bluuebunny/crossref_metadata_2025 huggingface dataset:
Teaching and assessment of physics measurement uncertainty in remote delivery during Covid-19 Lockdown
Authors: Dehipawala Sunil , Schanning Ian , Sukmayadi Dodi , Tremberger George , Cheung Tak
Published: January 2024

The teaching and assessment of measurement uncertainty in physics lab class has been an ongoing challenge under the Covid-19 no-access policy, especially in a Two-year community college setting with less budget. The tactile experience as a tacit knowledge must be delivered in words and students are presumed to be able to learn from reading and following the rules in a simulation, with an analogy of the learning of emotions in a literature class with the original words in the novel and the related movies. The transference learning process offers guidance to design the remote delivery of experiential learning in a lab class. The quantitative uncertainty in physics lab is an assessment of how well we know. The misconception that a simulation lab would carry zero uncertainty was found to be the more difficult for students to eliminate. When the teaching of uncertainty percent calculation be classified as a lesson at the average difficulty level, then the teaching of the uncertainty in graphical representation would be deemed to be at the next difficulty level. For the case with a single formula in several variables, the small change concept in algebra can be used to estimate the uncertainty when the small changes are in absolute magnitudes.  For the case with two or more cascade formulas, the use of simulation to estimate uncertainty from the variation of the simulation results would be practical. Teaching uncertainty examples and assessment rubric examples for experiential learning in remote delivery during Covid -19 pandemic are discussed.
Robust myoelectric pattern recognition methods for reducing users’ calibration burden: challenges and future
Authors: Wang Xiang , Ao Di , Li Le
Published: January 2024

Myoelectric pattern recognition (MPR) has evolved into a sophisticated technology widely employed in controlling myoelectric interface (MI) devices like prosthetic and orthotic robots. Current MIs not only enable multi-degree-of-freedom control of prosthetic limbs but also demonstrate substantial potential in consumer electronics. However, the non-stationary random characteristics of myoelectric signals poses challenges, leading to performance degradation in practical scenarios such as electrode shifting and switching new users. Conventional MIs often necessitate meticulous calibration, imposing a significant burden on users. To address user frustration during the calibration process, researchers have focused on identifying MPR methods that alleviate this burden. This article categorizes common scenarios that incur calibration burdens as based on data distribution shift and based on dynamic data categories. Then further investigated and summarized the popular robust MPR algorithms used to reduce the user’s calibration burden. We categorize these algorithms as based on data manipulate, feature manipulation and, model structure. And describes the scenarios to which each method is applicable and the conditions required for calibration. Finally, this review is concluded with the advantages of robust MPR and the remaining challenges and future opportunities.
Osteoporosis guidelines on TCM drug therapies: a systematic quality evaluation and content analysis
Authors: Zhang Luan , Li Jiahui , Xie Runsheng , Zeng Lingfeng , Chen Wenjia , Li Hui
Published: January 2024

Objective

The aims of this study were to evaluate the quality of osteoporosis guidelines on traditional Chinese medicine (TCM) drug therapies and to analyze the specific recommendations of these guidelines.

Methods

We systematically collected guidelines, evaluated the quality of the guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool, and summarized the recommendations of TCM drug therapies using the Patient-Intervention-Comparator-Outcome (PICO) model as the analysis framework.

Results and conclusions

A total of 20 guidelines were included. Overall quality evaluation results revealed that four guidelines were at level A, four at level B, and 12 at level C, whose quality needed to be improved in the domains of “stakeholder involvement”, “rigor of development”, “applicability” and “editorial independence”. Stratified analysis suggested that the post-2020 guidelines were significantly better than those published before 2020 in the domains of “scope and purpose”, “stakeholder involvement” and “editorial independence”. Guidelines with evidence systems were significantly better than those without evidence systems in terms of “stakeholder involvement”, “rigor of development”, “clarity of presentation” and “applicability”. The guidelines recommended TCM drug therapies for patients with osteopenia, osteoporosis and osteoporotic fracture. Recommended TCM drugs were mainly Chinese patent medicine alone or combined with Western medicine, with the outcome mainly focused on improving bone mineral density (BMD).
Recent insights into the role of hormones during development and their functional regulation
Authors: Aref Youssef , Fat Shelby Chun , Ray Edward
Published: January 2024

Introduction

Hormones play a vital role in development from conception to birth and throughout the human lifespan. These periods are logically divided into fetal development, pre-pubertal growth, puberty, and adulthood. Deviations from standard physiological levels and release patterns of constituent hormones can lead to pathology affecting the normal developmental trajectory. Research is ongoing to better understand the mechanisms of these hormones and how their modulation affects development.

Methods

This article focuses on recent developments in understanding the role hormones play in development. We also cover recent discoveries in signaling pathways and hormonal regulation.

Results

New and continuing research into functional hormone regulation focuses on sex hormones, gonadotropic hormones, growth hormones, insulin-like growth factor, thyroid hormone, and the interconnectedness of each of these functional axes. Currently, the abundance of work focuses on fertility and correction of sex hormone levels based on an individual’s condition and stage in life.

Discussion

Continuing research is needed to fully understand the long-term effects of hormone modulation in growth and sexual development. The role of each hormone in parallel endocrine axes should also be more thoroughly investigated to help improve the safety and efficacy in endocrine pharmacotherapeutics.
Paediatric Cushing’s disease: long-term outcome and predictors of recurrence
Authors: Savage Martin O. , Ferrigno Rosario
Published: January 2024

Paediatric Cushing’s disease (CD) is characterized by excess ACTH secretion from a pituitary adenoma, leading to hypercortisolism. It has approximately 5% of the incidence of adult CD and is a rare disorder in the paediatric age range. The four most specific presenting features of hypercortisolism are: change in facial appearance, weight gain, decreased linear growth and virilisation shown by advanced pubic hair for the stage of breast development or testicular volume. The main diagnostic priority is the demonstration of hypercortisolism followed by distinction between its ACTH-dependent and ACTH-independent origin, thus leading to identification of aetiology. All treatment options aim to resolve or control hypercortisolism. Consensus favours transsphenoidal (TSS) pituitary surgery with selective removal of the corticotroph adenoma. TSS in children with CD is now well established and induces remission in 70-100% of cases. External pituitary radiotherapy and bilateral adrenalectomy are second-line therapeutic approaches in subjects not responding to TSS. Long-term medical treatment is less frequently adopted. Recurrence in paediatric CD cases is low with factors predicting relapse being higher post-TSS cortisol and ACTH levels and rapid recovery of the hypothalamic-pituitary-adrenal axis after TSS. In summary, complete excision of the microadenoma with histological and biochemical evidence for this, predicts a low rate of recurrence of CD. Due to the need for rapid diagnosis and management to avoid the burden of prolonged exposure to hypercortisolism, tertiary university centres comprising both paediatric and adult endocrinology specialists together with experienced pituitary surgery and, eventually, radiotherapy units are recommended for referral of these patients.
Opportunities for rail in the transport of carbon dioxide in the United States
Authors: Ho Alina , Giannopoulos Diamantoula , Pilorgé Hélène , Psarras Peter
Published: January 2024

The deployment of carbon management strategies like carbon capture and storage (CCS) and carbon dioxide removal (CDR) at scale will require significant investments in transport infrastructure to deliver CO2to reliable storage. While pipeline transport has dominated the conversation due to economic reasons, there is increasing evidence that other modes may become viable alternatives when considering scale, regional opportunities, and social acceptance. This paper assesses the viability of rail for CO2transport in the United States using market analysis, techno-economic assessment and geographic information systems mapping. We believe rail presents many advantages, notably in existing infrastructure with established right-of-ways, but also as an instrument to address unwanted effects of our energy transition, particularly in coal communities. We find that the strategic replacement of coal as a freight commodity could translate into 100 Mt/yr of CO2movement by rail by 2050, and support up to 60,000 jobs in that industry. Further, we find that while rail pricing is notoriously volatile, there is strong support for rail being the least cost option over pipeline for volumes under 2 Mt CO2per year, which aligns well with smaller, more risk-averse, and distributed carbon management projects that are scheduled to deploy over the next decade. Rail can also be an alternative in regions where CO2pipeline projects have had limited success, like in the Midwest, where CO2is captured from ethanol plants that are already serviced by rail networks. Likewise, rail can service roughly 25% of point-source CCS opportunities that are not proximal to projected trunk pipeline networks, of which 94% are located 1-mile from railroad. Finally, rail may be an integral part of CDR development in regions that are not coterminous with geologic storage, particularly in the Western and Northern US.
Prenatal diagnosis of fetuses with ultrasound anomalies by whole-exome sequencing in Luoyang city, China
Authors: Wang Yanan , Yin Fan , Chai Yuqiong , Jin Jiapei , Zhang Pai , Tan Qianqian , Chen Zhigang
Published: January 2024

Background: There is a great obstacle in prenatal diagnosis of fetal anomalies due to their considerable genetic and clinical heterogeneity. Whole-exome sequencing (WES) has been confirmed as a successful option for genetic diagnosis in pediatrics, but its clinical utility for prenatal diagnosis remains to be limited.

Methods: A total of 60 fetuses with abnormal ultrasound findings underwent karyotyping or chromosomal microarray analysis (CMA), and those with negative results were further subjected to WES. The identified variants were classified as pathogenic or likely pathogenic (P/LP) and the variant of uncertain significance (VUS). Pregnancy outcomes were obtained through a telephone follow-up.

Results: Twelve (20%, 12/60) fetuses were diagnosed to have chromosomal abnormalities using karyotyping or CMA. Of the remaining 48 cases that underwent WES, P/LP variants were identified in 14 cases (29.2%), giving an additional diagnostic yield of 23.3% (14/60). The most frequently affected organ referred for prenatal WES was the head or neck system (40%), followed by the skeletal system (39.1%). In terms of pathogenic genes, FGFR3 was the most common diagnostic gene in this cohort. For the first time, we discovered five P/LP variants involved in SEC24D, FIG4, CTNNA3, EPG5, and PKD2. In addition, we identified three VUSes that had been reported previously. Outcomes of pregnancy were available for 54 cases, of which 24 cases were terminated.

Conclusion: The results confirmed that WES is a powerful tool in prenatal diagnosis, especially for fetuses with ultrasonographic anomalies that cannot be diagnosed using conventional prenatal methods. Additionally, newly identified variants will expand the phenotypic spectrum of monogenic disorders and greatly enrich the prenatal diagnostic database.
Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of- heterozygosity and common HLA-B and TAP transcriptional silencing across advanced pediatric solid cancers
Authors: Lim Wan Ching , Marques Da Costa Maria Eugenia , Godefroy Karine , Jacquet Eric , Gragert Loren , Rondof Windy , Marchais Antonin , Nhiri Naima , Dalfovo Davide , Viard Mathias , Labaied Nizar , Khan Asif M. , Dessen Philippe , Romanel Alessandro , Pasqualini Claudia , Schleiermacher Gudrun , Carrington Mary , Zitvogel Laurence , Scoazec Jean-Yves , Geoerger Birgit , Salmon Jerome
Published: January 2024

The human leukocyte antigen (HLA) system is a major factor controlling cancer immunosurveillance and response to immunotherapy, yet its status in pediatric cancers remains fragmentary. We determined high-confidence HLA genotypes in 576 children, adolescents and young adults with recurrent/refractory solid tumors from the MOSCATO-01 and MAPPYACTS trials, using normal and tumor whole exome and RNA sequencing data and benchmarked algorithms. There was no evidence for narrowed HLA allelic diversity but discordant homozygosity and allele frequencies across tumor types and subtypes, such as in embryonal and alveolar rhabdomyosarcoma, neuroblastoma MYCN and 11q subtypes, and high-grade glioma, and several alleles may represent protective or susceptibility factors to specific pediatric solid cancers. There was a paucity of somatic mutations in HLA and antigen processing and presentation (APP) genes in most tumors, except in cases with mismatch repair deficiency or genetic instability. The prevalence of loss-of-heterozygosity (LOH) ranged from 5.9 to 7.7% in HLA class I and 8.0 to 16.7% in HLA class II genes, but was widely increased in osteosarcoma and glioblastoma (~15-25%), and for DRB1-DQA1-DQB1 in Ewing sarcoma (~23-28%) and low-grade glioma (~33-50%). HLA class I and HLA-DR antigen expression was assessed in 194 tumors and 44 patient-derived xenografts (PDXs) by immunochemistry, and class I and APP transcript levels quantified in PDXs by RT-qPCR. We confirmed that HLA class I antigen expression is heterogeneous in advanced pediatric solid tumors, with class I loss commonly associated with the transcriptional downregulation of HLA-B and transporter associated with antigen processing (TAP) genes, whereas class II antigen expression is scarce on tumor cells and occurs on immune infiltrating cells. Patients with tumors expressing sufficient HLA class I and TAP levels such as some glioma, osteosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft-tissue sarcoma cases may more likely benefit from T cell-based approaches, whereas strategies to upregulate HLA expression, to expand the immunopeptidome, and to target TAP-independent epitopes or possibly LOH might provide novel therapeutic opportunities in others. The consequences of HLA class II expression by immune cells remain to be established. Immunogenetic profiling should be implemented in routine to inform immunotherapy trials for precision medicine of pediatric cancers.
The current landscape of the antimicrobial peptide melittin and its therapeutic potential
Authors: Zhang Hai-Qian , Sun Chengbiao , Xu Na , Liu Wensen
Published: January 2024

Melittin, a main component of bee venom, is a cationic amphiphilic peptide with a linear α-helix structure. It has been reported that melittin can exert pharmacological effects, such as antitumor, antiviral and anti-inflammatory effects in vitro and in vivo. In particular, melittin may be beneficial for the treatment of diseases for which no specific clinical therapeutic agents exist. Melittin can effectively enhance the therapeutic properties of some first-line drugs. Elucidating the mechanism underlying melittin-mediated biological function can provide valuable insights for the application of melittin in disease intervention. However, in melittin, the positively charged amino acids enables it to directly punching holes in cell membranes. The hemolysis in red cells and the cytotoxicity triggered by melittin limit its applications. Melittin-based nanomodification, immuno-conjugation, structural regulation and gene technology strategies have been demonstrated to enhance the specificity, reduce the cytotoxicity and limit the off-target cytolysis of melittin, which suggests the potential of melittin to be used clinically. This article summarizes research progress on antiviral, antitumor and anti-inflammatory properties of melittin, and discusses the strategies of melittin-modification for its future potential clinical applications in preventing drug resistance, enhancing the selectivity to target cells and alleviating cytotoxic effects to normal cells.
Highly heterogenous humoral immune response in Lyme disease patients revealed by broad machine learning-assisted antibody binding profiling with random peptide arrays
Authors: Kelbauskas L. , Legutki J. B. , Woodbury N. W.
Published: January 2024

Introduction

Lyme disease (LD), a rapidly growing public health problem in the US, represents a formidable challenge due to the lack of detailed understanding about how the human immune system responds to its pathogen, the Borrelia burgdorferi bacterium. Despite significant advances in gaining deeper insight into mechanisms the pathogen uses to evade immune response, substantial gaps remain. As a result, molecular tools for the disease diagnosis are lacking with the currently available tests showing poor performance. High interpersonal variability in immune response combined with the ability of the pathogen to use a number of immune evasive tactics have been implicated as underlying factors for the limited test performance.

Methods

This study was designed to perform a broad profiling of the entire repertoire of circulating antibodies in human sera at the single-individual level using planar arrays of short linear peptides with random sequences. The peptides sample sparsely, but uniformly the entire combinatorial sequence space of the same length peptides for profiling the humoral immune response to a B.burg. infection and compare them with other diseases with etiology similar to LD and healthy controls.

Results

The study revealed substantial variability in antibody binding profiles between individual LD patients even to the same antigen (VlsE protein) and strong similarity between individuals diagnosed with Lyme disease and healthy controls from the areas endemic to LD suggesting a high prevalence of seropositivity in endemic healthy control.

Discussion

This work demonstrates the utility of the approach as a valuable analytical tool for agnostic profiling of humoral immune response to a pathogen.
The α-Gal epitope - the cause of a global allergic disease
Authors: Perusko Marija , Grundström Jeanette , Eldh Maria , Hamsten Carl , Apostolovic Danijela , van Hage Marianne
Published: January 2024

The galactose-α-1,3-galactose (α-Gal) epitope is the cause of a global allergic disease, the α-Gal syndrome (AGS). It is a severe form of allergy to food and products of mammalian origin where IgE against the mammalian carbohydrate, α-Gal, is the cause of the allergic reactions. Allergic reactions triggered by parenterally administered α-Gal sources appear immediately, but those triggered via the oral route appear with a latency of several hours. The α-Gal epitope is highly immunogenic to humans, apes and old-world monkeys, all of which produce anti-α-Gal antibodies of the IgM, IgA and IgG subclasses. Strong evidence suggests that in susceptible individuals, class switch to IgE occurs after several tick bites. In this review, we discuss the strong immunogenic role of the α-Gal epitope and its structural resemblance to the blood type B antigen. We emphasize the broad abundance of α-Gal in different foods and pharmaceuticals and the allergenicity of various α-Gal containing molecules. We give an overview of the association of tick bites with the development of AGS and describe innate and adaptive immune response to tick saliva that possibly leads to sensitization to α-Gal. We further discuss a currently favored hypothesis explaining the mechanisms of the delayed effector phase of the allergic reaction to α-Gal. We highlight AGS from a clinical point of view. We review the different clinical manifestations of the disease and the prevalence of sensitization to α-Gal and AGS. The usefulness of various diagnostic tests is discussed. Finally, we provide different aspects of the management of AGS. With climate change and global warming, the tick density is increasing, and their geographic range is expanding. Thus, more people will be affected by AGS which requires more knowledge of the disease.
Unraveling the complex interplay between anti-tumor immune response and autoimmunity mediated by B cells and autoantibodies in the era of anti-checkpoint monoclonal antibody therapies
Authors: Soussan Sarah , Pupier Guilhem , Cremer Isabelle , Joubert Pierre-Emmanuel , Sautès-Fridman Catherine , Fridman Wolf Herman , Sibéril Sophie
Published: January 2024

The intricate relationship between anti-tumor immunity and autoimmunity is a complex yet crucial aspect of cancer biology. Tumor microenvironment often exhibits autoimmune features, a phenomenon that involves natural autoimmunity and the induction of humoral responses against self-antigens during tumorigenesis. This induction is facilitated by the orchestration of anti-tumor immunity, particularly within organized structures like tertiary lymphoid structures (TLS). Paradoxically, a significant number of cancer patients do not manifest autoimmune features during the course of their illness, with rare instances of paraneoplastic syndromes. This discrepancy can be attributed to various immune-mediated locks, including regulatory or suppressive immune cells, anergic autoreactive lymphocytes, or induction of effector cells exhaustion due to chronic stimulation. Overcoming these locks holds the risk to induce autoimmune mechanisms during cancer progression, a phenomenon notably observed with anti-immune checkpoint therapies, in contrast to more conventional treatments like chemotherapy or radiotherapy. Therefore, the challenge arises in managing immune-related adverse events (irAEs) induced by immune checkpoint inhibitors treatment, as decoupling them from the anti-tumor activity poses a significant clinical dilemma. This review summarizes recent advances in understanding the link between B-cell driven anti-tumor responses and autoimmune reactions in cancer patients, and discusses the clinical implications of this relationship.
Spicy food for the egg-cowries: the evolution of corallivory in the Ovulidae (Gastropoda: Cypraeoidea)
Authors: Nocella Elisa , Zvonareva Sofya Sergeevna , Fassio Giulia , Pica Daniela , Buge Barbara , Villa Raimondo , Puillandre Nicolas , Modica Maria Vittoria , Oliverio Marco
Published: January 2024

Introduction

Host-parasite associations provide very useful models to study adaptive processes. We investigated the interaction between carnivorous marine gastropods, the Ovulidae or egg-cowries, and their cnidarian food targets. Ovulidae (Fleming, 1828), is a family of specialized carnivorous caenogastropods that feed by browsing on octocorals (Anthozoa: Octocorallia: Malacalcyonacea and Scleralcyonacea) or, to a much lesser degree, on antipatharians (Anthozoa: Hexacorallia: Antipatharia) and Stylasteridae (Hydrozoa: Hydroidolina: Anthoathecata). Very scanty information is available on the phylogenetic relationships and the degree of specificity of the relationship with the cnidarians of this corallivorous lineage, especially for deep-water taxa.

Methods

To assess taxonomic identifications and investigate cnidarian/ovulid relationships in the context of their evolution, we generated an extensive molecular dataset comprising two mitochondrial (cox1 and 16S rDNA) and one nuclear gene (28S rDNA) from 524 specimens collected worldwide. The coral hosts of the ovulid species have been identified by integrating literature data with new records, employing morphological and/or molecular (the mitochondrial 16S rDNA and mtMSH, and the nuclear ITS2) markers.

Results

We obtained a molecular phylogenetic framework for the Ovulidae, time-calibrated with nine reliable fossil records. An ancestral state reconstruction allowed to identify Hexacorallia or Hydroidolina as the most likely ancestral cnidarian host for the Ovulidae.

Discussion

Our phylogenetic hypothesis revealed the existence of groups that do not completely correspond to the currently employed subfamilial arrangement. Concerning trophic ecology, while only pediculariines (Pedicularia and allied) are associated with hydrozoans (Stylasteridae), our results suggest that some ovulid lineages shifted independently between octocorals and hexacorals.
Exploring the role of IL-1β in inflammatory bowel disease pathogenesis
Authors: Aggeletopoulou Ioanna , Kalafateli Maria , Tsounis Efthymios P. , Triantos Christos
Published: January 2024

Interleukin 1β (IL-1β) is a significant mediator of inflammation and tissue damage in IBD. The balance between IL-1β and its endogenous inhibitor-IL-1Ra-, plays a critical role in both initiation and regulation of inflammation. However, the precise role of IL-1β as a causative factor in IBD or simply a consequence of inflammation remains unclear. This review summarizes current knowledge on the molecular and cellular characteristics of IL-1β, describes the existing evidence on the role of this cytokine as a modulator of intestinal homeostasis and an activator of inflammatory responses, and also discusses the role of microRNAs in the regulation of IL-1β-related inflammatory responses in IBD. Current evidence indicates that IL-1β is involved in several aspects during IBD as it greatly contributes to the induction of pro-inflammatory responses through the recruitment and activation of immune cells to the gut mucosa. In parallel, IL-1β is involved in the intestinal barrier disruption and modulates the differentiation and function of T helper (Th) cells by activating the Th17 cell differentiation, known to be involved in the pathogenesis of IBD. Dysbiosis in the gut can also stimulate immune cells to release IL-1β, which, in turn, promotes inflammation. Lastly, increasing evidence pinpoints the central role of miRNAs involvement in IL-1β-related signaling during IBD, particularly in the maintenance of homeostasis within the intestinal epithelium. In conclusion, given the crucial role of IL-1β in the promotion of inflammation and immune responses in IBD, the targeting of this cytokine or its receptors represents a promising therapeutic approach. Further research into the IL-1β-associated post-transcriptional modifications may elucidate the intricate role of this cytokine in immunomodulation.
Case report: Recovery from refractory myasthenic crisis to minimal symptom expression after add-on treatment with efgartigimod
Authors: Watanabe Keiko , Ohashi Shinichi , Watanabe Takuya , Kakinuma Yuki , Kinno Ryuta
Published: January 2024

Myasthenic crisis, a life-threatening exacerbation of myasthenia gravis, is a significant clinical challenge, particularly when refractory to standard therapies. Here, we described a case of myasthenic crisis in which the patient transitioned from refractory myasthenic crisis to minimal symptom expression after receiving add-on treatment with efgartigimod, a novel neonatal Fc receptor antagonist. A 54 years-old woman who was diagnosed with anti-acetylcholine receptor antibody-positive myasthenia gravis experienced respiratory failure necessitating mechanical ventilation. Despite aggressive treatment with plasmapheresis, intravenous immunoglobulins, and high-dose corticosteroids, her condition continued to deteriorate, culminating in persistent myasthenic crisis. Efgartigimod was administered as salvage therapy. Remarkable improvement in neuromuscular function was observed within days, allowing for successful weaning from mechanical ventilation. Over the subsequent weeks, the patient’s symptoms continued to ameliorate, ultimately reaching a state of minimal symptom expression. Serial assessments of her serum anti-acetylcholine receptor antibody titer showed a consistent decline in parallel with this clinical improvement. This case highlights efgartigimod’s potential as an effective therapeutic option for refractory myasthenic crisis, offering new hope for patients facing this life-threatening condition.
Acupuncture in circadian rhythm sleep–wake disorders and its potential neurochemical mechanisms
Authors: Wu Junmei , Zhao Zhengyu
Published: January 2024

Circadian rhythm sleep–wake disorders (CRSWDs) are becoming increasingly common in modern societies due to lifestyle changes. The detrimental effects of CRSWDs on sleep and psychological health have attracted considerable attention recently. Alternative remedies for the treatment of CRSWDs have also gained attention in recent years owing to the limitations of medications. Several in vivo and clinical investigations have shown that acupuncture, one of the most important components of traditional Chinese medicine (TCM), has been shown to modulate sleep-related circadian rhythms. Owing to the lack of research on the mechanism and effectiveness of acupuncture in treating CRSWDs, clinical applications of acupuncture have not gained popularity. This paper reviews the acupuncture methods, acupoint selection, and biochemical indicators supplied by in vivo and clinical studies to explore the effectiveness of acupuncture, and summarizes the circadian rhythm mechanisms and the acupuncture characteristics on circadian rhythm. The neurochemical mechanisms linked to acupuncture in treating CRSWDs are also outlined from the perspective of the central and peripheral biological clocks. Lastly, the inadequacy of previous studies on CRSWDs and conflicting results regarding acupuncture are explored and future research directions are envisioned.
Role of C9orf72 hexanucleotide repeat expansions in ALS/FTD pathogenesis
Authors: Geng Yanyan , Cai Qixu
Published: January 2024

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurological disorders that share neurodegenerative pathways and features. The most prevalent genetic causes of ALS/FTD is the GGGGCC hexanucleotide repeat expansions in the first intron region of the chromosome 9 open reading frame 72 (C9orf72) gene. In this review, we comprehensively summarize the accumulating evidences elucidating the pathogenic mechanism associated with hexanucleotide repeat expansions in ALS/FTD. These mechanisms encompass the structural polymorphism of DNA and transcribed RNA, the formation of RNA foci via phase separation, and the cytoplasmic accumulation and toxicities of dipeptide-repeat proteins. Additionally, the formation of G-quadruplex structures significantly impairs the expression and normal function of the C9orf72 protein. We also discuss the sequestration of specific RNA binding proteins by GGGGCC RNA, which further contributes to the toxicity of C9orf72 hexanucleotide repeat expansions. The deeper understanding of the pathogenic mechanism of hexanucleotide repeat expansions in ALS/FTD provides multiple potential drug targets for these devastating diseases.
Development of trofinetide for the treatment of Rett syndrome: from bench to bedside
Authors: Kennedy Melissa , Glass Larry , Glaze Daniel G. , Kaminsky Steve , Percy Alan K. , Neul Jeffrey L. , Jones Nancy E. , Tropea Daniela , Horrigan Joseph P. , Nues Paige , Bishop Kathie M. , Youakim James M.
Published: January 2024

Rett syndrome (RTT) is rare neurodevelopmental disorder caused by mutations in the MECP2 gene that encodes methyl-CpG-binding protein 2 (MeCP2), a DNA-binding protein with roles in epigenetic regulation of gene expression. Functional loss of MeCP2 results in abnormal neuronal maturation and plasticity, characterized by loss of verbal communication and loss of fine and gross motor function, among others. Trofinetide, a synthetic analog of glycine-proline-glutamate, was approved by the US Food and Drug Administration for the treatment of RTT in adult and pediatric patients aged 2 years and older. Here, we present the development of trofinetide from bench research to clinical studies and emphasize how the collaboration between academia, the pharmaceutical industry, and patient advocacy led to the recent approval. The bench-to-bedside development of trofinetide underscores the value of collaboration between these groups in the development and approval of treatments for rare diseases.
The reporting quality of randomized controlled trials in Chinese herbal medicine (CHM) formulas for diabetes based on the consort statement and its extension for CHM formulas
Authors: Liu Yan , Hu Chaoyue , Zhou Kehua , Zhang Ye , Kang Jing , Wen Yalu , Yuan Ruyue , Li Jiaoyue , Zhao Qiyao , Zhang Li , Yang Xiaohui
Published: January 2024

Background: This study aimed to assess the overall reporting quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) formulas for patients with diabetes, and to identify factors associated with better reporting quality.

Methods: Four databases including PubMed, Embase, Cochrane Library and Web of Science were systematically searched from their inception to December 2022. The reporting quality was assessed based on the Consolidated Standards of Reporting Trials (CONSORT) statement and its CHM formula extension. The overall CONSORT and its CHM formula extension scores were calculated and expressed as proportions separately. We also analyzed the pre-specified study characteristics and performed exploratory regressions to determine their associations with the reporting quality.

Results: Seventy-two RCTs were included. Overall reporting quality (mean adherence) were 53.56% and 45.71% on the CONSORT statement and its CHM formula extension, respectively. The strongest associations with reporting quality based on the CONSORT statement were multiple centers and larger author numbers. Compliance with the CHM formula extension, particularly regarding the disclosure of the targeted traditional Chinese medicine (TCM) pattern (s), was generally insufficient.

Conclusion: The reporting quality of RCTs in CHM formulas for diabetes remains unsatisfactory, and the adherence to the CHM formula extension is even poorer. In order to ensure transparent and standardized reporting of RCTs, it is essential to advocate for or even mandate adherence of the CONSORT statement and its CHM formula extension when reporting trials in CHM formulas for diabetes by both authors and editors.
Modulation of the vitamin D receptor by traditional Chinese medicines and bioactive compounds: potential therapeutic applications in VDR-dependent diseases
Authors: Yao Minghe , Oduro Patrick Kwabena , Akintibu Ayomide M. , Yan Haifeng
Published: January 2024

The Vitamin D receptor (VDR) is a crucial nuclear receptor that plays a vital role in various physiological functions. To a larger extent, the genomic effects of VDR maintain general wellbeing, and its modulation holds implications for multiple diseases. Current evidence regarding using vitamin D or its synthetic analogs to treat non-communicable diseases is insufficient, though observational studies suggest potential benefits. Traditional Chinese medicines (TCMs) and bioactive compounds derived from natural sources have garnered increasing attention. Interestingly, TCM formulae and TCM-derived bioactive compounds have shown promise in modulating VDR activities. This review explores the intriguing potential of TCM and bioactive compounds in modulating VDR activity. We first emphasize the latest information on the genetic expression, function, and structure of VDR, providing a comprehensive understanding of this crucial receptor. Following this, we review several TCM formulae and herbs known to influence VDR alongside the mechanisms underpinning their action. Similarly, we also discuss TCM-based bioactive compounds that target VDR, offering insights into their roles and modes of action.
Cardiorespiratory and metabolic consequences of detraining in endurance athletes
Authors: Barbieri Arianna , Fuk Andrea , Gallo Gabriele , Gotti Daniel , Meloni Andrea , La Torre Antonio , Filipas Luca , Codella Roberto
Published: January 2024

Background: A training program can stimulate physiological, anatomical, and performance adaptations, but these improvements can be partially or entirely reversed due to the cessation of habitual physical activity resulting from illness, injury, or other influencing factors.

Purpose: To investigate the effects of detraining on cardiorespiratory, metabolic, hormonal, muscular adaptations, as well as short-term and long-term performance changes in endurance athletes.

Methods: Eligible studies were sourced from databases and the library up until July 2023. Included studies considered endurance athletes as subjects and reported on detraining duration.

Results: Total cessation of training leads to a decrease in VO2max due to reductions in both blood and plasma volume. Cardiac changes include decreases in left ventricular mass, size, and thickness, along with an increase in heart rate and blood pressure, ultimately resulting in reduced cardiac output and impaired performance. Metabolically, there are declines in lactate threshold and muscle glycogen, increased body weight, altered respiratory exchange ratio, and changes in power parameters. In the short term, there is a decrease in insulin sensitivity, while glucagon, growth hormone, and cortisol levels remain unchanged. Skeletal muscle experiences reductions in arterial-venous oxygen difference and glucose transporter-4. Implementing a partial reduction in training may help mitigate drastic losses in physiological and performance parameters, a consideration when transitioning between training seasons.

Conclusion: There is a dearth of data investigating the detraining effects of training reduction/cessation among endurance athletes. Delving deeper into this topic may be useful for professionals and researchers to identify the optimal strategies to minimize these effects.
Mutations in nuclear pore complex promote osmotolerance in Arabidopsis by suppressing the nuclear translocation of ACQOS and its osmotically induced immunity
Authors: Mori Kento , Murakoshi Yusuke , Tamura Masashi , Kunitake Satoru , Nishimura Kohji , Ariga Hirotaka , Tanaka Keisuke , Iuchi Satoshi , Yotsui Izumi , Sakata Yoichi , Taji Teruaki
Published: January 2024

We have previously reported a wide variation in salt tolerance among Arabidopsis thaliana accessions and identified ACQOS, encoding a nucleotide-binding leucine-rich repeat (NLR) protein, as the causal gene responsible for the disturbance of acquired osmotolerance induced after mild salt stress. ACQOS is conserved among Arabidopsis osmosensitive accessions, including Col-0. In response to osmotic stress, it induces detrimental autoimmunity, resulting in suppression of osmotolerance, but how ACQOS triggers autoimmunity remains unclear. Here, we screened acquired osmotolerance (aot) mutants from EMS-mutagenized Col-0 seeds and isolated the aot19 mutant. In comparison with the wild type (WT), this mutant had acquired osmotolerance and decreased expression levels of pathogenesis-related genes. It had a mutation in a splicing acceptor site in NUCLEOPORIN 85 (NUP85), which encodes a component of the nuclear pore complex. A mutant with a T-DNA insertion in NUP85 acquired osmotolerance similar to aot19. The WT gene complemented the osmotolerant phenotype of aot19. We evaluated the acquired osmotolerance of five nup mutants of outer-ring NUPs and found that nup96, nup107, and aot19/nup85, but not nup43 or nup133, showed acquired osmotolerance. We examined the subcellular localization of the GFP–ACQOS protein and found that its nuclear translocation in response to osmotic stress was suppressed in aot19. We suggest that NUP85 is essential for the nuclear translocation of ACQOS, and the loss-of-function mutation of NUP85 results in acquired osmotolerance by suppressing ACQOS-induced autoimmunity in response to osmotic stress.
Assessment of the reliability and quality of breast cancer related videos on TikTok and Bilibili: cross-sectional study in China
Authors: Liu Hui , Peng Jialun , Li Lu , Deng Ao , Huang Xiangxin , Yin Guobin , Ming Jia , Luo Haojun , Liang Yinyin
Published: January 2024

Background

As the most common malignant tumor in the world, breast cancer also brings a huge disease burden to China. Ordinary people are increasingly inclined to use the Internet, especially video social platforms, as a source of health information. Educating the public to obtain correct information is important to reduce the incidence of breast cancer and improve the prognosis. However, the quality and reliability of breast cancer-related video content have not been fully studied.

Objective

This study aims to evaluate the quality of the information of breast cancer-related videos on TikTok and Bilibili video sharing platforms and factors related to video quality.

Methods

We collected the top 100 videos about breast cancer on TikTok and Bilibili, respectively. Categorize videos according to video source and video content. Video quality and reliability were assessed using Global Quality Score (GQS) and modified DISCERN (mDISCERN) tools. We also analyzed the correlation between video quality and video likes, comments, saves, and shares.

Results

Although the quality and reliability of Bilibili’s breast cancer videos were higher than TikTok (p = 0.002 and p = 0.001, respectively), the video quality of both video sharing platforms was not satisfactory, with a median GQS scores of 2.00 and 3.00 and mDISCERN scores of 1.00 and 2.00, respectively. In general, the quality and reliability of videos released by medical practitioners were higher than those of non-medical practitioners, and the quality and reliability of videos covering disease-related knowledge were higher than those of news reports (all p < 0.001). Among medical practitioners, the quality of videos uploaded by doctors in breast disease was significantly lower than that of doctors in other areas (p < 0.05). There was a significant positive correlation between video quality and duration (r = 0.240, p < 0.001), a weak negative correlation between video quality and likes (r = 0.191, p < 0.01), video quality and comments (r = 0.256, p < 0.001), video reliability and likes (r = 0.198, p < 0.001), video reliability and comments (r = 0.243, p < 0.01).

Conclusion

Our study shows that the quality and reliability of breast cancer-related videos on TikTok and Bilibili are poor, and the overall quality is unsatisfactory. But videos uploaded by medical practitioners covering disease knowledge, prevention and treatment are of higher quality. Medical practitioners are encouraged to publish more high-quality videos, while video social platforms should formulate relevant policies to censor and supervise health education videos, so as to enable the public to obtain reliable health information.
Antimicrobial resistance of Streptococcus pneumoniae from invasive pneumococcal diseases in Latin American countries: a systematic review and meta-analysis
Authors: Sandoval María Macarena , Ruvinsky Silvina , Palermo María Carolina , Alconada Tomás , Brizuela Martín Eduardo , Wierzbicki Eugenia Ramirez , Cantos Joaquín , Bardach Ariel , Ciapponi Agustín , Gagetti Paula
Published: January 2024

Background

Invasive pneumococcal disease has declined since pneumococcal conjugate vaccine introduction in Latin America and the Caribbean (LAC). However, serotype distribution and antimicrobial resistance patterns have changed.

Methods

We conducted a systematic review to evaluate the frequency of antimicrobial resistance of Streptococcus pneumoniae from invasive disease in LAC. Articles published between 1 January 2000, and 27 December 2022, with no language restriction, were searched in major databases and gray literature. Pairs of reviewers independently selected extracted data and assessed the risk of bias in the studies. The quality of antimicrobial resistance (AMR) studies was evaluated according to WHO recommendations (PROSPERO CRD42023392097).

Results

From 8,600 records identified, 103 studies were included, with 49,660 positive samples of S. pneumoniae for AMR analysis processed. Most studies were from Brazil (29.1%) and Argentina (18.4%), were cross-sectional (57.3%), reported data on AMR from IPD cases (52.4%), and were classified as moderate risk of bias (50.5%). Resistance to penicillin was 21.7% (95%IC 18.7–25.0, I2: 95.9), and for ceftriaxone/cefotaxime it was 4.7% (95%IC 3.2–6.9, I2: 96.1). The highest resistance for both penicillin and ceftriaxone/cefotaxime was in the age group of 0 to 5 years (32.1% [95%IC 28.2–36.4, I2: 87.7], and 9.7% [95%IC 5.9–15.6, I2: 96.9] respectively). The most frequent serotypes associated with resistance were 14 for penicillin and 19A for ceftriaxone/cefotaxime.

Conclusion

Approximately one-quarter of invasive pneumococcal disease isolates in Latin America and the Caribbean displayed penicillin resistance, with higher rates in young children. Ongoing surveillance is essential to monitor serotype evolution and antimicrobial resistance patterns following pneumococcal conjugate vaccine introduction.
The characteristic and size–frequency distribution of rocks at the Zhurong landing site, Mars
Authors: Sun Xiukuo , Li Shouding , Li Juan , Wu Yanfang , Zhang Shuo , Zheng Bo , Zhang Zhaobin , Xu Tao , Chen Xinshuo , Diao Yiming
Published: January 2024

The rock characteristic and size–frequency distribution (SFD) on Mars are important for understanding the geologic and geomorphic history of the surface, for evaluating the trafficability of roving, and for planning the potential infrastructure construction. Tianwen-1, China’s first autonomous Mars exploration mission, formed an excavated depression during touchdown, which has been the deepest depression on the Martian surface so far compared with others. According to the images captured using the Navigation and Terrain Cameras (NaTeCams) onboard the rover, Zhurong, the SFD of rocks is calculated and compared inside the excavated depression, within and out of the blast zone. For the first time, the rock size distribution inside the excavated depression is obtained, exposing the geological features of the shallow subsurface on Mars at a depth of tens of centimeters, which will surely be important for future drilling missions. It is found that the rock abundance in the depression is smaller than the original abundance on the surface, and the distribution of rocks in the blast zone on the surface is greatly influenced by the touchdown. In addition, based on the fractal dimension of rock sizes, the rocks (>10 mm) at the shallow subsurface of the Zhurong landing site may experience two different geological processes.