bluuebunny/crossref_metadata_2025 huggingface dataset:
Multidisciplinary amyloidosis care in the era of personalized medicine
Authors: Bumma Naresh , Kahwash Rami , Parikh Samir V. , Isfort Michael , Freimer Miriam , Vallakati Ajay , Redder Elyse , Campbell Courtney M. , Sharma Nidhi , Efebera Yvonne , Stino Amro
Published: October 2022

Amyloidosis refers to a group of conditions where abnormal protein—or amyloid—deposits in tissues or organs, often leading to organ malfunction. Amyloidosis affects nearly any organ system, but especially the heart, kidneys, liver, peripheral nervous system, and gastrointestinal tract. Neuromuscular deficits comprise some of its ubiquitous manifestations. Amyloidosis can be quite challenging to diagnose given its clinical heterogeneity and multi-system nature. Early diagnosis with accurate genetic and serologic subtyping is key for effective management and prevention of organ decline. In this review, we highlight the value of a multidisciplinary comprehensive amyloidosis clinic. While such a model exists at numerous clinical and research centers across the globe, the lack of more widespread adoption of such a model remains a major hindrance to the timely diagnosis of amyloidosis. Such a multidisciplinary care model allows for the timely and effective diagnosis of amyloidosis, be it acquired amyloid light amyloidosis (AL), hereditary transthyretin amyloidosis (hATTR), or wild type amyloidosis (TTR-wt), especially in the current era of personalized genomic medicine. A multidisciplinary clinic optimizes the delivery of singular or combinatorial drug therapies, depending on amyloid type, fibril deposition location, and disease progression. Such an arrangement also helps advance research in the field. We present our experience at The Ohio State University, as one example out of many, to highlight the centrality of a multi-disciplinary clinic in amyloidosis care.
Changes in the higher-level functional capacities for modern daily living in community-dwelling stroke survivors: A preliminary case series
Authors: Kawasaki Tsubasa , Ohira Masahiro , Endo Ryu , Muto Keita , Sakai Hiroki , Goto Keisuke
Published: October 2022

Along with the development of modern technology, the variety of higher-level activities of daily living has steadily expanded. However, no reports have examined the capacities for the higher-level activities in stroke survivors. Moreover, the relationship between these capacities and executive functions has not been reported. This preliminary study longitudinally measured changes in the capacities for high-level activities of modern daily living in community-dwelling stroke survivors. In addition, we examined whether changes in these capacities were correlated with executive functions. The results showed no significant reduction in the capacities for high-level activities of modern daily living at 1 year after stroke. Significant improvements were observed in one aspect of executive functions: planning. The changes in the capacities for higher-level activities of modern daily living were significantly correlated with executive function. The results suggest that, in stroke survivors, (a) it is likely feasible to maintain the capacities for higher-level activities of modern daily living, and (b) these capacities are related to executive functions.
Multimodal magnetic resonance imaging of youth sport-related concussion reveals acute changes in the cerebellum, basal ganglia, and corpus callosum that resolve with recovery
Authors: Pinky Najratun Nayem , Debert Chantel T. , Dukelow Sean P. , Benson Brian W. , Harris Ashley D. , Yeates Keith O. , Emery Carolyn A. , Goodyear Bradley G.
Published: October 2022

Magnetic resonance imaging (MRI) can provide a number of measurements relevant to sport-related concussion (SRC) symptoms; however, most studies to date have used a single MRI modality and whole-brain exploratory analyses in attempts to localize concussion injury. This has resulted in highly variable findings across studies due to wide ranging symptomology, severity and nature of injury within studies. A multimodal MRI, symptom-guided region-of-interest (ROI) approach is likely to yield more consistent results. The functions of the cerebellum and basal ganglia transcend many common concussion symptoms, and thus these regions, plus the white matter tracts that connect or project from them, constitute plausible ROIs for MRI analysis. We performed diffusion tensor imaging (DTI), resting-state functional MRI, quantitative susceptibility mapping (QSM), and cerebral blood flow (CBF) imaging using arterial spin labeling (ASL), in youth aged 12-18 years following SRC, with a focus on the cerebellum, basal ganglia and white matter tracts. Compared to controls similar in age, sex and sport (N= 20), recent SRC youth (N= 29; MRI at 8 ± 3 days post injury) exhibited increased susceptibility in the cerebellum (p= 0.032), decreased functional connectivity between the caudate and each of the pallidum (p= 0.035) and thalamus (p= 0.021), and decreased diffusivity in the mid-posterior corpus callosum (p< 0.038); no changes were observed in recovered asymptomatic youth (N= 16; 41 ± 16 days post injury). For recent symptomatic-only SRC youth (N= 24), symptom severity was associated with increased susceptibility in the superior cerebellar peduncles (p= 0.011) and reduced activity in the cerebellum (p= 0.013). Fewer days between injury and MRI were associated with reduced cerebellar-parietal functional connectivity (p< 0.014), reduced activity of the pallidum (p= 0.002), increased CBF in the caudate (p= 0.005), and reduced diffusivity in the central corpus callosum (p< 0.05). Youth SRC is associated with acute cerebellar inflammation accompanied by reduced cerebellar activity and cerebellar-parietal connectivity, as well as structural changes of the middle regions of the corpus callosum accompanied by functional changes of the caudate, all of which resolve with recovery. Early MRI post-injury is important to establish objective MRI-based indicators for concussion diagnosis, recovery assessment and prediction of outcome.
Salivary microRNA profiling dysregulation in autism spectrum disorder: A pilot study
Authors: Kalemaj Zamira , Marino Maria Michela , Santini Annamaria Chiara , Tomaselli Giovanni , Auti Amogh , Cagetti Maria Grazia , Borsello Tiziana , Costantino Antonella , Inchingolo Francesco , Boccellino Mariarosaria , Di Domenico Marina , Tartaglia Gianluca Martino
Published: October 2022

Introduction

Autism spectrum disorders (ASD) are the most prevalent neurobiological disorders in children. The etiology comprises genetic, epigenetic, and environmental factors such as dysfunction of the immune system. Epigenetic mechanisms are mainly represented by DNA methylation, histone modifications, and microRNAs (miRNA). The major explored epigenetic mechanism is mediated by miRNAs which target genes known to be involved in ASD pathogenesis. Salivary poly-omic RNA measurements have been associated with ASD and are helpful to differentiate ASD endophenotypes. This study aims to comprehensively examine miRNA expression in children with ASD and to reveal potential biomarkers and possible disease mechanisms so that they can be used to improve faction between individuals by promoting more personalized therapeutic approaches.

Materials and methods

Saliva samples were collected from 10 subjects: 5 samples of children with ASD and 5 from healthy controls. miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system.

Results

Preliminary data highlighted the presence of 365 differentially expressed miRNAs. Pathway analysis, molecular function, biological processes, and target genes of 41 dysregulated miRNAs were assessed, of which 20 were upregulated, and 21 were downregulated in children with ASD compared to healthy controls.

Conclusion

The results of this study represent preliminary but promising data, as the identified miRNA pathways could represent useful biomarkers for the early non-invasive diagnosis of ASD.
Co-transduction of dual-adeno-associated virus vectors in the neonatal and adult mouse utricles
Authors: Chen Zhong-Rui , Guo Jing-Ying , He Lu , Liu Shan , Xu Jun-Yi , Yang Zi-Jing , Su Wei , Liu Ke , Gong Shu-Sheng , Wang Guo-Peng
Published: October 2022

Adeno-associated virus (AAV)-mediated gene transfer is an efficient method of gene over-expression in the vestibular end organs. However, AAV has limited usefulness for delivering a large gene, or multiple genes, due to its small packaging capacity (< 5 kb). Co-transduction of dual-AAV vectors can be used to increase the packaging capacity for gene delivery to various organs and tissues. However, its usefulness has not been well validated in the vestibular sensory epithelium. In the present study, we characterized the co-transduction of dual-AAV vectors in mouse utricles following inoculation of two AAV-serotype inner ear (AAV-ie) vectors via canalostomy. Firstly, co-transduction efficiencies were compared between dual-AAV-ie vectors using two different promoters: cytomegalovirus (CMV) and CMV early enhancer/chicken β-actin (CAG). In the group of dual AAV-ie-CAG vectors, the co-transduction rates for striolar hair cells (HCs), extrastriolar HCs, striolar supporting cells (SCs), and extrastriolar SCs were 23.14 ± 2.25%, 27.05 ± 2.10%, 57.65 ± 7.21%, and 60.33 ± 5.69%, respectively. The co-transduction rates in the group of dual AAV-ie-CMV vectors were comparable to those in the dual AAV-ie-CAG group. Next, we examined the co-transduction of dual-AAV-ie-CAG vectors in the utricles of neonatal mice and damaged adult mice. In the neonatal mice, co-transduction rates were 52.88 ± 3.11% and 44.93 ± 2.06% in the striolar and extrastriolar HCs, respectively, which were significantly higher than those in adult mice. In the Pou4f3+/DTR mice, following diphtheria toxin administration, which eliminated most HCs and spared the SCs, the co-transduction rate of SCs was not significantly different to that of normal utricles. Transgene expression persisted for up to 3 months in the adult mice. Furthermore, sequential administration of two AAV-ie-CAG vectors at an interval of 1 week resulted in a higher co-transduction rate in HCs than concurrent delivery. The auditory brainstem responses and swim tests did not reveal any disruption of auditory or vestibular function after co-transduction with dual-AAV-ie vectors. In conclusion, dual-AAV-ie vectors allow efficient co-transduction in the vestibular sensory epithelium and facilitate the delivery of large or multiple genes for vestibular gene therapy.
Non-invasive brain neuromodulation techniques for chronic low back pain
Authors: Chang Tian-Tian , Chang Yu-Hao , Du Shu-Hao , Chen Pei-Jie , Wang Xue-Qiang
Published: October 2022

Structural and functional changes of the brain occur in many chronic pain conditions, including chronic low back pain (CLBP), and these brain abnormalities can be reversed by effective treatment. Research on the clinical applications of non-invasive brain neuromodulation (NIBS) techniques for chronic pain is increasing. Unfortunately, little is known about the effectiveness of NIBS on CLBP, which limits its application in clinical pain management. Therefore, we summarized the effectiveness and limitations of NIBS techniques on CLBP management and described the effects and mechanisms of NIBS approaches on CLBP in this review. Overall, NIBS may be effective for the treatment of CLBP. And the analgesic mechanisms of NIBS for CLBP may involve the regulation of pain signal pathway, synaptic plasticity, neuroprotective effect, neuroinflammation modulation, and variations in cerebral blood flow and metabolism. Current NIBS studies for CLBP have limitations, such as small sample size, relative low quality of evidence, and lack of mechanistic studies. Further studies on the effect of NIBS are needed, especially randomized controlled trials with high quality and large sample size.
Development of ASIC1a ligand-gated ion channel drug screening assays across multiple automated patch clamp platforms
Authors: Ridley John , Manyweathers Sam , Tang Raymond , Goetze Tom , Becker Nadine , Rinke-Weiß Ilka , Kirby Robert , Obergrussberger Alison , Rogers Marc
Published: October 2022

Human acid-sensing ion channels (ASIC) are ligand-gated ionotropic receptors expressed widely in peripheral tissues as well as sensory and central neurons and implicated in detection of inflammation, tissue injury, and hypoxia-induced acidosis. This makes ASIC channels promising targets for drug discovery in oncology, pain and ischemia, and several modulators have progressed into clinical trials. We describe the use of hASIC1a as a case study for the development and validation of low, medium and high throughput automated patch clamp (APC) assays suitable for the screening and mechanistic profiling of new ligands for this important class of ligand-gated ion channel. Initial efforts to expand on previous manual patch work describing an endogenous hASIC1a response in HEK cells were thwarted by low current expression and unusual pharmacology, so subsequent work utilized stable hASIC1a CHO cell lines. Ligand-gated application protocols and screening assays on the Patchliner, QPatch 48, and SyncroPatch 384 were optimized and validated based on pH activation and nM-μM potency of reference antagonists (e.g., Amiloride, Benzamil, Memantine, Mambalgin-3, A-317567, PcTx1). By optimizing single and stacked pipette tip applications available on each APC platform, stable pH-evoked currents during multiple ligand applications enabled cumulative EC50 and IC50 determinations with minimized receptor desensitization. Finally, we successfully demonstrated for the first time on an APC platform the ability to use current clamp to implement the historical technique of input resistance tracking to measure ligand-gated changes in membrane conductance on the Patchliner platform.
The nutritional functions of dietary sphingomyelin and its applications in food
Authors: Yang Fang , Chen Guoxun
Published: October 2022

Sphingolipids are common structural components of cell membranes and are crucial for cell functions in physiological and pathophysiological conditions. Sphingomyelin and its metabolites, such as sphingoid bases, ceramide, ceramide-1-phosphate, and sphingosine-1-phosphate, play signaling roles in the regulation of human health. The diverse structures of sphingolipids elicit various functions in cellular membranes and signal transduction, which may affect cell growth, differentiation, apoptosis, and maintain biological activities. As nutrients, dietary sphingomyelin and its metabolites have wide applications in the food and pharmaceutical industry. In this review, we summarized the distribution, classifications, structures, digestion, absorption and metabolic pathways of sphingolipids, and discussed the nutritional functioning of sphingomyelin in chronic metabolic diseases. The possible implications of dietary sphingomyelin in the modern food preparations including dairy products and infant formula, skin improvement, delivery system and oil organogels are also evaluated. The production of endogenous sphingomyelin is linked to pathological changes in obesity, diabetes, and atherosclerosis. However, dietary supplementations of sphingomyelin and its metabolites have been shown to maintain cholesterol homeostasis and lipid metabolism, and to prevent or treat these diseases. This seemly paradoxical phenomenon shows that dietary sphingomyelin and its metabolites are candidates for food additives and functional food development for the prevention and treatment of chronic metabolic diseases in humans.
Metabolic folate profiling as a function of time during cultivation suggests potential C2-metabolism in Saccharomyces cerevisiae
Authors: Schillert Lena , Wirtz Daniela , Weber Nadine , Schaller Franziska , Striegel Lisa , Schmitt-Kopplin Philippe , Rychlik Michael
Published: October 2022

Yeasts are reported to be rich in folates, a group of vitamers known to be involved in several biosynthetic reactions such as methylation reactions, oxidation and reduction processes, and nucleotide synthesis. Not being able to synthesize folates, humans rely on external folate supply. Here, we show the application of LC/MS-MS methods using SIDA (stable isotope dilution analysis) assays for the quantitative analysis of different folate mono- and polyglutamates during growth of Saccharomyces cerevisiae. Molecular networking (MN) was applied for detailed analysis of further folate metabolites. Highest folate contents of 13,120 μg/100 g were observed after 20 h of cultivation. The main vitamers 5-CH3-H4folate and H4folate decreased during cultivation, while 5-CHO-H4folate increased during cultivation. The hexa- and heptaglutamate of 5-CH3-H4folate accounted for >96% of the total 5-CH3-H4folate content. A shift of the major polyglutamate from hexa- to heptaglutamate was observed after 29 h. MN unraveled two groups of novel folates which could be assigned to a potentially existing C2-metabolism in yeast. In detail, 5,10-ethenyl-tetrahydrofolate and a further CO-substituted 5-CH3-H4folate were identified as hexa- and heptaglutamates. The latter was neither identified as 5-acetyl-tetrahydrofolate nor as EthylFox, the oxidation product of 5-ethyl-tetrahydrofolate. The structure needs to be elucidated in future studies.
Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons via neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gain
Authors: Wang Lei , Suyama Shigetomo , Lee Samantha A. , Ueta Yoichi , Seino Yutaka , Sharp Geoffrey W. G. , Yada Toshihiko
Published: October 2022

Fasting with varying intensities is used to treat obesity-related diseases. Re-feeding after fasting exhibits hyperphagia and often rebound weight gain. However, the mechanisms underlying the hyperphagia and rebound remain elusive. Here we show that 24 h food restriction (24 h FR) and milder 50% FR, both depress synaptic transmission in the hypothalamic paraventricular nucleus (PVN) and induce acute hyperphagia in rats. 24 h FR is followed by weight rebound but 50% FR is not. Orexigenic neuropeptide Y (NPY) via the Y1 receptor (Y1R) inhibited the miniature excitatory postsynaptic current (mEPSC) on anorexigenic oxytocin neurons in the PVN. 24 h FR and 50% FR activated this neuronal pathway to induce acute hyperphagia on Days 1–3 and Days 1–2 after FR, respectively. 24 h FR induced large mEPSC depression, recurrent hyperphagia on Days 9–12 and rebound weight gain on Days 12–17, whereas 50% FR induced moderate mEPSC depression and sustained weight reduction. Transverse data analysis on Day 1 after 24 h FR and 50% FR demonstrated saturation kinetics for the mEPSC depression-hyperphagiacurve, implying hysteresis. The results reveal FR-driven synaptic plasticity in the NPY-Y1R-oxytocin neurocircuit that drives acute hyperphagia. FR with the intensity that regulates the synapse-feeding relay without hysteresis is the key for successful dieting.
Construction of survival prediction model for elderly esophageal cancer
Authors: Qie Shuai , Shi Hongyun , Wang Fang , Liu Fangyu , Gu Jinling , Liu Xiaohui , Li Yanhong , Sun Xiaoyue
Published: October 2022

Background

The purpose of this study was to analyze the clinical characteristics and prognosis of EPEC and to construct a prediction model based on the SEER database.

Methods

All EPECs from the SEER database were retrospectively analyzed. A comprehensive and practical nomogram that predicts the overall survival (OS) of EPEC was constructed. Univariate and multivariate Cox regression analysis was performed to explore the clinical factors influencing the prognosis of EPEC, and finally, the 1 -, 3 - and 5-year OS were predicted by establishing the nomogram. The discriminant and predictive ability of the nomogram was evaluated by consistency index (C-index), calibration plot, area under the curve (AUC), and receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was used to evaluate the clinical value of the nomogram.

Results

A total of 3478 patients diagnosed with EPEC were extracted from the SEER database, and the data were randomly divided into the training group (n=2436) and the validation group (n=1402). T stage, N stage, M stage, surgery, chemotherapy, radiotherapy, age, grade, and tumor size were independent risk factors for 1 -, 3 - and 5-year OS of EPEC (P< 0.05), and these factors were used to construct the nomogram prediction mode. The C-index of the validation and training cohorts was 0.718 and 0.739, respectively, which were higher than those of the TNM stage system. The AUC values of the nomogram used to predict 1-, 2-, and 3-year OS were 0.751, 0.744, and 0.786 in the validation cohorts (0.761, 0.777, 0.787 in the training cohorts), respectively. The calibration curve of 1-, 2-, and 3-year OS showed that the prediction of the nomogram was in good agreement with the actual observation. The nomogram exhibited higher clinical utility after evaluation with the 1-, 2-, and 3-year DCA compared with the AJCC stage system.

Conclusions

This study shows that the nomogram prediction model for EPEC based on the SEER database has high accuracy and its prediction performance is significantly better than the TNM staging system, which can accurately and individually predict the OS of patients and help clinicians to formulate more accurate and personalized treatment plans.
EGFR mutations and high PD-L1 expression of lung squamous cell carcinoma patients achieving pCR following neoadjuvant immuno-chemotherapy: Case report
Authors: Xu Xiangyu , Shi Zixia , Fu Dan , Huang Depei , Ma Zheng
Published: October 2022

The treatment of lung cancer has fully entered the era of immunotherapy, which has significantly elevated the survival rate of patients with advanced non-small cell lung cancer (NSCLC), thus shedding light on resectable NSCLC. Previous clinical trial data suggested that neoadjuvant immuno-chemotherapy obtained a significant objective response rate (ORR) and disease control rate (DCR). Here, a case that achieved an excellent outcome following neoadjuvant immuno-chemotherapy was reported. The patient admitted to our hospital was 58 years old, female, with a rare case of stage IB lung squamous cell carcinoma (LUSC) harboring both epidermal growth factor receptor (EGFR) p.L858R mutations and high expression of programmed death ligand-1 (PD-L1) (tumor proportion score (TPS)=80%). Her tumor substantially shrunk following two cycles of neoadjuvant immuno-chemotherapy. The patient successively received single-port right upper thoracoscopic lobectomy + mediastinal lymph node dissection, which attained pathologic complete response (pCR). Additionally, the patient had grade 2 myelosuppression during the two cycles, which was treated with polyethylene glycol recombinant human granulocyte colony-stimulating factor (rhG-CSF). The patient was discharged uneventfully without any procedure-related complications. Two courses of adjuvant immuno-chemotherapy were administered postoperatively, leaving the patient in good physical condition at the 5-month follow-up visit. This case provided evidence for the feasibility and effectiveness of neoadjuvant immuno-chemotherapy in treating early-stage LUSC with EGFR mutations and high expression of PD-L1. However, randomized and multi-center controlled trials are required to validate the findings.
Heterogeneity of glioblastoma stem cells in the context of the immune microenvironment and geospatial organization
Authors: Silver Aryeh , Feier Diana , Ghosh Tanya , Rahman Maryam , Huang Jianping , Sarkisian Matthew R. , Deleyrolle Loic P.
Published: October 2022

Glioblastoma (GBM) is an extremely aggressive and incurable primary brain tumor with a 10-year survival of just 0.71%. Cancer stem cells (CSCs) are thought to seed GBM’s inevitable recurrence by evading standard of care treatment, which combines surgical resection, radiotherapy, and chemotherapy, contributing to this grim prognosis. Effective targeting of CSCs could result in insights into GBM treatment resistance and development of novel treatment paradigms. There is a major ongoing effort to characterize CSCs, understand their interactions with the tumor microenvironment, and identify ways to eliminate them. This review discusses the diversity of CSC lineages present in GBM and how this glioma stem cell (GSC) mosaicism drives global intratumoral heterogeneity constituted by complex and spatially distinct local microenvironments. We review how a tumor’s diverse CSC populations orchestrate and interact with the environment, especially the immune landscape. We also discuss how to map this intricate GBM ecosystem through the lens of metabolism and immunology to find vulnerabilities and new ways to disrupt the equilibrium of the system to achieve improved disease outcome.
The function and clinical implication of circular RNAs in lung cancer
Authors: Ren Wenjun , Yuan Yixiao , Peng Jun , Mutti Luciano , Jiang Xiulin
Published: October 2022

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite the recent advent of promising new targeted therapies, lung cancer diagnostic strategies still have difficulty in identifying the disease at an early stage. Therefore, the characterizations of more sensible and specific cancer biomarkers have become an important goal for clinicians. Circular RNAs are covalently close, endogenous RNAs without 5′ end caps or 3′poly (A) tails and have been characterized by high stability, abundance, and conservation as well as display cell/tissue/developmental stage-specific expressions. Numerous studies have confirmed that circRNAs act as microRNA (miRNA) sponges, RNA-binding protein, and transcriptional regulators; some circRNAs even act as translation templates that participate in multiple pathophysiological processes. Growing evidence have confirmed that circRNAs are involved in the pathogenesis of lung cancers through the regulation of proliferation and invasion, cell cycle, autophagy, apoptosis, stemness, tumor microenvironment, and chemotherapy resistance. Moreover, circRNAs have emerged as potential biomarkers for lung cancer diagnosis and prognosis and targets for developing new treatments. In this review, we will summarize recent progresses in identifying the biogenesis, biological functions, potential mechanisms, and clinical applications of these molecules for lung cancer diagnosis, prognosis, and targeted therapy.
Hyperthermic intraperitoneal chemotherapy following up-front cytoreductive surgery versus cytoreductive surgery alone for isolated synchronous colorectal peritoneal metastases: A retrospective, observational study
Authors: Qin Xiusen , Siyad Mohamed Mohamed , Zhang Yuanxin , Chen Yuefang , Wu Zhijie , Luo Rui , Yi Liang , Wang Hui , Wang Huaiming
Published: October 2022

Background

To date, the value of hyperthermic intraperitoneal chemotherapy (HIPEC) following up-front resection for isolated synchronous colorectal peritoneal metastases seems controversial.

Patients and Methods

This retrospective cohort study was conducted from September 1, 2012, to September 1, 2019, at a tertiary medical center in China. Patients with isolated synchronous colorectal peritoneal metastases were included in CRS plus HIPEC group or CRS alone group based on the treatment history. Overall survival and relapse-free survival were estimated using Cox proportional hazards regression analysis and Kaplan–Meier method.

Results

78 patients with isolated synchronous colorectal peritoneal metastases were identified among 396 patients with synchronous colorectal peritoneal metastases. 43 were in the cytoreductive surgery plus HIPEC group and 35 were in the cytoreductive surgery alone group. Among them, 61 patients had relapse-free survival data. The median peritoneal cancer index was 4 in all patients. After a median follow-up of 46.0 months, 5-year overall survival was 66.8% and the median relapse-free survival was 36.0 (95% CI, 6.8-65.1) months in the CRS plus HIPEC group. 5-year overall survival was 31.2% and the median relapse-free survival was 12.0 (95% CI, 9.0-15.0) months in the CRS alone group. Cox regression analyses showed that HIPEC was the independent prognostic factor for overall survival (P = 0.004) and relapse-free survival (P = 0.049).

Conclusion

Findings of the present study suggest that HIPEC following up-front CRS could improve overall survival and relapse-free survival in patients with isolated synchronous colorectal peritoneal metastases.
Efficacy and safety of stereotactic body radiotherapy for painful bone metastases: Evidence from randomized controlled trials
Authors: Wang Zilan , Li Longyuan , Yang Xingyu , Teng Haiying , Wu Xiaoxiao , Chen Zhouqing , Wang Zhong , Chen Gang
Published: October 2022

Background

Pain relief is one of the main objectives of radiotherapy for cancer patients with bone metastases. Stereotactic body radiotherapy (SBRT) enables precise delivery of a higher dosage to the target area. Several trials have reported comparisons between SBRT and conventional radiotherapy (cRT) in patients with painful bone metastasis. However, the results of those investigations were inconsistent, and no systematic review or meta-analysis has been done till now.

Methods

We systematically searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov up to May 1, 2022 for relevant studies. Patients with painful bone metastasis who received SBRT or cRT were included. The primary outcome was the patients’ pain response rate at three months. The secondary outcomes included the rate of pain responders at one month and six months, oral morphine equivalent dose (OMED) use, and any adverse events. STATA software 12.0 was used for the statistical analysis.

Results

We collected 533 patients’ data from 4 randomized controlled trials (RCTs), there was a significant difference of pain response rate at 3 months between two groups (RR = 1.41, 95% CI: 1.12-1.77, I2 = 0.0%, P = 0.003). However, no significant difference was found in pain response rate at 1 month (RR = 1.19, 95% CI: 0.91-1.54, I2 = 31.5%, P = 0.201) and 6 months (RR = 1.25, 95% CI: 0.93-1.69, I2 = 0.0%, P = 0.140). OMED consumption was not significantly different in patients treated with SBRT compared with control group (WMD = -1.11, 95% CI: -17.51-15.28, I2 = 0.0%, P = 0.894). For safety outcome, no statistical difference was found between SBRT and cRT (RR = 0.72, 95% CI: 0.46-1.14, I2=20.1%, P = 0.162).

Conclusion

This study shows that for painful bone metastases, patients with SBRT experienced better pain relief 3 months after radiation than patients with cRT, and SBRT did not increase the incidence of adverse events.

Systematic review registration

https://inplasy.com/inplasy-2022-6-0099/, identifier INPLASY202260099.
Gonadotropin-releasing hormone agonist protects ovarian function in young patients with ovarian malignancy undergoing platinum-based chemotherapy: A prospective study
Authors: Xie Ya , Duan Haoran , Wang Dong , Li Huiqing , Jia Jia , Zhang Jialin , Li Linlin
Published: October 2022

Purpose

We aimed to ascertain the effectiveness of gonadotropin-releasing hormone (GnRH) agonist co-therapy for the preservation of ovarian function in patients with ovarian malignancy who underwent unilateral salpingo-oophorectomy and platinum-based chemotherapy.

Methods

We enrolled 158 patients with ovarian malignancy who underwent fertility preservation surgery and postoperative platinum-based chemotherapy between January 2018 and December 2020. Patients were divided into two groups based on the use of GnRH agonist (GnRHa) during chemotherapy. Two patients withdrew from the study. Laboratory tests (serum follicle-stimulating hormone [FSH], serum luteinizing hormone [LH], and serum anti-Müllerian hormone [AMH]) were performed pre-chemotherapy and one year post-chemotherapy. Data on menstruation resumption, perimenopausal symptoms (modified Kupperman Menopausal Index [KMI]), health-related quality of life (Medical Outcomes Study Short Form-36 [MOS SF-36]), and obstetric outcomes were collected.

Results

One year post-chemotherapy, the serum AMH level in the GnRHa group was higher than that in the control group (P<0.001), while the serum FSH and FSH/LH levels in the GnRHa group were lower than those in the control group (P<0.001). The mean period from last chemotherapy to menstrual resumption was 3.86 and 5.78 months in the GnRHa and control groups (P<0.001), respectively. The rate of menstrual resumption post-chemotherapy was 93.5% and 82.3% in the GnRHa and control groups (P<0.05), respectively. GnRHa co-administration during chemotherapy reduced the likelihood of low AMH levels post-chemotherapy and was significant in the multivariate analysis (P<0.05). The modified KMI scores and MOS SF-36 scores were better in the GnRHa group than in the control group (both P<0.001).

Conclusion

GnRHa protects ovarian function during platinum-based adjuvant chemotherapy in young patients with ovarian malignancy. This study provides a therapeutic reference for gynecologists, especially for those in economically and medically underdeveloped areas.

Trial registration

Chinese Clinical Trial Registry (chiCTR1800019114; October 26, 2018; http://www.chictr.org.cn/index.aspx)
Outcome analysis of immediate and delayed laparoscopic pyeloplasty in infants with severe ureteropelvic junction obstruction
Authors: Bao Qiao , Ma Weijun , Zhang Xiewu , Chen Shuhan , Luo Jiayao , Zhang Gang , Lao Weihua , Chen Yueqing
Published: October 2022

Objective

The treatment timing of ureteropelvic junction obstruction (UPJO) in infants remains controversial. This study aimed to compare the recovery effect of renal morphology of immediate and delayed laparoscopic pyeloplasty in infants with severe UPJO.

Methods

The infants with severe UPJO-induced hydronephrosis who underwent laparoscopic pyeloplasty according to their age at the time of surgery [the immediate treatment (IT) group: ≤1 month of birth, the delayed treatment (LT) group: 3–6 months of birth] in our center between 2010 and 2019 were enrolled in this study. Ultrasonography was used to assess renal morphology, including anteroposterior diameter (APD) of a pelvic, parenchymal thickness (PT), polar length (PL), and Society of Fetal Urology (SFU) grade. Preoperative and postoperative renal morphological outcomes at 6, 12, and 24 months were measured and compared.

Results

During this period, a total of 135 patients were assigned to receive either IT (n = 73) or LT (n = 62) and were included for analysis. There were no significant differences in renal morphology indices at baseline between groups of IT and LT. The APD, PT, and PL in both groups all recovered to certain degrees compared with those at baseline, however, the IT group recovered more significantly than the LT group. Despite there being no significant difference in SFU grade between the two groups before and after surgery, the reduction of SFU grade in the IT group was more significant than that in the LT group during the 6-, 12- and 24-month follow-up periods. The PL, SFU, and APD were greater in the IT group than in the LT group at 6, 12, and 24 months of follow-up. At 6 months PL was not significantly higher between the two groups, while the outcome was significantly different at 12 months and 24 months.

Conclusion

Immediate laparoscopic pyeloplasty for the infant with severe ureteropelvic junction obstruction is effective, and it can accelerate the recovery of renal morphological indices in infants with severe UPJO-induced hydronephrosis.
Development and external validation of a simple nomogram for predicting apnea in children hospitalized with bronchiolitis
Authors: Xu Qiuyan , Li Linlin , Shen Li , Huang Xia , Lu Min , Hu Chunxia
Published: October 2022

Background

Apnea is one of the most life-threatening complications of bronchiolitis in children. This study aimed to determine early predictors of apnea in children hospitalized with bronchiolitis and develop a simple nomogram to identify patients at risk of apnea.

Methods

This retrospective, observational study included children hospitalized with bronchiolitis in two hospitals in China. Demographic and clinical characteristics, laboratory results, pathogens, and pulmonary iconography results were recorded. A training cohort of 759 patients (one hospital) was used to identify early predictors of apnea during hospitalization. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used to optimize variable selection. The nomogram was developed visually based on the variables selected by multivariable logistic regression analysis. Discrimination (concordance index, C-index), calibration, and decision curve analysis (DCA) were used to assess the model performance and clinical effectiveness.

Results

A total of 1,372 children hospitalized with bronchiolitis were retrospectively evaluated, 133 (9.69%) of whom had apnea. Apnea was observed in 80 of the 759 patients with bronchiolitis in the training cohort and 53 of the 613 patients in the external validation cohort. Underlying diseases, feeding difficulties, tachypnea, retractions and pulmonary atelectasis in the training cohort were independent risk factors for apnea and were assembled into the nomogram. The nomogram exhibited good discrimination with a C-index of 0.883 (95% CI: 0.839–0.927) and good calibration. The DCA showed that the nomogram was clinically useful in estimating the net benefit to patients.

Conclusion

We developed a nomogram that is convenient to use and able to identify the individualized prediction of apnea risk in patients with bronchiolitis. These patients might benefit from early triage and more intensive monitoring.
Self-efficacy of emergency management of domestic helpers in pediatric home accidents: A cross-sectional survey in Hong Kong
Authors: Ho Jonathan Ka-Ming , Chung Jessie Yuk-Seng , Cheung Shu-Nam , Pang Winnie Wing-Yan , Yau Po-Yi , Lam Simon Ching
Published: October 2022

Background

Accidental injuries are the leading cause of deaths and disabilities in children globally and most of them occur at home. To save life and prevent sequelae, domestic helpers (DHs) require providing emergency management (i.e., first aid) to children involved in home accidents. However, their self-efficacy in emergency management for children is rarely investigated. Hence, this study aimed to tap that research gap.

Methods

This study adopted a cross-sectional descriptive survey design. A convenience sample of 385 DHs was obtained in Hong Kong. DHs' self-efficacy in emergency management for children involved in home accidents was measured using a 12-item well-validated survey instrument “Self-Efficacy of First Aid in Unintentional Injury at Home”. The total score ranged from 0 to 48. A higher score indicates greater confidence in emergency management for children involved in home accidents.

Results

All the participants were women and most of them were aged between 31 and 35 years (N = 103, 26.8%). The mean score for DHs' self-efficacy in emergency management was 29.0 (SD 10.1). The three items with the lowest self-efficacy were managing bone fractures, performing cardiopulmonary resuscitation, and providing artificial respiration. Bivariate analysis showed that DHs' self-efficacy was significantly related to their educational level, first aid training, caring experience, and working experience. Multiple linear regression indicated that DHs' educational level (β = 0.136, p = 0.001) and first aid training (β = 0.532, p < 0.001) were significantly predicting their self-efficacy.

Conclusion

DH's self-efficacy of emergency management for children involved in home accidents was low, particularly in those severe situations and complicated first aid procedures.
Identification of target groups and individuals for adherence interventions using tree-based prediction models
Authors: Wendl Johannes , Simon Andreas , Kistler Martin , Hapfelmeier Jana , Schneider Antonius , Hapfelmeier Alexander
Published: October 2022

Background: In chronically ill patients, medication adherence during implementation can be crucial for treatment success and can decrease health costs. In some populations, regression models do not show this relationship. We aim to estimate subgroup-specific and personalized effects to identify target groups for interventions.

Methods: We defined three cohorts of patients with type 1 diabetes (n = 12,713), type 2 diabetes (n = 85,162) and hyperlipidemia (n = 117,485) from German claims data between 2012 and 2015. We estimated the association of adherence during implementation in the first year (proportion of days covered) and mean total costs in the three following years, controlled for sex, age, Charlson’s Comorbidity Index, initial total costs, severity of the disease and surrogates for health behavior. We fitted three different types of models on training data: 1) linear regression models for the overall conditional associations between adherence and costs, 2) model-based trees to identify subgroups of patients with heterogeneous adherence effects, and 3) model-based random forests to estimate personalized adherence effects. To assess the performance of the latter, we conditionally re-estimated the personalized effects using test data, the fixed structure of the forests, and fixed effect estimates of the remaining covariates.

Results: 1) our simple linear regression model estimated a positive adherence effect, that is an increase in total costs of 10.73 Euro per PDC-point and year for diabetes type 1, 3.92 Euro for diabetes type 2 and 1.92 Euro for hyperlipidemia (all p ≤ 0.001). 2) The model-based tree detected subgroups with negative estimated adherence effects for diabetes type 2 (-1.69 Euro, 24.4% of cohort) and hyperlipidemia (-0.11 Euro, 36.1% and -5.50 Euro, 5.3%). 3) Our model-based random forest estimated personalized adherence effects with a significant proportion (4.2%–24.1%) of negative effects (up to -8.31 Euro). The precision of these estimates was high for diabetes type 2 and hyperlipidemia patients.

Discussion: Our approach shows that tree-based models can identify patients with different adherence effects and the precision of personalized effects is measurable. Identified patients can form target groups for adherence-promotion interventions. The method can also be applied to other outcomes such as hospitalization risk to maximize positive health effects of an intervention.
Biofunctional roles of estrogen in coronavirus disease 2019: Beyond a steroid hormone
Authors: Wang Zhong-Ping , Hua Mao , Jiu Tai , Ge Ri-Li , Bai Zhenzhong
Published: October 2022

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), epidemic poses a major global public health threat with more than one million daily new infections and hundreds of deaths. To combat this global pandemic, efficient prevention and management strategies are urgently needed. Together with the main characteristics of COVID-19, impaired coagulation with dysfunctions of the immune response in COVID-19 pathophysiology causes high mortality and morbidity. From recent clinical observations, increased expression of specific types of estrogen appears to protect patients from SARS-CoV-2 infection, thereby, reducing mortality. COVID-19 severity is less common in women than in men, particularly in menopausal women. Furthermore, estrogen levels are negatively correlated with COVID-19 severity and mortality. These findings suggest that estrogen plays a protective role in the pathophysiology of COVID-19. In this review, we discuss the potential roles of estrogen in blocking the SARS-CoV-2 from invading alveolar cells and replicating, and summarize the potential mechanisms of anti-inflammation, immune modulation, reactive oxygen species resistance, anti-thrombosis, vascular dilation, and vascular endothelium protection. Finally, the potential therapeutic effects of estrogen against COVID-19 are reviewed. This review provides insights into the role of estrogen and its use as a potential strategy to reduce the mortality associated with COVID-19, and possibly other viral infections and discusses the possible challenges and pertinent questions.
Current advances on the phytochemical composition, pharmacologic effects, toxicology, and product development of Phyllanthi Fructus
Authors: Yan Xiaoyu , Li Qiuju , Jing Lin , Wu Shuangyue , Duan Wei , Chen Yan , Chen Dayi , Pan Xiaoqi
Published: October 2022

Phyllanthi Fructus (PF), the edible fruits of Phyllanthus emblica L., serves as an important resource for some health products, foods and drugs due to its high safety and sufficient nutritional value. In recent years, in vivo and in vitro experiments have been conducted to reveal the active components of PF. More than 180 compounds have been isolated and identified from the PF so far, primarily including tannins, phenolic acids, flavonoids, terpenoids, polysaccharides, fatty acids and amino acids. In traditional Chinese medicine (TCM), PF is used to cure several diseases such as bronchitis, asthma, diabetes, peptic ulcer, hepatopathy, leprosy, and jaundice. Consistent with ethnopharmacology, numerous modern studies have demonstrated that the extracts or monomeric compounds derived from PF exhibit various pharmacological effects including anti-oxidation, anti-bacteria, anti-inflammation, anti-tumour, anti-virus, immunity improvement, hypoglycemic and hypolipidemic effects, and multiple organ protective protection. Toxicological studies on PF indicated the absence of any adverse effects even at a high dose after oral administration. Due to strict quality control, these pharmacological activities and the safety of PF greatly improve the development and utilization of products. Our comprehensive review aims to summarize the phytochemistry, pharmacological effects, toxicology, and product development of PF to provide theoretical guidance and new insights for further research on PF in the future.
Targeting pancreatic stellate cells in chronic pancreatitis: Focus on therapeutic drugs and natural compounds
Authors: Wu Yang , Zhang Chun , Guo Mei , Hu Weikang , Qiu Yangling , Li Mengran , Xu Dong , Wu Pengfei , Sun Jing , Shi Run , Zhang Zili , Jiang Kuirong
Published: October 2022

Chronic pancreatitis (CP) is a precancerous illness linked to pancreatic ductal adenocarcinoma (PDAC), although the evolutionary mechanism is uncertain. CP is distinguished by severe fibrosis caused by the activation of pancreatic stellate cells (PSCs). The current clinical therapeutic protocol for CP lacks specific therapeutic medicines for the prevention and suppression of inflammation and fibrosis aggravating in CP. More research on specifically targeting PSCs would help facilitate the development of novel therapies for pancreatic fibrosis. Notably, using natural compounds from medicinal plants as new antifibrotic agents has become a focus of recent research and is widely employed as an alternative and complementary approach. Our goal was to shed light on the role of PSCs in the development of CP and provide a focused update on the new potential therapeutic strategies against PSCs in CP models. Future studies can refer to these possible strategies for drug design, bioavailability, pharmacokinetics, and other issues to obtain better clinical outcomes for treating CP.