bluuebunny/crossref_metadata_2025 huggingface dataset:
Syncope (fainting on standing from squatting) due to massive venous reflux into lower limb varicose veins – Case report
Authors: Whiteley Mark S , Kiely Melissa J
Published: December 2023

A 42-year-old man presented with very large lower limb varicose veins bilaterally and an 8-month history of fainting when standing up from a squatting position. He had been investigated for syncope by a cardiologist with no abnormality found on electrocardiogram, echocardiogram, 24-h electrocardiogram or 48-h blood pressure monitoring. Venous duplex ultrasonography showed bilaterally great saphenous vein reflux, with each vein having a diameter of 23.5 and 24.0 mm at the groin, and a similar dilation along the whole vein to ankle. These veins were successfully ablated with endovenous laser ablation, immediately following which the syncope disappeared and has not returned. We calculate that before treatment, the patient had approximately 500 ml of blood refluxing passively with gravity from his deep venous system on standing into his incompetent great saphenous veins and associated varicosities, which would account for his postural syncope.
How the Social Relations Affect Performance in Chinese High-tech New Ventures: The Role of Legitimacy Acquisition and Symbolic Strategy
Authors: Liu Yunqing , Dai Zekun , Wu Yiting , Da Fang
Published: December 2023

Existing research on the relationship between social relations and new venture’s performance remains inconsistent. From the perspective of institutional theory, we introduce legitimacy acquisition and symbolic strategy to develop a theoretical model to explain the disparities in the Chinese transition economy. Based on the survey data of 242 small and medium-sized enterprises (SMEs) in China’s strategic emerging industries (SEIs), this paper (1) investigates the role of legitimacy acquisition as the mediator through which the two sub levels of social relations (political and business) affecting new venture’s performance. (2) Explores the moderating role of symbolic strategies to further illustrate the conditional nature of legitimacy acquisition. The results show that legitimacy acquisition plays a complete mediating role in the relationship between social relations and new venture’s performance. Symbolic strategy improves the positive effect of political ties on legitimacy acquisition, but weakens the positive effect of business relations on legitimacy acquisition. The findings contribute to the entrepreneurial literature and make significant empirical implications.
Statistical Optimization of Process Variables for the Dyeing of Jute with Marigold Petals Using a Dual Mordant System
Authors: Chakraborty Ritwik , Samanta Ashis Kumar , Vankar Padma Shree
Published: December 2023

Natural dye was extracted from the petals of orange-colored marigold flowers in aqueous medium, and extraction process parameters were optimized based on the color yield (optical density) of an aqueous extract of marigold petals. The extracted natural colorant was used to dye jute fabric and characterized by ultraviolet–visible spectroscopy. Extracts from gallnut and natural alum (fitkiri) were applied as mordants onto the bleached jute fabric by padding method followed by drying in air. The fabrics were treated with the mordants separately before dyeing, and then, both mordants were applied in sequence. Jute was premordanted first with gallnut followed by alum. Jute fibers were mordanted prior to dyeing with either gallnut or alum or both mordants (gallnut followed by alum treatment). Premordanted jute fabric was dyed with the natural dye extracted from marigold petals, and process conditions were standardized. The dual-mordanting process was found more effective to produce better color yield than the single mordanting process. Standardization of the process conditions was also examined statistically by the Box–Behnken design method after choosing the significant variables by the Plackett–Burman design method. The standardized dyeing process conditions were found to be dyeing temperature: 90°C; material to liquor ratio: 1:40; dyeing time: 60 min; dye concentration: 30% o.w.f.; and pH: 11.
One-pot, degradable, silica nanocarriers with encapsulated oligonucleotides for mitochondrial specific targeting
Authors: Trayford Chloe , Wilhalm Alissa , Habibovic Pamela , Smeets Hubert , van Tienen Florence , van Rijt Sabine
Published: December 2023

Mutations in nuclear and mitochondrial genes are responsible for severe chronic disorders such as mitochondrial myopathies. Gene therapy using antisense oligonucleotides is a promising strategy to treat mitochondrial DNA (mtDNA) diseases by blocking the replication of the mutated mtDNA. However, transport vehicles are needed for intracellular, mitochondria-specific transport of oligonucleotides. Nanoparticle (NP) based vectors such as large pore mesoporous silica nanoparticles (LP) often rely on surface complexation of oligonucleotides exposing them to nucleases and limiting mitochondria targeting and controlled release ability. In this work, stable, fluorescent, hollow silica nanoparticles (HSN) that encapsulate and protect oligonucleotides in the hollow core were synthesized by a facile one-pot procedure. Both rhodamine B isothiocyanate and bis[3-(triethoxysilyl)propyl]tetrasulfide were incorporated in the HSN matrix by co-condensation to enable cell tracing, intracellular-specific degradation and controlled oligonucleotide release. We also synthesized LP as a benchmark to compare the oligonucleotide loading and release efficacy of our HSN. Mitochondria targeting was enabled by NP functionalization with cationic, lipophilic Triphenylphosphine (TPP) and, for the first time a fusogenic liposome based carrier, previously reported under the name MITO-Porter. HSN exhibited high oligonucleotide incorporation ratios and release dependent on intracellular degradation. Further, MITO-Porter capping of our NP enabled delayed, glutathione (GSH) responsive oligonucleotide release and mitochondria targeting at the same efficiency as TPP functionalized NP. Overall, our NP are promising vectors for anti-gene therapy of mtDNA disease as well as many other monogenic disorders worldwide.

Graphical Abstract
A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease: the ACCESS-ESLD study protocol
Authors: Nasr Patrik , Forsgren Mikael , Balkhed Wile , Jönsson Cecilia , Dahlström Nils , Simonsson Christian , Cai Shan , Cederborg Anna , Henriksson Martin , Stjernman Henrik , Rejler Martin , Sjögren Daniel , Cedersund Gunnar , Bartholomä Wolf , Rydén Ingvar , Lundberg Peter , Kechagias Stergios , Leinhard Olof Dahlqvist , Ekstedt Mattias
Published: December 2023

Background

Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients.

Methods

In this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations.

Discussion

The anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes.

Trial registration

Clinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic.clinicaltrials.gov/ct2/show/NCT05502198.
Efficacy comparison of 7- and 14-day P-CAB based bismuth-containing quadruple regimen with PPI based bismuth-containing quadruple regimen for Helicobacter pylori infection: rationale and design of an open-label, multicenter, randomized controlled trial
Authors: Oh Chang Kyo , Lim Hyun , Seo Seung In , Lee Sang Pyo , Bang Chang Seok , Shin Woon Geon , Kim Jin Bae , Jang Hyun Joo , Baik Gwang Ho
Published: December 2023

Background

Owing to its strong acid inhibition, potassium-competitive acid blocker (P-CAB) based regimens for Helicobacter pylori (H. pylori) eradication are expected to offer clinical advantages over proton pump inhibitor (PPI) based regimens. This study aims to compare the efficacy and adverse effects of a 7-day and a 14-day P-CAB-based bismuth-containing quadruple regimen (PC-BMT) with those of a 14-day PPI-based bismuth-containing quadruple regimen (P-BMT) in patients with high clarithromycin resistance.

Methods

This randomized multicenter controlled clinical trial will be performed at five teaching hospitals in Korea. Patients with H. pylori infection who are naive to treatment will be randomized into one of three regimens: 7-day or 14-day PC-BMT (tegoprazan 50 mg BID, bismuth subcitrate 300 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or 14-day P-BMT. The eradication rate, treatment-related adverse events, and drug compliance will be evaluated and compared among the three groups. Antibiotic resistance testing by culture will be conducted during the trial, and these data will be used to interpret the results. A total of 366 patients will be randomized to receive 7-day PC-BMT (n = 122), 14-day PC-BMT (n = 122), or 14-day P-BMT (n = 122). The H. pylori eradication rates in the PC-BMT and P-BMT groups will be compared using intention-to-treat and per-protocol analyses.

Discussion

This study will demonstrate that the 7-day or 14-day PC-BMT is well tolerated and achieve similar eradication rates to those of 14-day P-BMT. Additionally, the 7-day PC-BMT will show fewer treatment-related adverse effects and higher drug compliance, owing to its reduced treatment duration.

Trial registration

Korean Clinical Research Information Service registry, KCT0007444. Registered on 28 June 2022, https://cris.nih.go.kr/cris/index/index.do.
GRB7 plays a promoting role in the progression of gastric cancer
Authors: Zhu Guomin , Cai Hu , Xiao Qiang , Zeng Shukun , Jiang Xiaohua , Liu Donglan
Published: December 2023

Background

Gastric cancer is a clinically common tumor, showing an upward trend of both incidence and mortality. GRB7 has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of GRB7 in gastric cancer process.

Methods

immunohistochemical (IHC) staining using a tissue microarray (TMA), quantitative reverse transcription PCR (qRT-PCR) and Western blotting were performed to detect the expression of genes. Furthermore, gastric cancer cell lines AGS and MGC-803 were transfected with short hairpin RNAs against GRB7. The biological function of GRB7 in gastric cancer cells were examined by CCK-8, flow cytometry, wound healing and Transwell assays. Then, in vivo tumor formation assay was conducted to explore the effects of GRB7 on tumor growth. Finally, expression levels of proteins related to cell functions were determined by Western blotting. Coimmunoprecipitation (CoIP) assay was performed to assess the protein-protein interaction.

Results

GRB7 was up-regulated in gastric cancer tissues and cell lines, and its expression was inversely proportional to survival of gastric cancer patients. Moreover, GRB7 knockdown inhibited proliferative, migratory abilities, as well as promoted cell apoptosis in gastric cancer cells. Further study suggested that GRB7 silencing could suppress gastric cancer tumor growth in vivo. Furthermore, our study uncovered an important interaction between GRB7 and MyD88. Silencing MyD88 was observed to alleviate the malignant phenotypes promoted by GRB7 in gastric cancer cells.

Conclusions

Together, this study provided evidence that GRB7 may be an effective molecular targets for the treatment of gastric cancer.
Appropriate dose of regorafenib based on body weight of colorectal cancer patients: a retrospective cohort study
Authors: Nakashima Masayuki , Li Kan , Chen Qichen , de Silva Sajith , Li Hal , Kawakami Koji , Wei Qingyi , Luo Sheng , Zhao Hong
Published: December 2023

Purpose

Previous randomized studies have shown a survival benefit of using regorafenib but a high rate of adverse events in unresectable colorectal cancer patients. To reduce these adverse events and improve the tolerability, we examined the appropriate dose of regorafenib based on body weight.

Methods

We used a nationwide claims database in Japan and examined the efficacy and safety of regorafenib for patients with metastatic colorectal cancer between groups divided by body weight (60 kg) and median average dose (120 mg) between 2013 and 2018. We also assessed overall survival (OS) and adverse events between these groups.

Results

We identified 2530 Japanese patients (heavy weight/high dose: 513, light weight/low dose: 921, heavy weight/low dose: 452, and light weight/high dose: 644). There was no significant difference in the adverse events and OS after inverse probability treatment weighting (IPTW) adjustment between heavy weight/high dose group and light weight/low dose group (hazard ratio, HR=0.97). Among the light-weight patients, higher average dose was associated with shorter OS (IPTW adjusted HR=1.21, 95% CI 1.05 – 1.39, Table 3) while among the heavy-weight patients, there was no significant difference in OS between high and low dose groups (IPTW adjusted HR=1.14, 95% CI 0.95 – 1.37).

Conclusion

The findings suggest that a low dose of regorafenib for light-weight patients may be as safe and effective as high doses for heavy-weight patients. Further studies should be conducted to identify an appropriate dose based on each patient's physique and condition.
Patients’ perspectives and the perceptions of healthcare providers in the treatment of early rectal cancer; a qualitative study
Authors: Smits Lisanne J. H. , van Lieshout Annabel S. , Debets Saskia , Spoor Sacha , Moons Leon M. G. , Peeters Koen C. M. J. , van Oostendorp Stefan E. , Damman Olga C. , Janssens Rien J. P. A. , Lameris Wytze , van Grieken Nicole C. T. , Tuynman Jurriaan B.
Published: December 2023

Background

Shared decision-making has become of increased importance in choosing the most suitable treatment strategy for early rectal cancer, however, clinical decision-making is still primarily based on physicians’ perspectives. Balancing quality of life and oncological outcomes is difficult, and guidance on patients’ involvement in this subject in early rectal cancer is limited. Therefore, this study aimed to explore preferences and priorities of patients as well as physicians’ perspectives in treatment for early rectal cancer.

Methods

In this qualitative study, semi-structured interviews were performed with early rectal cancer patients (n = 10) and healthcare providers (n = 10). Participants were asked which factors influenced their preferences and how important these factors were. Thematic analyses were performed. In addition, participants were asked to rank the discussed factors according to importance to gain additional insights.

Results

Patients addressed the following relevant factors: the risk of an ostomy, risk of poor bowel function and treatment related complications. Healthcare providers emphasized oncological outcomes as tumour recurrence, risk of an ostomy and poor bowel function. Patients perceived absolute risks of adverse outcome to be lower than healthcare providers and were quite willing undergo organ preservation to achieve a better prospect of quality of life.

Conclusion

Patients’ preferences in treatment of early rectal cancer vary between patients and frequently differ from assumptions of preferences by healthcare providers. To optimize future shared decision-making, healthcare providers should be aware of these differences and should invite patients to explore and address their priorities more explicitly during consultation. Factors deemed important by both physicians and patients should be expressed during consultation to decide on a tailored treatment strategy.
Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis
Authors: Kim Seul , Jun Kyoungho , Kim Ye-Hyun , Jung Kwan-Young , Oh Jeong Su , Kim Jae-Sung
Published: December 2023

Background

The maintenance of spindle pole integrity is essential for spindle assembly and chromosome segregation during mitosis. However, the underlying mechanisms governing spindle pole integrity remain unclear.

Methods

ENSA was inhibited by siRNA or MKI-2 treatment and its effect on cell cycle progression, chromosome alignment and microtubule alignment was observed by immunohistochemical staining and western blotting. PP2A-B55α knockdown by siRNA was performed to rescue the phenotype caused by ENSA inhibition. The interaction between ENSA and Aurora A was detected by in situ PLA. Furthermore, orthotopic implantation of 4Tl-luc cancer cells was conducted to confirm the consistency between the in vitro and in vivo relationship of the ENSA-Aurora A interaction.

Results

During mitosis, p-ENSA is localized at the spindle poles, and the inhibition of ENSA results in mitotic defects, such as misaligned chromosomes, multipolar spindles, asymmetric bipolar spindles, and centrosome defects, with a delay in mitotic progression. Although the mitotic delay caused by ENSA inhibition was rescued by PP2A-B55α depletion, spindle pole defects persisted. Notably, we observed a interaction between ENSA and Aurora A during mitosis, and inhibition of ENSA reduced Aurora A expression at the mitotic spindle poles. Injecting MKI-2-sensitized tumors led to increased chromosomal instability and downregulation of the MASTL-ENSA-Aurora A pathway in an orthotopic breast cancer mouse model.

Conclusions

These findings provide novel insights into the regulation of spindle pole integrity by the MASTL-ENSA-Aurora A pathway during mitosis, highlighting the significance of ENSA in recruiting Aurora A to the spindle pole, independent of PP2A-B55α.
Eating disorders symptoms and depressive symptoms in Chinese Tibetan University students: a network analysis
Authors: Wu Ruipeng , Guang Zixuan , Wang Yingting , Xue Bei , Zhang Ailing , Dawa Yundan , Guo Chenghui , Tong Xiaopeng , Wang Shaokang , Lu Ciyong
Published: December 2023

Background

Depression is being increasingly acknowledged as a global public health concern, and following this trend, attention towards eating disorders (EDs) has surged within China’s national consciousness. EDs symptoms frequently coexist with various mental health conditions, including depression. However, research focusing on EDs symptoms and depressive symptoms among Tibetan students in China remains scant. This study employs network analysis to estimate the relational network between EDs and depressive symptoms.

Methods

Tibetan (n = 2,582) and Han (n = 1,743) students from two universities in the Xizang Autonomous Region, China, completed the Eating Attitude Test-26 (EAT-26) and the Patient Health Questionnaire-9 (PHQ-9). We estimated the network structure of EDs symptoms and depressive symptoms, identified central and bridge symptoms, and examined whether network characteristics differed by gender and ethnic.

Results

The core symptoms identified within this study were Calorie_awareness, Desire_to_thin and Fatigue. Conversely, bridge symptoms included Appetite, Suicide, Anhedonia, Guilty, Body_fat_awareness, and Food_preoccupation. The study also revealed no significant gender differences within the network model. However, disparities among ethnic groups were observed within the network structure.

Conclusions

Our study examined the correlation between EDs symptoms and depressive symptoms in Tibetan college students. Focusing on the individual's quest for the perfect body shape and some Tibetan students' appetite problems – potentially stemming from transitioning to a new university environment, adapting to the school canteen's diet, or being away from their hometown – could aid in the prevention and management of EDs and depression symptoms. It could reduce the incidence of complications by helping students maintain good physical and mental health. Concurrently, our research provides insights into the relatively higher levels of depression triggered by the unique plateau environment.
Re-assessing the social climate of physical (in)activity in Canada
Authors: Fagan Matthew James , Vanderloo Leigh M. , Banerjee Ananya , Ferguson Leah J. , Lee Eun-Young , O’Reilly Norman , Rhodes Ryan E. , Spence John C. , Tremblay Mark S. , Faulkner Guy
Published: December 2023

Social-ecological models suggest that a strategy for increasing population physical activity participation is to reconstruct the “social climate” through changing social norms and beliefs about physical activity (PA). In this study, we assessed whether the PA social climate in Canada has changed over a five-year period after controlling for sociodemographic factors and PA levels. Replicating a survey administered in 2018, a sample of adults in Canada (n = 2,507) completed an online survey assessing social climate dimensions, including but not limited to descriptive and injunctive norms. Descriptive statistics were calculated, and binary logistic regressions were conducted to assess the associations of sociodemographic factors and year of the survey with social climate dimensions. Results suggest some social climate constructs are trending in a positive direction between 2018 and 2023. Physical inactivity was considered a serious public health concern by 49% of respondents, second to unhealthy diets (52%). Compared to those who participated in the 2018 survey, participants in 2023 were less likely to see others walking or wheeling in their neighbourhood (OR = 1.58, 95% CI: 1.41, 1.78), but more likely to see people exercising (OR = 0.82, 95% CI: 0.73, 0.92) and kids playing in their neighbourhood (OR = 0.75, 95% CI: 0.66, 0.85). No changes were reported between 2018 and 2023 in individuals’ perceptions of whether physical inactivity is due to individual versus external factors (OR = 0.99, 95% CI: 0.87, 1.13). The findings of this work indicate a modest positive shift in some measured components of the social climate surrounding PA although attributing causes for these changes remain speculative.
Associations of long-term exposure to air pollution and physical activity with the risk of systemic inflammation-induced multimorbidity in Chinese adults: results from the China multi-ethnic cohort study (CMEC)
Authors: Li Yajie , Guo Bing , Meng Qiong , Yin Li , Chen Lin , Wang Xing , Jiang Ye , Wei Jing , Wang Junhua , Xia Jinjie , Wang Zihao , Duoji Zhuoma , Li Xianzhi , Nima Qucuo , Zhao Xing
Published: December 2023

Objective

Previous studies proved the effect of long-term exposure to air pollution or physical activity (PA) on the risk of systemic inflammation-induced multimorbidity (SIIM), while the evidence regarding their joint effects was rare, especially in low- and middle-income countries. Therefore, we aimed to examine the extent of interaction or joint relations of PA and air pollution with SIIM.

Methods

This study included 72,172 participants from China Multi-Ethnic Cohort.The average concentrations of ambient particulate matter pollutants (PM1, PM2.5, and PM10) were estimated using satellite-based random forest models. Self-reported information on a range of physical activities related to occupation, housework, commuting, and leisure activities was collected by an interviewer-administered questionnaire. A total of 11 chronic inflammatory systemic diseases were assessed based on self-reported lifetime diagnosis or medical examinations. SIIM was defined as having ≥ 2 chronic diseases related to systemic inflammation. Logistic regression models were used to assess the complex associations of air pollution particulate matter and PA with SIIM.

Results

We found positive associations between long-term air pollution particulates exposure and SIIM, with odds ratios (95%CI) of 1.07 (1.03 to 1.11), 1.18 (1.13 to 1.24), and 1.08 (1.05 to 1.12) per 10 µg/m3 increase in PM1, PM2.5, and PM10. No significant multiplicative interaction was found between ambient air pollutant exposure and PA on SIIM, whereas negative additive interaction was observed between long-term exposure to PM2.5 and PA on SIIM. The positive associations between low volume PA and SIIM were stronger among those exposed to high-level air pollution particulates. Compared with individuals engaged in high volume PA and exposed to low-level ambient air pollutants, those engaged in low volume PA and exposed to high-level ambient air pollutants had a higher risk of SIIM (OR = 1.49 in PM1 exposure, OR = 1.84 in PM2.5 exposure, OR = 1.19 in PM10 exposure).

Conclusions

Long-term (3 years average) exposure to PM1, PM2.5, and PM10 was associated with an increased risk of SIIM. The associations were modified by PA, highlighting PA’s importance in reducing SIIM for all people, especially those living in high-level air pollution regions.
Prevalence of oral mucosal lesions in patients with systemic Lupus Erythematosus: a systematic review and meta-analysis
Authors: Du Fei , Qian Wanying , Zhang Xinna , Zhang Le , Shang Jianwei
Published: December 2023

Background

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause a range of symptoms, including oral mucosal lesions (OMLs). The prevalence of OMLs in SLE patients and their associated factors have been studied in various regions, but the results are inconsistent. This study aims to evaluate the prevalence of OMLs in patients with SLE.

Methods

Observational studies of OML prevalence in SLE patients published before 2022 were retrieved from PubMed, Embase, Web of Science, Google Scholar, and the Cochrane Library without language restriction. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ).

Results

Our meta-analysis included 113 studies with a total of 53,307 SLE patients. We found that the prevalence of OMLs in SLE patients was 31% (95% CI: 28%, 35%), with oral ulcers being present in 30% of SLE patients (95% CI: 26%, 33%). Subgroup analysis showed that the prevalence of OMLs varied significantly by region, disease activity, and sample size (p ≤ 0.01). However, gender and year of publication had little effect on the prevalence of OMLs (p = 0.78 and 0.30, respectively). Oral ulcers were significantly associated with age of onset (p = 0.02), geographic location (p < 0.01), and race (p < 0.01). We also found that the prevalence of oral erythema was 9%, oral candidiasis was 9%, petechiae was 8%, cheilitis was 6%, and white plaque was 3%.

Conclusions

Our analysis showed that the prevalence of OMLs varied significantly by region and disease activity, and child-onset patients of Indian, Malay, and Caucasian descent were more likely to have oral ulcers. The high prevalence of OML in SLE patients emphasizes the importance of regular oral examination and management in the comprehensive care of individuals with SLE.
Selection on the promoter regions plays an important role in complex traits during duck domestication
Authors: Yin Zhong-Tao , Li Xiao-Qin , Sun Yun-Xiao , Smith Jacqueline , Hincke Maxwell , Yang Ning , Hou Zhuo-Cheng
Published: December 2023

Background

Identifying the key factors that underlie complex traits during domestication is a great challenge for evolutionary and biological studies. In addition to the protein-coding region differences caused by variants, a large number of variants are located in the noncoding regions containing multiple types of regulatory elements. However, the roles of accumulated variants in gene regulatory elements during duck domestication and economic trait improvement are poorly understood.

Results

We constructed a genomics, transcriptomics, and epigenomics map of the duck genome and assessed the evolutionary forces that have been in play across the whole genome during domestication. In total, 304 (42.94%) gene promoters have been specifically selected in Pekin duck among all selected genes. Joint multi-omics analysis reveals that 218 genes (72.01%) with selected promoters are located in open and active chromatin, and 267 genes (87.83%) with selected promoters were highly and differentially expressed in domestic trait-related tissues. One important candidate gene ELOVL3, with a strong signature of differentiation on the core promoter region, is known to regulate fatty acid elongation. Functional experiments showed that the nearly fixed variants in the top selected ELOVL3 promoter in Pekin duck decreased binding ability with HLF and increased gene expression, with the overexpression of ELOVL3 able to increase lipid deposition and unsaturated fatty acid enrichment.

Conclusions

This study presents genome resequencing, RNA-Seq, Hi-C, and ATAC-Seq data of mallard and Pekin duck, showing that selection of the gene promoter region plays an important role in gene expression and phenotypic changes during domestication and highlights that the variants of the ELOVL3 promoter may have multiple effects on fat and long-chain fatty acid content in ducks.
Longitudinal multi-omics study reveals common etiology underlying association between plasma proteome and BMI trajectories in adolescent and young adult twins
Authors: Drouard Gabin , Hagenbeek Fiona A. , Whipp Alyce M. , Pool René , Hottenga Jouke Jan , Jansen Rick , Hubers Nikki , Afonin Aleksei ,   BIOS Consortium, BBMRI-N. L. Metabolomics Consortium, Willemsen Gonneke , de Geus Eco J. C. , Ripatti Samuli , Pirinen Matti , Kanninen Katja M. , Boomsma Dorret I. , van Dongen Jenny , Kaprio Jaakko
Published: December 2023

Background

The influence of genetics and environment on the association of the plasma proteome with body mass index (BMI) and changes in BMI remains underexplored, and the links to other omics in these associations remain to be investigated. We characterized protein–BMI trajectory associations in adolescents and adults and how these connect to other omics layers.

Methods

Our study included two cohorts of longitudinally followed twins: FinnTwin12 (N = 651) and the Netherlands Twin Register (NTR) (N = 665). Follow-up comprised 4 BMI measurements over approximately 6 (NTR: 23–27 years old) to 10 years (FinnTwin12: 12–22 years old), with omics data collected at the last BMI measurement. BMI changes were calculated in latent growth curve models. Mixed-effects models were used to quantify the associations between the abundance of 439 plasma proteins with BMI at blood sampling and changes in BMI. In FinnTwin12, the sources of genetic and environmental variation underlying the protein abundances were quantified by twin models, as were the associations of proteins with BMI and BMI changes. In NTR, we investigated the association of gene expression of genes encoding proteins identified in FinnTwin12 with BMI and changes in BMI. We linked identified proteins and their coding genes to plasma metabolites and polygenic risk scores (PRS) applying mixed-effects models and correlation networks.

Results

We identified 66 and 14 proteins associated with BMI at blood sampling and changes in BMI, respectively. The average heritability of these proteins was 35%. Of the 66 BMI-protein associations, 43 and 12 showed genetic and environmental correlations, respectively, including 8 proteins showing both. Similarly, we observed 7 and 3 genetic and environmental correlations between changes in BMI and protein abundance, respectively. S100A8 gene expression was associated with BMI at blood sampling, and the PRG4 and CFI genes were associated with BMI changes. Proteins showed strong connections with metabolites and PRSs, but we observed no multi-omics connections among gene expression and other omics layers.

Conclusions

Associations between the proteome and BMI trajectories are characterized by shared genetic, environmental, and metabolic etiologies. We observed few gene-protein pairs associated with BMI or changes in BMI at the proteome and transcriptome levels.
Perspectives of African stakeholders on gene drives for malaria control and elimination: a multi-country survey
Authors: Finda Marceline F. , Juma Elijah O. , Kahamba Najat F. , Mthawanji Rhosheen S. , Sambo Maganga , Emidi Basiliana , Wiener Susan , O’Brochta David , Santos Michael , James Stephanie , Okumu Fredros O.
Published: December 2023

Background

Gene drive modified mosquitoes (GDMMs) have the potential to address Africa’s persistent malaria problem, but are still in early stages of development and testing. Continuous engagement of African stakeholders is crucial for successful evaluation and implementation of these technologies. The aim of this multi-country study was, therefore, to explore the insights and recommendations of key stakeholders across Africa on the potential of GDMMs for malaria control and elimination in the continent.

Methods

A concurrent mixed-methods study design was used, involving a structured survey administered to 180 stakeholders in 25 countries in sub-Saharan Africa, followed by 18 in-depth discussions with selected groups and individuals. Stakeholders were drawn from academia, research and regulatory institutions, government ministries of health and environment, media and advocacy groups. Thematic content analysis was used to identify key topics from the in-depth discussions, and descriptive analysis was done to summarize information from the survey data.

Results

Despite high levels of awareness of GDMMs among the stakeholders (76.7%), there was a relatively low-level of understanding of their key attributes and potential for malaria control (28.3%). When more information about GDMMs was provided to the stakeholders, they readily discussed their insights and concerns, and offered several recommendations to ensure successful research and implementation of the technology. These included: (i) increasing relevant technical expertise within Africa, (ii) generating local evidence on safety, applicability, and effectiveness of GDMMs, and (iii) developing country-specific regulations for safe and effective governance of GDMMs. A majority of the respondents (92.9%) stated that they would support field trials or implementation of GDMMs in their respective countries. This study also identified significant misconceptions regarding the phase of GDMM testing in Africa, as several participants incorrectly asserted that GDMMs were already present in Africa, either within laboratories or released into the field.

Conclusion

Incorporating views and recommendations of African stakeholders in the ongoing research and development of GDMMs is crucial for instilling stakeholder confidence on their potential application. These findings will enable improved planning for GDMMs in Africa as well as improved target product profiles for the technologies to maximize their potential for solving Africa’s enduring malaria challenge.
Capsaicin orchestrates metastasis in gastric cancer via modulating expression of TRPV1 channels and driving gut microbiota disorder
Authors: Deng Rui , Yu Suyun , Ruan Xingqiu , Liu Huan , Zong Gangfan , Cheng Peng , Tao Ruizhi , Chen Wenxing , Wang Aiyun , Zhao Yang , Wei Zhonghong , Lu Yin
Published: December 2023

The association between capsaicin, the major natural pungent compound of chili peppers, and gastric cancer progression has engendered conflicting findings. In this work, we sought to explore the character of a high capsaicin diet in gastric cancer metastasis and its possible mechanism. The impact of high capsaicin consumption on gastric cancer metastasis was investigated in vivo (xenograft mouse and zebrafish models) and in vitro (biochemical and molecular assays). It was demonstrated that high diet of capsaicin gave rise to accelerate tumor metastasis, which was partially mediated by elevating the expression of transient receptor potential vanilloid 1 (TRPV1) in gastric cancer cells. Importantly, we found that genetic depletion of TRPV1 could reduce gastric cancer metastasis by diminishing the motility of tumor cells in vitro, but acted poorly in xenograft mouse model. Considering the distribution of capsaicin in vivo, 16S rRNA sequencing and fecal microbiota transplantation (FMT) were used to appraise whether the gut microbiota involved in the high capsaicin diet induced metastasis. It was demonstrated that the level of Firmicutes and Clostridiales was expressively boosted following the high consumption of capsaicin. This microbial shift contributed to the increased peripheral 5-hydroxytryptamine (5-HT) levels, yielding the aggravated metastatic burden. Collectively, our findings highlighted the potential risk of high capsaicin diet in promoting gastric cancer metastasis by virtue of modulating TRPV1 expression and gut microbiota composition, indicating the importance of controlled consumption of chili peppers for patients with gastric cancer.
Task-oriented exercise effects on walking and corticospinal excitability in multiple sclerosis: protocol for a randomized controlled trial
Authors: Moslemi Zahra , Toledo-Aldana Eduardo A. , Baldwin Bruce , Donkers Sarah J. , Eng Janice J. , Mondal Prosanta , de Zepetnek Julia O. Totosy , Buttigieg Josef , Levin Michael C. , Mang Cameron S.
Published: December 2023

Background

Multiple sclerosis (MS) is a degenerative disease of the central nervous system (CNS) that disrupts walking function and results in other debilitating symptoms. This study compares the effects of ‘task-oriented exercise’ against ‘generalized resistance and aerobic exercise’ and a ‘stretching control’ on walking and CNS function in people with MS (PwMS). We hypothesize that task-oriented exercise will enhance walking speed and related neural changes to a greater extent than other exercise approaches.

Methods

This study is a single-blinded, three-arm randomized controlled trial conducted in Saskatchewan, Canada. Eligible participants are those older than 18 years of age with a diagnosis of MS and an expanded Patient-Determined Disease Steps (PDDS) score between 3 (‘gait disability’) and 6 (‘bilateral support’). Exercise interventions are delivered for 12 weeks (3 × 60-min per week) in-person under the supervision of a qualified exercise professional. Interventions differ in exercise approach, such that task-oriented exercise involves weight-bearing, walking-specific activities, while generalized resistance and aerobic exercise uses seated machine-based resistance training of major upper and lower body muscle groups and recumbent cycling, and the stretching control exercise involves seated flexibility and relaxation activities. Participants are allocated to interventions using blocked randomization that stratifies by PDDS (mild: 3–4; moderate: 5–6). Assessments are conducted at baseline, post-intervention, and at a six-week retention time point. The primary and secondary outcome measures are the Timed 25-Foot Walk Test and corticospinal excitability for the tibialis anterior muscles determined using transcranial magnetic stimulation (TMS), respectively. Tertiary outcomes include assessments of balance, additional TMS measures, blood biomarkers of neural health and inflammation, and measures of cardiorespiratory and musculoskeletal fitness.

Discussion

A paradigm shift in MS healthcare towards the use of “exercise as medicine” was recently proposed to improve outcomes and alleviate the economic burden of MS. Findings will support this shift by informing the development of specialized exercise programming that targets walking and changes in corticospinal excitability in PwMS.

Trial registration

ClinicalTrials.gov, NCT05496881, Registered August 11, 2022. https://classic.clinicaltrials.gov/ct2/show/NCT05496881. Protocol amendment number: 01; Issue date: August 1, 2023; Primary reason for amendment: Expand eligibility to include people with all forms of MS rather than progressive forms of MS only.
The effect of transcranial direct current stimulation on bilateral asymmetry and joint angles of the lower limb for females when crossing obstacles
Authors: Wang I-Lin , Gu Chin-Yi , Lei Tze-Huan , Chen Che-Hsiu , Chiu Chih-Hui , Su Yu
Published: December 2023

Background

Gait asymmetry is often accompanied by the bilateral asymmetry of the lower limbs. The transcranial direct current stimulation (tDCS) technique is widely used in different populations and scenarios as a potential tool to improve lower limb postural control. However, whether cerebral cortex bilateral tDCS has an interventional effect on postural control as well as bilateral symmetry when crossing obstacles in healthy female remains unknown.

Methods

Twenty healthy females were recruited in this prospective study. Each participant walked and crossed a height-adjustable obstacle. Two-way repeated ANOVA was used to evaluate the effect of group (tDCS and sham-tDCS) and height (30%, 20%, and 10% leg length) on the spatiotemporal and maximum joint angle parameters for lower limb crossing obstacles. The Bonferroni post-hoc test and paired t-test were used to determine the significance of the interaction effect or main effect. The statistically significant differences were set at p < 0.05.

Results

The Swing time (SW) gait asymmetry (GA), Stance time (ST) GA, leading limb hip-knee-ankle maximum joint angles and trailing limb hip-knee maximum joint angles decreased in the tDCS condition compared to the sham-tDCS condition at 30%, 20% leg’s length crossing height except for 10% leg’s length, whereas there was a significant decrease in SW/ST GA between the tDCS condition and the sham-tDCS condition at 30%, 20%, 10% leg’s length crossing height (P < 0.05).

Conclusion

We conclude that tDCS intervention is effective to reduce bilateral asymmetry in spatio-temporal parameters and enhance dynamic balance in female participants during obstacle crossing when the heights of the obstacles were above 10% of the leg’s length.

Trial registration No

ChiCTR2100053942 (date of registration on December 04, 2021). Prospectively registered in the Chinese Clinical Trial Registry.
Recurrent malignant ventricular arrhythmias and paresthesia—a mystery revealed as aconitine poisoning: a case report
Authors: Mjølstad Ole Christian , Radtke Maria , Brodtkorb Eylert , Edvardsen Frode , Brede Wenche Rødseth , Aamo Trond Oskar , Jacobsen Dag , Stokke Mathis Korseberg , Helland Arne
Published: December 2023

Background

We report a case of a clinical challenge lasting for 12 months, with severe and unresolved clinical features involving several medical disciplines.

Case presentation

A 53-year-old Caucasian male, who had been previously healthy apart from a moderate renal impairment, was hospitalized 12 times during a 1-year period for a recurrent complex of neurological, cardiovascular, and gastrointestinal symptoms and signs, without any apparent etiology. On two occasions, he suffered a cardiac arrest and was successfully resuscitated. Following the first cardiac arrest, a cardiac defibrillator was inserted. During the 12th admission to our hospital, aconitine poisoning was suspected after a comprehensive multidisciplinary evaluation and confirmed by serum and urine analyses. Later, aconitine was also detected in a hair segment, indicating exposure within the symptomatic period. After the diagnosis was made, no further episodes occurred. His cardiac defibrillator was later removed, and he returned to work. A former diagnosis of epilepsy was also abandoned. Criminal intent was suspected, and his wife was sentenced to 11 years in prison for attempted murder. To make standardized assessments of the probability for aconitine poisoning as the cause of the eleven prior admissions, an “aconitine score” was established. The score is based on neurological, cardiovascular, gastrointestinal, and other clinical features reported in the literature. We also make a case for the use of hair analysis to confirm suspected poisoning cases evaluated after the resolution of clinical features.

Conclusion

This report illustrates the medical challenge raised by cases of covert poisoning. In patients presenting with symptoms and signs from several organ systems without apparent cause, poisoning should always be suspected. To solve such cases, insight into the effects of specific toxic agents is needed. We present an “aconitine score” that may be useful in cases of suspected aconitine poisoning.
Effect of miR-21 in mesenchymal stem cells-derived extracellular vesicles behavior
Authors: Morente-López Miriam , Mato-Basalo Rocio , Lucio-Gallego Sergio , Gil Concha , Carrera Mónica , Fafián-Labora Juan A. , Mateos Jesús , Arufe María C.
Published: December 2023

Background

A challenging new branch of research related to aging-associated diseases is the identification of miRNAs capable of modulating the senescence-associated secretory phenotype (SASP) which characterizes senescent cells and contributes to driving inflammation.

Methods

Mesenchymal stem cells (MSC) from human umbilical cord stroma were stable modified using lentivirus transduction to inhibit miR-21-5p and shotgun proteomic analysis was performed in the MSC-derived extracellular vesicles (EV) to check the effect of miR-21 inhibition in their protein cargo. Besides, we studied the paracrine effect of those modified extracellular vesicles and also their effect on SASP.

Results

Syndecan-1 (SDC1) was the most decreased protein in MSC-miR21−-derived EV, and it was involved in inflammation and EV production. MSC-miR21−-derived EV were found to produce a statistically significant inhibitory effect on SASP and inflammaging markers expression in receptor cells, and in the opposite way, these receptor cells increased their SASP and inflammaging expression statistically significantly when treated with MSC-miR-21+-derived EV.

Conclusion

This work demonstrates the importance of miR-21 in inflammaging and its role in SASP through SDC1.

Graphical abstract