bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of nutrition knowledge, practice, supplement use, and nutrient intake with strength performance among Taekwondo players in Nepal
Authors: Sunuwar Dev Ram , Singh Devendra Raj , Bohara Man Prasad , Shrestha Vintuna , Karki Kshitij , Pradhan Pranil Man Singh
Published: November 2022

Background

Optimum dietary intake and adequate nutritional knowledge have been recognized as the key factors that play a critical role in improving the athlete's health and nutrition status. This study aimed to measure the association of nutritional knowledge, practice, supplement use, and nutrient intake with strength performance among Nepalese Taekwondo players.

Methods

Between August 2019 and January 2020, a cross-sectional study was conducted among 293 Taekwondo players in Kathmandu Metropolitan City (mean age, 18 years; 63.1% male, 36.9% female). Face-to-face interviews were conducted using semi-structured questionnaires. Anthropometric measures, nutritional intake, nutrition knowledge, and practice were all recorded. The handgrip strength was measured using a handgrip dynamometer as a proxy for strength performance. Univariate and bivariate analyses were used to find out the association between predictor and outcome variables.

Results

More than half of the participants had poor nutrition knowledge [54.3% (159/293)], and poor nutrition practice [55.3% (162/293)] scores. Daily mean energy, carbohydrate, protein and fat intake were 48.0 kcal.kg−1.d−1, 8.6, 1.6, and 1.5 g.kg−1.d−1, respectively among Taekwondo players. Daily total energy and carbohydrate intake were 48.2 kcal.kg−1.d−1 and 8.7 g.kg−1.d−1, respectively among male players which is higher than female players. However, daily protein and fat intake were higher in female players (1.7 and 1.6 g.kg−1.d−1, respectively). Both calcium (375.3 mg) and iron (9 mg) intake among Taekwondo players were significantly lower than current sports nutrition guidelines. Nutritional knowledge score (r = 0.117), height (r = 0.538), weight (r = 0.651), body mass index (r = 0.347), fat (r = 0.075), and energy (r = 0.127) intake showed significant positive correlation with strength performance of athletes. The strength performance was positively associated with training hours per day (β = 0.41, 95% CI: 0.09–0.91), body mass index (β = 0.35, 95% CI: 0.09–0.61), nutrition knowledge score (β = 0.13, 95% CI: 0.01–0.25), and energy intake (β = 0.13, 95% CI: 0.12–0.14).

Conclusions

The nutritional knowledge and practice both were suboptimal among Taekwondo athletes. Height, weight, body mass index, nutritional knowledge, energy, and fat intake showed a positive correlation with strength performance. Future studies can build on the premise of this study to identify the robust relationship between nutritional knowledge, practice, different supplement use, and nutrient intake among other athletes too.
Anthocyanin-rich extract from black beans exerts anti-diabetic effects in rats through a multi-genomic mode of action in adipose tissue
Authors: Damián-Medina Karla , Milenkovic Dragan , Salinas-Moreno Yolanda , Corral-Jara Karla Fabiola , Figueroa-Yáñez Luis , Marino-Marmolejo Erika , Lugo-Cervantes Eugenia
Published: November 2022

Black beans (BB) are an important source of a range of plant bioactive compounds including polyphenols, particularly anthocyanins. Several studies support that consumption of BB is associated with health benefits, including prevention of type 2 diabetes mellitus (T2DM). However, molecular mechanisms underlying the potential health properties of BB on adipose tissue (AT) are still largely unknown. The purpose of this study was to investigate multi-genomic effects of BB intake and identify regulatory networks potentially mediating T2DM on AT. Male Wistar diabetic rats consumed an anthocyanin-rich black bean extract for 5 weeks. Global gene expression from AT, protein coding and non-coding RNA profiles were determined using RNAseq. Biological function analyses were performed using a variety of bioinformatic tools. The evaluation of global gene expression profiles exhibited significant change following BB consumption with 406 significantly differentially expressed genes, 33 miRNA and 39 lncRNA and 3 snRNA. Functional analyses indicated that these genes play an important role in regulation of PI3K signaling, NIN/NF-kB signaling, insulin secretion, and endoplasmic reticulum (ER) organization. Interestingly, transcription factors such as GATA2, or POU2AF1 demonstrated to modulate their activity by BB extract by direct interaction with polyphenol metabolites, or by interactions with cell signaling proteins, like PKB, AKT or PI3K, that could control transcription factor activity and as a result impact on adipogenesis regulation. Therefore, the constant consumption of an anthocyanin-rich black bean extract may have anti-diabetic protective effects by modulating gene expression, resulting in a promising alternative for T2DM patients.
Fermented Astragalus and its metabolites regulate inflammatory status and gut microbiota to repair intestinal barrier damage in dextran sulfate sodium-induced ulcerative colitis
Authors: Li Junxiang , Ma Yingchun , Li Xiaofeng , Wang Yafei , Huo Zeqi , Lin Yang , Li Jiaru , Yang Hui , Zhang Zhiming , Yang Pingrong , Zhang Chunjiang
Published: November 2022

Fermentation represents an efficient biotechnological approach to increase the nutritional and functional potential of traditional Chinese medicine. In this study, Lactobacillus plantarum was used to ferment traditional Chinese medicine Astragalus, the differential metabolites in the fermented Astragalus (FA) were identified by ultra-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS), and the ameliorating effect of FA on dextran sulfate sodium (DSS)-induced colitis in mice were further explored. The results showed that 11 differential metabolites such as raffinose, progesterone and uridine were identified in FA, which may help improve the ability of FA to alleviate colitis. Prophylactic FA supplementation effectively improved DAI score, colon length and histopathological lesion in DSS-treated mice. The abnormal activation of the intestinal immune barrier in mice was controlled after FA supplementation, the contents of myeloperoxidase (MPO) and IgE were reduced and the contents of IgA were increased. The intestinal pro-inflammatory factors TNF-α, IL-1β, IL-6, and IL-17 were down-regulated and the anti-inflammatory factors IL-10 and TGF-β were up-regulated, suggesting that FA can intervene in inflammatory status by regulating the balance of Th1/Th2/Th17/Treg related cytokines. In addition, FA supplementation modified the structure of the intestinal microbiota and enriched the abundance of Akkermansia and Alistipes, which were positively associated with the production of short-chain fatty acids. These microbes and their metabolites induced by FA also be involved in maintaining the intestinal mucosal barrier integrity by affecting mucosal immunity. We observed that intestinal tight junction protein and mucous secreting protein ZO-1, occludin, and MUC2 genes expression were more pronounced in mice supplemented with FA compared to unfermented Astragalus, along with modulation of intestinal epithelial cells (IECs) apoptosis, verifying the intestinal mucosal barrier repaired by FA. This study is the first to suggest that FA as a potential modulator can more effectively regulate the inflammatory status and gut microbiota to repair the intestinal barrier damage caused by colitis.
Optimizing margin status for improving prognosis in patients with oral cavity squamous cell carcinoma: A retrospective study from the two highest-volume Taiwanese hospitals
Authors: Liao Chun-Ta , Lee Li-Yu , Lee Shu-Ru , Ng Shu-Hang , Liu Tsang-Wu , Chien Chih-Yen , Lin Jin-Ching , Wang Cheng Ping , Terng Shyuang-Der , Hua Chun-Hung , Chen Tsung-Ming , Chen Wen-Cheng , Tsai Yao-Te , Kang Chung-Jan , Tsai Chi-Ying , Chu Ying-Hsia , Lin Chien-Yu , Fan Kang-Hsing , Wang Hung-Ming , Hsieh Chia-Hsun , Yeh Chih-Hua , Lin Chih-Hung , Tsao Chung-Kan , Yen Tzu-Chen , Cheng Nai-Ming , Fang Tuan-Jen , Huang Shiang-Fu , Lee Li-Ang , Fang Ku-Hao , Wang Yu-Chien , Lin Wan-Ni , Hsin Li-Jen , Wen Yu-Wen
Published: November 2022

Background

In the treatment of oral cavity squamous cell carcinoma (OCSCC), surgical quality measures which are expected to affect outcomes, including the achievement of a clear margin, are surgeon-dependent but might not be invariably associated with hospital volume. Our objective was to explore surgical margin variations and survival differences of OCSCC between two highest-volume hospitals in Taiwan.

Materials and methods

A total of 2009 and 1019 patients with OCSCC who were treated at the two highest-volume Taiwanese hospitals (termed Hospital 1 and Hospital 2, respectively) were included. We examined how a pathological margin <5 mm impacted patient outcomes before and after propensity score (PS) matching.

Results

The prevalence of margins <5 mm was markedly lower in Hospital 1 than in Hospital 2 (34.5%/65.2%, p<0.0001). Compared with Hospital 2, tumor severity was higher in Hospital 1. On univariable analysis, being treated in Hospital 2 (versus Hospital 1; hazard ratio [HR] for 5-year disease-specific survival [DSS] = 1.34, p=0.0002; HR for 5-year overall survival [OS] = 1.17, p=0.0271) and margins <5 mm (versus ≥5 mm; HR for 5-year DSS = 1.63, p<0.0001; HR for 5-year OS = 1.48, p<0.0001) were identified as adverse factors. The associations of treatment in Hospital 2 and margins <5 mm with less favorable outcomes remained significant after adjustment for potential confounders in multivariable analyses, as well as in the PS-matched cohort. The 5-year survival differences between patients operated in Hospital 1 and Hospital 2 were even more pronounced in the PS-matched cohort (before PS matching: DSS, 79%/74%, p=0.0002; OS, 71%/68%, p=0.0269; after PS matching: DSS, 84%/72%, p<0.0001; OS, 75%/66%, p<0.0001). In the entire cohort, the rate of adjuvant therapy was found to be lower in patients with margins ≥5 mm than in those with margins <5 mm (42.7%/57.0%, p<0.0001).

Conclusions

Within the two highest-volume hospitals in Taiwan, patients with OCSCC with a clear margin status (≥5 mm) achieved more favorable outcomes. These results have clinical implications and show how initiatives aimed at improving the margin quality can translate in better outcomes. A clear margin status can reduce the need for adjuvant therapy, ultimately improving quality of life.
RET fusion mutation detected by re-biopsy 7 years after initial cytotoxic chemotherapy: A case report
Authors: Morikawa Kei , Handa Hiroshi , Ueno Junko , Tsuruoka Hajime , Inoue Takeo , Shimada Naoki , Koike Junki , Nakamura Seiji , Sato Yoshiharu , Mineshita Masamichi
Published: November 2022

Personalized medicine using molecular-targeted drugs to achieve better therapeutic response and long-term prognosis is common practice for lung cancer treatment. However, in cases before gene batch tests were available, medical treatment continued without the detection of rare mutations. We report a sixty-seven-old year man diagnosed with adenocarcinoma T1cN3M1a, stage IVA. Initial screening performed 7 years earlier using EGFR mutation and ALK immunohistochemical tests were negative. Although first-line cytotoxic combination chemotherapy was remarkably effective, a gradual regression of the primary lesion was noted. After a recent bronchoscopic re-biopsy, RET fusion was detected by gene panel test. In addition, we were able to confirm RET from FFPE specimens obtained from 7-year-old pleural effusion cell blocks. Subsequent administration of the molecular-targeted drug selpercatinib, was highly effective for the primary lesion and all metastatic lesions including brain metastases. We describe a case of RET fusion-positive lung cancer where molecular targeted therapy and cytotoxic drug showed a drastic response and long-term therapy was well maintained. Next generation sequencing was able to correctly diagnose RET fusion mutation using re-biopsy specimen after going undiagnosed for 7 years.
Triglyceride glucose index and Atherogenic index of plasma for predicting colorectal neoplasms in patients without cardiovascular diseases
Authors: Han Muzhou , Wang Hao , Yang Shuyue , Zhu Siying , Zhao Guiping , Shi Haiyun , Li Peng
Published: November 2022

Background and aims

Colorectal neoplasms (CRN) include colorectal cancer (CRC) and colorectal adenoma (CRA). The relationship between CRN and triglyceride-glucose (TyG) index or between CRN and atherogenic index of plasma (AIP) is unclear. This study aims to investigate the roles of TyG index and AIP in predicting CRN in people without cardiovascular disease (CVD).

Methods

2409 patients without CVD underwent colonoscopy were enrolled. Clinical information and relevant laboratory test results of these patients were collected and recorded. According to endoscopic and pathological results, all participants were divided into a neoplasms group and a non-neoplasms group. The TyG index was calculated as ln (TGs×FPG/2), while AIP was calculated as log (TGs/HDL-C). We used uni- and multivariate logistic regression and restricted cubic spline (RCS) to analyze the association between the TyG inedx, AIP and CRN, develop predictive models and construct the nomograms. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive value for CRN.

Results

Participants in the neoplasms group were more likely to be older, have higher TyG index, higher AIP and higher rates of fecal occult blood test positivity, and were more likely to be male, smokers and those with the family history of CRC (P < 0.05). The higher TyG index was related to the higher risk of CRN [OR (95% CI): 1.23 (1.08 - 1.41), P = 0.003]. The higher AIP was related to the higher risk of CRN [OR (95% CI): 1.55 (1.16 - 2.06), P = 0.003]. These two indicators are better for predicting CRN in women than men. The combined use of the TyG index and other independent risk factors (age, sex, smoking status, family history and FOBT) to distinguish CRN was effective, with a sensitivity of 61.0%, a specificity of 65.1% and an AUC of 0.669 (95%CI, 0.639 - 0.698). Likewise, the combined use of the AIP and other independent risk factors to distinguish CRN was also effective, the model had an overall 56.3% sensitivity and 68.7% specificity with an AUC of 0.667 (95%CI, 0.638 - 0.697).

Conclusion

This study showed that the TyG index and the AIP might be biomarkers that could be used to predict the risk of CRN in patients without CVD.
Poly(rC)-binding proteins as pleiotropic regulators in hematopoiesis and hematological malignancy
Authors: Zhao Huijuan , Wei Ziqing , Shen Guomin , Chen Yixiang , Hao Xueqin , Li Sanqiang , Wang Rong
Published: November 2022

Poly(rC)-binding proteins (PCBPs), a defined subfamily of RNA binding proteins, are characterized by their high affinity and sequence-specific interaction with poly-cytosine (poly-C). The PCBP family comprises five members, including hnRNP K and PCBP1-4. These proteins share a relatively similar structure motif, with triple hnRNP K homology (KH) domains responsible for recognizing and combining C-rich regions of mRNA and single- and double-stranded DNA. Numerous studies have indicated that PCBPs play a prominent role in hematopoietic cell growth, differentiation, and tumorigenesis at multiple levels of regulation. Herein, we summarized the currently available literature regarding the structural and functional divergence of various PCBP family members. Furthermore, we focused on their roles in normal hematopoiesis, particularly in erythropoiesis. More importantly, we also discussed and highlighted their involvement in carcinogenesis, including leukemia and lymphoma, aiming to clarify the pleiotropic roles and molecular mechanisms in the hematopoietic compartment.
Diffusion-weighted MRI to determine response and long-term clinical outcomes in muscle-invasive bladder cancer following neoadjuvant chemotherapy
Authors: Hafeez Shaista , Koh Mu , Jones Kelly , Ghzal Amir El , D’Arcy James , Kumar Pardeep , Khoo Vincent , Lalondrelle Susan , McDonald Fiona , Thompson Alan , Scurr Erica , Sohaib Aslam , Huddart Robert Anthony
Published: November 2022

Objective

This study aims to determine local treatment response and long-term survival outcomes in patients with localised muscle-invasive bladder cancer (MIBC) patients receiving neoadjuvant chemotherapy (NAC) using diffusion-weighted MRI (DWI) and apparent diffusion coefficient (ADC) analysis.

Methods

Patients with T2-T4aN0-3M0 bladder cancer suitable for NAC were recruited prospectively. DWI was performed prior to NAC and was repeated following NAC completion. Conventional response assessment was performed with cystoscopy and tumour site biopsy. Response was dichotomised into response (<T2) or poor response (≥T2). Patients proceeded to either radical cystectomy or chemo-radiotherapy as standard of care. Tumour ADC values were calculated for all b-values (ADCall) and high b-values (ADCb100). Mean ADC, percentiles, skew, kurtosis, and their change (ΔADC and %ΔADC) were determined. Threshold predictive of response with highest specificity was ascertained using receiver operating characteristic (ROC) analysis. Median overall survival (OS), bladder-cancer-specific survival (bCSS), progression-free survival (PFS), and time to cystectomy were estimated using Kaplan–Meier method. Significant area under the curve (AUC) cut points were used to determine relationship with long-term endpoints and were compared using log-rank test.

Results

Forty-eight patients (96 DWI) were evaluated. NAC response was associated with significant increase in mean ΔADC and %ΔADC compared to poor response (ΔADCall 0.32×10−3 versus 0.11×10−3 mm2/s; p=0.009, and %ΔADCall 21.70% versus 8.23%; p=0.013). Highest specificity predicting response was seen at 75th percentile ADC (AUC, 0.8; p=0.01). Sensitivity, specificity, positive predictive power, and negative predictive power of %ΔADCb100 75th percentile was 73.7%, 90.0%, 96.6%, and 52.9%, respectively. %ΔADCb100 75th percentile >15.5% was associated with significant improvement in OS (HR, 0.40; 95% CI, 0.19–0.86; p=0.0179), bCSS (HR, 0.26; 95% CI, 0.08–0.82; p=0.0214), PFS (HR, 0.16; 95% CI, 0.05–0.48; p=0.0012), and time to cystectomy (HR, 0.19; 95% CI, 0.07–0.47; p=0.0004).

Conclusions

Quantitative ADC analysis can successfully identify NAC response and improved long-term clinical outcomes. Multi-centre validation to assess reproducibility and repeatability is required before testing within clinical trials to inform MIBC treatment decision making.

Advances in knowledge

We successfully demonstrated that measured change in DWI can successfully identify NAC response and improved long-term survival outcomes.
Back to basic: Trials and tribulations of alkalizing agents in cancer
Authors: Gillies Robert J. , Ibrahim-Hashim Arig , Ordway Bryce , Gatenby Robert A.
Published: November 2022

“Dysregulated” metabolism is a characteristic of the cancer cell phenotype. This includes persistent use of glycolytic metabolism in normoxic environments (Warburg effect) leading to increased acid production and accumulation of protons in the interstitial space. Although often thought to be disordered, altered cancer metabolism is the outcome of intense Darwinian selection and, thus, must have evolved to maximize cancer cell fitness. In an evolutionary context, cancer-induced acidification of the microenvironment represents a niche construction strategy to promote proliferation. Ecological advantages conferred on the cancer population included remodeling of the extracellular matrix to promote local invasion, suppression of potential competitive proliferation of fibroblasts, and suppression of host immune response. Preclinical data demonstrates that increasing the serum buffering capacity (through, for example, oral sodium bicarbonate and TRIS) can neutralize the acidic tumor microenvironment with inhibition local invasion and proliferation which can be synergistic with the effects of chemotherapy and immunotherapy agents. Here, we describe the proton dynamics in cancer and their influence on tumor progression and metastasis. Additionally, we will discuss targeting the tumor acidosis with alkalizing agents including our bicarbonate clinical trial results.

Clinical Trial Registration

clinicaltrials.gov, identifier NCT01350583, NCT01198821 and NCT01846429.
Development and validation of nomograms predicting postoperative survival in patients with chromophobe renal cell carcinoma
Authors: Li Shuaishuai , Zhu Jiawei , He Zhenwei , Ashok Raj , Xue Ning , Liu Zijie , Ding Li , Zhu Haitao
Published: November 2022

Objective

The purpose of our study is to construct and validate nomograms that effectively predict postoperative overall survival and cancer-specific survival for patients with chromophobe renal cell carcinoma (chRCC).

Method

Clinical, social, and pathological data from 6016 patients with chRCC collected from the SEER database were screened from 2004 to 2015. They were randomly assigned to a training cohort (n = 4212) and a validation cohort (n = 1804) at a 7:3 ratio. Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were used to identify the prognostic factors affecting overall survival (OS) and cancer-specific survival (CSS) and establish nomograms. Their performance was validated internally and externally by calculating Harrell’s C-indexes, area under the curve (AUC), calibration, and decision curves. For external validation, samples from postoperative patients with chRCC at 3 independent centers in Xuzhou, China, were collected. Risk stratification models were built according to the total scores of each patient. Kaplan-Meier curves were generated for the low-risk, intermediate-risk, and high-risk groups to evaluate survival.

Results

The C-indexes, AUC curves, and decision curves revealed the high ability of the nomograms in predicting OS and CSS, overall better than that of AJCC and TNM staging. Moreover, in internal and external validation, the calibration curves of 5-, 8-, and 10-year OS agreed with the actual survival. Kaplan-Meier curves indicated significant differences in survival rates among the 3 risk groups in OS or CSS.

Conclusion

The nomograms showed favourable predictive power for OS and CSS. Thus, they should contribute to evaluating the prognosis of patients with chRCC. Furthermore, the risk stratification models established on the nomograms can guide the prognosis of patients and further treatment.
Acquired von Willebrand syndrome (AVWS) type 2, characterized by decreased high molecular weight multimers, is common in children with severe pulmonary hypertension (PH)
Authors: Wieland Ivonne , Diekmann Franziska , Carlens Julia , Hinze Laura , Lambeck Katharina , Jack Thomas , Hansmann Georg
Published: November 2022

Background and objectives

Emerging evidence suggests that increased degradation of von Willebrand factor and decrease in high molecular weight multimers occurs in patients with pulmonary hypertension (PH). However, the link between acquired von Willebrand Syndrome (AVWS) type 2 and PH remains poorly understood.

Material and methods

We retrospectively evaluated the charts of 20 children with PH who underwent bilateral lung transplantation (LuTx) between 2013 and 2022. Von Willebrand variables were determined in 14 of these patients; 11 patients had complete diagnostics including multimer analysis.

Results

We confirmed AVWS in 82% of the children studied (9 of 11 patients by multimer analysis). The two remaining patients had suspected AVWS type 2 because of a VWF:Ac/VWF:Ag ratio of <0.7. Platelet dysfunction or suspicion of VWD type 1 were found in two separate patients. All but one of the 14 children with severe PH had a coagulation disorder. Most patients (9 proven, 2 suspected) had AVWS type 2. Notably, 3 of 5 patients (60%) with normal VWF:Ac/VWF:Ag ratio >0.7 had abnormal VWF multimers, indicating AVWS type 2. Hemostatic complications were observed in 4 of 12 (33%) patients with VWS and 3 of 6 (50%) patients without diagnostics and therapy.

Conclusion

For children with moderate to severe PH, we recommend systematic analysis of von Willebrand variables, including multimer analysis, PFA-100 and platelet function testing. Awareness of the diagnosis “AVWS” and adequate therapy may help to prevent these patients from bleeding complications in case of surgical interventions or trauma.
Case Report: Novel LIM domain-binding protein 3 (LDB3) mutations associated with hypertrophic cardiomyopathy family
Authors: Zheng Junmin , Huang Zhuangzhuang , Hou Shan , Jiang Xunwei , Zhang Yongwei , Liu Wei , Jia Jia , Li Yun , Sun Xiaomin , Xie Lijian , Zhao Xiaopei , Hou Cuilan , Xiao Tingting
Published: November 2022

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant cardiomyopathy, which is one of the most common reasons for cardiac arrest in children or adolescents. It is characterized by ventricular hypertrophy (usually left ventricle), small ventricular cavity, and reduced ventricular diastolic compliance found by echocardiography in the absence of abnormal load (such as hypertension or aortic stenosis). HCM is usually caused by mutations in genes encoding sarcomere or sarcomere-related genes. Whole exome sequencing (WES) is performed to identify probable causative genes. Through WES, we identified LIM domain-binding protein 3 (LDB3) mutations (R547Q and P323S) respectively in an 11-year-old HCM girl and a 6-year-old HCM boy. Neural network analyses showed that the LDB3 (R547Q and P323S) mutation decreased its protein stability, with confidence scores of −0.9211 and −0.8967. The STRUM server also confirmed that the mutation decreased its protein stability. Thus, LDB3 mutation may be associated with heritable HCM. To our knowledge, this is the first time to report LDB3 heterozygous variants (R547Q and P323S) responsible for heritable HCM.
SARS-CoV-2 viral clearance and viral load kinetics in young children (1–6 years) compared to adults: Results of a longitudinal study in Germany
Authors: Sandoni Anna , Schaffrath Rosario Angelika , Michel Janine , Kuttig Tim , Wurm Juliane , Damerow Stefan , Iwanowski Helena , Finkel Bianca , Schrick Livia , Buchholz Udo , Haas Walter , Varnaccia Gianni , Kubisch Ulrike , Jordan Susanne , Schienkiewitz Anja , Nitsche Andreas , Loss Julika
Published: November 2022

Objective

To investigate SARS-COV-2 viral clearance and viral load kinetics in the course of infection in children aged 1–6 years in comparison with adults.

Methods

Prospective cohort study of infected daycare children and staff and their close contacts in households from 11/2020 to 06/2021. Adult participants took upper respiratory tract specimen from themselves and/or their children, for PCR tests on SARS-CoV-2. Data on symptoms and exposure were used to determine the date of probable infection for each participant. We determined (a) viral clearance, and (b) viral load dynamics over time. Samples were taken from day 4–6 to day 16–18 after diagnosis of the index case in the respective daycare group (5 samples per participant).

Results

We included 40 children (1–6 years) and 67 adults (18–77 years) with SARS-CoV-2 infection. Samples were available at a mean of 4.3 points of time per participant. Among the participants, the 12-day study period fell in different periods within the individual course of infection, ranging from day 5–17 to day 15–26 after assumed infection.

Children reached viral clearance at a median of 20 days after assumed infection (95% CI 17–21 days, Kaplan-Meier Analysis), adults at 23 days (95% CI 20–25 days, difference not significant). In both children and adults, viral load decreased over time with trajectories of the mean viral load not being statistically different between groups. Kaplan-Meier calculations show that from day 15 (95% CI 13–15), 50% of all participants had a viral load <1 million copies/ml, i.e. were no longer infectious or negative.

Conclusion

Children aged 1–6 and adults infected with SARS-CoV-2 (wild type and Alpha variant) did not differ significantly in terms of viral load kinetics and time needed to clear the virus. Therefore, containment measures are important also in the daycare settings as long as the pandemic continues.
Efficacy and safety of oncolytic virus combined with chemotherapy or immune checkpoint inhibitors in solid tumor patients: A meta-analysis
Authors: Liu Xiangxing , Zhang Jiaojiao , Feng Keqing , Wang Simin , Chen Liming , Niu Suping , Lu Qian , Fang Yi
Published: November 2022

Background: In recent years, several clinical trials have focused on oncolytic virus (OVs) combined with chemotherapy or immune checkpoint inhibitors (ICIs) in solid tumor patients, which showed encouraging effects. However, few studies have concentrated on the summary on the safety and efficacy of the combined treatments. Therefore, we conducted this meta-analysis to explore the safety and curative effect of the combined therapy.

Methods: We searched the PubMed, Cochrane Library, Embase, and Clinicaltrials.gov databases to comprehensively select articles on OVs combined with chemotherapy or ICIs for the solid tumor treatment. Overall survival (OS), progression-free survival (PFS), 1-year survival rate, 2-year survival rate, objective response rate (ORR), and adverse events (AEs) were the outcomes.

Results: Fifteen studies with 903 patients were included in this meta-analysis. The pooled ORR was 32% [95% confidence interval (CI): 27–36%, I2 = 24.9%, p = 0.239]. Median OS and median PFS were 6.79 months (CI: 4.29–9.30, I2 = 62.9%, p = 0.044) and 3.40 months (CI: 2.59–4.22, I2 = 0.0%, p = 0.715), respectively. The 1-year survival rate was 38% (CI: 0.29–0.47, I2 = 62.9%, p = 0.044), and the 2-year survival rate was 24% (CI: 12–37%, I2 = 0.0%, p = 0.805). The most common AEs were fever (63%, CI: 57–69%, I2 = 2.3%, p = 0.402), fatigue (58%, CI: 51–65%, I2 = 49.2%, p = 0.096), chill (52%, CI: 43–60%, I2 = 0.0%, p = 0.958), and neutropenia (53%, CI: 47–60%, I2 = 0.0%, p = 0.944).

Conclusion: OVs combined with ICIs showed a better efficacy than OVs combined with chemotherapy, which lends support to further clinical trials of OVs combined with ICIs. In addition, OVs combined with pembrolizumab can exert increased safety and efficacy. The toxicity of grades ≥3 should be carefully monitored and observed. However, high-quality, large-scale clinical trials should be completed to further confirm the efficacy and safety of OVs combined with ICIs.

Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/login.php], identifier [RD42022348568].
Gut microbiota mediated hypoglycemic effect of Astragalus membranaceus polysaccharides in db/db mice
Authors: Song Qianbo , Cheng Sau Wan , Li Dan , Cheng Huiyuan , Lai Yuen Sze , Han Quanbin , Wu Hoi Yan , Shaw Pang Chui , Zuo Zhong
Published: November 2022

Gut microbiota has been reported to be closely associated with Type-II diabetes. Restoration of disordered gut microbiota ecosystem has been developed into a therapeutic strategy and gradually applied on Type-II diabetes treatment with both western drugs and herbal polysaccharides. Although Astragalus membranaceus polysaccharides (AMP) have also been used to treat Type-II diabetes, no study investigated correlations between gut microbiota regulation and its hypoglycemic effect. In the present study, the role of gut microbiota on the hypoglycemic effect of AMP in db/db mice was investigated for the first time. Sixteen days treatment of AMP at the dosage of 600 mg/kg in db/db mice not only alleviated its diabetic symptoms significantly but also restored its gut microbiota community with increased production of fecal short chain fatty acids (SCFA). Our further Pearson correlation analyses revealed that the relative abundance of two intestinal bacteria, Akkermansia and Faecalibaculum, were significantly positively correlated with the hypoglycemic effect of AMP as well as fecal SCFA production. It was also noted that treatment of AMP resulted in increased secretion of glucagon-like peptide-1 (GLP-1) in serum and enhanced intestinal integrity. Further mechanistic study revealed that the increased SCFA after AMP treatment could stimulate GLP-1 secretion and improve intestinal integrity via enhancing the expression of G protein-coupled receptors 41/43 and tight junction proteins (Occudin and ZO-1), respectively, leading to the alleviation of diabetic symptoms in db/db mice.
Surface-enhanced Raman spectroscopic activity study on topological ZnSe nanostructures
Authors: Liu Mei , Duan Pengyi , Shafi Muhammad , Liu Wenying , Zhang Wenjie , Zhang Can , Hu Xiaoxuan , Gao Jing , Zhang Chao
Published: November 2022

Topological nanomaterials generally exhibit different defect structures, high specific surface areas, and varying bandgaps. These special geometries, energy-level structures, and interfacial interaction properties provide possibilities to explore interesting properties in the surface-enhanced Raman scattering (SERS). Such properties offer unexplored possibilities for exploring interesting physics and materials science in the field of SERS physical property research and further enhancing substrate materials’ SERS activity. In this paper, the ZnSe topological nanowire crystallite structure was grown using the chemical vapor deposition method, twin defects were introduced, and a topological branched structure that caused the corresponding changes in SERS activity was systematically investigated. On topological ZnSe nanowires, rhodamine 6G (R6G), methylene blue (MB), and crystalline violet (CV) molecules were detected using Raman spectroscopy. The Raman signal enhancement of MB on topological branched nanowires was about 1.9 times that of the trunk nanowires. Finally, the national standard measurement of malachite green (MG) content in water bodies were realized. The results suggest that semiconductor ZnSe topographical nanowires are an emerging class of SERS substrates, and a thorough investigation into the relationship between material structure and SERS performance in specific topological regions will provide new evidence for the principle of chemical enhancement of SERS, as well as recommendations for developing precisely functionalized SERS substrate nanomaterials.
Enhanced nitrogen use efficiency, growth and yield of wheat through soil urea hydrolysis inhibition by Vachellia nilotica extract
Authors: Rana Muhammad Ajmal , Mahmood Rashid , Nadeem Faisal , Wang Yun , Jin Chongwei , Liu Xingxing
Published: November 2022

Soil urease inhibition slows down the urea hydrolysis and prolongs nitrogen (N) stay in soil, resulting in an increased N uptake by plants. Apart from several chemical urease inhibitors, the urease inhibition potential of plant extracts is rarely reported. In our previous study, the soil urease inhibition by Vachellia nilotica leaf extract was reported; however, its role in relation to growth and yield of wheat (Triticum aestivum) under pot and field conditions remains unknown. The acetonic extracts of 10, 20, and 50 g Vachellia nilotica leaves were given code names viz. Vn.Fl-10, Vn.Fl-20 and Vn.Fl-50, respectively, and coated on 100 g of urea individually. The enhancements of growth (total number of tillers, number of productive tillers, number of spikelets per spike, number of grains per spike, and 1000-grains weight) and yield (biological yield, straw yield, and grain yield) parameters of wheat by Vn.Fl-20 and Vn.Fl-50 coated urea treatments were compared with uncoated urea in a pot experiment. The experiment indicated that the Vachellia nilotica extract coatings were effective at improving N persistence in soil, as reflected by increased grain and straw N concentrations as well as uptakes. The reproduction of the aforementioned results, at the half and full recommended dose of urea under field conditions, reconfirmed the effectiveness of Vachellia nillotica coatings. Moreover, the Vn.Fl-20 and Vn.Fl-50 coated urea, at the half as well as full recommended dose under field conditions, proved equally effective in terms of higher biological, straw, and grain yield, and grain N uptake. The increments in the total number of tillers, number of productive tillers, 1000-grain weight, biological yield, straw yield, grain yield, grain N concentration, grain N-, and straw N uptake along with nitrogen use efficiency (NUE) components, i.e. nitrogen partial factor productivity (NPFP), nitrogen agronomic efficiency (NAE), partial nitrogen balance (PNB), and nitrogen recovery efficiency (NRE) of wheat highlighted the superiority of Vn.Fl-20 coating over the hydroquinone (Hq) coating on urea at the full recommended dose under field conditions. Given the findings of this study, Vachellia nilotica leaf extract coating (Vn.Fl-20) can be used as a natural urease inhibitor to reduce urea hydrolysis and enhance wheat productivity.
Five new secondary metabolites from an endophytic fungus Phomopsis sp. SZSJ-7B
Authors: Chen Yan , Wang Huan , Ke Xin , Sang Zihuan , Kuang Min , Peng Weiwei , Tan Jianbing , Zheng Yuting , Zou Zhenxing , Tan Haibo
Published: November 2022

Two previously undescribed lactones, phomolides A and B (1 and 2), and three new sesquiterpenoids, phomenes A–C (3–5), together with one known compound, colletotricholide A (6), were isolated from the endophytic fungus Phomopsis sp. SZSJ-7B. Their chemical structures, including the absolute configurations, were comprehensively established by extensive analyses of NMR, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism powered by theoretical calculations, and X-ray diffractions. Moreover, the cytotoxic and antibacterial activities of compounds 1–6 were also evaluated, and the results demonstrated that compound 2 showed significant antibacterial effects towards methicillin-resistant Staphylococcus aureus and S. aureus strains with minimum inhibitory concentration as low as 6.25 μg/ml, which was comparable to that of the clinical drug vancomycin. Moreover, all compounds showed no cytotoxic activity.
A systematic review of the pharmacological modulation of autobiographical memory specificity
Authors: Cawley Emma , Piazza Giulia , Das Ravi K. , Kamboj Sunjeev K.
Published: November 2022

Background

Over-general autobiographical memory (AM) retrieval is proposed to have a causal role in the maintenance of psychological disorders like depression and PTSD. As such, the identification of drugs that modulate AM specificity may open up new avenues of research on pharmacological modeling and treatment of psychological disorders.

Aim

The current review summarizes randomized, placebo-controlled studies of acute pharmacological modulation of AM specificity.

Method

A systematic search was conducted of studies that examined the acute effects of pharmacological interventions on AM specificity in human volunteers (healthy and clinical participants) measured using the Autobiographical Memory Test.

Results

Seventeen studies were identified (986 total participants), of which 16 were judged to have low risk of bias. The presence and direction of effects varied across drugs and diagnostic status of participants (clinical vs. healthy volunteers). The most commonly studied drug—hydrocortisone—produced an overall impairment in AM specificity in healthy volunteers [g = −0.28, CI (−0.53, −0.03), p = 0.03], although improvements were reported in two studies of clinical participants. In general, studies of monoamine modulators reported no effect on specificity.

Conclusion

Pharmacological enhancement of AM specificity is inconsistent, although monaminergic modulators show little promise in this regard. Drugs that reduce AM specificity in healthy volunteers may be useful experimental-pharmacological tools that mimic an important transdiagnostic impairment in psychological disorders.

Systematic review registration

PROSPERO, identifier CRD42020199076, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020199076.
Invariance-based causal prediction to identify the direct causes of suicidal behavior
Authors: Goddard Austin V. , Xiang Yu , Bryan Craig J.
Published: November 2022

Despite decades of research, the direct causes of suicide remain unknown. Some researchers have proposed that suicide is sufficiently complex that no single variable or set of variables can be determined causal. The invariance-based causal prediction (ICP) is a contemporary data analytic method developed to identify the direct causal relationships, but the method has not yet been applied to suicide. In this study, we used ICP to identify the variables that were most directly related to the emergence of suicidal behavior in a prospective sample of 2,744 primary care patients. Fifty-eight (2.1%) participants reported suicidal behavior during the following year. Of 18 predictors tested, shame was most likely to be directly causal only under the least restrictive conditions. No single variable or set of variables was identified. Results support the indeterminacy hypothesis that suicide is caused by many combinations of factors, none of which are necessary for suicide to occur.
Anthracycline-induced cardiotoxicity and senescence
Authors: Booth Laura K. , Redgrave Rachael E. , Folaranmi Omowumi , Gill Jason H. , Richardson Gavin D.
Published: November 2022

Cancer continues to place a heavy burden on healthcare systems around the world. Although cancer survivorship continues to improve, cardiotoxicity leading to cardiomyopathy and heart failure as a consequence of cancer therapy is rising, and yesterday’s cancer survivors are fast becoming today’s heart failure patients. Although the mechanisms driving cardiotoxicity are complex, cellular senescence is gaining attention as a major contributor to chemotherapy-induced cardiotoxicity and, therefore, may also represent a novel therapeutic target to prevent this disease. Cellular senescence is a well-recognized response to clinical doses of chemotherapies, including anthracyclines, and is defined by cell cycle exit, phenotypic alterations which include mitochondrial dysfunction, and the expression of the pro-senescent, pro-fibrotic, and pro-inflammatory senescence-associated phenotype. Senescence has an established involvement in promoting myocardial remodeling during aging, and studies have demonstrated that the elimination of senescence can attenuate the pathophysiology of several cardiovascular diseases. Most recently, pharmacology-mediated elimination of senescence, using a class of drugs termed senolytics, has been demonstrated to prevent myocardial dysfunction in preclinical models of chemotherapy-induced cardiotoxicity. In this review, we will discuss the evidence that anthracycline-induced senescence causes the long-term cardiotoxicity of anticancer chemotherapies, consider how the senescent phenotype may promote myocardial dysfunction, and examine the exciting possibility that targeting senescence may prove a therapeutic strategy to prevent or even reverse chemotherapy-induced cardiac dysfunction.
Fatty acid profile driven by maternal diet is associated with the composition of human milk microbiota
Authors: Marsh Alan J. , Azcarate-Peril M. Andrea , Aljumaah Mashael R. , Neville Jessica , Perrin Maryanne T. , Dean Lisa L. , Wheeler Michael D. , Hines Ian N. , Pawlak Roman
Published: November 2022

Little is known regarding the impact of diet on the breast milk microbiome. We hypothesized that vegan, vegetarian, and omnivore diets would impact the human milk microbiota. We also aimed to explore associations between human milk fatty acid concentrations and microbial composition. A cross-sectional microbiome diversity analysis of human milk samples (N = 72) was performed using 16S rRNA amplicon sequencing. Human milk microbial diversity was not associated with diet type. However, analysis of microbiome in relation to fatty acid profiles revealed significant differences in the overall composition of the human milk microbiota between high (> 0.7% of total fat) and low (< 0.7%) trans-fatty acid groups (TF) (p = 0.039, pairwise PERMANOVA p = 0.035), high (> 40%) versus low (< 40%) saturated fatty acids (UniFrac p = 0.083, PERMANOVA p = 0.094), and high (>60%) versus low (<60%) unsaturated fatty acids (UF) (UniFrac p = 0.094, PERMANOVA p = 0.093). 84% of samples from omnivore mothers were in the high TF group compared to only 12% of samples from vegans. Gut-associated species (Faecalibacterium, Blautia, Roseburia and Subdoligranulum) and Lactobacillus were characteristic of both high UF and TF groups, but not the low-fat groups. Functional analysis revealed 2,4-dichlorophenol 6-monooxygenase was differentially abundant in the high UF group. Although microbiome diversity did not differ by diet type, TF breast milk content differed by diet group, highlighting the relationship between maternal diet and the microbial profile of human milk.
Charisma™ virtual social training: A digital health platform and protocol
Authors: Johnson Maria , Tate Aaron M. , Tate Kathleen , Laane Sarah A. , Chang Zhengsi , Chapman Sandra Bond
Published: November 2022

Low immersion virtual reality (LIVR) is a computer-generated, three-dimensional virtual environment that allows for authentic social interactions through a personal avatar, or digital representation of oneself. Lab-based delivery of LIVR social skills intervention has been shown to support social learning through controlled, targeted practice. Recent remote technological advancements allow LIVR-based social skills training to potentially overcome accessibility barriers by delivering to youth in their home. This study investigated the impact of 10-h of Charisma™ Virtual Social Training (CHARISMA-VST), a LIVR-based intervention, on social skill changes in children and adolescents who struggle socially via either in-person or remote training protocols. Specifically, the aims examined both the impact of training location (in-person vs remote access) and diagnosis (parent report of autism spectrum disorder (ASD) diagnosis versus parent report of other non-ASD diagnosis) on objective measures of social skill change following CHARISMA-VST. Researchers delivered the CHARISMA-VST via Charisma 1.0, a customized virtual gaming environment. Sixty-seven participants (49 males, 18 females) between the ages of 9–17, with parent reported social challenges, completed 10, 1-h CHARISMA-VST sessions during which nine social cognitive strategies were taught and then practiced within a LIVR environment with interspersed social coaching. Four social cognitive domains were measured pre-post training: emotion recognition, social inferencing, social attribution, and social self-schemata. Results revealed improvements in emotion recognition, social inferencing, social attribution, and social self-schemata with medium to large effect sizes following the CHARISMA-VST. There was no moderating effect of training location on emotion recognition, social inferencing, and social self-schemata, suggesting comparable gains whether participants accessed the technology in their own homes or from a school or specialty center. There was no moderating effect of ASD versus non-ASD diagnosis on performance measures, suggesting CHARISMA-VST may be effective in improving social skills in individuals beyond its initially designed use focused on individuals with ASD. These encouraging findings from this pilot intervention study provide some of the first evidence of potential new virtual technology tools, as exemplified by CHARISMA-VST, to improve one of the most important aspects of human behavior—social skills and human connectedness in youth with a range of social competency challenges.