bluuebunny/crossref_metadata_2025 huggingface dataset:
Melodic Intonation Therapy on Non-fluent Aphasia After Stroke: A Systematic Review and Analysis on Clinical Trials
Authors: Zhang Xiaoying , Li Jianjun , Du Yi
Published: January 2022

Melodic intonation therapy (MIT) is a melodic musical training method that could be combined with language rehabilitation. However, some of the existing literature focuses on theoretical mechanism research, while others only focus on clinical behavioral evidence. Few clinical experimental studies can combine the two for behavioral and mechanism analysis. This review aimed at systematizing recent results from studies that have delved explicitly into the MIT effect on non-fluent aphasia by their study design properties, summarizing the findings, and identifying knowledge gaps for future work. MIT clinical trials and case studies were retrieved and teased out the results to explore the validity and relevance of these results. These studies focused on MIT intervention for patients with non-fluent aphasia in stroke recovery period. After retrieving 128 MIT-related articles, 39 valid RCT studies and case reports were provided for analysis. Our summary shows that behavioral measurements at MIT are excessive and provide insufficient evidence of MRI imaging structure. This proves that MIT still needs many MRI studies to determine its clinical evidence and intervention targets. The strengthening of large-scale clinical evidence of imaging observations will result in the clear neural circuit prompts and prediction models proposed for the MIT treatment and its prognosis.
Nutritional Impact on Metabolic Homeostasis and Brain Health
Authors: Carneiro Lionel , Pellerin Luc
Published: January 2022

Aging in modern societies is often associated with various diseases including metabolic and neurodegenerative disorders. In recent years, researchers have shown that both dysfunctions are related to each other. Although the relationship is not fully understood, recent evidence indicate that metabolic control plays a determinant role in neural defects onset. Indeed, energy balance dysregulation affects neuroenergetics by altering energy supply and thus neuronal activity. Consistently, different diets to help control body weight, blood glucose or insulin sensitivity are also effective in improving neurodegenerative disorders, dampening symptoms, or decreasing the risk of disease onset. Moreover, adapted nutritional recommendations improve learning, memory, and mood in healthy subjects as well. Interestingly, adjusted carbohydrate content of meals is the most efficient for both brain function and metabolic regulation improvement. Notably, documented neurological disorders impacted by specific diets suggest that the processes involved are inflammation, mitochondrial function and redox balance as well as ATP production. Interestingly, processes involving inflammation, mitochondrial function and redox balance as well as ATP production are also described in brain regulation of energy homeostasis. Therefore, it is likely that changes in brain function induced by diets can affect brain control of energy homeostasis and other brain functions such as memory, anxiety, social behavior, or motor skills. Moreover, a defect in energy supply could participate to the development of neurodegenerative disorders. Among the possible processes involved, the role of ketone bodies metabolism, neurogenesis and synaptic plasticity, oxidative stress and inflammation or epigenetic regulations as well as gut-brain axis and SCFA have been proposed in the literature. Therefore, the goal of this review is to provide hints about how nutritional studies could help to better understand the tight relationship between metabolic balance, brain activity and aging. Altogether, diets that help maintaining a metabolic balance could be key to both maintain energy homeostasis and prevent neurological disorders, thus contributing to promote healthy aging.
Fzd3 Expression Within Inner Ear Afferent Neurons Is Necessary for Central Pathfinding
Authors: Stoner Zachary A. , Ketchum Elizabeth M. , Sheltz-Kempf Sydney , Blinkiewicz Paige V. , Elliott Karen L. , Duncan Jeremy S.
Published: January 2022

During development the afferent neurons of the inner ear make precise wiring decisions in the hindbrain reflective of their topographic distribution in the periphery. This is critical for the formation of sensory maps capable of faithfully processing both auditory and vestibular input. Disorganized central projections of inner ear afferents in Fzd3 null mice indicate Wnt/PCP signaling is involved in this process and ear transplantation in Xenopus indicates that Fzd3 is necessary in the ear but not the hindbrain for proper afferent navigation. However, it remains unclear in which cell type of the inner ear Fzd3 expression is influencing the guidance of inner ear afferents to their proper synaptic targets in the hindbrain. We utilized Atoh1-cre and Neurod1-cre mouse lines to conditionally knockout Fzd3 within the mechanosensory hair cells of the organ of Corti and within the inner ear afferents, respectively. Following conditional deletion of Fzd3 within the hair cells, the central topographic distribution of inner ear afferents was maintained with no gross morphological defects. In contrast, conditional deletion of Fzd3 within inner ear afferents leads to central pathfinding defects of both cochlear and vestibular afferents. Here, we show that Fzd3 is acting in a cell autonomous manner within inner ear afferents to regulate central pathfinding within the hindbrain.
Bi-Stable Perception: Self-Coordinating Brain Regions to Make-Up the Mind
Authors: Devia Christ , Concha-Miranda Miguel , Rodríguez Eugenio
Published: January 2022

Bi-stable perception is a strong instance of cognitive self-organization, providing a research model for how ‘the brain makes up its mind.’ The complexity of perceptual bistability prevents a simple attribution of functions to areas, because many cognitive processes, recruiting multiple brain regions, are simultaneously involved. The functional magnetic resonance imaging (fMRI) evidence suggests the activation of a large network of distant brain areas. Concurrently, electroencephalographic and magnetoencephalographic (MEEG) literature shows sub second oscillatory activity and phase synchrony on several frequency bands. Strongly represented are beta and gamma bands, often associated with neural/cognitive integration processes. The spatial extension and short duration of brain activities suggests the need for a fast, large-scale neural coordination mechanism. To address the range of temporo-spatial scales involved, we systematize the current knowledge from mathematical models, cognitive sciences and neuroscience at large, from single-cell- to system-level research, including evidence from human and non-human primates. Surprisingly, despite evidence spanning through different organization levels, models, and experimental approaches, the scarcity of integrative studies is evident. In a final section of the review we dwell on the reasons behind such scarcity and on the need of integration in order to achieve a real understanding of the complexities underlying bi-stable perception processes.
BuMPing Into Neurogenesis: How the Canonical BMP Pathway Regulates Neural Stem Cell Divisions Throughout Space and Time
Authors: Le Dréau Gwenvael
Published: January 2022

Bone morphogenetic proteins (BMPs) are secreted factors that contribute to many aspects of the formation of the vertebrate central nervous system (CNS), from the initial shaping of the neural primordium to the maturation of the brain and spinal cord. In particular, the canonical (SMAD1/5/8-dependent) BMP pathway appears to play a key role during neurogenesis, its activity dictating neural stem cell fate decisions and thereby regulating the growth and homeostasis of the CNS. In this mini-review, I summarize accumulating evidence demonstrating how the canonical BMP activity promotes the amplification and/or maintenance of neural stem cells at different times and in diverse regions of the vertebrate CNS, and highlight findings suggesting that this function is evolutionarily conserved.
Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis Pain
Authors: Minnema Laura , Gupta Ankita , Mishra Santosh K. , Lascelles B. Duncan X.
Published: January 2022

Osteoarthritis (OA) associated pain (OA-pain) is a significant global problem. OA-pain limits limb use and mobility and is associated with widespread sensitivity. Therapeutic options are limited, and the available options are often associated with adverse effects. The lack of therapeutic options is partly due to a lack of understanding of clinically relevant underlying neural mechanisms of OA-pain. In previous work in naturally occurring OA-pain in dogs, we identified potential signaling molecules (artemin/GFRα3) that were upregulated. Here, we use multiple approaches, including cellular, mouse genetic, immunological suppression in a mouse model of OA, and clinically relevant measures of sensitivity and limb use to explore the functional role of artemin/GFRα3 signaling in OA-pain. We found the monoiodoacetate (MIA)-induced OA-pain in mice is associated with decreased limb use and hypersensitivity. Exogenous artemin induces mechanical, heat, and cold hypersensitivity, and systemic intraperitoneal anti-artemin monoclonal antibody administration reverses this hypersensitivity and restores limb use in mice with MIA-induced OA-pain. An artemin receptor GFRα3 expression is increased in sensory neurons in the MIA model. Our results provide a molecular basis of arthritis pain linked with artemin/GFRα3 signaling and indicate that further work is warranted to investigate the neuronal plasticity and the pathways that drive pain in OA.
Dietary and Exercise Interventions for Perimenopausal Women: A Health Status Impact Study
Authors: Hao Shuping , Tan Sisi , Li Jing , Li Weimin , Li Jingyun , Cai Xiaochen , Hong Zhongxin
Published: January 2022

Purpose

To explore the impact of different intervention methods on physical health indexes of perimenopausal women.

Methods

Seventy-eight perimenopausal women were divided into three groups. Group A received routine gynecological diagnosis and treatment and participated in centralized lifestyle health education. Group B was required to participate in all intensive education content, and professional dietitians gave individualized dietary guidance. Group C received intensive education, individualized diet intervention and intensified resistance exercise. Dietary scores, exercise habits, waist circumference, body mass index, fat and muscle mass were observed after three months.

Results

After the intervention, the total diet score of group C was higher than groups A and B, and the red meat score was significantly reduced. The number of patients in groups B and C who exercised >3 times per week and the number of resistance exercises were significantly increased, while the number of aerobic exercises per week in group C was significantly increased. The body fat and waist circumference were significantly reduced, and skeletal muscle weight was significantly increased. Body mass index, trunk fat ratio and waist-to-hip ratio were significantly decreased in groups B and C, while trunk muscle was significantly increased in group C.

Conclusion

The combined intervention of the three methods can give full play to the synergistic effect of various interventions. The improvement effect of increasing the appropriate amount of resistance exercise is more obvious, which is worthy of further promotion and application.
In vitro Bioaccessibility and Intestinal Absorption of Selected Bioactive Compounds in Terminalia ferdinandiana
Authors: Akter Saleha , Addepalli Rama , Netzel Michael , Tinggi Ujang , Fletcher Mary , Sultanbawa Yasmina , Osborne Simone
Published: January 2022

Terminalia ferdinandiana (or Kakadu plum), a native Australian fruit with potential health benefits, contains bioactive compounds such as ellagic acid (EA), ascorbic acid (AA) and calcium, and antinutrients such as oxalic acid (OA). However, few is known about the biological fate of these compounds following ingestion; therefore, the aim of this study was to evaluate in vitro bioaccessibility and intestinal absorption of T. ferdinandiana compounds using the INFOGEST static digestion model and Caco-2-HT29-MTX-E12 intestinal absorption model. No significant changes (p > 0.05) were observed in total AA content throughout in vitro digestion, whereas bioaccessibility of EA, OA, and calcium increased significantly from 33, 72, and 67% in the gastric phase to 48, 98, and 90% in the intestinal phase, respectively. The intestinal absorption study revealed variable rates of movement across the cell barrier. Findings reveal novel and important insights for the prediction of in vivo bioavailability of selected T. ferdinandiana compounds.
Effects of Branched-Chain Amino Acids on Parameters Evaluating Sarcopenia in Liver Cirrhosis: Systematic Review and Meta-Analysis
Authors: Ismaiel Abdulrahman , Bucsa Camelia , Farcas Andreea , Leucuta Daniel-Corneliu , Popa Stefan-Lucian , Dumitrascu Dan L.
Published: January 2022

Introduction

Sarcopenia is a major element of malnutrition in liver cirrhosis (LC) and is present in 30–70% of this population, being associated with a poor overall prognosis due to related complications such as hepatic encephalopathy, ascites, and portal hypertension. This systematic review and meta-analysis aimed to evaluate the effects of branched-chain amino acids (BCAA) supplementation on several parameters used to assess sarcopenia in LC.

Materials and Methods

A comprehensive systematic electronic search was performed in PubMed, EMBASE, Scopus, Cochrane Library, and ClinicalTrials.gov databases using predefined keywords. We included full articles that satisfied the inclusion and exclusion criteria. Quality assessment of included studies was conducted using Cochrane Collaboration's tool and NHLBI quality assessment tools for interventional and observational studies, respectively. The principal summary outcome was the mean difference (MD) in the evaluated parameters. We performed a pre- and post-intervention analysis and comparison between two intervention groups (BCAA vs. controls) of the evaluated parameters when applicable.

Results

A total of 12 studies involving 1,225 subjects were included in our qualitative synthesis and five in our quantitative synthesis. At baseline vs. post-intervention assessment, subjects receiving BCAA supplementation were found to have a significant improvement in skeletal muscle index (SMI) (−0.347 [95% CI −0.628–0.067; p-value 0.015]) and mid-arm muscle circumference (MAMC) (−1.273 [95% CI (−2.251–0.294; p-value 0.011]). However, no improvements were reported in handgrip (-0.616 [95% CI −2.818–1.586; p-value 0.584]) and triceps subcutaneous fat (1.10 [95% CI −0.814–3.014; p-value 0.263]).

Conclusion

Following BCAA supplementation, several parameters used to evaluate sarcopenia in LC patients were found to be improved, including SMI and MAMC. Nevertheless, no improvements were seen in handgrip and triceps subcutaneous fat. Results should be interpreted with caution due to the limited methodological quality of the included studies.
Associations of Adherence to the DASH Diet and the Mediterranean Diet With All-Cause Mortality in Subjects With Various Glucose Regulation States
Authors: Wang Jun-Sing , Liu Wei-Ju , Lee Chia-Lin
Published: January 2022

Background and Aims

A dietary pattern concordant with either the Dietary Approaches to Stop Hypertension (DASH) diet or the Mediterranean diet has been associated with a lower risk of all-cause mortality in general population. We investigated the associations of adherence to the DASH diet and the Mediterranean diet with all-cause mortality across three glucose regulation states (normal glucose tolerance, prediabetes, and diabetes) using data from the National Health and Nutrition Examination Survey (NHANES).

Methods

Data from the NHANES participants from 1999 to 2010, including their vital status linked to the National Death Index through the end of 2011, were analyzed. Adherence to the DASH diet and the Mediterranean diet was assessed using the DASH score and the alternative Mediterranean Diet Index (aMED), respectively. Weighted Cox proportional hazards regression models were used to compare the hazard ratios for the associations of adherence (diet score >median vs. ≤ median) to the DASH diet and the Mediterranean diet with all-cause mortality.

Results

A total of 28,905 participants were analyzed, and 2,598 of them had died after a median follow-up of 6.3 years. The median DASH score and aMED were 2 and 3, respectively. Adherence to the Mediterranean diet (aMED >3 vs. ≤ 3), but not the DASH diet, was associated with a lower risk of all-cause mortality (adjusted HR 0.74, 95% CI 0.66–0.83, p < 0.001) in the overall population. The findings were consistent across the three glucose regulation states. A joint effect of aMED >3 and DASH score >2 (adjusted HR 0.71, 95% CI 0.52–0.99, p = 0.042) was noted in participants with diabetes.

Conclusions

Adherence to the Mediterranean diet (aMED >median) was associated with reduced all-cause mortality in a general population. For people with diabetes, a dietary pattern concordant with both the DASH diet and the Mediterranean diet (DASH score >median and aMED >median) was associated with a lower risk of mortality.
Identification of a 3-miRNA Signature Associated With the Prediction of Prognosis in Nasopharyngeal Carcinoma
Authors: Zhou Jinhui , Zhang Bo , Zhang Xin , Wang Chengyu , Xu Yu
Published: January 2022

Nasopharyngeal carcinoma (NPC) is a malignant tumor caused by an infection of the epithelial cells of the nasopharynx, which is highly metastatic and aggressive. Due to the deep anatomical site and atypical early symptoms, the majority of NPC patients are diagnosed at terminal stages. There is growing evidence that microRNAs offer options for early detection, accurate diagnosis, and prediction of malignancy treatment response. Therefore, the purpose of this article was to identify microRNAs that predict the prognosis of patients with NPC by integrating biological information analysis. In this study, we utilized the GSE36682 dataset rooted in the Gene Expression Omnibus (GEO) data bank, including 62 cases of NPC tissues and six cases of non-cancerous tissues. The miRNAs were subjected to weighted gene co-expression network analysis, and hub miRNAs were screened for differentially upregulated miRNAs from modules highly correlated with tumor progression. We took a lot of time to calculate the risk scores of miRNA markers for 62 NPC patients, and incidentally combined the clinical survival information of patients to finally identify the three key miRNAs, and then divided the patients into low- and high-risk groups. Kaplan-Meier curve analysis revealed that the overall survival of patients in the high-risk group was obviously shorter than that of the low-risk group. Subsequently, the target genes of the three miRNAs were predicted and analyzed for functional enrichment. In summary, a prognostic predictive risk model based on three miRNA profiles may increase prognostic predictive value and provide reference information for the precise treatment of nasopharyngeal carcinoma.
Patient-Reported Outcomes and Complications Following Breast Reconstruction: A Comparison Between Biological Matrix-Assisted Direct-to-Implant and Latissimus Dorsi Flap
Authors: Gao Peng , Bai Ping , Kong Xiangyi , Fang Yi , Gao Jidong , Wang Jing
Published: January 2022

Background

Implant-based breast reconstruction is increasingly becoming the most common method of postmastectomy breast reconstruction in use today. As the traditional autologous reconstruction technique, latissimus dorsi flap (LDF) is employed by surgeons for reconstruction after breast cancer surgery, including partial mastectomy, modified radical mastectomy, and others. The authors aim to compare patient-reported outcomes (PROs) and complications between the SIS matrix-assisted direct-to-implant (DTI) breast reconstruction and the autologous LDF breast reconstruction.

Methods

Patients undergoing the SIS matrix-assisted DTI reconstruction or mastectomy with LDF reconstruction or partial mastectomy with mini latissimus dorsi flap (MLDF) reconstruction were enrolled in a single institution from August 2010 to April 2019. Patients were included for analysis and divided into three groups: those who underwent LDF reconstruction, those who underwent MLDF reconstruction, and patients who underwent SIS matrix-assisted DTI breast reconstruction. PROs (using the BREAST-Q version 2.0 questionnaire) and complications were evaluated.

Results

A total of 135 patients met the inclusion criteria: 79 patients (58.5%) underwent SIS matrix-assisted DTI, 29 patients (21.5%) underwent LDF breast reconstruction, and 27 patients (20%) underwent MLDF breast reconstruction. PROs and complication rates between LDF reconstruction group and MLDF reconstruction group showed no statistically significant differences. Furthermore, BREAST-Q responses found that patients in the whole autologous LDF reconstruction group had better psychosocial well-being, showing a mean score of 84.31 ± 17.28 compared with SIS matrix-assisted DTI reconstruction, with a mean score of 73.52 ± 19.96 (p = 0.005), and expressed higher sexual well-being (69.65 ± 24.64 vs. 50.95 ± 26.47; p = 0.016). But there were no statistically significant differences between the two groups for postoperative complications.

Conclusion

This retrospective study showed no statistically significant differences between LDF breast reconstruction and MLDF breast reconstruction. However, patients in the whole autologous LDF reconstruction group yielded superior PROs than patients in the SIS matrix-assisted DTI reconstruction group in the psychosocial well-being and sexual well-being domains.
Exosomes in Pathogenesis, Diagnosis, and Treatment of Hepatocellular Carcinoma
Authors: Li Shuang , Chen Limin
Published: January 2022

Exosomes are extracellular vesicles with a diameter of 30-150 nm that are released by most types of cells and have been confirmed to be involved in many physical and pathological processes, especially in cell to cell communication. Compared with other vesicles, exosomes have a unique double-layer saclike structure that allows them to be present stably in various body fluids, including blood, cerebrospinal fluid, urine, saliva, and serous cavity effusion. The cargoes of exosomes reflect the characteristics of host cells. Due to the nature of hepatocellular carcinoma (HCC) cells, heterogeneity in the bioactive substances usually exist in exosomes. In addition, exosomes can efficiently deliver cargoes to the target cells to exert pathological functions, playing important role in tumor occurrence, development, metastasis, immune regulation, and drug resistance. Previous studies have been shown that exosomes have wide applications in diagnosis and treatment of HCC. In this review, we discuss these recent findings and highlight the significant roles of exosomes in HCC, focusing on the effect and underlying mechanisms of exosomes to regulate HCC progression and the potential clinical value of exosomes as biomarkers and therapeutic targets.
Clinical Significance and Immune Landscape of Recurrence-Associated Ferroptosis Signature in Early-Stage Lung Adenocarcinoma
Authors: Yi Lilan , Huang Ping , Gu Yinfang , Wu Guowu , Zou Xiaofang , Guo Longhua , Wen Chunling , Zhu Junlin , Zhao Dongdong
Published: January 2022

Background

The prevalence of patients newly diagnosed with early-stage lung adenocarcinoma (LUAD) is growing alongside significant advances in screening approaches. This study aimed to construct ferroptosis-related gene score (FRGscore) for predicting recurrence, explore immune-molecular characteristics, and determine the benefit of immunotherapy in distinct ferroptosis-based patterns and FRGscore-defined subgroups.

Methods

A total of 1,085 early-stage LUAD patients from four independent cohorts were included. Consensus clustering analysis was performed using 217 co-expressed FRGs to explore different ferroptosis-mediated patterns. An FRG scoring system was established to predict relapse, quantify ferroptosis-mediated patterns, and evaluate the response to immunotherapy in individual patients based on Lasso-penalized and stepwise Cox regression analyses. Immune landscape involving multiple parameters was further evaluated, stratified by cluster subtypes and FRGscore subgroups.

Results

Two ferroptosis-mediated patterns were identified and verified, which were characterized by significantly distinct prognosis and immune profiles. Analyses of immune characteristics showed that identified ferroptosis patterns were characterized as immune-inflamed phenotype and immune-exhausted phenotype. The FRG scoring model based on 11 FRG-derived signatures panel classified patients into the FRGscore-high and FRGscore-low subgroups. Significantly longer recurrence-free survival (RFS) and overall survival (OS) were observed in the FRGscore-low subgroup. FRGscore-low patients were characterized by higher tumor mutational burden (TMB), immunoscore, immunophenoscore, and PD-L1 expression level and were associated with lower Tumor Immune Dysfunction and Exclusion (TIDE) score, whereas the opposite was observed in FRGscore-high patients. Immune-active pathways were remarkably enriched in the FRGscore-low subgroup. This scoring model remained highly predictive of prognosis across different clinical, molecular, and immune subgroups. Further analysis indicated that FRGscore-low patients exhibited higher response to anti-PD-1/PD-L1 immunotherapy and better clinical benefits based on two independent immunotherapy cohorts.

Conclusion

The proposed FRGscore could highly distinguish the recurrence patterns and molecular and immune characteristics and could predict immunotherapy prognosis, potentially representing a powerful prognostic tool for further optimization of individuated treatment and management strategies in early-stage LUAD.
High Efficacy of Stem Cell Mobilization With Etoposide+Cytarabine Plus G-CSF in Patients With Multiple Myeloma
Authors: Zhu Zhijuan , Li Xiaofan , Liu Yiping , Chen Ping , Chen Xianling , Li Hua , Huang Jiafu , Chen Yuanzhong , Li Nainong
Published: January 2022

Background

Efficient mobilization of CD34+ hematopoietic stem cells plays a vital role in successful autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM), especially in cases with high-risk cytogenetic recommended for tandem ASCT. However, the optimal mobilization strategy remains a matter of debate in the era of lenalidomide. The combination of etoposide with Cytarabine plus G-CSF as a novel mobilization regimen in MM has not been reported previously.

Methods

This research retrospectively studied mobilization efficacy and safety using etoposide combined with Cytarabine (etoposide 50–100 mg/m2, qd d1–3; AraC 0.5 g/m2, q12h d1~3) plus G-CSF (5 µg/kg/day, from d5 until the day of apheresis) in 128 patients with MM. 70(54.7%) patients received lenalidomide-based induction regimens treatment

Results

A median of 27.75×106 CD34+ cells/kg was collected in the first apheresis, and 28.23×106 CD34+ cells/kg were collected overall. Of the 128 patients, all achieved adequate collection (≥2×106 CD34+ cells/kg), 121(94.5%) achieved optimal collection for single ASCT (≥5×106 CD34+ cells/kg), and 114(89.1%) harvested optimal collection for tandem ASCT (≥10×106 CD34+ cells/kg). In particular, the target yield of optimal collection for tandem ASCT was reached in 82.8% (106/128) by a single apheresis procedure. 14 patients obtained deeper response post mobilization. In multivariate analysis, cycles of prior chemotherapy independently affected the optimal achievement of CD34+ cells (p=0.004, OR 0.695, 95% CI 0.544~0.888). Previous lenalidomide exposure did not significantly impair CD34+ cells collection. Although 68% episodes of antibiotic usage were observed, no severe infection or treatment-related mortality occurred.

Conclusion

Stem cell mobilization with Etoposide + Cytarabine plus G-CSF was highly efficient and safe in patients with MM, which could be considered in high-risk MM patients who were referred for tandem ASCT.
Xpert Bladder Cancer Monitor May Avoid Cystoscopies in Patients Under “Active Surveillance” for Recurrent Bladder Cancer (BIAS Project): Longitudinal Cohort Study
Authors: Fasulo Vittorio , Paciotti Marco , Lazzeri Massimo , Contieri Roberto , Casale Paolo , Saita Alberto , Lughezzani Giovanni , Diana Pietro , Frego Nicola , Avolio Pier Paolo , Colombo Piergiuseppe , Elefante Grazia Maria , Guazzoni Giorgio , Buffi Nicolò Maria , Bates Michael , Hurle Rodolfo
Published: January 2022

Objectives

To test the hypothesis that patients under active surveillance (AS) for Non-muscle Invasive Bladder Cancer (NMIBC) who were negative on longitudinal re-testing by the Xpert® Bladder Cancer Monitor (Xpert BC Monitor) assay may avoid unnecessary cystoscopies and urine cytology (UC).

Subjects/Patients (or Materials) and Methods

This is a prospective cohort study of patients enrolled in the AS protocol for recurrent NMIBC (Bladder Cancer Italian Active Surveillance, BIAS project), whose urine samples were analyzed by Xpert BC Monitor upon entry in the study (T0). Patients who had a negative Xpert test and did not fail AS, underwent additional Xpert tests after 4 (T1), 8 (T2), and 12 (T3) months. The clinical utility of Xpert was assessed by determining the number of cystoscopies and UC that could be avoided within 1 year.

Results

Overall, 139 patients were tested with Xpert at T0. Median follow-up was 23 (IQR 17–27) months. Sixty-eight (48.9%) patients failed AS, 65 (46.7%) are currently on AS, and 6 (4.3%) were lost at follow-up. At T0 57 (41.0%) patients had a negative test and 36 (63.2%) are still in AS. In patients with 2 consecutives negative Xpert tests, we could have avoided 73.9% of unnecessary cystoscopies, missing 26.4% failure, up to avoid all cystoscopies with 4 negative tests missing only 12% of failure. All the patients with negative Xpert had negative UC. Failure-free-survival at median follow-up (23 month) stratified for having 0, 1, or ≥2 negative tests was 67.0, 55.1. and 84.1, respectively.

Conclusion

Our findings suggest that Xpert BC Monitor assay, when it is longitudinally repeated, could significantly reduce the number of unnecessary cystoscopies and UC during their follow-up.
Applying Theory of Planned Behavior to Understand Physicians’ Shared Decision-Making With Patients With Acute Respiratory Infections in Primary Care: A Cross-Sectional Study
Authors: Wang Dan , Zhang Xinping , Chen Haihong , Liu Chenxi
Published: January 2022

Background: To understand the physicians’ shared decision-making behavior (SDM) with patients with acute respiratory infections (ARIs) based on the theory of planned behavior (TPB) and identify barriers to the implementation of SDM in primary care.

Methods: A cross-sectional study of 617 primary care physicians was conducted in primary facilities in Hubei province, China from December 2019 to January 2020. A self-administered questionnaire based on TPB theory was applied for measuring the physicians’ SDM behavior with patients presenting with ARIs.

Results: The proposed TPB model revealed that attitude and subjective norms predicted behavior intention, and behavior intention was one significant predictor of SDM behavior (p < 0.001). After controlling for physicians’ demographic characteristics, receiving training regarding antibiotics was significantly associated with physicians’ attitudes toward SDM, while educational level and gender were significantly associated with physicians’ intention of engaging in SDM (p < 0.05). Physicians’ perceptions of patients’ expectations and incapability of making decisions were the most frequently reported barriers to the implementation of SDM.

Conclusion: The TPB theory provides insights for understanding physicians’ SDM behavior with patients with ARIs in primary care. Since attitudes, subjective norms, and behavior intention were demonstrated as significant predictors of SDM behavior, these may be a promising focus of SDM interventions based on TPB theory. The results of the TPB model and potential barriers of SDM behavior would help determine future directions for SDM training and educating the public.
A Comparison of Intranasal Dexmedetomidine, Esketamine or a Dexmedetomidine-Esketamine Combination for Induction of Anaesthesia in Children: A Randomized Controlled Double-Blind Trial
Authors: Lu Xinlei , Tang Ling , Lan Haiyan , Li Chunli , Lin Han
Published: January 2022

Objective: To compare the efficacy of dexmedetomidine, esketamine or combined intranasal administration on the induction of inhalation anaesthesia in children.

Methods: Ninety children aged 1–6 years were randomly allocated into three equal groups to be premedicated with either intranasal dexmedetomidine 2 μg/kg (Group D), esketamine 1 mg/kg (Group S), or dexmedetomidine 1 μg/kg combined with esketamine 0.5 mg/kg (Group DS). The primary endpoint was the Induction Compliance Checklist (ICC) Scale. Secondary outcomes included the sedation success rate; the modified Yale Preoperative Anxiety Scale score; the time of reaching up to two points on the University of Michigan Sedation Scale (UMSS); Parental Separation Anxiety Scale; anaesthesiologist satisfaction with induction based on the visual analogue scale; emergence agitation scale score; and adverse effects.

Results: The children in the DS group showed a high degree of cooperation with inhalation anaesthesia induction, and their ICC score was significantly lower than that of the D and S groups (p = 0.001), but there was no difference between the D and S groups. The success rate of sedation was higher in Group DS (90%) than in Group D (70%) and Group S (53.3%) (p = 0.007). Anaesthesiologist satisfaction with induction was significantly higher in Group DS than in Groups D and S (p = 0.001). The incidence of emergence agitation and the Paediatric Anaesthesia Emergence Delirium (PAED) score in the DS group were lower than those in the D and S groups.

Conclusions: Preoperative intranasal administration of dexmedetomidine combined with esketamine can significantly improve the cooperation of children with inhalation anaesthesia masks. It is a sedation method that has a high success rate and reduces the incidence and degree of emergence agitation.
Active Components of Traditional Chinese Medicinal Material for Multiple Myeloma: Current Evidence and Future Directions
Authors: Yu Chao-Chao , Li Yi , Cheng Zhao-Jun , Wang Xi , Mao Wei , Zhang Ying-Wen
Published: January 2022

Multiple myeloma (MM) is a hematological malignancy characterized by clonal expansion of plasma cells in bone marrow, leading to the overproduction of monoclonal immunoglobulins. The clinical manifestations resulting from monoclonal proteins and malignant cells include signs of end-organ damage, such as hypercalcemia, renal failure, anemia, and bone lesions. Despite improvement in the survival of MM patients with use of myeloma-targeted and immunomodulatory therapies, MM remains an incurable disease. Moreover, patients with relapsed or refractory MM show poor survival outcomes. In recent years, there has been a growing interest in the use of traditional Chinese medicinal materials (TCMMs) for management of a wide spectrum of diseases. The bioactive ingredients derived from TCMMs hold great potential for the development of anticancer drugs. Here we summarize the evidence of the pharmacological effects of the active components in TCMMs on MM, including curcumin, resveratrol, baicalein, berberine, bufalin, cinobufagin, gambogic acid, ginsenoside, icariin, daidzin, formononetin, polysaccharides extracts from Hedyotis difus, and scutellarein. Available evidence indicates that the anti-MM effects of these bioactive ingredients are mediated via regulation of proliferation, apoptosis, autophagy, cell cycle, osteogenic differentiation, and drug resistance. In the future, the underlying mechanisms of the anti-MM effects of these components should be further investigated. Large-scale and well-designed clinical trials are also required to validate the efficacy of these bioactive constituents for MM.
Towards Structure-Guided Development of Pain Therapeutics Targeting Voltage-Gated Sodium Channels
Authors: Nguyen Phuong T. , Yarov-Yarovoy Vladimir
Published: January 2022

Voltage-gated sodium (NaV) channels are critical molecular determinants of action potential generation and propagation in excitable cells. Normal NaV channel function disruption can affect physiological neuronal signaling and lead to increased sensitivity to pain, congenital indifference to pain, uncoordinated movement, seizures, or paralysis. Human genetic studies have identified human NaV1.7 (hNaV1.7), hNaV1.8, and hNaV1.9 channel subtypes as crucial players in pain signaling. The premise that subtype selective NaV inhibitors can reduce pain has been reinforced through intensive target validation and therapeutic development efforts. However, an ideal therapeutic has yet to emerge. This review is focused on recent progress, current challenges, and future opportunities to develop NaV channel targeting small molecules and peptides as non-addictive therapeutics to treat pain.
Use of hiPSC-Derived Cardiomyocytes to Rule Out Proarrhythmic Effects of Drugs: The Case of Hydroxychloroquine in COVID-19
Authors: Sala Luca , Leonov Vladislav , Mura Manuela , Giannetti Federica , Khudiakov Aleksandr , Moretti Alessandra , Crotti Lia , Gnecchi Massimiliano , Schwartz Peter J.
Published: January 2022

In the early phases of the COVID-19 pandemic, drug repurposing was widely used to identify compounds that could improve the prognosis of symptomatic patients infected by SARS-CoV-2. Hydroxychloroquine (HCQ) was one of the first drugs used to treat COVID-19 due to its supposed capacity of inhibiting SARS-CoV-2 infection and replication in vitro. While its efficacy is debated, HCQ has been associated with QT interval prolongation and potentially Torsades de Pointes, especially in patients predisposed to developing drug-induced Long QT Syndrome (LQTS) as silent carriers of variants associated with congenital LQTS. If confirmed, these effects represent a limitation to the at-home use of HCQ for COVID-19 infection as adequate ECG monitoring is challenging. We investigated the proarrhythmic profile of HCQ with Multi-Electrode Arrays after exposure of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from two healthy donors, one asymptomatic and two symptomatic LQTS patients. We demonstrated that: I) HCQ induced a concentration-dependent Field Potential Duration (FPD) prolongation and halted the beating at high concentration due to the combined effect of HCQ on multiple ion currents. II) hiPSC-CMs from healthy or asymptomatic carriers tolerated higher concentrations of HCQ and showed lower susceptibility to HCQ-induced electrical abnormalities regardless of baseline FPD. These findings agree with the clinical safety records of HCQ and demonstrated that hiPSC-CMs potentially discriminates symptomatic vs. asymptomatic mutation carriers through pharmacological interventions. Disease-specific cohorts of hiPSC-CMs may be a valid preliminary addition to assess drug safety in vulnerable populations, offering rapid preclinical results with valuable translational relevance for precision medicine.
Agro-Morphological Characterization of Lentil Germplasm of Indian National Genebank and Development of a Core Set for Efficient Utilization in Lentil Improvement Programs
Authors: Tripathi Kuldeep , Kumari Jyoti , Gore Padmavati G. , Mishra Dwijesh C. , Singh Amit Kumar , Mishra Gyan P. , Gayacharan C. , Dikshit H. K. , Singh Neeta , Semwal D. P. , Mehra Reena , Bhardwaj Rakesh , Bansal Ruchi , Rana J. C. , Kumar Ashok , Gupta Veena , Singh Kuldeep , Sarker Ashutosh
Published: January 2022

Lentil (Lens culinaris Medik.) is one of the major cool-season pulse crops worldwide. Its increasing demand as a staple pulse has led to the unlocking of diverse germplasm collections conserved in the genebanks to develop its superior varieties. The Indian National Genebank, housed at the Indian Council of Agricultural Research (ICAR)-National Bureau of Plant Genetic Resources, New Delhi, India, currently has 2,324 accessions comprising 1,796 indigenous and 528 exotic collections. This study was conducted to unveil the potential of lentil germplasm by assessing its agro-morphological characteristics and diversity, identifying trait-specific germplasm, and developing a core set. The complete germplasm set was characterized for two years, i.e., 2017–2018 and 2018–2019, and data were recorded on 26 agro-morphological traits. High phenotypic variability was observed for nine quantitative and 17 qualitative traits. A core set comprising 170 accessions (137 Indian and 33 exotic) was derived based on the characterization data as well as geographical origin using a heuristic method and PowerCore software. This core set was found to be sufficiently diverse and representative of the entire collection based on the comparison made using Shannon–Weaver diversity indices and χ2 test. These results were further validated by summary statistics. The core set displayed high genetic diversity as evident from a higher coefficient of variance in comparison to the entire set for individual traits and overall Shannon–Weaver diversity indices (entire: 1.054; core: 1.361). In addition, the total variation explained by the first three principal components was higher in the core set (70.69%) than in the entire collection (68.03%). Further, the conservation of pairwise correlation values among descriptors in the entire and core set reflected the maintenance of the structure of the whole set. Based on the results, this core set is believed to represent the entire collection, completely. Therefore, it constitutes a potential set of germplasm that can be used in the genetic enhancement of lentils.
The Complex Biodiversity-Ecosystem Function Relationships for the Qinghai-Tibetan Grassland Community
Authors: Qi Wei , Kang Xiaomei , Knops Johannes M. H. , Jiang Jiachang , Abuman A. , Du Guozhen
Published: January 2022

Despite the long history of the study of the biodiversity-ecosystem function relationship, uncertainty remains about the relationship of natural grassland ecosystems under stressful conditions. Recently, trait- and phylogenetic-based tests provide a powerful way to detect the relationship in different spaces but have seldom been applied to stressful zones on a large spatial scale. We selected Qinghai-Tibetan as the study area and collected a grassland community database involving 581 communities. We calculated biomass and species’, functional, and phylogenetic diversity of each community and examined their relationships by using linear and non-linear regression models. Results showed an overall positive biodiversity-productivity relationship in species’, functional and phylogenetic space. The relationship, however, was non-linear, in which biodiversity explained better the variation in community biomass when species diversity was more than a threshold, showing a weak effect of biodiversity on ecosystem function in low species diversity communities. We also found a filled triangle for the limit of the relationship between species and functional diversity, implying that functional diversity differs significantly among communities when their species diversity is low but finally converges to be a constant with increasing communities’ species diversity. Our study suggests that multiple niche processes may structure the grassland communities, and their forces tend to balance in high-biodiversity communities.
Architecture and Dynamics of the Wounding-Induced Gene Regulatory Network During the Oolong Tea Manufacturing Process (Camellia sinensis)
Authors: Zheng Yucheng , Hu Qingcai , Yang Yun , Wu Zongjie , Wu Liangyu , Wang Pengjie , Deng Huili , Ye Naixing , Sun Yun
Published: January 2022

Understanding extensive transcriptional reprogramming events mediated by wounding during the oolong tea manufacturing process is essential for improving oolong tea quality. To improve our comprehension of the architecture of the wounding-induced gene regulatory network, we systematically analyzed the high-resolution transcriptomic and metabolomic data from wounding-treated (after turnover stage) tea leaves at 11 time points over a 220-min period. The results indicated that wounding activates a burst of transcriptional activity within 10 min and that the temporal expression patterns over time could be partitioned into 18 specific clusters with distinct biological processes. The transcription factor (TF) activity linked to the TF binding motif participated in specific biological processes within different clusters. A chronological model of the wounding-induced gene regulatory network provides insight into the dynamic transcriptional regulation event after wounding treatment (the turnover stage). Time series data of wounding-induced volatiles reveal the scientific significance of resting for a while after wounding treatment during the actual manufacturing process of oolong tea. Integrating information-rich expression data with information on volatiles allowed us to identify many high-confidence TFs participating in aroma formation regulation after wounding treatment by using weighted gene co-expression network analysis (WGCNA). Collectively, our research revealed the complexity of the wounding-induced gene regulatory network and described wounding-mediated dynamic transcriptional reprogramming events, serving as a valuable theoretical basis for the quality formation of oolong tea during the post-harvest manufacturing process.
Physiological and Multi-Omics Approaches for Explaining Drought Stress Tolerance and Supporting Sustainable Production of Rice
Authors: Zargar Sajad Majeed , Mir Rakeeb Ahmad , Ebinezer Leonard Barnabas , Masi Antonio , Hami Ammarah , Manzoor Madhiya , Salgotra Romesh K. , Sofi Najeebul Rehman , Mushtaq Roohi , Rohila Jai Singh , Rakwal Randeep
Published: January 2022

Drought differs from other natural disasters in several respects, largely because of the complexity of a crop’s response to it and also because we have the least understanding of a crop’s inductive mechanism for addressing drought tolerance among all abiotic stressors. Overall, the growth and productivity of crops at a global level is now thought to be an issue that is more severe and arises more frequently due to climatic change-induced drought stress. Among the major crops, rice is a frontline staple cereal crop of the developing world and is critical to sustaining populations on a daily basis. Worldwide, studies have reported a reduction in rice productivity over the years as a consequence of drought. Plants are evolutionarily primed to withstand a substantial number of environmental cues by undergoing a wide range of changes at the molecular level, involving gene, protein and metabolite interactions to protect the growing plant. Currently, an in-depth, precise and systemic understanding of fundamental biological and cellular mechanisms activated by crop plants during stress is accomplished by an umbrella of -omics technologies, such as transcriptomics, metabolomics and proteomics. This combination of multi-omics approaches provides a comprehensive understanding of cellular dynamics during drought or other stress conditions in comparison to a single -omics approach. Thus a greater need to utilize information (big-omics data) from various molecular pathways to develop drought-resilient crop varieties for cultivation in ever-changing climatic conditions. This review article is focused on assembling current peer-reviewed published knowledge on the use of multi-omics approaches toward expediting the development of drought-tolerant rice plants for sustainable rice production and realizing global food security.