bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular evolution of Phytocyanin gene and analysis of expression at different coloring periods in apple (Malus domestica)
Authors: Shao Miao , Feng Yongqing , Yang Shangwen , Feng Tong , Zeng Fanwei , Lu Shixiong , Ma Zonghuan , Chen Baihong , Mao Juan
Published: May 2024

Background

PC (phytocyanin) is a class of copper-containing electron transfer proteins closely related to plant photosynthesis, abiotic stress responses growth and development in plants, and regulation of the expression of some flavonoids and phenylpropanoids, etc., however, compared with other plants, the PC gene family has not been systematically characterized in apple.

Results

A total of 59 MdPC gene members unevenly distributed across 12 chromosomes were identified at the genome-wide level. The proteins of the MdPC family were classified into four subfamilies based on differences in copper binding sites and glycosylation sites: Apple Early nodulin-like proteins (MdENODLs), Apple Uclacyanin-like proteins (MdUCLs), Apple Stellacyanin-like proteins (MdSCLs), and Apple Plantacyanin-like proteins (MdPLCLs). Some MdPC members with similar gene structures and conserved motifs belong to the same group or subfamily. The internal collinearity analysis revealed 14 collinearity gene pairs among members of the apple MdPC gene. Interspecific collinearity analysis showed that apple had 31 and 35 homologous gene pairs with strawberry and grape, respectively. Selection pressure analysis indicated that the MdPC gene was under purifying selection. Prediction of protein interactions showed that MdPC family members interacted strongly with the Nad3 protein. GO annotation results indicated that the MdPC gene also regulated the biosynthesis of phenylpropanoids. Chip data analysis showed that (MdSCL3, MdSCL7 and MdENODL27) were highly expressed in mature fruits and peels. Many cis-regulatory elements related to light response, phytohormones, abiotic stresses and flavonoid biosynthetic genes regulation were identified 2000 bp upstream of the promoter of the MdPC gene, and qRT-PCR results showed that gene members in Group IV (MdSCL1/3, MdENODL27) were up-regulated at all five stages of apple coloring, but the highest expression was observed at the DAF13 (day after fruit bag removal) stage. The gene members in Group II (MdUCL9, MdPLCL3) showed down-regulated or lower expression in the first four stages of apple coloring but up-regulated and highest expression in the DAF 21 stage.

Conclusion

Herein, one objective of these findings is to provide valuable information for understanding the structure, molecular evolution, and expression pattern of the MdPC gene, another major objective in this study was designed to lay the groundwork for further research on the molecular mechanism of PC gene regulation of apple fruit coloration.
A method for mining condition-specific co-expressed genes in Camellia sinensis based on k-means clustering
Authors: Zheng Xinghai , Lim Peng Ken , Mutwil Marek , Wang Yuefei
Published: May 2024

Background

As one of the world’s most important beverage crops, tea plants (Camellia sinensis) are renowned for their unique flavors and numerous beneficial secondary metabolites, attracting researchers to investigate the formation of tea quality. With the increasing availability of transcriptome data on tea plants in public databases, conducting large-scale co-expression analyses has become feasible to meet the demand for functional characterization of tea plant genes. However, as the multidimensional noise increases, larger-scale co-expression analyses are not always effective. Analyzing a subset of samples generated by effectively downsampling and reorganizing the global sample set often leads to more accurate results in co-expression analysis. Meanwhile, global-based co-expression analyses are more likely to overlook condition-specific gene interactions, which may be more important and worthy of exploration and research.

Results

Here, we employed the k-means clustering method to organize and classify the global samples of tea plants, resulting in clustered samples. Metadata annotations were then performed on these clustered samples to determine the “conditions” represented by each cluster. Subsequently, we conducted gene co-expression network analysis (WGCNA) separately on the global samples and the clustered samples, resulting in global modules and cluster-specific modules. Comparative analyses of global modules and cluster-specific modules have demonstrated that cluster-specific modules exhibit higher accuracy in co-expression analysis. To measure the degree of condition specificity of genes within condition-specific clusters, we introduced the correlation difference value (CDV). By incorporating the CDV into co-expression analyses, we can assess the condition specificity of genes. This approach proved instrumental in identifying a series of high CDV transcription factor encoding genes upregulated during sustained cold treatment in Camellia sinensis leaves and buds, and pinpointing a pair of genes that participate in the antioxidant defense system of tea plants under sustained cold stress.

Conclusions

To summarize, downsampling and reorganizing the sample set improved the accuracy of co-expression analysis. Cluster-specific modules were more accurate in capturing condition-specific gene interactions. The introduction of CDV allowed for the assessment of condition specificity in gene co-expression analyses. Using this approach, we identified a series of high CDV transcription factor encoding genes related to sustained cold stress in Camellia sinensis. This study highlights the importance of considering condition specificity in co-expression analysis and provides insights into the regulation of the cold stress in Camellia sinensis.
Triple-drug combination therapy versus six-month proton pump inhibitor monotherapy in non-Helicobacter pylori Helicobacter eradication, and hyperacid environment preference of Helicobacter suis: a clinical study
Authors: Tsukadaira Toshihisa , Hayashi Seiichi , Ota Hiroyoshi , Kobayashi Natsuko , Agawa Hiroyuki , Kodaira Himiko , Sekiguchi Yasuhiro , Matsumoto Takehisa , Horiuchi Kazuki , Negishi Tatsuya , Tada Toshifumi
Published: May 2024

Background

At present, eradication regimens for non-Helicobacter pylori Helicobacter (NHPH) have not been established yet. We investigated effectiveness of the standard triple-drug combination therapy for Helicobacter pylori eradication and of a proton pump inhibitor (PPI) monotherapy in eradication of NHPH.

Methods

Subjects were the patients who were diagnosed with NHPH-infected gastritis based on microscopic findings, helical-shaped organisms obviously larger than Helicobacter pylori, in the gastric mucosal specimens using Giemsa staining at Kenwakai Hospital between November 2010 and September 2021, whose NHPH species were identified by polymerase chain reaction (PCR) analysis of urease genes in endoscopically-biopsied samples, and who consented to NHPH eradication with either the triple-drug combination therapy for one week or a PPI monotherapy for six months. Six months after the completion of eradication, its result was determined with esophagogastroduodenoscopy, microscopic examination, and PCR analysis. In cases of unsuccessful eradication, a second eradication with the other therapy was suggested to the patient.

Results

PCR analysis detected NHPH in 38 patients: 36 as Helicobacter suis and two as Helicobacter heilmannii/Helicobacter ailurogastricus. Fourteen Helicobacter suis-infected and one Helicobacter heilmannii/Helicobacter ailurogastricus-infected patients requested eradication therapy. The triple-drug combination therapy succeeded in four of five patients, while the PPI monotherapy succeeded in five of 10 patients. Three of five patients who had been unsuccessful with the latter therapy requested the triple-drug combination therapy as the second eradication and all three were successful. In total, the triple-drug combination therapy succeeded in seven out of eight (87.5%) attempted cases, while the PPI monotherapy in five out of 10 (50%) attempted cases.

Conclusions

In NHPH eradication, the triple-drug combination therapy was considered to be effective to some extent and to become the first-line therapy. While, although less successful, PPI monotherapy appeared to be a potentially promising option particularly for patients with allergy or resistance to antibiotics. Effectiveness of PPI monotherapy may be attributed to hyperacid environment preference of Helicobacter suis and PPI’s acid-suppressive effect. Additionally, male predominance in NHPH-infected gastritis patients may be explained by gender difference in gastric acid secretory capacity. However, further evidence needs to be accumulated.

Study registration

This study was approved by the Research Ethics Committee of Kenwakai Hospital (No. 2,017,024).
The relationship between childhood adversity and sleep quality among rural older adults in China: the mediating role of anxiety and negative coping
Authors: Zhang Yuqin , Lin Chengwei , Li Hongwei , Li Lei , Zhou Xueyan , Xiong Ying , Yan Jin , Xie Mengxue , Zhang Xueli , Zhou Chengchao , Yang Lian
Published: May 2024

Background

Studies have revealed the effects of childhood adversity, anxiety, and negative coping on sleep quality in older adults, but few studies have focused on the association between childhood adversity and sleep quality in rural older adults and the potential mechanisms of this influence. In this study, we aim to evaluate sleep quality in rural older adults, analyze the impact of adverse early experiences on their sleep quality, and explore whether anxiety and negative coping mediate this relationship.

Methods

Data were derived from a large cross-sectional study conducted in Deyang City, China, which recruited 6,318 people aged 65 years and older. After excluding non-agricultural household registration and lack of key information, a total of 3,873 rural older adults were included in the analysis. Structural equation modelling (SEM) was used to analyze the relationship between childhood adversity and sleep quality, and the mediating role of anxiety and negative coping.

Results

Approximately 48.15% of rural older adults had poor sleep quality, and older adults who were women, less educated, widowed, or living alone or had chronic illnesses had poorer sleep quality. Through structural equation model fitting, the total effect value of childhood adversity on sleep quality was 0.208 (95% CI: 0.146, 0.270), with a direct effect value of 0.066 (95% CI: 0.006, 0.130), accounting for 31.73% of the total effect; the total indirect effect value was 0.142 (95% CI: 0.119, 0.170), accounting for 68.27% of the total effect. The mediating effects of childhood adversity on sleep quality through anxiety and negative coping were significant, with effect values of 0.096 (95% CI: 0.078, 0.119) and 0.024 (95% CI: 0.014, 0.037), respectively. The chain mediating effect of anxiety and negative coping between childhood adversity and sleep quality was also significant, with an effect value of 0.022 (95% CI: 0.017, 0.028).

Conclusions

Anxiety and negative coping were important mediating factors for rural older adult’s childhood adversity and sleep quality. This suggests that managing anxiety and negative coping in older adults may mitigate the negative effects of childhood adversity on sleep quality.
SARS-CoV-2 vaccine breakthrough infection and the evaluation of safety precaution practice before and after vaccination among healthcare workers in South West, Nigeria
Authors: Oni Oluwatosin Idowu , Osho Patrick Olanrewaju , Odesanmi Tayelolu Mary , Raji Habeebat Motunrayo , Oluranti Faith Titilayo , Ibina Demian
Published: May 2024

Introduction

Worldwide, it has been reported that fully vaccinated people still die of COVID-19-associated symptoms, generating public uncertainty about the safety and effectiveness of the vaccines. Hence, this research is aimed at assessing the incidence of COVID-19 breakthrough infection among vaccinated Health Workers and the possible effect of changes in the practice of post-vaccination safety precautions.

Method

This was a Health facility-based descriptive cross-sectional study. Data were collected using self-administered questionnaires distributed at the participant’s work unit across the selected health facilities. The nasopharyngeal specimen was also obtained from the participants and analysed using STANDARD Q COVID-19 Ag Test rapid chromatographic immunoassay for the detection of antigens to SARS-CoV-2. All data were input and analyzed using SPSS version 20.

Results

There was a statistically significant relationship between the vaccination status of respondents and the post-vaccination test result (χ2 = 6.816, df = 1, p = 0.009). The incidence of COVID-19 infection among the vaccinated and unvaccinated HCWs was 2% and 8% respectively. 5 of the 15 respondents who tested positive for COVID-19 had been fully vaccinated. However, all 5 of them did not practice safety measures after vaccination. None of the respondents who practised safety measures after vaccination tested positive for COVID-19. The remaining 10 respondents that tested positive for COVID-19 had not been vaccinated though they practised safety precautions.

Conclusion

Vaccination and the practice of safety precautions will go a long way to preventing future COVID-19 breakthrough infections.
Simvastatin attenuates silica-induced pulmonary inflammation and fibrosis in rats via the AMPK-NOX pathway
Authors: Bo Cunxiang , Liu Fang , Zhang Zewen , Du Zhongjun , Xiu Haidi , Zhang Zhenling , Li Ming , Zhang Caiqing , Jia Qiang
Published: May 2024

Background

Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms.

Methods

The rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway.

Results

Sim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α and transforming growth factor-β1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions.

Conclusions

Sim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.
Real-world efficacy of adjuvant therapy for totally resected stage I lung adenocarcinoma patients with pathological high-risk factors: propensity score analysis
Authors: Zhao Ke , Yang Libing , Liu Lei , Wang Guige , Zhang Jiaqi , Gao Xuehan , Guo Chao , Huang Cheng , Chen Yeye , Li Shanqing
Published: May 2024

Background

We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors.

Methods

Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan–Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance.

Results

A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative.

Conclusions

Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.
Association of phthalate metabolites with periodontitis: a population-based study
Authors: Bian Mengyao , Jiang Wenxiang , Wang Manting , Shi Ying , Wu Zhifang
Published: May 2024

Background

Widespread exposure to phthalates may raise the probability of various diseases. However, the association of phthalate metabolites with periodontitis remains unclear.

Methods

Totally 3402 participants from the National Health and Nutrition Examination Survey (NHANES) 2009 to 2014 cycles were enrolled in the cross-sectional investigation. We utilized weighted logistic regression to evaluate the association of ten phthalate metabolites with periodontitis. Restricted cubic spline analysis was applied to investigate potential nonlinear relationships.

Results

The weighted prevalence of periodontitis in the study was 42.37%. A one standard deviation (SD) rise in log-transformed levels of mono-2-ethyl-5-carboxypenty phthalate (MECPP), mono-n-butyl phthalate (MnBP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-isobutyl phthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-benzyl phthalate (MBzP) was associated with higher odds of periodontitis, with odds ratios (95% confidence intervals) of 1.08 (1.02-1.14), 1.07 (1.02-1.11), 1.10 (1.05-1.15), 1.05 (1.01-1.09), 1.09 (1.04-1.14), and 1.08 (1.03-1.13), respectively. Individuals with the highest quartile concentrations of MECPP, MnBP, MEHHP, MEOHP, and MBzP were associated with 32%, 20%, 30%, 25%, and 26% increased odds of periodontitis, respectively, compared to those with the lowest quartile. Additionally, mono-(3-carboxypropyl) phthalate (MCPP) demonstrated an interesting inverted J-shaped relationship with periodontitis.

Conclusions

The findings indicate an association of certain phthalate metabolites with periodontitis among US adults.
Structural and social changes due to the COVID-19 pandemic and their impact on engagement in substance use disorder treatment services: a qualitative study among people with a recent history of injection drug use in Baltimore, Maryland
Authors: Patel Eshan U. , Grieb Suzanne M. , Winiker Abigail K. , Ching Jennifer , Schluth Catherine G. , Mehta Shruti H. , Kirk Gregory D. , Genberg Becky L.
Published: May 2024

Background

Substance use disorder treatment and recovery support services are critical for achieving and maintaining recovery. There are limited data on how structural and social changes due to the COVID-19 pandemic impacted individual-level experiences with substance use disorder treatment-related services among community-based samples of people who inject drugs.

Methods

People with a recent history of injection drug use who were enrolled in the community-based AIDS Linked to the IntraVenous Experience study in Baltimore, Maryland participated in a one-time, semi-structured interview between July 2021 and February 2022 about their experiences living through the COVID-19 pandemic (n = 28). An iterative inductive coding process was used to identify themes describing how structural and social changes due to the COVID-19 pandemic affected participants’ experiences with substance use disorder treatment-related services.

Results

The median age of participants was 54 years (range = 24–73); 10 (36%) participants were female, 16 (57%) were non-Hispanic Black, and 8 (29%) were living with HIV. We identified several structural and social changes due the pandemic that acted as barriers and facilitators to individual-level engagement in treatment with medications for opioid use disorder (MOUD) and recovery support services (e.g., support group meetings). New take-home methadone flexibility policies temporarily facilitated engagement in MOUD treatment, but other pre-existing rigid policies and practices (e.g., zero-tolerance) were counteracting barriers. Changes in the illicit drug market were both a facilitator and barrier to MOUD treatment. Decreased availability and pandemic-related adaptations to in-person services were a barrier to recovery support services. While telehealth expansion facilitated engagement in recovery support group meetings for some participants, other participants faced digital and technological barriers. These changes in service provision also led to diminished perceived quality of both virtual and in-person recovery support group meetings. However, a facilitator of recovery support was increased accessibility of individual service providers (e.g., counselors and Sponsors).

Conclusions

Structural and social changes across several socioecological levels created new barriers and facilitators of individual-level engagement in substance use disorder treatment-related services. Multilevel interventions are needed to improve access to and engagement in high-quality substance use disorder treatment and recovery support services among people who inject drugs.
Microinvasion in hepatocellular carcinoma: predictive factor and application for definition of clinical target volume for radiotherapy
Authors: Yan Huamei , Liu Lili , Wang Donghui , Xu Jianliang , Sun Yaling , Liang Shaobo , Huang Yongheng , Hao Xinzhao , Lin Nan , Xu Xiangying
Published: May 2024

Background

To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC.

Methods

HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging.

Results

The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from − 29.03% to 34.78%.

Conclusions

CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.
Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury
Authors: Shad Ali , Rewell Sarah S. J. , Macowan Matthew , Gandasasmita Natasha , Wang Jiping , Chen Ke , Marsland Ben , O’Brien Terence J. , Li Jian , Semple Bridgette D.
Published: May 2024

Pneumonia is a common comorbidity in patients with severe traumatic brain injury (TBI), and is associated with increased morbidity and mortality. In this study, we established a model of intratracheal Klebsiella pneumoniae administration in young adult male and female mice, at 4 days following an experimental TBI, to investigate how K. pneumoniae infection influences acute post-TBI outcomes. A dose-response curve determined the optimal dose of K. pneumoniae for inoculation (1 x 10^6 colony forming units), and administration at 4 days post-TBI resulted in transient body weight loss and sickness behaviors (hypoactivity and acute dyspnea). K. pneumoniae infection led to an increase in pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid at 24 h post-infection, in both TBI and sham (uninjured) mice. By 7 days, when myeloperoxidase + neutrophil numbers had returned to baseline in all groups, lung histopathology was observed with an increase in airspace size in TBI + K. pneumoniae mice compared to TBI + vehicle mice. In the brain, increased neuroinflammatory gene expression was observed acutely in response to TBI, with an exacerbated increase in Ccl2 and Hmox1 in TBI + K. pneumoniae mice compared to either TBI or K. pneumoniae alone. However, the presence of neuroinflammatory immune cells in the injured brain, and the extent of damage to cortical and hippocampal brain tissue, was comparable between K. pneumoniae and vehicle-treated mice by 7 days. Examination of the fecal microbiome across a time course did not reveal any pronounced effects of either injury or K. pneumoniae on bacterial diversity or abundance. Together, these findings demonstrate that K. pneumoniae lung infection after TBI induces an acute and transient inflammatory response, primarily localized to the lungs with some systemic effects. However, this infection had minimal impact on secondary injury processes in the brain following TBI. Future studies are needed to evaluate the potential longer-term consequences of this dual-hit insult.
Social protection and the International Monetary Fund: promise versus performance
Authors: Kentikelenis Alexandros , Stubbs Thomas
Published: May 2024

Background

Countries in the Global South are currently facing momentous economic and social challenges, including major debt service problems. As in previous periods of global financial instability, a growing number of countries have turned to the International Monetary Fund (IMF) for financial assistance. The organization has a long track-record of advocating for extensive fiscal consolidation—commonly known as ‘austerity’—for its borrowers. However, in recent years, the IMF has announced major initiatives for ensuring that its loans support social spending, thus aiding countries in meeting their development targets and the Sustainable Development Goals. To assess this track record, we collected spending data on 21 loans signed in the 2020–2022 period, including from all their periodic reviews up to August 2023.

Results

We find that austerity measures remain a core part of the organization’s mandated policies for its borrowers: 15 of the 21 countries studied here experience a decrease in fiscal space over the course of their IMF programs. Against this fiscal backdrop, social spending floors have failed to live up to their promise. There is no streamlined definition of these floors, thus rendering their application haphazard and inconsistent. But even on their own terms, these floors lack ambition: they often do not foresee trajectories of meaningful social spending increases over time, and, when they do, many of these gains are eaten up by soaring inflation. In addition, a third of social spending floors are not implemented—a much lower implementation rate from that for austerity conditions, which the IMF prioritizes. In several instances, where floors are implemented, they are not meaningfully exceeded, thus—in practice—acting as social spending ceilings.

Conclusions

The IMF’s lending programs are still heavily focused on austerity, and its strategy on social spending has not represented the sea-change that the organization advertised. At best, social spending floors act as damage control for the painful budget cuts: they are instruments of social amelioration, underpinned by principles of targeted assistance for highly disadvantaged groups. Alternative approaches rooted in principles of universalism can be employed to build up durable and resilient social protection systems.
Assessing the effect of sample storage time on viral detection using a rapid and cost-effective CTAB-based extraction method
Authors: Mark Deogratius , Tairo Fred , Ndunguru Joseph , Kweka Elisiana , Saggaf Maliha , Bachwenkizi Hilda , Chiunga Evangelista , Lusana James Leonard , Sikazwe Geofrey , Maghembe Reuben
Published: May 2024

Background

Cassava leaf samples degrade quickly during storage and transportation from distant areas. Proper sampling and efficient, low-cost storage methods are critical for obtaining sufficient quality DNA and RNA for plant virus epidemiology and improving disease control understanding. This is useful when samples are collected from remote areas far from a laboratory or in developing countries where money and materials for virus diagnostics are scarce.

Results

The effect of sample storage duration on nucleic acid (N.A.) quality on virus detection was investigated in this study. A simple, rapid, and cost-effective CTAB-based approach (M3) for single N.A. extraction was optimized and tested alongside two existing CTAB-based methods (M1 and M2) for N.A. extraction from fresh and herbarium cassava leaves stored for; 1, 8, 26, and 56 months. The amount and quality of DNA and RNA were determined using Nanodrop 2000 c U.V.–vis Spectrophotometer and agarose gel electrophoreses. The sample degradation rate was estimated using a simple mathematical model in Matlab computational software. The results show no significant difference in mean DNA concentration between M1 and M2 but a significant difference between M3 and the other two methods at p < 0.005. The mean DNA concentration extracted using M3 was higher for 1 and 8 months of leave storage. M3 and M2 produced high concentrations at 26 and 56 months of leave storage. Using a developed scale for quality score, M3 and M2 produced high-quality DNA from fresh samples. All methods produced poor-quality DNA and RNA at 8 and 26 months of leave storage and no visual bands at the age of 56 months. Statistically, there was a significant difference in the mean DNA quality between M1 and M2, but there was no significant difference between M3 and the other two methods at p < 0.005. However, Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV) were readily detected by RT-PCR from RNA isolated using M3. The quality of DNA declined per storage time at 0.0493 and 0.0521/month, while RNA was 0.0678 and 0.0744/month. Compared to the existing two methods, modified CTAB extracted enough high-quality N.A. in one-third the time of the existing two methods.

Conclusion

Our method provides cost-effective, quick, and simple processing of fresh and dry samples, which will quicken and guide the decision on when and what type of sample to process for plant disease management and surveillance actions.
Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial
Authors: Nguyen Ngoc-Huynh Ton , Phan Hao Thanh , Le Phong Minh , Nguyen Lan-Huong Thi , Do Thuy Thi , Phan Thien-Phuc Thanh , Van Le Trinh , Dang Thanh Minh , Phan Chinh-Nhan Lu , Dang Tung-Loan Thi , Truong Nhung Hai
Published: May 2024

Background

Inflamm-aging is associated with the rate of aging and is significantly related to diseases such as Alzheimer’s disease, Parkinson’s disease, atherosclerosis, heart disease, and age-related degenerative diseases such as type II diabetes and osteoporosis. This study aims to evaluate the safety and efficiency of autologous adipose tissue-derived mesenchymal stem cell (AD-MSC) transplantation in aging-related low-grade inflammation patients.

Methods

This study is a single-group, open-label, phase I clinical trial in which patients treated with 2 infusions (100 million cells i.v) of autologous AD-MSCs were initially evaluated in 12 inflamm-aging patients who concurrently had highly proinflammatory cytokines and 2 of the following 3 diseases: diabetes, dyslipidemia, and obesity. The treatment effects were evaluated based on plasma cytokines.

Results

During the study’s follow-up period, no adverse effects were observed in AD-MSC injection patients. Compared to baseline (D-44), the inflammatory cytokines IL-1α, IL-1β, IL-8, IL-6, and TNF-α were significantly reduced after 180 days (D180) of MSC infusion. IL-4/IL-10 at 90 days (D90) and IL-2/IL-10 at D180 increased, reversing the imbalance between proinflammatory and inflammatory ratios in the patients.

Conclusion

AD-MSCs represent a potential intervention to prevent age-related inflammation in patients.

Trial registration

ClinicalTrials.gov number is NCT05827757, first registered on 13th Oct 2020
Characterizing genetic variation on the Z chromosome in Schistosoma japonicum reveals host-parasite co-evolution
Authors: Zhou An , Zhang Wei , Ge Xueling , Liu Qi , Luo Fang , Xu Shuhua , Hu Wei , Lu Yan
Published: May 2024

Background

Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems. Schistosoma japonicum is endemic to Asia; the Z chromosome of S. japonicum comprises one-quarter of the entire genome. Detection of positive selection using resequencing data to understand adaptive evolution has been applied to a variety of pathogens, including S. japonicum. However, the contribution of the Z chromosome to evolution and adaptation is often neglected.

Methods

We obtained 1,077,526 high-quality SNPs on the Z chromosome in 72 S. japonicum using re-sequencing data publicly. To examine the faster Z effect, we compared the sequence divergence of S. japonicum with two closely related species, Schistosoma haematobium and S. mansoni. Genetic diversity was compared between the Z chromosome and autosomes in S. japonicum by calculating the nucleotide diversity (π) and Dxy values. Population structure was also assessed based on PCA and structure analysis. Besides, we employed multiple methods including Tajima’s D, FST, iHS, XP-EHH, and CMS to detect positive selection signals on the Z chromosome. Further RNAi knockdown experiments were performed to investigate the potential biological functions of the candidate genes.

Results

Our study found that the Z chromosome of S. japonicum showed faster evolution and more pronounced genetic divergence than autosomes, although the effect may be smaller than the variation among genes. Compared with autosomes, the Z chromosome in S. japonicum had a more pronounced genetic divergence of sub-populations. Notably, we identified a set of candidate genes associated with host-parasite co-evolution. In particular, LCAT exhibited significant selection signals within the Taiwan population. Further RNA interference experiments suggested that LCAT is necessary for S. japonicum survival and propagation in the definitive host. In addition, we identified several genes related to the specificity of the intermediate host in the C-M population, including Rab6 and VCP, which are involved in adaptive immune evasion to the host.

Conclusions

Our study provides valuable insights into the adaptive evolution of the Z chromosome in S. japonicum and further advances our understanding of the co-evolution of this medically important parasite and its hosts.

Graphical Abstract
The nutritional benefits of maize-soybean rotational systems in the North-Western Free State, South Africa
Authors: de Bruyn Melanie , Nel Andrè , van Niekerk Johan
Published: May 2024

Background

Malnutrition is one of the major health concerns, particularly in the developing and under-developed world. In South Africa, maize is produced as a staple food and is the primary food for most of the country’s population. The North-Western Free State which forms part of the Nala municipality in the Lejweleputswa district of South Africa is a main producer of the country’s maize. However, the area is known for its sandy soil which contains little organic material, silt and clay. Maize in this area is normally grown in monoculture but with a focus on sustainable agriculture has recently incorporated soybean. As a means of fighting malnutrition, the objective of this study was to determine the influence that soybean incorporation as a rotation crop has on the nutritional value of maize.

Methods

A trial was conducted on the farm Christinasrus in the North-Western Free State to compare the nutritional value of monoculture maize and maize in rotation with soybean over three consecutive seasons. Maize kernel samples were taken each season and its nutritional properties analyzed. Subsequent data were further analyzed using statistical analysis.

Results

Results showed that there was a seasonal effect on all nutritional properties with a general decrease in nutritional values in wetter years. Cropping systems had an effect on fibre content, with increased values observed in maize after soybean. In addition, there was a significant interaction between season and cropping systems on the total digestible nutritional value, with maize after soybean being more nutritious in wetter seasons.

Conclusion

Results suggest that maize in cropping systems with soybean has potential to be more nutritious while the soybean in the cropping system can act as a protein-rich companion, providing a more balanced diet for human consumption, thereby fighting malnutrition.
Changes in vitamins and trace elements after initiation of highly effective CFTR modulator therapy in children and adults with cystic fibrosis – a real-life insight
Authors: Fabricius Dorit , Knieling Tina , Zurmuehl Noelle , Makedon Leandra , Freihorst Joachim , Schmidt Hanna , Bode Sebastian
Published: May 2024

Background

Highly-effective CFTR-modulator therapy with elexa-/teza-/ivacaftor (ETI) has led to improvements in pulmonary outcomes, sweat chloride, body mass index (BMI) and quality of life in people with cystic fibrosis (CF). Improved uptake of fat-soluble vitamins and micronutrients has been reported for CFTR-modulators but data regarding ETI therapy is lacking.

Methods

This single-center retrospective study evaluated forced expiratory volume in one second (FEV-1), sweat chloride, BMI, transaminases (AST, ALT), bilirubin, vitamins A, D, E, zinc and selenium in children and adults eligible for ETI. Parameters were assessed before and up to one year after initiation of ETI.

Results

58 patients (median age m = 28 years, SD ± 11.6 years, 51.7% female14 < 18 years old) were included. FEV-1 and sweat chloride improved significantly after ETI. There were no changes in BMI or AST. ALT was increased significantly after 4 weeks of ETI but returned to normal levels in further course. Bilirubin levels remained elevated after ETI. Vitamin A was significantly higher 12 months after ETI. No changes were found for vitamins D, E, zinc and selenium.

Conclusions

This study adds to the evidence that improvements of some fat-soluble vitamin levels can be found after ETI. No changes regarding micronutrients were noted. Individualized follow-up and supplementation are recommended.
Stress change in southwest Japan due to the 1944–1946 Nankai megathrust rupture sequence based on a 3-D heterogeneous rheological model
Authors: Hashima Akinori , Hori Takane , Iinuma Takeshi , Murakami Sota , Fujita Kohei , Ichimura Tsuyoshi
Published: May 2024

The Nankai trough has repeatedly experienced large megathrust earthquakes at intervals of 100–200 years. The inland region of southwest (SW) Japan has a seismically active period from 50 years before to 10 years after megathrust earthquakes. To assess the activities of inland earthquakes after megathrust earthquakes, we need to quantitatively evaluate the postseismic stress accumulation on the inland source faults considering plausible viscoelastic relaxation. Recent studies have shown the importance of low-viscosity layers along the lithosphere-asthenosphere boundary (LAB layer) in postseismic deformation. In the present study, we focus on the most recent ruptures, the 1944 M7.9 Tonankai and the 1946 M8.0 Nankai earthquakes, estimating the 4-year stress change on the source faults in SW Japan in a forward modeling approach. The 1944–1946 megathrust rupture sequence was followed by severe ~ M7 inland earthquakes, such as the 1945 M6.8 Mikawa and 1948 M7.1 Fukui earthquakes. For stress calculation, we used a highly detailed finite element model incorporating the actual topography and the plausible viscoelastic underground structure from past studies. The calculated inland stress field shows the dominance of the coseismic change during the 1944 and 1946 earthquakes and little contribution from viscoelastic relaxation. In contrast, viscoelastic relaxation has a significant effect on stress in the slab, indicating the importance of quantifying the viscosity of the LAB layer. Based on the calculated stress, we evaluated the change in the Coulomb failure stress (ΔCFS) on each source fault. The ΔCFS is generally positive on the strike-slip faults east of 135°E due to the 1944 rupture. In contrast, the ΔCFS on the faults west of 135°E, including the Median Tectonic Line segments, became positive due to the 1946 rupture. The occurrence of the damaging earthquakes in 1945 and 1948 can be explained by the calculated ΔCFS. The ΔCFS on the recent earthquake faults of the recent damaging earthquakes such as the 2016 M7.2 Kumamoto earthquake is generally negative, suggesting the delay in stress accumulation. The ΔCFS on the source faults of the intra-slab earthquakes differ significantly as large as tens of kilopascals depending on the viscosity of the LAB layer.

Graphical Abstract
Numerical experiment toward simultaneous estimation of the spatiotemporal evolution of interseismic fault slips and block motions in southwest Japan
Authors: Tanaka Yusuke , Kano Masayuki , Nishimura Takuya , Ohta Yusaku , Yano Keisuke
Published: May 2024

Interseismic strain around southwest Japan can be attributed to slip phenomena on the plate interface and processes inside the continental plate, such as block motions and inland fault slips. Although many crustal deformation analyses have been carried out, the simultaneous estimation of these phenomena and comprehensive discussion regarding the effect on the total strain budget remain topics to be investigated. In this study, we conducted numerical experiment to evaluate the possibility of simultaneously monitoring the spatiotemporal evolution of interseismic fault slips and block motions based on state-space modeling. We aimed to estimate fault slips and block motions using the time series of dense continuous Global Navigation Satellite System sites covering southwest Japan, encompassing 25 years from 1996 onward. We calculated synthetic block motions of the forearc region, monotonically increasing back slips on block boundary faults, and long-term slow slip events in the Tokai region, Kii Channel, and Bungo Channel. Subsequently, we generated the expected synthetic displacement time-series at GNSS stations. Applying Kalman filtering, we successfully estimated the spatiotemporal evolution of block motions, cumulative back slips, multiple slow slip events occurring in different regions. Although the contributions of fault slips and block motions showed slight trade-off, main characteristics of the slip distributions and the direction of block motions were well-recovered. We recovered slow slip events with slips of 5–10 cm or larger. We investigated the estimation uncertainty and separation precision of the unknown parameters using the covariance matrix estimated by Kalman filtering. Focusing on the structure of the non-diagonal component of the covariance matrix, we evaluated the complex effects of site and subfault locations on the estimated slip spatial distribution bias. For instance, the extent of the correlation between subfaults suggested that the three slow slip regions have different tendency of the uncertainties of slip areas, extending toward landside, seaward, or both of them. Our framework enables the comprehensive evaluation of the contributions and uncertainties of various deformation sources covering the entire subduction zone.

Graphical abstract
Primus Inter PARES: First among equals—practical strategies for young adult PAtient RESearch partners (PARES) by young adult PARES
Authors: Rao Sandy , Dimitropoulos Gina , Jardine Rae , Quickstad Julien , Satam Laetitia , Qureshi Mohammad , Bui Thyra , Todorova Antoaneta Alexandrova , Tumaneng Ysabelle , Suthakaran Abitha , Dalley Kaiden , Smith Stacie , Patten Scott B. ,   the entire HEARTS Study Team
Published: May 2024

Background

This manuscript is coauthored by 15 young adult Patient RESearch partners (PARES) with lived and living mental health experiences and three institutional researchers across Canada involved in a patient-oriented research (POR) study called the HEARTS Study: Helping Enable Access and Remove Barriers To Support for Young Adults with Mental Health-Related Disabilities. We share our reflections, experiences and lessons learned as we grapple with the field of POR for its lack of clarity, hierarchical structures, internalized ableism, and accessibility challenges, among others. To mitigate the difficulties of POR, we started by laying the groundwork for equality by embracing the principle of Primus Inter Pares: First Among Equals as the foundation of our approach. In this way, we began with what we know for certain: the inherent worth and dignity of young adults as equal partners, recognizing their expertise, worldviews, creativity, and capacity to contribute meaningfully and intentionally to the research that affects their lives and futures.

Main Body

The manuscript underscores the need to reconceptualize meaningful engagement in POR, advocating a shift from traditional, biased paradigms that fail to address the complexities faced by young adults with mental illness. It introduces what we have termed Adaptive and Differential Engagement, underscoring the necessity of tailoring participation to individual preferences and circumstances alongside a Tripartite Compensation model that promotes fair and holistic remuneration in research collaborations. Then we discuss the approaches we have conceptualized, such as Equitable Dialogue, Trust Architecture, Community Continuum, Unity in Diversity, Shared Stewardship, and Agile Frameworks that collectively aim to overcome barriers like language intimidation, power imbalances, framework fatigue, consultation burnout, trust deficits, and systemic discrimination and exclusion. The manuscript does not seek to prescribe any universal or standardized solutions; in fact, it seeks the opposite. Instead, it offers a thoughtful and transparent contribution to the POR canon, providing resources for young adults eager to engage in research and institutional researchers aspiring to collaborate with them.

Conclusion

This manuscript is a product of our collective learning and critical self-evaluation. By integrating theoretical insights with practical strategies, we present a justice-oriented blueprint for an inclusive and egalitarian approach to POR. We advocate for applications of POR that are responsive to the individualized contexts of young adult PARES, ensuring their perspectives are central to the research with the resources to take the lead should they choose.