bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic diversity and population structure of Epichloë fungal pathogens of plants in natural ecosystems
Authors: Treindl Artemis D. , Stapley Jessica , Leuchtmann Adrian
Published: June 2023

Understanding the population genetic processes driving the evolution of plant pathogens is of central interest to plant pathologists and evolutionary biologists alike. However, most studies focus on host-pathogen associations in agricultural systems of high genetic and environmental homogeneity and less is known about the genetic structure of pathogen populations infecting wild plants in natural ecosystems. We performed parallel population sampling of two pathogenic Epichloë species occurring sympatrically on different host grasses in natural and seminatural grasslands in Europe: E. typhina infecting Dactylis glomerata and E. clarkii infecting Holcus lanatus. We sequenced 422 haploid isolates and generated genome-wide SNP datasets to investigate genetic diversity and population structure. In both species geographically separated populations formed genetically distinct groups, however, population separation was less distinct in E. typhina compared to E. clarkii. The patterns of among population admixture also differed between species across the same geographic range: we found higher levels of population genetic differentiation and a stronger effect of isolation by distance in E. clarkii compared to E. typhina, consistent with lower levels of gene flow in the former. This pattern may be explained by the different dispersal abilities of the two pathogens and is expected to be influenced by the genetic structure of host populations. In addition, genetic diversity was higher in E. typhina populations compared to E. clarkii, indicative of higher effective population size in E. typhina. These results suggest that the effect of genetic drift and the efficacy of selection may differ in the two species. Our study provides evidence of how ecologically similar species occupying the same geographical space can experience different evolutionary contexts, which could influence local adaptation and co-evolutionary dynamics of these fungal pathogens.
A scoping review of smoking cessation pharmacogenetic studies to advance future research across racial, ethnic, and ancestral populations
Authors: Prom-Wormley Elizabeth C. , Wells Jonathan L. , Landes Lori , Edmondson Amy N. , Sankoh Mariam , Jamieson Brendan , Delk Kayla J. , Surya Sanya , Bhati Shambhavi , Clifford James
Published: June 2023

Abstinence rates among smokers attempting to quit remain low despite the wide availability and accessibility of pharmacological smoking cessation treatments. In addition, the prevalence of cessation attempts and abstinence differs by individual-level social factors such as race and ethnicity. Clinical treatment of nicotine dependence also continues to be challenged by individual-level variability in effectiveness to promote abstinence. The use of tailored smoking cessation strategies that incorporate information on individual-level social and genetic factors hold promise, although additional pharmacogenomic knowledge is still needed. In particular, genetic variants associated with pharmacological responses to smoking cessation treatment have generally been conducted in populations with participants that self-identify as White race or who are determined to be of European genetic ancestry. These results may not adequately capture the variability across all smokers as a result of understudied differences in allele frequencies across genetic ancestry populations. This suggests that much of the current pharmacogenetic study results for smoking cessation may not apply to all populations. Therefore, clinical application of pharmacogenetic results may exacerbate health inequities by racial and ethnic groups. This scoping review examines the extent to which racial, ethnic, and ancestral groups that experience differences in smoking rates and smoking cessation are represented in the existing body of published pharmacogenetic studies of smoking cessation. We will summarize results by race, ethnicity, and ancestry across pharmacological treatments and study designs. We will also explore current opportunities and challenges in conducting pharmacogenomic research on smoking cessation that encourages greater participant diversity, including practical barriers to clinical utilization of pharmacological smoking cessation treatment and clinical implementation of pharmacogenetic knowledge.
An effective hyper-parameter can increase the prediction accuracy in a single-step genetic evaluation
Authors: Neshat Mehdi , Lee Soohyun , Momin Md. Moksedul , Truong Buu , van der Werf Julius H. J. , Lee S. Hong
Published: June 2023

The H-matrix best linear unbiased prediction (HBLUP) method has been widely used in livestock breeding programs. It can integrate all information, including pedigree, genotypes, and phenotypes on both genotyped and non-genotyped individuals into one single evaluation that can provide reliable predictions of breeding values. The existing HBLUP method requires hyper-parameters that should be adequately optimised as otherwise the genomic prediction accuracy may decrease. In this study, we assess the performance of HBLUP using various hyper-parameters such as blending, tuning, and scale factor in simulated and real data on Hanwoo cattle. In both simulated and cattle data, we show that blending is not necessary, indicating that the prediction accuracy decreases when using a blending hyper-parameter <1. The tuning process (adjusting genomic relationships accounting for base allele frequencies) improves prediction accuracy in the simulated data, confirming previous studies, although the improvement is not statistically significant in the Hanwoo cattle data. We also demonstrate that a scale factor,α, which determines the relationship between allele frequency and per-allele effect size, can improve the HBLUP accuracy in both simulated and real data. Our findings suggest that an optimal scale factor should be considered to increase prediction accuracy, in addition to blending and tuning processes, when using HBLUP.
Unraveling the therapeutic mechanisms of dichloroacetic acid in lung cancer through integrated multi-omics approaches: metabolomics and transcriptomics
Authors: Feng Malong , Wang Ji , Zhou Jianying
Published: June 2023

Objective: The aim of this study was to investigate the molecular mechanisms underlying the therapeutic effects of dichloroacetic acid (DCA) in lung cancer by integrating multi-omics approaches, as the current understanding of DCA’s role in cancer treatment remains insufficiently elucidated.

Methods: We conducted a comprehensive analysis of publicly available RNA-seq and metabolomic datasets and established a subcutaneous xenograft model of lung cancer in BALB/c nude mice (n = 5 per group) treated with DCA (50 mg/kg, administered via intraperitoneal injection). Metabolomic profiling, gene expression analysis, and metabolite-gene interaction pathway analysis were employed to identify key pathways and molecular players involved in the response to DCA treatment. In vivo evaluation of DCA treatment on tumor growth and MIF gene expression was performed in the xenograft model.

Results: Metabolomic profiling and gene expression analysis revealed significant alterations in metabolic pathways, including the Warburg effect and citric acid cycle, and identified the MIF gene as a potential therapeutic target in lung cancer. Our analysis indicated that DCA treatment led to a decrease in MIF gene expression and an increase in citric acid levels in the treatment group. Furthermore, we observed a potential interaction between citric acid and the MIF gene, suggesting a novel mechanism underlying the therapeutic effects of DCA in lung cancer.

Conclusion: This study underscores the importance of integrated omics approaches in deciphering the complex molecular mechanisms of DCA treatment in lung cancer. The identification of key metabolic pathways and the novel finding of citric acid elevation, together with its interaction with the MIF gene, provide promising directions for the development of targeted therapeutic strategies and improving clinical outcomes for lung cancer patients.
A Rab33b missense mouse model for Smith-McCort dysplasia shows bone resorption defects and altered protein glycosylation
Authors: Dimori Milena , Pokrovskaya Irina D. , Liu Shijie , Sherrill John T. , Gomez-Acevedo Horacio , Fu Qiang , Storrie Brian , Lupashin Vladimir V. , Morello Roy
Published: June 2023

Smith McCort (SMC) dysplasia is a rare, autosomal recessive, osteochondrodysplasia that can be caused by pathogenic variants in either RAB33B or DYM genes. These genes codes for proteins that are located at the Golgi apparatus and have a role in intracellular vesicle trafficking. We generated mice that carry a Rab33b disease-causing variant, c.136A>C (p.Lys46Gln), which is identical to that of members from a consanguineous family diagnosed with SMC. In male mice at 4 months of age, the Rab33b variant caused a mild increase in trabecular bone thickness in the spine and femur and in femoral mid-shaft cortical thickness with a concomitant reduction of the femoral medullary area, suggesting a bone resorption defect. In spite of the increase in trabecular and cortical thickness, bone histomorphometry showed a 4-fold increase in osteoclast parameters in homozygous Rab33b mice suggesting a putative impairment in osteoclast function, while dynamic parameters of bone formation were similar in mutant versus control mice. Femur biomechanical tests showed an increased in yield load and a progressive elevation, from WT to heterozygote to homozygous mutants, of bone intrinsic properties. These findings suggest an overall impact on bone material properties which may be caused by disturbed protein glycosylation in cells contributing to skeletal formation, supported by the altered and variable pattern of lectin staining in murine and human tissue cultured cells and in liver and bone murine tissues. The mouse model only reproduced some of the features of the human disease and was sex-specific, manifesting in male but not female mice. Our data reveal a potential novel role of RAB33B in osteoclast function and protein glycosylation and their dysregulation in SMC and lay the foundation for future studies.
Impacts of marine heat extremes on bivalves
Authors: Masanja Fortunatus , Yang Ke , Xu Yang , He Guixiang , Liu Xiaolong , Xu Xin , Xiaoyan Jiang , Xin Luo , Mkuye Robert , Deng Yuewen , Zhao Liqiang
Published: June 2023

As the global ocean continues to experience the consequences of an increase in the frequency and intensity of heat waves, the trend is expected to persist into the 21st century, with a projected tripling of heat waves by 2040. This phenomenon poses a significant threat to marine ecosystems and the survival of marine organisms, including the ecologically and economically vital bivalves. Bivalves are vulnerable to harm from heat stress at various levels of biological organization, and their growth can be negatively impacted by high temperatures, potentially leading to mass mortalities and posing a threat to ecosystem quality and food security. In light of these concerns, this review aims to provide a comprehensive examination of the effects of heat stress on bivalves. It summarizes the physiological and biochemical changes that bivalves undergo in response to extreme heat events and offers an overview of the strategies they employ to mitigate their impacts. A better understanding of the underlying mechanisms of bivalve responses to heat stress is crucial in order to fully appreciate the impact of these events on these organisms. This review synthesizes the current knowledge on heat stress in bivalves and highlights the importance of further research in this area. By providing a comprehensive overview of the physiological and biochemical changes that bivalves experience during heat stress and the strategies they use to mitigate its impact, this review aims to support the development of more effective approaches to minimize heat stress in bivalves.
Advances in electronic skin research: a bibliometric analysis
Authors: Xu Shiyong , Yu Xiaona , Chen Jie , Jing Yuan
Published: June 2023

Background: E-skin (electronic skin) is an active research area in human-computer interaction and artificial intelligence.

Methods: A bibliometric analysis was performed to evaluate publications in the E-skin field between 2000 and 2021 based on the Web of Science (WoS) databases.

Results: A total of 4,954 documents were identified. A detailed overview of E-skin research was presented from aspects of productive countries/regions, institutions, journals, citations, highly cited papers, keywords, and emerging topics. With the emergence of new functional materials, structural design, 3D printing, and nanofabrication techniques, E-skin research has achieved dramatic progress after 2013. Scholars and institutions in China, the United States and South Korea are leading the way in E-skin research. Pressure sensor, strain sensor, and flexible electronics are the most focused directions at present and Internet of things is the most emerging topic.

Conclusion: E-skin research has achieved dramatic progress but there is still quite a challenging task in practical applications. Manufacturing process simplification, cost reduction, functional integration, energy supply, and biocompatibility are vital for the future development of E-skin.
Accuracy of Deep Neural Network in Triaging Common Skin Diseases of Primary Care Attention
Authors: Giavina-Bianchi Mara , Cordioli Eduardo , Santos André P. dos
Published: June 2023

Graphical Abstract

Graphical Abstract showing the research flow from the dataset base images, classification of the dermatoses according to categories, referral and level of priority; training and validation in different scenarios to the final test, using the algorithm with the best performance.
Case report: An unusual case of small bowel bleeding and common iliac artery pseudoaneurysm caused by an unnoticed swallowed toothpick
Authors: Xiong Yao , Yan Jing , Yan Gaowu , Feng Lei , Li Yong , He Suyu , Li Ruyi , Tan Gangcheng , Feng Bo
Published: June 2023

Gastrointestinal (GI) bleeding is a common clinical condition that can be caused by a variety of reasons. Bleeding can occur anywhere in the GI tract, and it usually presents as vomiting of blood, melena or black stools. We herein present a case of a 48-year-old man who was ultimately diagnosed with perforation of the lower ileum, pseudoaneurysm of the right common iliac artery, lower ileum-right common iliac artery fistula, and pelvic abscess caused by accidental ingestion of a toothpick. This case suggests that accidental ingestion of a toothpick may also be the cause of GI bleeding in some patients. For patients with unexplained GI bleeding, especially those with small bowel bleeding, a rational and combined use of gastroduodenoscopy, colonoscopy, unenhanced and contrast-enhanced abdominal CT can help detect the causes of GI bleeding and improve diagnostic accuracy.
White-rot fungi scavenge reactive oxygen species, which drives pH-dependent exo-enzymatic mechanisms and promotes CO2 efflux
Authors: Jofré-Fernández Ignacio , Matus-Baeza Francisco , Merino-Guzmán Carolina
Published: June 2023

Soil organic matter (SOM) decomposition mechanisms in rainforest ecosystems are governed by biotic and abiotic procedures which depend on available oxygen in the soil. White-rot fungi (WRF) play an important role in the primary decomposition of SOM via enzymatic mechanisms (biotic mechanism), which are linked to abiotic oxidative reactions (e.g., Fenton reaction), where both processes are dependent on reactive oxygen species (ROS) and soil pH variation, which has yet been studied. In humid temperate forest soils, we hypothesize that soil pH is a determining factor that regulates the production and consumption of ROS during biotic and abiotic SOM decomposition. Three soils from different parent materials and WRF inoculum were considered for this study: granitic (Nahuelbuta, Schizophyllum commune), metamorphic (Alerce Costero, Stereum hirsutum), and volcanic-allophanic (Puyehue, Galerina patagonica). CO2 fluxes, lignin peroxidase, manganese peroxidase, and dye-decolorizing peroxidase levels were all determined. Likewise, the production of superoxide anion (O2•-), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH) were assessed in soils microcosms after 36 days of anaerobic incubation with WRF inoculum and induced Fenton reaction under pH variations ranging from 2.5 to 5.1. ROS significantly increased biotic and abiotic CO2 emissions in all tested soils, according to the findings. The highest values (217.45 mg C kg−1) were found during the anaerobic incubation of sterilized and inoculated soils with WRF at a natural pH of 4.5. At pH 4.0, the lowest levels of C mineralization (82 mg C kg−1) were found in Nahuelbuta soil. Enzyme activities showed different trends as pH changed. The Fenton reaction consumed more H2O2 between pH 3 and 4, but less between pH 4.5 and 2.5. The mechanisms that oxidized SOM are extremely sensitive to variations in soil pH and the stability of oxidant radical and non-radical compounds, according to our findings.
Modulating gastrointestinal microbiota to alleviate diarrhea in calves
Authors: Du Wenjuan , Wang Xianghuang , Hu Mingyang , Hou Jinxiu , Du Yufeng , Si Wenjin , Yang Linhai , Xu Le , Xu Qingbiao
Published: June 2023

The calf stage is a critical period for the development of heifers. Newborn calves have low gastrointestinal barrier function and immunity before weaning, making them highly susceptible to infection by various intestinal pathogens. Diarrhea in calves poses a significant threat to the health of young ruminants and may cause serious economic losses to livestock farms. Antibiotics are commonly used to treat diarrhea and promote calf growth, leading to bacterial resistance and increasing antibiotic residues in meat. Therefore, finding new technologies to improve the diarrhea of newborn calves is a challenge for livestock production and public health. The operation of the gut microbiota in the early stages after birth is crucial for optimizing immune function and body growth. Microbiota colonization of newborn animals is crucial for healthy development. Early intervention of the calf gastrointestinal microbiota, such as oral probiotics, fecal microbiota transplantation and rumen microbiota transplantation can effectively relieve calf diarrhea. This review focuses on the role and mechanisms of oral probiotics such as Lactobacillus, Bifidobacterium and Faecalibacterium in relieving calf diarrhea. The aim is to develop appropriate antibiotic alternatives to improve calf health in a sustainable and responsible manner, while addressing public health issues related to the use of antibiotics in livestock.
Monitoring of breast cancer progression via aptamer-based detection of circulating tumor cells in clinical blood samples
Authors: Kolovskaya Olga S. , Zyuzyukina Alena V. , Dassie Justin P. , Zamay Galina S. , Zamay Tatiana N. , Boyakova Nina V. , Khorzhevskii Vladimir A. , Kirichenko Daria A. , Lapin Ivan N. , Shchugoreva Irina A. , Artyushenko Polina V. , Tomilin Felix N. , Veprintsev Dmitry V. , Glazyrin Yury E. , Minic Zoran , Bozhenko Vladimir K. , Kudinova Elena A. , Kiseleva Yana Y. , Krat Alexey V. , Slepov Eugene V. , Bukatin Anton S. , Zukov Ruslan A. , Shesternya Pavel A. , Berezovski Maxim V. , Giangrande Paloma H. , Kichkailo Anna S.
Published: June 2023

Introduction: Breast cancer (BC) diagnostics lack noninvasive methods and procedures for screening and monitoring disease dynamics. Admitted CellSearch® is used for fluid biopsy and capture of circulating tumor cells of only epithelial origin. Here we describe an RNA aptamer (MDA231) for detecting BC cells in clinical samples, including blood. The MDA231 aptamer was originally selected against triple-negative breast cancer cell line MDA-MB-231 using cell-SELEX.

Methods: The aptamer structure in solution was predicted using mFold program and molecular dynamic simulations. The affinity and specificity of the evolved aptamers were evaluated by flow cytometry and laser scanning microscopy on clinical tissues from breast cancer patients. CTCs were isolated form the patients’ blood using the developed method of aptamer-based magnetic separation. Breast cancer origin of CTCs was confirmed by cytological, RT-qPCR and Immunocytochemical analyses.

Results: MDA231 can specifically recognize breast cancer cells in surgically resected tissues from patients with different molecular subtypes: triple-negative, Luminal A, and Luminal B, but not in benign tumors, lung cancer, glial tumor and healthy epithelial from lungs and breast. This RNA aptamer can identify cancer cells in complex cellular environments, including tumor biopsies (e.g., tumor tissues vs. margins) and clinical blood samples (e.g., circulating tumor cells). Breast cancer origin of the aptamer-based magnetically separated CTCs has been proved by immunocytochemistry and mammaglobin mRNA expression.

Discussion: We suggest a simple, minimally-invasive breast cancer diagnostic method based on non-epithelial MDA231 aptamer-specific magnetic isolation of circulating tumor cells. Isolated cells are intact and can be utilized for molecular diagnostics purposes.
A primary Rosai-Dorfman-Destombes disease of the scalp: case report and literature review
Authors: Song Wenxiong , Ding Feiyu , Xiao Yong , Hu Xinhua , Yang Kun , Geng Liangyuan , Zou Yuanjie
Published: June 2023

Background

Rosai-Dorfman-Destombes disease (RDD) was first described in 1965 as a benign histiocytic proliferative disorder of unknown cause. Cases of RDD limited to cutaneous tissue have been reported over the past few decades, but single cutaneous RDD of the scalp is rare.

Case presentation

We report a 31-year-old male with a lump on the parietal scalp without extranodal lesion lasting 1 month with gradual enlargement. The surgical incision ruptured with purulent after the first resection. Then the patient was treated with plastic surgery after disinfection and antibiotic treatment. Finally, he recovered well and discharged after 20 days.

Conclusions

RDD of the scalp is rare. Surgical incision can cure the lesion but it may become infected because of increased lymphocytic infiltration. Early diagnosis and differential diagnosis of RDD are necessary. For treatment, individualized therapy is critical to patient prognosis.
Altered regional brain activity and functional connectivity in resting-state brain networks associated with psychological erectile dysfunction
Authors: Liu Xue , Liu Shaowei , Liu Tao , Tang Liang , Ji Mufan , Xu Yan , Xiang Ziliang , Zhou Jianwen , Chen Yun , Chen Jianhuai
Published: June 2023

Introduction

Erectile dysfunction (ED), especially psychological ED (pED), is usually accompanied with psychological factors, which are related to abnormal activity in brain regions involved in sexual behavior. However, the mechanisms underlying functional changes in the brain of pED are still unclear. The present study aimed to explore the abnormalities of brain function, as well as their relationships with sexual behavior and emotion in pED patients.

Materials and methods

Resting state functional magnetic resonance imaging (rs-fMRI) data were collected from 31 pED patients to 31 healthy controls (HCs). The values of amplitude of fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) were calculated and compared between groups. In addition, the associations between abnormal brain regions and clinical features were evaluated by Pearson correlation analyses.

Results

Compared to HCs, pED patients demonstrated decreased fALFF values in the left medial superior frontal gyrus (had decreased FC values with the left dorsolateral superior frontal gyrus), the left lingual gyrus (had decreased FC values with the left parahippocamal gyrus and insula), the left putamen (had decreased FC values with the right caudate) and the right putamen (had decreased FC values with the left putamen and the right caudate). The fALFF values of the left medial superior frontal gyrus were negatively correlated with the fifth item scores of International Index of Erectile Function (IIEF-5). Negative relationships were found between fALFF values of the left putamen and the second item scores of Arizona Sexual Scale (ASEX). FC values between the right putamen and caudate were negatively related to the state scores of State-Trait Anxiety Inventory (STAI-S).

Conclusion

Altered brain function were found in the medial superior frontal gyrus and caudate-putamen of pED patients, which were associated with sexual function and psychological condition. These findings provided new insights into the central pathological mechanisms of pED.
A nomogram combining thoracic CT and tumor markers to predict the malignant grade of pulmonary nodules ≤3 cm in diameter
Authors: Qiu Jianhao , Li Rongyang , Wang Yukai , Ma Xiuyuan , Qu Chenghao , Liu Binyan , Yue Weiming , Tian Hui
Published: June 2023

Background

With the popularity of computed tomography (CT) of the thorax, the rate of diagnosis for patients with early-stage lung cancer has increased. However, distinguishing high-risk pulmonary nodules (HRPNs) from low-risk pulmonary nodules (LRPNs) before surgery remains challenging.

Methods

A retrospective analysis was performed on 1064 patients with pulmonary nodules (PNs) admitted to the Qilu Hospital of Shandong University from April to December 2021. Randomization of all eligible patients to either the training or validation cohort was performed in a 3:1 ratio. Eighty-three PNs patients who visited Qianfoshan Hospital in the Shandong Province from January through April of 2022 were included as an external validation. Univariable and multivariable logistic regression (forward stepwise regression) were used to identify independent risk factors, and a predictive model and dynamic web nomogram were constructed by integrating these risk factors.

Results

A total of 895 patients were included, with an incidence of HRPNs of 47.3% (423/895). Logistic regression analysis identified four independent risk factors: the size, consolidation tumor ratio, CT value of PNs, and carcinoembryonic antigen levels in blood. The area under the ROC curves was 0.895, 0.936, and 0.812 for the training, internal validation, and external validation cohorts, respectively. The Hosmer-Lemeshow test demonstrated excellent calibration capability, and the fit of the calibration curve was good. DCA has shown the nomogram to be clinically useful.

Conclusion

The nomogram performed well in predicting the likelihood of HRPNs. In addition, it identified HRPNs in patients with PNs, achieved accurate treatment with HRPNs, and is expected to promote their rapid recovery.
Platelet role in the prediction of MIS-C severity
Authors: Snipaitiene Ausra , Sirataviciene Aurelija , Varoneckaite Leila , Sileikiene Rima , Jankauskaite Lina
Published: June 2023

Introduction

Multisystem inflammatory syndrome in children (MIS-C) has been reported as one of the cytokine storm syndromes associated with COVID-19. Despite the several proposed diagnostic criteria, MIS-C remains a diagnostic and clinical challenge. Recent studies have demonstrated that platelets (PLTs) play a crucial role in COVID-19 infection and its prognosis. This study aimed to investigate the clinical importance of PLT count and PLT indices in predicting MIS-C severity in children.

Patients and methods

We conducted a retrospective single-center study at our university hospital. A total of 43 patients diagnosed with MIS-C during a 2-year period (from October 2020 to October 2022) were included in the study. MIS-C severity was evaluated according to the composite severity score.

Results

Half of the patients were treated in the pediatric intensive care unit. No single clinical sign was associated with a severe condition, except for shock (p = 0.041). All the routine biomarkers, such as complete blood count (CBC) and C-reactive protein (CRP), used for MIS-C diagnosis were significant in predicting MIS-C severity. Single PLT parameters, such as mean PLT volume, plateletcrit, or PLT distribution width, did not differ between the severity groups. However, we found that a combination of PLT count and the previously mentioned PLT indices had the potential to predict MIS-C severity.

Conclusions

Our study emphasizes the importance of PLT in MIS-C pathogenesis and severity. It revealed that together with routine biomarkers (e.g., CBC and CRP), it could highly improve the prediction of MIS-C severity.
A systematic review: facial, dental and orthodontic findings and orofacial diagnostics in patients with FASD
Authors: Blanck-Lubarsch Moritz , Dirksen Dieter , Feldmann Reinhold , Hohoff Ariane
Published: June 2023

Background

The fetal alcohol spectrum disorder is a group of developmental disorders caused by maternal alcohol consumption. Patients with fetal alcohol syndrome show abnormal orofacial features. This review presents an overview over the facial, oral, dental or orthodontic findings and diagnostic tools concerning these features.

Methods

For this systematic review Cochrane, Medline and Embase databases were considered and the review was performed according to the PRISMA checklist. Two independent reviewers evaluated all studies and recorded results in a summary of findings table. Risk of bias was analyzed via Quadas-2 checklist.

Results

61 studies were eligible for inclusion. All included studies were clinical studies. Methods and results of the studies were not comparable, guidelines or methods for the detection of FASD varied across studies. Facial features most often measured or found as distinguishing parameter were: palpebral fissure length, interpupillary or innercanthal distance, philtrum, upper lip, midfacial hypoplasia or head circumference.

Conclusions

This review shows that to date a multitude of heterogeneous guidelines exists for the diagnosis of FASD. Uniform, objective diagnostic criteria and parameters for the orofacial region in FASD diagnosis are needed. A bio database with values and parameters for different ethnicities and age groups should be made available for diagnosis.
Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case report
Authors: Kawamura Hiroshi , Ikawa Masamichi , Hirono Keiichi , Kimura Junya , Okuno Takashi , Kawatani Masao , Inai Kunihiro , Hata Yukiko , Nishida Naoki , Yoshida Yoshio
Published: June 2023

Background

Left ventricular noncompaction (LVNC) is a rare inherited cardiomyopathy with a broad phenotypic spectrum. The genotype-phenotype correlations in fetal-onset LVNC have not yet been fully elucidated. In this report, we present the first case of severe fetal-onset LVNC caused by maternal low-frequency somatic mosaicism of the novel myosin heavy chain 7 (MYH7) mutation.

Case presentation

A 35-year-old pregnant Japanese woman, gravida 4, para 2, with no significant medical or family history of genetic disorders, presented to our hospital. In her previous pregnancy at 33 years of age, she delivered a male neonate at 30 weeks of gestation with cardiogenic hydrops fetalis. Fetal echocardiography confirmed LVNC prenatally. The neonate died shortly after birth. In the current pregnancy, she again delivered a male neonate with cardiogenic hydrops fetalis caused by LVNC at 32 weeks of gestation. The neonate died shortly after birth. Genetic screening of cardiac disorder-related genes by next-generation sequencing (NGS) was performed which revealed a novel heterozygous missense MYH7 variant, NM_000257.3: c.2729A > T, p.Lys910Ile. After targeted and deep sequencing by NGS, the same MYH7 variant (NM_000257.3: c.2729A > T, p.Lys910Ile) was detected in 6% of the variant allele fraction in the maternal sequence but not in the paternal sequence. The MYH7 variant was not detected by conventional direct sequencing (Sanger sequencing) in either parent.

Conclusions

This case demonstrates that maternal low-frequency somatic mosaicism of an MYH7 mutation can cause fetal-onset severe LVNC in the offspring. To differentiate hereditary MYH7 mutations from de novo MYH7 mutations, parental targeted and deep sequencing by NGS should be considered in addition to Sanger sequencing.
Pharmacological targeting of gastric mucosal barrier with traditional Chinese medications for repairing gastric mucosal injury
Authors: Jia Xueyan , He Yihuai , Li Lin , Xu Delin
Published: June 2023

Introduction: The gastric mucosa (GM) is the first barrier and vital interface in the stomach that protects the host from hydrochloric acid in gastric juice and defends against exogenous insults to gastric tissues. The use of traditional Chinese medications (TCMs) for the treatment of gastric mucosal injury (GMI) has long-standing history and a good curative effect. Whereas there are poor overall reports on the intrinsic mechanisms of these TCM preparations that pharmacology uses to protect body from GMI, which is crucial to treating this disease. These existing reviews have deficiencies that limit the clinical application and development of both customary prescriptions and new drugs.

Methods: Further basic and translational studies must be done to elucidate the intrinsic mechanisms of influence of these TCM preparations. Moreover, well-designed and well-conducted experiences and clinical trials are necessary to ascertain the efficacy and mechanisms of these agents. Therefore, this paper presents a focused overview of currently published literature to assess how TCMs action that facilitates the cures for GMI. It offers a whole train of current state of pharmacological evidence, identifies the pharmacological mechanisms of TCMs on GM, and highlights that remarkable capacity of TCMs to restore GM after damage.

Results: These TCMs preparations promote the repair of multicomponent targets such as the gastric mucus, epithelial layer, blood flow (GMBF) and lamina propria barrier.

Summary: Overall, this study has summarized the essential regulatory mechanisms and pharmacological efficacy of TCMs on new and productive therapeutic targets.

Discussion: This review provides an avenue for studying various drugs with potentially promising effects on mucosal integrity, as well as subsequent pharmacological studies, clinical applications, and new drug development.
Association of combination antiretroviral therapy with risk of neurological diseases in patients with HIV/AIDS in Taiwan: a nested case-control study
Authors: Chou Chen-Hsing , Chiou Jian-Shiun , Ho Mao-Wang , Tien Ni , Li Te-Mao , Chiu Mu-Lin , Tsai Fuu-Jen , Wu Yang-Chang , Chou I-Ching , Lu Hsing-Fang , Lin Ting-Hsu , Liao Chiu-Chu , Huang Shao-Mei , Liang Wen-Miin , Lin Ying-Ju
Published: June 2023

Heterogeneous neurocognitive impairment remains an important issue, even in the era of combination antiretroviral therapy (cART), with an incidence ranging from 15% to 65%. Although ART drugs with higher penetration scores to the central nervous system (CNS) show better HIV replication control in the CNS, the association between CNS penetration effectiveness (CPE) scores and neurocognitive impairment remains inconclusive. To explore whether ART exposure is associated with the risk of neurological diseases among patients with HIV/AIDS, this study in Taiwan involved 2,571 patients with neurological diseases and 10,284 matched, randomly selected patients without neurological diseases between 2010 and 2017. A conditional logistic regression model was used in this study. The parameters for ART exposure included ART usage, timing of exposure, cumulative defined daily dose (DDD), adherence, and cumulative CPE score. Incident cases of neurological diseases, including CNS infections, cognitive disorders, vasculopathy, and peripheral neuropathy, were obtained from the National Health Insurance Research Database in Taiwan. Odds ratios (ORs) for the risk of neurological diseases were conducted using a multivariate conditional logistic regression model. Patients with a history of past exposure (OR: 1.68, 95% confidence interval [CI]:1.22–2.32), low cumulative DDDs (< 2,500) (OR: 1.28, 95% CI: 1.15–1.42), low adherence (0 < adherence (ADH) ≤ 0.8) (OR: 1.46, 95% CI: 1.30–1.64), or high cumulative CPE scores (>14) (OR: 1.34, 95% CI: 1.14–1.57) had a high risk of neurological diseases. When stratified by classes of ART drugs, patients with low cumulative DDDs or low adherence had a high risk of neurological diseases, including NRTIs, PIs, NNRTIs, INSTIs, and multi-drug tablets. Subgroup analyses also suggested that patients with low cumulative DDDs or low adherence had a high risk of neurological diseases when they had high cumulative CPE scores. Patients with high cumulative DDDs or medication adherence were protected against neurological diseases only when they had low cumulative CPE scores (≤ 14). Patients may be at risk for neurological diseases when they have low cumulative DDDs, low adherence, or usage with high cumulative CPE scores. Continuous usage and low cumulative CPE scores of ART drugs may benefit neurocognitive health in patients with HIV/AIDS.
Microbiome analysis reveals potential for modulation of gut microbiota through polysaccharide-based prebiotic feeding in Oreochromis niloticus (Linnaeus, 1758)
Authors: Bera Asit Kumar , Chowdhury Hemanta , Ghatak Sandeep , Malick Ramesh Chandra , Chakraborty Nabanita , Chakraborty Hirak Jyoti , Swain Himanshu Sekhar , Hassan M. A. , Das Basanta Kumar
Published: June 2023

Characterization and functional profiling of the gut microbiota are essential for guiding nutritional interventions in fish and achieving favorable host-microbe interactions. Thus, we conducted a 30 days study to explore and document the gut microbial community of O. niloticus, as well as to evaluate the effects of a polysaccharide-based prebiotics with 0.5% and 0.75% Aloe vera extract on the gut microbiome through genomic analysis. The V3–V4 region of 16S rRNA was amplified and sequenced using Illumina HiSeq 2500, resulting in 1,000,199 reads for operational taxonomic unit (OTU) identification. Out of 8,894 OTUs, 1,181 were selected for further analysis. Our results revealed that Planctomycetes, Firmicutes, Proteobacteria, Verrucomicrobia, Actinobacteria, and Fusobacteria were the dominant phyla in both control and treatment samples. Higher doses of prebiotics were found to improve Planctomycetes and Firmicutes while decreasing Proteobacteria and Verrucomicrobia. We observed increasing trends in the abundance of Bacilli, Bacillaceae, and Bacillus bacteria at the class, family, and genus levels, respectively, in a dose-dependent manner. These findings were consistent with the conventional colony count data, which showed a higher prevalence of Bacillus in prebiotic-supplemented groups. Moreover, predicted functional analysis using PICRUSt indicated a dose-dependent upregulation in glycolysis V, superpathway of glycol metabolism and degradation, glucose and xylose degradation, glycolysis II, and sulfoglycolysis pathways. Most of the energy, protein, and amino acid synthesis pathways were upregulated only at lower doses of prebiotic treatment. Our findings suggest that the gut microbiome of O. niloticus can be optimized through nutritional interventions with plant-based polysaccharides for improved growth performance in commercial fish.
The importance of mechanical conditions in the testing of excitation abnormalities in a population of electro-mechanical models of human ventricular cardiomyocytes
Authors: Dokuchaev Arsenii , Kursanov Alexander , Balakina-Vikulova Nathalie A. , Katsnelson Leonid B. , Solovyova Olga
Published: June 2023

Background: Populations of in silico electrophysiological models of human cardiomyocytes represent natural variability in cell activity and are thoroughly calibrated and validated using experimental data from the human heart. The models have been shown to predict the effects of drugs and their pro-arrhythmic risks. However, excitation and contraction are known to be tightly coupled in the myocardium, with mechanical loads and stretching affecting both mechanics and excitation through mechanisms of mechano-calcium-electrical feedback. However, these couplings are not currently a focus of populations of cell models.

Aim: We investigated the role of cardiomyocyte mechanical activity under different mechanical conditions in the generation, calibration, and validation of a population of electro-mechanical models of human cardiomyocytes.

Methods: To generate a population, we assumed 11 input parameters of ionic currents and calcium dynamics in our recently developed TP + M model as varying within a wide range. A History matching algorithm was used to generate a non-implausible parameter space by calibrating the action potential and calcium transient biomarkers against experimental data and rejecting models with excitation abnormalities. The population was further calibrated using experimental data on human myocardial force characteristics and mechanical tests involving variations in preload and afterload. Models that passed the mechanical tests were validated with additional experimental data, including the effects of drugs with high or low pro-arrhythmic risk.

Results: More than 10% of the models calibrated on electrophysiological data failed mechanical tests and were rejected from the population due to excitation abnormalities at reduced preload or afterload for cell contraction. The final population of accepted models yielded action potential, calcium transient, and force/shortening outputs consistent with experimental data. In agreement with experimental and clinical data, the models demonstrated a high frequency of excitation abnormalities in simulations of Dofetilide action on the ionic currents, in contrast to Verapamil. However, Verapamil showed a high frequency of failed contractions at high concentrations.

Conclusion: Our results highlight the importance of considering mechanoelectric coupling in silico cardiomyocyte models. Mechanical tests allow a more thorough assessment of the effects of interventions on cardiac function, including drug testing.
Achievement of higher biomass, yield and quality of essential oil of Tagetes minuta L. through optimizing the sowing method and seeding rate
Authors: Pal Probir Kumar , Mahajan Mitali , Thakur Babit Kumar , Kapoor Priya , Shivani
Published: June 2023

Tagetes minuta L. is known as an industrial crop in the world as it possesses an essential oil that is extensively used in the perfumery and flavor industries. The crop performance is influenced by the planting/sowing method (SM) and seeding rate (SR); however, the effects of these variables on biomass yield and quality of the essential oil of T. minuta remain unclear. As a comparatively new crop, the responses of T. minuta to different SMs and SRs have not been studied in the mild temperate eco-region. Thus, the biomass and essential oil yield response of T. minuta (variety ‘Himgold’) to SM (line sowing and broadcasting) and SR (at 2, 3, 4, 5, and 6 kg ha−1) were investigated. The overall fresh biomass of T. minuta ranged from 16.86 to 28.13 Mg ha−1, while the essential oil concentration in fresh biomass varied from 0.23% to 0.33%. Irrespective of the SR, the broadcasting method produced significantly (p ≤ 0.05) higher fresh biomass yield by approximately 15.8% and 7.6% compared with line sowing during 2016 and 2017, respectively. An increase in biomass yield was noted as the SR increased up to 4 kg ha−1. The SR at 4 kg ha−1 registered approximately 41.9%–56.1% and 3.3%−10.3% higher biomass yield than the SR at 2 and 6 kg ha−1, respectively. No significant (p ≥ 0.05) differences in essential oil concentration in fresh biomass were observed due to the different SMs and SRs. Thus, T. minuta may be sown by the broadcasting method in the mild temperate eco-region with an SR of 4 kg ha−1.
Minerals and chelated-based manganese fertilization influences the productivity, uptake, and mobilization of manganese in wheat (Triticum aestivum L.) in sandy loam soils
Authors: Dhaliwal Salwinder Singh , Sharma Vivek , Shukla Arvind Kumar , Verma Vibha , Kaur Manmeet , Alsuhaibani Amnah Mohammed , Gaber Ahmed , Singh Prabhjot , Laing Alison M. , Hossain Akbar
Published: June 2023

Manganese (Mn) is an essential micronutrient in plants, and it is necessary for hydrolysis in photosystem II, chlorophyll biosynthesis, and also chloroplast breakdown. Limited Mn availability in light soil resulted in interveinal chlorosis, poor root development, and the development of fewer tillers, particularly staple cereals including wheat, while foliar Mn fertilizers were found efficient in improving crop yield as well as Mn use efficiency. In the above context, a study was conducted in consecutive two wheat growing seasons for screening of the most effective and economical Mn treatment for improving the yield and Mn uptake in wheat and to compare the relative effectiveness of MnCO3against the recommended dose of MnSO4for wheat. To fulfill the aims of the study, three manganese products, namely, 1) manganese carbonate MnCO3(26% Mn w/w and 3.3% N w/w), 2) 0.5% MnSO4·H2O (30.5% Mn), and 3) Mn-EDTA solution (12% Mn), were used as experimental treatments. Treatments and their combinations were as follows: two levels of MnCO3(26% Mn) @ 750 and 1,250 ml ha−1were applied at the two stages (i.e., 25–30 and 35–40 days after sowing) of wheat, and three sprays each of 0.5% MnSO4(30.5% Mn) and Mn-EDTA (12% Mn) solution were applied in other plots. The 2-year study showed that Mn application significantly increased the plant height, productive tillers plant−1, and 1,000 grain weight irrespective of fertilizer source. The results of MnSO4for grain yield wheat as well as uptake of Mn were statistically at par with both levels (750 and 1,250 ml ha−1) of MnCO3with two sprays at two stages of wheat. However, the application of Mn in the form of 0.5% MnSO4·H2O (30.5% Mn) was found more economical than MnCO3, while the mobilization efficiency index (1.56) was found maximum when Mn was applied in MnCO3with two sprays (750 and 1,250 ml ha−1) in the two stages of wheat. Thus, the present study revealed that MnCO3can be used as an alternative to MnSO4to enhance the yield and Mn uptake of wheat.
Metabolomics and genetics of reproductive bud development in Ficus carica var. sativa (edible fig) and in Ficus carica var. caprificus (caprifig): similarities and differences
Authors: Marcotuli Ilaria , Mandrone Manuela , Chiocchio Ilaria , Poli Ferruccio , Gadaleta Agata , Ferrara Giuseppe
Published: June 2023

In figs, reproductive biology comprises cultivars requiring or not pollination, with female trees (edible fig) and male trees (caprifig) bearing different types of fruits. Metabolomic and genetic studies may clarify bud differentiation mechanisms behind the different fruits. We used a targeted metabolomic analysis and genetic investigation through RNA sequence and candidate gene investigation to perform a deep analysis of buds of two fig cultivars, ‘Petrelli’ (San Pedro type) and ‘Dottato’ (Common type), and one caprifig. In this work, proton nuclear magnetic resonance (1H NMR-based metabolomics) has been used to analyze and compare buds of the caprifig and the two fig cultivars collected at different times of the season. Metabolomic data of buds collected on the caprifig, ‘Petrelli’, and ‘Dottato’ were treated individually, building three separate orthogonal partial least squared (OPLS) models, using the “y” variable as the sampling time to allow the identification of the correlations among metabolomic profiles of buds. The sampling times revealed different patterns between caprifig and the two edible fig cultivars. A significant amount of glucose and fructose was found in ‘Petrelli’, differently from ‘Dottato’, in the buds in June, suggesting that these sugars not only are used by the ripening brebas of ‘Petrelli’ but also are directed toward the developing buds on the current year shoot for either a main crop (fruit in the current season) or a breba (fruit in the successive season). Genetic characterization through the RNA-seq of buds and comparison with the literature allowed the identification of 473 downregulated genes, with 22 only in profichi, and 391 upregulated genes, with 21 only in mammoni.