bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential functions of RhoGDIβ in malignant transformation and progression of urothelial cell following N-butyl-N-(4-hydmoxybutyl) nitrosamine exposure
Authors: Hua Xiaohui , Zou Ronghao , Bai Xiaoyue , Yang Yuyao , Lu Juan , Huang Chuanshu
Published: August 2023

Background

Functional role of Rho GDP-dissociation inhibitor beta (RhoGDIβ) in tumor biology appears to be contradictory across various studies. Thus, the exploration of the molecular mechanisms underlying the differential functions of this protein in urinary bladder carcinogenesis is highly significant in the field. Here, RhoGDIβ expression patterns, biological functions, and mechanisms leading to transformation and progression of human urothelial cells (UROtsa cells) were evaluated following varying lengths of exposure to the bladder carcinogen N-butyl-N-(4-hydmoxybutyl) nitrosamine (BBN).

Results

It was seen that compared to expression in vehicle-treated control cells, RhoGDIβ protein expression was downregulated after 2-month of BBN exposure, but upregulated after 6-month of exposure. Assessments of cell function showed that RhoGDIβ inhibited UROtsa cell growth in cells with BBN for 2-month exposure, whereas it promoted the invasion of cells treated with BBN for 6 months. Mechanistic studies revealed that 2-month of BBN exposure markedly attenuated DNMT3a abundance, and this led to reduced miR-219a promoter methylation, increased miR-219a binding to the RhoGDIβ mRNA 3’UTR, and reduced RhoGDIβ protein translation. While after 6-mo of BBN treatment, the cells showed increased PP2A/JNK/C-Jun axis phosphorylation and this in turn mediated overall RhoGDIβ mRNA transcription and protein expression as well as invasion.

Conclusions

These findings indicate that RhoGDIβ is likely to inhibit the transformation of human urothelial cells during the early phase of BBN exposure, whereas it promotes invasion of the transformed/progressed urothelial cells in the late stage of BBN exposure. The studies also suggest that RhoGDIβ may be a useful biomarker for evaluating the progression of human bladder cancers.
Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis
Authors: Prem Kiesha , Choi Yoon Hong , Bénard Élodie , Burger Emily A. , Hadley Liza , Laprise Jean-François , Regan Mary Caroline , Drolet Mélanie , Sy Stephen , Abbas Kaja , Portnoy Allison , Kim Jane J. , Brisson Marc , Jit Mark
Published: August 2023

Background

To eliminate cervical cancer as a public health problem, the World Health Organization had recommended routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual initiation. However, many countries have yet to implement HPV vaccination because of financial or logistical barriers to delivering two doses outside the infant immunisation programme.

Methods

Using three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 188 countries, under scenarios in which one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g. 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021–2120, with a 1-year catch-up campaign up to age 14 at 80% coverage in the first year of the programme.

Results

Over the years 2021–2120, one-dose vaccination at 80% coverage was projected to avert 115.2 million (range of medians: 85.1–130.4) and 146.8 million (114.1–161.6) cervical cancers assuming one dose of the vaccine confers 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 147.8 million (140.6–169.7) cervical cancer cases could be prevented. If protection wanes after 20 years, 65 to 889 additional girls would need to be vaccinated with the second dose to prevent one cervical cancer, depending on the epidemiological profiles of the country. Across all income groups, the threshold cost for the second dose was low: from 1.59 (0.14–3.82) USD in low-income countries to 44.83 (3.75–85.64) USD in high-income countries, assuming one dose confers 30-year protection.

Conclusions

Results were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs, and alleviating vaccine supply constraints. The second dose may become cost-effective if there is a shorter duration of protection from one dose, cheaper vaccine and vaccination delivery strategies, and high burden of cervical cancer.
The recurrent WASF1 nonsense variant identified in two unaffected Chinese families with neurodevelopmental disorder: case report and review of the literatures
Authors: Tang Xiang , Liu Guoqing , Lin Li , Xiao Nong , Chen Yuxia
Published: August 2023

Background

Neurodevelopmental disorder with absent language and variable seizures (NEDALVS, # 618707) are characterized by delayed speech and motor development, ocular abnormalities, and seizures. NEDAVLS is an autosomal dominant disorder caused by de novo mutations in the wasp protein family member 1 (WASF1) gene.

Case presentation

We identified a de novo nonsense variant c.1516 C > T (p.Arg506*) of WASF1 gene (NM_003931.3) in two pediatric female patients with delayed motor and language development.

Conclusion

This case demonstrates the effective role of WES in the diagnosis of NEDALVS. To the best of our knowledge, this variant has not been reported in the Chinese population. This contributes to our further understanding of the disease and to research related to the genetic and clinical heterogeneity, the treatment and prognosis of the disease.
A comparative study of in vitro air–liquid interface culture models of the human airway epithelium evaluating cellular heterogeneity and gene expression at single cell resolution
Authors: Prescott Rachel A. , Pankow Alec P. , de Vries Maren , Crosse Keaton M. , Patel Roosheel S. , Alu Mark , Loomis Cynthia , Torres Victor , Koralov Sergei , Ivanova Ellie , Dittmann Meike , Rosenberg Brad R.
Published: August 2023

Background

The airway epithelium is composed of diverse cell types with specialized functions that mediate homeostasis and protect against respiratory pathogens. Human airway epithelial (HAE) cultures at air–liquid interface are a physiologically relevant in vitro model of this heterogeneous tissue and have enabled numerous studies of airway disease. HAE cultures are classically derived from primary epithelial cells, the relatively limited passage capacity of which can limit experimental methods and study designs. BCi-NS1.1, a previously described and widely used basal cell line engineered to express hTERT, exhibits extended passage lifespan while retaining the capacity for differentiation to HAE. However, gene expression and innate immune function in BCi-NS1.1-derived versus primary-derived HAE cultures have not been fully characterized.

Methods

BCi-NS1.1-derived HAE cultures (n = 3 independent differentiations) and primary-derived HAE cultures (n = 3 distinct donors) were characterized by immunofluorescence and single cell RNA-Seq (scRNA-Seq). Innate immune functions were evaluated in response to interferon stimulation and to infection with viral and bacterial respiratory pathogens.

Results

We confirm at high resolution that BCi-NS1.1- and primary-derived HAE cultures are largely similar in morphology, cell type composition, and overall gene expression patterns. While we observed cell-type specific expression differences of several interferon stimulated genes in BCi-NS1.1-derived HAE cultures, we did not observe significant differences in susceptibility to infection with influenza A virus and Staphylococcus aureus.

Conclusions

Taken together, our results further support BCi-NS1.1-derived HAE cultures as a valuable tool for the study of airway infectious disease.
Association of prior outpatient diabetes screening with cardiovascular events and mortality among people with incident diabetes: a population-based cohort study
Authors: Ke Calvin , Chu Anna , Shah Baiju R. , Tobe Sheldon , Tu Karen , Fang Jiming , Vaid Haris , Liu Peter , Cader Aishah , Lee Douglas S.
Published: August 2023

Background

Outcomes of diabetes screening in contemporary, multi-ethnic populations are unknown. We examined the association of prior outpatient diabetes screening with the risks of cardiovascular events and mortality in Ontario, Canada.

Methods

We conducted a population-based cohort study using administrative databases among adults aged ≥ 20 years with incident diabetes diagnosed during 2014–2016. The exposure was outpatient diabetes screening performed within 3 years prior to diabetes diagnosis. The co-primary outcomes were (1) a composite of all-cause mortality and hospitalization for myocardial infarction, stroke, coronary revascularization, and (2) all-cause mortality (followed up until 2018). We calculated standardized rates of each outcome and conducted cause-specific hazard modelling to determine the adjusted hazard ratio (HR) of the outcomes, adjusting for prespecified confounders and accounting for the competing risk of death.

Results

We included 178,753 Ontarians with incident diabetes (70.2% previously screened). Individuals receiving prior screening were older (58.3 versus 53.4 years) and more likely to be women (49.6% versus 40.0%) than previously unscreened individuals. Individuals receiving prior screening had relatively lower standardized event rates than those without prior screening across all outcomes (composite: 12.8 versus 18.1, mortality: 8.2 versus 11.1 per 1000 patient-years). After multivariable adjustment, prior screening was associated with 34% and 32% lower risks of the composite (HR 0.66, 0.63–0.69) and mortality (0.68, 0.64–0.72) outcomes. Among those receiving prior screening, a result in the prediabetes range was associated with lower risks of the composite (0.82, 0.77–0.88) and mortality (0.71, 0.66–0.78) outcomes than a result in the normoglycemic range.

Conclusions

Previously screened individuals with diabetes had lower risks of cardiovascular events and mortality versus previously unscreened individuals. Better risk assessment tools are needed to support wider and more appropriate uptake of diabetes screening, especially among young adults.
Discovery of novel JAK1 inhibitors through combining machine learning, structure-based pharmacophore modeling and bio-evaluation
Authors: Wang Zixiao , Sun Lili , Xu Yu , Liang Peida , Xu Kaiyan , Huang Jing
Published: August 2023

Background

Janus kinase 1 (JAK1) plays a critical role in most cytokine-mediated inflammatory, autoimmune responses and various cancers via the JAK/STAT signaling pathway. Inhibition of JAK1 is therefore an attractive therapeutic strategy for several diseases. Recently, high-performance machine learning techniques have been increasingly applied in virtual screening to develop new kinase inhibitors. Our study aimed to develop a novel layered virtual screening method based on machine learning (ML) and pharmacophore models to identify the potential JAK1 inhibitors.

Methods

Firstly, we constructed a high-quality dataset comprising 3834 JAK1 inhibitors and 12,230 decoys, followed by establishing a series of classification models based on a combination of three molecular descriptors and six ML algorithms. To further screen potential compounds, we constructed several pharmacophore models based on Hiphop and receptor-ligand algorithms. We then used molecular docking to filter the recognized compounds. Finally, the binding stability and enzyme inhibition activity of the identified compounds were assessed by molecular dynamics (MD) simulations and in vitro enzyme activity tests.

Results

The best performance ML model DNN-ECFP4 and two pharmacophore models Hiphop3 and 6TPF 08 were utilized to screen the ZINC database. A total of 13 potentially active compounds were screened and the MD results demonstrated that all of the above molecules could bind with JAK1 stably in dynamic conditions. Among the shortlisted compounds, the four purchasable compounds demonstrated significant kinase inhibition activity, with Z-10 being the most active (IC50 = 194.9 nM).

Conclusion

The current study provides an efficient and accurate integrated model. The hit compounds were promising candidates for the further development of novel JAK1 inhibitors.
Multiparametric chemical exchange saturation transfer MRI detects metabolic changes in breast cancer following immunotherapy
Authors: Hoffmann Emily , Schache Daniel , Höltke Carsten , Soltwisch Jens , Niland Stephan , Krähling Tobias , Bergander Klaus , Grewer Martin , Geyer Christiane , Groeneweg Linda , Eble Johannes A. , Vogl Thomas , Roth Johannes , Heindel Walter , Maus Bastian , Helfen Anne , Faber Cornelius , Wildgruber Moritz , Gerwing Mirjam , Hoerr Verena
Published: August 2023

Background

With metabolic alterations of the tumor microenvironment (TME) contributing to cancer progression, metastatic spread and response to targeted therapies, non-invasive and repetitive imaging of tumor metabolism is of major importance. The purpose of this study was to investigate whether multiparametric chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) allows to detect differences in the metabolic profiles of the TME in murine breast cancer models with divergent degrees of malignancy and to assess their response to immunotherapy.

Methods

Tumor characteristics of highly malignant 4T1 and low malignant 67NR murine breast cancer models were investigated, and their changes during tumor progression and immune checkpoint inhibitor (ICI) treatment were evaluated. For simultaneous analysis of different metabolites, multiparametric CEST-MRI with calculation of asymmetric magnetization transfer ratio (MTRasym) at 1.2 to 2.0 ppm for glucose-weighted, 2.0 ppm for creatine-weighted and 3.2 to 3.6 ppm for amide proton transfer- (APT-) weighted CEST contrast was conducted. Ex vivo validation of MRI results was achieved by 1H nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization mass spectrometry imaging with laser postionization and immunohistochemistry.

Results

During tumor progression, the two tumor models showed divergent trends for all examined CEST contrasts: While glucose- and APT-weighted CEST contrast decreased and creatine-weighted CEST contrast increased over time in the 4T1 model, 67NR tumors exhibited increased glucose- and APT-weighted CEST contrast during disease progression, accompanied by decreased creatine-weighted CEST contrast. Already three days after treatment initiation, CEST contrasts captured response to ICI therapy in both tumor models.

Conclusion

Multiparametric CEST-MRI enables non-invasive assessment of metabolic signatures of the TME, allowing both for estimation of the degree of tumor malignancy and for assessment of early response to immune checkpoint inhibition.
Immune response in influenza virus infection and modulation of immune injury by viral neuraminidase
Authors: Jiang Hongyu , Zhang Zongde
Published: August 2023

Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza virus infection results in hypercytokinemia, which is responsible for mortality and morbidity. The influenza A virus surface glycoprotein neuraminidase (NA) plays a vital role in viral attachment, entry, and virion release from infected cells. NA acts as a sialidase, which cleaves sialic acids from cell surface proteins and carbohydrate side chains on nascent virions. Here, we review progress in understanding the role of NA in modulating host immune response to influenza virus infection. We also discuss recent exciting findings targeting NA protein to interrupt influenza-induced immune injury.
Inequalities in early initiation of breastfeeding in Bangladesh: an estimation of relative and absolute measures of inequality
Authors: Kundu Satyajit , Chowdhury Syed Sharaf Ahmed , Hasan Md Tamzid , Sharif Azaz Bin
Published: August 2023

Background

Evidence suggested that inequalities based on education, wealth status, place of residence, and geographical regions significantly influence the key breastfeeding indicators including early initiation of breastfeeding. This study aimed to estimate the trends and magnitude of inequalities in early initiation of breastfeeding practice in Bangladesh from 2004 to 2017 applying both absolute and relative measures of inequality.

Methods

We used data from the last five Bangladesh Demographic Health Survey (BDHS) from 2004 to 2017 to measure the inequalities in early initiation of breastfeeding practice using the WHO’s Health Equity Assessment Toolkit (HEAT) software. Following summary measures were estimated to measure the inequalities: Population Attributable Risk (PAR), Population Attributable Fraction (PAF), Difference (D), and Ratio (R) where the equity dimensions were wealth status, education level, sex of child, place of residence, and subnational regions (divisions). For each measure, point estimates along with a 95% confidence interval (CI) were reported.

Results

An uprising pattern in the prevalence of early initiation of breastfeeding was found, where early initiation of breastfeeding increased from 24.9% to 2004 to 59.0% in 2017. We found significant wealth-driven inequalities in early initiation of breastfeeding practice in every wave of survey favoring the poorest wealth quintile (in 2017, D -10.5; 95% CI -16.6 to -4.3). We also identified geographical disparities in early initiation of breastfeeding practice (in 2017, PAF 11.1; 95% CI 2.2 to 19.9) favoring the Rangpur (65.5%), and Sylhet (65.3%) divisions. Education-related disparities were observed in 2004 only, but not in later survey years, which was due to a much lower level of adherence among those with secondary or higher education. There were no significant disparities in early initiation of breastfeeding based on the urban vs. rural residence and sex of the child.

Conclusions

The highest attention should be placed in Bangladesh to attain the WHO’s 100% recommendation of timely initiation of breastfeeding. This study emphasizes on addressing the existing socioeconomic and geographic inequalities. Awareness-raising outreach programs focusing the mothers from wealthier sub-groups and divisions with lower prevalence should be planned and implemented by the joint effort of the government and non-government organizations.
A high-resolution genotype–phenotype map identifies the TaSPL17 controlling grain number and size in wheat
Authors: Liu Yangyang , Chen Jun , Yin Changbin , Wang Ziying , Wu He , Shen Kuocheng , Zhang Zhiliang , Kang Lipeng , Xu Song , Bi Aoyue , Zhao Xuebo , Xu Daxing , He Zhonghu , Zhang Xueyong , Hao Chenyang , Wu Jianhui , Gong Yan , Yu Xuchang , Sun Zhiwen , Ye Botao , Liu Danni , Zhang Lili , Shen Liping , Hao Yuanfeng , Ma Youzhi , Lu Fei , Guo Zifeng
Published: August 2023

Background

Large-scale genotype–phenotype association studies of crop germplasm are important for identifying alleles associated with favorable traits. The limited number of single-nucleotide polymorphisms (SNPs) in most wheat genome-wide association studies (GWASs) restricts their power to detect marker-trait associations. Additionally, only a few genes regulating grain number per spikelet have been reported due to sensitivity of this trait to variable environments.

Results

We perform a large-scale GWAS using approximately 40 million filtered SNPs for 27 spike morphology traits. We detect 132,086 significant marker-trait associations and the associated SNP markers are located within 590 associated peaks. We detect additional and stronger peaks by dividing spike morphology into sub-traits relative to GWAS results of spike morphology traits. We propose that the genetic dissection of spike morphology is a powerful strategy to detect signals for grain yield traits in wheat. The GWAS results reveal that TaSPL17 positively controls grain size and number by regulating spikelet and floret meristem development, which in turn leads to enhanced grain yield per plant. The haplotypes at TaSPL17 indicate geographical differentiation, domestication effects, and breeding selection.

Conclusion

Our study provides valuable resources for genetic improvement of spike morphology and a fast-forward genetic solution for candidate gene detection and cloning in wheat.
A machine learning classifier using 33 host immune response mRNAs accurately distinguishes viral and non-viral acute respiratory illnesses in nasal swab samples
Authors: Pandya Rushika , He Yudong D. , Sweeney Timothy E. , Hasin-Brumshtein Yehudit , Khatri Purvesh
Published: August 2023

Background

Viral acute respiratory illnesses (viral ARIs) contribute significantly to human morbidity and mortality worldwide, but their successful treatment requires timely diagnosis of viral etiology, which is complicated by overlap in clinical presentation with the non-viral ARIs. Multiple pandemics in the twenty-first century to date have further highlighted the unmet need for effective monitoring of clinically relevant emerging viruses. Recent studies have identified conserved host response to viral infections in the blood.

Methods

We hypothesize that a similarly conserved host response in nasal samples can be utilized for diagnosis and to rule out viral infection in symptomatic patients when current diagnostic tests are negative. Using a multi-cohort analysis framework, we analyzed 1555 nasal samples across 10 independent cohorts dividing them into training and validation.

Results

Using six of the datasets for training, we identified 119 genes that are consistently differentially expressed in viral ARI patients (N = 236) compared to healthy controls (N = 146) and further down-selected 33 genes for classifier development. The resulting locked logistic regression-based classifier using the 33-mRNAs had AUC of 0.94 and 0.89 in the six training and four validation datasets, respectively. Furthermore, we found that although trained on healthy controls only, in the four validation datasets, the 33-mRNA classifier distinguished viral ARI from both healthy or non-viral ARI samples with > 80% specificity and sensitivity, irrespective of age, viral type, and viral load. Single-cell RNA-sequencing data showed that the 33-mRNA signature is dominated by macrophages and neutrophils in nasal samples.

Conclusion

This proof-of-concept signature has potential to be adapted as a clinical point-of-care test (‘RespVerity’) to improve the diagnosis of viral ARIs.
Pancreatic draining lymph nodes (PLNs) serve as a pathogenic hub contributing to the development of type 1 diabetes
Authors: Sun Fei , Yang Chun-Liang , Wang Fa-Xi , Rong Shan-Jie , Luo Jia-Hui , Lu Wan-Ying , Yue Tian-Tian , Wang Cong-Yi , Liu Shi-Wei
Published: August 2023

Type 1 diabetes (T1D) is a chronic, progressive autoinflammatory disorder resulting from the breakdown of self-tolerance and unrestrained β cell-reactive immune response. Activation of immune cells is initiated in islet and amplified in lymphoid tissues, especially those pancreatic draining lymph nodes (PLNs). The knowledge of PLNs as the hub of aberrant immune response is continuously being replenished and renewed. Here we provide a PLN-centered view of T1D pathogenesis and emphasize that PLNs integrate signal inputs from the pancreas, gut, viral infection or peripheral circulation, undergo immune remodeling within the local microenvironment and export effector cell components into pancreas to affect T1D progression. In accordance, we suggest that T1D intervention can be implemented by three major ways: cutting off the signal inputs into PLNs (reduce inflammatory β cell damage, enhance gut integrity and control pathogenic viral infections), modulating the immune activation status of PLNs and blocking the outputs of PLNs towards pancreatic islets. Given the dynamic and complex nature of T1D etiology, the corresponding intervention strategy is thus required to be comprehensive to ensure optimal therapeutic efficacy.
Milk oligosaccharide-driven persistence of Bifidobacterium pseudocatenulatum modulates local and systemic microbial metabolites upon synbiotic treatment in conventionally colonized mice
Authors: Larke Jules A. , Heiss Britta E. , Ehrlich Amy M. , Taft Diana H. , Raybould Helen E. , Mills David A. , Slupsky Carolyn M.
Published: August 2023

Background

Bifidobacteria represent an important gut commensal in humans, particularly during initial microbiome assembly in the first year of life. Enrichment of Bifidobacterium is mediated though the utilization of human milk oligosaccharides (HMOs), as several human-adapted species have dedicated genomic loci for transport and metabolism of these glycans. This results in the release of fermentation products into the gut lumen which may offer physiological benefits to the host. Synbiotic pairing of probiotic species with a cognate prebiotic delivers a competitive advantage, as the prebiotic provides a nutrient niche.

Methods

To determine the fitness advantage and metabolic characteristics of an HMO-catabolizing Bifidobacterium strain in the presence or absence of 2′-fucosyllactose (2′-FL), conventionally colonized mice were gavaged with either Bifidobacterium pseudocatenulatum MP80 (B.p. MP80) (as the probiotic) or saline during the first 3 days of the experiment and received water or water containing 2′-FL (as the prebiotic) throughout the study.

Results

16S rRNA gene sequencing revealed that mice provided only B.p. MP80 were observed to have a similar microbiota composition as control mice throughout the experiment with a consistently low proportion of Bifidobacteriaceae present. Using 1H NMR spectroscopy, similar metabolic profiles of gut luminal contents and serum were observed between the control and B.p. MP80 group. Conversely, synbiotic supplemented mice exhibited dramatic shifts in their community structure across time with an overall increased, yet variable, proportion of Bifidobacteriaceae following oral inoculation. Parsing the synbiotic group into high and moderate bifidobacterial persistence based on the median proportion of Bifidobacteriaceae, significant differences in gut microbial diversity and metabolite profiles were observed. Notably, metabolites associated with the fermentation of 2′-FL by bifidobacteria were significantly greater in mice with a high proportion of Bifidobacteriaceae in the gut suggesting metabolite production scales with population density. Moreover, 1,2-propanediol, a fucose fermentation product, was only observed in the liver and brain of mice harboring high proportions of Bifidobacteriaceae.

Conclusions

This study reinforces that the colonization of the gut with a commensal microorganism does not guarantee a specific functional output.
Risk of imported malaria infections in Zanzibar: a cross-sectional study
Authors: Fakih Bakar S. , Holzschuh Aurel , Ross Amanda , Stuck Logan , Abdul Ramadhan , Al-Mafazy Abdul-Wahid H. , Irema Imani , Mbena Abdallah , Thawer Sumaiyya G. , Shija Shija J. , Aliy Safia M. , Ali Abdullah , Fink Günther , Yukich Joshua , Hetzel Manuel W.
Published: August 2023

Background

Zanzibar has made substantial progress in malaria control with vector control, improved diagnosis, and artemisinin-based combination therapy. Parasite prevalence in the population has remained around 1% but imported infections from mainland Tanzania contribute to sustained local transmission. Understanding travel patterns between mainland Tanzania and Zanzibar, and the risk of malaria infection, may help to control malaria importation to Zanzibar.

Methods

A rolling cross-sectional survey linked to routine reactive case detection of malaria was carried out in Zanzibar between May 2017 and October 2018. Households of patients diagnosed with malaria at health facilities were surveyed and household members were tested for malaria using rapid diagnostic tests and a sub-sample by quantitative PCR (qPCR). Interviews elicited a detailed travel history of all household members who had travelled within the past two months, including trips within and outside of Zanzibar. We estimated the association of malaria infection with travel destinations in pre-defined malaria endemicity categories, trip duration, and other co-variates using logistic regression.

Results

Of 17,891 survey participants, 1177 (7%) reported a recent trip, of which 769 (65%) visited mainland Tanzania. Among travellers to mainland Tanzania with travel destination details and a qPCR result available, 241/378 (64%) reported traveling to districts with a ‘high’ malaria endemicity and for 12% the highest endemicity category was ‘moderate’. Travelers to the mainland were more likely to be infected with malaria parasites (29%, 108/378) than those traveling within Zanzibar (8%, 16/206) or to other countries (6%, 2/17). Among travellers to mainland Tanzania, those visiting highly endemic districts had a higher odds of being qPCR-positive than those who travelled only to districts where malaria-endemicity was classified as low or very low (adjusted odd ratio = 7.0, 95% confidence interval: 1.9–25.5). Among travellers to the mainland, 110/378 (29%) never or only sometimes used a mosquito net during their travel.

Conclusions

Strategies to reduce malaria importation to Zanzibar may benefit from identifying population groups traveling to highly endemic areas in mainland Tanzania. Targeted interventions to prevent and clear infections in these groups may be more feasible than attempting to screen and treat all travellers upon arrival in Zanzibar.
Relationships between drinking habits, psychological resilience, and salivary cortisol responses on the Trier Social Stress Test-Online among Japanese people
Authors: Ueno Masaharu
Published: August 2023

Background

This study aimed to determine whether individual differences in resilience interacted with those in alcohol consumption habits in situations involving exposure to psychosocial stressors (Trier Social Stress Test-Online; TSST-OL). Additionally, we investigated whether individuals exhibiting resilience in their psychological scale scores showed biological responses that could be interpreted as resilience in stressful situations, such as the TSST-OL. We hypothesized that there would be no association between drinking habits and stress responses in the high-resilience group. Furthermore, high drinking habits would be associated with high stress responses in the low-resilience group.

Methods

We recruited 22 and 20 individuals from the high and low-resilience groups, respectively, from among those who completed the online survey comprising the Alcohol Use Disorders Identification Test (AUDIT) and resilience scales; we excluded individuals with AUDIT scores of 15 or higher, and divided them by the median total resilience scale score. During the TSST-OL, self-rated stress measurement and saliva sample collection were performed seven times. Frozen samples were collected at the Tokyo site, and salivary hormonal (cortisol and dehydroepiandrosterone) levels were measured after transport in frozen state. Finally, 36 participants were included in the analysis of self-rated stress and cortisol levels.

Results

We observed the typical subjective stress responses to the TSST-OL. People with higher psychological scale scores for resilience traits showed significantly higher salivary cortisol levels than those with lower scores. Due to deficiencies in the survey and experimental design, the classification criteria were changed and an exploratory analysis was performed to investigate the interaction of individual differences in resilience and drinking habits. In contrast to our expectation, those with low resilience scores showed stress responses, regardless of their drinking habits. Furthermore, those with high resilience and drinking habits showed a specific insensitivity to salivary cortisol levels. Their self-rated stress scores were similar to those of other groups.

Conclusions

Our study showed the applicability of the TSST-OL in the Japanese population, the individual relationship between psychological resilience measures and biological stress responses, and a specific insensitivity in the salivary cortisol response as a result of individual differences in high resilience and drinking habits.
MGMT methylation pattern of long-term and short-term survivors of glioblastoma reveals CpGs of the enhancer region to be of high prognostic value
Authors: Leske Henning , Camenisch Gross Ulrike , Hofer Silvia , Neidert Marian Christoph , Leske Sabine , Weller Michael , Lehnick Dirk , Rushing Elisabeth Jane
Published: August 2023

Treatment with the alkylating agent temozolomide is known to be prognostically beneficial in a subset of glioblastoma patients. Response to such chemotherapeutic treatment and the prognostic benefit have been linked to the methylation status of O6-methylguanine-DNA methyltransferase (MGMT). To date, it has not been entirely resolved which methylation pattern of MGMT is most relevant to predict response to temozolomide treatment and outcome. In this retrospective study, we compared the methylation patterns, analyzed by Sanger sequencing, of 27 isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients that survived more than 3 years (long-term survivors) with those of 24 patients who survived less than a year after initial surgery (short-term survivors). Random Forest-, Correlation-, and ROC-curve analyses were performed. The data showed that MGMT is typically methylated in long-term survivors, whereas no prominent methylation is observed in short-term survivors. The methylation status of CpGs, especially in the promoter and exon1/enhancer region correlated highly with outcome. In addition, age and temozolomide treatment were strongly associated with overall survival. Some CpGs in the enhancer region, in particular CpG 86 (bp + 154), demonstrated high values associated with overall survival in the Random Forest analysis. Our data confirm previously published prognostic factors in IDH-wildtype glioblastoma patients, including age and temozolomide treatment as well as the global MGMT methylation status. The area frequently used for decision making to administer temozolomide at the end of exon1 of MGMT, was associated with outcome. However, our data also suggest that the enhancer region, especially CpG 86 (bp + 154) is of strong prognostic value. Therefore, we propose further investigation of the enhancer region in a large prospective study in order to confirm our findings, which might result in an optimized prediction of survival in glioblastoma patients, likely linked to response to temozolomide treatment.
Analyzing protein concentration from intact wheat caryopsis using hyperspectral reflectance
Authors: Zhang Xiaomei , Hou Xiaoxiang , Su Yiming , Yan XiaoBin , Qiao Xingxing , Yang Wude , Feng Meichen , Kong Huihua , Zhang Zhou , Shafiq Fahad , Han Wenjie , Li Guangxin , Chen Ping , Wang Chao
Published: August 2023

Background

Winter wheat grain samples from 185 sites across southern Shanxi region were processed and analyzed using a non-destructive approach. For this purpose, spectral data and protein content of grain and grain powder were obtained. After combining six types of preprocessed spectra and four types of multivariate statistical models, a relationship between hyperspectral datasets and grain protein is presented.

Results

It was found that the hyperspectral reflectance of winter wheat grain and powder was positively correlated with the protein contents, which provide the possibility for hyperspectral quantitative assessment. The spectral characteristic bands of protein content in winter wheat extracted based on the SPA algorithm were proved to be around 350–430 nm; 851–1154 nm; 1300–1476 nm; and 1990–2050 nm. In powder samples, SG-BPNN had the best monitoring effect, with the accuracy of Rv2 = 0.814, RMSEv = 0.024 g/g, and RPDv = 2.318. While in case of grain samples, the SG-SVM model exhibited the best monitoring effect, with the accuracy of Rv2 = 0.789, RMSEv = 0.026 g/g, and RPDv = 2.177.

Conclusions

Based on the experimental findings, we propose that a combination of spectral pretreatment and multivariate statistical modeling is helpful for the non-destructive and rapid estimation of protein content in winter wheat.

Graphical Abstract
Effect of mixing at weaning and nutrient density of the weaner diet on growth performance and welfare of pigs to slaughter
Authors: González-Solé Francesc , Camp Montoro Jordi , Solà-Oriol David , Pérez José Francisco , Lawlor Peadar G. , Boyle Laura A. , Garcia Manzanilla Edgar
Published: August 2023

Background

Mixing pigs at weaning can compromise pig welfare and growth. Therefore, grouping littermates together may allow a diet nutrient and energy density reduction during the nursery period to reduce feed cost without affecting slaughter weight. This study investigated the combined effect of mixing and reducing dietary energy and nutrient density on growth performance, body lesions (BL), and behaviour in pigs from weaning to slaughter.

Results

Forty-eight litters [554 pigs, 11–12 pigs/litter; Danish Duroc × (Large White × Landrace)] were included in the trial. At 28 days of age, pigs were weaned and housed in nursery rooms in litter groups (INTACT, n = 24) or mixed with other litters and grouped by weight to reduce within-pen pig weight variation (MIXED, n = 24). A dietary regimen meeting pigs’ nutritional requirements (CON) and a low-density dietary regimen (LOW; -10% energy and protein) completed a 2 × 2 factorial arrangement (Mixing x Diet, n = 12). On day 74 of age, pigs moved to the grower-finisher accommodation without further mixing and all pigs received the CON dietary regimen. Mixing increased FCR by 4.0% during the nursery period (p = 0.003). Nursery pigs fed LOW experienced a growth retardation which was maintained until slaughter (-2.6 kg slaughter weight; p = 0.025). Initial differences in the coefficient of variation (CV) between MIXED (10.4%) and INTACT (17.6%; p < 0.001) pigs were reduced in CON pens but not in LOW pens (interaction p = 0.025) at the end of the nursery period. MIXED pigs had more fights and BL (p < 0.001) at weaning and showed more aggression (p = 0.003) after being moved to the grower-finisher rooms. At the end of the nursery period, MIXED pigs fed LOW showed the highest number of aggressive behaviours around the feeder (interaction; p = 0.003) and pigs fed LOW showed more damaging behaviour (p < 0.001).

Conclusions

Mixing animals at weaning had limited impact on growth performance but impaired welfare which was aggravated by energy and nutrient reduction in the nursery diet. Decreasing dietary nutrient density in the nursery stage retarded growth, which could not be compensated for during the growing-finishing period.
Unilateral neurostimulation-assisted cervical epidural anesthesia for upper limb surgeries—a case series
Authors: Diwan Sandeep , Nair Abhijit , Dongre Himaunshu , Sancheti Parag
Published: August 2023

Background

The role of neurostimulation-aided cervical epidural anesthesia (CEA) in shoulder surgery has been described in the literature. The use of nerve stimulators and the infusion of local anesthetic (LA) in the cervical epidural space has also been mentioned. Epidural needle rotation prior to insertion of the catheter is not described, and it is not clear if general anesthesia was administered in these cases.

Case presentation

In this case series, we performed CEA at the level of C7-T1 in 12 patients undergoing various surgeries on the proximal open shoulder and mid humerus after informed consent. Ipsilateral motor responses elicited by continuous electrical stimulation were used to identify lateralization of the epidural catheter tip. The placement of catheters was confirmed under an intraoperative image intensifier. Using the median approach at the level of C7-T1, an ipsilateral twitch was noted in all patients. Neurostimulation persisted with an advancement of stimulating catheter 3–4 cm in the cervical epidural space in all patients. A cervical radiograph confirmed the placement of an ipsilateral catheter and contrast injection there upon revealing the spread of the LA agent. All patients had successful awake shoulder and mid-humerus surgeries under sole cervical epidural anesthesia as evidenced by the absence of pain response at the surgical incision.

Conclusions

Ipsilateral CEA can be offered for unilateral upper limb surgeries. Low volumes of LA can be injected after precise placement of the tip of the catheter corresponding to the level of surgical incision.
Systematic development of a set of implementation strategies for transitional care innovations in long-term care
Authors: Fakha Amal , de Boer Bram , Hamers Jan. P. , Verbeek Hilde , van Achterberg Theo
Published: August 2023

Background

Numerous transitional care innovations (TCIs) are being developed and implemented to optimize care continuity for older persons when transferring between multiple care settings, help meet their care needs, and ultimately improve their quality of life. Although the implementation of TCIs is influenced by contextual factors, the use of effective implementation strategies is largely lacking. Thus, to improve the implementation of TCIs targeting older persons receiving long-term care services, we systematically developed a set of viable strategies selected to address the influencing factors.

Methods

As part of the TRANS-SENIOR research network, a stepwise approach following Implementation Mapping (steps 1 to 3) was applied to select implementation strategies. Building on the findings of previous studies, existing TCIs and factors influencing their implementation were identified. A combination of four taxonomies and overviews of change methods as well as relevant evidence on their effectiveness were used to select the implementation strategies targeting each of the relevant factors. Subsequently, individual consultations with scientific experts were performed for further validation of the process of mapping strategies to implementation factors and for capturing alternative ideas on relevant implementation strategies.

Results

Twenty TCIs were identified and 12 influencing factors (mapped to the Consolidated Framework for Implementation Research) were designated as priority factors to be addressed with implementation strategies. A total of 40 strategies were selected. The majority of these target factors at the organizational level, e.g., by using structural redesign, public commitment, changing staffing models, conducting local consensus discussions, and organizational diagnosis and feedback. Strategies at the level of individuals included active learning, belief selection, and guided practice. Each strategy was operationalized into practical applications.

Conclusions

This project developed a set of theory and evidence-based implementation strategies to address the influencing factors, along further tailoring for each context, and enhance the implementation of TCIs in daily practice settings. Such work is critical to advance the use of implementation science methods to implement innovations in long-term care successfully.
Paraspinal myositis in a patient with COVID-19 infection: a case report
Authors: Pangkanon Watsachon , Leelaviwat Natnicha , Saowapa Sakditad , Liao En-Dien , Payne J. Drew
Published: August 2023

Myalgia is one of the most common symptoms of COVID-19 infection. With the progression of the COVID-19 pandemic, emerging cases of COVID-related myositis have been reported. However, COVID-19-related myositis of the paraspinal muscle is uncommon. We present a 66-year-old female who was admitted to the hospital for hemorrhagic shock secondary to gastrointestinal bleeding. She developed COVID-19 respiratory tract infection symptoms on the second day of admission with reported severe lower back pain 3 days later. Serum creatinine kinase level was slightly elevated, and magnetic resonance imaging (MRI) revealed paraspinal myositis.
A call for aflatoxin control in Asia
Authors: Umar Abeera , Bhatti Hamzah Shahbaz , Honey Sabyan Faris
Published: August 2023

Aflatoxins are secondary metabolites, produced by some fungal species of the genus Aspergillus, posing health and economic implications throughout the world. Developing countries in Asia usually have tropical conditions and grow crops susceptible to aflatoxin proliferation. Aflatoxin proliferation is more frequent in tropical regions due to optimal climate conditions required for their production. In general, the developing countries in Asia lack control and regulation strategies, like poor harvesting practices, improper storage and poor transportation conditions resulting in major losses from farm to fork level. A number of aflatoxin positive cases above safe limits have been reported in Asia in various commodities being consumed by the local population. This not only exposes to health issues like growth impairment, immunosuppression, hepatic disorders etc. but also result in heavy economic losses due to trade restrictions. However, rigorous aflatoxin standards mean that many nations would export their best quality food and keep contaminated food domestically, resulting in higher aflatoxin exposure in low or middle-income nations, where hepatitis prevalence is high. Aflatoxin control is needed to protect the Asian population from the risks of aflatoxins and to ensure good quality safe availability of commodities throughout the world by trade. In recent years a number of bioproducts have been introduced successfully worldwide that are safe, efficient and ecofriendly. Such initiatives may be taken in Asia as well to protect our food and feed commodities from aflatoxin contamination.
Combined use of zoophytophagous mirids for sustainable biological protection of greenhouse tomato crops
Authors: Konan Kouassi A. J. , Jaworski Coline C. , Monticelli Lucie S. , Zuma Mnqobi , Boll Roger , Kouadio Marie-France N. , Martin Thibaud , Gard Benjamin , Souriau Roselyne , Lavoir Anne-Violette , Desneux Nicolas
Published: August 2023

Tuta absoluta and Bemisia tabaci are two key worldwide tomato pests. In response to chemical control limits, the use of zoophytophagous mirid predators as biocontrol agents is being increasingly studied and proposed for the management of these pests. However, the use of some mirid species and in particular Nesidiocoris tenuis, which naturally occurs in European tomato crops, is controversial due to its ability to inflict significant damage on tomato plants (necrotic rings) in parallel of its high predation capacity. Combining other mirid species such as Macrolophus pygmaeus and Dicyphus errans with N. tenuis could reduce the population growth of T. absoluta and of B. tabaci, while maintaining N. tenuis populations below a critical crop damage threshold. In this study, we tested the effect of combining N. tenuis with M. pygmaeus (at two densities: 10 and 15 individuals per plant) and with or without D. errans (five individuals per plant) on the abundance of all insects (predators and pests) for 8 weeks. We also measured leaf damage by T. absoluta and plant and flower damage (necrotic rings, flower abortion rate) by N. tenuis. We found that the combined presence of D. errans, M. pygmaeus and N. tenuis rapidly and significantly reduced the densities of B. tabaci adults, and T. absoluta larvae and damage compared to when M. pygmaeus (with both densities) was only present with N. tenuis. The presence of D. errans was critical to reduce N. tenuis population growth and necrotic rings on tomato plants, while higher densities of M. pygmaeus density reduced the rate of aborted flowers by N. tenuis. The manipulation of M. pygmaeus densities added to the presence of D. errans could provide a sustainable solution to control multiple pests simultaneously while reducing the damaging phytophagous activity of N. tenuis in tomato crops.