bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulsed field ablation of superior vena cava in paroxysmal atrial fibrillation: a case report
Authors: Tao Yirao , Zhou Yang , Sun Xuerong , Liao Wenkai , Wang Yanjiang , Shi Liang , Liu Xingpeng
Published: June 2023

Paroxysmal atrial fibrillation originates most commonly in the pulmonary veins. However, the superior vena cava has proved to be arrhythmogenic in some cases. Pulsed field ablation, an emerging ablation technology, selectively affects myocardial tissue. Herein, we present a case of paroxysmal atrial fibrillation in a 64-year-old man who was admitted to our hospital for pulsed field ablation. The tachycardia was recurrent despite four successful pulmonary vein isolations. The superior vena cava was determined to be involved in arrhythmogenesis. The atrial fibrillation terminated immediately after the pulsed field ablation discharge at the superior vena cava.
Investigating the role of ASCC1 in the causation of bone fragility
Authors: Voraberger Barbara , Mayr Johannes A. , Fratzl-Zelman Nadja , Blouin Stéphane , Uday Suma , Kopajtich Robert , Koedam Marijke , Hödlmayr Helena , Wortmann Saskia B. , Csillag Bernhard , Prokisch Holger , van der Eerden Bram C. J. , El-Gazzar Ahmed , Högler Wolfgang
Published: June 2023

Bi-allelic variants in ASCC1 cause the ultrarare bone fragility disorder “spinal muscular atrophy with congenital bone fractures-2” (SMABF2). However, the mechanism by which ASCC1 dysfunction leads to this musculoskeletal condition and the nature of the associated bone defect are poorly understood. By exome sequencing, we identified a novel homozygous deletion in ASCC1 in a female infant. She was born with severe muscular hypotonia, inability to breathe and swallow, and virtual absence of spontaneous movements; showed progressive brain atrophy, gracile long bones, very slender ribs, and a femur fracture; and died from respiratory failure aged 3 months. A transiliac bone sample taken postmortem revealed a distinct microstructural bone phenotype with low trabecular bone volume, low bone remodeling, disordered collagen organization, and an abnormally high bone marrow adiposity. Proteomics, RNA sequencing, and qPCR in patient-derived skin fibroblasts confirmed that ASCC1 was hardly expressed on protein and RNA levels compared with healthy controls. Furthermore, we demonstrate that mutated ASCC1 is associated with a downregulation of RUNX2, the master regulator of osteoblastogenesis, and SERPINF1, which is involved in osteoblast and adipocyte differentiation. It also exerts an inhibitory effect on TGF-β/SMAD signaling, which is important for bone development. Additionally, knockdown of ASCC1 in human mesenchymal stromal cells (hMSCs) suppressed their differentiation capacity into osteoblasts while increasing their differentiation into adipocytes. This resulted in reduced mineralization and elevated formation of lipid droplets. These findings shed light onto the pathophysiologic mechanisms underlying SMABF2 and assign a new biological role to ASCC1 acting as an important pro-osteoblastogenic and anti-adipogenic regulator.
Bioclimatic inference based on mammal community using machine learning regression models: perspectives for paleoecological studies
Authors: Linchamps Pierre , Stoetzel Emmanuelle , Robinet François , Hanon Raphaël , Latouche Pierre , Cornette Raphaël
Published: June 2023

Climate has played a significant role in shaping the distribution of mammal species across the world. Mammal community composition can therefore be used for inferring modern and past climatic conditions. Here, we develop a novel approach for bioclimatic inference using machine learning (ML) algorithms, which allows for accurate prediction of a set of climate variables based on the composition of the faunal community. The automated dataset construction process aggregates bioclimatic variables with modern species distribution maps, and includes multiple taxonomic ranks as explanatory variables for the predictions. This yields a large dataset that can be used to produce highly accurate predictions. Various ML algorithms that perform regression have been examined. To account for spatial dependence in our data, we employed a geographical block validation approach for model validation and selection. The random forest (RF) outperformed the other evaluated algorithms. Ultimately, we used unseen modern mammal surveys to assess the high predictive performances and extrapolation abilities achieved by our trained models. This contribution introduces a framework and methodology to construct models for developing models based on neo-ecological data, which could be utilized for paleoclimate applications in the future. The study aimed to satisfy specific criteria for interpreting both modern and paleo faunal assemblages, including the ability to generate reliable climate predictions from faunal lists with varying taxonomic resolutions, without the need for published wildlife inventory data from the study area. This method demonstrates the versatility of ML techniques in climate modeling and highlights their promising potential for applications in the fields of archaeology and paleontology.
Analysis of sediment from an irrigation dam in an agricultural valley impacted by the mega-drought in central Chile
Authors: Jaque Jennery , Melo Pinochet Naveska , Aránguiz-Acuña Adriana , Pizarro Héctor
Published: June 2023

Central Chile has been affected since 2010 by an increasing mega-drought accompanied by a historically low precipitation rate, as a probable consequence of climate change. Additionally, the increasing pressure exerted by the withdrawals of human activities, such as agriculture and metal mining, promotes conditions of hydric scarcity. Despite this intensive use of the watersheds and the sustained and increasing aridity, it has not been explored whether an artificial sedimentary record can trace these changes in the agricultural valleys of the region. To unravel and evaluate the recent environmental/climatic variability, the effects of the mega-drought that has pertained since 2010, extractivist pressures on a Mediterranean valley in central Chile, and sediment records were obtained from an irrigation dam and studied through a multi-proxy analysis. The dam was built and has been in operation since 1975 and is located in the Aconcagua River Valley, Valparaíso, Chile. Magnetic properties, carbon content, mineral composition, and metal content were analyzed from sediments of a 120 cm long core. Changes in vegetation cover from 1990 to 2020 were analyzed through NDVI filters. Horizons associated with drier conditions were observed in the upper zone of the core, which corresponded from the year 2001 to the present, assuming a constant sedimentation rate of 2.72 cm·yr−1. Additionally, the characteristic alternation of dry–wet conditions was observed in the deep horizon of the dam sediments. The concentrations of Cu, Pb, Al, and As have increased over the years, while the concentration of Mo has decreased. Some of these elements are associated with copper mining, existing in the valley. Analysis of Landsat images from the year 2000 to the present has identified a significant decrease in vegetation cover associated with dry/wet periods, which may be related to cycles of El Niño/La Niña events. Although not all the proxies analyzed were sensitive enough to detect changes at the desired resolution, since the dam is very recent, the results shed light on the effects of the interaction between industrial activities and the decrease of water availability in multiple-use watersheds, suggesting variations in metals concentrations and changes in water availability, probably promoted by anthropic activities, climatic events, and increasing aridity in the Aconcagua River Valley.
An ecological and neurobiological perspective on the evolution of vocal learning
Authors: Brenowitz Eliot A. , Beecher Michael D.
Published: June 2023

Vocal production learning (VPL) involves the use of auditory experience to guide the production of novel signals or to modify pre-existing signals. It allows animals to develop signals that are more complex and/or more flexible than innately developed signals. It has evolved rarely in vocal animals, widespread only in three avian and four mammalian taxa. The evolution of VPL was accompanied by innovations of the vocal motor neural circuitry. VPL is rare because of its various costs. Ecology, social spacing, and social fluidity can favor the evolution of VPL. It is striking that most taxa with VPL evolved in visually limited habitats, where sound is the only effective channel for communicating over distance from sender to receiver. Selective factors that favor the ability to produce complex and/or flexible signals would act predominantly on acoustic signals, and favor the evolution of VPL. Learning may be the only practical way to develop a signal complex enough to encode different types of information for assessment by receivers in animals that rely on acoustic communication, or to modify signals as local social factors dictate.
Exploration of the association between the single-nucleotide polymorphism of co-stimulatory system and rheumatoid arthritis
Authors: Chen Ding-Ping , Wen Ying-Hao , Lin Wei-Tzu , Hsu Fang-Ping , Yu Kuang-Hui
Published: June 2023

Introduction

The human leukocyte antigen (HLA) has been linked to the majority of autoimmune diseases (ADs). However, non-HLA genes may be risk factors for ADs. A number of genes encoding proteins involved in regulating T-cell and B-cell function have been identified as rheumatoid arthritis (RA) susceptibility genes.

Methods

In this study, we investigated the association between RA and single-nucleotide polymorphisms (SNPs) of co-stimulatory or co-inhibitory molecules in 124 RA cases and 100 healthy controls without immune-related diseases [including tumor necrosis factor superfamily member 4 (TNFSF4), CD28, cytotoxic T-lymphocyte–associated protein 4 (CTLA4), and programmed cell death protein 1 (PDCD1)].

Results

The results showed that there were 13 SNPs associated with RA, including rs181758110 of TNFSF4 (CC vs. CT, p = 0.038); rs3181096 of CD28 (TT vs. CC + CT, p = 0.035; CC vs. TT, p = 0.047); rs11571315 (TT vs. CT, p = 0.045), rs733618 (CC vs. TT + CT, p = 0.043), rs4553808 (AA vs. AG vs. GG, p = 0.035), rs11571316 (GG vs. AG vs. AA, p = 0.048; GG vs. AG + AA, p = 0.026; GG vs. AG, p = 0.014), rs16840252 (CC vs. CT vs. TT, p = 0.007; CC vs. CT, p = 0.011), rs5742909 (CC vs. CT vs. TT, p = 0.040), and rs11571319 of CTLA4 (GG vs. AG vs. AA, p < 0.001; GG vs. AG + AA, p = 0.048; AA vs. GG + AG, p = 0.001; GG vs. AA, p = 0.008; GG vs. AG, p ≤ 0.001); and rs10204525 (TT vs. CT + CC, p = 0.024; TT vs. CT, p = 0.021), rs2227982 (AA vs. GG, p = 0.047), rs36084323 (TT vs. CT vs. CC, p = 0.022; TT vs. CT + CC, p = 0.013; CC vs. TT + CT, p = 0.048; TT vs. CC, p = 0.008), and rs5839828 of PDCD1 (DEL vs. DEL/G vs. GG, p = 0.014; DEL vs. DEL/G + GG, p = 0.014; GG vs. DEL + DEL/G, p = 0.025; DEL vs. GG, p = 0.007).

Discussion

Consequently, these SNPs may play an important role in immune regulation, and further research into the role of these SNPs of immune regulatory genes in the pathogenesis of RA is required.
Characterizing distinct profiles of immune and inflammatory response with age to Omicron infection
Authors: Zhang Lina , Wang Zhanwen , Lyu Feng , Liu Chun , Li Chunhui , Liu Wei , Ma Xinhua , Zhou Jieyu , Qian Xinyu , Qian Zhaoxin , Lu Yong
Published: June 2023

Background

Understanding inflammatory and immune responses to Omicron infection based on age is crucial when addressing this global health threat. However, the lacking of comprehensive elucidation hinders the development of distinct treatments tailored to different age populations.

Methods

1299 cases of Omicron infection in Shanghai were enrolled between April 10, 2022 and June 3, 2022, dividing into three groups by ages: Adult group (18-59 years), Old group (60-79 years), and Elder group (≥ 80 years). Laboratory data including inflammatory cytokines, cellular, and humoral immunity were collected and analyzed.

Results

The mean age of Adult, Old, and Elder groups were 44.14, 69.98, and 89.35 years, respectively, with 40.9% being men. The Elder group patients exhibited higher white blood cell (WBC) counts and elevated levels of inflammatory cytokines, but their lymphocyte counts were relatively lower. In comparison to the Old group patients, the Elder group patients demonstrated significantly lower CD3+ T-cell counts, CD3+ T-cell proportion, CD4+ T-cell counts, CD8+ T-cell counts, and CD19+ B-cell counts, while the NK-cell counts were higher. Omicron negative patients displayed a higher proportion of CD19+ B-cells and higher levels of Complement-3 and IL-17 compared to the positive patients in the Old group. Omicron negative patients had lower WBC counts, CD3+CD8+ T-cells proportion, and the levels of serum amyloid A and IgA in the Elder group, but the CD4+/CD8+ ratio was higher.

Conclusions

Our study identified the distinct profiles of inflammatory and immune responses to Omicron infection varying with age and highlighted the diverse correlations between the levels of various biomarkers and Omicron infected/convalescent patients.
Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis
Authors: Sampath Pavithra , Moorthy Manju , Menon Athul , Madhav Lekshmi , Janaki Aishwarya , Dhanapal Madhavan , Natarajan Alangudi Palaniappan , Hissar Syed , Ranganathan Uma Devi , Ramaswamy Gopalakrishna , Bethunaickan Ramalingam
Published: June 2023

Background

Monocyte miRNAs govern both protective and pathological responses during tuberculosis (TB) through their differential expression and emerged as potent targets for biomarker discovery and host-directed therapeutics. Thus, this study examined the miRNA profile of sorted monocytes across the TB disease spectrum [drug-resistant TB (DR-TB), drug-sensitive TB (DS-TB), and latent TB] and in healthy individuals (HC) to understand the underlying pathophysiology and their regulatory mechanism.

Methods

We sorted total monocytes including three subsets (HLA-DR+CD14+, HLA-DR+CD14+CD16+, and HLA-DR+CD16+cells) from peripheral blood mononuclear cells (PBMCs) of healthy and TB-infected individuals through flow cytometry and subjected them to NanoString-based miRNA profiling.

Results

The outcome was the differential expression of 107 miRNAs particularly the downregulation of miRNAs in the active TB groups (both drug-resistant and drug-sensitive). The miRNA profile revealed differential expression signatures: i) decline of miR-548m in DR-TB alone, ii) decline of miR-486-3p in active TB but significant elevation only in LTB iii) elevation of miR-132-3p only in active TB (DR-TB and DS-TB) and iv) elevation of miR-150-5p in DR-TB alone. The directionality of functions mediated by monocyte miRNAs from Gene Set Enrichment Analysis (GSEA) facilitated two phenomenal findings: i) a bidirectional response between active disease (activation profile in DR-TB and DS-TB compared to LTB and HC) and latent infection (suppression profile in LTB vs HC) and ii) hyper immune activation in the DR-TB group compared to DS-TB.

Conclusion

Thus, monocyte miRNA signatures provide pathological clues for altered monocyte function, drug resistance, and disease severity. Further studies on monocyte miRNAs may shed light on the immune regulatory mechanism for tuberculosis.
Case Report: Cord blood-derived natural killer cells as new potential immunotherapy drug for solid tumor: a case study for endometrial cancer
Authors: Mu Yongxu , Tong Jiabei , Wang Yujun , Yang Yuxiao , Wu Xiaoyun
Published: June 2023

Adoptive transfer of natural killer (NK) cells represents a viable treatment method for patients with advanced malignancies. Our team previously developed a simple, safe, and cost-effective method for obtaining high yields of pure and functional NK cells from cord blood (CB) without the need for cell sorting, feeder cells, or multiple cytokines. We present the case of a 52-year-old female patient diagnosed with poorly differentiated stage IVB (T3N2M1) endometrial cancer, who exhibited leukemoid reaction and pretreatment thrombocytosis as paraneoplastic syndromes. The patient received two courses of CB-derived NK (CB-NK) cell immunotherapy between March and September 2022, due to her extremely low NK cell activity. Two available CB units matched at 8/10 HLA with KIR-mismatch were chosen, and we were able to produce NK cells with high yield (>1.0×1010 NK cells), purity (>90%), and function (>80%) from CB without cell sorting, feeder cells, or multiple cytokines. These cells were then adoptively transferred to the patient. No adverse effects or graft-versus-host disease were observed after infusion of CB-NK cells. Our clinical experience supports the efficacy of CB-NK cell treatment in increasing NK cell activity, depleting tumor activity, improving quality of life, and reducing the size of abdominal and pelvic masses with the disappearance of multiple lymph node metastases through the regulation of systemic antitumor immunity. Remarkably, the white blood cell and platelet counts decreased to normal levels after CB-NK cell immunotherapy. This clinical work suggests that CB-NK cell immunotherapy holds promise as a therapeutic approach for endometrial cancer.
Tidewater glaciers as “climate refugia” for zooplankton-dependent food web in Kongsfjorden, Svalbard
Authors: Hop Haakon , Wold Anette , Vihtakari Mikko , Assmy Philipp , Kuklinski Piotr , Kwasniewski Slawomir , Griffith Gary P. , Pavlova Olga , Duarte Pedro , Steen Harald
Published: June 2023

With climate warming, many tidewater glaciers are retreating. Fresh, sediment-rich sub-glacial meltwater is discharged at the glacier grounding line, where it mixes with deep marine water resulting in an upwelling of a plume visible in front of the glacial wall. Zooplankton may suffer increased mortality within the plume due to osmotic shock when brought in contact with the rising meltwater. The constant replenishment of zooplankton and juvenile fish to the surface areas attracts surface-foraging seabirds. Because access to other feeding areas, such as the marginal ice zone, has become energetically costly due to reduced sea-ice extent, glacial plumes may become increasingly important as “climate refugia” providing enhanced prey availability. Here, we investigated zooplankton concentrations within the plume and adjacent waters of four tidewater glaciers in Kongsfjorden, Svalbard, in early August 2016 and late July 2017. Our aim was to compare the zooplankton composition, abundance, and isotopic signatures within the plumes to those in adjacent fjord and shelf waters. Our hypothesis was that the plumes resulted in increased zooplankton mortality through osmotic shock and increased prey availability to predators. The mortality due to osmotic shock in the glacial plume was low (<5% dead organisms in samples), although slightly higher than in surrounding waters. This indicates that plumes are inefficient “death traps” for zooplankton. However, the high abundance and biomass of zooplankton within plume areas suggest that the “elevator effect” of rising glacial water supplies zooplankton to the sea surface, thereby enhancing prey availability for surface-feeding seabirds. Thus, our study provides evidence that glacial plumes are important as “climate refugia” for foraging seabirds. Stable isotope signatures showed that the glacial bay zooplankton and fish community represent a distinct isotopic niche. Additionally, zooplankton mortality associated with the plume estimated over 100-days of melt season supports a flux of 12.8 tonnes of organic carbon to benthic communities in the glacial bays. Benthic scavengers, such as Onisimus caricus and Anonyx nugax, were abundant in the glacial bay, where they feed on sinking organic matter.
Gonadotropin inhibitory-hormone modulates neurosteroids-synthesizing enzymes expression and aggressive behavior in male sea bass, Dicentrarchus labrax
Authors: Paullada-Salmerón José Antonio , Loentgen Guillaume Henri , Fuentès Michaël , Besseau Laurence , Ubuka Takayoshi , Mañanos Evaristo Luis , Muñoz-Cueto José Antonio
Published: June 2023

Neurosteroids are involved in the regulation of multiple behavioral and physiological processes and metabolic activities in the vertebrate brain. However, central mechanisms of how neurosteroid synthesis is regulated is far to be understood. Gonadotropin-inhibitory hormone (GNIH) is a hypothalamic neuropeptide that negatively regulates gonadotropin secretion but also inhibits sexual and aggressive behaviors in birds and mammals by modulating aromatase enzyme and neuroestrogen synthesis. In a previous study performed in male sea bass, we reported that Gnih inhibited the reproductive axis by acting at the three levels of the brain-pituitary-gonad axis. Moreover, the presence of Gnih cells and fibers in the telencephalon, mesencephalon and rhombencephalon suggests a role of Gnih in regulating other important brain functions in sea bass, including behavior. In this study, we have analyzed the effects of the intracerebroventricular (icv) injection of sbGnih-2 on the brain and pituitary expression of the main neurosteroids-synthesizing enzymes (stAR, cyp17, 3β-hsd, 17β-hsd, cyp19b, cyp7b), as well as on estrogen and androgen receptors (erα, erβ1, erβ2, ar). A combination of immunohistochemistry and in situ hybridization was also used to identify putative interaction of Gnih- and aromatase-positive cells. We also performed a mirror test study as a proxy to measure aggression levels and agonistic behavior after icv injection of sbGnih-2. Central administration of sbGnih-2 at different doses reduced the transcript levels of 3β-hsd and 17β-hsd, and increased the expression of cyp19b (brain aromatase) in the sea bass brain. Neuroanatomical results suggest that paracrine and neuroendocrine actions could mediate Gnih effects on aromatase expression. Central administration of sbGnih-2 also decreased the pituitary expression of 17β-hsd and estrogen receptors (erβ2). The mirror test analysis showed that sbGnih-2 affected the agonistic/aggressive behavior of sea bass as revealed by the decreased interaction with the mirror, lower time spent in the mirror zone, increased latency to establish contact with the mirror and higher mean distance to the mirror zone. In contrast, locomotor activity parameters measured were not affected by sbGnih-2 injection. Taken together, our results showed for the first time in fish that Gnih inhibits social-aggressive behavior and affects the gene expression of neurosteroid-synthesizing enzymes giving rise to neuroandrogens and neuroestrogens in the sea bass brain.
The baseline is already shifted: marine microbiome restoration and rehabilitation as essential tools to mitigate ecosystem decline
Authors: Peixoto Raquel S. , Voolstra Christian R.
Published: June 2023

Climate change is turning formerly pristine ecosystems into ever-changing states, causing major disturbance and biodiversity loss. Such impacted marine ecosystems and organisms exhibit clear microbiome shifts that alter their function. Microbiome-targeted interventions appear as feasible tools to support organismal and ecosystem resilience and recovery by restoring symbiotic interactions and thwarting dysbiotic processes. However, microbiome restoration and rehabilitation are perceived as drastic measures, since they alter ‘natural relationships’. What is missing from this notion is that microbiomes already drastically differ from any pre-anthropogenic state. As such, our perception and definition of even ‘pristine states’ may in fact represent an already disturbed/derived condition. Following this, we argue that restoring and rehabilitating marine microbiomes are essential tools to mitigate ecosystem and organismal decline.
Eliminating financial disincentives to living kidney donation – a call to action
Authors: Polireddy Karunesh , Crepeau Rebecca L. , Matar Abraham J.
Published: June 2023

The incidence of end stage renal disease (ESRD) in the United States (US) is increasing each year. The lone curative treatment for ESRD remains kidney transplantation. Despite the demonstrated medical and economic benefits, living donor kidney transplantation (LDKT) only accounts for a small number of kidney transplantations each year. Direct and indirect costs exist that disincentivize potential living kidney donors from coming forward, such as the cost of travel and lodging, risk of death, potential loss of income due to an extended recovery time, and the inability to donate to a relative in the future if needed. Herein, we advocate for policy changes that make living kidney donation (LKD) a financially neutral process thereby incentivizing increased LDKT and mitigating the kidney donor shortage.
Women's health, hormonal balance, and personal autonomy
Authors: Segarra Ignacio , Menárguez Micaela , Roqué María Victoria
Published: June 2023

Hormone-based contraception disrupts hormonal balance, creating artificial states of anovulation and threatening women's health. We reviewed its main adverse effects and mechanisms on accelerated ovarian aging, mental health (emotional disruptions, depression, and suicide), sexuality (reduced libido), cardiovascular (brain stroke, myocardial infarction, hypertension, and thrombosis), and oncological (breast, cervical, and endometrial cancers). Other “collateral damage” includes negative effects on communication, scientific mistrust, poor physician–patient relationships, increased patient burden, economic drain on the healthcare system, and environmental pollution. Hormone-sensitive tumors present a dilemma owing to their potential dual effects: preventing some cancers vs. higher risk for others remains controversial, with denial or dismissal as non-relevant adverse effects, information avoidance, and modification of scientific criteria. This lack of clinical assessment poses challenges to women's health and their right to autonomy. Overcoming these challenges requires an anthropological integration of sexuality, as the focus on genital bodily union alone fails to encompass the intimate relational expression of individuals, complete sexual satisfaction, and the intertwined feelings of trust, safety, tenderness, and endorsement of women's femininity.
Protocol for the development of a reporting guideline for clinical trials with integrated Chinese and western medicine interventions: the CONSORT extension for ICWM
Authors: Wang Juan , Zhang Xuan , Wang Ping , Han Fei , Li Ji , Ma Yanfang , Lyu Aiping , Bian Zhaoxiang
Published: June 2023

Background

While Integrated Chinese and Western Medicine (ICWM) has become widely accepted as a necessary intervention for treating various diseases, key information about ICWM interventions is often missing in published clinical trials. To facilitate complete, transparent, and consistent reporting of clinical trials with ICWM interventions, an extension of the CONSORT guideline is necessary to be developed: the CONSORT-ICWM guideline.

Methods

The CONSORT-ICWM guideline will be developed in five stages in accordance with recommendations for the development of reporting guidelines from the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network, including (1) project launch and registration; (2) literature review and checklist draft; (3) Delphi survey; (4) consensus meeting; and (5) finalization of the guideline. Additionally, the working group will be composed of professors with expertise in integrated medicines, traditional Chinese medicines, biomedical informatics, statistics, methodology, development of reporting guidelines, epidemiology, health economics, and paper publications.

Discussion

The CONSORT-ICWM guideline is to improve the reporting quality of clinical trials with ICWM interventions by ensuring the reports are complete, informative, clear, and transparent.
Kunxian capsule alleviates podocyte injury and proteinuria by inactivating β-catenin in db/db mice
Authors: Jin Bo , Liu Jing , Zhu Yan , Lu Jian , Zhang Qingyan , Liang Yan , Shao Qiuyuan , Jiang Chunming
Published: June 2023

Background

Diabetic kidney disease (DKD) remains the primary cause of end-stage renal disease (ESRD) globally, but treatment options are limited. Kunxian capsule (KXC) has been utilized for the treatment of autoimmune diseases and IgA nephropathy in China. However, its effect on DKD remains poorly investigated. Therefore, this study aimed to explore the protective effect of KXC in db/db mice and elucidate its underlying mechanism.

Methods

The renoprotective effects of KXC were assessed in a DKD mouse model using male BKS db/db diabetic mice. After 8 weeks of treatment, the urinary albumin-to-creatinine ratio (UACR), blood biochemical parameters, renal histopathological manifestation, and podocyte ultrastructural changes were evaluated. Additionally, the expression of podocyte epithelial-to-mesenchymal transition (EMT) markers [WT1, ZO-1, and collogen I (Col1a1)] was quantitatively analyzed. Furthermore, we explored the role of KXC in the β-catenin signaling pathway to elucidate the underlying mechanism of KXC’s renoprotective effect.

Results

KXC treatment effectively reduced albuminuria and attenuated renal structural abnormalities in db/db mice. Additionally, KXC restored the protein and mRNA expression of WT1 and ZO-1 while suppressing the expression of Col1a1 in db/db mice, indicating its ability to alleviate podocyte EMT. Mechanistically, KXC exerted a significant suppressive effect on the activation of β-catenin signaling in diabetic kidneys.

Conclusion

KXC has the potential to protect podocytes during DKD by alleviating podocyte EMT through inactivating β-catenin signaling.
Shifts in the diversity of root endophytic microorganisms across the life cycle of the ratooning rice Jiafuzhan
Authors: Dong Meng , Shi Longqing , Xie Zhenxing , Lian Ling , Zhang Junian , Jiang Zhaowei , Wu Chunzhu
Published: June 2023

The diversity of root endophytic microorganisms, which is closely related to plant life activities, is known to vary with the plant growth stage. This study on the ratooning rice Jiafuzhan explored the diversity of the root endophytic bacteria and fungi and their dynamics during the plant life cycle. By sequencing the 16S ribosomal ribonucleic acid (16S rRNA) and internal transcribed spacer (ITS) genes, 12,154 operational taxonomic units (OTUs) and 497 amplicon sequence variants (ASVs) were obtained, respectively. The root endophytic microorganisms of rice in the seedling, tillering, jointing, heading, and mature stages of the first crop and at 13, 25, and 60 days after regeneration (at the heading, full heading, and mature stages of the second crop, respectively) were analyzed using diversity and correlation analyses. There were significant differences in the α-diversity and β-diversity of root endophytic bacteria and fungi in the growth stage. Additionally, linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed biomarker bacteria for each growth stage, but biomarker fungi did not exist in every stage. Moreover, the correlation analysis showed that the bacterial and fungal biomarkers interacted with each other. Furthermore, the nitrogen-fixing genus Bradyrhizobium existed in all growth stages. These findings indicate the pattern of root endophytic microorganisms of ratooning rice at different growth stages, and they provide new insights into the high yield of the second crop of ratooning rice (in light of the abundance of various bacteria and fungi).
Whole genome sequence analysis of Aeromonas spp. isolated from ready-to-eat seafood: antimicrobial resistance and virulence factors
Authors: Lee Hye-Jeong , Storesund Julia E. , Lunestad Bjørn-Tore , Hoel Sunniva , Lerfall Jørgen , Jakobsen Anita Nordeng
Published: June 2023

Aeromonas are widespread in aquatic environments and are considered emerging pathogens in humans and animals. Multidrug resistant (MDR) Aeromonas circulating in the aquatic environment and food production chain can potentially disseminate antimicrobial resistance (AMR) to humans via the foodborne route. In this study, we aimed to investigate AMR and virulence factors of 22 Aeromonas strains isolated from ready-to-eat (RTE) seafood. A multilocus phylogenetic analysis (MLPA) using the concatenated sequences of six housekeeping genes (gyrB, rpoD, gyrA, recA, dnaJ, and dnaX) in the 22 Aeromonas genomes and average nucleotide identity (ANI) analysis revealed eight different species; A. caviae, A. dhakensis, A. hydrophila, A. media, A. rivipollensis, A. salmonicida, A. bestiarum, and A. piscicola. The presence of virulence genes, AMR genes and mobile genetic elements (MGEs) in the Aeromonas genomes was predicted using different databases. Our data showed that the genes responsible for adherence and motility (Msh type IV pili, tap type IV pili, polar flagella), type II secretion system (T2SS) and hemolysins were present in all strains, while the genes encoding enterotoxins and type VI secretion system (T6SS) including major effectors were highly prevalent. Multiple AMR genes encoding β-lactamases such as cphA and blaOXA were detected, and the distribution of those genes was species-specific. In addition, the quinolone resistance gene, qnrS2 was found in a IncQ type plasmid of the A. rivopollensis strain A539. Furthermore, we observed the co-localization of a class I integron (intl1) with two AMR genes (sul1 and aadA1), and a Tn521 transposon carrying a mercury operon in A. caviae strain SU4-2. Various MGEs including other transposons and insertion sequence (IS) elements were identified without strongly associating with detected AMR genes or virulence genes. In conclusion, Aeromonas strains in RTE seafood were potentially pathogenic, carrying several virulence-related genes. Aeromonas carrying multiple AMR genes and MGEs could potentially be involved in the dissemination and spread of AMR genes to other bacterial species residing in the same environment and possibly to humans. Considering a One-Health approach, we highlight the significance of monitoring AMR caused by Aeromonas circulating in the food chain.
Genomic evidence for the first symbiotic Deferribacterota, a novel gut symbiont from the deep-sea hydrothermal vent shrimp Rimicaris kairei
Authors: Qi Li , Shi Mengke , Zhu Fang-Chao , Lian Chun-Ang , He Li-Sheng
Published: June 2023

The genus Rimicaris is the dominant organism living in hydrothermal vents. However, little research has been done on the functions of their intestinal flora. Here, we investigated the potential functions of Deferribacterota, which is dominant in the intestine of Rimicaris kairei from the Central Indian Ridge. In total, six metagenome-assembled genomes (MAGs) of Deferribacterota were obtained using the metagenomic approach. The six Deferribacterota MAGs (Def-MAGs) were clustered into a new branch in the phylogenetic tree. The six Def-MAGs were further classified into three species, including one new order and two new genera, based on the results of phylogenetic analysis, relative evolutionary divergence (RED), average nucleotide identity (ANI), average amino acid identity (AAI) and DNA–DNA hybridization (DDH) values. The results of the energy metabolism study showed that these bacteria can use a variety of carbon sources, such as glycogen, sucrose, salicin, arbutin, glucose, cellobiose, and maltose. These bacteria have a type II secretion system and effector proteins that can transport some intracellular toxins to the extracellular compartment and a type V CRISPR–Cas system that can defend against various invasions. In addition, cofactors such as biotin, riboflavin, flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD) synthesized by R. kairei gut Deferribacterota may also assist their host in surviving under extreme conditions. Taken together, the potential function of Deferribacterota in the hydrothermal R. kairei gut suggests its long-term coevolution with the host.
Hypocretins, sleep, and maternal behavior
Authors: Rivas Mayda , Ferreira Annabel , Torterolo Pablo , Benedetto Luciana
Published: June 2023

The postpartum period is a demanding time during which mothers experience numerous physiological adaptations that enable them to care for their offspring while maintaining their wellbeing. Hypocretins, also known as orexins, are neuropeptides synthesized by hypothalamic neurons that play a fundamental role in several functions, including the promotion of wakefulness and motivated behaviors, such as maternal care. In this regard, several findings suggest that the activity of the hypocretinergic system increases in the early postpartum period and begins to decline as weaning approaches. In particular, hypocretins within the medial preoptic area, a crucial region during this period, modulate both maternal behavior and sleep. Although further studies are necessary to obtain a comprehensive understanding of the role of hypocretins in lactating females, current research suggests that this system participates in promoting active components of maternal behavior and regulating wakefulness and sleep adjustments during the postpartum period, potentially leading to increased wakefulness during this stage. These adaptive adjustments enable the mother to cope with the continuously changing demands of the pups.
Targeted multidomain intervention for complex mTBI: protocol for a multisite randomized controlled trial in military-age civilians
Authors: Elbin R. J. , Trbovich Alicia , Womble Melissa N. , Mucha Anne , Fedor Sheri , Stephenson Katie , Holland Cyndi , Dollar Christina , Sparto Patrick , Durfee Kori , Patterson Charity G. , Smith Clair N. , Huppert Theodore J. , Okonkwo David O. , Collins Michael W. , Kontos Anthony P.
Published: June 2023

Background

Mild traumatic brain injury (mTBI) affects ~18,000 military personnel each year, and although most will recover in 3–4 weeks, many experience persisting symptoms and impairment lasting months or longer. Current standard of care for U.S. military personnel with complex mTBI involves initial (<48 h) prescribed rest, followed by behavioral (e.g., physical activity, sleep regulation, stress reduction, hydration, nutrition), and symptom-guided management. There is growing agreement that mTBI involves different clinical profiles or subtypes that require a comprehensive multidomain evaluation and adjudication process, as well as a targeted approach to treatment. However, there is a lack of research examining the effectiveness of this approach to assessing and treating mTBI. This multisite randomized controlled trial (RCT) will determine the effectiveness of a targeted multidomain (T-MD) intervention (anxiety/mood, cognitive, migraine, ocular, vestibular; and sleep, autonomic) compared to usual care (behavioral management) in military-aged civilians with complex mTBI.

Methods

This study employs a single-blinded, two-group repeated measures design. The RCT will enroll up to 250 military-aged civilians (18-49 yrs) with a diagnosed complex mTBI within 8 days to 6 months of injury from two concussion specialty clinics. The two study arms are a T-MD intervention and a usual care, behavioral management control group. All participants will complete a comprehensive, multidomain clinical evaluation at their first clinical visit. Information gathered from this evaluation will be used to adjudicate mTBI clinical profiles. Participants will then be randomized to either the 4-week T-MD or control arm. The T-MD group will receive targeted interventions that correspond to the patient’s clinical profile (s) and the control group will receive behavioral management strategies. Primary outcomes for this study are changes from enrollment to post-intervention on the Neurobehavioral Symptom Inventory (NSI), Patient Global Impression of Change (PGIC), and functional near-infrared spectroscopy (fNIRS). Time to return to activity (RTA), and healthcare utilization costs will also be assessed.

Discussion

Study findings may inform a more effective approach to treat complex mTBI in military personnel and civilians, reduce morbidity, and accelerate safe return-to-duty/activity.

Ethics and dissemination

The study is approved by the University of Pittsburgh Institutional Review board and registered at clinicaltrials.gov. Dissemination plans include peer-reviewed publications and presentations at professional meetings.

Clinical Trial Registration:

www.clinicaltrials.gov, identifier: NCT04549532.
Automatic risk prediction of intracranial aneurysm on CTA image with convolutional neural networks and radiomics analysis
Authors: Xie Yuan , Liu Shuyu , Lin Hen , Wu Min , Shi Feng , Pan Feng , Zhang Lichi , Song Bin
Published: June 2023

Background

Intracranial aneurysm (IA) is a nodular protrusion of the arterial wall caused by the localized abnormal enlargement of the lumen of a brain artery, which is the primary cause of subarachnoid hemorrhage. Accurate rupture risk prediction can effectively aid treatment planning, but conventional rupture risk estimation based on clinical information is subjective and time-consuming.

Methods

We propose a novel classification method based on the CTA images for differentiating aneurysms that are prone to rupture. The main contribution of this study is that the learning-based method proposed in this study leverages deep learning and radiomics features and integrates clinical information for a more accurate prediction of the risk of rupture. Specifically, we first extracted the provided aneurysm regions from the CTA images as 3D patches with the lesions located at their centers. Then, we employed an encoder using a 3D convolutional neural network (CNN) to extract complex latent features automatically. These features were then combined with radiomics features and clinical information. We further applied the LASSO regression method to find optimal features that are highly relevant to the rupture risk information, which is fed into a support vector machine (SVM) for final rupture risk prediction.

Results

The experimental results demonstrate that our classification method can achieve accuracy and AUC scores of 89.78% and 89.09%, respectively, outperforming all the alternative methods.

Discussion

Our study indicates that the incorporation of CNN and radiomics analysis can improve the prediction performance, and the selected optimal feature set can provide essential biomarkers for the determination of rupture risk, which is also of great clinical importance for individualized treatment planning and patient care of IA.
Legal medicine implications of a multidisciplinary approach to managing Traumatic Encephalopathy Syndrome in Australia
Authors: Kim Peter S. , Beran Roy G.
Published: June 2023

The medical profession has a fundamental obligation to accurately diagnose and effectively treat a range of diseases and conditions. In the case of Traumatic Encephalopathy Syndrome (TES), where there are no universally accepted clinical diagnostic criteria, a clear clinical diagnosis can pose significant challenges for healthcare providers and for subsequent appropriate management. “Nihilism” or an uncertain working diagnosis is not acceptable in the medical field and deserves further consideration. This paper explores the legal obligations that are placed upon healthcare professionals, both individually and as a part of a multidisciplinary team. This article analyses the responsibilities and expectations of medical professionals in diagnosing and treating complex medical conditions, such as TES. The authors address legal issues that must be considered for an effective operation of integrated medicine to enhance the overall quality of care and improving patient outcomes for those affected with underlying Chronic Traumatic Encephalopathy (CTE).
Role of endothelial cells and angiotensin converting enzyme-II in COVID-19 and brain damages post-infection
Authors: Mehboob Riffat , von Kries Jens Peter , Ehsan Kashifa , Almansouri Majid , Bamaga Ahmed K.
Published: June 2023

Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) causes coronavirus disease 2019 (COVID-19), which became a pandemic in late 2019 and early 2020. Apart from many other symptoms of this infection, such as loss of smell and taste, rashes, body aches, fatigue, and psychological and cardiac symptoms, it also causes vasodilation in response to inflammation via nitric oxide release. SARS CoV-2 affects microcirculation, resulting in the swelling and damage of endothelial cells, micro thrombosis, constriction of capillaries, and damage to pericytes that are vital for the integrity of capillaries, angiogenesis, and the healing process. Cytokine storming has been associated with COVID-19 illness. Capillary damage and congestion may cause limited diffusion exchange of oxygen in the lungs and hence hypoxemia and tissue hypoxia occur. This perspective study will explore the involvement of capillary damage and inflammation by their interference with blood and tissue oxygenation as well as brain function in the persistent symptoms and severity of COVID-19. The overall effects of capillary damage due to COVID-19, microvascular damage, and hypoxia in vital organs are also discussed in this perspective. Once initiated, this vicious cycle causes inflammation due to hypoxia, resulting in limited capillary function, which in turn causes inflammation and tissue damage. Low oxygen levels and high cytokines in brain tissue may lead to brain damage. The after-effects may be in the form of psychological symptoms such as mood changes, anxiety, depression, and many others that need to be investigated.
Trends in deaths and disability-adjusted life-years of stroke attributable to high body-mass index worldwide, 1990–2019
Authors: Guo Xiucai , Li Junxiao , Yin Xueyan , Zhang Ziping , Zhong Qiongqiong , Zhu Feng
Published: June 2023

Background

High body mass index (HBMI) is an independent risk factor for stroke. Previous studies on the incremental burden of the rapid growth of stroke attributable to HBMI are incomplete and lag behind. We aim to assess the global burden of stroke attributable to HBMI based on a public database online.

Materials and methods

Study data were taken from the Global Burden of Disease, Injuries, and Risk Factors Study; deaths, the Disability-Adjusted Life-Years (DALYs), and their age-standardized rates were screened. The join point regression was used, wherein age-standardized rates were referred to as temporal trends in disease burden.

Results

Deaths from stroke attributable to HBMI worldwide were on the rise during 1990–2019, with an increase of 88.75%. Age-standardized DALYs were on the rise during 1990–2003 but declined during 2003–2013, with a turning point in 2013 and an increasing trend since then [the Annual Percentage Change (APC) = 0.30%, p < 0.05]. China, India, Indonesia, the Russian Federation, and the United States of America shared in sequence the rate of leading deaths and DALYs in 2019. The Socio-Demographic Index (SDI) was associated with an increasing trend in age-standardized deaths (R = −0.24, p < 0.001) and age-standardized DALYs (R = −0.22, p = 0.0018).

Conclusion

A range of indicators for the global burden of stroke attributable to HBMI have been on the rise for the past three decades. Tremendous efforts worldwide should be in place to control and treat stroke attributable to HBMI, especially in regions with high-middle and middle SDIs and among middle-aged and aged populations.
Case report: Psychedelic-induced seizures captured by intracranial electrocorticography
Authors: Blond Benjamin N. , Schindler Emmanuelle A. D.
Published: June 2023

Classic psychedelics are currently re-emerging as therapeutic agents with unique clinical benefits; however, it is also important to recognize the adverse effects of this drug class. While the risk of seizures with this drug class is known, the literature is lacking in detail. We present a case of psychedelic mushroom-induced seizures in a person with refractory right temporal lobe epilepsy implanted with a responsive neurostimulation (RNS) system. A large increase in typical seizure frequency coincided with the ingestion of a large dose of the mushrooms. This is the first reported case of electrographically confirmed seizures associated with classic psychedelic drug use. With the surge of research and movements toward the clinical application of classic psychedelic compounds, the risk for drug-induced seizures should be considered, including factors such as a history of epilepsy and drug doses and regimens.