bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole exome sequencing highlights rare variants in CTCF, DNMT1, DNMT3A, EZH2 and SUV39H1 as associated with FSHD
Authors: Strafella Claudia , Caputo Valerio , Bortolani Sara , Torchia Eleonora , Megalizzi Domenica , Trastulli Giulia , Monforte Mauro , Colantoni Luca , Caltagirone Carlo , Ricci Enzo , Tasca Giorgio , Cascella Raffaella , Giardina Emiliano
Published: August 2023

Introduction: Despite the progress made in the study of Facioscapulohumeral Dystrophy (FSHD), the wide heterogeneity of disease complicates its diagnosis and the genotype-phenotype correlation among patients and within families. In this context, the present work employed Whole Exome Sequencing (WES) to investigate known and unknown genetic contributors that may be involved in FSHD and may represent potential disease modifiers, even in presence of a D4Z4 Reduced Allele (DRA).

Methods: A cohort of 126 patients with clinical signs of FSHD were included in the study, which were characterized by D4Z4 sizing, methylation analysis and WES. Specific protocols were employed for D4Z4 sizing and methylation analysis, whereas the Illumina® Next-Seq 550 system was utilized for WES. The study included both patients with a DRA compatible with FSHD diagnosis and patients with longer D4Z4 alleles. In case of patients harboring relevant variants from WES, the molecular analysis was extended to the family members.

Results: The WES data analysis highlighted 20 relevant variants, among which 14 were located in known genetic modifiers (SMCHD1, DNMT3B and LRIF1) and 6 in candidate genes (CTCF, DNMT1, DNMT3A, EZH2 and SUV39H1). Most of them were found together with a permissive short (4–7 RU) or borderline/long DRA (8–20 RU), supporting the possibility that different genes can contribute to disease heterogeneity in presence of a FSHD permissive background. The segregation and methylation analysis among family members, together with clinical findings, provided a more comprehensive picture of patients.

Discussion: Our results support FSHD pathomechanism being complex with a multigenic contribution by several known (SMCHD1, DNMT3B, LRIF1) and possibly other candidate genes (CTCF, DNMT1, DNMT3A, EZH2, SUV39H1) to disease penetrance and expressivity. Our results further emphasize the importance of extending the analysis of molecular findings within the proband’s family, with the purpose of providing a broader framework for understanding single cases and allowing finer genotype-phenotype correlations in FSHD-affected families.
Immediate postpartum family planning utilization and its associated factors among postpartum women in Ethiopia: a systematic review and meta-analysis
Authors: Silesh Mulualem , Demisse Tesfanesh Lemma , Taye Birhan Tsegaw , Moltot Tebabere , Chekole Moges Sisay , Wogie Girma , Kasahun Fetene , Adanew Solomon
Published: August 2023

Background

Family planning integration in areas where women contact the healthcare system routinely is essential for addressing the high unmet need for family planning among postpartum women and reducing the risk of short interpregnancies. Immediate postpartum family planning (IPPFP) is an integrated service, and opportunities exist for women by providing family planning (FP) counseling and contraceptives as part of care following childbirth within 48 h. Therefore, this review aimed to assess the pooled estimate of immediate postpartum family planning utilization and its associated factors in Ethiopia.

Method

Electronic databases were used to conduct an extensive search of all published studies, and the digital library was used to identify any unpublished studies. An observational study that reports the prevalence/magnitude and/or associated factors/predictors/determinants of IPPFP utilization in Ethiopia was included. Data were extracted on the Microsoft Excel spreadsheet and analyzed using STATA Version 11. A random-effects model was applied to determine the pooled prevalence of immediate postpartum family planning utilization with a 95% confidence interval (CI). Inverse variance (I2) was used to identify the presence of heterogeneity, and a funnel plot and Egger's test were used to check the presence of publication bias. Subgroup analysis was conducted based on the sample size, region, and year of study to identify the source of heterogeneity.

Result

Of 15 primary studies, the overall pooled prevalence of immediate postpartum family planning utilization among postpartum women in Ethiopia was 21.04% (95% CI: 13.08, 29.00). Received counseling on FP [OR: 3.59; 95% CI (1.84, 7.01; P < 0.001), having a positive attitude toward FP [OR: 3.2; 95% CI (1.23, 8.35); P = 0.017], and partner support to use FP [OR: 5.85; 95% CI (1.12, 30.54; P = 0.036) were significant predictors of immediate postpartum family planning utilization.

Conclusion

Generally, IPPFP utilization in Ethiopia was insufficient. Therefore, to enhance the utilization, integrating FP counseling at all maternal service care points, strengthening community awareness to develop a favorable attitude toward family planning, and promoting partner involvement in family planning counseling are essential.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=239053, identifier: CRD42021239053.
Development and optimization of an in-house heterologous ELISA for detection of prednisolone drug in enzyme conjugates using spacers
Authors: Kumar Dinesh , Oberoi Harinder Singh , Singh Harpal , Shrivastav Tulsidas G. , Bhukya Prudhvi Lal , Kumari Mansi , Koner Bidhan Chandra , Sonkar Subash Chandra
Published: August 2023

The introduction of spacers in coating steroid protein complexes and/or enzyme conjugates or immunogens is known to exert an influence on the sensitivity of steroid enzyme immunoassays. We investigated the impact of different homobifunctional spacers, ranging in atomic length from 3 to 10, on the sensitivity and specificity of prednisolone (PSL) enzyme immunoassays. In this study, four homo-bifunctional spacers, namely, carbohydrazide (CH), adipic acid dihydrazide (ADH), ethylene diamine (EDA), and urea (U), were incorporated between PSL and horseradish peroxidase (HRP) for preparing the enzyme conjugate with an aim to improve the sensitivity of the assay without compromising assay specificity. The assays were developed using these enzymes conjugated with antibodies raised against the PSL-21-HS-BSA immunogen. The sensitivity of the PSL assays after insertion of a bridge in the enzyme conjugate was 1.22 ng/mL, 0.59 ng/mL, 0.48 ng/mL, and 0.018 ng/mL with ADH, CH, EDA, and urea as a spacer, respectively. Among the four combinations, the PSL-21-HS-BSA-antibody with PSL-21-HS-U-HRP-enzyme conjugate gave better sensitivity and less cross-reaction. The percent recovery of PSL from the exogenously spiked human serum pools was in the range of 88.32%-102.50%. The intra and inter-assay CV% was< 8.46%. The PSL concentration was estimated in the serum samples of patients on PSL treatment. The serum PSL values obtained by this method correlated well with the commercially available kit (r2 = 0.98). The present study suggests that the nature of the spacer is related to assay sensitivity and not the spacer length.
Molecular immune monitoring in kidney transplant rejection: a state-of-the-art review
Authors: Chancharoenthana Wiwat , Traitanon Opas , Leelahavanichkul Asada , Tasanarong Adis
Published: August 2023

Although current regimens of immunosuppressive drugs are effective in renal transplant recipients, long-term renal allograft outcomes remain suboptimal. For many years, the diagnosis of renal allograft rejection and of several causes of renal allograft dysfunction, such as chronic subclinical inflammation and infection, was mostly based on renal allograft biopsy, which is not only invasive but also possibly performed too late for proper management. In addition, certain allograft dysfunctions are difficult to differentiate from renal histology due to their similar pathogenesis and immune responses. As such, non-invasive assays and biomarkers may be more beneficial than conventional renal biopsy for enhancing graft survival and optimizing immunosuppressive drug regimens during long-term care. This paper discusses recent biomarker candidates, including donor-derived cell-free DNA, transcriptomics, microRNAs, exosomes (or other extracellular vesicles), urine chemokines, and nucleosomes, that show high potential for clinical use in determining the prognosis of long-term outcomes of kidney transplantation, along with their limitations.
Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity
Authors: Povo-Retana Adrián , Fariñas Marco , Landauro-Vera Rodrigo , Mojena Marina , Alvarez-Lucena Carlota , Fernández-Moreno Miguel A. , Castrillo Antonio , de la Rosa Medina Juan Vladimir , Sánchez-García Sergio , Foguet Carles , Mas Francesc , Marin Silvia , Cascante Marta , Boscá Lisardo
Published: August 2023

In recent years, the central role of cell bioenergetics in regulating immune cell function and fate has been recognized, giving rise to the interest in immunometabolism, an area of research focused on the interaction between metabolic regulation and immune function. Thus, early metabolic changes associated with the polarization of macrophages into pro-inflammatory or pro-resolving cells under different stimuli have been characterized. Tumor-associated macrophages are among the most abundant cells in the tumor microenvironment; however, it exists an unmet need to study the effect of chemotherapeutics on macrophage immunometabolism. Here, we use a systems biology approach that integrates transcriptomics and metabolomics to unveil the immunometabolic effects of trabectedin (TRB) and lurbinectedin (LUR), two DNA-binding agents with proven antitumor activity. Our results show that TRB and LUR activate human macrophages toward a pro-inflammatory phenotype by inducing a specific metabolic rewiring program that includes ROS production, changes in the mitochondrial inner membrane potential, increased pentose phosphate pathway, lactate release, tricarboxylic acids (TCA) cycle, serine and methylglyoxal pathways in human macrophages. Glutamine, aspartate, histidine, and proline intracellular levels are also decreased, whereas oxygen consumption is reduced. The observed immunometabolic changes explain additional antitumor activities of these compounds and open new avenues to design therapeutic interventions that specifically target the immunometabolic landscape in the treatment of cancer.
Identification of Vancomycin Resistance in Methicillin-resistant Staphylococcus aureus in two macaque species and decolonization and long-term prevention of recolonization in Cynomolgus Macaques (Macaca fascicularis)
Authors: Bochart Rachele M. , Armantrout Kimberly , Crank Hugh , Tonelli Rachael , Shriver-Munsch Christine , Swanson Tonya , Fischer Miranda , Wu Helen , Axthelm Michael , Sacha Jonah , Smedley Jeremy V.
Published: August 2023

Methicillin-resistant Staphylococcus aureus (MRSA) is a S. aureus strain with resistance to beta-lactam antibiotics, making it a global human and veterinary health concern. Specifically, immunosuppressed patients have a remarkably higher risk of clinical MRSA infections with significantly increased rates of prolonged clinical recovery, morbidity, and mortality. The current treatment of choice for MRSA is vancomycin. Importantly, we report the first known vancomycin-resistant S. aureus (VRSA) carriers in a cohort of Mauritian cynomolgus macaques (CM) imported to the Oregon National Primate Research Center (ONPRC), with a MRSA carrier rate of 76.9% (10/13 animals). All MRSA isolates also demonstrated resistance to vancomycin with prevalence of vancomycin-intermediate Staphylococcus aureus (VISA) at 30% (3/10 MRSA-positive CMs) and VRSA at 70% (7/10 MRSA-positive CMs). Additionally, we identified VRSA in a rhesus macaque (RM) housed within the same room as the VRSA-positive CMs and identified a MRSA/VISA carrier rate of 18.8% in RMs (3/16 positive for both MRSA and VISA) in unexposed recently assigned animals directly from the ONPRC RM breeding colony. Considering that the MRSA and VRSA/VISA-positive CMs future study aims included significant immunosuppression, MRSA/VRSA/VISA decolonization treatment and expanded “MRSA-free” practices were employed to maintain this status. We report the first controlled study using in-depth analyses with appropriate diagnostic serial testing to definitively show an MRSA decolonization therapy (90% success rate) and expanded barrier practice techniques to successfully prevent recolonization (100%) of a cohort of CMs MRSA-free (up to 529 days with a total of 4,806 MRSA-free NHP days).
Treatment approaches for FGFR-altered urothelial carcinoma: targeted therapies and immunotherapy
Authors: Benjamin David J. , Hsu Robert
Published: August 2023

The treatment of metastatic urothelial carcinoma has dramatically changed over the past decade with the approval of several therapies from multiple drug classes including immune checkpoint inhibitors, targeted therapies, and antibody drug conjugates. Although next generation sequencing of urothelial carcinoma has revealed multiple recurring mutations, only one targeted therapy has been developed and approved to date. Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor, has been approved for treating patients with select FGFR2 and FGFR3 alterations and fusions since 2019. Since then, emerging data has demonstrated efficacy of combining erdafitinib with immunotherapy in treating FGFR-altered urothelial carcinoma. Ongoing trials are evaluating the use of erdafitinib in non-muscle invasive urothelial carcinoma as well as in combination with enfortumab vedotin in the metastatic setting, while other FGFR targeted agents such as infigratinib, AZD4547, rogaratinib and pemigatinib continue to be in development. Future challenges will include strategies to overcome FGFR acquired resistance and efficacy and safety of combination therapies with erdafitinib and other FGFR targeted agents.
Otolith characterization and integrative species identification of adult mesopelagic fishes from the western North Atlantic Ocean
Authors: Quigley Lucinda A. , Caiger Paul E. , Govindarajan Annette F. , McMonagle Helena , Jech J. Michael , Lavery Andone C. , Sosik Heidi M. , Llopiz Joel K.
Published: August 2023

Fish diversity and ecology in the ocean’s mesopelagic zone are understudied compared to other marine regions despite growing interest in harvesting these potential resources. Otoliths can provide a wealth of taxonomic and life history information about fish, which can help fill these knowledge gaps; however, there has been relatively little research to date on the otoliths of mesopelagic species. Here, a species-specific image library was assembled of sagittal otoliths from 70 mesopelagic fishes belonging to 29 families collected in the western North Atlantic Ocean. Images of adult sagittal otoliths from 12 species were documented and photographed for the first time. The fish were identified to species with a combination of morphological characters and DNA barcoding. Regressions between otolith size and fish length are presented for the six species with the largest sample sizes in this study. This otolith image library, coupled with otolith-length and width to fish-length relationships, can be used for prey identification and back-calculation of fish size, making it a valuable tool for studies relating to food webs in the important yet poorly understood mesopelagic zone. In addition, the 44 fish barcodes generated in this study highlight the benefit of using an integrative taxonomic approach to studies of this nature, as well as add to existing public databases that enable cryptic species and metabarcoding analyses of mesopelagic species.
Low temperature, mechanical wound, and exogenous salicylic acid (SA) can stimulate the SA signaling molecule as well as its downstream pathway and the formation of fruiting bodies in Flammulina filiformis
Authors: Li Ziyan , Wen Jin , Jing Zhuohan , Li Hui , Huang Jiahua , Yuan Chengjin , Xian Lijun , Gao Lingling , Zhu Jian , Xie Baogui , Tao Yongxin
Published: August 2023

Low temperature (LT) and mechanical wound (MW), as two common physics methods, have been empirically used in production to stimulate the primordia formation of Flammulina filiformis, which is typically produced using the industrial production mode. However, the detailed effect on the fruiting body formation and important endogenous hormones and signaling pathways in this process is poorly understood. In this study, LT, MW, their combination, i.e., MW + LT, and low concentration of SA (0.1 mM SA) treatments were applied to the physiologically mature mycelia of F. filiformis. The results showed that the primordia under the four treatments began to appear on the 5th−6th days compared with the 12th day in the control (no treatment). The MW + LT treatment produced the largest number of primordia (1,859 per bottle), followed by MW (757), SA (141), and LT (22), compared with 47 per bottle in the control. The HPLC results showed that the average contents of endogenous SA were significantly increased by 1.3 to 2.6 times under four treatments. A total of 11 SA signaling genes were identified in the F. filiformis genome, including 4 NPR genes (FfNpr1-4), 5 TGA genes (FfTga1-5), and 2 PR genes (FfPr1-2). FfNpr3 with complete conserved domains (ANK and BTB/POZ) showed significantly upregulated expression under all four above treatments, while FfNpr1/2/4 with one domain showed significantly upregulated response expression under the partial treatment of all four treatments. FfTga1-5 and FfPr1-2 showed 1.6-fold to 8.5-fold significant upregulation with varying degrees in response to four treatments. The results suggested that there was a correlation between “low temperature/mechanical wound—SA signal—fruiting body formation”, and it will help researchers to understand the role of SA hormone and SA signaling pathway genes in the formation of fruiting bodies in fungi.
Protocol for the safety and efficacy of fecal microbiota transplantation liquid in children with autism spectrum disorder: a randomized controlled study
Authors: Wei Jinying , Chen Jiayi , Fang Xiaohui , Liu Tianyu , Yuan Yanhan , Zhang Jinping
Published: August 2023

Background

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, repetitive behavior and language impairment, and its worldwide prevalence has been found to be increasing annually in recent years. Till now, ASD is uncurable as its pathogenesis remains unknown. However, studies on both animals and humans have demonstrated that fecal microbiota transplantation (FMT) may ameliorate the symptoms of ASD, as well as gastrointestinal symptoms. Nonetheless, there is still no agreement regarding the optimal dosage or duration of FMT treatment for individuals with ASD.

Methods

This clinical study is a double-blind, randomized, interventional trial conducted at a single center. The aim is to investigate the safety and efficacy of a pediatric formulation of FMT for ASD. A total of 42 children between the ages of 3–9 with ASD will be randomly assigned in a 2:1 ratio to either an FMT treatment group (n = 28) or a placebo group (n = 14), forming cohort 1. Additionally, 30 healthy children of similar age and gender will be recruited as the control group (cohort 2). Cohort 1 will be assessed using a variety of scales, including the Autism Behavior Checklist, Childhood Autism Rating Scale, Social Responsiveness Scale, Gastrointestinal Symptom Rating Scale, Children’s Sleep Habits Questionnaire, and Psychoeducational Profile (Third Edition). These assessments will evaluate the effectiveness of FMT in reducing core symptoms and comorbidities (such as gastrointestinal symptoms and sleep disturbances) in children with ASD. The study will use metagenomic and metabolomic sequencing to assess changes in the composition and structure of the intestinal flora and its metabolites in blood, urine, and feces following treatment. Furthermore, the study will evaluate the acceptability of the FMT formulation by participants’ legal guardians and investigate differences in the intestinal flora and metabolism in the FMT group before and after treatment compared to 30 healthy children.

Clinical trial registration

https://www.chictr.org.cn/, identifier ChiCTR2200058459.
Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases
Authors: Paluvai Harikrishnareddy , Shanmukha Kumar D. , Tyedmers Jens , Backs Johannes
Published: August 2023

Histone deacetylase 3 (HDAC3) and nuclear receptor co-repressor (NCoR1/2) are epigenetic regulators that play a key role in gene expression and metabolism. HDAC3 is a class I histone deacetylase that functions as a transcriptional co-repressor, modulating gene expression by removing acetyl groups from histones and non-histone proteins. NCoR1, on the other hand, is a transcriptional co-repressor that interacts with nuclear hormone receptors, including peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor (LXR), to regulate metabolic gene expression. Recent research has revealed a functional link between HDAC3 and NCoR1 in the regulation of metabolic gene expression. Genetic deletion of HDAC3 in mouse models has been shown to improve glucose intolerance and insulin sensitivity in the liver, skeletal muscle, and adipose tissue. Similarly, genetic deletion of NCoR1 has improved insulin resistance and reduced adiposity in mouse models. Dysregulation of this interaction has been associated with the development of cardio-metabolic diseases such as cardiovascular diseases, obesity and type 2 diabetes, suggesting that targeting this pathway may hold promise for the development of novel therapeutic interventions. In this review, we summarize the current understanding of individual functions of HDAC3 and NCoR1/2 and the co-repressor complex formation (HDAC3/NCoR1/2) in different metabolic tissues. Further studies are needed to thoroughly understand the mechanisms through which HDAC3, and NCoR1/2 govern metabolic processes and the implications for treating metabolic diseases.
Deep reinforcement learning-aided autonomous navigation with landmark generators
Authors: Wang Xuanzhi , Sun Yankang , Xie Yuyang , Bin Jiang , Xiao Jian
Published: August 2023

Mobile robots are playing an increasingly significant role in social life and industrial production, such as searching and rescuing robots, autonomous exploration of sweeping robots, and so on. Improving the accuracy of autonomous navigation of mobile robots is a hot issue to be solved. However, traditional navigation methods are unable to realize crash-free navigation in an environment with dynamic obstacles, more and more scholars are gradually using autonomous navigation based on deep reinforcement learning (DRL) to replace overly conservative traditional methods. But on the other hand, DRL's training time is too long, and the lack of long-term memory easily leads the robot to a dead end, which makes its application in the actual scene more difficult. To shorten training time and prevent mobile robots from getting stuck and spinning around, we design a new robot autonomous navigation framework which combines the traditional global planning and the local planning based on DRL. Therefore, the entire navigation process can be transformed into first using traditional navigation algorithms to find the global path, then searching for several high-value landmarks on the global path, and then using the DRL algorithm to move the mobile robot toward the designated landmarks to complete the final navigation, which makes the robot training difficulty greatly reduced. Furthermore, in order to improve the lack of long-term memory in deep reinforcement learning, we design a feature extraction network containing memory modules to preserve the long-term dependence of input features. Through comparing our methods with traditional navigation methods and reinforcement learning based on end-to-end depth navigation methods, it shows that while the number of dynamic obstacles is large and obstacles are rapidly moving, our proposed method is, on average, 20% better than the second ranked method in navigation efficiency (navigation time and navigation paths' length), 34% better than the second ranked method in safety (collision times), 26.6% higher than the second ranked method in success rate, and shows strong robustness.
CutFEM forward modeling for EEG source analysis
Authors: Erdbrügger Tim , Westhoff Andreas , Höltershinken Malte , Radecke Jan-Ole , Buschermöhle Yvonne , Buyx Alena , Wallois Fabrice , Pursiainen Sampsa , Gross Joachim , Lencer Rebekka , Engwer Christian , Wolters Carsten
Published: August 2023

Introduction

Source analysis of Electroencephalography (EEG) data requires the computation of the scalp potential induced by current sources in the brain. This so-called EEG forward problem is based on an accurate estimation of the volume conduction effects in the human head, represented by a partial differential equation which can be solved using the finite element method (FEM). FEM offers flexibility when modeling anisotropic tissue conductivities but requires a volumetric discretization, a mesh, of the head domain. Structured hexahedral meshes are easy to create in an automatic fashion, while tetrahedral meshes are better suited to model curved geometries. Tetrahedral meshes, thus, offer better accuracy but are more difficult to create.

Methods

We introduce CutFEM for EEG forward simulations to integrate the strengths of hexahedra and tetrahedra. It belongs to the family of unfitted finite element methods, decoupling mesh and geometry representation. Following a description of the method, we will employ CutFEM in both controlled spherical scenarios and the reconstruction of somatosensory-evoked potentials.

Results

CutFEM outperforms competing FEM approaches with regard to numerical accuracy, memory consumption, and computational speed while being able to mesh arbitrarily touching compartments.

Discussion

CutFEM balances numerical accuracy, computational efficiency, and a smooth approximation of complex geometries that has previously not been available in FEM-based EEG forward modeling.
A study protocol for a pilot randomized controlled trial to evaluate the effectiveness of a gene-based nutrition and lifestyle recommendation for weight management among adults: the MyGeneMyDiet® study
Authors: Nacis Jacus S. , Labrador Jason Paolo H. , Ronquillo Diana Glades D. , Rodriguez Marietta P. , Dablo Aurora Maria Francesca D. , Frane Ruby D. , Madrid Marilou L. , Santos Noelle Lyn C. , Carrillo Julianne Janine V. , Fernandez Mikko Glen , Gonzales Gerard Bryan L.
Published: August 2023

Introduction

Managing nutrition and lifestyle practices, nutrition phenotypes, and the genome forms the foundation of precision nutrition. Precision nutrition focuses on metabolic variability among individuals, and one approach to achieving its goals is to integrate gene-based nutrition and lifestyle recommendations in nutrition practice. However, scientific evidence proving the effectiveness of such recommendations is limited. This study will examine whether providing nutrition and lifestyle recommendations based on individual genotype can lead to better weight loss, along with reduction in body mass index (BMI), waist circumference, and body fat percentage among overweight and obese adults.

Methods and analysis

A parallel group, single-blind, randomized controlled trial will be conducted. Sixty-two overweight/obese individuals aged 19–59 years old will be recruited. Participants will be randomly allocated to either the intervention (n = 31) or the control arm (n = 31). Participants in the intervention group will receive the MyGeneMyDiet® Recommendation for Weight Management, a gene-based nutrition and lifestyle recommendation that was developed based on existing evidence of the effects of FTO rs9939609 on body weight, BMI, and physical activity; UCP1 rs1800592 on calorie intake; and TCF7L2 rs7903146 on dietary fat intake. Participants in the control group will receive the standard recommendations for weight management. The primary outcomes will be the differences in weight, BMI, waist circumference, and body fat percentage between arms in both the active phase (6 months) and inactive phase (last 6 months) of the trial. Participants in both arms will be evaluated at baseline and in months 3, 6, 9, and 12.

Discussion

To the best of our knowledge, this will be the first gene-based intervention that will adopt a phase of intensive nutrition counseling, followed by a simulation of a free-living state to determine adherence to a gene-based recommendation. This study will contribute to the future implementation of precision nutrition interventions by providing evidence on the effectiveness of a gene-based nutrition and lifestyle recommendation for weight loss.

Clinical trial registration

clinicaltrials.gov, identifier [NCT05098899].
In vitro and in silico perspectives on the activation of antioxidant responsive element by citrus-derived flavonoids
Authors: Guan Tianzhu , Bian Canfeng , Ma Zheng
Published: August 2023

Introduction

Oxidative stress plays an essential role in the pathogenesis of chronic diseases. Disrupting the Keap1-Nrf2 pathway by binding Keap1 is identified as a potential strategy to prevent oxidative stress-related chronic diseases. Therefore, of special interest is the utilization of dietary antioxidations from citrus, including narirutin, naringenin, hesperetin, hesperidin, naringin, neohesperidin dihydrochalcone, neohesperidin, and nobiletin, has been exploited as a prospective way to treat or prevent several human pathologies as Keap1-Nrf2 inhibitors for modulation of antioxidant properties.

Methods

To probe into the structural foundation of the molecular identification of citrus-derived antioxidations, we calculated the antioxidant responsive element activation ability of citrus-derived flavonoids after binding with Keap1. Also, the quantum chemistry properties and binding mode were performed theoretically with frontier molecular orbitals, molecular electrostatic potential analysis, molecular docking, and absorption, distribution, metabolism, excretion (ADME) calculation.

Results and discussion

Experimental findings combining computational assays revealed that the tested citrus-derived flavonoids can be grouped into strong agonists and weak agonists. The citrus-derived antioxidations were well housed in the bound zone of Keap1 via stable hydrogen bonding and hydrophobic interaction. Eventually, three of eight antioxidations were identified after ADME and physicochemical evaluations. The citrus-derived flavonoids were identified as potential dietary antioxidants of the Keap1-Nrf2 interaction, and can be used to improve oxidative stress-related chronic diseases.
Anti-cancer treatment within two weeks serves as a risk factor for clinical outcomes among cancer patients with COVID-19
Authors: Huang Jia-Xin , Liu Bo , Cong Xiao-Feng , Guan Yan-Jie , Zhang Yi-Qun , Song Wei , Li Zhi , Liu Zi-Ling , Wang Nan-Ya
Published: August 2023

Background

The coronavirus disease 2019 (COVID-19) pandemic has resulted in infections among patients with cancer. Our study aimed to investigate the potential adverse impact of anti-cancer treatments within 2 weeks of COVID-19 infection on clinical outcomes in patients with cancer.

Methods

This retrospective cohort study analyzed 70 cancer patients with COVID-19 infection from the First Hospital of Jilin University in Changchun City, Jilin Province, between March and June 2022. Data on demographic characteristics, vaccination status, COVID-19 clinical classification, symptoms, complications, tumor-related characteristics, laboratory examinations and medical interventions were extracted from electronic medical record. The primary outcome of our study was Intensive Care Unit (ICU) admission. Logistic regression model was performed to investigate the association between anti-cancer treatments within 2 weeks after COVID-19 infection and the risk of ICU admission.

Results

Of the 70 patients enrolled in this study, 37 received anti-cancer treatments within 2 weeks after COVID-19 infection. Patients receiving anti-cancer treatment were more likely to experience non-mild COVID-19, require oxygen therapy, develop acute respiratory distress syndrome (ARDS) and exhibit elevated inflammatory levels. The risk of ICU admission (P<0.001) and 30-day mortality after reverse transcriptase polymerase chain reaction (RT-PCR) negative conversion (P=0.007) was significantly higher in patients receiving anti-cancer treatments. In multivariate Logistic regression analysis, non-mild classification of COVID-19, anti-cancer treatments within 2 weeks and ECOG > 1were all independently associated with ICU admission after adjusting for confounder factors. The risk of ICU admission rose to 43.63 times (95% confidence interval=1.31–1452.94, P=0.035) in patients receiving anti-cancer treatments within 2 weeks.

Conclusion

Anti-cancer treatments within 2 weeks of COVID-19 infection increase the risk of ICU admission and 30-day mortality after RT-PCR negative conversion in patients with cancer. It may be recommended to postpone cancer-related treatments for more than 2 weeks in cancer patients with COVID-19 infection.
Dissecting the effects of METTL3 on alternative splicing in prostate cancer
Authors: Wang Lin , Shi Ling , Liang Yonghao , Ng Judy Kin-Wing , Yin Chan Hoi , Wang Lingyi , Hou Jinpao , Wang Yiwei , Fung Cathy Sin-Hang , Chiu Peter Ka-Fung , Ng Chi-Fai , Tsui Stephen Kwok-Wing
Published: August 2023

Although the role of METTL3 has been extensively studied in many cancers, its role in isoform switching in prostate cancer (PCa) has been poorly explored. To investigate its role, we applied standard RNA-sequencing and long-read direct RNA-sequencing from Oxford Nanopore to examine how METTL3 affects alternative splicing (AS) in two PCa cell lines. By dissecting genome-wide METTL3-regulated AS events, we noted that two PCa cell lines (representing two different PCa subtypes, androgen-sensitive or resistant) behave differently in exon skipping and intron retention events following METTL3 depletion, suggesting AS heterogeneity in PCa. Moreover, we revealed that METTL3-regulated AS is dependent on N6-methyladenosine (m6A) and distinct splicing factors. Analysis of the AS landscape also revealed cell type specific AS signatures for some genes (e.g., MKNK2) involved in key functions in PCa tumorigenesis. Finally, we also validated the clinical relevance of MKNK2 AS events in PCa patients and pointed to the possible regulatory mechanism related to m6A in the exon14a/b region and SRSF1. Overall, we characterize the role of METTL3 in regulating PCa-associated AS programs, expand the role of METTL3 in tumorigenesis, and suggest that MKNK2 AS events may serve as a new potential prognostic biomarker.
The impact of COVID-19 on chronic pain
Authors: Lavin Abraham , LeBlanc Félix , El Helou Antonios
Published: August 2023

A reduced quality of life is often a hefty burden that those with chronic pain are left to bear. This review of literature from PubMed, Google Scholar and other relevant studies focuses on the complex relationship between COVID-19 and chronic pain, which is challenging to study during the COVID-19 pandemic. In this review, we will briefly discuss the epidemiologic facts and risk factors, followed by the proposed pathophysiologic mechanisms. Furthermore, we will cover the therapeutic avenues regarding various molecules and their possible interactions, with the most promising being those whose mechanism of action can be directly linked to the pathophysiologic aspects of the condition. Finally, we will describe how to deal with a chronic pain patient who consults during the pandemic.
LIBS at high duty-cycles: effect of repetition rate and temporal width on the excitation laser pulses
Authors: Riedel Jens , Hufgard Josefin , You Yi
Published: August 2023

Laser-induced breakdown spectroscopy (LIBS) is becoming a more mature technology every year with new variants such as laser ablation molecular isotopic spectrometry, reheating by various discharge techniques, and multiple pulse excitation schemes, in which sometimes lasers of different pulse lengths are used. However, lasers with inherent parameters like pulse length and repetition rate are still almost exclusively employed. Recent years have witnessed the advent of novel high-repetition-rate laser concepts for machining processes, like welding, milling, and engraving. Here, a comprehensive study of single-pulse LIBS spectra of a single aluminum target is presented to showcase the applicability of flexible high duty-cycle master oscillator power amplifier (MOPA) lasers. Although traditional flashlamp-pumped Fabry–Pérot lasers only permit a variation in the pulse energy and are operated at very low duty-cycles, MOPA lasers add repetition rate and pulse length as variable parameters. A thorough analysis of the temporal plasma behavior revealed the emission dynamic to closely match the excitation laser pulse pattern. An aluminum sample’s spectral response was shown to be significantly impacted by variations in both rate and length. Although the spectral emission strength of the elemental lines of Al, Sr, and Ca all peaked at slightly different parameter settings, the strongest impact was found on the relative abundance of molecular AlO bands. Unlike in previous laser ablation molecular isotopic spectrometry (LAMIS) publications, the latter could be readily detected with a good intensity and well-resolved spectral features without any temporal gating of the detector. This finding, together with the fact that MOPA lasers are both inexpensive and dependable, makes for a promising combination for future studies including the detection of diatomic band structures.
Automatic coronary artery segmentation of CCTA images using UNet with a local contextual transformer
Authors: Wang Qianjin , Xu Lisheng , Wang Lu , Yang Xiaofan , Sun Yu , Yang Benqiang , Greenwald Stephen E.
Published: August 2023

Coronary artery segmentation is an essential procedure in the computer-aided diagnosis of coronary artery disease. It aims to identify and segment the regions of interest in the coronary circulation for further processing and diagnosis. Currently, automatic segmentation of coronary arteries is often unreliable because of their small size and poor distribution of contrast medium, as well as the problems that lead to over-segmentation or omission. To improve the performance of convolutional-neural-network (CNN) based coronary artery segmentation, we propose a novel automatic method, DR-LCT-UNet, with two innovative components: the Dense Residual (DR) module and the Local Contextual Transformer (LCT) module. The DR module aims to preserve unobtrusive features through dense residual connections, while the LCT module is an improved Transformer that focuses on local contextual information, so that coronary artery-related information can be better exploited. The LCT and DR modules are effectively integrated into the skip connections and encoder-decoder of the 3D segmentation network, respectively. Experiments on our CorArtTS2020 dataset show that the dice similarity coefficient (DSC), Recall, and Precision of the proposed method reached 85.8%, 86.3% and 85.8%, respectively, outperforming 3D-UNet (taken as the reference among the 6 other chosen comparison methods), by 2.1%, 1.9%, and 2.1%.
Is it the end of TILLING era in plant science?
Authors: Szurman-Zubrzycka Miriam , Kurowska Marzena , Till Bradley J. , Szarejko Iwona
Published: August 2023

Since its introduction in 2000, the TILLING strategy has been widely used in plant research to create novel genetic diversity. TILLING is based on chemical or physical mutagenesis followed by the rapid identification of mutations within genes of interest. TILLING mutants may be used for functional analysis of genes and being nontransgenic, they may be directly used in pre-breeding programs. Nevertheless, classical mutagenesis is a random process, giving rise to mutations all over the genome. Therefore TILLING mutants carry background mutations, some of which may affect the phenotype and should be eliminated, which is often time-consuming. Recently, new strategies of targeted genome editing, including CRISPR/Cas9-based methods, have been developed and optimized for many plant species. These methods precisely target only genes of interest and produce very few off-targets. Thus, the question arises: is it the end of TILLING era in plant studies? In this review, we recap the basics of the TILLING strategy, summarize the current status of plant TILLING research and present recent TILLING achievements. Based on these reports, we conclude that TILLING still plays an important role in plant research as a valuable tool for generating genetic variation for genomics and breeding projects.
Untargeted metabolomics reveal rhizosphere metabolites mechanisms on continuous ramie cropping
Authors: Fu Yafen , Liu Tongying , Wang Xin , Wang Yanzhou , Gong Qiulin , Li Guang , Lin Qian , Zhu Siyuan
Published: August 2023

Ramie is an important fiber feed dual-purpose crop in China and plays an important role in the national economy. However, ramie yield and quality can be reduced after many years of continuous cultivation. Currently, relatively little research has been conducted on rhizosphere metabolites and their pathways in continuous ramie cropping. Therefore, a healthy group (CK) and obstacle groups (XZQG, JZ, DJY, and GXD) with 8 years of continuous cultivation were selected for the study. LC-MS and GC-MS untargeted metabolomics were used to explore and analyze ramie rhizosphere metabolites and pathways. The results revealed that significant differences in the agronomic traits of ramie occurred after 8 years of continuous cultivation, with dwarfed plants and decreased yields in the obstacle groups. Metabolomic analysis identified 49 and 19 rhizosphere metabolites, including lipids, organic acids, phenols, and amino acids. In addition, four differential metabolic pathways (phenylpropanoid biosynthesis, fatty acid metabolism, amino acid metabolism, and ascorbate and aldarate metabolism) were elucidated. It was also clarified that sinapic acid, jasmonic acid, glutamine, and inositol might be the main metabolites affecting ramie continuous-cropping obstacle groups, and they were significantly correlated with ramie agronomic traits and physiological indicators. This provided important insights into the mechanisms affecting continuous ramie cropping. Accordingly, it is expected that the increase or decrease of sinapic acid, jasmonic acid, glutamine, and inositol in the soil will alleviate obstacles to continuous ramie cropping and promote the healthy development of the ramie industry in the future.
Reliable change in developmental outcomes of Brain Balance® participants stratified by baseline severity
Authors: Jackson Rebecca , Jordan Joshua T.
Published: August 2023

The effects of comprehensive multimodal programs on developmental outcomes have not been well-studied. Emerging evidence suggests a possible role for the Brain Balance® (BB) program, a multimodal training program, in serving as a nonpharmacologic approach to addressing cognitive, attentional, and emotional issues in youth. In this analysis, we examined the effects of 3 months of participation in the BB program on the outcomes of children and adolescents with developmental difficulties (N = 4,041; aged 4–18 years; 69.7% male). Parent-rated scores on the Brain Balance–Multidomain Developmental Survey (BB-MDS) were used to assess six areas at baseline and post-program: (1) negative emotionality; (2) reading/writing difficulties; (3) hyperactive/disruptive behavior; (4) academic disengagement; (5) motor/coordination problems; and (6) social communication problems. To estimate change from pre- to post-program, we calculated effect size (Cohen’s d) and the Reliable Change Index (RCI) for groups stratified by baseline severity. There was a very large effect size for the moderate/high severity (d = 1.63) and extreme severity (d = 2.08) groups, and a large effect size for the mild severity group (d = 0.87). The average percentage of participants who observed reliable change over all BB-MDS domains was 60.1% (RCICTT) for extreme severity, 46.6% (RCICTT) for moderate/high severity, and 21.1% (RCICTT) for baseline mild severity. In additional assessments of primitive reflexes and sensory motor activity, students demonstrated significantly diminished primitive reflexes from pre- to post-participation and significant improvements in sensory motor skills including fine motor skills, gait and aerobic ability, proprioception, rhythm and timing, and eye-gaze stability. Overall, these results demonstrate improvements in primitive reflex integration and sensory motor skills, as well as statistically significant reliable change in emotionality, reading/writing, behavior, academic engagement, motor skills, and social communication in BB participants from pre- to post-program, with the probability and degree of change increasing as the participants’ baseline severity increases. These results contribute to the growing literature on the need for evidence-based nonpharmacologic approaches to addressing developmental issues. Future research with well-controlled designs, longitudinal follow-up, implementation across settings, and participant groups in which diagnoses are known, will help to more fully characterize the effects of the BB program.
Home-administered transcranial direct current stimulation is a feasible intervention for depression: an observational cohort study
Authors: Charvet Leigh , George Allan , Charlson Erik , Lustberg Matthew , Vogel-Eyny Amy , Eilam-Stock Tehila , Cho Hyein , Best Pamela , Fernandez Luis , Datta Abhishek , Bikson Marom , Nazim Kamran , Pilloni Giuseppina
Published: August 2023

Transcranial direct current stimulation (tDCS) is an emerging treatment for major depression. We recruited participants with moderate-to-severe major depressive episodes for an observational clinical trial using Soterix Medical's tDCS telehealth platform as a standard of care. The acute intervention consisted of 28 sessions (5 sessions/week, 6 weeks) of the left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA × 30 min) followed by a tapering phase of weekly sessions for 4 weeks (weeks 7–10). The n = 16 completing participants had a significant reduction in depressive symptoms by week 2 of treatment [Montgomery–Åsberg Depression Rating Scale (MADRS), Baseline: 28.00 ± 4.35 vs. Week 2: 17.12 ± 5.32, p < 0.001] with continual improvement across each biweekly timepoint. Acute intervention responder and remission rates were 75 and 63% and 88 and 81% following the taper period (week 10).