bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of abnormalities at the neuromuscular junction in the SOD1-G93A mouse model of ALS: dysfunction then disruption of postsynaptic structure precede overt motor symptoms
Authors: McIntosh Jayne , Mekrouda Imane , Dashti Maryam , Giuraniuc Claudiu V. , Banks Robert W. , Miles Gareth B. , Bewick Guy S.
Published: May 2023

Introduction

The ultimate deficit in amyotrophic lateral sclerosis (ALS) is neuromuscular junction (NMJ) loss, producing permanent paralysis, ultimately in respiratory muscles. However, understanding the functional and structural deficits at NMJs prior to this loss is crucial for therapeutic strategy design. Should early interventions focus on reversing denervation, or supporting largely intact NMJs that are functionally impaired? We therefore determined when functional and structural deficits appeared in diaphragmatic NMJs relative to the onset of hindlimb tremor (the first overt motor symptoms) in vivo in the SOD1-G93A mouse model of ALS.

Materials and methods

We employed electrophysiological recording of NMJ postsynaptic potentials for spontaneous and nerve stimulation-evoked responses. This was correlated with fluorescent imaging microscopy of the postsynaptic acetylcholine receptor (AChR) distribution throughout the postnatal developmental timecourse from 2 weeks to early symptomatic ages.

Results

Significant reduction in the amplitudes of spontaneous miniature endplate potentials (mEPPs) and evoked EPPs emerged only at early symptomatic ages (in our colony, 18-22 weeks). Reductions in mEPP frequency, number of vesicles per EPP, and EPP rise time were seen earlier, at 16weeks, but this reversed by early symptomatic ages. However, the earliest and most striking impairment was an inability to maintain EPP amplitude during a 20 Hz stimulus train, which appeared 6 weeks before overt in vivo motor symptoms. Despite this, fluorescent α-bungarotoxin labelling revealed no systematic, progressive changes in 11 comprehensive NMJ morphological parameters (area, shape, compactness, number of acetylcholine receptor, AChR, regions, etc.) with disease progression. Rather, while NMJs were largely normally-shaped, from 16 weeks there was a progressive and substantial disruption in AChR concentration and distribution within the NMJ footprint.

Discussion

Thus, NMJ functional deficits appear at least 6 weeks before motor symptoms in vivo, while structural deficits occur 4 weeks later, and predominantly within NMJs. These data suggest initial therapies focused on rectifying suboptimal NMJ function could produce effective relief of symptoms of weakness.
The association between diet quality index-international and inflammatory markers in Iranian overweight and obese women
Authors: Shiraseb Farideh , Ebrahimi Sara , Noori Sahar , Bagheri Reza , Alvarez-Alvarado Stacey , Wong Alexei , Mirzaei Khadijeh
Published: May 2023

Objectives

The present study was conducted to evaluate whether there is a link between the diet quality index (DQI) and markers of systemic inflammation in Iranian overweight and obese women.

Methods

This cross-sectional study included 200 Iranian overweight and obese women aged 18–48 years. The DQI-international (DQI-I) comprises four main components: variety, adequacy, moderation, and overall balance. Blood samples were collected in a fasted state to measure inflammatory markers.

Results

After adjusting for age, body mass index (BMI), physical activity, total energy intake, economic status, education, supplement intake, age of starting obesity, and history of body mass loss, a marginally significant negative association was observed between the homeostasis model assessment of insulin resistance (HOMA–IR) and the DQI–I (β: −0.015, 95% CI: −0.03, 0.000; p = 0.061). The results after adjustment showed that DQI–I has a negative association with high-sensitivity C-reactive protein (hs–CRP) concentrations (β: −0.031, 95% CI: −0.104, −0.031; p = 0.023). Furthermore, negative associations were observed between the adequacy component and levels of HOMA–IR (β: −0.025, 95% CI: −0.100, 0.047, p = 0.050) and hs-CRP (β: −0.615, 95% CI: −1.191, −0.020; p = 0.045). In addition, negative associations were found between transforming growth factor-β (TGF-β) and balance score (β: −6.270, 95% CI: −39.211, −3.661, p = 0.020), as well as HOMA–IR (β: −0.080, 95% CI: −0.202, −0.000, p = 0.041) and chemoattractant protein−1 (MCP−1) (β: −0.562, 95% CI: −11.414, −0.282, p = 0.021), with the various component. A marginally significant negative association between galectin 3 (Gal-3) and moderation score (β: −0.451, 95% CI: −1.171, 0.060, p = 0.060) was found. In addition, a marginally significant inverse association was also established between hs–CRP and variety score (β: −0.311, 95% CI: −0.970, 0.001, p = 0.052). The Receiver Operating characteristic (ROC) curve analysis demonstrated that DQI–I might better predict HOMA–IR with a cut point of 3.13 (AUC = 0.698, 0.511–0.699, p = 0.050).

Conclusion

These findings showed that a higher adherence to diet quality and its components could probably be related to lowering the inflammatory markers considerably in overweight and obese women.
Widely targeted metabolomics reveals the antioxidant and anticancer activities of different colors of Dianthus caryophyllus
Authors: Zhou Xuhong , Wang Miaomaio , Li Hong , Ye Shilong , Tang Wenru
Published: May 2023

Carnation is edible flower that has potent antioxidant properties and is used in traditional Chinese medicinal system and food industry. The phytochemicals responsible for these various proprieties, however, are not fully understood. Thus, in order to recognize metabolite diversity and variability in carnation flowers of different colors and to discover key metabolites that contribute to the differences in antioxidant and anticancer activities, widely targeted LC-MS/MS-based metabolomics analysis was conducted on purple, green, yellow, and white carnation flowers. We identified and chemically categorized 932 metabolites. Metabolic compounds varied significantly with flower color. Several flavonoids, organic acids, phenolic acids, and nucleotides and their derivatives were found to be specific differential metabolites in purple flowers. A total of 128 key differential metabolites were screened. The purple flowers were found to have the highest antioxidant and anticancer activities compared to the other colored flowers. Correlation analysis revealed that the 6-hydroxykaempferol-3,6-O-diglucoside, 6-hydroxykaempferol-7-O-glucoside, quercetin-3-O-sophoroside, and 2′-deoxyguanosine were found to be the major constituents of the antioxidant and anticancer activities. 2′-Deoxyguanosine has effective antiproliferative activity against A549 and U2OS cells for the first report. At the same time, the combination of 2′-deoxyguanosine with 6-hydroxykaempferol-3, 6-O-diglucoside, or quercetin-3-O-sophoroside have also been found to increase the antitumor activity of 2′-deoxyguanosine. These discoveries enrich information on the phytochemical composition of carnation of different colors and provide resources for the overall use and improvement of carnation flowers quality.
Comprehensive metabolic analyses provide new insights into primary and secondary metabolites in different tissues of Jianghua Kucha tea (Camellia sinensis var. assamica cv. Jianghua)
Authors: Wu Wenliang , Shi Jiang , Jin Jiqiang , Liu Zhen , Yuan Yong , Chen Zhida , Zhang Shuguang , Dai Weidong , Lin Zhi
Published: May 2023

Background

Jianghua Kucha (JHKC) is a special tea germplasm with enriched specialized secondary metabolites, including theacrine, non-epimeric flavanols and methylated flavanols. Moreover, primary metabolites provide precursors and energy for the production of secondary metabolites. However, the accumulation patterns of primary and secondary metabolites in different tissues of JHKC are unclear.

Methods

The changes of primary and secondary metabolites and related metabolic pathways (primary and secondary metabolism) in different JHKC tissues (the bud, 1st-4th leaves, and new stem) were investigated via metabolomics analysis with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS).

Results

Significant differences were observed in 68 primary and 51 secondary metabolites mainly related with the pathways of starch and sucrose, amino acids, caffeine, and flavanols metabolism and TCA cycle. The bud exhibited higher levels of glucose-6-phosphate, citric acid, most amino acids, theobromine, catechin-gallate, epicatechin-gallate, procyanidins, and theasinensins; the 1st leaf showed higher levels of caffeine and epigallocatechin-3-gallate; and the 4th leaf contained higher levels of most monosaccharides, theacrine, and epigallocatechin-3-O-(3”-O-methyl)-gallate. In addition, primary metabolites and important secondary metabolites had certain correlations.

Conclusion

This study provides comprehensive insight into primary and secondary metabolites in JHKC and offers guidelines for efficiently utilizing specialized metabolites of JHKC in the future.
Acute radiotherapy-associated oral pain may promote tumor growth at distant sites
Authors: Meneses Constanza S. , Gidcumb Emily M. , Marcus Karen L. , Gonzalez Yarines , Lai Yen Hao , Mishra Santosh K. , Lascelles B. Duncan X. , Nolan Michael W.
Published: May 2023

Introduction

Patients developing acute radiotherapy induced dermatitis or oral mucositis commonly experience pain. When severe, this radiotherapy-associated pain (RAP) can necessitate treatment breaks; unfortunately, in a variety of cancers, prolongation of the radiotherapy course has been associated with early cancer relapse and/or death. This is often attributed to accelerated repopulation, but it is unknown whether pain or pain signaling constituents might alter tumor behavior and hasten metastatic disease progression. We studied this by testing the hypothesis that severe acute RAP at one site can hasten tumor growth at a distant site.

Methods

Mice underwent single fraction tongue irradiation (27 Gy, or 0 Gy “sham” control) to induce severe glossitis. At the time of maximal oral RAP, one of three luciferase-transfected tumor cell lines were injected via tail vein (4T1, B16F10, MOC2; each paired to their syngeneic host: BALB/c or C57BL/6); tumor burden was assessed via in vivo transthoracic bioluminescence imaging and ex vivo pulmonary nodule quantification. Survival was compared using Kaplan-Meier statistics.

Results

Tongue irradiation and resultant RAP promoted lung tumor growth of 4T1-Luc2 cells in BALB/c mice. This effect was not a result of off-target radiation, nor an artefact of environmental stress caused by standard (subthermoneutral) housing temperatures. RAP did not affect the growth of B16F10-Luc2 cells, however, C57BL/6 mice undergoing tail vein injection of MOC2-Luc2 cells at the time of maximal RAP experienced early lung tumor-attributable death. Lung tumor growth was normalized when RAP was reduced by treatment with resiniferatoxin (300 µg/kg, subcutaneously, once).

Discussion

This research points towards radiation-induced activation of capsaicin-responsive (TRPV1) neurons as the cause for accelerated growth of tumors at distant (unirradiated) sites.
Junction of the redox dynamic, orchestra of signaling, and altered metabolism in regulation of T- cell lymphoma
Authors: Singh Shantanu , Maurya Akhilendra Kumar
Published: May 2023

T-cell lymphoma is a hematologic neoplasm derived from the lymphoid lineage. It belongs to a diverse group of malignant disorders, mostly affecting the young population worldwide, that vary with respect to molecular features as well as genetic and clinical complexities. Cancer cells rewire the cellular metabolism, persuading it to meet new demands of growth and proliferation. Furthermore, the metabolic alterations and heterogeneity are aberrantly driven in cancer by a combination of genetic and non-genetic factors, including the tumor microenvironment. New insight into cancer metabolism highlights the importance of nutrient supply to tumor development and therapeutic responses. Importantly, oxidative stress due to an imbalance in the redox status of reactive speciesviaexogenous and/or endogenous factors is closely related to multiple aspects of cancer. This alters the signaling pathways governed through the multiple intracellular signal transduction and transcription factors, leading to tumor progression. These oncogenic signaling molecules are regulated through different redox sensors, including nuclear factor-erythroid 2 related factor 2 (Nrf2), phase-II antioxidant enzyme, and NQO1 (NADPH quinone oxidoreductase (1). The existing understanding of the molecular mechanisms of T-cell lymphoma regulation through the cross-talk of redox sensors under the influence of metabolic vulnerability is not well explored. This review highlights the role of the redox dynamics, orchestra of signaling, and genetic regulation involved in T-cell lymphoma progression in addition to the challenges to their etiology, treatment, and clinical response in light of recent updates.
Characterization of LIMA1 and its emerging roles and potential therapeutic prospects in cancers
Authors: Wang Xiaoxiao , Zhang Chao , Song Huangqin , Yuan Junlong , Zhang Xiaomin , Yuan Yiran , Zhang Lei , He Jiefeng
Published: May 2023

Actin is the most abundant and highly conserved cytoskeletal protein present in all eukaryotic cells. Remodeling of the actin cytoskeleton is controlled by a variety of actin-binding proteins that are extensively involved in biological processes such as cell motility and maintenance of cell shape. LIM domain and actin-binding protein 1 (LIMA1), as an important actin cytoskeletal regulator, was initially thought to be a tumor suppressor frequently downregulated in epithelial tumors. Importantly, the deficiency of LIMA1 may be responsible for dysregulated cytoskeletal dynamics, altered cell motility and disrupted cell-cell adhesion, which promote tumor proliferation, invasion and migration. As research progresses, the roles of LIMA1 extend from cytoskeletal dynamics and cell motility to cell division, gene regulation, apical extrusion, angiogenesis, cellular metabolism and lipid metabolism. However, the expression of LIMA1 in malignant tumors and its mechanism of action have not yet been elucidated, and many problems and challenges remain to be addressed. Therefore, this review systematically describes the structure and biological functions of LIMA1 and explores its expression and regulatory mechanism in malignant tumors, and further discusses its clinical value and therapeutic prospects.
Cutaneous malignancies in patients with Parkinson’s disease at a dermato-oncological university centre in Hungary
Authors: Tóth Veronika , Diakoumakou Stefani Christina , Kuroli Enikő , Tóth Béla , Kuzmanovszki Daniella , Szakonyi József , Lőrincz Kende Kálmán , Somlai Beáta , Kárpáti Sarolta , Holló Péter
Published: May 2023

Background

The possible correlation between melanoma and Parkinson’s disease (PD) has been intensively studied. In this work, we aimed to assess the coincidence of skin malignancies and PD at a dermato-oncological university centre in Central-Eastern Europe, Hungary.

Methods

From 2004 to 2017, a retrospective analysis of the centre’s database was performed based on International Statistical Classification of Diseases-10 codes.

Results

Out of the patients who visited the clinic during the study period, 20,658 were treated for malignant skin tumours. Over the 14 years, 205 dermatological patients had PD simultaneously, 111 (54%) of whom had at least one type of skin malignancy: melanoma (n=22), basal cell carcinoma (BCC) (n=82), or squamous cell carcinoma (SCC) (n=36) (in some patients, multiple skin tumours were identified). Compared to the age- and sex-matched control group, patients with PD had a significantly lower risk for basal cell carcinoma (OR, 0.65; 95% CI, 0.47–0.89, p=0.0076) and for all skin tumours (OR, 0.74; 95% CI, 0.56–0.98, p=0.0392) but not for melanoma.

Conclusions

We found a decreased risk of all skin tumours and basal cell carcinoma and an unchanged risk of melanoma among patients with PD. However, it should be kept in mind that some large-scale meta-analyses suggest a higher incidence of melanoma after a diagnosis of PD, indicating the importance of skin examination in this vulnerable population.
Relapse of skull osteoma after hydroxyapatite cement cranioplasty: Case Report
Authors: Yang Xiang , Liu Yanhui , Zhang Yuekang
Published: May 2023

In this case report, we present an extremely rare and previously unreported case of skull osteoma relapse without any attachment to the skull after hydroxyapatite cement (HAC) cranioplasty. The 49-year-old male patient was admitted with recurrence of the left frontal skull lesion; he underwent craniectomy and HAC cranioplasty for a left frontal osteoma 14 years before. Intraoperative findings disclosed multiple irregular lesions located on the HAC flap without any attachment to the bony structure and the roots of the lesions originating from the outer layer of the dura through several reserved holes. Pathological diagnosis was osteoma. The purpose of this report is to document this rare occurrence and provide the most probable pathogenesis for this rare event.
Venetoclax plus cyclophosphamide and cytarabine as induction regimen for adult acute myeloid leukemia
Authors: Zhang Baohang , Liu Qingguo , Li Junfan , Hu Yimin , Zhao Xin , Huang Pingping , Li Shangzhu , Wang Ying
Published: May 2023

Background

The efficacy of induction chemotherapy (IC) for acute myeloid leukemia (AML) has improved significantly with the application of targeting drugs. Our previous study showed that a 4-day IC regimen of cyclophosphamide (CTX) and Ara-C [CA (4 + 3)] achieved similar complete remission (CR) rate (80%) compared with the traditional 7-day regimen, and the survival rate appeared to be better.

Methods

In this pilot study, we further shortened the CA regimen to 3 days, added low-dose venetoclax (VEN, 200 mg/day) (VCA), and reported the efficacy and safety here.

Results

Twenty-five newly diagnosed adult AML patients were enrolled in this study and evaluated for the remission rate after one cycle of the VCA regimen. The CR/Cri was 92%, and all these patients had undetectable minimal residual disease (MRD−). The estimated overall survival at 12 months was 79.3%. The median time for both platelet recovery and absolute neutrophil count recovery was 16 days, faster than that of traditional IC. Compared with the previous CA (4 + 3) regimen, a higher CR rate (92% vs. 80%, P < 0.01) and a deeper degree of remission (CRMRD− rate, 92% vs. 45%, P < 0.01) were found in the VCA group.

Conclusions

This study showed that the 3-day CTX and Ara-C regimen is highly effective in newly diagnosed AML patients, and the addition of VEN to the CA regimen achieves higher and deeper one-course remission.
Thoracic epidural analgesia prolongs postoperative QT interval on electrocardiogram in major non-cardiac surgery: a randomized comparison and a prospective cohort analysis
Authors: Hori Kotaro , Tsujikawa Shogo , Egami Mika , Waki Sayaka , Watanabe Ryota , Hino Hideki , Matsuura Tadashi , Mori Takashi
Published: May 2023

Introduction: Prolongation of QT interval on electrocardiogram can be associated with perioperative lethal arrhythmia. Epidural analgesia is a commonly used modality to relieve surgical pain by blocking sensory nerves, which also blocks the autonomic nervous system and can affect QT interval. Since patient monitoring becomes much less frequent after surgery than intraoperative period, we investigated the effects of epidural analgesia on postoperative QT interval with a randomized clinical trial and a prospective cohort study.

Methods: In a randomized study, we assigned 60 patients undergoing thoracic epidural analgesia to an epidural analgesia or no-epidural analgesia group, in which 3 ml/h of 0.25% epidural levobupivacaine (7.5 mg/h) was administered only in the epidural analgesia group during surgery. The primary outcome was the postoperative heart rate-corrected QT interval. In a prospective cohort study, patients were assigned to receive 5 ml/h epidural levobupivacaine (12.5 mg/h). The plasma concentration of levobupivacaine was measured using liquid chromatography-mass spectrometry.

Results: The median postoperative corrected QT interval interval with 3 ml/h epidural levobupivacaine was significantly longer than that without epidural analgesia. Using multiple regression analysis for the factors known to affect postoperative corrected QT interval interval, epidural analgesia was found to be an independent variable for prolongation, and the mean difference of the corrected QT interval interval with or without epidural analgesia was 23 ms after adjustment. The median plasma concentration of levobupivacaine at the end of surgery was 164 ng/ml with 3 ml/h epidural levobupivacaine, and the correlation coefficient to the postoperative corrected QT interval interval was 0.14, showing a not significant correlation. A prospective cohort study showed that 5 ml/h epidural levobupivacaine significantly prolonged postoperative corrected QT interval interval compared to preoperative baseline. The median plasma concentration of levobupivacaine was 166 ng/ml with 5 ml/h, the correlation coefficient of which showed no significant correlation.

Conclusion: Thoracic epidural analgesia could enhance postoperative corrected QT interval prolongation after general anesthesia. The mechanism is possibly caused by blocking neighboring or part of the cardiac sympathetic nerves, rather than by systemic effects of epidurally administered levobupivacaine.

Clinical trial number: UMIN000013347 for the randomized study and UMIN000041518 for the prospective cohort study, which were registered at University hospital Medical Information Network Center.
Feature semantic alignment and information supplement for Text-based person search
Authors: Zhou Hang , Li Fan , Tian Xuening , Huang Yuling
Published: May 2023

The goal of person text-image matching is to retrieve images of specific pedestrians using natural language. Although a lot of research results have been achieved in persona text-image matching, existing methods still face two challenges. First,due to the ambiguous semantic information in the features, aligning the textual features with their corresponding image features is always tricky. Second, the absence of semantic information in each local feature of pedestrians poses a significant challenge to the network in extracting robust features that match both modalities. To address these issues, we propose a model for explicit semantic feature extraction and effective information supplement. On the one hand, by attaching the textual and image features with consistent and clear semantic information, the course-grained alignment between the textual and corresponding image features is achieved. On the other hand, an information supplement network is proposed, which captures the relationships between local features of each modality and supplements them to obtain more complete local features with semantic information. In the end, the local features are then concatenated to a comprehensive global feature, which capable of precise alignment of the textual and described image features. We did extensive experiments on CUHK-PEDES dataset and RSTPReid dataset, the experimental results show that our method has better performance. Additionally, the ablation experiment also proved the effectiveness of each module designed in this paper.
Social dynamics through kinetic exchange: the BChS model
Authors: Biswas Soumyajyoti , Chatterjee Arnab , Sen Parongama , Mukherjee Sudip , Chakrabarti Bikas K.
Published: May 2023

This review presents an overview of the current research in kinetic exchange models for opinion formation in a society. The review begins with a brief introduction to previous models and subsequently provides an in-depth discussion of the progress achieved in the Biswas-Chatterjee-Sen model proposed in 2012, also known as the BChS model in some later research publications. The unique feature of the model is its inclusion of negative interaction between agents. The review covers various topics, including phase transitions between different opinion states, critical behavior dependent on various parameters, and applications in realistic scenarios such as the United States presidential election and Brexit.
Biological sex differences in renin angiotensin system enzymes ACE and ACE2 regulate normal tissue response to radiation injury
Authors: Sharma Guru Prasad , Frei Anne , Fish Brian , Gasperetti Tracy , Veley Dana , Szalewski Nathan , Nissen Austen , Himburg Heather A.
Published: May 2023

Introduction: In experimental animal models, biological sex-differences in the manifestation and severity of normal tissue radiation injury have been well-documented. Previously we demonstrated male and female rats have differential and highly reproducible responses to high-dose partial body irradiation (PBI) with male rats having greater susceptibility to both gastrointestinal acute radiation syndrome (GI-ARS) and radiation pneumonitis than female rats.

Methods: In the current study, we have investigated whether differential expression of the renin-angiotensin system (RAS) enzymes angiotensin converting enzyme (ACE) and ACE2 contribute to the observed sex-related differences in radiation response.

Results: During the period of symptomatic pneumonitis, the relative ratio of ACE to ACE2 (ACE/ACE2) protein in the whole lung was significantly increased by radiation in male rats alone. Systemic treatment with small molecule ACE2 agonist diminazene aceturate (DIZE) increased lung ACE2 activity and reduced morbidity during radiation pneumonitis in both sexes. Notably DIZE treatment also abrogated morbidity in male rats during GI-ARS. We then evaluated the contribution of the irradiated bone marrow (BM) compartment on lung immune cell infiltration and ACE imbalance during pneumonitis. Transplantation of bone marrow from irradiated donors increased both ACE-expressing myeloid cell infiltration and immune ACE activity in the lung during pneumonitis compared to non-irradiated donors.

Discussion: Together, these data demonstrate radiation induces a sex-dependent imbalance in the renin-angiotensin system enzymes ACE and ACE2. Additionally, these data suggest a role for ACE-expressing myeloid cells in the pathogenesis of radiation pneumonitis. Finally, the observed sex-differences underscore the need for consideration of sex as a biological variable in the development of medical countermeasures for radiation exposure.
Mapping of the bs5 and bs6 non-race-specific recessive resistances against bacterial spot of pepper
Authors: Sharma Anuj , Li Jian , Wente Rebecca , Minsavage Gerald V. , Gill Upinder S. , Ortega Arturo , Vallejos C. Eduardo , Hart John P. , Staskawicz Brian J. , Mazourek Michael R. , Stall Robert E. , Jones Jeffrey B. , Hutton Samuel F.
Published: May 2023

Bacterial spot caused by Xanthomonas euvesicatoria is a major disease of pepper (Capsicum annuum L.) in warm and humid production environments. Use of genetically resistant cultivars is an effective approach to manage bacterial spot. Two recessive resistance genes, bs5 and bs6, confer non-race-specific resistance against bacterial spot. The objective of our study was to map these two loci in the pepper genome. We used a genotyping-by-sequencing approach to initially map the position of the two resistances. Segregating populations for bs5 and bs6 were developed by crossing susceptible Early CalWonder (ECW) with near-isogenic lines ECW50R (bs5 introgression) or ECW60R (bs6 introgression). Following fine-mapping, bs5 was delimited to a ~535 Kbp interval on chromosome 3, and bs6 to a ~666 Kbp interval in chromosome 6. We identified 14 and 8 candidate resistance genes for bs5 and bs6, respectively, based on predicted protein coding polymorphisms between ECW and the corresponding resistant parent. This research enhances marker-assisted selection of bs5 and bs6 in breeding programs and is a crucial step towards elucidating the molecular mechanisms underlying the resistances.
Site-specific gene knock-in and bacterial phytase gene expression in Chlamydomonas reinhardtii via Cas9 RNP-mediated HDR
Authors: Zadabbas Shahabadi Hassan , Akbarzadeh Arash , Ofoghi Hamideh , Kadkhodaei Saeid
Published: May 2023

In the present study, we applied the HDR (homology-directed DNA repair) CRISPR-Cas9-mediated knock-in system to accurately insert an optimized foreign bacterial phytase gene at a specific site of the nitrate reductase (NR) gene (exon 2) to achieve homologous recombination with the stability of the transgene and reduce insertion site effects or gene silencing. To this end, we successfully knocked-in the targeted NR gene of Chlamydomonas reinhardtii using the bacterial phytase gene cassette through direct delivery of the CRISPR/Cas9 system as the ribonucleoprotein (RNP) complex consisting of Cas9 protein and the specific single guide RNAs (sgRNAs). The NR insertion site editing was confirmed by PCR and sequencing of the transgene positive clones. Moreover, 24 clones with correct editing were obtained, where the phytase gene cassette was located in exon 2 of the NR gene, and the editing efficiency was determined to be 14.81%. Additionally, site-specific gene expression was analyzed and confirmed using RT-qPCR. Cultivation of the positive knocked-in colonies on the selective media during 10 generations indicated the stability of the correct editing without gene silencing or negative insertion site effects. Our results demonstrated that CRISPR-Cas9-mediated knock-in could be applied for nuclear expression of the heterologous gene of interest, and also confirmed its efficacy as an effective tool for site-specific gene knock-in, avoiding nuclear positional effects and gene silencing in C. reinhardtii. These findings could also provide a new perspective on the advantageous application of RNP-CRISPR/Cas9 gene-editing to accelerate the commercial production of complex recombinant proteins in the food-grade organism “C. reinhardtii”.
Policy incentives for smallholder adoption of climate-smart agricultural practices
Authors: van Asseldonk Marcel , Girvetz Evan , Pamuk Haki , Wattel Cor , Ruben Ruerd
Published: May 2023

There is a large and growing literature on the potential use of policy instruments for stimulating the adoption of Climate-Smart Agriculture (CSA) practices amongst smallholders. The objective of this article is to review and understand how the array of potential policy incentives can serve as mechanisms for enhancing adoption and upscaling of potential CSA practices by small-scale farmers in low-income countries. The review follows a matrix approach capturing where specific CSA practices (rows) are supported by typical policy instruments (columns) for enhancing widespread adoption. We first identify six key CSA practices, namely water management, soil and nutrient management, crop tolerance to stress, agroforestry and intercropping, crop rotation and mixed systems, and pest and disease management. Then we discuss the impact of those typical policy instruments, namely market prices, taxes and subsidies, land rights, rural finance, training and information, and certification and labeling. The review finds that most studies on this subject have a rather narrow focus on functional properties of a specific policy instrument and a particular CSA practice, thereby ignoring substitution, complementary or conditional effects between policy measures and CSA practices. Consequently, previous studies identify few incentives, particularly effective on their own. Wider perspectives on impact pathways point to the importance of sequencing and scaling for enhancing farmers' CSA adoption. We therefore advocate for more integrated approaches that also consider indirect effects of policy instruments on CSA adoption and pursue their systematic anchoring through successful policies that enhance widespread adoption.
Effectiveness and mechanisms of the arts therapies in forensic care. A systematic review, narrative synthesis, and meta analysis
Authors: Abbing Annemarie , Haeyen Suzanne , Nyapati Sashank , Verboon Peter , Hooren Susan van
Published: May 2023

Introduction

Mental health care provided to offenders with psychiatric problems in forensic settings mainly consists of verbal oriented treatments. In addition, experience-based therapies are used such as (creative) arts therapies: (visual) art therapy, music therapy, drama therapy and dance (movement) therapy. There are indications for effectiveness of arts therapies, but a systematic overview of effect studies of all arts therapies in forensic care is lacking.

Methods

First, we performed a systematic review. Second, Thematic Analysis was used to synthesize the qualitative narrative results and define the hypothesized mechanisms of change. Third, we performed a meta-analysis to investigate the effects of arts therapies in reducing psychosocial problems of offenders. Twenty-three studies were included in the review. Quality and risk of bias was assessed using EPHPP (Effective Public Health Practice Project).

Results

The included studies were heterogeneous in type of outcome measures and intervention characteristics. Synthesis of mechanisms of change involved in the methodical use of the arts in arts therapies resulted in a description of regulatory processes which are stimulated in arts therapies: perceptive awareness (interoceptive and exteroceptive), the regulation of emotions, stress, impulses, cognitions, social regulation, and self-expression. These processes play a role in developing prevention, coping and self-management skills. Eighteen studies were included in the meta-analyses (11 RCTs/CCTs; 7 pre-post studies). The meta-analyses indicated significant effects on both risk factors (psychiatric symptoms and addiction) and protective factors for criminal behavior (social functioning and psychological functioning). Effects on criminal and/or antisocial behavior were not significant, but this outcome measure was scarcely used among the studies.

Discussion

The analyses in this study should be considered explorative. More research is needed to gain more solid conclusions about effectiveness and mechanisms of change of arts therapies in forensic institutions. However, the results of this first systematic review, synthesis of mechanisms and meta-analysis in this field are promising and show effects of arts therapies on risk and protective factors in individuals in forensic institutions.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020217884, identifier: CRD42020217884.
Cigarette smoking and risk of suicide in bipolar disorder: a systematic review
Authors: García-Jiménez Jesús , Gómez-Sierra Francisco José , Martínez-Hortelano Alicia , Moreno-Merino Paula , Girela-Serrano Braulio , Molero Patricio , Gutiérrez-Rojas Luis
Published: May 2023

Objective

Bipolar disorder (BD) is a highly prevalent, chronic and recurrent mental illness. The smoking rates in patients with BD are much higher than those of the general population, and BD is associated with an increased risk of suicide. An association between smoking and suicidal behavior has been found in the general population, this systematic review examines whether there is evidence of an association between smoking and suicide behavior in patients with BD.

Method

A database search was carried out in Medline, Embase, The Cochrane Library, Scopus, and Web of Science, updated until December 31st, 2021, according to the 2020 PRISMA guidelines. We identified prospective and retrospective studies that included patients diagnosed with BD types I, II, and not otherwise specified, and in which smoking and suicidal behavior were correlated. Articles that focused exclusively on other mental disorders were excluded. The Ottawa-Newcastle scale was used to assess the methodological quality of the included articles.

Results

Fifteen articles (n = 7,395) met all the inclusion criteria. In nine of these articles, the authors found an association between smoking and suicidal behavior in BD, while in the remaining six articles, this association was not found. A great deal of variability was observed between articles, particularly in the measurement of suicidal behavior and tobacco consumption. The risk of bias, as assessed by the NOS, was high for most of the included articles, except for two papers, whose risk was low.

Conclusion

It was not possible to establish a clear relationship between tobacco use and the risk of suicide in BD patients due to the heterogeneity of the articles included in this systematic review, which had different sample sizes and methodological issues. However, both conditions are highly prevalent and have a negative impact on the prognosis of BD. Therefore, a systematic approach is needed, based on accurate measurement of a patient’s smoking habits and their risk of suicidal behavior, in order to establish an appropriate therapeutic plan.

Additional information

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors and was registered on PROSPERO with the CRD42022301570 on January 21th 2022.
Decreased plasma neuropeptides in first-episode schizophrenia, bipolar disorder, major depressive disorder: associations with clinical symptoms and cognitive function
Authors: Yu Hua , Ni Peiyan , Zhao Liansheng , Tian Yang , Li Mingli , Li Xiaojing , Wei Wei , Wei Jinxue , Deng Wei , Du Xiangdong , Wang Qiang , Guo Wanjun , Ma Xiaohong , Coid Jeremy , Li Tao
Published: May 2023

Background

There is an urgent need to identify differentiating and disease-monitoring biomarkers of schizophrenia, bipolar disorders (BD), and major depressive disorders (MDD) to improve treatment and management.

Methods

We recruited 54 first-episode schizophrenia (FES) patients, 52 BD patients, 35 MDD patients, and 54 healthy controls from inpatient and outpatient clinics. α-Melanocyte Stimulating Hormone (α-MSH), β-endorphin, neurotensin, orexin-A, oxytocin, and substance P were investigated using quantitative multiplex assay method. Psychotic symptoms were measured using the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS), manic symptoms using the Young Mania Rating Scale (YMRS), and depressive symptoms using 17 item-Hamilton Depression Rating Scale (HAMD). We additionally measured cognitive function by using a battery of tests given to all participants.

Results

α-MSH, neurotensin, orexin-A, oxytocin, and substance P were decreased in the three patient groups compared with controls. Neurotensin outperformed all biomarkers in differentiating patient groups from controls. There were no significant differences for 6 neuropeptides in their ability to differentiate between the three patient groups. Higher neurotensin was associated with better executive function across the entire sample. Lower oxytocin and higher substance p were associated with more psychotic symptoms in FES and BD groups. β-endorphin was associated with early morning wakening symptom in all three patient groups.

Conclusion

Our research shows decreased circulating neuropeptides have the potential to differentiate severe mental illnesses from controls. These neuropeptides are promising treatment targets for improving clinical symptoms and cognitive function in FES, BD, and MDD.
Unraveling the pathophysiology of schizophrenia: insights from structural magnetic resonance imaging studies
Authors: Adamu Mohammed Jajere , Qiang Li , Nyatega Charles Okanda , Younis Ayesha , Kawuwa Halima Bello , Jabire Adamu Halilu , Saminu Sani
Published: May 2023

Background

Schizophrenia affects about 1% of the global population. In addition to the complex etiology, linking this illness to genetic, environmental, and neurobiological factors, the dynamic experiences associated with this disease, such as experiences of delusions, hallucinations, disorganized thinking, and abnormal behaviors, limit neurological consensuses regarding mechanisms underlying this disease.

Methods

In this study, we recruited 72 patients with schizophrenia and 74 healthy individuals matched by age and sex to investigate the structural brain changes that may serve as prognostic biomarkers, indicating evidence of neural dysfunction underlying schizophrenia and subsequent cognitive and behavioral deficits. We used voxel-based morphometry (VBM) to determine these changes in the three tissue structures: the gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). For both image processing and statistical analysis, we used statistical parametric mapping (SPM).

Results

Our results show that patients with schizophrenia exhibited a significant volume reduction in both GM and WM. In particular, GM volume reductions were more evident in the frontal, temporal, limbic, and parietal lobe, similarly the WM volume reductions were predominantly in the frontal, temporal, and limbic lobe. In addition, patients with schizophrenia demonstrated a significant increase in the CSF volume in the left third and lateral ventricle regions.

Conclusion

This VBM study supports existing research showing that schizophrenia is associated with alterations in brain structure, including gray and white matter, and cerebrospinal fluid volume. These findings provide insights into the neurobiology of schizophrenia and may inform the development of more effective diagnostic and therapeutic approaches.
Impact of the COVID-19 pandemic on some modifiable risk factors of dementia in an aging, rural Indian population
Authors: Sundarakumar Jonas S. , Mensegere Abhishek L. , Malo Palash K. , Ravindranath Vijayalakshmi ,   on behalf of SANSCOG Collaborators
Published: May 2023

Introduction

The impact of the COVID-19 pandemic and associated lockdowns is likely to have caused adverse changes in lifestyle-related/cardiovascular risk factors and other such modifiable risk factors of dementia. We aimed to examine the pandemic’s impact on some modifiable risk factors of dementia among rural Indians belonging to a large, prospective aging cohort—Srinivaspura Aging, NeuoSenescence, and COGnition (SANSCOG).

Methods

This was a cross-sectional study among adults aged ≥ 45 years (n = 3,148; 1,492 males and 1,656 females) residing in the villages of Srinivaspura in Karnataka state, India. SANSCOG study data (clinical and biochemical assessments) of these participants were obtained from three distinct periods: (i) the “pre-COVID period”—before India’s nationwide lockdown on 24 March 2020, (ii) the “COVID period”—during the first and second waves of the pandemic, wherein the social restrictions were prominent (25 March 2020 to 30 September 2021), and (iii) the “post-COVID period”—after easing of restrictions (from 1 October 2021 onward). Proportions of participants with diabetes, hypertension, obesity, dyslipidemia (diagnosed using standard criteria), and depression (diagnosed using the Geriatric Depression Scale) were compared between the above three periods.

Results

The odds of having obesity, abnormal triglycerides, and depression among individuals in the COVID period were 1.42 times, 1.38 times, and 2.65 times more than the odds in the pre-COVID period, respectively. The odds of having hypertension, obesity, abnormal total cholesterol, abnormal triglycerides, abnormal LDL, and depression among individuals in the post-COVID period were 1.27 times, 1.32 times, 1.58 times, 1.95, 1.23, and 3.05 times more than the odds in the pre-COVID period, respectively. The odds of diabetes did not differ between any of the three periods.

Discussion

We found significantly higher odds of some of the studied risk factors in the COVID and post-COVID periods compared to the pre-COVID period, suggesting that the pandemic adversely impacted the physical and psychological health of this marginalized, rural Indian population. We call for urgent public health measures, such as multimodal, lifestyle-based, and psychosocial interventions, to mitigate this negative impact and reduce the future risk of dementia.
Rural-urban disparities in healthcare factors and long-term health outcomes in individuals with pediatric-onset spinal cord injury
Authors: Deane Kyle C. , Kurapati Nikhil , Gill Emma , Vogel Lawrence C. , Zebracki Kathy
Published: May 2023

Objective

Adults with pediatric-onset spinal cord injury (SCI) require long-term care and demonstrate elevated risk of secondary health conditions and psychosocial challenges. Medical providers are typically found in more populous and wealthy areas, resulting in a relative lack of providers in rural areas, a discrepancy even more pronounced among specialty providers. As a result, those who reside in rural regions potentially have unmet medical needs, representing a significant public health concern. The purpose of this study was to assess differences between rural and urban-residing participants with pediatric-onset SCI in factors affecting healthcare usage (e.g., employment, income, access to private insurance, community integration) and long-term healthcare outcomes (i.e., secondary health conditions and psychosocial functioning).

Methods

Data were gathered from an ongoing study examining long-term outcomes of adults with pediatric-onset SCI. Participants (N = 490) completed measures of sociodemographics, injury characteristics, and medical outcomes. Participant zip codes were classified as rural or urban using the ProximityOne database based on the ZIP Code Tabulation Areas from the 2020 census.

Results

Individuals residing in rural regions report lower levels of education, income, employment rates, private health insurance, and community integration (mobility, occupation, and social engagement), as well increased incidence of pressure injuries, urinary tract infections, hospitalizations, bowel incontinence, sleep difficulties, and perceived physical health. No differences in incidence of psychosocial functioning were identified.

Conclusion

Mitigating identified disparities and obstacles to treatment of SCI due to residing in rural environments would result in important improvements in treatment outcomes and future prevention efforts of secondary health complications, improving the overall health of adults with pediatric-onset SCI.
Humans Can’t Resist Robot Eyes – Reflexive Cueing With Pseudo-Social Stimuli
Authors: Onnasch Linda , Kostadinova Eleonora , Schweidler Paul
Published: May 2023

Joint attention is a key mechanism for humans to coordinate their social behavior. Whether and how this mechanism can benefit the interaction with pseudo-social partners such as robots is not well understood. To investigate the potential use of robot eyes as pseudo-social cues that ease attentional shifts we conducted an online study using a modified spatial cueing paradigm. The cue was either a non-social (arrow), a pseudo-social (two versions of an abstract robot eye), or a social stimulus (photographed human eyes) that was presented either paired (e.g. two eyes) or single (e.g. one eye). The latter was varied to separate two assumed triggers of joint attention: the social nature of the stimulus, and the additional spatial information that is conveyed only by paired stimuli. Results support the assumption that pseudo-social stimuli, in our case abstract robot eyes, have the potential to facilitate human-robot interaction as they trigger reflexive cueing. To our surprise, actual social cues did not evoke reflexive shifts in attention. We suspect that the robot eyes elicited the desired effects because they were human-like enough while at the same time being much easier to perceive than human eyes, due to a design with strong contrasts and clean lines. Moreover, results indicate that for reflexive cueing it does not seem to make a difference if the stimulus is presented single or paired. This might be a first indicator that joint attention depends rather on the stimulus’ social nature or familiarity than its spatial expressiveness. Overall, the study suggests that using paired abstract robot eyes might be a good design practice for fostering a positive perception of a robot and to facilitate joint attention as a precursor for coordinated behavior.