bluuebunny/crossref_metadata_2025 huggingface dataset:
The generation mechanism of cold eddies and the related heat flux exchanges in the upper ocean during two sequential tropical cyclones
Authors: Shen Zheyue , Zhang Shuwen
Published: November 2022

The impacts of two sequential tropical cyclones (TCs), Kyarr and Maha, [from October 24 to November 06, 2019, over the Arabian Sea (AS)] on upper ocean environments were investigated using multiple satellite observations, Argo float profiles and numerical model outputs. To obtain a realistic TC strength, the Weather Research and Forecasting (WRF) model was used to reproduce Kyarr and Maha. During Kyarr and Maha, three distinct cold patches were observed at the sea surface with a maximum sea surface cooling of approximately 5°C. The comparison between WRF model simulation results and ERA5 wind field showed that the WRF model simulation indicated high simulation accuracy with respect to the SST decrease in the AS under the influence of Kyarr and Maha’s wind stress curls. Meanwhile, concentration of chlorophyll a (chl-a) and positive relative vorticity of sea surface also appeared in the three cold patch areas. Through the use of eddy detection algorithms, three mesoscale cold cyclonic eddies were identified along the track of TC Kyarr, and the locations of these cold eddies were highly correlated with three obvious negative sea surface height anomalies (SSHAs). The radii of the three cold eddies were 69 km, 50 km, and 41 km. With a focus on the thermodynamic responses of the three cold eddy fields to Kyarr and Maha, the central regions of the three cold eddies were explored. The central regions of the three cold eddies exhibited relatively shallow mixed-layer depths (MLDs) and low mixed-layer temperatures (MLTs). The depth integrated heat (DIH) content was also calculated to explore the heat flux exchanges occurring in different layers in the upper 200 m of the centre of each eddy. The results showed that DIH in each eddy centre varied by one order of magnitude, accounting for between 127.3 MJ m-2 and 1220.0 MJ m-2 of heat loss. This study suggests that the effect of long forcing time on intense positive wind stress curls can produce upwelling caused by Ekman response, which is the main influencing factor of the three cold eddies generation mechanism. At the same time, the positive relative vorticity injected into the sea surface also has some contribution. TC-induced vertical mixing and upwelling (strengthened by unstable structures inside the cold eddies) cause substantial redistribution of the DIH, and related heat flux exchanges at different layers occur in the eddy fields.
Predisposing and precipitating risk factors for delirium in gastroenterology and hepatology: Subgroup analysis of 718 patients from a hospital-wide prospective cohort study
Authors: Hildenbrand Florian F. , Murray Fritz R. , von Känel Roland , Deibel Ansgar R. , Schreiner Philipp , Ernst Jutta , Zipser Carl M. , Böettger Soenke
Published: November 2022

Background and Aims

Delirium is the most common acute neuropsychiatric syndrome in hospitalized patients. Higher age and cognitive impairment are known predisposing risk factors in general hospital populations. However, the interrelation with precipitating gastrointestinal (GI) and hepato-pancreato-biliary (HPB) diseases remains to be determined.

Patients and methods

Prospective 1-year hospital-wide cohort study in 29’278 adults, subgroup analysis in 718 patients hospitalized with GI/HPB disease. Delirium based on routine admission screening and a DSM-5 based construct. Regression analyses used to evaluate clinical characteristics of delirious patients.

Results

Delirium was detected in 24.8% (178/718). Age in delirious patients (median 62 years [IQR 21]) was not different to non-delirious (median 60 years [IQR 22]), p = 0.45). Dementia was the strongest predisposing factor for delirium (OR 66.16 [6.31–693.83], p < 0.001). Functional impairment, and at most, immobility increased odds for delirium (OR 7.78 [3.84–15.77], p < 0.001). Patients with delirium had higher in-hospital mortality rates (18%; OR 39.23 [11.85–129.93], p < 0.001). From GI and HPB conditions, cirrhosis predisposed to delirium (OR 2.11 [1.11–4.03], p = 0.023), while acute renal failure (OR 4.45 [1.61–12.26], p = 0.004) and liver disease (OR 2.22 [1.12–4.42], p = 0.023) were precipitators. Total costs were higher in patients with delirium (USD 30003 vs. 10977; p < 0.001).

Conclusion

Delirium in GI- and HPB-disease was not associated with higher age per se, but with cognitive and functional impairment. Delirium needs to be considered in younger adults with acute renal failure and/or liver disease. Clinicians should be aware about individual risk profiles, apply preventive and supportive strategies early, which may improve outcomes and lower costs.
Case report: A rare case of death due to end-stage renal disease caused by Tripterygium wilfordii-induced myelosuppression
Authors: Zhang Wen , Liu Xinyin , Xia Cong , He Lingzhi , Ma Hongzhen , Wang Xiaoran , Zhang Peipei
Published: November 2022

Tripterygium wilfordii—a traditional Chinese herbal medicine—is used to treat several diseases, including chronic kidney disease, rheumatic autoimmune disorder, and skin disorders. With the development of modern pharmacology, scientists have gradually realized that T. wilfordii has side effects on several organs and systems of the human body, including the liver, kidney, reproductive system, hematopoietic system, and immune system. Our understanding of its toxicity remains unclear. The incidence of problems in the hematopoietic system is not low but few related studies have been conducted. The serious consequences need to be of concern to clinicians and scientists. To ensure the safety of patients, it is important to elucidate the mechanism underlying the damage to the hematopoietic system caused by T. wilfordii and strategies to reduce its toxicity. Routine blood and biochemical tests should be conducted when administering T. wilfordii, and in case of any abnormality, the medication should be terminated in time along with a comprehensive symptomatic treatment. Herein, we report the case of a 50-year-old Chinese female with end-stage renal disease (ESRD) who developed severe bone marrow suppression after taking a short-term normal dose of a T. wilfordii-containing decoction. She died of sepsis and septic shock, although timely therapeutic measures (e.g., stimulating hematopoiesis, anti-infection treatment, and hemodialysis) were administered. To the best of our knowledge, this is the first report of death by T. wilfordii-induced myelosuppression from a short term, conventional dose in an adult female with ESRD. Although the underlying mechanism remains unclear, this case contradicts the notion that side effects on the hematopoietic system are non-lethal.
Interleukin-34-regulated T-cell responses in rheumatoid arthritis
Authors: Park Hye Eun , Oh Hanna , Baek Jea-Hyun
Published: November 2022

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a multifaceted etiology, which primarily affects and results in the deterioration of the synovium of patients. While the exact etiology of RA is still largely unknown, there is growing interest in the cytokine interleukin-34 (IL-34) as a driver or modulator of RA pathogenesis on the grounds that IL-34 is drastically increased in the serum and synovium of RA patients. Several studies have so far revealed the relationship between IL-34 levels and RA disease progression. Nevertheless, the significance and role of IL-34 in RA have remained ambiguous, as illustrated by two most recent studies, which reported contrasting effects of genetic IL-34 deletion in RA. Of note, IL-34 is a macrophage growth factor and is increasingly perceived as a master regulator of T-cell responses in RA via macrophage-dependent as well as T cell-intrinsic mechanisms. In this regard, several studies have demonstrated that IL-34 potentiates helper T-cell (Th) responses in RA, whereas studies also suggested that IL-34 alleviates synovial inflammation, potentially by inducing regulatory T-cells (Treg). Herein, we provide an overview of the current understanding of IL-34 involvement in RA and outline IL-34-mediated mechanisms in regulating T-cell responses in RA.
A metabotropic glutamate receptor affects the growth and development of Schistosoma japonicum
Authors: Wang Xiaoling , Cheng Shaoyun , Chen Xiangyu , Zhang Wei , Xie Yuxiang , Liu Wanling , You Yanmin , Yi Cun , Zhu Bingkuan , Gu Mengjie , Xu Bin , Lu Yan , Wang Jipeng , Hu Wei
Published: November 2022

Schistosomiasis is a zoonotic parasitic disease caused by schistosome infection that severely threatens human health. Therapy relies mainly on single drug treatment with praziquantel. Therefore, there is an urgent need to develop alternative medicines. The glutamate neurotransmitter in helminths is involved in many physiological functions by interacting with various cell-surface receptors. However, the roles and detailed regulatory mechanisms of the metabotropic glutamate receptor (mGluR) in the growth and development of Schistosoma japonicum remain poorly understood. In this study, we identified two putative mGluRs in S. japonicum and named them SjGRM7 (Sjc_001309, similar to GRM7) and SjGRM (Sjc_001163, similar to mGluR). Further validation using a calcium mobilization assay showed that SjGRM7 and SjGRM are glutamate-specific. The results of in situ hybridization showed that SjGRM is mainly located in the nerves of both males and gonads of females, and SjGRM7 is principally found in the nerves and gonads of males and females. In a RNA interference experiment, the results showed that SjGRM7 knockdown by double-stranded RNA (dsRNA) in S. japonicum caused edema, chassis detachment, and separation of paired worms in vitro. Furthermore, dsRNA interference of SjGRM7 could significantly affect the development and egg production of male and female worms in vivo and alleviate the host liver granulomas and fibrosis. Finally, we examined the molecular mechanisms underlying the regulatory function of mGluR using RNA sequencing. The data suggest that SjGRM7 propagates its signals through the G protein-coupled receptor signaling pathway to promote nervous system development in S. japonicum. In conclusion, SjGRM7 is a potential target for anti-schistosomiasis. This study enables future research on the mechanisms of action of Schistosomiasis japonica drugs.
Rouxiella badensis, a new bacterial pathogen of onion causing bulb rot
Authors: Zhao Mei , Tyson Chris , Gitaitis Ron , Kvitko Brian , Dutta Bhabesh
Published: November 2022

Onion bulb rot can be caused by multiple plant pathogens including bacterial pathogens. During our routine survey of commercial onion farms in 2014, 2020, and 2021, seven putative Rouxiella spp. strains were isolated from symptomatic onion samples in Georgia, United States. Upon fulfilling Koch’s postulates on onion, a genome analysis was conducted. Whole-genome indices (ANI and dDDH) showed that the strains belonged to Rouxiella badensis. Although the seven R. badensis strains were not pathogenic on onion foliage, the strains were able to cause bulb rot and could also produce necrotic lesions in a red onion scale assay. R. badensis populations increased significantly and to a level comparable to P. ananatis PNA 97-1R in a red onion scale infection assay. The core-genome analysis grouped all onion R. badensis strains from Georgia together, and distinct from R. badensis strains isolated from other sources and locations. Based on the genome analysis of strains (from the current study and available genomes in the repository), type I, III (Ssa-Esc and Inv-Mxi-Spa types), and V secretion systems are present in R. badensis genomes, while type II, IV, and VI secretion systems are absent. However, various secondary metabolite gene clusters were identified from R. badensis genomes, and a thiol/redox-associated enzyme gene cluster similar to the Pantoea alt cluster mediating thiosulfinate tolerance was also present in onion strains of R. badensis. This is the first report of R. badensis as a plant pathogen.
Scrophulariae Radix-Atractylodes sinensis pair and metformin inhibit inflammation by modulating gut microbiota of high-fat diet/streptozotocin-induced diabetes in rats
Authors: Guo Xiaoxia , Wang Chong , Zhang Ranran , Hao Xuliang , Lv Lei , Ni Yan , Fan Xiaohong , Zhang Weiliang , Jiao Yunhong , Song Wei , Dong Qi , Qi Yuqi , Song Meiqing , Qin Xuemei
Published: November 2022

Introduction

Type 2 mellitus (T2DM), a chronic metabolic disorder, causes severe impairment of patients’ quality of life and has attracted global attention. Many studies have suggested the importance of the gut microbiota in the occurrence of T2DM. The Scrophulariae Radix and Atractylodes sinensis (XC) pair, recommended in traditional Chinese medicine (TCM), have been used for treating diabetes for many years. However, research on the role of the XC pair in modulating gut microbial communities is lacking, but it is important to elucidate the underlying mechanism.

Methods

In this study, we detected bacterial communities by high-throughput 16S rRNA gene sequencing.

Results

The results showed that XC + MET reduced postprandial hyperglycemia and inflammatory response in diabetic rats more effectively than metformin (MET) alone. The XC + MET treatment reshaped the intestinal microbial composition of diabetic rats. XC can help MET regulate carbohydrate, amino acid, and lipid metabolism, particularly the insulin signaling pathway.

Discussion

This research would help elucidate potential mechanisms and the treatment methods.
TMPRSS2 gene polymorphism common in East Asians confers decreased COVID-19 susceptibility
Authors: Sekiya Takeshi , Ogura Yukino , Kai Hirayasu , Kawaguchi Atsushi , Okawa Shino , Hirohama Mikako , Kuroki Takahiro , Morii Wataru , Hara Akira , Hiramatsu Yuji , Hitomi Shigemi , Kawakami Yasushi , Arakawa Yoshihiro , Maruo Kazushi , Chiba Shigeru , Suzuki Hiromichi , Kojima Hiroshi , Tachikawa Hirokazu , Yamagata Kunihiro
Published: November 2022

COVID-19 has a wide range of clinical presentations, and the susceptibility to SARS-CoV-2 infection and the mortality rate also vary by region and ethnicity. Here, we found that rs12329760 in the TMPRSS2 gene, a missense variant common in East Asian populations, contributes to protection against SARS-CoV-2 infection. TMPRSS2 is a protease responsible for SARS-CoV-2 entry and syncytium formation. rs12329760 (c.478G>A, p. V160M) was associated with a reduced risk of moderate symptoms. The enzymatic activity of Met160-TMPRSS2 was lower than that of Val160-TMPRSS2, and thus the viral entry and the syncytium formation of SARS-CoV-2 were impaired. Collectively, these results indicate that the genetic variation in TMPRSS2, which is common in East Asians, is one of the molecular determinants of COVID-19 susceptibility.
Genomics assisted functional characterization of Bacillus velezensis E as a biocontrol and growth promoting bacterium for lily
Authors: Li Bingyu , Wan Junyi , Sha Jingjing , Tian Mengyuan , Wang Mengchen , Zhang Xinyuan , Sun Wei , Mao Yanrong , Min Jie , Qin Yiyuan , Liu Yuqing , Wang Wenhe , He Xiangfeng
Published: November 2022

Lily (Lilium spp.) is one of the most famous ornamental flowers globally. Lily basal rot (also known as root rot or stem rot) and lily gray mold have seriously affected the yield and quality of lily, resulting in huge economic losses. In this study, bacterial strain E was isolated from a continuous lily cropping field. Strain E displayed high control efficiency against lily basal rot and gray mold, caused by Fusarium oxysporum and Botrytis cinerea respectively, and promoted the occurrence of scale bulblets. Strain E displayed strong inhibitory effects against several other plant pathogenic fungi and two pathogenic bacteria in dual culture and disc diffusion assays, respectively. Whole genome sequencing revealed that strain E contained a 3,929,247 bp circular chromosome with 4,056 protein-coding genes and an average GC content of 47.32%. Strain E was classified as Bacillus velezensis using genome-based phylogenetic analysis and average nucleotide identity and digital DNA–DNA hybridization analyses. A total of 86 genes and 13 secondary metabolite biosynthetic gene clusters involved in antifungal and antibacterial activity, plant growth promotion, colonization, nutrient uptake and availability were identified in the genome of strain E. In vitro biochemical assays showed that strain E produced siderophores, proteases, cellulases, biofilms, antifungal and antibacterial substances, and exhibited organic phosphate solubilization and swimming and swarming motility, which were consistent with the results of the genome analysis. Colonization analysis showed that strain E could colonize the root of the lily, but not the leaf. Overall, these results demonstrate that B. velezensis strain E can be used as a potential biofertilizer and biocontrol agent for lily production.
Systematic evaluation of urinary formic acid as a new potential biomarker for Alzheimer’s disease
Authors: Wang Yifan , Wang Ying , Zhu Jinhang , Guan Yihui , Xie Fang , Cai Xiao , Deng Jiale , Wei Yan , He Rongqiao , Fang Zhuo , Guo Qihao
Published: November 2022

Introduction

The accumulation of endogenous formaldehyde is considered a pathogenic factor in Alzheimer’s disease (AD). The purpose of this study was to investigate the relationship between urinary formic acid and plasma biomarkers in AD.

Materials and methods

Five hundred and seventy-four participants were divided into five groups according to their diagnosis: 71 with normal cognitive (NC), 101 with subjective cognitive decline (SCD), 131 with cognitive impairment without mild cognitive impairment (CINM), 158 with mild cognitive impairment (MCI), and 113 with AD.

Results

With the progression of the disease, urinary formic acid levels showed an overall upward trend. Urinary formic acid was significantly correlated with Mini-Mental State Examination (MMSE) scores, the Chinese version of Addenbrooke’s Cognitive Examination III (ACE-III) scores, and Montreal Cognitive Assessment-Basic (MoCA-B) time. The areas under the receiver operating characteristic curves (AUC) of urinary formic acid in distinguishing NC from AD was 0.797, which was similar to that of plasma neurofilament light chain (NfL; AUC = 0.768) and better than other plasma biomarkers (Aβ40, Aβ42, Aβ42/Aβ40, T-tau, P-tau181, and P-tau181/T-tau). We also found that using urinary formic acid and formaldehyde levels could improve the accuracy of using plasma biomarkers to determine AD disease stage.

Discussion

Our study revealed the possibility of urinary formic acid as a potential novel biomarker for the early diagnosis of AD.
Neurobiology and changing ecosystems: Toward understanding the impact of anthropogenic influences on neurons and circuits
Authors: Michaiel Angie M. , Bernard Amy
Published: November 2022

Rapid anthropogenic environmental changes, including those due to habitat contamination, degradation, and climate change, have far-reaching effects on biological systems that may outpace animals’ adaptive responses. Neurobiological systems mediate interactions between animals and their environments and evolved over millions of years to detect and respond to change. To gain an understanding of the adaptive capacity of nervous systems given an unprecedented pace of environmental change, mechanisms of physiology and behavior at the cellular and biophysical level must be examined. While behavioral changes resulting from anthropogenic activity are becoming increasingly described, identification and examination of the cellular, molecular, and circuit-level processes underlying those changes are profoundly underexplored. Hence, the field of neuroscience lacks predictive frameworks to describe which neurobiological systems may be resilient or vulnerable to rapidly changing ecosystems, or what modes of adaptation are represented in our natural world. In this review, we highlight examples of animal behavior modification and corresponding nervous system adaptation in response to rapid environmental change. The underlying cellular, molecular, and circuit-level component processes underlying these behaviors are not known and emphasize the unmet need for rigorous scientific enquiry into the neurobiology of changing ecosystems.
Quasicriticality explains variability of human neural dynamics across life span
Authors: Fosque Leandro J. , Alipour Abolfazl , Zare Marzieh , Williams-García Rashid V. , Beggs John M. , Ortiz Gerardo
Published: November 2022

Aging impacts the brain's structural and functional organization and over time leads to various disorders, such as Alzheimer's disease and cognitive impairment. The process also impacts sensory function, bringing about a general slowing in various perceptual and cognitive functions. Here, we analyze the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) resting-state magnetoencephalography (MEG) dataset—the largest aging cohort available—in light of the quasicriticality framework, a novel organizing principle for brain functionality which relates information processing and scaling properties of brain activity to brain connectivity and stimulus. Examination of the data using this framework reveals interesting correlations with age and gender of test subjects. Using simulated data as verification, our results suggest a link between changes to brain connectivity due to aging and increased dynamical fluctuations of neuronal firing rates. Our findings suggest a platform to develop biomarkers of neurological health.
Longitudinal changes in functional connectivity in speech motor networks in apraxia of speech after stroke
Authors: Hybbinette Helena , Östberg Per , Schalling Ellika , Deboussard Catharina , Plantin Jeanette , Borg Jörgen , Lindberg Påvel G.
Published: November 2022

Objective

The cerebral substrates of apraxia of speech (AOS) recovery remain unclear. Resting state fMRI post stroke can inform on altered functional connectivity (FC) within cortical language networks. Some initial studies report reduced FC between bilateral premotor cortices in patients with AOS, with lowest FC in patients with the most severe AOS. However, longitudinal FC studies in stroke are lacking. The aims of the present longitudinal study in early post stroke patients with AOS were (i) to compare connectivity strength in AOS patients to that in left hemisphere (LH) lesioned stroke patients without a speech-language impairment, (ii) to investigate the relation between FC and severity of AOS, aphasia and non-verbal oral apraxia (NVOA) and (iii) to investigate longitudinal changes in FC, from the subacute phase to the chronic phase to identify predictors of AOS recovery.

Methods

Functional connectivity measures and comprehensive speech-language assessments were obtained at 4 weeks and 6 months after stroke in nine patients with AOS after a LH stroke and in six LH lesioned stroke patients without speech-language impairment. Functional connectivity was investigated in a network for speech production: inferior frontal gyrus (IFG), anterior insula (aINS), and ventral premotor cortex (vPMC), all bilaterally to investigate signs of adaptive or maladaptive changes in both hemispheres.

Results

Interhemispheric vPMC connectivity was significantly reduced in patients with AOS compared to LH lesioned patients without speech-language impairment. At 6 months, the AOS severity was associated with interhemispheric aINS and vPMC connectivity. Longitudinal changes in FC were found in individuals, whereas no significant longitudinal change in FC was found at the group level. Degree of longitudinal AOS recovery was strongly associated with interhemispheric IFG connectivity strength at 4 weeks.

Conclusion

Early interhemispheric IFG connectivity may be a strong predictor of AOS recovery. The results support the importance of interhemispheric vPMC connection in speech motor planning and severity of AOS and suggest that also bilateral aINS connectivity may have an impact on AOS severity. These findings need to be validated in larger cohorts.
Single-textured insole for the less affected leg in freezing of gait: A hypothesis
Authors: Etoom Mohammad , Altaim Thamer Ahmad , Alawneh Anoud , Aljuhini Yazan , Alanazi Fahad Salam , Gaowgzeh Riziq Allah Mustafa , Alanazi Abdullah Owaid , Neamatallah Ziyad , Alfawaz Saad , Abdullahi Auwal
Published: November 2022

Freezing of gait (FoG) is one of the most widely distributed and disabling gait phenomena in people with Parkinson's disease (PD). The current therapeutic interventions show suboptimal efficacy in FoG. Lower extremity proprioception impairments, especially in the most affected leg, gait initiation hesitation, and gait asymmetry are FoG factors, and there is a need to accurately consider them in terms of therapeutic approaches. Accordingly, we hypothesize that using a single-textured insole for the less affected leg may improve FoG by providing proprioceptive stimulation that enhances sensory processing and reduces gait hesitation and asymmetry. Proprioceptive sensory stimulation for the less affected limb could be more effective than for the double legs that are currently used in rehabilitation settings due to the sensory processing in the less affected basal ganglia being better.
Deafness and early language deprivation influence arithmetic performances
Authors: Buyle Margot , Crollen Virginie
Published: November 2022

It has been consistently reported that deaf individuals experience mathematical difficulties compared to their hearing peers. However, the idea that deafness and early language deprivation might differently affect verbal (i.e., multiplication) vs. visuospatial (i.e., subtraction) arithmetic performances is still under debate. In the present paper, three groups of 21 adults (i.e., deaf signers, hearing signers, and hearing controls) were therefore asked to perform, as fast and as accurately as possible, subtraction and multiplication operations. No significant group effect was found for accuracy performances. However, reaction time results demonstrated that the deaf group performed both arithmetic operations slower than the hearing groups. This group difference was even more pronounced for multiplication problems than for subtraction problems. Weaker language-based phonological representations for retrieving multiplication facts, and sensitivity to interference are two hypotheses discussed to explain the observed dissociation.
Overcoming the phenomenological Perpetuum mobile in clinical cognitive neuroscience for the benefit of replicability in research and the societal view on mental disorders
Authors: Beste Christian
Published: November 2022

Cognitive neuroscience comes in many facets, and a particularly large branch of research is conducted in individuals with mental health problems. This article outlines why it is important that cognitive neuroscientists re-shape their role in mental health research and re-define directions of research for the next decades. At present, cognitive neuroscience research in mental health is too firmly rooted in categorial diagnostic definitions of mental health conditions. It is discussed why this hampers a mechanistic understanding of brain functions underlying mental health problems and why this is a problem for replicability in research. A possible solution to these problems is presented. This solution affects the strategy of research questions to be asked, how current trends to increase replicability in research can or cannot be applied in the mental health field and how data are analyzed. Of note, these aspects are not only relevant for the scientific process, but affect the societal view on mental disorders and the position of affected individuals as members of society, as well as the debate on the inclusion of so-called WEIRD and non-WEIRD people in studies. Accordingly, societal and science political aspects of re-defining the role of cognitive neuroscientists in mental health research are elaborated that will be important to shape cognitive neuroscience in mental health for the next decades.
The impact of genetic risk for Alzheimer’s disease on the structural brain networks of young adults
Authors: Mirza-Davies Anastasia , Foley Sonya , Caseras Xavier , Baker Emily , Holmans Peter , Escott-Price Valentina , Jones Derek K. , Harrison Judith R. , Messaritaki Eirini
Published: November 2022

Introduction

We investigated the structural brain networks of 562 young adults in relation to polygenic risk for Alzheimer’s disease, using magnetic resonance imaging (MRI) and genotype data from the Avon Longitudinal Study of Parents and Children.

Methods

Diffusion MRI data were used to perform whole-brain tractography and generate structural brain networks for the whole-brain connectome, and for the default mode, limbic and visual subnetworks. The mean clustering coefficient, mean betweenness centrality, characteristic path length, global efficiency and mean nodal strength were calculated for these networks, for each participant. The connectivity of the rich-club, feeder and local connections was also calculated. Polygenic risk scores (PRS), estimating each participant’s genetic risk, were calculated at genome-wide level and for nine specific disease pathways. Correlations were calculated between the PRS and (a) the graph theoretical metrics of the structural networks and (b) the rich-club, feeder and local connectivity of the whole-brain networks.

Results

In the visual subnetwork, the mean nodal strength was negatively correlated with the genome-wide PRS (r = –0.19, p = 1.4 × 10–3), the mean betweenness centrality was positively correlated with the plasma lipoprotein particle assembly PRS (r = 0.16, p = 5.5 × 10–3), and the mean clustering coefficient was negatively correlated with the tau-protein binding PRS (r = –0.16, p = 0.016). In the default mode network, the mean nodal strength was negatively correlated with the genome-wide PRS (r = –0.14, p = 0.044). The rich-club and feeder connectivities were negatively correlated with the genome-wide PRS (r = –0.16, p = 0.035; r = –0.15, p = 0.036).

Discussion

We identified small reductions in brain connectivity in young adults at risk of developing Alzheimer’s disease in later life.
Case Report: Durable complete pathologic response and organ preservation following ipilimumab and nivolumab for locally advanced primary vaginal mucosal melanoma
Authors: Tarhini Ahmad A. , Hanayneh Wissam B. , Powers John J. , Segura Carlos M. Moran , Conejo-Garcia Jose R. , Lam Cesar A. , Hakam Ardeshir , Hoffman Mitchel S.
Published: November 2022

Optimal management of locally advanced vaginal mucosal melanoma is poorly understood because of its rarity and unique biology. Patients have a poor prognosis despite aggressive management approaches including pelvic exenteration and adjuvant radiation that carry major morbidities. We report a case of a patient in early 40’s who experienced complete pathologic response and organ preservation following immunotherapy consisting of 3 cycles of ipilimumab and nivolumab. Treatment was complicated by a high-grade immune mediated hepatitis that eventually resolved with immunosuppressive therapy. Immune monitoring studies utilizing vaginal tumor biopsies showed evidence of enhanced infiltration by CD3+/CD8+ cytotoxic T-cells and increased expression of MHC-I/PD-L1 within the tumor microenvironment following immunotherapy. The patient continues to be without evidence of disease recurrence by radiologic and gynecologic examinations with more than 2 years of follow up from the time of immunotherapy initiation. To our knowledge, this is the only case report in the literature of a patient with locally advanced vaginal mucosal melanoma experiencing a durable complete pathologic response and organ preservation following immune checkpoint blockade as the only treatment approach.
The prevention of disease relapse after allogeneic hematopoietic cell transplantation in acute myeloid leukemia
Authors: Maffini Enrico , Ursi Margherita , Barbato Francesco , Dicataldo Michele , Roberto Marcello , Campanini Elena , Dan Elisa , De Felice Francesco , De Matteis Serena , Storci Gianluca , Bonafè Massimiliano , Arpinati Mario , Bonifazi Francesca
Published: November 2022

Disease relapse represents by far the most frequent cause of hematopoietic cell transplantation (HCT) failure. Patients with acute leukemia suffering relapse after HCT have limited conventional treatment options with little possibility of cure and represent, de facto, suitable candidates for the evaluation of novel cellular and biological-based therapies. Donor lymphocyte infusions (DLI) has been one of the first cellular therapies adopted to treat post HCT relapse of acute leukemia patients and still now, it is widely adopted in preemptive and prophylactic settings, with renewed interest for manipulated cellular products such as NK-DLI. The acquisition of novel biological insights into pathobiology of leukemia relapse are translating into the clinic, with novel combinations of target therapies and novel agents, helping delineate new therapeutical landscapes. Hypomethylating agents alone or in combination with novel drugs demonstrated their efficacy in pre-clinical models and controlled trials. FLT3 inhibitors represent an essential therapeutical instrument incorporated in post-transplant maintenance strategies. The Holy grail of allogeneic transplantation lies in the separation of graft-vs.-host disease from graft vs. tumor effects and after more than five decades, is still the most ambitious goal to reach and many ways to accomplish are on their way.
Co-targeting triple-negative breast cancer cells and endothelial cells by metronomic chemotherapy inhibits cell regrowth and migration via downregulation of the FAK/VEGFR2/VEGF axis and autophagy/apoptosis activation
Authors: Scagliotti Arianna , Capizzi Laura , Cazzaniga Marina Elena , Ilari Alice , De Giorgi Marco , Cordani Nicoletta , Gallazzi Matteo , Bruno Antonino , Pelosi Giuseppe , Albini Adriana , Lavitrano Marialuisa , Grassilli Emanuela , Cerrito Maria Grazia
Published: November 2022

High-dose standard-of-care chemotherapy is the only option for triple-negative breast cancer (TNBC) patients, which eventually die due to metastatic tumors. Recently, metronomic chemotherapy (mCHT) showed advantages in treating TNBCs leading us to investigate the anti-metastatic and anti-angiogenic potential of metronomic 5-Fluorouracil plus Vinorelbine (5-FU+VNR) on endothelial cells (ECs) and TNBCs in comparison to standard treatment (STD). We found that 10-fold lower doses of 5-FU+VNR given mCHT vs. STD inhibits cell proliferation and survival of ECs and TNBC cells. Both schedules strongly affect ECs migration and invasion, but in TNBC cells mCHT is significantly more effective than STD in impairing cell migration and invasion. The two treatments disrupt FAK/VEGFR/VEGF signaling in both ECs and TNBC cells. mCHT, and to a much lesser extent STD treatment, induces apoptosis in ECs, whereas it switches the route of cell death from apoptosis (as induced by STD) to autophagy in TNBC cells. mCHT-treated TNBCs-derived conditioned medium also strongly affects ECs’ migration, modulates different angiogenesis-associated proteins, and hampers angiogenesis in matrix sponge in vivo. In conclusion, mCHT administration of 5-FU+VNR is more effective than STD schedule in controlling cell proliferation/survival and migration/invasion of both ECs and TNBC cells and has a strong anti-angiogenic effect. Our data suggest that the stabilization of tumor growth observed in TNBC patients treated with mCHT therapy schedule is likely due not only to direct cytotoxic effects but also to anti-metastatic and anti-angiogenic effects.
Expression patterns and prognostic implications of tumor-infiltrating lymphocytes dynamics in early breast cancer patients receiving neoadjuvant therapy: A systematic review and meta-analysis
Authors: Zhu Yajing , Tzoras Evangelos , Matikas Alexios , Bergh Jonas , Valachis Antonios , Zerdes Ioannis , Foukakis Theodoros
Published: November 2022

Purpose

High levels of tumor-infiltrating lymphocytes (TILs) are associated with better outcomes in early breast cancer and higher pathological response rates to neoadjuvant chemotherapy especially in the triple-negative (TNBC) and HER2+ subtypes. However, the dynamic changes in TILs levels after neoadjuvant treatment (NAT) are less studied. This systematic review and meta-analysis aimed to investigate the patterns and role of TILs dynamics change in early breast cancer patients receiving NAT.

Methods

Medline, Embase, Web of Science Core Collection and PubMed Central databases were searched for eligible studies. Data were extracted independently by two researchers and discordances were resolved by a third. Pooled TILs rates pre- & post-treatment (overall and per subtype), pooled rates of ΔTILs and direction of change after NAT as well as correlation of ΔTILs with survival outcomes were generated in the outcome analysis.

Results

Of 2116 identified entries, 34 studies fulfilled the criteria and provided adequate data for the outcomes of interest. A decreased level of TILs was observed after NAT in paired samples across all subtypes. The effect of NAT on TILs was most prominent in TNBC subtype with a substantial change, either increase or decrease, in 79.3% (95% CI 61.7-92.6%) of the patients as well as in HER2+ disease (14.4% increased vs 46.2% decreased). An increase in ΔTILs in TNBC was associated with better disease-free/relapse-free survival in pooled analysis (univariate HR = 0.59, 95% CI: 0.37–0.95, p = 0.03).

Conclusion

This meta-analysis illustrates the TILs dynamics during NAT for breast cancer and indicates prognostic implications of ΔTILs in TNBC. The potential clinical utility of the longitudinal assessment of TILs during neoadjuvant therapy warrants further validation.
Selective Vulnerability of the Locus Coeruleus Noradrenergic System and its Role in Modulation of Neuroinflammation, Cognition, and Neurodegeneration
Authors: Evans Andrew K. , Defensor Erwin , Shamloo Mehrdad
Published: November 2022

Locus coeruleus (LC) noradrenergic (NE) neurons supply the main adrenergic input to the forebrain. NE is a dual modulator of cognition and neuroinflammation. NE neurons of the LC are particularly vulnerable to degeneration both with normal aging and in neurodegenerative disorders. Consequences of this vulnerability can be observed in both cognitive impairment and dysregulation of neuroinflammation. LC NE neurons are pacemaker neurons that are active during waking and arousal and are responsive to stressors in the environment. Chronic overactivation is thought to be a major contributor to the vulnerability of these neurons. Here we review what is known about the mechanisms underlying this neuronal vulnerability and combinations of environmental and genetic factors that contribute to confer risk to these important brainstem neuromodulatory and immunomodulatory neurons. Finally, we discuss proposed and potential interventions that may reduce the overall risk for LC NE neuronal degeneration.
An exceed 60% efficiency Nd:YAG transparent ceramic laser with low attenuation loss effect
Authors: Chang Jin-Quan , Shen Yu , Bian Qi , Zong Nan , Lv Ze , Bo Yong , Peng Qin-Jun
Published: November 2022

Here, the attenuation loss effect and laser performance enhancement of Nd:YAG transparent ceramics were investigated. Using a 0.6 at.% Nd:YAG ceramic rod of 3 mm diameter and 65 mm length, the scattering coefficient and absorption coefficient at 1,064 nm were measured to be 0.0001 cm−1 and 0.0017 cm−1, respectively. For the 808-nm side-pumped laser experiment, an average output power of 44.9 W was achieved with an optical-to-optical conversion efficiency of 26.4%, which was nearly the same with that of a 1 at% single crystal. Adopting the 885-nm direct end-pumped scheme, the following laser tests demonstrated a high optical efficiency of 62.5% and maximum output power of 144.8 W obtained at an absorbed pump power of 231.5 W. This was until now the highest optical conversion efficiency acquired in an Nd:YAG ceramic laser to our knowledge. It proves that high-power and high-efficiency laser output could be generated by a high-optical quality Nd:YAG ceramic rod along with the 885-nm direct pumping technology.
Identification of two quantitative genes controlling soybean flowering using bulked-segregant analysis and genetic mapping
Authors: Lv Tianxiao , Wang Lingshuang , Zhang Chunyu , Liu Shu , Wang Jinxing , Lu Sijia , Fang Chao , Kong Lingping , Li Yunlong , Li Yuge , Hou Xingliang , Liu Baohui , Kong Fanjiang , Li Xiaoming
Published: November 2022

Photoperiod responsiveness is important to soybean production potential and adaptation to local environments. Varieties from temperate regions generally mature early and exhibit extremely low yield when grown under inductive short-day (SD) conditions. The long-juvenile (LJ) trait is essentially a reduction and has been introduced into soybean cultivars to improve yield in tropical environments. In this study, we used next-generation sequencing (NGS)-based bulked segregant analysis (BSA) to simultaneously map qualitative genes controlling the LJ trait in soybean. We identified two genomic regions on scaffold_32 and chromosome 18 harboring loci LJ32 and LJ18, respectively. Further, we identified LJ32 on the 228.7-kb scaffold_32 as the soybean pseudo-response-regulator gene Tof11 and LJ18 on a 301-kb region of chromosome 18 as a novel PROTEIN FLOWERING LOCUS T-RELATED gene, Glyma.18G298800. Natural variants of both genes contribute to LJ trait regulation in tropical regions. The molecular identification and functional characterization of Tof11 and LJ18 will enhance understanding of the molecular mechanisms underlying the LJ trait and provide useful genetic resources for soybean molecular breeding in tropical regions.
Cost-effectiveness of two screening strategies based on Chinese diabetes risk score for pre-diabetes in China
Authors: Hao Jingjing , Yao Qiang , Lin Yidie , Sun Yue , Zhang Baiyang , Hu Meijing , Zhang Jing , Zhao Ningxuan , Pei Jiao , Liu Zhonghua , Zhu Cairong
Published: November 2022

Objective

Studies have shown that screening for pre-diabetes mellitus (pre-DM) is essential to prevent type 2 diabetes mellitus (T2DM). This study evaluates the cost-effectiveness of two screening strategies that apply the Chinese Diabetes Risk Score (CDRS) to screen for pre-DM in China.

Methods

A Markov microsimulation model was conducted from a social perspective, and the input parameters were obtained from published literature or publicly available data. Two screening strategies for pre-DM based on CDRS were built and compared with the control group to determine the cost-effective strategy. The screening strategy of the control group was screening for pre-DM by fasting plasma glucose (FPG) test in adults undergoing annual health examination and no screening in adults without an annual health examination (status quo). Two screening strategies were strategy 1: screening for pre-DM using CDRS in all adults (including with or without an annual health examination); and strategy 2: supplemental self-screening for pre-DM using CDRS in adults without an annual health examination, based on the status quo. We focus on the cumulative prevalence of T2DM and the incremental cost-effectiveness ratio which signifies the cost per case of T2DM prevented. We also evaluated the cost-effectiveness from the health system perspective. One-way and probabilistic sensitivity analyses were conducted to verify the robustness of the results.

Results

The costs a case of T2DM prevented for strategy 1 compared with the control group and strategy 2 were $299.67 (95% CI 298.88, 300.46) and $385.89 (95% CI 381.58, 390.20), respectively. In addition, compared with the control group, the cost of strategy 2 to prevent a case of T2DM was $272.23 (95% CI 271.50, 272.96).

Conclusions

Screening for pre-DM using CDRS in all adults was the most cost-effective health policy. We suggest that medical institutions replace FPG with CDRS for pre-DM screening; at the same time, self-screening for pre-DM using CDRS is widely promoted among adults without an annual health examination. There were still some disputes about how CDRS is included in the health examination projects, so strategy 2 should be considered as an alternative screening strategy. Findings provide a reference for the application of the CDRS in pre-DM screening and contribute to T2DM prevention.
Global trends and hotspots in research on osteoporosis rehabilitation: A bibliometric study and visualization analysis
Authors: Wang Liqiong , Jiang Jiaojiao , Li Yi , Huang Jinming , Wang Renjie , Liang Yuxiang , He Chengqi , Liu Shaxin
Published: November 2022

Background

The field of rehabilitation medicine plays an essential role in the comprehensive management of osteoporosis and its consequences. The benefits of therapeutic exercise are increasingly being recognized in this area, which receives an increasing number of publications. this study was designed to comprehensively identify collaborative networks, parse and track research trends, spotlight present hotspots, and accurately predict frontiers and focus on the health topics related to osteoporosis rehabilitation.

Methods

This research adopted computer retrieval of osteoporosis rehabilitation-related research published in the Web of Science Core Collection (WoSCC) from inception to June 14, 2022. The bibliometric visualization and comparative analysis involving countries, institutions, journals, authors, references, and keywords were performed using the CiteSpace and VOSviewer software.

Results

A total of 3,268 articles were included, and the number of articles published each year has demonstrated a steady increase. The United States and the University of Melbourne were the highest productive country and institution, with 1,325 and 87 articles, respectively. The journal of osteoporosis international has published the greatest number of articles, with 221 publications, and the journal of bone and mineral research ranked first in the co-citation counts (cited by 11,792 times). The most productive and highly-cited authors were Heinonen A and Cummings S, with 35 publications and 680 citations.

Conclusions

At present, “physical activity,” “weight bearing exercise,” “muscle strength,” “whole body vibration,” “postmenopausal women,” “older women,” children, men are the noteworthy research hot topics. Future research that focus on the major modes and parameters of physical activity/exercise for osteoporosis (including whole body vibration, weight bearing exercises, resistance training), targeted multicomponent training regimens, rehabilitation therapy for postmenopausal women, older women, children and men, osteoporosis related-sarcopenia and fractures, and mesenchymal stem cells are becoming frontiers and focus on the health topics related to osteoporosis rehabilitation in the upcoming years, which are worthy of further exploration.