly conserved small ColKP3 plasmids that matched those found in other countries and continents. These observations highlight the importance of understanding the wider distribution of plasmids of concern.IncHI2/IncHI2A plasmids were important vehicles for carbapenemase genes and were found withblaKPC-2,blaIMP-1,blaIMP-4orblaNDM-1, sometimes with the colistin resistance genemcr-9in addition. Representatives ofK. pneumoniaesequence type (ST) 147 from seven hospitals carried IncFIB(pNDM-Mar)/IncHI1B(pNDM-MAR) hybrid virulence resistance plasmids of 325 to 352 kb that combinedblaNDM-5and other resistance genes with genes found in virulence plasmids. A similar plasmid was also found in an isolate ofK. pneumoniaeST1558 and has been described in representatives of ST383.Nanopore sequencing has been instrumental in improving our knowledge of plasmids carrying carbapenemase genes leading to a better understanding of their epidemiology.
Molecular basis of mRNA delivery to the bacterial ribosome
Authors: Webster Michael W. , Chauvier Adrien , Rahil Huma , Graziadei Andrea , Charles Kristine , Takacs Maria , Saint-André Charlotte , Rappsilber Juri , Walter Nils G. , Weixlbaumer Albert 
Published: March 2024

ABSTRACTProtein synthesis begins with the formation of a ribosome-mRNA complex. In bacteria, the 30S ribosomal subunit is recruited to many mRNAs through base pairing with the Shine Dalgarno (SD) sequence and RNA binding by ribosomal protein bS1. Translation can initiate on nascent mRNAs and RNA polymerase (RNAP) can promote recruitment of the pioneering 30S subunit. Here we examined ribosome recruitment to nascent mRNAs using cryo-EM, single-molecule fluorescence co-localization, and in-cell crosslinking mass spectrometry. We show that bS1 delivers the mRNA to the ribosome for SD duplex formation and 30S subunit activation. Additionally, bS1 mediates the stimulation of translation initiation by RNAP. Together, our work provides a mechanistic framework for how the SD duplex, ribosomal proteins and RNAP cooperate in 30S recruitment to mRNAs and establish transcription-translation coupling.
Calcineurin promotes adaptation to chronic stress through two distinct mechanisms
Authors: Flynn Mackenzie J. , Harper Nicholas W. , Li Rui , Zhu Lihua Julie , Lee Michael J. , Benanti Jennifer A. 
Published: March 2024

ABSTRACTAdaptation to environmental stress requires coordination between stress-defense programs and cell cycle progression. The immediate response to many stressors has been well characterized, but how cells survive in challenging environments long-term is unknown. Here, we investigate the role of the stress-activated phosphatase calcineurin (CN) in adaptation to chronic CaCl2stress inSaccharomyces cerevisiae.We find that prolonged exposure to CaCl2impairs mitochondrial function and demonstrate that cells respond to this stressor using two CN-dependent mechanisms – one that requires the downstream transcription factor Crz1 and another that is Crz1-independent. Our data indicate that CN maintains cellular fitness by promoting cell cycle progression and preventing CaCl2-induced cell death. When Crz1 is present, transient CN activation suppresses cell death and promotes adaptation despite high levels of mitochondrial loss. However, in the absence of Crz1, prolonged activation of CN prevents mitochondrial loss and further cell death by upregulating glutathione (GSH) biosynthesis genes thereby mitigating damage from reactive oxygen species. These findings illustrate how cells maintain long-term fitness during chronic stress and suggest that CN promotes adaptation in challenging environments by multiple mechanisms.