bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocan, a novel glycoprotein with multiple biological activities, may play important roles in neurological diseases
Authors: Liu Shuo , Bai Tao , Feng Juan
Published: September 2024

Endothelial cell specific-1 (ESM-1), also known as endocan, is a soluble dermatan sulfate proteoglycan that is mainly secreted by endothelial cells. Endocan is associated with tumorigenesis and cancer progression and is also related to cardiovascular disorders, autoimmune diseases, and sepsis. The phenylalanine-rich region and linear polysaccharide of endocan are necessary for the protein to exert its biological functions. Elevated plasma endocan levels reflect endothelial activation and dysfunction. In addition, endocan participates in complex inflammatory responses and proliferative processes. Here, we reviewed current research on endocan, elaborated the protein’s structure and biological functions, and speculated on its possible clinical value in nervous system diseases. We conclude that endocan may be a glycoprotein that plays an important role in neurological disorders.
Systematic review of photobiomodulation for multiple sclerosis
Authors: Oliveira de Andrade Filho Vander , Amarante Marina Oliveira Coura , Gonzalez-Lima Francisco , Gomes da Silva Sérgio , Cardoso Fabrízio dos Santos
Published: September 2024

Background

Multiple sclerosis (MS) is an inflammatory chronic autoimmune and neurodegenerative disorder of the brain and spinal cord, resulting in loss of motor, sensorial, and cognitive function. Among the non-pharmacological interventions for several brain conditions, photobiomodulation (PBM) has gained attention in medical society for its neuroprotective effects. We systematically reviewed the effects of PBM on MS.

Methods

We conducted a systematic search on the bibliographic databases (PubMed and ScienceDirect) with the keywords based on MeSH terms: PBM, low-level laser therapy, multiple sclerosis, autoimmune encephalomyelitis, demyelination, and progressive multiple sclerosis. Data search was limited from 2012 to July 2024. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The initial systematic search identified 126 articles. Of these, 68 articles were removed by duplicity and 50 by screening. Thus, 8 studies satisfied the inclusion criteria.

Results

The reviewed studies showed that PBM modulates brain markers linked to inflammation, oxidative stress, and apoptosis. Improvements in motor, sensorial, and cognitive functions in MS patients were also observed after PBM therapy. No study reported adverse effects of PBM.

Conclusion

These findings suggest the potential of PBM as a promising non-pharmacological intervention for the management of MS, although further research is needed to standardize PBM protocols and assess its long-term effects.
The corpus callosum and creativity revisited
Authors: Brown Warren S. , Paul Lynn K.
Published: September 2024

In 1969 Joseph Bogen, a colleague of Roger Sperry and the neurosurgeon who performed commissurotomy on Sperry’s “split-brain” study participants, wrote an article subtitled “The Corpus Callosum and Creativity.” The article argued for the critical role of the corpus callosum and hemispheric specialization in creativity. Building on a four-stage model of creativity (learning, incubation, illumination, refinement) and Sperry’s innovative studies, the Bogens posited that in the intact brain, creativity relies on two opposing functions of the corpus callosum: (a) interhemispheric inhibition to facilitate simultaneous and independent activity of uniquely-specialized processing centers during learning and incubation and (b) interhemispheric facilitation to support the increased bi-hemispheric integration and coordination which produces illumination. This article revisits the Bogens’ theory considering scientific discoveries over the past 50 years. We begin by reviewing relevant findings from split-brain studies, and then briefly consider findings from studies that examine the association of creativity with callosal structure and function in neurotypical participants. Finally, we provide an in-depth discussion of creativity in persons with agenesis of the corpus callosum (ACC)—the congenital absence of the corpus callosum. These three lines of inquiry strongly support the theory suggested by Bogen and Bogen in 1969 and provide further clarification regarding the critical and unique role of the corpus callosum in creative cognition.
Status quo and influencing factors of readiness for hospital discharge in patients with brain tumours after surgery
Authors: Qin Yue-Hong , Shi Xiao-Mei
Published: September 2024

Objective

This study aimed to investigate the status quo of readiness for hospital discharge in patients with brain tumours after surgery and to analyse its influencing factors.

Method

A total of 300 patients with brain tumours who were admitted to the neurosurgery ward of our hospital between September 2020 and December 2022 were selected as the study participants using the convenient sampling method. The readiness for hospital discharge in patients with brain tumours after surgery was investigated using a general information questionnaire, the Readiness for Hospital Discharge Scale (RHDS), the Quality of Discharge Teaching Scale (QDTS), the University of Washington Quality of Life Questionnaire (UW-QOL), and the Social Support Rating Scale (SSRS), and its influencing factors were analysed.

Results

The total RHDS score of patients with brain tumours was (155.02 ± 14.67), which was at a medium level. There was a positive correlation between readiness for hospital discharge in patients with brain tumours after surgery and the UW-QOL score (r = 0.459, p = 0.001), SSRS score (r = 0.322, p = 0.000), and QDTS score (r = 0.407, p = 0.001). The influencing factors of readiness for hospital discharge in patients with brain tumours included the content actually obtained by patients (health guidance) before discharge (p = 0.001), discharge teaching skills (p = 0.001), age (p = 0.006), swallowing status (p = 0.021), education level (p = 0.016), and objective support (p = 0.022).

Conclusion

The readiness for hospital discharge in patients with brain tumours is at a medium level. Medical staff should give inpatients more targeted knowledge and implement personalised health education according to the patient’s age, education level, swallowing status, and objective support to improve the patient’s readiness for hospital discharge.
2-methoxyestradiol inhibits the malignant behavior of triple negative breast cancer cells by altering their miRNome
Authors: Subramani Ramadevi , Chatterjee Animesh , Pedroza Diego A. , Poudel Seeta , Rajkumar Preetha , Annabi Jeffrey , Penner Elizabeth , Lakshmanaswamy Rajkumar
Published: September 2024

Background

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with no effective targeted treatment currently available. Estrogen and its metabolites influence the growth of mammary cancer. Previously, we demonstrated the anti-cancer effects of 2-methoxyestradiol (2ME2) on mammary carcinogenesis.

Materials and methods

In the present study, we investigated the effects of 2ME2 on TNBC cells. TNBC (MDA-MB-231 and MDA-MB-468) and non-tumorigenic breast (MCF10A) cell lines were used to determine the effects of 2ME2 on cell proliferation (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; MTS assay), cell cycle (flow cytometric assay), migration (transwell migration assay), invasion (matrigel invasion assay), apoptosis (annexin V/propidium iodide assay), colony formation (soft agar assay), and miRNome (human miRNA profiling array). The miRNome data were analyzed using the c-BioPortal and Xena platforms. Moreover, Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and reactome pathway analyses were performed.

Results

We found that 2ME2 effectively inhibited cell proliferation and induced apoptosis. Furthermore, 2ME2 treatment arrested TNBC cells in the S-phase of the cell cycle. Treatment with 2ME2 also significantly decreased the aggressiveness of TNBC cells by inhibiting their migration and invasion. In addition, 2ME2 altered the miRNA expression in these cells. In silico analysis of the miRNome profile of 2ME2-treated MDA-MB-468 cells revealed that miRNAs altered the target genes involved in many different cancer hallmarks.

Conclusion

2ME2 inhibits triple negative breast cancer by impacting major cellular processes like proliferation, apoptosis, metastasis, etc. It further modifies gene expression by altering the miRNome of triple negative breast cancer cells. Overall, our findings suggest 2ME2 as a potent anti-cancer drug for the treatment of TNBC.
Biomarkers of lymph node metastasis in colorectal cancer: update
Authors: Zhu Xiao , Lin Shui-quan , Xie Jun , Wang Li-hui , Zhang Li-juan , Xu Ling-ling , Xu Jian-guang , Lv Yang-bo
Published: September 2024

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths globally, trailing only behind lung cancer, and stands as the third most prevalent malignant tumor, following lung and breast cancers. The primary cause of mortality in colorectal cancer (CRC) stems from distant metastasis. Among the various routes of metastasis in CRC, lymph node metastasis predominates, serving as a pivotal factor in both prognostication and treatment decisions for patients. This intricate cascade of events involves multifaceted molecular mechanisms, highlighting the complexity underlying lymph node metastasis in CRC. The cytokines or proteins involved in lymph node metastasis may represent the most promising lymph node metastasis markers for clinical use. In this review, we aim to consolidate the current understanding of the mechanisms and pathophysiology underlying lymph node metastasis in colorectal cancer (CRC), drawing upon insights from the most recent literatures. We also provide an overview of the latest advancements in comprehending the molecular underpinnings of lymph node metastasis in CRC, along with the potential of innovative targeted therapies. These advancements hold promise for enhancing the prognosis of CRC patients by addressing the challenges posed by lymph node metastasis.
Effect of prehabilitation exercises on postoperative frailty in patients undergoing laparoscopic colorectal cancer surgery
Authors: Yang Fuyu , Yuan Ye , Liu Wenwen , Tang Chenglin , He Fan , Chen Defei , Xiong Junjie , Huang Guoquan , Qian Kun
Published: September 2024

Background

To improve perioperative frailty status in patients undergoing laparoscopic colorectal cancer surgery (LCCS), we explored a new intensive prehabilitation program that combines prehabilitation exercises with standard enhanced recovery after surgery (ERAS) and explored its impact.

Methods

We conducted a prospective randomized controlled trial. Between April 2021 to August 2021, patients undergoing elective LCCS were randomized into the standardized ERAS (S-ERAS) group or ERAS based on prehabilitation (group PR-ERAS). Patients in the PR-ERAS group undergoing prehabilitation exercises in the perioperative period in addition to standard enhanced recovery after surgery. We explored the effects of this prehabilitation protocol on frailty, short-term quality of recovery (QoR), psychological status, postoperative functional capacity, postoperative outcomes, and pain.

Results

In total, 125 patients were evaluated, and 95 eligible patients were enrolled and randomly allocated to the S-ERAS (n = 45) and PR-ERAS (n = 50) groups. The Fried score was higher in the PR-ERAS group on postoperative day (7 (2(2,3) vs. 3(2,4), P = 0.012). The QoR-9 was higher in the PR-ERAS group than in the S-ERAS group on the 1st, 2nd, 3rd, and 7th postoperative days. The PR-ERAS group had an earlier time to first ambulation (P < 0.050) and time to first flatus (P < 0.050).

Conclusion

Prehabilitation exercises can improve postoperative frailty and accelerate recovery in patients undergoing LCCS but may not improve surgical safety. Therefore, better and more targeted prehabilitation recovery protocols should be explored.

Clinical trial registration

www.clinicaltrials.org, identifier NCT04964856.
Clinicopathological features, treatment patterns, and survival outcomes among Syrian patients with advanced breast cancer
Authors: Muhammad Muhammad , Alali Mousa , Saifo Maher
Published: September 2024

Background

Advanced breast cancer (ABC) is a heterogeneous disease with varied prognoses, that is affected by many clinicopathological features. This study aimed to investigate the clinicopathological characteristics, first-line treatment (FLx), and prognostic impact of these features on survival among Syrian patients with ABC.

Materials and methods

This retrospective cohort study included patients with ABC. The association of clinicopathological factors with survival was assessed using Kaplan-Meier curves and the log-rank test, as well as the Cox proportional hazards regression model to calculate the hazard ratio (HaR).

Results

A total of 423 patients with ABC were included in the study, with a median age (range) of 47 years (23-82). 83% of metastases were metachronous. Most patients (91.8%) received chemotherapy as the FLx. The median progression-free survival (PFS) and overall survival (OS) of all the patients were 7 and 16 months, respectively. The median PFS was associated with four factors, which were time of metastasis (adjusted HaR=1.861, 95% CI 1.420-2.438, P<0.0001), performance status (PS) (adjusted HaR=1.456, 95% CI 1.049-2.021, P=0.025), ovarian metastasis (adjusted HaR=7.907, 95% CI 1.049-59.576, P=0.045), and FLx (adjusted HaR=2.536, 95% CI 1.581-4.068, P<0.0001). Similarly, the OS was associated with three factors, including hormone receptors (HRs) status (adjusted HaR=1.124, 95% CI 1.009-1.252, P=0.034), time of metastasis (adjusted HaR=2.099, 95% CI 1.588-2.775, P<0.0001), and PS (adjusted HaR=1.787, 95% CI 1.429-2.233, P<0.0001). In the HR-positive/human epidermal growth receptor 2 (HER2)-negative group, endocrine therapy was significantly associated with longer PFS compared with chemotherapy (15 vs 7 months, adjusted HaR=2.699, 95% CI 1.417-5.143, P=0.003). Furthermore, there was no difference in OS between the two treatment modalities (P=0.855).

Conclusions

ABC survival varies depending on the location of metastases. Good PS and synchronous stage 4 disease were independent prognostic factors for longer PFS and OS. In the HR-positive/HER2-negative group, PFS for endocrine therapy was significantly longer than chemotherapy, with no differences in OS. This study confirms that endocrine therapy is preferred as an FLx for ABC in the HR-positive/HER2-negative group.
Digital Spatial Profiling identifies distinct patterns of immuno-oncology-related gene expression within oropharyngeal tumours in relation to HPV and p16 status
Authors: Brooks Jill M. , Zheng Yuanning , Hunter Kelly , Willcox Benjamin E. , Dunn Janet , Nankivell Paul , Gevaert Olivier , Mehanna Hisham
Published: September 2024

Background

The incidence of oropharyngeal cancer (OPC) is increasing, due mainly to a rise in Human Papilloma Virus (HPV)-mediated disease. HPV-mediated OPC has significantly better prognosis compared with HPV-negative OPC, stimulating interest in treatment de-intensification approaches to reduce long-term sequelae. Routine clinical testing frequently utilises immunohistochemistry to detect upregulation of p16 as a surrogate marker of HPV-mediation. However, this does not detect discordant p16-/HPV+ cases and incorrectly assigns p16+/HPV- cases, which, given their inferior prognosis compared to p16+/HPV+, may have important clinical implications. The biology underlying poorer prognosis of p16/HPV discordant OPC requires exploration.

Methods

GeoMx digital spatial profiling was used to compare the expression patterns of selected immuno-oncology-related genes/gene families (n=73) within the tumour and stromal compartments of formalin-fixed, paraffin-embedded OPC tumour tissues (n=12) representing the three subgroups, p16+/HPV+, p16+/HPV- and p16-/HPV-.

Results

Keratin (multi KRT) and HIF1A, a key regulator of hypoxia adaptation, were upregulated in both p16+/HPV- and p16-/HPV- tumours relative to p16+/HPV+. Several genes associated with tumour cell proliferation and survival (CCND1, AKT1 and CD44) were more highly expressed in p16-/HPV- tumours relative to p16+/HPV+. Conversely, multiple genes with potential roles in anti-tumour immune responses (immune cell recruitment/trafficking, antigen processing and presentation), such as CXCL9, CXCL10, ITGB2, PSMB10, CD74, HLA-DRB and B2M, were more highly expressed in the tumour and stromal compartments of p16+/HPV+ OPC versus p16-/HPV- and p16+/HPV-. CXCL9 was the only gene showing significant differential expression between p16+/HPV- and p16-/HPV- tumours being upregulated within the stromal compartment of the former.

Conclusions

In terms of immune-oncology-related gene expression, discordant p16+/HPV- OPCs are much more closely aligned with p16-/HPV-OPCs and quite distinct from p16+/HPV+ tumours. This is consistent with previously described prognostic patterns (p16+/HPV+ >> p16+/HPV- > p16-/HPV-) and underlines the need for dual p16 and HPV testing to guide clinical decision making.
Pulmonary alveolar proteinosis complicated by lung cancer with favorable prognosis: a case report and literature review
Authors: Wu Ying , Guan Wenhui , Deng Jiaxi , Mo Wenwei , Xu Beini , Zhang Jiahao , Jiang Huixin , Liu Jie , Lin Xinqing , Zhou Chengzhi
Published: September 2024

With the increasing incidence of lung cancer, the coexistence of pulmonary alveolar proteinosis (PAP) and lung cancer is becoming more common. However, the standard treatment protocols for patients with both conditions are still being explored. The conflict between the rapidly evolving therapeutic approaches for tumors and the limited treatment options for PAP presents a significant challenge for clinicians. Determining the optimal timing of treatment for both conditions to maximize patient benefit is a clinical conundrum. Here, we report a rare case of PAP complicated by lung adenocarcinoma, where interstitial lung changes worsened after neoadjuvant therapy but improved significantly following surgical resection of the lung adenocarcinoma. This case highlights the importance of prioritizing tumor treatment in patients with lung cancer complicated by PAP and examines the interplay between the two conditions, as well as potential therapeutic strategies.
ABHD5 as a friend or an enemy in cancer biology?
Authors: Cai Jianya , Cheng Hongwei , Xu Shuangta
Published: September 2024

Alpha beta hydrolase domain containing 5 (ABHD5) is an essential coactivator of adipose triglyceride lipase (ATGL), a rate-limiting enzyme in various cell types that promotes the hydrolysis of triacylglycerol (TG) into diacylglycerol (DG) and fatty acid (FA). It acts as a critical regulatory factor in cellular lipid metabolism. The reprogramming of lipid metabolism is one of the hallmarks of cancer, suggesting that altering lipid metabolism could become a new strategy for tumor treatment. Research has revealed a close association between ABHD5 and the development and progression of malignancies. This review summarizes the role of ABHD5 in various malignant tumors and explores the different signaling pathways and metabolic routes that may be involved, providing a comprehensive mechanistic understanding of ABHD5.
Case Report: Clinical manifestations and treatment of two Chinese patients with FINCA syndrome carrying a novel variant of NHLRC2
Authors: Liu Yuemei , Wang Hongling , Tang Yu , Zhang Lei , Su Yanyan , Wang Yanqion , Xu Shasha , Mei Shiyue , Jia Chunyang , Shen Yuelin , Tang Xiaolei
Published: September 2024

Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome is an autosomal recessive genetic disorder caused by mutations in NHL-repeat-containing protein 2 (NHLRC2) gene. This case report describes two Chinese siblings with FINCA syndrome carrying a novel frameshift variant, c.1610dupT (p.L537Ffs*17), of NHLRC2 gene. They shared similar symptoms of interstitial lung disease (ILD) and neurodegeneration, with early onset during infancy, and shared similar chest CT findings of bilateral ground-glass opacities and consolidations. The elder brother died of infantile respiratory failure, while the younger brother showed improvement in respiratory symptoms, chest CT, and Krebs von den Lungen-6 levels after long-term systemic glucocorticoid therapy, indicating that anti-inflammatory treatment may be beneficial in the treatment of ILD caused by FINCA syndrome.
Case report: Epilepsy during the use of recombinant human growth hormone: a report on two cases and a literature review
Authors: Zhou Yuan , Jia Ruofan , Xu Zhuangjian , Ma Yaping
Published: September 2024

Background

Epilepsy during recombinant human growth hormone (rhGH) therapy is rare in children. The potential association between rhGH treatment and epilepsy remains unclear.

Methods

We retrospectively analyzed the clinical data of two Chinese boys who experienced epilepsy during the use of rhGH and reviewed the relevant literature.

Results:

Case 1, an 8-year and 2-month-old boy, was diagnosed with short stature, malnutrition, and congenital hypothyroidism. He was on levothyroxine sodium tablets for a long time. Recurrent febrile convulsions were present at 6–7 years. Electroencephalogram and magnetic resonance imaging (MRI) showed no abnormality, and no treatment was given. He was diagnosed with complex febrile convulsions. The boy started rhGH treatment (approximately 0.15 IU/kg/day, sc, qd) at 8 years and 4 months. Epilepsy occurred three times during the 6 months of rhGH treatment. Electroencephalography confirmed a definitive diagnosis of epilepsy. Then, he discontinued rhGH treatment at 8 years and 11 months and started taking levetiracetam (0.25 g, po, bid) for antiepileptic therapy. Epilepsy was well-controlled 4 months later. He continued rhGH treatment at 10 years and 3 months and has been on rhGH treatment until now, with no recurrence of epilepsy. He has been taking levetiracetam to date. Case 2, a 9-year and 1-month-old boy, was diagnosed with central precocious puberty, predicted short final height, and overweight. He started treatment with triptorelin (3.75 mg, im, q4w) and rhGH (approximately 0.15 IU/kg/day, sc, qd) at 9 years and 3 months. He tended to fall repeatedly when he was approximately 10 years old. Electroencephalography showed a few medium- to high-amplitude sharp waves and sporadic sharp slow waves in the left middle temporal region, sometimes involving the left posterior temporal region. He was diagnosed with epilepsy. Triptorelin discontinuance provided no symptom relief, which worsened further. Subsequently, he withdrew from rhGH treatment, and the symptoms occurred occasionally within a week and stopped after 15 days. The electroencephalogram returned to normal. No further seizures occurred during follow-up to date.

Conclusion

During the use of rhGH in short-stature children with complex febrile convulsions or underlying lesions related to neurological impairment or those being treated with antiepileptic drugs, epilepsy may be induced.
Angiotensin II, blood–brain barrier permeability, and microglia interplay during the transition from pre-to hypertensive phase in spontaneously hypertensive rats
Authors: Makuch-Martins Mariana , Vieira-Morais Camilla G. , Perego Sany M. , Ruggeri Adriana , Ceroni Alexandre , Michelini Lisete C.
Published: September 2024

Background

Hypertension is characterized by upregulation of the renin–angiotensin system, increased blood–brain barrier (BBB) permeability, microglia activation within autonomic nuclei, and an intense sympathoexcitation. There is no information on the interplay of these events during the development of neurogenic hypertension. We sought to identify the interaction and time-course changes of Ang II availability, barrier dysfunction, microglia activation, and autonomic imbalance within autonomic areas during the development of neurogenic hypertension.

Methods

Sequential changes of hemodynamic/autonomic parameters, BBB permeability, microglia structure/density (IBA-1), and angiotensin II (Ang II) immunofluorescence were evaluated within the paraventricular hypothalamic nucleus, nucleus of the solitary tract, and rostral ventrolateral medulla of Wistar and spontaneously hypertensive rats (SHRs) aged 4 weeks, 5 weeks, 6 weeks, 8 weeks, and 12 weeks. The somatosensory cortex and hypoglossal nucleus were also analyzed as non-autonomic control areas.

Results

Increased brain Ang II availability (4th–5th week) was the first observed change, followed by the incipient BBB leakage and increased microglia density (6th week). From the 5th–6th weeks on, BBB leakage, Ang II, and IBA-1 densities increased continuously, allowing a parallel increase in both Ang II-microglia colocalization and the transition of microglial cells from highly ramified in the basal surveillant condition (4th–5th week) to shorter process arbors, fewer endpoints, and enlarged soma in the disease-associate condition (6th week to the 12th week). Simultaneously with increased Ang II-microglia colocalization and microglia morphologic phenotypic changes, sympathetic activity and pressure variability increased, autonomic control deteriorated, and blood pressure increased. These responses were not specific for autonomic nuclei but also occurred at a lower magnitude in the somatosensory cortex and hypoglossal nucleus, indicating the predominance of hypertension-induced effects on autonomic areas. No changes were observed in age-matched controls where Ang II density did not change.

Conclusion

Brain Ang II density is the initial stimulus to drive coordinated changes in BBB permeability and microglial reactivity. Increased BBB dysfunction allows access of plasma Ang II and increases its local availability and the colocalization and activation of microglial cells. It is a potent stimulus to augments vasomotor sympathetic activity, autonomic imbalance, and pressure elevation during the establishment of hypertension.
Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for modeling cardiac arrhythmias: strengths, challenges and potential solutions
Authors: Joshi Jyotsna , Albers Cora , Smole Nathan , Guo Shuliang , Smith Sakima A.
Published: September 2024

Ion channels and cytoskeletal proteins in the cardiac dyad play a critical role in maintaining excitation-contraction (E-C) coupling and provide cardiac homeostasis. Functional changes in these dyad proteins, whether induced by genetic, epigenetic, metabolic, therapeutic, or environmental factors, can disrupt normal cardiac electrophysiology, leading to abnormal E-C coupling and arrhythmias. Animal models and heterologous cell cultures provide platforms to elucidate the pathogenesis of arrhythmias for basic cardiac research; however, these traditional systems do not truly reflect human cardiac electro-pathophysiology. Notably, patients with the same genetic variants of inherited channelopathies (ICC) often exhibit incomplete penetrance and variable expressivity which underscores the need to establish patient-specific disease models to comprehend the mechanistic pathways of arrhythmias and determine personalized therapies. Patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) inherit the genetic background of the patient and reflect the electrophysiological characteristics of the native cardiomyocytes. Thus, iPSC-CMs provide an innovative and translational pivotal platform in cardiac disease modeling and therapeutic screening. In this review, we will examine how patient-specific iPSC-CMs historically evolved to model arrhythmia syndromes in a dish, and their utility in understanding the role of specific ion channels and their functional characteristics in causing arrhythmias. We will also examine how CRISPR/Cas9 have enabled the establishment of patient-independent and variant-induced iPSC-CMs-based arrhythmia models. Next, we will examine the limitations of using human iPSC-CMs with respect to in vitro arrhythmia modeling that stems from variations in iPSCs or toxicity due to gene editing on iPSC or iPSC-CMs and explore how such hurdles are being addressed. Importantly, we will also discuss how novel 3D iPSC-CM models can better capture in vitro characteristics and how all-optical platforms provide non-invasive and high- throughput electrophysiological data that is useful for stratification of emerging arrhythmogenic variants and drug discovery. Finally, we will examine strategies to improve iPSC-CM maturity, including powerful gene editing and optogenetic tools that can introduce/modify specific ion channels in iPSC-CMs and tailor cellular and functional characteristics. We anticipate that an elegant synergy of iPSCs, novel gene editing, 3D- culture models, and all-optical platforms will offer a high-throughput template to faithfully recapitulate in vitro arrhythmogenic events necessary for personalized arrhythmia monitoring and drug screening process.
The empathy and stress mindset of healthcare workers: the chain mediating roles of self-disclosure and social support
Authors: Wu Jinxia , Dou Jinhua , Wang Daofeng , Wang Lizhuo , Chen Feng , Lu Guohua , Sun Lin , Liu Jianlan
Published: September 2024

The hospital is a workplace full of stressful events for healthcare workers (HCWs) due to unpredictable changes in their daily routines. Perceptions of stressful events (stress mindset) have a significant impact on an individual’s health and well-being. However, few studies have reported the factors and potential counter mechanisms influencing these perceptions. This study aimed to evaluate the relationship between empathy, self-disclosure, social support, and stress mindset of HCWs, and to explore the mechanism of empathy on stress mindset. Five hundred and eight HCWs (35.2% men and 64.8% women) completed the Interpersonal Reactivity Index (IRI), the Distress Disclosure Index (DDI), the Social Support Rating Scale (SSRS), the Stress Mindset Measure (SMM), and demographic questionnaires online in China. The results showed that empathy was positively linked with stress mindset and positively correlated with self-disclosure and social support. In the multiple mediating model, self-disclosure and social support mediated the association between empathy and stress mindset sequentially. The results imply that empathy, self-disclosure, and social support play a significant role in the formation of HCWs’ stress mindset. These findings have substantial ramifications for reducing stress and creating successful government interventions to fortify stress mindset in healthcare.
Racial disparities in the diagnosis of disruptive behavior disorders: a U.S. national inpatient sample analysis
Authors: Savage William M. , Saint-Hilaire Sidney A. , Shah Mansi , Lugo-Candelas Claudia
Published: September 2024

Disruptive behavior disorders (DBDs) are comprised of conduct disorder and oppositional defiant disorder. Limited literature exists on the demographics of patients diagnosed with these conditions. Despite the clinical overlap of DBDs and attention-deficit hyperactivity disorder (ADHD), there is a stark divergence in the treatment and societal accommodation for these two diagnoses, amplifying the importance of this diagnostic challenge. Thus, potential diagnostic differences must be urgently and rigorously explored. Small, regional studies have reported potential “racial” disparities in the diagnosis of DBDs, especially when compared to the diagnosis of ADHD. Our study uses the National Inpatient Sample (NIS) database to provide the largest, most comprehensive investigation of “racial” disparities in the diagnosis of DBDs. Discharge data from 700,770 pediatric inpatients (mean age = 9.32 years) were included in this analysis. To explore potential disparities among children with symptoms in this area of clinical overlap, we assessed the relationship of “race” and the diagnosis of DBDs. Among the subgroup of pediatric inpatients diagnosed with ADHD or a DBD, Native American (OR = 2.18; 95% = 1.76, 2.70), Asian (OR = 1.88, 95% = 1.56, 2.26), Black (OR = 1.40; 95% = 1.32, 1.48), and Hispanic (OR = 1.20; 95% = 1.12, 1.28) “race” correlated with DBD diagnosis. By highlighting these diagnostic disparities, this study raises essential questions about race and the diagnosis of DBDs.
Establishing age- and sex-specific anthropometric growth references standards for South Punjab adolescents utilizing the LMS method: findings from the Pakistani population
Authors: Long Liu , Hamdani Syed Danish , Hamdani Syed Muhammad Zeeshan Haider , Zhuang Jie , Khurram Haris , Hadier Syed Ghufran
Published: September 2024

Background

The physical health of adolescents is crucial for the prosperity and sustainable development of a nation. Developing specific growth standards is essential for prioritizing the wellbeing of the youth of Pakistan. This study aimed to establish normative standards for height, weight, and body mass index (BMI) among 12- to 16-year-olds in South Punjab, facilitating accurate health assessments and tailored interventions.

Method

This study utilized a cross-sectional design and stratified random sampling to select 2,970 adolescents (49.73% boys and 50.26% girls) aged 12–16 years from South Punjab, Pakistan. Anthropometric measurements, including height, weight, and BMI, were collected. The data were stratified by age and sex, and smoothed percentile curves were computed using the LMS method, which incorporates the L (γ-lambda), M (μ-mu), and S (δ-sigma) parameters. The results were compared to international references to provide a comprehensive analysis.

Results

The results highlight sex-specific trends in anthropometric indicators among adolescents. Boys exhibited higher mean values in height (160.50 ± 11.50 cm), weight (45.02 ± 9.78 kg), and BMI (17.30 ± 2.41) than girls (158.57 ± 9.34 cm, 41.00 ± 7.89 kg, and 16.29 ± 2.82, respectively). Growth patterns indicate boys grow faster in height and weight between ages 12 and 14, whereas girls show slower annual increases. Comparative analysis with international standards reveals that boys’ height and weight were generally lower than international medians (P50th), whereas girls’ height was comparable or higher. BMI values for both sexes were lower than international norms, reflecting unique regional growth patterns.

Conclusion

This research establishes updated age- and sex-specific normative reference standards for adolescents in South Punjab, Pakistan. The study revealed that Pakistani adolescent boys exhibit higher mean values in height, weight, and BMI than girls, with faster growth rates between ages 12 and 14. Compared to international standards, Pakistani adolescents show lower BMI values, highlighting unique regional growth patterns. These standards have practical applications in screening, monitoring, and health strategy planning, contributing to efforts to promote a healthier future for the population. Future studies are recommended to utilize these local growth references for health surveillance and treatment in the local population.
Human Health Thrives Thanks To Biodiversity
Authors: Muylaert Renata , Hayman David T. S. , Fernandez Miguel , Hildebrand Alexander von , Willetts Elizabeth , Machalaba Catherine , Mensah Paul Kojo , Prist Paula R.
Published: September 2024

Did you know health is not just about not being sick? It is about feeling well. In healthy ecosystems, you can find plants, animals, water, rocks, and soil, all interacting with many microbes. Thanks to this biodiversity we have clean air, fresh water, and nutritious food. Bees and other animals pollinate flowers to help grow fruits and vegetables. Birds spread seeds that grow into trees and forests. Plants clean the air we breathe. And people feel better in nature. Healthy ecosystems, therefore, keep people healthy. While public health programs teach people about healthy food and give them access to medicines, people make ecosystems healthier by protecting nature. You can help too, by taking care of your health and your surrounding ecosystem, learning about the world, and supporting decisions and actions that protect nature and people. By becoming guardians of Earth’s biodiversity, we can all have a healthy future together.
Decompression sickness-induced skeletal muscle injury: an animal model and pathological analysis
Authors: Chen Guanghua , Huang Yongbin , Huang Chunman , Li Liwei , Pang Jingqun , Li Hongqiang , Zhang Wenxi
Published: September 2024

Aims

The primary objective of this investigation is to establish an animal model that accurately represents skeletal muscle injury as a consequence of decompression sickness. Additionally, this study aims to delineate the potential mechanisms underlying the development and progression of skeletal muscle damage associated with decompression sickness.

Materials and methods

(1) In this research, rats were utilized as experimental models and subjected to 600 kPa pressure in an air medium for a duration of 60 min, followed by decompression at a consistent rate of 1.5 min to reach atmospheric pressure in order to establish an animal model for decompression injury. Assessment of decompression injury involved the observation of general symptoms and signs, as well as histopathological examination of lung tissue to determine the extent of damage in the pulmonary system of rats. (2) Building on the rat decompression injury model, we conducted pathological and serological examinations to assess the status of rat skeletal muscle. Additionally, we investigated the signaling mechanism of the TLR9-MyD88 pathway in mediating alterations in rat skeletal muscle resulting from decompression injury, and evaluated the effects of decompression injury on apoptosis in rat skeletal muscle.

Results

Repeated decompression induces significant damage to skeletal muscle tissue, characterized by edema, fiber rupture, and atrophy. This process also leads to a transient elevation in creatine kinase (CK-MM) levels in rat serum, as well as an upregulation of proteins such as TLR9, MyD88, p38, and ERK in rat skeletal muscle tissue. Furthermore, repeated decompression results in a temporary increase in the transcription levels of Atrogen-1mRNA and MuRF-1mRNA in rat skeletal muscle tissue.

Discussion

The decompression protocol applied in this study successfully induced decompression sickness in a rat model, leading to skeletal muscle damage that was consistent with the expected pathology of decompression injury. Despite the initial injury, the rats showed evidence of adaptation following prolonged exposure to decompression conditions.
Evaluation of the rational prescription of linezolid, the prevalence of thrombocytopenia and major drug interactions in patients with cardiovascular diseases: are there any cautions?
Authors: Dianatkhah Mehrnoush , Salami Hamed , Soltani Rasool , Hosseini Alireza
Published: September 2024

The present study evaluated the rational prescription of linezolid, the prevalence of thrombocytopenia, and major drug interactions in patients with cardiovascular diseases. We conducted a retrospective cross-sectional study on linezolid-treated patients at Shahid Chamran Heart Hospital in Isfahan from March 21, 2021, to March 20, 2022. Our research involved 132 patients who received linezolid. We reported 43.18% of linezolid prescriptions as irrational. Linezolid-induced thrombocytopenia is more common than previous studies, with a prevalence of 47.9%. We found a significant relationship between thrombocytopenia and the concomitant use of aspirin. The duration of treatment was identified as predicting factor for linezolid-induced thrombocytopenia. Moreover, the prevalence of interactions in the X and D categories was determined. Serotonergic and catecholamine medications were associated with 56.1% and 47.7% medication interactions, respectively. Our study found a high prevalence of linezolid-induced thrombocytopenia among patients with cardiovascular diseases. Based on this study, physicians should focus more closely on prescribing linezolid to patients with cardiovascular diseases. In addition to following rational antibiotic use, this susceptible group is also at an elevated risk of side effects (thrombocytopenia) and medication interactions.
Unveiling the Influence of Big Data Disclosure on Audit Quality: Evidence from Omani Financial Firms
Authors: Al Lawati Hidaya , Sanad Zakeya , Al Farsi Mohammed
Published: September 2024

Purpose: This study aims to investigate the impact of big data disclosure on audit quality in the Omani context. Design/methodology/approach: This study used data extracted from annual reports for a sample from financial companies listed on the Muscat Stock Exchange over the period from 2014 to 2020. We applied a content analysis approach to measure the level of big data disclosure in these firms. This study used ordinary least squares and panel data regression analysis to investigate the relationship between big data disclosure and audit quality. Moreover, we moderated the relationship between big data disclosure and audit quality with family members who are serving on the board of directors and with royal membership. Findings: The findings of the study indicated that big data disclosure played a vital role in enhancing the audit quality of the financial firms in the Omani context. In addition, family memberships positively moderated the association between big data disclosure and audit quality in these firms. However, royal members negatively moderated such relationship. Research limitations/implications: We included only financial institutions in the sample. Practical implications: The study offers practical implications for investors, managers, and policymakers. It will raise awareness on the importance of implementing regulations necessary for disclosing such information in annual reports, thereby enhancing the audit quality of firms and increasing the reliability and validity of financial reports. Originality/value: The study is considered the first, to the best of our knowledge, to examine the impact of big data disclosure on the audit quality in the Omani context. It contributes to the existing knowledge of digital transformation in the Omani financial firms.
Ground Measurements and Remote Sensing Modeling of Gross Primary Productivity and Water Use Efficiency in Almond Agroecosystems
Authors: Gabaldón-Leal Clara , Sánchez-Virosta Álvaro , Doña Carolina , González-Piqueras José , Sánchez Juan Manuel , López-Urrea Ramón
Published: September 2024

Agriculture plays a crucial role as a carbon sink in the atmosphere, contributing to a climate-neutral economy, which requires a comprehensive understanding of Earth’s complex biogeochemical processes. This study aims to quantify, for the first time, Gross Primary Productivity (GPP) and ecosystem water use efficiency (eWUE) in almond orchards during their vegetative phase. The study was conducted over six growing seasons (2017–2022) across two drip-irrigated commercial almond groves located in Albacete, SE Spain. Eddy covariance flux tower systems were used to measure Net Ecosystem Exchange (NEE) and evapotranspiration (ET), which were then used to calculate GPP and eWUE. A novel approach was developed to estimate eWUE by integrating the Normalized Difference Vegetation Index (NDVI), reference ET, and air temperature. The results show similar almond orchard carbon-fixing capacity rates to those of other natural and agro-ecosystems. Seasonal and interannual variability in GPP and eWUE were observed. The NDVI-ET combination proved to be effective for GPP estimations (regression coefficient of 0.78). Maximum carbon-fixing values were observed at ET values of around 4–5 mm/d. In addition, a novel method was developed to estimate eWUE from NDVI, reference ET and air temperature (RMSE of 0.38 g·C/kg·H2O). This study highlights the carbon capture potential of almond orchards during their vegetative phase and introduces a novel approach for eWUE monitoring, with the intention of underscoring their significance in a climate change context and to encourage further research.
The Microbiological Activity of Soil in Response to Gliotoxin, the “Lethal Principle” of Trichoderma
Authors: Teslya Anastasia V. , Gurina Elena V. , Stepanov Artyom A. , Iashnikov Aleksandr V. , Vasilchenko Alexey S.
Published: September 2024

Trichoderma is a soil-dwelling microorganism that has many benefits for plants and is therefore widely used in agriculture. Among the secondary metabolites produced by Trichoderma, gliotoxin (GT) is one of the most studied. The antagonistic effect of GT on other fungi was first discovered by R. Weindling in 1934. He referred to it as the “lethal principle” of Trichoderma. Despite the long history of studying GT, its impact on the soil microbial community has remained largely unexplored. In our work, we investigated the response of the soil microbial community to different doses of GT (10–500 µM per kg) and different durations (7–56 days) of exposure. We measured microbiological parameters (CO2 emission, microbial biomass (MB)), calculated the eco-physiological indices and determined the activity of soil enzymes involved in the C, N, P and S cycles. We identified three types of microbial responses to GT: inhibition, stress and stimulation. The inhibitory effect developed only by day 56 and in the samples treated with 500 μM GT. The stress effect (increased CO2 emission and decreased MB) of GT on microbial communities was predominant. Soil extracellular enzymes also responded to GT to varying degrees. A stimulating effect of GT on enzyme activity was noted for β-D-1,4-cellobiosidase and β-1,4-glucosidase. The activity of arylsulfatase and leucine aminopeptidase decreased under the influence of GT up to day 28, but by the end of the experiment, there was a restoration of activity. We did not observe any significant changes in the activity of β-1,4-xylosidase, β-1,4-N-acetyl-glucosaminidase or acid phosphatase. The results obtained showed that GT at high, “man-made” doses can inhibit the microbiological activity of soil, but at naturally occurring concentrations, it can have a stimulating effect on soil microbiome functionality.
Reducing Nitrogen Application Rates and Straw Mulching Can Alleviate Greenhouse Gas Emissions from Wheat Field Soil and Improve Soil Quality
Authors: Du Mengyin , Yao Yao , Liu Shuainan , Li Guang , Yuan Jianyu
Published: September 2024

Sustainable agriculture faces challenges balancing the need for increasing crop production with environmental protection. Straw mulching is widely used to improve crop productivity, while reducing nitrogen application is an effective strategy to reduce greenhouse gas (GHG) emissions. However, the comprehensive evaluation of soil properties, GHG emissions, and soil quality under straw mulching conditions with different N application rates has not been extensively studied, especially in the Loess Plateau region of Central Gansu. Therefore, a two-year field experiment was conducted, involving two tillage practices (CT: conventional tillage, CTS: conventional tillage + straw mulching) and three fertilization levels (LN: low nitrogen fertilizer, 55 kg N ha−1; MN: medium nitrogen fertilizer, 110 kg N ha−1 HN: high nitrogen fertilizer, 220 kg N ha−1). Based on the greenhouse gas emission intensity (GHGI), the minimum data set (MDS) was constructed by principal component analysis, correlation analysis, and Norm value, and the weighted index method was applied to comprehensively evaluate the soil quality. Our results showed that compared with CT, CTS significantly increased crop yields and improved the content of soil nutrients, and it was more effective when applying moderate amounts of nitrogen fertilizer. Wheat field soil behaves as a nitrous oxide (N2O) emission source and a methane (CH4) absorption sink. CTS–MN and CTS–LN reduced N2O emission by 52.95–87.76%, increased total CH4 uptake by 16.69–43.60%, and slowed down global warming potential (GWP) by 35.70–48.17% compared with CTS–HN in 2021–2022. They also reduced GHGI. Furthermore, CTS enhanced soil quality at different nitrogen application levels compared with CT, with CTS–MN exhibiting the highest Soil Quality Index (SQI) over the two years. Consequently, considering both economic and environmental benefits, CTS–MN can be regarded as a key practice for the sustainable development of agroecosystems in the Loess Plateau region of Central Gansu.