bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxylipin secretion by human CD3+ T lymphocytes in vitro is modified by the exogenous essential fatty acid ratio and life stage
Authors: von Gerichten Johanna , West Annette L. , Irvine Nicola A. , Miles Elizabeth A. , Calder Philip C. , Lillycrop Karen A. , Burdge Graham C. , Fielding Barbara A.
Published: June 2023

Immune function changes across the life stages; for example, senior adults exhibit a tendency towards a weaker cell-mediated immune response and a stronger inflammatory response than younger adults. This might be partly mediated by changes in oxylipin synthesis across the life course. Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that modulate immune function and inflammation. A number of PUFAs are precursors to oxylipins, including the essential fatty acids (EFAs) linoleic acid (LA) and α-linolenic acid (ALA). LA and ALA are also substrates for synthesis of longer chain PUFAs. Studies with stable isotopes have shown that the relative amounts of LA and ALA can influence their partitioning by T lymphocytes between conversion to longer chain PUFAs and to oxylipins. It is not known whether the relative availability of EFA substrates influences the overall pattern of oxylipin secretion by human T cells or if this changes across the life stages. To address this, the oxylipin profile was determined in supernatants from resting and mitogen activated human CD3+ T cell cultures incubated in medium containing an EFA ratio of either 5:1 or 8:1 (LA : ALA). Furthermore, oxylipin profiles in supernatants of T cells from three life stages, namely fetal (derived from umbilical cord blood), adults and seniors, treated with the 5:1 EFA ratio were determined. The extracellular oxylipin profiles were affected more by the EFA ratio than mitogen stimulation such that n-3 PUFA-derived oxylipin concentrations were higher with the 5:1 EFA ratio than the 8:1 ratio, possibly due to PUFA precursor competition for lipoxygenases. 47 oxylipin species were measured in all cell culture supernatants. Extracellular oxylipin concentrations were generally higher for fetal T cells than for T cells from adult and senior donors, although the composition of oxylipins was similar across the life stages. The contribution of oxylipins towards an immunological phenotype might be due to the capacity of T cells to synthesize oxylipins rather than the nature of the oxylipins produced.
Vulnerability and resilience of living marine resources to the Deepwater Horizon oil spill: an overview
Authors: Murawski Steven A. , Schwing Patrick T. , Patterson William F. , Sutton Tracey T. , Montagna Paul A. , Milligan Rosanna J. , Joye Samantha B. , Thomas Len , Kilborn Joshua P. , Paris Claire B. , Faillettaz Robin , Portnoy David S. , Gilbert Sherryl
Published: June 2023

The 2010Deepwater Horizon(DWH) oil well blowout in the Gulf of Mexico (GoM) was the largest and perhaps most consequential accidental marine oil spill in global history. This paper provides an overview of aResearch Topicconsisting of four additional papers that: (1) assemble time series data for ecosystem components in regions impacted by the spill, and (2) interpret temporal changes related to the vulnerability of species and ecosystems to DWH and the ensuing resilience to perturbation. Time series abundance data for many taxa pre-date DWH, often by decades, thus allowing an assessment of population- and community-level impacts. We divided the north central GoM into four interconnected “eco-types”: the coastal/nearshore, continental shelf, open-ocean pelagic and deep benthic. Key taxa in each eco-type were evaluated for their vulnerability to the circumstances of the DWH spill based on population overlap with oil, susceptibility to oil contamination, and other factors, as well their imputed resilience to population-level impacts, based on life history metrics, ecology and post-spill trajectories. Each taxon was scored as low, medium, or high for 13 vulnerability attributes and 11 resilience attributes to produce overall vulnerability and resilience scores, which themselves were also categorical (i.e., low, medium, or high). The resulting taxon-specific V-R scores provide important guidance on key species to consider and monitor in the event of future spills similar to DWH. Similar analyses may also guide resource allocation to collect baseline data on highly vulnerable taxa or those with low resilience potential in other ecosystems. For some species, even a decade of observation has been insufficient to document recovery given chronic, long-term exposure to DWH oil remaining in all eco-types and because of impacts to the reproductive output of long-lived species. Due to the ongoing threats of deep-water blowouts, continued surveillance of populations affected by DWH is warranted to document long-term recovery or change in system state. The level of population monitoring in the open-ocean and deep benthic eco-types has historically been low and is inconsistent with the continued migration of the oil industry to the ultra-deep (≥1,500 m) where the majority of leasing, exploration, and production now occurs.
Second language learning role-play: effects of patient and doctor roles on motivation and competence
Authors: Yu Hao , Isahakyan Anna , van Merrienboer Jeroen J. G. , Köhler S. Eleonore , Asoodar Maryam
Published: June 2023

Objectives

Role-playing has motivated foreign language learners for decades. In doctor–patient medical consultation role-plays, the doctor role has always been considered an important learning opportunity, whilst the patient role remained obscured. Our study, therefore, had a dual focus. We first explored how intrinsic motivation changes medical second-language (L2) learning through the lens of self-determination theory. We subsequently examined if playing the role of the patient provides additional value to medical L2 learning.

Methods

We performed a mixed-methods study using a one-group pretest–posttest design. Participants were 15 student volunteers learning medical Dutch through peer role-play in medical consultations. Students completed a questionnaire before and after the course that measured changes in their intrinsic motivation to experience stimulation (IMES), feeling of relatedness, and feeling of competence. We also measured students' competence through a peer-rated checklist and the final course grades. At the end of the course, the students participated in semi-structured interviews to discuss their experience acting as patients. The data were subjected to the Wilcoxon signed-rank test and a thematic analysis.

Results

The pre- and post-questionnaires revealed that students' IMES as well as their feeling of relatedness increased. Their self-perceptions, feeling of competence, peer assessments, and final course grades demonstrated that students were competent in medical L2. Our thematic analysis led to the identification of five themes of the role-play exercise for medical L2 learning: (1) motivational experience, (2) supportive peer interaction, (3) setting up a role-play environment for medical L2 learning, (4) utilizing the patient role to benefit medical L2 learning, and (5) a novel patient perspective on the doctor's role.

Discussion

Our study found that role-play, by enhancing students' intrinsic motivation, feeling of relatedness, and competence development, aids the medical L2 learning process. Interestingly, playing a patient role in medical consultation was also found to support this process. We welcome future controlled experiments to confirm the positive impact of playing the role of the patient in medical consultation.
Oxazolidinone resistance genes in florfenicol-resistant enterococci from beef cattle and veal calves at slaughter
Authors: Nüesch-Inderbinen Magdalena , Biggel Michael , Haussmann Adrian , Treier Andrea , Heyvaert Lore , Cernela Nicole , Stephan Roger
Published: June 2023

Background

Linezolid is a critically important oxazolidinone antibiotic used in human medicine. Although linezolid is not licensed for use in food-producing animals, the use of florfenicol in veterinary medicine co-selects for oxazolidinone resistance genes.

Objective

This study aimed to assess the occurrence of cfr, optrA, and poxtA in florfenicol-resistant isolates from beef cattle and veal calves from different herds in Switzerland.

Methods

A total of 618 cecal samples taken from beef cattle and veal calves at slaughter originating from 199 herds were cultured after an enrichment step on a selective medium containing 10 mg/L florfenicol. Isolates were screened by PCR for cfr, optrA, and poxtA which are genes known to confer resistance to oxazolidinones and phenicols. One isolate per PCR-positive species and herd was selected for antimicrobial susceptibility testing (AST) and whole-genome sequencing (WGS).

Results

Overall, 105 florfenicol-resistant isolates were obtained from 99 (16%) of the samples, corresponding to 4% of the beef cattle herds and 24% of the veal calf herds. Screening by PCR revealed the presence of optrA in 95 (90%) and poxtA in 22 (21%) of the isolates. None of the isolates contained cfr. Isolates included for AST and WGS analysis were Enterococcus (E.) faecalis (n = 14), E. faecium (n = 12), E. dispar (n = 1), E. durans (n = 2), E. gallinarum (n = 1), Vagococcus (V.) lutrae (n = 2), Aerococcus (A.) urinaeequi (n = 1), and Companilactobacillus (C.) farciminis (n = 1). Thirteen isolates exhibited phenotypic linezolid resistance. Three novel OptrA variants were identified. Multilocus sequence typing identified four E. faecium ST18 belonging to hospital-associated clade A1. There was a difference in the replicon profile among optrA- and poxtA-harboring plasmids, with rep9 (RepA_N) plasmids dominating in optrA-harboring E. faecalis and rep2 (Inc18) and rep29 (Rep_3) plasmids in poxtA-carrying E. faecium.

Conclusion

Beef cattle and veal calves are reservoirs for enterococci with acquired linezolid resistance genes optrA and poxtA. The presence of E. faecium ST18 highlights the zoonotic potential of some bovine isolates. The dispersal of clinically relevant oxazolidinone resistance genes throughout a wide variety of species including Enterococcus spp., V. lutrae, A. urinaeequi, and the probiotic C. farciminis in food-producing animals is a public health concern.
Homologous genes shared between probiotics and pathogens affect the adhesion of probiotics and exclusion of pathogens in the gut mucus of shrimp
Authors: Sha Yujie , Yan Qingyun , Liu Jian , Yu Jiafeng , Xu Shicai , He Zhili , Ren Jing , Qu Jie , Zheng Shiying , Wang Guomin , Dong Weiying
Published: June 2023

Clarifying mechanisms underlying the selective adhesion of probiotics and competitive exclusion of pathogens in the intestine is a central theme for shrimp health. Under experimental manipulation of probiotic strain (i.e., Lactiplantibacillus plantarum HC-2) adhesion to the shrimp mucus, this study tested the core hypothesis that homologous genes shared between probiotic and pathogen would affect the adhesion of probiotics and exclusion of pathogens by regulating the membrane proteins of probiotics. Results indicated that the reduction of FtsH protease activity, which significantly correlated with the increase of membrane proteins, could increase the adhesion ability of L. plantarum HC-2 to the mucus. These membrane proteins mainly involved in transport (glycine betaine/carnitine/choline ABC transporter choS, ABC transporter, ATP synthase subunit a atpB, amino acid permease) and regulation of cellular processes (histidine kinase). The genes encoding the membrane proteins were significantly (p < 0.05) up-regulated except those encoding ABC transporters and histidine kinases in L. plantarum HC-2 when co-cultured with Vibrio parahaemolyticus E1, indicating that these genes could help L. plantarum HC-2 to competitively exclude pathogens. Moreover, an arsenal of genes predicted to be involved in carbohydrate metabolism and bacteria-host interactions were identified in L. plantarum HC-2, indicating a clear strain adaption to host’s gastrointestinal tract. This study advances our mechanistic understanding of the selective adhesion of probiotics and competitive exclusion of pathogens in the intestine, and has important implications for screening and applying new probiotics for maintaining gut stability and host health.
Altered intestinal microbiota in children with bronchiolitis
Authors: Wu Xiao-bin , Wang Jian , Tang Yuan , Jiang Jing , Li Xue-mei
Published: June 2023

Objective

To investigate the correlation between the alteration of intestinal microbiota and disease in children with bronchiolitis.

Methods

Fifty seven children diagnosed with bronchiolitis from January 2020 to January 2022 in our pediatric department were included as the case group, and another 36 normal children were included as the control group. Stool and blood were collected from both groups for high-throughput sequencing, untargeted metabolite detection and ELISA. A mouse model of RSV infection was established to validate the results of clinical case detection.

Results

Body weight, passive smoking, and a host of other factors were possible as acute bronchiolitis influencing factors in the onset of acute bronchiolitis. The alpha diversity Shannon, Simpson and Pielou’s evenness indices were significantly lower in children with acute bronchiolitis than in healthy children with gated levels of Firmicutes, Bacteroidetes and genus levels of Clostridium and other short chain fatty acid-producing bacteria. The relative abundance of short-chain fatty acid (SCFAs)-producing bacteria decreased and the abundance of genus-level sphingolipid-producing bacteria Sphingomonas increased; the progression of acute bronchiolitis is likely to be associated with the abundance of Clostridium and Sphingomonas and higher fecal amino acid concentrations, including FF-MAS, L-aspartic acid, thioinosinic acid, picolinic acid; supplementation with Clostridium butyricum significantly alleviated RSV infection-induced lung inflammation.

Conclusion

The progression of bronchiolitis may be associated with altered intestinal microbiota, decreased SCFAs and elevated sphingolipids metabolism in children. Some fecal bacteria and metabolites may predict the onset of bronchiolitis, and oral administration of Clostridium butyricum may alleviate RSV infection-induced pulmonary inflammation.
Characterizing conjugative plasmids from an antibiotic-resistant dataset for use as broad-host delivery vectors
Authors: Loyola Irizarry Héctor G. , Brito Ilana L.
Published: June 2023

Human microbiome engineering is increasingly proposed as a way to modulate health outcomes. However, one of the current limitations to engineering microbial communities in situ is delivery of a genetic payload for introducing or modifying genes. Indeed, there is a need to identify novel broad-host delivery vectors for microbiome engineering. Therefore, in this study, we characterized conjugative plasmids from a publicly available dataset of antibiotic-resistant isolate genomes in order to identify potential broad-host vectors for further applications. From the 199 closed genomes available in the CDC & FDA AR Isolate Bank, we identified 439 plasmids, of which 126 were predicted to be mobilizable and 206 conjugative. Various characteristics of the conjugative plasmids, such as size, replication origin, conjugation machinery, host defense mechanisms, and plasmid stability proteins, were analyzed to determine these plasmids’ potential host-range. Following this analysis, we clustered plasmid sequences and chose 22 unique, broad-host range plasmids that would be suitable for use as delivery vectors. This novel set of plasmids will provide a valuable resource for engineering microbial communities.
Research on antibiotic resistance in Helicobacter pylori: a bibliometric analysis of the past decade
Authors: Yuan Chengzhi , Yu Chang , Sun Qifang , Xiong Meng , Zhou Sainan , Zeng Meiyan , Song Houpan
Published: June 2023

Resistance of Helicobacter pylori (H. pylori) to antibiotics has reached alarming levels worldwide, and the efficacy of the H. pylori eradication treatment has decreased dramatically because of antibiotic resistance. To gain a more comprehensive understanding of the development status, research hotspots, and future trends related to H. pylori antibiotic resistance, we conducted a thorough retrospective analysis via the bibliometrics method. We searched the Science Citation Index Expanded of the Web of Science Core Collection for all pertinent articles on H. pylori antibiotic resistance from 2013 to 2022. R-bibliometrix, CiteSpace, and VOSviewer tools were utilized to depict statistical evaluations in order to provide an unbiased presentation and forecasts in the field. We incorporated a total of 3,509 articles related to H. pylori antibiotic resistance. Publications were inconsistent prior to 2017, but steadily increased after 2017. China generated the most papers and the United States of America received the most citations and the highest H-index. Baylor College of Medicine was the most influential institution in this field, with the highest number of publications and citations, as well as the highest H-index. Helicobacter was the most productive journal, followed by the World Journal of Gastroenterology and Frontiers in Microbiology. The World Journal of Gastroenterology had the highest citation. Graham, David Y was the most productive and cited author. Clarithromycin resistance, prevalence, gastric cancer, quadruple therapy, sequential therapy, 23S rRNA, whole genome sequencing, bismuth, and probiotics appeared with a high frequency in the keywords. The top keywords with the highest citation bursts were vonoprazan, RdxA, biofilm formation, and fatty acid chain. Our research illustrated a multi-dimensional facet and a holistic knowledge structure for H. pylori antibiotic resistance research over the past decade, which can serve as a guide for the H. pylori research community to conduct in-depth investigations in the future.
Comparative genomics of food-derived probiotic Lactiplantibacillus plantarum K25 reveals its hidden potential, compactness, and efficiency
Authors: Aziz Tariq , Naveed Muhammad , Shabbir Muhammad Aqib , Sarwar Abid , Ali Khan Ayaz , Zhennai Yang , Alharbi Metab , Alsahammari Abdulrahman , Alasmari Abdullah F.
Published: June 2023

This study aimed to investigate the intricate genetic makeup of the Lactiplantibacillus plantarum K25 strain by conducting a comprehensive analysis of comparative genomics. The results of our study demonstrate that the genome exhibits a high-level efficiency and compactness, comprising a total of 3,199 genes that encode proteins and a GC content of 43.38%. The present study elucidates the evolutionary lineage of Lactiplantibacillus plantarum strains through an analysis of the degree of gene order conservation and synteny across a range of strains, thereby underscoring their closely interrelated evolutionary trajectories. The identification of various genetic components in the K25 strain, such as bacteriocin gene clusters and prophage regions, highlights its potential utility in diverse domains, such as biotechnology and medicine. The distinctive genetic elements possess the potential to unveil innovative therapeutic and biotechnological remedies in future. This study provides a comprehensive analysis of the L. plantarum K25 strain, revealing its remarkable genomic potential and presenting novel prospects for utilizing its unique genetic features in diverse scientific fields. The present study contributes to the existing literature on Lactiplantibacillus plantarum and sets the stage for prospective investigations and practical implementations that leverage the exceptional genetic characteristics of this adap organism.
Genomic and pathogenicity islands of Listeria monocytogenes—overview of selected aspects
Authors: Wiktorczyk-Kapischke Natalia , Skowron Krzysztof , Wałecka-Zacharska Ewa
Published: June 2023

Listeria monocytogenes causes listeriosis, a disease characterized by a high mortality rate (up to 30%). Since the pathogen is highly tolerant to changing conditions (high and low temperature, wide pH range, low availability of nutrients), it is widespread in the environment, e.g., water, soil, or food. L. monocytogenes possess a number of genes that determine its high virulence potential, i.e., genes involved in the intracellular cycle (e.g., prfA, hly, plcA, plcB, inlA, inlB), response to stress conditions (e.g., sigB, gadA, caspD, clpB, lmo1138), biofilm formation (e.g., agr, luxS), or resistance to disinfectants (e.g., emrELm, bcrABC, mdrL). Some genes are organized into genomic and pathogenicity islands. The islands LIPI-1 and LIPI-3 contain genes related to the infectious life cycle and survival in the food processing environment, while LGI-1 and LGI-2 potentially ensure survival and durability in the production environment. Researchers constantly have been searching for new genes determining the virulence of L. monocytogenes. Understanding the virulence potential of L. monocytogenes is an important element of public health protection, as highly pathogenic strains may be associated with outbreaks and the severity of listeriosis. This review summarizes the selected aspects of L. monocytogenes genomic and pathogenicity islands, and the importance of whole genome sequencing for epidemiological purposes.
RelB is a potential molecular biomarker for immunotherapy in human pan-cancer
Authors: Wu Jintao , Yu Xinyu , Zhu Hongyu , Chen Peng , Liu Tongyan , Yin Rong , Qiang Yan , Xu Lin
Published: June 2023

Introduction: The nuclear factor kB (NF-κB) pathway emerges as a critical regulator of immune responses and is often dysregulated in human cancers. It consists of a family of transcription factors involved in many biological responses. Activated NF-κB subunits results in the nuclear translocation and activation of transcription, and the NF-κB pathway is known to influence the transcription of many genes. Noncanonical NF-κB and its components have been shown to have effects, usually protumorigenic, in many different cancer types. Besides, NF-κB signaling had diverse and complicated roles in cancer with studies that NF-κB could both contribute to tumor promotion and suppression of oncogenesis relying on the cellular context. RelB, a member of noncanonical NF-κB was abnormally regulated in most cancer types, however the molecular features and clinical signature of RelB expression, as well as its role in cancer immunity in human pan-cancer remains to be elucidated.

Methods: We used the open databases to explore RelB expression, clinical features and the association with tumor-infiltration cells in human pan-cancer. In this study, we investigated the aberration expression and prognostic significance of RelB, and the correlation with clinicopathological characters and immune cells infiltration in various cancers. The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to analyze the mRNA expression level in different cancer types. Kaplan-Meier analysis and Cox regression were used to explore the prognostic significance of RelB in human pan-cancer. Then we took advantage of the TCGA database to analyze the relationship between RelB expression and DNA methylation, the infiltration of immune cells, immune checkpoint genes, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MSS).

Results: Higher expression of RelB was significantly detected in human cancer tissues and a high level of RelB expression was significantly linked with a worse outcome in LGG, KIPAN, ACC, UVM, LUAD,THYM, GBM, LIHC and TGCT but associated with a favorable overall survival (OS) in SARC, SKCM and BRCA. According to the Human Protein Altas database, RelB was considered as an independent factor in breast cancer and renal cancer prognosis. GSEA results revealed that RelB was involved in many oncogenesisrelated processes and immunity-related pathways. RelB was significantly correlated with DNA methylation in 13 types of cancer. Meanwhile, RelB expression was associated with TMB in 5 types of cancer and MSI in 8 types of cancer. In the final, we analyzed the relationship between RelB expression and immune-infiltration cells in human pan-cancer, which suggested RelB could be a promising therapeutic target for cancer immunotherapy.

Discussion: Our study further provided insights into a deeper understanding of RelB as a prognostic biomarker.
Characteristics of autonomic dysfunction in neuronal intranuclear inclusion disease
Authors: Zhou Lu , Tian Yun , Zhang Sizhe , Jiao Bin , Liao Xinxin , Zhou Yafang , Xiao Qiao , Xue Jin , Duan Ranhui , Tang Beisha , Shen Lu
Published: June 2023

Background

This study aimed to investigate the features of autonomic dysfunction (AutD) in a large cohort of patients with neuronal intranuclear inclusion disease (NIID).

Methods

A total of 122 patients with NIID and 122 controls were enrolled. All participants completed the Scales for Outcomes in Parkinson’s Disease-Autonomic Questionnaire (SCOPA-AUT) and genetic screening for GGC expanded repeats within the NOTCH2NLC gene. All patients underwent neuropsychological and clinical assessments. SCOPA-AUT was performed to compare AutD between patients and controls. The associations between AutD and disease-related characteristics of NIID were studied.

Results

94.26% of patients had AutD. Compared with controls, patients had more severe AutD in total SCOPA-AUT, gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor and sexual domains (all p < 0.05). The area under the curve (AUC) value for the total SCOPA-AUT (AUC = 0.846, sensitivity = 69.7%, specificity = 85.2%, cutoff value = 4.5) was high in differentiating AtuD of patients with NIID from controls. The total SCOPA-AUT was significantly and positively associated with age (r = 0.185, p = 0.041), disease duration (r = 0.207, p = 0.022), Neuropsychiatric Inventory (NPI) (r = 0.446, p < 0.01), and Activities of Daily Living (ADL) (r = 0.390, p < 0.01). Patients with onset-of-AutD had higher SCOPA-AUT scores than patients without onset-of-AutD (p < 0.001), especially in the urinary system (p < 0.001) and male sexual dysfunction (p < 0.05).

Conclusion

SCOPA-AUT can be used as a diagnostic and quantitative tool for autonomic dysfunction in NIID. The high prevalence of AutD in patients suggests that NIID diagnosis should be considered in patients with AutD, especially in those with unexplained AutD alone. AutD in patients is related to age, disease duration, impairment of daily living ability, and psychiatric symptoms.
Predicting the fatigue in Parkinson's disease using inertial sensor gait data and clinical characteristics
Authors: Wang Hui , Hu Binbin , Huang Juan , Chen Lin , Yuan Min , Tian Xingfu , Shi Ting , Zhao Jiahao , Huang Wei
Published: June 2023

Objectives

The study aimed to analyze the clinical features and gait characteristics of patients with Parkinson's disease (PD) who also suffer from fatigue and to develop a model that can help identify fatigue states in the early stages of PD.

Methodology

A total of 81 PD patients have been enrolled for the Parkinson's Fatigue Scale (PFS-16) assessment and divided into two groups: patients with or without fatigue. Neuropsychological assessments of the two groups, including motor and non-motor symptoms, were collected. The patient's gait characteristics were collected using a wearable inertial sensor device.

Results

PD patients who experienced fatigue had a more significant impairment of motor symptoms than those who did not, and the experience of fatigue became more pronounced as the disease progressed. Patients with fatigue had more significant mood disorders and sleep disturbances, which can lead to a poorer quality of life. PD patients with fatigue had shorter step lengths, lower velocity, and stride length and increased stride length variability. As for kinematic parameters, PD patients with fatigue had lower shank-forward swing max, trunk-max sagittal angular velocity, and lumbar-max coronal angular velocity than PD patients without fatigue. The binary logistic analysis found that Movement Disorder Society-Unified Parkinson's Disease Rating Scale-I (MDS-UPDRS-I) scores, Hamilton Depression Scale (HAMD) scores, and stride length variability independently predicted fatigue in PD patients. The area under the curve (AUC) of these selected factors in the receiver operating characteristic (ROC) analysis was 0.900. Moreover, HAMD might completely mediate the association between Hamilton Anxiety Scale (HAMA) scores and fatigue (indirect effect: β = 0.032, 95% confidence interval: 0.001–0.062), with a percentage of mediation of 55.46%.

Conclusion

Combining clinical characteristics and gait cycle parameters, including MDS-UPDRS-I scores, HAMD scores, and stride length variability, can identify PD patients with a high fatigue risk.
Association between cognitive diagnosis and a range of significant life events in an elderly essential tremor cohort: a longitudinal, prospective analysis
Authors: Berry Diane S. , Nguyen Diep , Cosentino Stephanie , Louis Elan D.
Published: June 2023

Background

Although essential tremor (ET) patients have greater odds of mild cognitive impairment (MCI) and dementia than age-matched controls, the functional consequences of these enhanced odds are unknown. We examined associations between cognitive diagnosis and the occurrence of near falls, falls, use of a walking aid or a home health aide, non-independent living, or hospitalizations within a prospective, longitudinal study of ET patients.

Methods

A total of 131 ET patients (mean baseline age = 76.4 ± 9.4 years) completed a battery of neuropsychological tests and questions about life events and were assigned diagnoses of normal cognition (NC), MCI, or dementia at the baseline and at 18-, 36-, and 54-month follow-ups. Kruskall–Wallis, chi-square, and Mantel–Haenszel tests assessed whether the diagnosis was associated with the occurrence of these life events.

Results

Patients with final diagnoses of dementia were more often reported as living non-independently than NC or MCI patients and more often used walking aids than NC patients, with a p-value of <0.05. Patients with a final MCI or dementia diagnosis more often employed a home health aide than NC patients, with a p-value of <0.05. Moreover, Mantel–Haenzsel tests revealed linear associations between the occurrence of these outcomes and the level of cognitive impairment, with a p-value of <0.001 (i.e., dementia > MCI > NC).

Conclusion

Cognitive diagnosis was associated with reported life events of ET patients, including the use of a mobility aid, employment of a home health aide, and removal from an independent living situation. These data provide rare insights into the important role cognitive decline plays in the experiences of ET patients.
Neuromodulation in new-onset refractory status epilepticus
Authors: Stavropoulos Ioannis , Khaw Jin Han , Valentin Antonio
Published: June 2023

Background

New-onset refractory status epilepticus (NORSE) and its subset of febrile infection-related epilepsy syndrome (FIRES) are devastating clinical presentations with high rates of mortality and morbidity. The recently published consensus on the treatment of these conditions includes anesthetics, antiseizure drugs, antivirals, antibiotics, and immune therapies. Despite the internationally accepted treatment, the outcome remains poor for a significant percentage of patients.

Methods

We conducted a systematic review of the use of neuromodulation techniques in the treatment of the acute phase of NORSE/FIRES using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results

Our search strategy brought up 74 articles of which 15 met our inclusion criteria. A total of 20 patients were treated with neuromodulation. Thirteen cases represented FIRES and in 17 cases the NORSE remained cryptogenic. Ten had electroconvulsive therapy (ECT), seven had vagal nerve stimulation (VNS), and four had deep brain stimulation (DBS); one patient had initially VNS and later DBS. Eight patients were female and nine were children. In 17 out of 20 patients, the status epilepticus was resolved after neuromodulation, while three patients died.

Conclusion

NORSE can have a catastrophic course and the first treatment goal should be the fastest possible termination of status epilepticus. The data presented are limited by the small number of published cases and the variability of neuromodulation protocols used. However, they show some potential clinical benefits of early neuromodulation therapy, suggesting that these techniques could be considered within the course of FIRES/NORSE.
Classification of temporal lobe epilepsy based on neuropsychological tests and exploration of its underlying neurobiology
Authors: Meng Xianghong , Deng Kan , Huang Bingsheng , Lin Xiaoyi , Wu Yingtong , Tao Wei , Lin Chuxuan , Yang Yang , Chen Fuyong
Published: June 2023

Objective

To assist improving long-term postoperative seizure-free rate, we aimed to use machine learning algorithms based on neuropsychological data to differentiate temporal lobe epilepsy (TLE) from extratemporal lobe epilepsy (extraTLE), as well as explore the relationship between magnetic resonance imaging (MRI) and neuropsychological tests.

Methods

Twenty-three patients with TLE and 23 patients with extraTLE underwent neuropsychological tests and MRI scans before surgery. The least absolute shrinkage and selection operator were firstly employed for feature selection, and a machine learning approach with neuropsychological tests was employed to classify TLE using leave-one-out cross-validation. A generalized linear model was used to analyze the relationship between brain alterations and neuropsychological tests.

Results

We found that logistic regression with the selected neuropsychological tests generated classification accuracies of 87.0%, with an area under the receiver operating characteristic curve (AUC) of 0.89. Three neuropsychological tests were acquired as significant neuropsychological signatures for the diagnosis of TLE. We also found that the Right-Left Orientation Test difference was related to the superior temporal and the banks of the superior temporal sulcus (bankssts). The Conditional Association Learning Test (CALT) was associated with the cortical thickness difference in the lateral orbitofrontal area between the two groups, and the Component Verbal Fluency Test was associated with the cortical thickness difference in the lateral occipital cortex between the two groups.

Conclusion

These results showed that machine learning-based classification with the selected neuropsychological data can successfully classify TLE with high accuracy compared to previous studies, which could provide kind of warning sign for surgery candidate of TLE patients. In addition, understanding the mechanism of cognitive behavior by neuroimaging information could assist doctors in the presurgical evaluation of TLE.
Representation and decoding of bilateral arm motor imagery using unilateral cerebral LFP signals
Authors: Lin Jiafan , Lai Dongrong , Wan Zijun , Feng Linqing , Zhu Junming , Zhang Jianmin , Wang Yueming , Xu Kedi
Published: June 2023

Introduction

In the field of upper limb brain computer interfaces (BCIs), the research focusing on bilateral decoding mostly based on the neural signals from two cerebral hemispheres. In addition, most studies used spikes for decoding. Here we examined the representation and decoding of different laterality and regions arm motor imagery in unilateral motor cortex based on local field potentials (LFPs).

Methods

The LFP signals were recorded from a 96-channel Utah microelectrode array implanted in the left primary motor cortex of a paralyzed participant. There were 7 kinds of tasks: rest, left, right and bilateral elbow and wrist flexion. We performed time-frequency analysis on the LFP signals and analyzed the representation and decoding of different tasks using the power and energy of different frequency bands.

Results

The frequency range of <8 Hz and >38 Hz showed power enhancement, whereas 8–38 Hz showed power suppression in spectrograms while performing motor imagery. There were significant differences in average energy between tasks. What’s more, the movement region and laterality were represented in two dimensions by demixed principal component analysis. The 135–300 Hz band signal had the highest decoding accuracy among all frequency bands and the contralateral and bilateral signals had more similar single-channel power activation patterns and larger signal correlation than contralateral and ipsilateral signals, bilateral and ipsilateral signals.

Discussion

The results showed that unilateral LFP signals had different representations for bilateral motor imagery on the average energy of the full array and single-channel power levels, and different tasks could be decoded. These proved the feasibility of multilateral BCI based on the unilateral LFP signal to broaden the application of BCI technology.

Clinical trial registration

https://www.chictr.org.cn/showproj.aspx?proj=130829, identifier ChiCTR2100050705.
Age-integrated artificial intelligence framework for sleep stage classification and obstructive sleep apnea screening
Authors: Kang Chaewon , An Sora , Kim Hyeon Jin , Devi Maithreyee , Cho Aram , Hwang Sungeun , Lee Hyang Woon
Published: June 2023

Introduction

Sleep is an essential function to sustain a healthy life, and sleep dysfunction can cause various physical and mental issues. In particular, obstructive sleep apnea (OSA) is one of the most common sleep disorders and, if not treated in a timely manner, OSA can lead to critical problems such as hypertension or heart disease.

Methods

The first crucial step in evaluating individuals’ quality of sleep and diagnosing sleep disorders is to classify sleep stages using polysomnographic (PSG) data including electroencephalography (EEG). To date, such sleep stage scoring has been mainly performed manually via visual inspection by experts, which is not only a time-consuming and laborious process but also may yield subjective results. Therefore, we have developed a computational framework that enables automatic sleep stage classification utilizing the power spectral density (PSD) features of sleep EEG based on three different learning algorithms: support vector machine, k-nearest neighbors, and multilayer perceptron (MLP). In particular, we propose an integrated artificial intelligence (AI) framework to further inform the risk of OSA based on the characteristics in automatically scored sleep stages. Given the previous finding that the characteristics of sleep EEG differ by age group, we employed a strategy of training age-specific models (younger and older groups) and a general model and comparing their performance.

Results

The performance of the younger age-specific group model was similar to that of the general model (and even higher than the general model at certain stages), but the performance of the older age-specific group model was rather low, suggesting that bias in individual variables, such as age bias, should be considered during model training. Our integrated model yielded an accuracy of 73% in sleep stage classification and 73% in OSA screening when MLP algorithm was applied, which indicates that patients with OSA could be screened with the corresponding accuracy level only with sleep EEG without respiration-related measures.

Discussion

The current outcomes demonstrate the feasibility of AI-based computational studies that when combined with advances in wearable devices and relevant technologies could contribute to personalized medicine by not only assessing an individuals’ sleep status conveniently at home but also by alerting them to the risk of sleep disorders and enabling early intervention.
In Type 2 Diabetes Mellitus, normalization of hemoglobin A1c accompanies reduced sensitivity to pressure at the sternum
Authors: Faber Jens , Ballegaard Søren , Ørsted Nanna , Eldrup Ebbe , Karpatschof Benny , Gyntelberg Finn , Hecquet Sofie Korsgaard , Gjedde Albert
Published: June 2023

Background

The autonomic nervous system (ANS) maintains glucose homeostasis. While higher than normal glucose levels stimulate the ANS toward reduction, previous findings suggest an association between sensitivity to, or pain from, pressure at the chest bone (pressure or pain sensitivity, PPS) and activity of the ANS. A recent randomized controlled trial (RCT) of type 2 diabetes (T2DM) suggested that addition of an experimental, non-pharmacological intervention more effectively than conventional treatment lowered the levels of both PPS and HbA1c.

Materials and analyses

We tested the null hypothesis that conventional treatment (n = 60) would reveal no association between baseline HbA1c and normalization of HbA1c in 6 months, related to change of PPS. We compared the changes of HbA1c in PPS reverters who experienced a minimum reduction of 15 units of PPS and in PPS non-reverters who experienced no reduction. Depending on the result, we tested the association in a second group of participants with addition of the experimental program (n = 52).

Results

In the conventional group, PPS reverters experienced normalization of HbA1c that corrected the basal increase, thus disproving the null hypothesis. With the addition of the experimental program, PPS reverters experienced similar reduction. The reduction of HbA1c among reverters averaged 0.62 mmol/mol per mmol/mol increase of baseline HbA1c (P < 0.0001 compared to non-reverters). For baseline HbA1c ≥ 64 mmol/mol, reverters averaged 22% reduction of HbA1c (P < 0.01).

Conclusion

In consecutive analyses of two different populations of individuals with T2DM, we demonstrated that the higher the baseline HbA1c, the greater the reduction of HbA1c but only in individuals with a concomitant reduction of sensitivity to PPS, suggesting a homeostatic effect of the autonomic nervous system on glucose metabolism. As such, ANS function, measured as PPS, is an objective measure of HbA1c homeostasis. This observation may be of great clinical importance.
Multi-neuronal recording in unrestrained animals with all acousto-optic random-access line-scanning two-photon microscopy
Authors: Yamaguchi Akihiro , Wu Rui , McNulty Paul , Karagyozov Doycho , Mihovilovic Skanata Mirna , Gershow Marc
Published: June 2023

To understand how neural activity encodes and coordinates behavior, it is desirable to record multi-neuronal activity in freely behaving animals. Imaging in unrestrained animals is challenging, especially for those, like larval Drosophila melanogaster, whose brains are deformed by body motion. A previously demonstrated two-photon tracking microscope recorded from individual neurons in freely crawling Drosophila larvae but faced limits in multi-neuronal recording. Here we demonstrate a new tracking microscope using acousto-optic deflectors (AODs) and an acoustic GRIN lens (TAG lens) to achieve axially resonant 2D random access scanning, sampling along arbitrarily located axial lines at a line rate of 70 kHz. With a tracking latency of 0.1 ms, this microscope recorded activities of various neurons in moving larval Drosophila CNS and VNC including premotor neurons, bilateral visual interneurons, and descending command neurons. This technique can be applied to the existing two-photon microscope to allow for fast 3D tracking and scanning.
Probiotics for the prevention of mortality and sepsis in preterm very low birth weight neonates from low- and middle-income countries: a Bayesian network meta-analysis
Authors: Thomas Deena , Sharma Akash , Sankar M. Jeeva
Published: June 2023

Background

Probiotics have been shown to reduce the risk of mortality and necrotizing enterocolitis (NEC) in very low birth weight (VLBW) neonates. The probiotic species with the maximal benefits in neonates from low- and middle-income countries are unknown.

Objective

To identify the strain of probiotics with the maximum benefit in preventing neonatal mortality, sepsis, and NEC using the Bayesian network meta-analysis.

Search methods

We searched Medline via PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We also hand-searched reference lists of previous systematic reviews to identify eligible studies.

Selection criteria

Randomized controlled trials (RCTs) from LMICs comparing enteral supplementation of one or more probiotics with another probiotic species or placebo were included.

Data collection and analysis

Two authors screened the studies, extracted the data, and examined the risk of bias using the Cochrane risk of bias 2 (RoB 2) tools. Bayesian network meta-analysis was performed using the “BUGSnet” package in R and RStudio (version 1.4.1103). The confidence in the findings was assessed using the Confidence in Network Meta-analysis (CINeMA) web application.

Results

Twenty-nine RCTs enrolling 4,906 neonates and evaluating 24 probiotics were included. Only 11 (38%) studies had a low risk of bias. All the studies compared the probiotics with a placebo; none had a head-to-head comparison of different probiotic species. Also, only one study each had evaluated most probiotic regimens. When compared to placebo, the combination of B longum, B bifidum, B infantis, and L acidophilus may reduce the risk of mortality (relative risk [RR] 0.26; 95% credible interval [CrI] 0.07 to 0.72), sepsis (RR 0.47; 95% CrI 0.25 to 0.83), and NEC (RR 0.31; 95% CrI 0.10 to 0.78) but the evidence is very uncertain. There is low certainty evidence that the single probiotic species, B lactis, could reduce the risk of mortality (RR 0.21; 0.05 to 0.66) and NEC (RR 0.09; 0.01 to 0.32).

Conclusion

Given the low to very low certainty of evidence for the efficacy of the two probiotics found to reduce mortality and necrotizing enterocolitis, no firm conclusions can be made on the optimal probiotics for use in preterm neonates in low- and middle-income countries.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022353242, identifier: CRD42022353242.