bluuebunny/crossref_metadata_2025 huggingface dataset:
IgE and IgG4 epitopes of the peanut allergens shift following oral immunotherapy
Authors: Rambo Ian M. , Kronfel Christina M. , Rivers Adam R. , Swientoniewski Lauren T. , McBride Jane K. , Cheng Hsiaopo , Simon Reyna J. , Ryan Robert , Tilles Stephen A. , Nesbit Jacqueline B. , Kulis Michael D. , Hurlburt Barry K. , Maleki Soheila J.
Published: November 2023

Background

Oral immunotherapy (OIT) with peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; Aimmune Therapeutics) is an FDA-approved treatment to desensitize peanut allergic participants.

Objective

Here we assessed shifts in IgE and IgG4 binding to peanut allergens and their epitopes recognized by United States (US) peanut allergic participants (n = 20) enrolled in phase 3 PTAH OIT clinical trials.

Methods

Pre- and post- trial participant sera were collected approximately 12 months apart and tested for IgE binding to intact peanut proteins via ImmunoCAP ISAC immunoassays. IgE and IgG4 linear epitopes were identified based on binding to synthetic overlapping 15-mer linear peptides of 10 peanut allergens (Ara h 1-11) synthesized on microarray slides.

Results

Statistically significant decreases in IgE binding were identified for intact Ara h 2, 3, and 6, and known and newly identified IgE epitopes were shown to exhibit shifts towards IgG4 binding post-OIT, with most linear peptides having increased IgG4 binding after treatment with PTAH. While PTAH does not seem to alter the actual peptide binding patterns significantly after one year of treatment, the IgE and IgG4 binding ratios and intensity are altered.

Conclusion

At a population level, the linear IgE and IgG4 epitopes of 10 peanut allergens overlap and that increase in IgG4 with OIT results in displacement of IgE binding to both conformational and linear epitopes. Furthermore, it appears as though the increase in IgG4 is more important to achieve desensitization at the 12-month timepoint than the decrease in IgE. This type of knowledge can be useful in the identification of IgE and IgG4-binding allergen and peptide biomarkers that may indicate desensitization or sustained unresponsiveness of allergic individuals to peanut.
Recent insight into the role of macrophage in alcohol-associated liver disease: a mini-review
Authors: Sun Jialiang , Zhao Peiliang , Shi Ying , Li Yanan
Published: November 2023

Alcohol-associated liver disease (ALD) is a condition that develops due to prolonged and excessive alcohol consumption. It encompasses various stages of liver damage, including fatty liver, alcoholic hepatitis, and cirrhosis. Immune cells, particularly macrophages, of various types play a significant role in the onset and progression of the disease. Macrophages observed in the liver exhibit diverse differentiation forms, and perform a range of functions. Beyond M1 and M2 macrophages, human macrophages can polarize into distinct phenotypes in response to various stimuli. Recent advancements have improved our understanding of macrophage diversity and their role in the progression of ALD. This mini-review provides a concise overview of the latest findings on the role and differentiation of macrophages in ALD. Additionally, it discusses potential therapeutic targets associated with macrophages and explores potential therapeutic strategies.
The obesity paradox in intracerebral hemorrhage: a systematic review and meta-analysis
Authors: Wang Zexu , Wang Jie , Wang Jiayan , Liao Yinghua , Hu Xin , Wang Manni
Published: November 2023

Background

Intracerebral hemorrhage (ICH) has a mortality rate which can reach 30–40%. Compared with other diseases, obesity is often associated with lower mortality; this is referred to as the ‘obesity paradox’. Herein, we aimed to summarize the studies of the relations between obesity and mortality after ICH.

Method

For this systematic review and meta-analysis (PROSPERO registry CRD42023426835), we conducted searches for relevant articles in both PubMed and Embase. Non-English language literature, irrelevant literature, and non-human trials were excluded. All included publications were then qualitatively described and summarized. Articles for which quantitative analyses were possible were evaluated using Cochrane’s Review Manager.

Results

Ten studies were included. Qualitative analysis revealed that each of the 10 studies showed varying degrees of a protective effect of obesity, which was statistically significant in 8 of them. Six studies were included in the quantitative meta-analysis, which showed that obesity was significantly associated with lower short-term (0.69 [0.67, 0.73], p<0.00001) and long-term (0.62 [0.53, 0.73], p<0.00001) mortality. (Data identified as (OR [95%CI], p)).

Conclusion

Obesity is likely associated with lower post-ICH mortality, reflecting the obesity paradox in this disease. These findings support the need for large-scale trials using standardized obesity classification methods.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023426835, identifier CRD42023426835.
Prognostic algorithms for post-discharge readmission and mortality among mother-infant dyads: an observational study protocol
Authors: Wiens Matthew O. , Trawin Jessica , Pillay Yashodani , Nguyen Vuong , Komugisha Clare , Kenya-Mugisha Nathan , Namala Angella , Bebell Lisa M. , Ansermino J. Mark , Kissoon Niranjan , Payne Beth A. , Vidler Marianne , Christoffersen-Deb Astrid , Lavoie Pascal M. , Ngonzi Joseph
Published: November 2023

Introduction

In low-income country settings, the first six weeks after birth remain a critical period of vulnerability for both mother and newborn. Despite recommendations for routine follow-up after delivery and facility discharge, few mothers and newborns receive guideline recommended care during this period. Prediction modelling of post-delivery outcomes has the potential to improve outcomes for both mother and newborn by identifying high-risk dyads, improving risk communication, and informing a patient-centered approach to postnatal care interventions. This study aims to derive post-discharge risk prediction algorithms that identify mother-newborn dyads who are at risk of re-admission or death in the first six weeks after delivery at a health facility.

Methods

This prospective observational study will enroll 7,000 mother-newborn dyads from two regional referral hospitals in southwestern and eastern Uganda. Women and adolescent girls aged 12 and above delivering singletons and twins at the study hospitals will be eligible to participate. Candidate predictor variables will be collected prospectively by research nurses. Outcomes will be captured six weeks following delivery through a follow-up phone call, or an in-person visit if not reachable by phone. Two separate sets of prediction models will be built, one set of models for newborn outcomes and one set for maternal outcomes. Derivation of models will be based on optimization of the area under the receiver operator curve (AUROC) and specificity using an elastic net regression modelling approach. Internal validation will be conducted using 10-fold cross-validation. Our focus will be on the development of parsimonious models (5–10 predictor variables) with high sensitivity (>80%). AUROC, sensitivity, and specificity will be reported for each model, along with positive and negative predictive values.

Discussion

The current recommendations for routine postnatal care are largely absent of benefit to most mothers and newborns due to poor adherence. Data-driven improvements to postnatal care can facilitate a more patient-centered approach to such care. Increasing digitization of facility care across low-income settings can further facilitate the integration of prediction algorithms as decision support tools for routine care, leading to improved quality and efficiency. Such strategies are urgently required to improve newborn and maternal postnatal outcomes.

Clinical trial registration

https://clinicaltrials.gov/, identifier (NCT05730387).
A hypothesis about the influence of oxidative stress on amino acid protein composition during evolution
Authors: González-Tortuero Enrique , Rodríguez-Rojas Alexandro
Published: November 2023

Life emerged in an anoxic world, but the release of molecular oxygen, the by-product of photosynthesis, forced adaptive changes to counteract its toxicity. However, reactive oxygen species can damage all cellular components, including proteins. Therefore, several mechanisms have evolved to balance the intracellular redox state and maintain a reductive environment more compatible with many essential biological functions. In this study, we statistically interrogated the amino acid composition of E. coli proteins to investigate how the proneness or susceptibility to oxidation of amino acids biased their sequences. By sorting the proteins into five compartments (cytoplasm, internal membrane, periplasm, outer membrane, and extracellular), we found that various oxidative lesions constrain protein composition and depend on the cellular compartments, impacting the evenness of distribution or frequency. Our findings suggest that oxidative susceptibility could influence the observed differences in amino acid abundance across cellular compartments. This result reflects how the oxidative atmosphere could restrict protein amino acid composition and impose a codon bias trend.
Long-term N addition reduced the diversity of arbuscular mycorrhizal fungi and understory herbs of a Korean pine plantation in northern China
Authors: Wang Wei , Feng Yuhan , Wu Ruotong , Wang Xiaohui , He Xue , Zhang Mengmeng , Li Kun , Jin Guangze , Song Fuqiang
Published: November 2023

With the development of agriculture and industry, the increase in nitrogen (N) deposition has caused widespread concern among scientists. Although emission reduction policies have slowed N releases in Europe and North America, the threat to biodiversity cannot be ignored. Arbuscular mycorrhizal (AM) fungi play an important role in the establishment and maintenance of plant communities in forest ecosystems, and both their distribution and diversity have vital ecological functions. Therefore, we analyzed the effects of long-term N addition on AM fungi and understory herbaceous plants in a Korean pine plantation in northern China. The soil properties, community structure, and diversity of AM fungi and understory herbaceous plants were detected at different concentrations of NH4NO3 (0, 20, 40, 80 kg N ha−1 year−1) after 7 years. The results showed that long-term N deposition decreased soil pH, increased soil ammonium content, and caused significant fluctuations in P elements. N deposition improved the stability of soil aggregates by increasing the content of glomalin-related soil protein (GRSP) and changed the AM fungal community composition. The Glomus genus was more adaptable to the acidic soil treated with the highest N concentration. The species of AM fungi, understory herbaceous plants, and the biomass of fine roots were decreased under long-term N deposition. The fine root biomass was reduced by 78.6% in the highest N concentration treatment. In summary, we concluded that long-term N deposition could alter soil pH, the distribution of N, P elements, and the soil aggregate fractions, and reduce AM fungal and understory herb diversity. The importance of AM fungi in maintaining forest ecosystem diversity was verified under long-term N deposition.
Analyses of intra-annual density fluctuation signals in Himalayan cedar trees from Himachal Pradesh, western Himalaya, India, and its relationship with apple production
Authors: Maurya Ravi S. , Misra Krishna G. , Vishwakarma Sadhana , Singh Vikram , Misra Sandhya , Yadava Akhilesh K.
Published: November 2023

Intra-annual density fluctuation (IADF) refers to anatomical changes in the tree ring caused by a sudden change in wood density triggered by a combination of climate variations and various biotic and abiotic influences. To reveal the occurrence of IADFs, we analyze the growth rings of Himalayan cedar (Cedrus deodara) growing over the Kullu region, Himachal Pradesh, western Himalaya. Using 30 increment cores, we precisely dated and developed a 214-year-long tree-ring chronology extending back to AD 1808. The tree–growth–climate relationship using ring-width chronology and observed climate data revealed that cool and moist condition provides favorable condition for Himalayan cedar tree growth. Delving deeper into wood anatomy of growth rings, we revealed the frequent occurrences of IADFs in both earlywood (IADFe) and latewood (IADFl). The formation of IADFs in earlywood (IADFe) is related to the reduced precipitation from April to July, causing moisture stress in the soil and surrounding climate. However, wetter conditions in the late growing season, mainly August–October, activated the formation of IADFs in latewood (IADFl). The study revealed several IADF years in earlywood and latewood, such as 1901, 1902, 1903, 1914, 1915, 1919, 1920, 1923, 1925, 1943, 1958, 1959 and 1937, 1955, 1956, 1988, respectively. These IADF years corresponded with unusual climatic fluctuations that severely affected apple production, the major cash crop in the region. The analyses demonstrated that the IADF chronology of Himalayan cedar would be a valuable proxy to understand abrupt and unusual climatic fluctuations from a long-term perspective for the data-scarce western Himalayan region.
Integration of transcriptomic, proteomic, and metabolomic data to identify lncRNA rPvt1 associations in lipopolysaccharide-treated H9C2 cardiomyocytes
Authors: Zhang Tie-Ning , Wen Ri , Yang Yu-Hang , Yang Ni , Liu Chun-Feng
Published: November 2023

Background: Recent evidence has shown that the long non-coding RNA (lncRNA) rPvt1 is elevated in septic myocardial tissues and that its knockdown attenuates sepsis-induced myocardial injury. However, the mechanism underlying the role of rPvt1 in septic myocardial dysfunction has not been elucidated.

Methods: In this study, we performed transcriptomic, proteomic, and metabolomic assays and conducted an integrated multi-omics analysis to explore the association between rPvt1 and lipopolysaccharide (Lipopolysaccharide)-induced H9C2 cardiomyocyte injury. LncRNA rPvt1 silencing was achieved using a lentiviral transduction system.

Results: Compared to those with the negative control, rPvt1 knockdown led to large changes in the transcriptome, proteome, and metabolome. Specifically, 2,385 differentially expressed genes (DEGs), 272 differentially abundant proteins and 75 differentially expressed metabolites (DEMs) were identified through each omics analysis, respectively. Gene Ontology functional annotation, Kyoto Encyclopedia of Genes and Genomes, Nr, eukaryotic orthologous groups, and Clusters of Orthologous Groups of Proteins pathway analyses were performed on these differentially expressed/abundant factors. The results suggested that mitochondrial energy metabolism might be closely related to the mechanism through which Pvt1 functions.

Conclusion: These genes, proteins, metabolites, and their related dysregulated pathways could thus be promising targets for studies investigating the rPvt1-regluatory mechanisms involved in septic myocardial dysfunction, which is important for formulating novel strategies for the prevention, diagnosis and treatment of septic myocardial injury.
The link between surface and sub-surface chlorophyll-a in the centre of the Atlantic subtropical gyres: a comparison of observations and models
Authors: Quartly Graham D. , Aiken Jim , Brewin Robert J. W. , Yool Andrew
Published: November 2023

Satellite observations have given us a clear idea of the changes in chlorophyll in the surface ocean on both a seasonal and interannual basis, but repeated observations at depth are much rarer. The permanently-stratified subtropical gyres in the Atlantic are highly oligotrophic, with most production centred on a deep chlorophyll maximum (DCM) just above the nitracline. This study explores the variations in this feature in the core of both gyres, considering both seasonal and interannual variations, and the linkages between changes at the surface and sub-surface. The in situ observations come from the Atlantic Meridional Transect (AMT), a long-running UK monitoring programme, and also from biogeochemical Argo floats. AMT provides measurements spanning more than 25 years directed through the centres of these gyres, but samples only 2 to 4 months per year and thus cannot resolve the seasonal variations, whereas the profiling floats give coverage throughout the year, but without the rigid spatial repeatability. These observational records are contrasted with representation of the centres of the gyres in two different biogeochemical models: MEDUSA and ERSEM, thus fulfilling one of AMT’s stated aims: the assessment of biogeochemical models. Whilst the four datasets show broadly the same seasonal patterns and that the DCM shallows when surface chlorophyll increases, the depth and peak concentration of the DCM differ among datasets. For most of the datasets the column-integrated chlorophyll for both gyres is around 19 mg m-2 (with the AMT fluorescence-derived values being much lower); however the MEDUSA model has a disparity between the northern and southern gyres that is not understood. Although the seasonal increase in surface chlorophyll is tied to a commensurate decrease in concentration at depth, on an interannual basis years with enhanced surface levels of chlorophyll correspond to increases at depth. Satellite-derived observations of surface chlorophyll concentration act as a good predictor of interannual changes in DCM depth for both gyres during their autumn season, but provide less skill in spring.
Insulin infusion sets associated with adverse events: strategies for improved diabetes education
Authors: Neves Ana Lucia Domingues , Martins Luiz Eduardo Galvão , Gabbay Mônica Andrade Lima , Pascali Paula , de Oliveira Tiago , Martinazzo Aldo , Dib Sérgio Atala , Casarini Dulce Elena , Aredes Sebastião Vagner , Tenorio Fernanda Silva , Cunha Tatiana Sousa
Published: November 2023

Introduction

Insulin Infusion Sets (IIS) play a crucial role in ensuring the safe delivery of insulin through a Continuous Subcutaneous Insulin Infusion (CSII) for individuals with Type 1 Diabetes (T1D). Recent advancements in therapy have highlighted the need to address issues such as unexplained hyperglycemia and IIS occlusion.

Objective

To investigate the adverse events (AEs) associated with IIS that impact the treatment of T1D, with a specific focus on promoting effective educational practices.

Methods

One hundred and eighteen patients under treatment at the Diabetes Center Insulin Pump Ambulatory, Federal University of São Paulo responded to a semi-structured questionnaire. Over 6 months, a nurse researcher interviewed them via video calls.

Results

Catheter-related adverse events (AEs) included catheter knots, folding, and accidental traction. AEs associated with cannula use were mainly related to cannula fixation adhesive, insulin leakage, bleeding episodes, and skin problems. The cannula patch tends to detach easily in hot conditions or when used for more than 3 days, leading to local itching. Adhesive glue can cause redness and pain. Insulin leakage typically occurs after the catheter disconnects from the cannula, accidental cannula traction, or beneath the cannula patch. Bleeding has been reported inside the cannula or at the insertion site, resulting in local pain and, in some cases, obstruction of insulin flow. When accidental cannula traction occurs, it is recommended to replace the entire IIS system. In situations involving bleeding, leakage, insulin odor, or unsuccessful attempts to correct hyperglycemic episodes with a “bolus” of insulin, it is advisable to change the IIS system and evaluate appropriate techniques for handling and infusing the device. Moreover, regular inspections of the device and reservoir/cartridge are essential.

Conclusion

Serious AEs can occur even in cases where the occlusion alarm is not activated, leading to interruptions in insulin flow. Conversely, in less severe situations, alarm activation can occur even in the absence of insulin flow interruption. Accidental catheter traction and catheter bending are commonly encountered in everyday situations, while issues related to the cannula directly affect blood glucose levels. AEs related to the IIS cannula often involve insulin leakage into the skin, bleeding, and skin events attributed to adhesive issues with the cannula.
Crosstalk between short- and long-term calorie restriction transcriptomic signatures with anxiety-like behavior, aging, and neurodegeneration: implications for drug repurposing
Authors: Hazi Agnes , Ebrahimie Esmaeil , Levay Elizabeth A. , Mohammadi-Dehcheshmeh Manijeh , Zelko Matt , Govic Antonina , Nasser Helen
Published: November 2023

Calorie restriction (CR) is considered an effective intervention for anxiety, aging, and obesity. We investigated the effects of short- and long-term CR on behavior as well as transcriptome profiles in the hypothalamus, amygdala, prefrontal cortex, pituitary, and adrenal glands of Hooded Wistar and Long Evans male rats. A reduction in anxiety-like behavior, as assessed via the elevated plus maze, was observed in both short- and long-term CR. Despite this, short- and long-term CR regulated different sets of genes, leading to distinct transcriptomic signatures. The employed models were able to simultaneously analyze categorical and numerical variables, evaluating the effect of tissue type along with expression data. In all tissues, transcription factors, zinc finger protein 45-like and zinc finger BTB domain-containing two, were the top selected genes by the models in short and long-term CR treatments, respectively. Text mining identified associations between genes of the short-term CR signature and neurodegeneration, stress, and obesity and between genes of the long-term signature and the nervous system. Literature mining-based drug repurposing showed that alongside known CR mimetics such as resveratrol and rapamycin, candidates not typically associated with CR mimetics may be repurposed based on their interaction with transcriptomic signatures of CR. This study goes some way to unravelling the global effects of CR and opens new avenues for treatment for emotional disorders, neurodegeneration, and obesity.
Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review
Authors: Noor Eddin Ahmed , Al-Rimawi Mohammed , Peer-Zada Feham , Hundallah Khalid , Alhashem Amal
Published: November 2023

The neurological complications of coronavirus disease 2019 (COVID-19) can range from simple tremors and dystonia to features of encephalopathy. Toll-like receptor 7 (TLR7) belongs to a family of innate immune receptors responsible for viral RNA detection (such as SARS-CoV-2) and immune response initiation. TLR7 loss of function variants have been previously reported as genetic risk factors for severe COVID-19 infection in young patients with no comorbidities. In this case, we report a pediatric patient who developed severe long-term neurological deterioration following his COVID-19 infection. Presenting first to the clinic with episodic dystonia and finger spasticity, the patient’s condition rapidly deteriorated with a significant drop in the Glasgow Coma Scale (GCS). Despite improvement following initial treatment with rituximab and intravenous immunoglobulin, the patient’s symptoms relapsed, and GCS further dropped to 3/15. Serial brain magnetic resonance imaging scans revealed diffuse parenchymal atrophy, ventricular enlargement, and spinal cord thickening. Autoimmune investigations were negative but clinical whole genome sequencing prioritized four gene variants, the most significant of which was a novel frameshift null variant of the X chromosomal TLR7 gene (c.1386_1389dup, p.[His464Ilefs*7]). This case illustrates a role for TLR7 in long-term COVID-19 complications and highlights that TLR7 deficiency in the future may be addressed as a therapeutic measure.
Potential neural substrates underlying circadian and olfactory disruptions in preclinical Alzheimer’s disease
Authors: Jeffs Quiana L. , Prather Jonathan F. , Todd William D.
Published: November 2023

Alzheimer’s disease (AD) is the leading cause of dementia, with over 45 million patients worldwide, and poses significant economic and emotional burdens to both patients and caregivers, significantly raising the number of those affected. Unfortunately, much of the existing research on the disease only addresses a small subset of associated symptomologies and pathologies. In this review, we propose to target the earliest stages of the disease, when symptomology first arises. In these stages, before the onset of hallmark symptoms of AD such as cognitive impairments and memory loss, circadian and olfactory disruptions arise and are detectable. Functional similarities between circadian and olfactory systems provide a basis upon which to seek out common mechanisms in AD which may target them early on in the disease. Existing studies of interactions between these systems, while intriguing, leave open the question of the neural substrates underlying them. Potential substrates for such interactions are proposed in this review, such as indirect projections that may functionally connect the two systems and dopaminergic signaling. These substrates may have significant implications for mechanisms underlying disruptions to circadian and olfactory function in early stages of AD. In this review, we propose early detection of AD using a combination of circadian and olfactory deficits and subsequent early treatment of these deficits may provide profound benefits to both patients and caregivers. Additionally, we suggest that targeting research toward the intersection of these two systems in AD could uncover mechanisms underlying the broader set of symptoms and pathologies that currently elude researchers.
Phasic and repetitive self-touch differ in hemodynamic response in the prefrontal cortex–An fNIRS study
Authors: von Au Sabrina , Helmich Ingo , Kieffer Simon , Lausberg Hedda
Published: November 2023

Introduction

Each individual touches the own body several 100 times a day. While some researchers propose a self-regulatory function of self-touch, others report that self-touching increases nervousness. This controversy appears to be caused by the fact that researchers did not define the kind of self-touch they examined and actually, referred to different types of self-touch. Thus, kinematically defining different types of self-touch, such as phasic (discrete), repetitive, and irregular, and exploring the neural correlates of the different types will provide insight into the neuropsychological function of self-touching behavior.

Methods

To this aim, we assessed hemodynamic responses in prefrontal brain areas using functional near-infrared spectroscopy (fNIRS) and behavioral responses with NEUROGES®. Fifty-two participants were recorded during three specific kinematically types of self-touch (phasic, irregular, repetitive) that were to be performed on command. The recently developed toolbox Satori was used for the visualization of neuronal processes.

Results

Behaviorally, the participants did not perform irregular self-touch reliably. Neurally, the comparison of phasic, irregular and repetitive self-touch revealed different activation patterns. Repetitive self-touch is associated with stronger hemodynamic responses in the left Orbitofrontal Cortex and the Dorsolateral Prefrontal Cortex than phasic self-touch.

Discussion

These brain areas have been reported to be associated with self-regulatory processes. Furthermore, irregular self-touch appears to be primarily generated by implicit neural control. Thus, by distinguishing kinematically different types of self-touch, our findings shed light on the controverse discussion on the neuropsychological function of self-touch.
Review of SCWR research in Japan
Authors: Oka Yoshiaki
Published: November 2023

SCWR (supercritical water cooled reactor) is one of the Generation IV reactors. This review summarizes the results of SCWR design concept development through numerical simulations carried out by the author-led team at the University of Tokyo and Waseda University from 1989 to 2014. They are core design, subchannel analysis, statistical thermal design, fuel rod design, development of fuel integrity criteria, plant system and heat balance, plant dynamics analysis, plant control, startup system, stability analysis, safety principle, safety criteria, safety analysis, transient subchannel analysis and fast reactor SCWR. A brief summary of experimental results on thermal hydraulics, materials and water chemistry follows. Discussion includes SCPR study by Japanese BWR manufacturers, comments on the 2005 INEEL SCWR report, misconceptions about SCWR and commercialization challenges. The SCWR is an innovation in light water reactors based on supercritical coal-fired power plant technology that has been in use worldwide for over half a century. This review covers most of the SCWR design and analysis. For researchers, it is a good subject to understand the design and analysis of light water reactors.
Case Report: Acute cerebral infarction as the initial manifestation of malignant tumors with trousseau syndrome in the elderly
Authors: Li Chen , Fan Miao , He Wen , Gong Yingying , Su Lei
Published: November 2023

Both acute cerebral infarction and malignant tumors are prevalent in the elderly. However, acute cerebral infarction is rarely present as the first clinical manifestation of malignant tumors. By searching the Picture Archiving and Communication System from 2010 to 2022 and the medical record database from 2003 to 2022, we found three cases of Trousseau syndrome, one male and two females with an average age of 69.3 ± 3.2 years, presenting with acute cerebral infarction. Two patients denied having hypertension, diabetes, and coronary heart disease. The average value of the D-dimer was 17.83 ± 12.39 mg/L (normal range, 0 to 0.55 mg/L). Magnetic resonance imaging (MRI) of the brain showed scattered and multiple small infarcts in the watershed area. The sites of infarction were not those that are typically caused by vascular atherosclerosis. One of the females was diagnosed with pancreatic cancer (T2N2M1, stage IV), the male was diagnosed with gastric cancer (T4N3M1, stage IV), and the other female was diagnosed with lung adenocarcinoma (rTxN3M1b, stage IV). The patient with pancreatic cancer underwent a comprehensive geriatric assessment, which revealed that she had a disability, dementia, malnutrition, short life expectancy, and high chemotherapy risk. Ultimately, the patient opted for conservative care, and 3 months after being discharged, she passed away from an acute upper gastrointestinal hemorrhage. Elderly patients with unexplained D-dimer elevation, multiple cerebral vascular lesions detected on MRI, and an absence of typical stroke risk factors need to be monitored for Trousseau syndrome. To screen for cancer, tumor markers and related imaging should be performed first. Trousseau syndrome is primarily treated with chemotherapy, radiotherapy and anticoagulant therapy. The risk of bleeding should be assessed carefully when using anticoagulant therapy in the elderly. Comprehensive geriatric assessment can assist in weighing the benefits and side effects of cancer treatment, making correct medical choices, and improving patients’ quality of life.
Two-dimensional calibration-free odds design for phase I drug-combination trials
Authors: Wang Wenliang , Jin Huaqing , Zhang Yan Dora , Yin Guosheng
Published: November 2023

In oncology, it is commonplace to treat patients with a combination of drugs that deliver different effects from different disease-curing or cancer-elimination perspectives. Such drug combinations can often achieve higher efficacy in comparison with single-drug treatment due to synergy or non-overlapping toxicity. Due to the small sample size, there is a growing need for efficient designs for phase I clinical trials, especially for drug-combination trials. In the existing experimental design for phase I drug-combination trials, most of the proposed methods are parametric and model-based, either requiring tuning parameters or prior knowledge of the drug toxicity probabilities. We propose a two-dimensional calibration-free odds (2dCFO) design for drug-combination trials, which utilizes not only the current dose information but also that from all the neighborhood doses (i.e., along the left, right, up and down directions). In contrast to interval-based designs which only use the current dose information, the 2dCFO is more efficient and makes more accurate decisions because of its additional leverage over richer resources of neighborhood data. Because our design makes decisions completely based on odds ratios, it does not rely upon any dose–toxicity curve assumption. The simulations show that the 2dCFO delivers satisfactory performances in terms of accuracy and efficiency as well as demonstrating great robustness due to its non-parametric or model-free nature. More importantly, the 2dCFO only requires the minimal specification of the target toxicity probability, which greatly eases the design process from the clinicians’ aspects.
Case report: Interleukin-17 targeted biological therapy in netherton syndrome
Authors: Mahajan Rahul , Bakshi Shirin , Kumar Anoop , De Dipankar , Handa Sanjeev
Published: November 2023

Netherton syndrome (NS) is rare and multisystemic congenital skin disorder classically distinguied as a triad of congenital ichthyosiform erythroderma, trichorrhexis invaginata (TI), and an atopic diathesis. Recent advances in pathogenesis have explored the role of IL-23/Th17 pathway in NS. Herein, we present a 17 years old girl harbouring homozygous four base pair deletion in exon 26 of the SPINK5 gene, presented with pruritus, scaling, dry skin and generalized eczematous lesions. She was administered anti IL17A (subcutaneous secukinumab) therapy. The treatment was well tolerated and resulted in a favourable clinical response, reduction of the IL17A gene expression and CD4 + Th17 cell population after 6 months which revealed an abrogation of Th17-skewing during therapy.
Effects of loading positions on the activation of trunk and hip muscles during flywheel and dumbbell single-leg Romanian deadlift exercises
Authors: Mo Ryan Chun Yin , Ngai Derrick Chung Wang , Ng Chapman Cheuk Man , Sin Kenson Ho Sang , Luk Jim Tze Chung , Ho Indy Man Kit
Published: November 2023

Objective: The study compared the activities of the surface electromyography (sEMG) of trunk and hip muscles during single-leg Romanian deadlift (SLRDL) exercises using a flywheel and dumbbell with different loading positions (ipsilateral and contralateral).

Method: Twelve active male subjects with at least 2 years of strength training experience (age: 26.7 ± 3.3 years; weight: 73.9 ± 6.2 kg) participated in this study. sEMG in the percentage of maximum voluntary isometric contraction of four SLRDL exercises (ipsilateral and contralateral loading position for dumbbell and flywheel) in a randomized order for superior gluteus maximus (SGM), inferior gluteus maximus (IGM), gluteus medius (GM), biceps femoris (BF), erector spinae (ES), external oblique (EO), and adductor longus (AL) were measured. One-way repeated measure ANOVA with Bonferroni adjustment (statistical significance at 0.05) and the non-clinical magnitude-based decision with a standardized difference were performed for statistical analysis.

Results: The overall results demonstrated a very high level of SGM (105.4%–168.6%) and BF (69.6%–122.4%) muscle activities. A significant moderate increase of sEMG signals in GM, IGM, and ES (dominant side) and a large increase in SGM activity during concentric action when the loading position of flywheel SLRDL was changed from ipsilateral to the contralateral side. No significant difference was observed between flywheel and dumbbell SLRDL exercises.

Conclusion: Strength coaches may adopt dumbbell or flywheel SLRDL exercises using the contralateral loading position to simultaneously strengthen the hip extensors and trunk stabilizers effectively.
Identification of QTNs, QTN-by-environment interactions for plant height and ear height in maize multi-environment GWAS
Authors: Shu Guoping , Wang Aifang , Wang Xingchuan , Chen Ruijie , Gao Fei , Wang Aifen , Li Ting , Wang Yibo
Published: November 2023

Plant height (PH) and ear height (EH) are important traits associated with biomass, lodging resistance, and grain yield in maize. There were strong effects of genotype x environment interaction (GEI) on plant height and ear height of maize. In this study, 203 maize inbred lines were grown at five locations across China’s Spring and Summer corn belts, and plant height (PH) and ear height (EH) phenotype data were collected and grouped using GGE biplot. Five locations fell into two distinct groups (or mega environments) that coincide with two corn ecological zones called Summer Corn Belt and Spring Corn Belt. In total, 73,174 SNPs collected using GBS sequencing platform were used as genotype data and a recently released multi-environment GWAS software package IIIVmrMLM was employed to identify QTNs and QTN x environment (corn belt) interaction (QEIs); 12 and 11 statistically significant QEIs for PH and EH were detected respectively and their phenotypic effects were further partitioned into Add*E and Dom*E components. There were 28 and 25 corn-belt-specific QTNs for PH and EH identified, respectively. The result shows that there are a large number of genetic loci underlying the PH and EH GEIs and IIIVmrMLM is a powerful tool in discovering QTNs that have significant QTN-by-Environment interaction. PH and EH candidate genes were annotated based on transcriptomic analysis and haplotype analysis. EH related-QEI S10_135 (Zm00001d025947, saur76, small auxin up RNA76) and PH related-QEI S4_4 (Zm00001d049692, mads32, encoding MADS-transcription factor 32), and corn-belt specific QTNs including S10_4 (Zm00001d023333, sdg127, set domain gene127) and S7_1 (Zm00001d018614, GLR3.4, and glutamate receptor 3.4 or Zm00001d018616, DDRGK domain-containing protein) were reported, and the relationship among GEIs, QEIs and phenotypic plasticity and their biological and breeding implications were discussed.
ABA signaling converts stem cell fate by substantiating a tradeoff between cell polarity, growth and cell cycle progression and abiotic stress responses in the moss Physcomitrium patens
Authors: Beier Marcel Pascal , Jinno Chiyo , Noda Natsumi , Nakamura Kohei , Sugano Sumio , Suzuki Yutaka , Fujita Tomomichi
Published: November 2023

Abscisic acid (ABA)-mediated abiotic stress tolerance causes plant growth inhibition. Under such stress conditions, some mosses generate de novo stress-resistant stem cells, also called brood cells or brachycytes, that do not exist under normal conditions. However, the cell physiological basis of the growth inhibition and the stem cell formation is not well understood. Here, we show that the ABA-induced growth inhibition of the moss Physcomitrium patens apical protonemal cells (protonemal stem cells) is mediated through a shift from asymmetric to symmetric cell division. This change of the cell division mode, and consequently change of stem cell activity, is substantiated by dampening cell polarity and cell proliferative activity through the altered distribution of cytoskeletal elements, the mitotic spindle and the vacuole, which results in the production of stress-resistant stem cells. Alteration of the cell physiological data is supported by the results of RNAseq analysis indicating rapid changes in both cell polarity and cell cycle regulation, while long-term treatments with ABA for 5 to 10 days impact mainly the transcriptional and translational regulation. The regulation of cell polarity and cell cycle genes suggests growth arrest mediated by small GTPases (ROPs) and their guanine exchange factors (ROPGEFs) and by cyclin and cyclin-dependent-kinase complex, respectively. Our data suggest that a tradeoff relationship between growth ability and abiotic stress response in the moss is substantiated by ABA signaling to suppress cell polarity and asymmetric cell growth and may play a pivotal role in stem cell fate conversion to newly produced stress-resistant stem cells.
Online cognitive-behavioral intervention for stress among English as a second language teachers: implications for school health policy
Authors: Eze Angela , Anyebe Mary O. , Nnamani Rebecca G. , Nwaogaidu John C. , Mmegwa Patricia U. , Akubo Esther A. , Bako Victoria N. , Ishaya Salome N. , Eze Matthew I. , Ekwueme Francis O. , Awokwe Ngozi N. , Ekwueme Uchechukwu H. , Omenma Zipporah O. , Chukwuma Joseph N. , Amujiri Benjamin A. , Bitrus Lucia A.
Published: November 2023

Introduction

Stress is one of the highest-ranked work-related injuries worldwide and has become almost universal among the Nigerian workforce. English as a Second Language (ESL) teachers face enormous work-related threats that lead to occupational stress. When ESL teachers are stressed, students' language development and entire educational progress are at risk. This is mostly underscored as English, though a second language, serves as the language of instruction in Nigerian schools. As a result, managing occupational stress is particularly important for ESL teachers, as it is among the definitive ways of improving ESL learning and overall educational outcomes. This study examined the effectiveness of online cognitive behavioral intervention (o-CBI) in lowering occupational stress among ESL teachers.

Method

ESL teachers with at least 1 year of experience were among the participants (N = 89). Participants were divided into two groups: the intervention group (N = 44) and the control group (N = 45). For 9 weeks, the experimental group engaged in nine sessions of 2 h of the o-CBI program. The Single Item Stress Questionnaire (SISQ), the Satisfaction with Therapy and Therapist Scale-Revised (STTS–R), and the Teachers' Stress Inventory (TSI) were the measures used to collect primary and secondary data. Four sets of data were collected at baseline, post-test, and follow-up 1 and 2 evaluations. The data were analyzed using mean, standard deviation, t-test statistics, repeated measures ANOVA, and bar charts.

Results and discussion

Compared to the control group, the o-CBT group had significantly lower TSI scores at the post-test (Time 2) and follow-up evaluations (Times 3 and 4). Between pre-, post-, and follow-up 1 and 2 measurements, there were no significant differences in occupational stress index scores in the control group. It was concluded that o-CBI is effective in job-stress treatment among ESL teachers. In addition, implications for school health policy are discussed. The o-CBI for occupational stress was well received by the participants, showing high acceptability among ESL teachers.
Delivery of a community-based peer mentorship program for people with spinal cord injury at a rehabilitation center
Authors: Shi Zhiyang , Comeau Jacques , Bloom Gordon A. , Gainforth Heather , Thomas Aliki , Sweet Shane N.
Published: November 2023

Introduction

Community-based spinal cord injury (SCI) organizations deliver peer mentorship programs in rehabilitation settings. Little is known on how these programs are delivered through the collaboration between community-based SCI organizations and rehabilitation institutions. This study aimed to identify barriers, facilitators, and collaboration processes within a SCI peer mentorship program provided by a community-based organization at a rehabilitation center.

Methods

A qualitative case study design was applied. Seven participants were recruited, including two mentees, two mentors, one program director of the community-based SCI organization, and two healthcare professionals of the rehabilitation center. Each participant completed a one-on-one interview. Data were analyzed inductively and deductively based on the Consolidated Framework for Implementation Research (CFIR).

Results

Ten factors were identified to influence the delivery of the peer mentorship program, including nine CFIR constructs. Successful delivery of the program required strong, collaborative inter-professional relationships between health professionals and community organizational staff (e.g., peer mentors) as facilitators; whereas potential cost, minimal patient needs, and limited mentor resources were found to be barriers. Engaging health professionals by initiating communications, reflecting and evaluating the program collectively with health professionals were important collaboration processes for the community-based organization to maintain effective partnership with the rehabilitation center.

Discussion

The collaboration processes and strategies to addressing/leveraging the barriers and facilitators may inform evidence-based practice to establish and optimize the delivery of SCI peer mentorship programs in various rehabilitation settings.
Urban agroecology enhances agrobiodiversity and resilient, biocultural food systems. The case of the semi-dryland and medium-sized Querétaro City, Mexico
Authors: Villavicencio-Valdez Gabriela Valeria , Jacobi J. , Schneider M. , Altieri M. A. , Suzán-Azpiri H.
Published: November 2023

Small-scale agroecological practices in the urban areas of Querétaro, México, as in other mid-sized cities, could maintain agrobiodiversity pools and sufficient productivity for a food sovereignty baseline. The application of agroecological principles fosters agrobiodiversity and socio-ecological resilience in urban food production. Emerging urban gardens result from an immediate necessity for food that does not appear in local statistics, nor is there any account of them in any cadastral source or land register of Querétaro City. Based on studies of 28 urban gardens, we survey and analyze farming practices using socio-ecological resilience methodologies and the Diagnostic Survey of Agroecological Practices. We find that the agroecological management of urban gardens results in significantly more species richness than in conventionally managed plots, likely due to the multifunctional purposes associated with biocultural memory. The number of social actors participating in agroecological management is increasing. It represents an urban strategy of resilience that contributes to enhancing the microclimate and nutrient cycling, as well as to improving water management and biodiversity. Results also indicate that gardens of approximately 200 m2 harbor the highest levels of agrobiodiversity. This area size for home vegetable production appears optimal for user-friendly management practices in urban settings and could represent the minimum benchmark for a family and a goal for urban planning and policy recommendations. Urban gardens contribute to the adaptive capacities of city dwellers to enhance their food security and sovereignty. Therefore, given that 70% of the national population face some level of food insecurity, we argue that, along with the protection of land-use rights, the promotion of a diverse urban landscape could improve long-term socio-ecological and food supply resilience. Additionally, urban gardens promote neighborhood social inclusion and affordable access to food. The empirical results and insights from this study in Querétaro can inform land-use policies for urban agriculture more broadly, especially in Latin American metropolitan areas.