bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochar Addition Altered Bacterial Community and Improved Photosynthetic Rate of Seagrass: A Mesocosm Study of Seagrass Thalassia hemprichii
Authors: Zhang Jian , Ling Juan , Zhou Weiguo , Zhang Wenqian , Yang Fangfang , Wei Zhangliang , Yang Qingsong , Zhang Ying , Dong Junde
Published: July 2023

Seagrass meadows, as typical “blue carbon” ecosystems, play critical ecological roles in the marine ecosystem and decline every year. The application of biochar in soil has been proposed as a potential soil amendment to improve soil quality and mitigate global climate change. The effects of biochar on soil bacterial activities are integrally linked to the potential of biochar in achieving these benefits. However, biochar has been rarely applied in marine ecosystems. Whether the application of biochar could work on the seagrass ecosystem remained unknown. In this study, we investigated the responses of sediment and rhizosphere bacterial communities of seagrass Thalassia hemprichii to the biochar addition derived from maize at ratios of 5% by dry weight in the soil during a one-month incubation. Results indicated that the biochar addition significantly changed the sedimental environment with increasing pH, total phosphorus, and total kalium while total nitrogen decreased. Biochar addition significantly altered both the rhizosphere and sediment bacterial community compositions. The significant changes in rhizosphere bacterial community composition occurred after 30days of incubation, while the significant variations in sediment bacterial community composition distinctly delayed than in sediment occurred on the 14th day. Biochar application improved nitrification and denitrification, which may accelerate nitrogen cycling. As a stabilizer to communities, biochar addition decreased the importance of deterministic selection in sediment and changed the bacterial co-occurrence pattern. The biochar addition may promote seagrass photosynthesis and growth by altering the bacterial community compositions and improving nutrient circulation in the seagrass ecosystem, contributing to the seagrass health improvement. This study provided a theoretical basis for applying biochar to the seagrass ecosystem and shed light on the feasible application of biochar in the marine ecosystem.
Tryptophan residue of plasmid-encoded Pgp3 is important for Chlamydia muridarum to induce hydrosalpinx in mice
Authors: Huang Yumeng , Wu Haoqing , Sun Yina , Liu Yuanjun
Published: July 2023

The crucial role of plasmid-encoded protein Pgp3 in Chlamydia pathogenesis has been demonstrated in various animal models. Previous studies have revealed that the Pgp3-deficient C. muridarum mutant fails to induce hydrosalpinx after vaginal inoculation in mice. Structural analysis of C. trachomatis Pgp3 trimer has indicated that Trp234 may play a critical role in trimeric crystal packing interactions and that Tyr197 is involved at predominant cation-binding sites. In this study, we constructed C. muridarum transformants harboring Pgp3, Trp234, or Tyr197 point mutations (Pgp3W234A and Pgp3Y197A). C3H/HeJ mice infected with Pgp3W234A mutant failed to induce severe hydrosalpinx in the oviduct tissue, which largely phenocopied the full-length Pgp3-deficient C. muridarum. The Pgp3Y197A variant induced an intermediate severity of pathology. The attenuated pathogenicity caused by the Pgp3W234A mutant may be due to its decreased survival in the lower genital tracts of mice, reduced ascension to the oviduct, and milder induction of inflammatory cell infiltration in the oviduct tissue. Thus, our results point to an important amino acid residue involved in Pgp3 virulence, providing a potential therapeutic target for chlamydial infection.
Top-down and bottom-up stimulation techniques combined with action observation treatment in stroke rehabilitation: a perspective
Authors: Qi Fengxue , Nitsche Michael A. , Ren Xiping , Wang Duanwei , Wang Lijuan
Published: July 2023

Stroke is a central nervous system disease that causes structural lesions and functional impairments of the brain, resulting in varying types, and degrees of dysfunction. The bimodal balance-recovery model (interhemispheric competition model and vicariation model) has been proposed as the mechanism of functional recovery after a stroke. We analyzed how combinations of motor observation treatment approaches, transcranial electrical (TES) or magnetic (TMS) stimulation and peripheral electrical (PES) or magnetic (PMS) stimulation techniques can be taken as accessorial physical therapy methods on symptom reduction of stroke patients. We suggest that top-down and bottom-up stimulation techniques combined with action observation treatment synergistically might develop into valuable physical therapy strategies in neurorehabilitation after stroke. We explored how TES or TMS intervention over the contralesional hemisphere or the lesioned hemisphere combined with PES or PMS of the paretic limbs during motor observation followed by action execution have super-additive effects to potentiate the effect of conventional treatment in stroke patients. The proposed paradigm could be an innovative and adjunctive approach to potentiate the effect of conventional rehabilitation treatment, especially for those patients with severe motor deficits.
Ketogenic dietary therapies in epilepsy: recommendations of the Italian League against Epilepsy Dietary Therapy Study Group
Authors: De Giorgis Valentina , Tagliabue Anna , Bisulli Francesca , Brambilla Ilaria , Camerini Alessandra , Cusmai Raffaella , Darra Francesca , Dianin Alice , Domenica Elia , Lodi Monica Anna Maria , Matricardi Sara , Messana Tullio , Operto Francesca , Ragona Francesca , Russo Emilio , Varesio Costanza , Volpi Lilia , Zanaboni Martina Paola , Pasca Ludovica , Veggiotti Pierangelo
Published: July 2023

A stepwise increase in the utilization of ketogenic dietary therapies for drug-resistant epilepsy has been observed in Italy in the last decade, although it is still considered often underused in many centers when compared to other countries. The Dietary Therapy Study Group of the Italian League against Epilepsy proposes practical recommendations to improve shared knowledge and facilitate the application of ketogenic dietary therapies, optimizing its efficacy and tolerability. The experts involved (11 child neuropsychiatrists, two adult neurologists, one psychologist, one pharmacologist, one pediatric endocrinologist, one representative of patients' associations, and three dietitians and clinical nutritionists) responded to a survey on current clinical practice issues and were asked to discuss controversial topics related to supplementation, long-term maintenance, transition, and a multidisciplinary approach to ketogenic dietary therapies. Practical indications for patient selection, diet initiation, management, side effects prevention, and follow-up are provided.
Development and validation of a deep-broad ensemble model for early detection of Alzheimer's disease
Authors: Ma Peixian , Wang Jing , Zhou Zhiguo , Chen C. L. Philip ,   The Alzheimer's Disease Neuroimaging Initiative, Duan Junwei
Published: July 2023

Introduction

Alzheimer's disease (AD) is a chronic neurodegenerative disease of the brain that has attracted wide attention in the world. The diagnosis of Alzheimer's disease is faced with the difficulties of insufficient manpower and great difficulty. With the intervention of artificial intelligence, deep learning methods are widely used to assist clinicians in the early recognition of Alzheimer's disease. And a series of methods based on data input with different dimensions have been proposed. However, traditional deep learning models rely on expensive hardware resources and consume a lot of training time, and may fall into the dilemma of local optima.

Methods

In recent years, broad learning system (BLS) has provided researchers with new research ideas. Based on the three-dimensional residual convolution module and BLS, a novel broad-deep ensemble model based on BLS is proposed for the early detection of Alzheimer's disease. The Alzheimer's Disease Neuroimaging Initiative (ADNI) MRI image dataset is used to train the model and then we compare the performance of proposed model with previous work and clinicians' diagnosis.

Results

The result of experiments demonstrate that the broad-deep ensemble model is superior to previously proposed related works, including 3D-ResNet and VoxCNN, in accuracy, sensitivity, specificity and F1.

Discussion

The proposed broad-deep ensemble model is effective for early detection of Alzheimer's disease. In addition, the proposed model does not need the pre-training process of its depth module, which greatly reduces the training time and hardware dependence.
The differential response to neuronal hyperexcitation and neuroinflammation of the hippocampal neurogenic niche
Authors: Ruiz-Clavijo Lorena , Martín-Suárez Soraya
Published: July 2023

Hippocampal neurogenesis is a tightly regulated process in which neural stem cells (NSCs) get activated, enter in the cell cycle and give rise to neurons after a multistep process. Quiescent and activated NSCs, neural precursors, immature and mature neurons and newborn astrocytes coexist in the neurogenic niche in a strictly controlled environment which maintains the correct functioning of neurogenesis. NSCs are the first step in the neurogenic process and are a finite and, mostly, non-renewable resource, therefore any alteration of the intrinsic properties of NSCs will impact the total neurogenic output. Neuronal hyperexcitation is a strong activator of NSCs prompting them to divide and therefore increasing neurogenesis. However, neuronal hyperactivity is not an isolated process but often also involves excitotoxicity which is subsequently accompanied by neuroinflammation. Neuroinflammation normally reduces the activation of NSCs. It is technically difficult to isolate the effect of neuronal hyperexcitation alone, but neuroinflammation without neuronal hyperexcitation can be studied in a variety of models. In order to shed light on how the balance of neuronal hyperexcitation and neuroinflammation affect NSCs we analyzed proliferation and morphology of NSCs. We used two models of neuronal hyperactivity [an epilepsy model induced by KA, and a model of traumatic brain injury (TBI)] and different models of inflammation (LPS, Poly I:C, IFN-α and IL-6). We observed that only those models that induce neuronal hyperactivity induce NSCs activation but neuroinflammation causes the opposite effect. We also analyzed the response of other cell types in the neurogenic niche, focusing on astrocytes.
Central nervous system-related safety and tolerability of add-on ketamine to standard of care treatment in treatment-resistant psychotic depression in patients with major depressive disorder and bipolar disorder
Authors: Gałuszko-Wȩgielnik Maria , Jakuszkowiak-Wojten Katarzyna , Wiglusz Mariusz Stanisław , Cubała Wiesław Jerzy , Pastuszak Michał
Published: July 2023

Background

Psychotic treatment-resistant depression represents a complex and challenging form of mood disorder in clinical practice. Despite its severity, psychotic depression is frequently underdiagnosed and inadequately treated. Ketamine has demonstrated rapid and potent antidepressant effects in clinical studies, while exhibiting a favorable safety and tolerability profile. Although there is limited literature available on the use of ketamine in psychotic TRD, reports on its efficacy, safety, and tolerability profile are of great interest to clinicians. The aim of this study is to investigate the relationship between dissociative symptomatology and psychomimetic effects in inpatients with treatment-resistant major psychotic depression and treatment-resistant bipolar psychotic depression, who receive intravenous ketamine treatment alongside psychotropic medication, both during and after treatment.

Materials and methods

A total of 36 patients diagnosed with treatment-resistant unipolar (17 patients) or bipolar (18 patients) depression with psychotic features were treated with eight intravenous infusions of 0.5 mg/kg ketamine twice a week over 4 weeks. Ketamine was given in addition to their standard of care treatment. The severity of depressive symptoms was evaluated using the MADRS, while dissociative and psychomimetic symptoms were assessed using the CADSS and BPRS, respectively.

Results

There were no statistically significant changes observed in MADRS, CADSS, and BPRS scores within the study group during ketamine infusions. However, significant improvements in MADRS, CADSS, and BPRS scores were observed during ketamine infusions in both the unipolar and bipolar depression groups.

Conclusion

This study provides support for the lack of exacerbation of psychotic symptoms in both unipolar and bipolar depression.
Efficacy of non-invasive brain stimulation for disorders of consciousness: a systematic review and meta-analysis
Authors: Dong Linghui , Li Hui , Dang Hui , Zhang Xiaonian , Yue Shouwei , Zhang Hao
Published: July 2023

Objective

The aim of this study is to evaluate the efficacy of non-invasive brain stimulation (NIBS) in patients with disorders of consciousness (DoC) and compare differences in efficacy between different stimulation modalities.

Methods

We searched the PubMed, Cochrane Library, Web of Science, and EMBASE databases for all studies published in English from inception to April 2023. Literature screening and quality assessment were performed independently by two investigators. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to evaluate the therapeutic effects of NIBS. The Cochrane Q test and I2 statistic were used to evaluate heterogeneity between studies. Subgroup analysis was performed to identify the source of heterogeneity, and differences in efficacy between different stimulation modalities were compared by Bayesian analysis.

Results

A total of 17 studies with 377 DoC patients were included. NIBS significantly improved the state of consciousness in DoC patients when compared to sham stimulation (WMD: 0.81; 95% CI: 0.46, 1.17; I2 = 78.2%, p = 0.000). When divided into subgroups according to stimulation modalities, the heterogeneity of each subgroup was significantly lower than before (I2: 0.00–30.4%, p >0.05); different stimulation modalities may be the main source of such heterogeneity. Bayesian analysis, based on different stimulation modalities, indicated that a patient’s state of consciousness improved most significantly after repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC). Diagnosis-based subgroup analysis showed that NIBS significantly improved the state of consciousness in patients with a minimal consciousness state (WMD: 1.11; 95% CI: 0.37, 1.86) but not in patients with unresponsive wakefulness syndrome or a vegetative state (WMD: 0.31; 95% CI: −0.09, 0.71). Subgroup analysis based on observation time showed that single treatment did not improve the state of consciousness in DoC patients (WMD: 0.28; 95% CI: −0.27, 0.82) while multiple treatments could (WMD: 1.05; 95% CI: 0.49, 1.61). Furthermore, NIBS had long-term effects on DoC patients (WMD: 0.79; 95% CI: 0.08–1.49).

Conclusion

Available evidence suggests that the use of NIBS on patients with DoC is more effective than sham stimulation, and that rTMS of the left DLPFC may be the most prominent stimulation modality.
Fibroblast growth factor 3 promotes spontaneous mammary tumorigenesis in Tientsin albino 2 mice via the FGF3/FGFR1/STAT3 pathway
Authors: Chen Lankai , Zhang Xipeng , Liu Guisheng , Chen Shuo , Zheng Minying , Zhu Siwei , Zhang Shiwu
Published: July 2023

Introduction

Tientsin albino 2 (TA2) mice can develop spontaneous breast cancer (SBC), which is associated with multiple pregnancies and infection with the mouse mammary tumor virus (MMTV). In this study, we sought to elucidate the molecular mechanisms underlying the development of SBC in TA2 mice induced by MMTV.

Methods

The integration site of MMTV in TA2 SBC was identified using whole-genome sequencing. The expression of fibroblast growth factor 3 (FGF3) in SBCs and normal breast tissues was compared. The primary cell line, TA-1106, derived from SBC, was cultured. The proliferation, cell cycle, migration, invasion, and tumorigenicity abilities, as well as the expression of epithelial-mesenchymal transition-related proteins, phosphorylated STAT3, and phosphorylated Akt, were assessed in MA-891cell line from TA2 and TA-1106 cells after FGF3 knockdown. The binding of FGF3 to FGF receptor 1 (FGFR1) was determined by co-immunoprecipitation. Additionally, the relationship between STAT3 and Akt phosphorylation was investigated using a small molecule inhibitor and STAT3 knockdown.

Results

MMTV integrated upstream of the FGF3 gene, and the FGF3 protein was highly expressed in TA2 SBCs. FGF3 knockdown in MA-891 and TA-1106 decreased their proliferation, migration, and invasion abilities, affected the cell cycle and expression of epithelial-mesenchymal transition-related proteins, and inhibited the growth of animal xenografts. FGF3 binds to FGFR1, and either FGF3 or FGFR1 knockdown decreases STAT3 and Akt phosphorylation levels. Inhibition of phosphorylation or expression of STAT3 resulted in decreased Akt phosphorylation levels. Inhibition of Akt phosphorylation also resulted in decreased STAT3 phosphorylation levels. Furthermore, treatment of MA-891 and TA-1106 cells with Wortmannin or Stattic caused FGFR1 upregulation in addition to inhibiting Akt or STAT3 phosphorylation.

Conclusion

The results of this study demonstrate that FGF3 plays a significant role in the development of SBC through the FGF3/FGFR1/STAT3 signaling pathway. There is a reciprocal activation between STAT3 and Akt. Inhibition of STAT3 or Akt phosphorylation promoted the expression of FGFR1. Validating the conclusions obtained in this study in human breast cancer (HBC) may contribute to targeted therapy and it is worth exploring whether the homologous sequences of MMTV in HBC have a similar oncogenic effect.
The role of cancer-associated fibroblasts in breast cancer metastasis
Authors: Li Yi , Wang Changyuan , Huang Ting , Yu Xijie , Tian Bole
Published: July 2023

Breast cancer deaths are primarily caused by metastasis. There are several treatment options that can be used to treat breast cancer. There are, however, a limited number of treatments that can either prevent or inhibit the spread of breast tumor metastases. Thus, novel therapeutic strategies are needed. Studies have increasingly focused on the importance of the tumor microenvironment (TME) in metastasis of breast cancer. As the most abundant cells in the TME, cancer-associated fibroblasts (CAFs) play important roles in cancer pathogenesis. They can remodel the structure of the extracellular matrix (ECM) and engage in crosstalk with cancer cells or other stroma cells by secreting growth factors, cytokines, and chemokines, as well as components of the ECM, which assist the tumor cells to invade through the TME and cause distant metastasis. Clinically, CAFs not only foster the initiation, growth, angiogenesis, invasion, and metastasis of breast cancer but also serve as biomarkers for diagnosis, therapy, and prediction of prognosis. In this review, we summarize the biological characteristics and subtypes of CAFs and their functions in breast cancer metastasis, focusing on their important roles in the diagnosis, prognosis, and treatment of breast cancer. Recent studies suggest that CAFs are vital partners of breast cancer cells that assist metastasis and may represent ideal targets for prevention and treatment of breast cancer metastasis.
Case Report: A rare synchronous multiple gastric carcinoma achieved progression-free disease through NGS-guided serial treatment
Authors: Shao Xinyi , Yin Jin , Wang Di , Huang Erjiong , Zhang Yini , Yin Jiani C. , Huang Chen , Wu Hao , Wu Xiaoli
Published: July 2023

Synchronous multiple gastric carcinoma (SMGC) is a rare condition characterized by the simultaneous occurrence of two or more primary malignant tumors in the stomach, each with its own distinct pathological morphology. SMGC differs from gastric metastases, which originate from primary gastric or non-gastric tumors. At present, the incidence of SMGC is low in China, with no established guidelines for standard treatment. Here, we report a rare case of advanced SMGC that achieved long-lasting clinical benefits through a treatment strategy informed by next-generation sequencing (NGS). Dynamically monitoring of the tumor and/or circulating cell-free DNA guided the patient’s treatment sequentially. The patient received anti-HER2 therapy, followed by immunotherapy, pembrolizumab in combination with trastuzumab and chemotherapy, and ultimately underwent successful total gastrectomy. This case highlights a novel approach of utilizing liquid biopsy-based NGS to gain insights into disease progression and molecular response to NGS-guided treatment in SMGC patients.
Parental perception of facilitators and barriers to health among young children with down syndrome: a qualitative study
Authors: Caldwell Angela R. , Kim Yeook , Alshahwan Nada , Vellody Kishore , Bendixen Roxanna M. , Renz Kayley , Duong Tiffany , Dodd Judith , Terhorst Lauren , Must Aviva
Published: July 2023

Background

Despite high rates of obesity and weight-related conditions observed in children with Down syndrome, little is known about how to prevent these conditions.

Purpose

The purpose of this study was to identify parent-perceived facilitators and barriers to health for toddlers (12–36 months old) with Down syndrome.

Materials and methods

We conducted in-depth, semi-structured interviews with the mothers of 25 toddlers with Down syndrome. All interviews were conducted using Zoom Video Technology, audio recorded and transcribed before being coded in NVivo software using a structured protocol. Thematic analysis was used to identify themes in perceived facilitators and barriers to health at the level of the child, family, and community. Data were triangulated using reflective journaling, video review of child meals, and member-checking techniques.

Results

We identified unique themes for facilitators (on the move and sound sleep) and barriers (co-occurring conditions and eating behaviors) at the level of the child. At the level of the family and community, overarching themes that were viewed as either a facilitator or barrier, depending on the context, were identified (role models matter, time is critical, the importance of place, and social support).

Conclusion

These themes can help clinicians and researchers tailor their health promotion interventions to meet the unique needs of children with Down syndrome by using strength-based approaches and providing families with the tools to overcome barriers.
Identification of collateral sensitivity and evolutionary landscape of chemotherapy-induced drug resistance using cellular barcoding technology
Authors: Danisik Nurseda , Yilmaz Kubra Celikbas , Acar Ahmet
Published: July 2023

Background: One of the most significant challenges impeding cancer treatment effectiveness is drug resistance. Combining evolutionary understanding with drug resistance can pave the way for the identification of second-line drug options that can overcome drug resistance. Although capecitabine and irinotecan are commonly used therapeutic agents in the treatment of CRC patients, resistance to these agents is common. The underlying clonal dynamics of resistance to these agents using high-resolution barcode technology and identification of effective second-line drugs in this context remain unclear.

Methods and materials: Caco-2 and HT-29 cell lines were barcoded, and then capecitabine and irinotecan resistant derivatives of these cell lines were established. The frequencies of barcodes from resistant cell lines and harvested medium, longitudinally, were determined. Collateral drug sensitivity testing was carried out on resistant Caco-2 and HT-29 cell lines using single agents or drug combinations. The SyngeryFinder tool was used to analyse drug combination testing.

Results: In Caco-2 and HT-29 cell lines, barcode frequency measurements revealed clonal dynamics of capecitabine and irinotecan formed by both pre-existing and de novo barcodes, indicating the presence of polyclonal drug resistance. The temporal dynamics of clonal evolution in Caco-2 and HT-29 cell lines were demonstrated by longitudinal analysis of pre-existing and de novo barcodes from harvested medium. In Caco-2 and HT-29 cell lines, collateral drug sensitivity revealed a number of drugs that were effective alone and in combination.

Conclusion: The use of barcoding technology reveals the clonal dynamics of chemotherapy-induced drug resistance not only from harvested cell populations, but also from longitudinal sampling throughout the course of clonal evolution. Second-line drugs that sensitize drug-resistant CRC cell lines are identified through collateral drug testing.
Case report: metoclopramide induced acute dystonic reaction in adolescent CYP2D6 poor metabolizers
Authors: Fink Franz-Martin , Bognar Marta , Hengl Petra , Paulmichl Markus , Nofziger Charity
Published: July 2023

Metoclopramide is indicated for the management of gastroesophageal reflux, gastric stasis, nausea, and vomiting. Metoclopramide-induced acute dystonic reactions (MIADRs), along with repetitive involuntary protrusion of the tongue, are well-known phenomena in children and young adults that may appear after the first dose. The drug is primarily metabolized via oxidation by the cytochrome P450 enzyme CYP2D6 and to a lesser extent by CYP3A4 and CYP1A2. A recommendation to decrease metoclopramide dosing in patients with severely limited to no CYP2D6 activity (i.e., poor metabolizers, PMs) is included in the drug label. It is important to note, however, that a requirement or recommendation for pre-emptive testing for CYP2D6 metabolizer status is not included in the drug label. We present two cases of acute dystonia in two non-consanguineous male adolescents: one following metoclopramide and cimetidine administration in a 14-year-old to treat gastroesophageal reflux, and another following metoclopramide and pantoprazole administration in a 17-year-old with acute gastroenteritis. A retrospective pharmacogenetic analysis revealed both patients as CYP2D6 PMs.
Performance of the modified clock skew estimator and its upper bound for the IEEE 1588v2 (PTP) case under packet loss and fractional Gaussian noise environment
Authors: Avraham Yehonatan , Pinchas Monika
Published: July 2023

Precision Time Protocol (PTP) is a time protocol based on the Master and Slave exchanging messages with time stamps. In practical PTP systems, we have packet loss, a phenomenon where some of the PTP messages get lost in the Network. Packet loss may reduce the performance of the clock skew estimator from the mean square error (MSE) perspective. Recently, the same authors presented simulation results that show the clock skew performance of the three clock skew estimators (the two-way delay (TWD) clock skew estimator and the one-way delay (OWD) clock skew estimator for the Forward and Reverse paths) under the packet loss case in the fractional Gaussian noise (fGn) environment with Hurst exponent parameter (H) in the range of 0.5 ≤ H < 1, where indeed the clock skew performance was degraded compared to the non-packet loss case. Please note that for 0.5 < H < 1, the corresponding fGn is of long-range dependency (LRD). This paper proposes an algorithm that estimates the missing timestamps in the packet loss and fGn (0.5 ≤ H < 1) case. We use those estimates to generate three modified clock skew estimators (the two-way delay (TWD) modified clock skew estimator and the one-way delay (OWD) modified clock skew estimator for the Forward and Reverse paths) applicable to the packet loss, non-packet loss, and fGn (0.5 ≤ H < 1) case based on the same authors’ previously developed clock skew estimators. Those modified clock skew estimators led, based on simulation results, to an improved clock skew performance in the packet loss and fGn (0.5 ≤ H < 1) case compared with the authors’ previously developed clock skew estimators and those known from the literature (the ML-like (MLLE) and Kalman clock skew estimators). With the MSE expression, the system designer can know how many Sync periods are needed for the clock skew synchronization task to reach the system’s requirements from the MSE perspective. But no MSE expression exists in the literature for the packet loss case. In this paper, we derive closed-form approximated expressions for the MSE upper bounds related to the modified TWD and OWD clock skew estimators valid for the packet loss and fGn (0.5 ≤ H < 1) cases.
Combination of personalized computational modeling and machine learning for optimization of left ventricular pacing site in cardiac resynchronization therapy
Authors: Dokuchaev Arsenii , Chumarnaya Tatiana , Bazhutina Anastasia , Khamzin Svyatoslav , Lebedeva Viktoria , Lyubimtseva Tamara , Zubarev Stepan , Lebedev Dmitry , Solovyova Olga
Published: July 2023

Introduction: The 30–50% non-response rate to cardiac resynchronization therapy (CRT) calls for improved patient selection and optimized pacing lead placement. The study aimed to develop a novel technique using patient-specific cardiac models and machine learning (ML) to predict an optimal left ventricular (LV) pacing site (ML-PS) that maximizes the likelihood of LV ejection fraction (LVEF) improvement in a given CRT candidate. To validate the approach, we evaluated whether the distance DPS between the clinical LV pacing site (ref-PS) and ML-PS is associated with improved response rate and magnitude.

Materials and methods: We reviewed retrospective data for 57 CRT recipients. A positive response was defined as a more than 10% LVEF improvement. Personalized models of ventricular activation and ECG were created from MRI and CT images. The characteristics of ventricular activation during intrinsic rhythm and biventricular (BiV) pacing with ref-PS were derived from the models and used in combination with clinical data to train supervised ML classifiers. The best logistic regression model classified CRT responders with a high accuracy of 0.77 (ROC AUC = 0.84). The LR classifier, model simulations and Bayesian optimization with Gaussian process regression were combined to identify an optimal ML-PS that maximizes the ML-score of CRT response over the LV surface in each patient.

Results: The optimal ML-PS improved the ML-score by 17 ± 14% over the ref-PS. Twenty percent of the non-responders were reclassified as positive at ML-PS. Selection of positive patients with a max ML-score >0.5 demonstrated an improved clinical response rate. The distance DPS was shorter in the responders. The max ML-score and DPS were found to be strong predictors of CRT response (ROC AUC = 0.85). In the group with max ML-score > 0.5 and DPS< 30 mm, the response rate was 83% compared to 14% in the rest of the cohort. LVEF improvement in this group was higher than in the other patients (16 ± 8% vs. 7 ± 8%).

Conclusion: A new technique combining clinical data, personalized heart modelling and supervised ML demonstrates the potential for use in clinical practice to assist in optimizing patient selection and predicting optimal LV pacing lead position in HF candidates for CRT.
Effects of black pepper and turmeric powder on growth performance, gut health, meat quality, and fatty acid profile of Japanese quail
Authors: Ashayerizadeh O. , Dastar B. , Shams Shargh M. , A. Soumeh E. , Jazi V.
Published: July 2023

In poultry production, the search for alternatives to in-feed antibiotics continues unabated. This study investigated the effects of dietary supplementation of black pepper and turmeric powder, separately or in combination, on the growth performance, gastrointestinal microbiota population, intestinal morphology, serum biochemical parameters, meat quality, and meat fatty acid profile in Japanese quails. Five hundred-day-old mixed-sex Japanese quail chicks were randomly assigned to one of five treatments: a control diet (CON); CON +0.2% antibiotic flavomycin as an antibiotic growth promoter (AGP); CON +0.5% turmeric powder (TUP); CON +0.5% black pepper powder (BPP); and CON +0.5% TUP, and 0.5% BPP (MIX). The findings showed that quail chicks fed AGP and TUP throughout the rearing period had better body weight gain (p = 0.007) and feed conversion ratio (p = 0.02) than the other treatments. The TUP, BPP, and MIX feeds reduced (p = 0.005) abdominal fat percentage. The MIX group had a better breast muscle water-holding capacity (p = 0.04) and lightness index (p = 0.02) and lower (p = 0.02) malondialdehyde concentration after 7 days of refrigerated storage. Feeding BPP, TUP, and MIX diets decreased (p = 0.001) serum cholesterol concentration. Quail chicks fed the CON diet showed significantly higher coliform counts in the crop and ileum (p < 0.001), whereas the lactic acid bacterial population was lower (p = 0.008) in the ileum. Birds that received the MIX diet exhibited a higher (p = 0.02) villus height to crypt depth ratio in the duodenum compared to the other groups. The tested feed additives increased (p < 0.001) villus height in the jejunum and ileum compared to other groups. Feeding the TUP, BPP, and MIX diets reduced (p < 0.001) total saturated fatty acid content and increased (p = 0.004) total polyunsaturated fatty acid concentration, where the MIX diet had the best results. Overall, the present data indicate that supplementing the basal diet with turmeric powder enhances the growth performance of Japanese quails. In some respects, such as gut health and meat quality, combining turmeric powder and black pepper powder was more effective than using them independently.
Role of the SLIT-ROBO signaling pathway in renal pathophysiology and various renal diseases
Authors: Feng Li , Shu Hua-Pan , Sun Lu-Lu , Tu Yu-Chi , Liao Qian-Qian , Yao Li-Jun
Published: July 2023

SLIT ligand and its receptor ROBO were initially recognized for their role in axon guidance in central nervous system development. In recent years, as research has advanced, the role of the SLIT-ROBO signaling pathway has gradually expanded from axonal repulsion to cell migration, tumor development, angiogenesis, and bone metabolism. As a secreted protein, SLIT regulates various pathophysiological processes in the kidney, such as proinflammatory responses and fibrosis progression. Many studies have shown that SLIT-ROBO is extensively involved in various aspects of kidney development and maintenance of structure and function. The SLIT-ROBO signaling pathway also plays an important role in different types of kidney disease. This article reviews the advances in the study of the SLIT-ROBO pathway in various renal pathophysiological and kidney disorders and proposes new directions for further research in this field.
Metabolic profiling reveals key metabolites regulating adventitious root formation in ancient Platycladus orientalis cuttings
Authors: Chang Ermei , Guo Wei , Dong Yao , Jia Zirui , Zhao Xiulian , Jiang Zeping , Zhang Li , Zhang Jin , Liu Jianfeng
Published: July 2023

Platycladus orientalis, a common horticultural tree species, has an extremely long life span and forms a graceful canopy. Its branches, leaves, and cones have been used in traditional Chinese medicine. However, difficulty in rooting is the main limiting factor for the conservation of germplasm resources. This study shows that the rooting rates and root numbers of cuttings were significantly reduced in ancient P. orientalis donors compared to 5-year-old P. orientalis donors. The contents of differentially accumulated metabolites (DAMs) in phenylpropanoid (caffeic acid and coniferyl alcohol) and flavonoid biosynthesis (cinnamoyl-CoA and isoliquiritigenin) pathways increased significantly in cuttings propagated from ancient P. orientalis donors compared to 5-year-old P. orientalis donors during adventitious root (AR) formation. These DAMs may prevent the ancient P. orientalis cuttings from rooting, and gradual lignification of callus was one of the main reasons for the failed rooting of ancient P. orientalis cuttings. The rooting rates of ancient P. orientalis cuttings were improved by wounding the callus to identify wounding-induced rooting-promoting metabolites. After wounding, the contents of DAMs in zeatin (5′-methylthioadenosine, cis-zeatin-O-glucoside, and adenine) and aminoacyl-tRNA biosynthesis (l-glutamine, l-histidine, l-isoleucine, l-leucine, and l-arginine) pathways increased, which might promote cell division and provided energy for the rooting process. The findings of our study suggest that breaking down the lignification of callus via wounding can eventually improve the rooting rates of ancient P. orientalis cuttings, which provides a new solution for cuttings of other difficult-to-root horticultural and woody plants.
Asymmetric interactions between barley yellow dwarf virus -PAV and wheat dwarf virus in wheat
Authors: Armand Thomas , Souquet Marlène , Korn Luâna , Gauthier Kevin , Jacquot Emmanuel
Published: July 2023

The deciphering of the epidemiology of a plant virus has long been focused on the study of interactions between partners of one pathosystem. However, plants are exposed to numerous viruses which lead to frequent co-infection scenarios. This can change characteristics of virus-vector-host interactions and could impact the epidemiology of viral diseases. Barley yellow dwarf virus-PAV (BYDV-PAV; species: Luteovirus pavhordei; genus Luteovirus), wheat dwarf virus (WDV; genus Mastrevirus) and their respective vectors (BYDV-PAV: e.g. Rhopalosiphum padi and WDV: Psammotettix alienus) are commonly found in cereal fields. Wheat plants co-infected with BYDV-PAV and WDV have been reported from field surveys, although epidemiological outcomes of BYDV-PAV – WDV interactions in planta have not yet been studied. Experiments were carried out to evaluate and compare, through different competition scenarios (i.e. single- and co- (simultaneous and sequential) inoculations), the efficiency of BYDV-PAV and WDV to infect, to accumulate in and to be spread between wheat plants. Moreover, the impact of competition scenarios on the biological parameters of these two viruses was evaluated at different stages of the infection and with plants at different ages at inoculation. Results showed i) that these viruses achieve their infection cycle and their plant-to-plant transmission with different efficiencies and ii) BYDV-PAV – WDV interactions lead to different phenotypes ranging from antagonism to synergism. Finally, when these two viruses share a host, the nature and strength of virus-virus interactions varied depending on the order of virus arrival, stages of the infection cycle and plant age at inoculation. Precisely, the introduction (i.e. co- and sequential inoculation) and infection process (i.e. virus accumulation) of BYDV-PAV in a wheat benefit from the presence of WDV. For the latter, the sympatry with BYDV-PAV exerts opposite pressure on parameters involved in virus introduction (i.e. benefit during sequential inoculation) and spread (i.e. lower transmission efficiency and virus accumulation in co-infected plants). In the context of increased potential exposure of crops to insect vectors, this study participates in a better understanding of the impact of BYDV-PAV and WDV co-infections on biological and ecological parameters of the diseases induced by these viruses.
Voice pitch is negatively associated with sociosexual behavior in males but not in females
Authors: Mailhos Alvaro , Egea-Caparrós Damián-Amaro , Cabana Álvaro , Martínez-Sánchez Francisco
Published: July 2023

Acoustic cues play a major role in social interactions in many animal species. In addition to the semantic contents of human speech, voice attributes – e.g., voice pitch, formant position, formant dispersion, etc. – have been proposed to provide critical information for the assessment of potential rivals and mates. However, prior studies exploring the association of acoustic attributes with reproductive success, or some of its proxies, have produced mixed results. Here, we investigate whether the mean fundamental frequency (F0), formant position (Pf), and formant dispersion (Df) – dimorphic attributes of the human voice – are related to sociosexuality, as measured by the Revised Sociosexual Orientation Inventory (SOI-R) – a trait also known to exhibit sex differences – in a sample of native Spanish-speaking students (101 males, 147 females). Analyses showed a significant negative correlation between F0 and sociosexual behavior, and between Pf and sociosexual desire in males but not in females. These correlations remained significant after correcting for false discovery rate (FDR) and controlling for age, a potential confounding variable. Our results are consistent with a role of F0 and Pf serving as cues in the mating domain in males but not in females. Alternatively, the association of voice attributes and sociosexual orientation might stem from the parallel effect of male sex hormones both on the male brain and the anatomical structures involved in voice production.
Construction and validation of a musculoskeletal disease risk prediction model for underground coal miners
Authors: Zhao Haili , Dou Hong , Yong Xianting , Liu Wei , Yalimaimaiti Saiyidan , Yang Ying , Liang Xiaoqiao , Sun Lili , Liu Jiwen , Ning Li
Published: July 2023

Objective

To understand the prevalence among underground coal miners of musculoskeletal disorders (MSDs), analyze the risk factors affecting MSDs, and develop and validate a risk prediction model for the development of MSDs.

Materials and methods

MSD questionnaires were used to investigate the prevalence of work-related musculoskeletal disorders among 860 underground coal miners in Xinjiang. The Chinese versions of the Effort-Reward Imbalance Questionnaire (ERI), the Burnout Scale (MBI), and the Self-Rating Depression Inventory (SDS) were used to investigate the occupational mental health status of underground coal miners. The R4.1.3 software cart installation package was applied to randomly divide the study subjects into a 1:1 training set and validation set, screen independent predictors using single- and multi-factor regression analysis, and draw personalized nomogram graph prediction models based on regression coefficients. Subject work characteristic (ROC) curves, calibration (Calibrate) curves, and decision curves (DCA) were used to analyze the predictive value of each variable on MSDs and the net benefit.

Results

(1) The prevalence of MSDs was 55.3%, 51.2%, and 41.9% since joining the workforce, in the past year, and in the past week, respectively; the highest prevalence was in the lower back (45.8% vs. 38.8% vs. 33.7%) and the lowest prevalence was in the hips and buttocks (13.3% vs. 11.4% vs. 9.1%) under different periods. (2) Underground coal miners: the mean total scores of occupational stress, burnout, and depression were 1.55 ± 0.64, 51.52 ± 11.53, and 13.83 ± 14.27, respectively. (3) Univariate regression revealed a higher prevalence of MSDs in those older than 45 years (49.5%), length of service > 15 years (56.4%), annual income <$60,000 (79.1%), and moderate burnout (43.2%). (4) Binary logistic regression showed that the prevalence of MSDs was higher for those with 5–20 years of service (OR = 0.295, 95% CI: 0.169–0.513), >20 years of service (OR = 0.845, 95% CI: 0.529–1.350), annual income ≥$60,000 (OR = 1.742, 95% CI: 1.100–2.759), and severe burnout (OR = 0.284, 95% CI: 0.109–0.739), and that these were independent predictors of the occurrence of MSDs among workers in underground coal mine operations (p <  0.05). (5) The areas under the ROC curve for the training and validation sets were 0.665 (95% CI: 0.615–0.716) and 0.630 (95% CI: 0.578–0.682), respectively, indicating that the model has good predictive ability; the calibration plots showed good agreement between the predicted and actual prevalence of the model; and the DCA curves suggested that the predictive value of this nomogram model for MSDs was good.

Conclusion

The prevalence of MSDs among workers working underground in coal mines was high, and the constructed nomogram showed good discriminatory ability and optimal accuracy.
How to move towards One Health surveillance? A qualitative study exploring the factors influencing collaborations between antimicrobial resistance surveillance programmes in France
Authors: Bourély Clémence , Rousset Léo , Colomb-Cotinat Mélanie , Collineau Lucie
Published: July 2023

Introduction

Antimicrobial resistance (AMR) is a major public health issue, against which international organisations and governmental bodies call for integration between surveillance programmes involved in human, animal, and environmental sectors. Collaborations are the primary feature of integration and deserve to be supported. However, little is known about the factors that can foster collaborations between surveillance programmes. This study aimed to provide a better understanding of the factors for setting-up collaborations between AMR surveillance programmes in France.

Methods

We performed a qualitative study based on 36 semi-structured interviews with programmes’ coordinators and 15 with key-informant experts involved in AMR surveillance.

Results

The implementation of collaboration between sectors was multifactorial: we identified 42 factors grouped into six categories (i.e., characteristics of the overall AMR surveillance system, features of the collaborating programme, profile of the actors involved, characteristics of the collaboration itself, broader context, and AMR research activities). Collaborations were mainly fostered by good interpersonal relationship between actors, their interest in transdisciplinary approaches and the benefits of collaboration on the programmes involved. Limited resources and the complexity of the AMR surveillance system hindered collaboration. Paradoxically, coordinators generally did not perceive collaborations as a resource-pooling tool since they generally set them up only after consolidating their own programme.

Discussion

Since most factors identified were not specific to AMR, these results can be useful for other collaborative surveillance system. Ultimately, they provide a better understanding of stakeholders’ motivations and influences driving collaboration, and can help researchers and risk managers promoting a One Health approach against public health threats.