bluuebunny/crossref_metadata_2025 huggingface dataset:
SHH and Notch regulate SOX9+ progenitors to govern arcuate POMC neurogenesis
Authors: Place Elsie , Manning Elizabeth , Kim Dong Won , Kinjo Arisa , Nakamura Go , Ohyama Kyoji
Published: August 2022

Pro-opiomelanocortin (POMC)-expressing neurons in the hypothalamic arcuate nucleus (ARC) play key roles in feeding and energy homoeostasis, hence their development is of great research interest. As the process of neurogenesis is accompanied by changes in adhesion, polarity, and migration that resemble aspects of epithelial-to-mesenchymal transitions (EMTs), we have characterised the expression and regulation within the prospective ARC of transcription factors with context-dependent abilities to regulate aspects of EMT. Informed by pseudotime meta-analysis of recent scRNA-seq data, we use immunohistochemistry and multiplex in situ hybridisation to show that SOX2, SRY-Box transcription factor 9 (SOX9), PROX1, Islet1 (ISL1), and SOX11 are sequentially expressed over the course of POMC neurogenesis in the embryonic chick. Through pharmacological studies ex vivo, we demonstrate that while inhibiting either sonic hedgehog (SHH) or Notch signalling reduces the number of SOX9+ neural progenitor cells, these treatments lead, respectively, to lesser and greater numbers of differentiating ISL1+/POMC+ neurons. These results are consistent with a model in which SHH promotes the formation of SOX9+ progenitors, and Notch acts to limit their differentiation. Both pathways are also required to maintain normal levels of proliferation and to suppress apoptosis. Together our findings demonstrate that hypothalamic neurogenesis is accompanied by dynamic expression of transcription factors (TFs) that mediate EMTs, and that SHH and Notch signalling converge to regulate hypothalamic cellular homoeostasis.
Cannabinoid type-2 receptors: An emerging target for regulating schizophrenia-relevant brain circuits
Authors: Ferranti Anthony S. , Foster Daniel J.
Published: August 2022

Although the cannabinoid type-2 receptor (CB2) is highly expressed in the immune system, emerging evidence points to CB2 playing a key role in regulating neuronal function in the central nervous system. Recent anatomical studies, combined with electrophysiological studies, indicate that CB2 receptors are expressed in specific dopaminergic and glutamatergic brain circuits that are hyperactive in schizophrenia patients. The ability of CB2 receptors to inhibit dopaminergic and hippocampal circuits, combined with the anti-inflammatory effects of CB2 receptor activation, make this receptor an intriguing target for treating schizophrenia, a disease where novel interventions that move beyond dopamine receptor antagonists are desperately needed. The development of new CB2-related pharmacological and genetic tools, including the first small molecule positive allosteric modulator of CB2 receptors, has greatly advanced our understanding of this receptor. While more work is needed to further elucidate the translational value of selectively targeting CB2 receptors with respect to schizophrenia, the studies discussed below could suggest that CB2 receptors are anatomically located in schizophrenia-relevant circuits, where the physiological consequence of CB2 receptor activation could correct circuit-based deficits commonly associated with positive and cognitive deficits.
Mediating effects of sleep duration on the association between natural menopause and stroke risk among Chinese women
Authors: Liu Xingyue , Zhang Juhua , Peng Shuzhi , Pei Mengyun , Dai Chunying , Wang Tingting , Zhang Peng
Published: August 2022

Background

Sleep disturbance is commonly reported by menopausal women. Stroke risk and poor stroke outcomes in women have usually been attributed to menopause. This study aimed to investigate the mediating effect of sleep duration on relationship between menopause and risk of stroke in natural menopause women.

Materials and methods

A cross-sectional study was performed, and participants were recruited through a multistage, stratified, probability proportional to size sampling method in this research. The stroke risk was measured using the risk assessment form for high-risk stroke population. The average sleep duration was calculated by adding up night sleep and afternoon nap duration. Multivariate regression analysis was conducted to identify the association between menopause, sleep duration, and stroke risk. The direct and indirect effects of menopause on stroke risk were analyzed by using the sleep duration in a mediation framework.

Results

Perimenopause, menopause, average sleep duration, and night sleep duration were significantly associated with stroke risk (P < 0.001), after adjusting for covariates. Perimenopause and menopause were significantly related to average sleep duration (P < 0.001) and night sleep duration (P < 0.001). The average sleep duration (ab = 0.016, 95% CI: 0.003, 0.030; ab = −0.048, 95% CI: −0.070, −0.027) partially mediated the relationship between menopause and stroke risk. And night sleep duration (ab = 0.024, 95% CI: 0.009, 0.040; ab = −0.054, 95% CI: −0.077, −0.033) played a major mediating role, in which night sleep duration of ≤5 h mediated the link between both perimenopause (ab = 0.707, 95% CI: 0.392, 1.021) and menopause (ab = −0.787, 95% CI: −1.096, −0.478) and stroke risk; both night sleep duration of >8–9 h (ab = 0.079, 95% CI: 0.010, 0.193) and >9 h (ab = 0.379, 95% CI: 0.086, 0.712) had mediating effects on perimenopause and stroke risk.

Conclusion

A significant relationship between menopause and stroke risk factors among natural menopausal status was found in this study. The average sleep duration, especially night sleep duration, partially mediated the association between menopause and stroke risk, which is a novel insight to the progression of stroke risk in Women. Suitable prevention methods and interventions for sleep in menopausal women may reduce the risk of stroke.
Synaptic spinules are reliable indicators of excitatory presynaptic bouton size and strength and are ubiquitous components of excitatory synapses in CA1 hippocampus
Authors: Gore Ashley , Yurina Amaliya , Yukevich-Mussomeli Anastasia , Nahmani Marc
Published: August 2022

Synaptic spinules are thin, finger-like projections from one neuron that become embedded within the presynaptic or postsynaptic compartments of another neuron. While spinules are conserved features of synapses across the animal kingdom, their specific function(s) remain unknown. Recent focused ion beam scanning electron microscopy (FIB-SEM) image volume analyses have demonstrated that spinules are embedded within ∼25% of excitatory boutons in primary visual cortex, yet the diversity of spinule sizes, origins, and ultrastructural relationships to their boutons remained unclear. To begin to uncover the function of synaptic spinules, we sought to determine the abundance, origins, and 3D ultrastructure of spinules within excitatory presynaptic spinule-bearing boutons (SBBs) in mammalian CA1 hippocampus and compare them with presynaptic boutons bereft of spinules (non-SBBs). Accordingly, we performed a comprehensive 3D analysis of every excitatory presynaptic bouton, their embedded spinules, and postsynaptic densities, within a 5 nm isotropic FIB-SEM image volume from CA1 hippocampus of an adult male rat. Surprisingly, we found that ∼74% of excitatory presynaptic boutons in this volume contained at least one spinule, suggesting they are fundamental components of excitatory synapses in CA1. In addition, we found that SBBs are 2.5-times larger and have 60% larger postsynaptic densities (PSDs) than non-SBBs. Moreover, synaptic spinules within SBBs are clearly differentiated into two groups: small clathrin-coated spinules, and 29-times larger spinules without clathrin. Together, these findings suggest that the presence of a spinule is a marker for stronger and more stable presynaptic boutons in CA1, and that synaptic spinules serve at least two separable and distinct functions.
The health effects of soy: A reference guide for health professionals
Authors: Messina Mark , Duncan Alison , Messina Virginia , Lynch Heidi , Kiel Jessica , Erdman John W.
Published: August 2022

Soy is a hotly debated and widely discussed topic in the field of nutrition. However, health practitioners may be ill-equipped to counsel clients and patients about the use of soyfoods because of the enormous, and often contradictory, amount of research that has been published over the past 30 years. As interest in plant-based diets increases, there will be increased pressure for practitioners to gain a working knowledge of this area. The purpose of this review is to provide concise literature summaries (400–500 words) along with a short perspective on the current state of knowledge of a wide range of topics related to soy, from the cholesterol-lowering effects of soy protein to the impact of isoflavones on breast cancer risk. In addition to the literature summaries, general background information on soyfoods, soy protein, and isoflavones is provided. This analysis can serve as a tool for health professionals to be used when discussing soyfoods with their clients and patients.
Anthropometric indices and cut-off points for screening of metabolic syndrome among South African taxi drivers
Authors: Sekgala Machoene Derrick , Opperman Maretha , Mpahleni Buhle , Mchiza Zandile June-Rose
Published: August 2022

Background

Detecting the early onset of metabolic syndrome (MetS) allows for quick intervention which may slow progression to a variety of health consequences, hence, determining the best measurement to detect MetS is essential.

Aim

This research aimed at examining the MetS predictive power of anthropometric indices, such as body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), body shape index (ABSI), body roundness index (BRI), percentage body fat (%BF), conicity index (CI), and Clínica Universidad de Navarra-body adiposity estimator (CUN-BAE) to determine the cut-off points to identify male South African taxi drivers with MetS.

Method

A cross-sectional study was conducted among 185 male taxi drivers. Their weight, height, WC, blood lipid profile were measured. International Diabetes Federation (IDF) definition was used to define MetS. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of Anthropometric indices to detect MetS.

Results

The mean age of the participants was 39.84 years. Overall, 41.6% (N = 77) of the participants presented with MetS. The mean values for BMI, WC, WHtR, %BF, BRI, CUN-BAE, ABSI and CI were 28.60 ± 6.20 kg/m2, 99.13 ± 17.59 cm, 0.58 ± 0.10, 27.28 ± 8.28%, 5.09 ± 2.33, 27.78 ± 8.34, 0.08 ± 0.01 and 1.70 ± 0.19, respectively. The mean values for these indices were significantly (p < 0.001) higher in participants with MetS. The highest area under the curve (AUC) outcomes for screening MetS were for the %BF and CUN-BAE, followed by the BMI and WHtR, and lastly the BRI. All these anthropometric indices had outstanding discriminatory powers for predicting MetS with AUCs and sensitivity values above 80%. The BMI, WHtR, %BF, BRI, and CUN-BAE, had cut-off points for detection of metS in South African men at 28.25 kg/m2, 0.55, 25.29%, 4.55, and 27.10, respectively. Based on the logistic regression models abnormal BMI, WHtR, %BF, BRI, CUN-BAE, TG, FBG, systolic BP, diastolic BP and WC showed increased risk of MetS.

Conclusion

While the %BF, CUN-BAE, BMI, WC, WHtR, BRI, CI and CUN-BAE could predict MetS among South African male taxi drivers, these indices were less effective in predicting the individual MetS risk factors such as TG, BP, and FBG.
The cardiometabolic profile and related dietary intake of Ugandans living with HIV and AIDS
Authors: Kiyimba Tonny , Kigozi Fred , Yiga Peter , Mukasa Barbara , Ogwok Patrick , Van der Schueren Bart , Matthys Christophe
Published: August 2022

Introduction

Suboptimal diet and physical inactivity downgrade the putative benefits of Antiretroviral Therapy (ART) among People Living with HIV (PLWH). However, there is paucity of literature on dietary intake and cardiometabolic profiles of PLWH in Uganda.

Methods

A cross-sectional study among PLWH in Uganda was conducted. Dietary intake was assessed using a 24h recall method of 2 non-consecutive days. The short International Physical Activity Questionnaire assessed participants' physical activity. Fasted blood samples were analyzed for Fasting Blood Glucose (FBG), total cholesterol, LDL-c, HDL-c and triglycerides. Blood pressure and anthropometric measurements were performed following step 2 of the WHO STEPS.

Results

253 patients completed in this study. A high prevalence of low HDL-c (31.9%), abdominal obesity (44.5%), high BMI (51.6%), raised FBG (45.3%), high SBP (31.5%), elevated triglycerides (26.4%) and metabolic syndrome (28%) was found. More women were identified with metabolic syndrome (31.5%) than men (19.2%). Low prevalence of high LDL-c (4.7%) and total cholesterol (9.8%) was found. Diets had a high carbohydrate (65.8 ± 10.4) E% and fiber intake (30.1 ± 12.7) g with minimal PUFA (6.1 ± 2.3) E%, fruits and vegetables (1.4 servings). High proportions were found of unmet intake for vitamin A (38.2%), B1(48.8%), B2 (29.6%), B12 (29%), folate (61.4%), Ca (76%), Zn (53.1%) and Mg (41.7%). Mean MET min was 6,700 ± 5,509 and over 68% of the participants had >3,000 MET min.

Conclusion

Our findings reveal a high prevalence of metabolic disturbances among PLWH in Uganda and further highlight that their diets are suboptimal with low fruits and vegetable intake
Salvia chinensis Benth Inhibits Triple-Negative Breast Cancer Progression by Inducing the DNA Damage Pathway
Authors: Wang Kai-nan , Hu Ye , Han Lin-lin , Zhao Shan-shan , Song Chen , Sun Si-wen , Lv Hui-yun , Jiang Ni-na , Xv Ling-zhi , Zhao Zuo-wei , Li Man
Published: August 2022

Objective

Triple-negative breast cancer (TNBC) is distinguished by early recurrence and metastases, a high proclivity for treatment resistance, and a lack of targeted medicines, highlighting the importance of developing innovative therapeutic techniques. Salvia chinensis Benth (SCH) has been widely studied for its anticancer properties in a variety of cancers. However, its significance in TNBC treatment is rarely discussed. Our study investigated the anticancer effect of SCH on TNBC and the underlying mechanisms.

Methods

First, we used clonogenic, cell viability, flow cytometry, and Transwell assays to assess the effect of SCH on TNBC. Bioinformatic studies, especially network pharmacology-based analysis and RNA sequencing analysis, were performed to investigate the constituents of SCH and its molecular mechanisms in the suppression of TNBC. High-performance liquid chromatography and thin-layer chromatography were used to identify two major components, quercetin and β-sitosterol. Then, we discovered the synergistic cytotoxicity of quercetin and β-sitosterol and assessed their synergistic prevention of cell migration and invasion. Breast cancer xenografts were also created using MDA-MB-231 cells to test the synergistic therapeutic impact of quercetin and β-sitosterol on TNBC in vivo. The impact on the DNA damage and repair pathways was investigated using the comet assay and Western blot analysis.

Results

Our findings showed that SCH decreased TNBC cell growth, migration, and invasion while also inducing cell death. We identified quercetin and β-sitosterol as the core active components of SCH based on a network pharmacology study. According to RNA sequencing research, the p53 signaling pathway is also regarded as a critical biological mechanism of SCH treatment. The comet assay consistently showed that SCH significantly increased DNA damage in TNBC cells. Our in vivo and in vitro data revealed that the combination of quercetin and β-sitosterol induced synergistic cytotoxicity and DNA damage in TNBC cells. In particular, SCH particularly blocked the inter-strand cross-link repair mechanism and the double-strand breach repair caused by the homologous recombination pathway, in addition to inducing DNA damage. Treatment with quercetin and β-sitosterol produced similar outcomes.

Conclusion

The current study provides novel insight into the previously unknown therapeutic potential of SCH as a DNA-damaging agent in TNBC.
Case report: Salvage capmatinib therapy in KIF5B-MET fusion-positive lung adenocarcinoma with resistance to telisotuzumab vedotin
Authors: Lin Chien-Yu , Wei Sheng-Huan , Chen Yi-Lin , Lee Chung-Ta , Wu Shang-Yin , Ho Chung-Liang , Pavlick Dean C. , Su Po-Lan , Lin Chien-Chung
Published: August 2022

Telisotuzumab vedotin is a MET-targeting antibody–drug conjugate that has demonstrated a good treatment response in patients with EGFR wild-type MET-overexpressing non-squamous non-small cell lung cancer. However, patients have been reported to acquire resistance to this drug, and the subsequent therapy has not been standardized. Here, we present a case of a 56-year-old woman diagnosed with KIF5B-MET fusion-positive non-small cell lung cancer who had a durable response to capmatinib after acquired resistance to telisotuzumab vedotin.
The role of fascin-1 in the pathogenesis, diagnosis and management of respiratory related cancers
Authors: Zhang Naibin , Gao Yankun , Bian Qiang , Wang Qianqian , Shi Ying , Zhao Zhankui , Yu Honglian
Published: August 2022

Human cancer statistics report that respiratory related cancers such as lung, laryngeal, oral and nasopharyngeal cancers account for a large proportion of tumors, and tumor metastasis remains the major reason for patient death. The metastasis of tumor cells requires actin cytoskeleton remodeling, in which fascin-1 plays an important role. Fascin-1 can cross-link F-actin microfilaments into bundles and form finger-like cell protrusions. Some studies have shown that fascin-1 is overexpressed in human tumors and is associated with tumor growth, migration and invasion. The role of fascin-1 in respiratory related cancers is not very clear. The main purpose of this study was to provide an updated literature review on the role of fascin-1 in the pathogenesis, diagnosis and management of respiratory related cancers. These studies suggested that fascin-1 can serve as an emerging biomarker and potential therapeutic target, and has attracted widespread attention.
Survival, treatment pattern, and treatment outcome in patients with cervical cancer metastatic to distant lymph nodes
Authors: Lin Haoliang , Wang Dongyan , Li Hui , Wu Chuling , Zhang Fengqian , Lin Zhongqiu , Yao Tingting
Published: August 2022

Background

Cervical cancer with nodal involvement beyond the pelvis was considered as distant nodal metastasis in the previous International Federation of Gynecology and Obstetrics staging system. With the improvement of cancer-directed therapies, some of these patients can receive curative treatment. Classifying them as distant metastasis may result in underestimation of their prognosis as well as undertreatment. However, limited research has been conducted on the survival and treatment pattern in distant lymphatic metastatic cervical cancer.

Objective

To investigate the survival, treatment pattern, and treatment outcome of patients with cervical cancer metastasized to distant lymph nodes (DLN) beyond the pelvis.

Methods

Patients with stage III-IV cervical cancer from 1988 to 2016 were identified using the Surveillance, Epidemiology, and End Results program. The cancer cause-specific survival (CSS) was analyzed using the Kaplan-Meier method, log-rank test, multivariable Cox proportional hazard regression, subgroup analysis, and propensity score-matched analysis.

Results

Of 17783 patients with stage III-IV cervical cancer, patients with distant nodal disease beyond the pelvis (n=1883; included para-aortic lymph nodes metastasis) had superior survival compared to those with pelvic organ invasion or with distant organ(s) metastasis (5-year CSS, 32.3%, 26.3%, and 11.5%, respectively; adjusted P<0.001). The T stage significantly affected the survival of patients with positive DLN (5-year CSS for T1, T2, and T3: 47.3%, 37.0%, and 19.8%, respectively, adjusted P<0.01). For patients with positive DLN, combination radiotherapy (external beam radiotherapy [EBRT] with brachytherapy) prolonged CSS compared to EBRT alone (5-year CSS, 38.0% vs 21.7%; propensity score-adjusted HR, 0.60; 95% CI 0.51-0.72; P<0.001). Despite the superiority of combination radiotherapy, EBRT was the most frequently used treatment after 2004 (483/1214, 39.8%), while the utilization of combination radiotherapy declined from 37.8% (253/669) during 1988 through 2003 to 25.2% (306/1214) during 2004 through 2016.

Conclusion

Patients with cervical cancer metastasized to DLN have favorable survival compared to those with pelvic organ invasion or with distant organ(s) metastasis. Their prognosis is significantly affected by local tumor burden and local treatment. Adequate and aggressive local radiotherapy, such as image-guided brachytherapy, can be considered for these patients to achieve better outcomes.
Microwave ablation with local pleural anesthesia for subpleural pulmonary nodules: our experience
Authors: Meng Liangliang , Wu Bin , Zhang Xiao , Zhang Xiaobo , Wei Yingtian , Xue Xiaodong , Zhang Zhongliang , Zhang Xin , Li Jing , He Xiaofeng , Ma Li , Xiao Yueyong
Published: August 2022

Objectives

To explore the efficacy and safety of local pleural anesthesia (LPA) for relieving pain during microwave ablation (MWA) of pulmonary nodules in the subpleural regions.

Materials and Methods

From June 2019 to December 2021, 88 patients with 97 subpleural nodules underwent percutaneous CT-guided MWA. Patients were divided into two groups according to whether LPA was applied; 53 patients with local pleural anesthesia during MWA; and 35 patients with MWA without LPA. The differences in technical success, pre-and post- and intra-operative visual analog scale (VAS) pain scores, complications of the procedure, and local progression-free survival (LPFS) between the two groups were assessed. Thus, to evaluate the efficacy and safety of MWA combined with LPA for treating subpleural nodules.

Results

In this study, the procedures in all patients of both groups achieved technical success according to pre-operative planning. There was no statistically significant difference in the pre-operative VAS pain scores between the two groups. Intra-operative VAS scores were significantly higher in the non-LPA (NLPA) group than in the LPA group. They remained significantly higher in the NLPA group than in the LPA group during the short postoperative period. Analgesics were used more in the NLPA group than in the LPA group intra- and postoperatively, with a statistically significant difference, especially during the MWA procedures. The overall LPFS rates were 100%, 98.333%, 98.333%, and 98.333% at 1, 3, 6, and 12 months postoperatively in the LPA group and 100%, 97.297%, 94.595%, and 94.595% postoperatively in the NLPA group, respectively. Tumor recurrence occurred in one and two patients with lung adenocarcinoma in the LPA and NLPA groups. The incidence of pneumothorax was significantly higher in the NLPA group (25,714%, 9/35) than in the LPA group (15.094%, 8/53), and there were three cases of pleural effusion (blood collection) and one case of pulmonary hemorrhage in the NLPA group.

Conclusion

Percutaneous CT-guided MWA is a safe and effective treatment for subpleural pulmonary nodules. Applying a combined LPA technique can reduce the patient’s pain and complications during and after the MWA. The long-term efficacy must be verified in more patients and a longer follow-up.
Are infections in children with juvenile idiopathic arthritis more frequent than in healthy children? A prospective multicenter observational study
Authors: Udaondo Clara , Núñez Cuadros Esmeralda , Murias Sara , Remesal Agustin , Alcobendas Rosa , Guerrero Concepción , Guillen-Martin Sara , Escuredo Marta , Aleo Esther , Alonso Daniel , Tagarro Alfredo , De Santiago Eloisa , Camacho-Lovillo Marisol , Diaz Fatima , Arenas Dolores , Camacho Pilar , Lirola Maria Jose , Díaz Almirón Mariana , Calvo Cristina
Published: August 2022

Background

Children with juvenile idiopathic arthritis (JIA) might be at a higher risk of infection. Our objectives are to describe and compare infection rates in patients with JIA vs. healthy patients.

Methods

A prospective, multicenter observational study was performed in Spain from January 2017 to June 2019. Patients with JIA from 7 participating hospitals and children without JIA (siblings of patients with JIA, and non-JIA children from primary health centers) were followed up with quarterly questionnaires to record infection episodes. Tuberculosis, herpes zoster, and infections requiring hospital admission were considered severe infections. Rates of infection (episodes/patient/year) were compared using a generalized estimating equations model.

Results

A total of 371 children (181 with and 190 without JIA) were included. The median age was 8.8 years (IQR 5.5–11.3); 75% of the patients with JIA received immunosuppressive treatment (24% methotrexate, 22% biologic, 26% both). A total of 667 infections were recorded; 15 (2.2%) were considered severe. The infection rate was 1.31 (95%CI 1.1–1.5) in JIA and 1.12 (95%CI 0.9–1.3) in non-JIA participants (p = 0.19). Age <4 years increased the infection rate by 2.5 times (2.72 vs. 1.12, p < 0.001) in both groups. The most frequent infection sites were upper respiratory (62.6% vs. 74.5%) and gastrointestinal (18.8% vs. 11.4%). There were no differences in severe infections (2.5% vs. 2%, p = 0.65) between the groups. In children with JIA, younger age and higher disease activity (JADAS71) were associated with a higher infection rate.

Conclusion

We found no differences in the infection rate or infection severity between patients with and without JIA. Most infections were mild. An age younger than 4 years increased the infection risk in both groups. Higher disease activity was associated with a higher infection rate.
Antenatal urolithiasis: A case report
Authors: Bose Sumona , Iyengar Arpana , Shubha Attibele Mahadevaiah
Published: August 2022

Introduction

Although pediatric urolithiasis is an established entity, its antenatal diagnosis is rare. We hereby report a case detected at 20 weeks gestation and discuss the etiopathogenesis, predisposition, and surveillance following intervention.

Case report

A 2-year-old girl with left renal pelvic calculus detected antenatally at 20 weeks was evaluated. Left hydronephrosis, obstructive pelvic calculus with a decrease in differential renal function on ethylene dicysteine (EC) renogram was confirmed. The metabolic workup was normal. Following stone extraction by left pyelolithotomy, a left ureteropelvic junction obstruction secondary to a mucosal valve was apparent which was excised and left pyeloplasty was done. Stone analysis revealed 100% cystine. Differential renal function and drainage improved post-surgery. The child, however, did not have a follow-up in the interim and presented with a recurrent stone one and a half years later.

Conclusion

Knowledge of antenatal urolithiasis ensures continued follow-up, evaluation for metabolic disorders, and associated structural defects, especially with increasing stone size and increasing hydronephrosis. This helps in timely intervention and continued surveillance.
A machine learning-based risk warning platform for potentially inappropriate prescriptions for elderly patients with cardiovascular disease
Authors: Xingwei Wu , Huan Chang , Mengting Li , Lv Qin , Jiaying Zhang , Enwu Long , Jiuqun Zhu , Rongsheng Tong
Published: August 2022

Potentially inappropriate prescribing (PIP), including potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs), is a major risk factor for adverse drug reactions (ADRs). Establishing a risk warning model for PIP to screen high-risk patients and implementing targeted interventions would significantly reduce the occurrence of PIP and adverse drug events. Elderly patients with cardiovascular disease hospitalized at the Sichuan Provincial People’s Hospital were included in the study. Information about PIP, PIM, and PPO was obtained by reviewing patient prescriptions according to the STOPP/START criteria (2nd edition). Data were divided into a training set and test set at a ratio of 8:2. Five sampling methods, three feature screening methods, and eighteen machine learning algorithms were used to handle data and establish risk warning models. A 10-fold cross-validation method was employed for internal validation in the training set, and the bootstrap method was used for external validation in the test set. The performances were assessed by area under the receiver operating characteristic curve (AUC), and the risk warning platform was developed based on the best models. The contributions of features were interpreted using SHapley Additive ExPlanation (SHAP). A total of 404 patients were included in the study (318 [78.7%] with PIP; 112 [27.7%] with PIM; and 273 [67.6%] with PPO). After data sampling and feature selection, 15 datasets were obtained and 270 risk warning models were built based on them to predict PIP, PPO, and PIM, respectively. External validation showed that the AUCs of the best model for PIP, PPO, and PIM were 0.8341, 0.7007, and 0.7061, respectively. The results suggested that angina, number of medications, number of diseases, and age were the key factors in the PIP risk warning model. The risk warning platform was established to predict PIP, PIM, and PPO, which has acceptable accuracy, prediction performance, and potential clinical application perspective.
Exploration of beta-arrestin isoform signaling pathways in delta opioid receptor agonist-induced convulsions
Authors: Blaine Arryn T. , Miao Yiming , Yuan Jinling , Palant Sophia , Liu Rebecca J. , Zhang Zhong-Yin , van Rijn Richard. M.
Published: August 2022

The δ-opioid receptor (δOR) has been considered as a therapeutic target in multiple neurological and neuropsychiatric disorders particularly as δOR agonists are deemed safer alternatives relative to the more abuse-liable µ-opioid receptor drugs. Clinical development of δOR agonists, however, has been challenging in part due to the seizure-inducing effects of certain δOR agonists. Especially agonists that resemble the δOR-selective agonist SNC80 have well-established convulsive activity. Close inspection suggests that many of those seizurogenic δOR agonists efficaciously recruit β-arrestin, yet surprisingly, SNC80 displays enhanced seizure activity in β-arrestin 1 knockout mice. This finding led us to hypothesize that perhaps β-arrestin 1 is protective against, whereas β-arrestin 2 is detrimental for δOR-agonist-induced seizures. To investigate our hypothesis, we characterized three different δOR agonists (SNC80, ADL5859, ARM390) in cellular assays and in vivo in wild-type and β-arrestin 1 and β-arrestin 2 knockout mice for seizure activity. We also investigated downstream kinases associated with β-arrestin-dependent signal transduction. We discovered that δOR agonist-induced seizure activity strongly and positively correlates with β-arrestin 2 efficacy for the agonist, but that indirect inhibition of ERK activation using the MEK inhibitor SL327 did not inhibit seizure potency and duration. Inhibition of the PI3K/AKT/mTOR signaling with honokiol but not PQR530, attenuated SNC80 seizure duration in β-arrestin 1 knockout, but honokiol did not reduce SNC80-induced seizures in wild-type mice. Ultimately, our results indicate that β-arrestin 2 is correlated with δOR agonist-induced seizure intensity, but that global β-arrestin 1 knockout mice are a poor model system to investigate their mechanism of action.
Herbal medicine used in the treatment of cardiovascular diseases in the Rif, North of Morocco
Authors: Chaachouay Noureddine , Azeroual Abdelhamid , Bencharki Bouchaib , Zidane Lahcen
Published: August 2022

Background:Since the dawn of time, Moroccans have used medicinal plants as a popular remedy to treat a wide range of human and cattle health issues. Nonetheless, very little research has been conducted in the past to record and disseminate indigenous ethnopharmacological knowledge adequately. This study was conducted in the Rif and attempted to identify medicinal plants used by indigenous people to treat cardiovascular problems and the ethnomedicinal knowledge linked with them.

Methods:The ethnobotanical study was carried out in the Moroccan Rif area over 2 years, from 2016 to 2018. We questioned 520 traditional herbalists and consumers of these herbs in total. The gathered data were examined and contrasted using quantitative ethnobotanical indicators such as family importance value (FIV), the relative frequency of citation (RFC), plant part value (PPV), fidelity level (FL), and informant consensus factor (ICF).

Results:The findings analysis revealed the presence of 33 plant species classified into 20 families, with the Poaceae dominating (7 species). Regarding disorders treated, the category of cardiac arrhythmias has the greatest ICF (0.98). The study discovered that the leaves were the most often utilized portion of the plants (PPV = 0.353) and that the most frequently used preparation was a decoction (31%).

Conclusions:The current study’s findings revealed the presence of indigenous ethnomedicinal knowledge of medicinal plants in the Moroccan Rif to treat cardiovascular illnesses. Further phytochemical, pharmacological, and toxicological investigations should be conducted to identify novel drugs from these documented medicinal plants.
A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma
Authors: Lv Wenchang , Zhan YuanYuan , Tan Yufang , Wu Yiping , Chen Hongbo
Published: August 2022

Background: Melanoma is the most lethal, and one of the most aggressive forms of cutaneous malignancies, which poor response to treatment has always puzzled clinicians. As is known to all, aging and immune microenvironment are two crucial factors impacting melanoma biological progress through the tumor microenvironment (TME). However, reliable biomarkers for predicting melanoma prognosis based on aging and immune microenvironment and therapeutic efficacy of immune checkpoints remain to be determined.

Methods: The aging-related genes (ARGs) were obtained from the Human Ageing Genomic Resources and immune-related genes (IRGs) were downloaded from the Immunology database as well as Analysis Portal (ImmPort) database. Next, we initially performed LASSO regression and multivariate Cox regression to identify prognostic ARGs and IRGs in the TCGA and GSE65904 datasets, and firstly constructed a novel comprehensive index of aging and immune (CIAI) signature. Finally, in vitro molecular biology experiments were performed to assess the regulatory role of CNTFR in melanoma cell lines proliferation and migration, macrophage recruitment, and M2 polarization.

Results: This novel CIAI signature consisted of 7 genes, including FOXM1, TP63, ARNTL, KIR2DL4, CCL8, SEMA6A, and CNTFR, in which melanoma patients in the high-CIAI group had shorter OS, DSS, and PFI, indicating CIAI model served as an independent prognostic index. Moreover, we found the CIAI score was potentially correlated with immune scores, estimate score, immune cell infiltration level, tumor microenvironment, immunotherapy effect, and drug sensitivity. Finally, CNTFR might function as oncogenes in melanoma cell lines and the silencing of CNTFR reduced macrophage recruitment and M2 polarization.

Conclusion: In this study, we have first presented a novel prognostic CIAI model applied to assess immune checkpoint therapy and the efficacy of conventional chemotherapy agents in melanoma patients. Thus providing a new insight for combating melanoma.
Reimbursed medication adherence enhancing interventions in 12 european countries: Current state of the art and future challenges
Authors: Kardas Przemysław , Bago Martina , Barnestein-Fonseca Pilar , Garuolienė Kristina , Granas Anne Gerd , Gregório João , Hadžiabdić Maja Ortner , Kostalova Barbora , Leiva-Fernández Francisca , Lewek Pawel , Mala-Ladova Katerina , Schneider Marie Paule , van Boven Job F. M. , Volmer Daisy , Ziampara Ioli , Ágh Tamás
Published: August 2022

Background: Medication non-adherence jeopardises the effectiveness of chronic therapies and negatively affects financial sustainability of healthcare systems. Available medication adherence-enhancing interventions (MAEIs) are utilised infrequently, and even more rarely reimbursed. The aim of this paper was to review reimbursed MAEIs across selected European countries.

Methods: Data on reimbursed MAEIs were collected from European countries at the ENABLE Cost Action expert meeting in September 2021. The identified MAEIs were analysed and clustered according to their characteristics, direct vs. indirect relation to adherence, and the targeted adherence phase.

Results: Out of 12 contributing countries, 10 reported reimbursed MAEIs, 28 in total, of which 20 were identified as MAEIs targeting adherence directly. Reimbursed MAEIs were most often performed by either doctors (n = 6), nurses (n = 6), or pharmacists (n = 3). The most common types of MAEIs were education (n = 6), medication regimen management (n = 5), and adherence monitoring feedback (n = 4). Only seven reimbursed MAEIs were technology-mediated, whereas 11 addressed two interlinked phases of medication adherence, i.e., implementation and persistence.

Conclusion: Our review highlights the scarcity of reimbursed MAEIs across the selected European countries, and calls for their more frequent use and reimbursement.
Potential protective benefits of Schisandrin B against severe acute hepatitis in children during the COVID-19 pandemic based on a network pharmacology analysis
Authors: Fang Yanhua , Zhang Lingling , Wang Zhe , Wang Ruoyu , Liang Shanshan
Published: August 2022

Aims: Reports of hepatitis in children during the coronavirus disease 2019 (COVID-19) pandemic garnered worldwide attention. The most probable culprits are adenovirus and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). At present, the optimal symptomatic treatment consists of a combination of anti-COVID-19 and hepatitis symptom alleviators. Schisandrin B (SchB) has been known to have liver-protective properties for a long time, whereas anti-COVID-19 properties only recently have been discovered. In the case of COVID-19 with hepatitis of unknown origin, we used network pharmacology to explore the symptomatic therapy and protective effects of SchB.

Main methods: The most probable protein targets of SchB were predicted in the SwissTargetPrediction database. The GeneCards, National Center for Biotechnology Information, and Online Mendelian Inheritance in Man databases were used to compile information on the diseases hepatitis, adenovirus, and SARS-CoV-2. Following the use of a Venn diagram viewer to identify intersection genes, we constructed a protein–protein interaction network and identified the core genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment, as well as molecular docking, were employed to highlight the mechanisms of SchB on hepatitis.

Key findings: SchB contains 27 targets on adenovirus_hepatitis and 16 targets on SARS-CoV-2_hepatitis, with 12 shared genes. Both target populations clustered in viral infection and cancer pathways, as well as in processes such as kinase activity phosphatase, cell adhesion, and ATPase binding. These genes might be closely related to liver damage and membrane binding from adenovirus or SARS-CoV-2 infections. In addition, epidermal growth factor receptor, HSP90AA1, and MAPK1 were among the top five targets of both SchB SARS-CoV-2 hepatitis and SchB adenovirus hepatitis.

Significance: SchB may target common protective targets and mechanisms against acute hepatitis caused by adenovirus or by SARS-CoV-2 in children during the COVID-19 pandemic. These findings indicate SchB’s potential as a treatment for hepatitis of unknown origin.
Alleviating effect of quercetin on cadmium-induced oxidative damage and apoptosis by activating the Nrf2-keap1 pathway in BRL-3A cells
Authors: Wang Jicang , Wang Ke , Ding Lulu , Zhao Pengli , Zhang Cai , Wang Hongwei , Yang Zijun , Liu Zongping
Published: August 2022

Cadmium (Cd) is a toxic heavy metal extensively used in industrial and agricultural production. Among the main mechanisms of Cd-induced liver damage is oxidative stress. Quercetin (QE) is a natural antioxidant. Herein, the protective effect of QE on Cd-induced hepatocyte injury was investigated. BRL-3A cells were treated with 12.5 μmol/L CdCl2 and/or 5 μmol/L QE for 24 h. The cells and medium supernatant were collected, and the ALT, AST, and LDH contents of the medium supernatant were detected. The activities or contents of SOD, CAT, GSH, and MDA in cells were determined. Intracellular ROS levels were examined by flow cytometry. Apoptosis rate and mitochondrial-membrane potential (ΔΨm) were detected by Hoechst 33,258 and JC-1 methods, respectively. The mRNA and protein expression levels of Nrf2, NQO1, Keap1, CytC, caspase-9, caspase-3, Bax, and Bcl-2 were determined by real-time PCR (RT-PCR) and Western blot methods. Results showed that Cd exposure injured BRL-3A cells, the activity of antioxidant enzymes decreased and the cell ROS level increased, whereas the ΔΨm decreased, and the expression of apoptotic genes increased. Cd inhibited the Nrf2-Keap1 pathway, decreased Nrf2 and NQO1, or increased Keap1 mRNA and protein expression. Through the combined action of Cd and QE, QE activated the Nrf2-Keap1 pathway. Consequently, antioxidant-enzyme activity decreased, cellular ROS level decreased, ΔΨm increased, Cd-induced BRL-3A cell damage was alleviated, and cell apoptosis was inhibited. After the combined action of QE and Cd, Nrf2 and NQO1 mRNA and protein expression increased, Keap1 mRNA and protein expression decreased. Therefore, QE exerted an antioxidant effect by activating the Nrf2-Keap1 pathway in BRL-3A cells.
Effects of space flight on sperm function and integrity: A systematic review
Authors: Ahrari Khulood , Omolaoye Temidayo S. , Goswami Nandu , Alsuwaidi Hanan , du Plessis Stefan S.
Published: August 2022

With the advancement in space exploration and the intention to establish an inhabitable human settlement on Mars, it is important to investigate the effects of exposure to space/microgravity and the associated radiations on procreation. Sperm function and integrity are fundamental to male reproduction and can potentially be affected by the environmental changes experienced in space. Therefore, this study was conducted to systematically gather, filter, and collate all the relevant information on the effects of spaceflight on male reproductive parameters and functions. A search was performed utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted from the major electronic databases including PubMed, and other credible literature sources. MeSH search terms that were employed included “spermatozoa”, “microgravity”, and “ionizing radiation”. The literature search did not discriminate against papers published before a certain date due to the very limited number of articles available. However, there was a restriction on the male gender and language (English). The parameters included in this study are sperm motility, total sperm count, sperm DNA fragmentation hormonal levels and testicular histology. Following a comprehensive literature search, a total of 273 articles were retrieved and screened, 252 articles were excluded due to the irrelevance to the topic, duplication, and non-original articles. A total of 21 articles met the inclusion criteria and are included in the current study. Findings from these studies showed that sperm motility was decreased after exposure to microgravity and ionizing radiation. Total sperm count was also found to be reduced by microgravity only. Sperm DNA fragmentation was increased by both ionizing radiation and microgravity. Testosterone levels and testicular weight were also decreased by microgravity. Although there is a dearth in the literature regarding the effects of microgravity and ionizing radiation on male reproductive parameters, the available findings showed that exposure to microgravity poses a risk to male reproductive health. Therefore, it is essential to develop countermeasures to either manage, treat, or prevent these consequential adverse effects. Hence, this review also highlights some potential countermeasure approaches that may mitigate the harmful effects of microgravity and associated exposures on male reproductive health.
Effectiveness of a fetal magnetic resonance imaging scoring system for predicting the prognosis of pernicious placenta previa: A retrospective study
Authors: Zou Lue , Wang Pengyuan , Song Zixuan , Wang Xiaoxue , Chen Xueting , Zhang Mingjie , Zhang Dandan
Published: August 2022

Background: The value of multiple magnetic resonance imaging (MRI) signs in predicting pernicious placenta previa (PPP) with placenta accreta spectrum disorders (PAS) is still controversial. This study aimed to investigate the value of a self-made fetal magnetic resonance imaging scoring system in predicting the different types of PAS in pernicious placenta previa and its associated risk of bleeding.

Methods: This retrospective study included 193 patients diagnosed with PPP based on MRI findings before delivery. Based on pathological and intraoperative findings, we divided patients into four groups: non-PAS, placental adhesion, placental implantation, and placenta percreta. Receiver operator characteristic curves of the MRI total score and placental implantation type were drawn using pROC packages in the R Studio environment, and cutoff values of each type were calculated, as well as diagnostic evaluation indexes, such as sensitivity, specificity, and the Youden index. Hemorrhage during surgery was compared between the groups.

Results: The boundary value between the non-PAS and placental adhesion was 5.5, that between placental adhesion and placental implantation was 11.5, and that between placental implantation and placenta percreta was 15.5 points. The respective specificities were 0.700, 0.869, and 0.958, and the respective sensitivities were 0.994, 0.802, and 0.577. The Youden indices were 0.694, 0.671, and 0.535, respectively. The median (minimum, maximum) quantities of hemorrhage during the operation in the non-PAS, placental adhesion, placental implantation, and placenta percreta groups were 225 (100, 3700), 600 (200, 6000), 1500 (300, 7000), and 3000 (400, 6300) ml, respectively. Hemorrhage was significantly different between the four groups (p < 0.001).

Conclusion: These results suggest that the proposed MRI scoring system could be an effective diagnostic tool for assessing PPP types and predicting the associated bleeding risk.
Landscape of the epigenetic regulation in wound healing
Authors: Yu Honghao , Wang Yichen , Wang Dawei , Yi Yi , Liu Zeming , Wu Min , Wu Yiping , Zhang Qi
Published: August 2022

Wound healing after skin injury is a dynamic and highly coordinated process involving a well-orchestrated series of phases, including hemostasis, inflammation, proliferation, and tissue remodeling. Epigenetic regulation refers to genome-wide molecular events, including DNA methylation, histone modification, and non-coding RNA regulation, represented by microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA). Epigenetic regulation is pervasively occurred in the genome and emerges as a new role in gene expression at the post-transcriptional level. Currently, it is well-recognized that epigenetic factors are determinants in regulating gene expression patterns, and may provide evolutionary mechanisms that influence the wound microenvironments and the entire healing course. Therefore, this review aims to comprehensively summarize the emerging roles and mechanisms of epigenetic remodeling in wound healing. Moreover, we also pose the challenges and future perspectives related to epigenetic modifications in wound healing, which would bring novel insights to accelerated wound healing.