bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of In2G Variant in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
Authors: Kocova Mirjana , Concolino Paola , Falhammar Henrik
Published: January 2022

Substantial research has been performed during the last decades on the clinical and genetic variability of congenital adrenal hyperplasia (CAH) and its most common form, 21-hydroxylase deficiency (21OHD). CAH is one of the most prevalent autosomal recessive diseases in humans, and it can be divided into classic—further subdivided into salt wasting (SW) and simple virilizing (SV)—and non-classic (NC) forms. Pathogenic variants of CYP21A2 gene, encoding the 21-hydroxylase enzyme, have been reported with variable prevalence in different populations. NM_000500.9:c.293-13C/A>G (In2G) variant represents the most common CYP21A2 gene changes related to the classic 21OHD form. However, the phenotype of In2G carriers is variable depending on the variant homozygous/heterozygous status and combination with other CYP21A2 pathogenic variants. In addition, identical genotypes, harboring the homozygous In2G variant, can present with variable phenotypes including the SW and SV or rarely NC form of the disease. Here, we analyze and present the clinical aspects, genotype/phenotype correlations, and other characteristics related to the CYP21A2 In2G variant.
Validation of PWR Neutronics Code Package TORCH V2.0 With Nuclear Power Plant Measurements
Authors: Zhang Bin , Peng Xingjie , Zhao Chen , Zhao Wenbo , Li Qing
Published: January 2022

This article presents the verification and validation (V and V) of PWR neutronics code package TORCH V2.0 with nuclear power plant (NPP) measurements. The advanced nuclear power engineering design software, TORCH V2.0, was developed by the Nuclear Power Institute of China (NPIC), China National Nuclear Corporation (CNNC). Based on the two-step calculation scheme, TORCH V2.0 mainly contains lattice physics code for assembly homogenization, link calculation code for few-group constant parameterization, and core simulation code for few-group core calculation. The calculation modules of each code were already verified against various benchmark problems, whereas this article focuses on the V and V of linked code system. The measured values of the reactor startup physics test and NPP operation from six PWR NPPs (Daya Bay NPP, Ling Ao NPP, Fangjiashan NPP, Qinshan NPP, Hainan Changjiang NPP, and Fuqing NPP) were utilized to perform the comparison and analysis of V and V. Compared parameters of the reactor startup physics test include critical boron concentration, control rod integral value, boron differential value, and isothermal temperature coefficient. Compared parameters of the NPP operation contain critical boron concentration, assembly-wise power distribution, hot spot factor, and nuclear enthalpy rise factor. The results show that the software TORCH V2.0 has reliable calculation ability and can be applied in the PWR nuclear power engineering design which is based on square fuel assembly.
RFtest: A Robust and Flexible Community-Level Test for Microbiome Data Powerfully Detects Phylogenetically Clustered Signals
Authors: Zhang Lujun , Wang Yanshan , Chen Jingwen , Chen Jun
Published: January 2022

Random forest is considered as one of the most successful machine learning algorithms, which has been widely used to construct microbiome-based predictive models. However, its use as a statistical testing method has not been explored. In this study, we propose “Random Forest Test” (RFtest), a global (community-level) test based on random forest for high-dimensional and phylogenetically structured microbiome data. RFtest is a permutation test using the generalization error of random forest as the test statistic. Our simulations demonstrate that RFtest has controlled type I error rates, that its power is superior to competing methods for phylogenetically clustered signals, and that it is robust to outliers and adaptive to interaction effects and non-linear associations. Finally, we apply RFtest to two real microbiome datasets to ascertain whether microbial communities are associated or not with the outcome variables.
Expression Profile Analysis to Identify Circular RNA Expression Signatures in the Prolificacy Trait of Yunshang Black Goat Pituitary in the Estrus Cycle
Authors: Liu Yufang , Wang Peng , Zhou Zuyang , He Xiaoyun , Tao Lin , Jiang Yanting , Lan Rong , Hong Qionghua , Chu Mingxing
Published: January 2022

The pituitary gland is an important organ. It is a complex area of the brain involved in endocrine function and reproductive regulation. However, the function of the pituitary in goat reproduction is still unclear. Herein, RNA sequencing was used to explore the expression patterns of circle RNAs (circRNAs) in the pituitary of Yunshang black goats during the various estrus phases. Then the host genes of the circRNAs were predicted, and a competing endogenous RNA (ceRNA) network was constructed. The results showed a total of 6,705 circRNAs in the pituitary of Yunshang black goats, among which 388 differentially expressed (DE) circRNAs (214 were upregulated, while 174 were downregulated) were identified between high- and low-yield Yunshang black goats in the follicular phase (HF vs. LF); moreover, 361 DE circRNAs (136 were upregulated, while 225 were downregulated) were identified between high- and low-yield Yunshang black goats in the luteal phase (HL vs. LL). There were 65 DE circRNAs targeting 40 miRNAs in the HF vs. LF comparison and 46 DE circRNAs targeting 31 miRNAs in the HL vs. LL comparison. We identified chi_circ_0030920, chi_circ_0043017, chi_circ_0008353, chi_circ_0041580, and chi_circ_0016478 as the key circRNAs through functional enrichment analysis. The ceRNA network analysis showed that chi_circ_0031209 and chi_circ_0019448 might play an important role in reproduction by influencing the expression of prolactin receptor (PRLR) in high- and low-yielding goats during the luteal phase, whereas chi_circ_0014542 regulates the expression of WNT5A during the follicular phase. Our study provided the overall expression profiles of circRNAs in the goat pituitary during the estrus phase, which provides new insight into the mechanism of high-yield goats, which can be helpful to guide goat breeding.
A Diagnostic Model With IgM Autoantibodies and Carcinoembryonic Antigen for Early Detection of Lung Adenocarcinoma
Authors: Zhang Xue , Li Jiaqi , Wang Yulin , Liu Man , Liu Fenghui , Zhang Xiuzhi , Pei Lu , Wang Tingting , Jiang Di , Wang Xiao , Zhang Jianying , Dai Liping
Published: January 2022

Immunoglobulin M (IgM) autoantibodies, as the early appearing antibodies in humoral immunity when stimulated by antigens, might be excellent biomarkers for the early detection of lung cancer (LC). We aimed to develop a multi-analyte integrative model combining IgM autoantibodies and a traditional tumor biomarker that could be a valuable and powerful auxiliary diagnostic tool and might improve the accuracy of early detection of lung adenocarcinoma (LUAD). A customized protein array based on cancer driver genes was constructed and applied in the discovery cohort consisting of 68 LUAD patients and 68 normal controls (NCs); 31 differentially expressed IgM autoantibodies were identified. The top 5 candidate IgM autoantibodies [based on the area under the receiver operating characteristic curve (AUC) ranking], namely, TSHR, ERBB2, survivin, PIK3CA, and JAK2, were validated in the validation cohort using enzyme-linked immunosorbent assay (ELISA), which included 147 LUAD samples, 72 lung squamous cell carcinoma (LUSC) samples, 44 small cell lung carcinoma (SCLC) samples, and 147 NCs. These indicators presented diagnostic capacity for LUAD, with AUCs of 0.599, 0.613, 0.579, 0.601, and 0.633, respectively (p < 0.05). However, none of them showed a significant difference between the SCLC and NC groups, and only the IgM autoantibody against JAK2 showed a higher expression in LUSC than in NC (p = 0.046). Through logistic regression analysis, with the five IgM autoantibodies and carcinoembryonic antigen (CEA), one diagnostic model was constructed for LUAD. The model yielded an AUC of 0.827 (sensitivity = 56.63%, specificity = 93.98%). The diagnostic efficiency was superior to that of either CEA (AUC = 0.692) or IgM autoantibodies alone (AUC = 0.698). Notably, the accuracy of this model in early-stage LUAD reached 83.02%. In conclusion, we discovered and identified five novel IgM indicators and developed a multi-analyte model combining IgM autoantibodies and CEA, which could be a valuable and powerful auxiliary diagnostic tool and might improve the accuracy of early detection of LUAD.
CX3CR1 Acts as a Protective Biomarker in the Tumor Microenvironment of Colorectal Cancer
Authors: Yue Yuanyi , Zhang Qiang , Sun Zhengrong
Published: January 2022

The tumor microenvironment (TME) plays an important role in the pathogenesis of many cancers. We aimed to screen the TME-related hub genes of colorectal adenoma (CRAD) and identify possible prognostic biomarkers. The gene expression profiles and clinical data of 464 CRAD patients in The Cancer Genome Atlas (TCGA) database were downloaded. The Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) algorithm was performed to calculate the ImmuneScore, StromalScore, and EstimateScore. Thereafter, differentially expressed genes (DEGs) were screened. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein–protein interaction (PPI) analysis were performed to explore the roles of DEGs. Furthermore, univariate and multivariate Cox analyses were accomplished to identify independent prognostic factors of CRAD. CX3CR1 was selected as a hub gene, and the expression was confirmed in colorectal cancer (CRC) patients and cell lines. The correlations between CX3CR1 and tumor-infiltrating immune cells were estimated by Tumor IMmune Estimation Resource database (TIMER) and CIBERSORT analysis. Besides, we investigated the effects of coculture with THP-1-derived macrophages with HCT8 cells with low CX3CR1 expression on immune marker expression, cell viability, and migration. There were significant differences in the ImmuneScore and EstimateScore among different stages. Patients with low scores presented significantly lower lifetimes than those in the high-score group. Moreover, we recognized 1,578 intersection genes in ImmuneScore and StromalScore, and these genes were mainly enriched in numerous immune-related biological processes. CX3CR1 was found to be associated with immune cell infiltration levels, immune marker expression, and macrophage polarization. Simultaneous silencing of CX3CR1 and coculture with THP-1 cells further regulated macrophage polarization and promoted the cell proliferation and migration of CRC cells. CX3CR1 was decreased in CRAD tissues and cell lines and was related to T and N stages, tumor differentiation, and prognosis. Our results suggest that CX3CR1 contributes to the recruitment and regulation of immune-infiltrating cells and macrophage polarization in CRC and TAM-induced CRC progression. CX3CR1 may act as a prognostic biomarker in CRC.
Phenomic Analysis of Chronic Granulomatous Disease Reveals More Severe Integumentary Infections in X-Linked Compared With Autosomal Recessive Chronic Granulomatous Disease
Authors: Chiu Timothy Lok-Hin , Leung Daniel , Chan Koon-Wing , Yeung Hok Man , Wong Chung-Yin , Mao Huawei , He Jianxin , Vignesh Pandiarajan , Liang Weiling , Liew Woei Kang , Jiang Li-Ping , Chen Tong-Xin , Chen Xiang-Yuan , Tao Yin-Bo , Xu Yong-Bin , Yu Hsin-Hui , Terblanche Alta , Lung David Christopher , Li Cheng-Rong , Chen Jing , Tian Man , Eley Brian , Yang Xingtian , Yang Jing , Chiang Wen Chin , Lee Bee Wah , Suri Deepti , Rawat Amit , Gupta Anju , Singh Surjit , Wong Wilfred Hing Sang , Chua Gilbert T. , Duque Jaime Sou Da Rosa , Cheong Kai-Ning , Chong Patrick Chun-Yin , Ho Marco Hok-Kung , Lee Tsz-Leung , Yang Wanling , Lee Pamela P. , Lau Yu Lung
Published: January 2022

Background

Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI), characterised by recurrent bacterial and fungal infections. It is inherited either in an X-linked (XL) or autosomal recessive (AR) mode. Phenome refers to the entire set of phenotypes expressed, and its study allows us to generate new knowledge of the disease. The objective of the study is to reveal the phenomic differences between XL and AR-CGD by using Human Phenotype Ontology (HPO) terms.

Methods

We collected data on 117 patients with genetically diagnosed CGD from Asia and Africa referred to the Asian Primary Immunodeficiency Network (APID network). Only 90 patients with sufficient clinical information were included for phenomic analysis. We used HPO terms to describe all phenotypes manifested in the patients.

Results

XL-CGD patients had a lower age of onset, referral, clinical diagnosis, and genetic diagnosis compared with AR-CGD patients. The integument and central nervous system were more frequently affected in XL-CGD patients. Regarding HPO terms, perianal abscess, cutaneous abscess, and elevated hepatic transaminase were correlated with XL-CGD. A higher percentage of XL-CGD patients presented with BCGitis/BCGosis as their first manifestation. Among our CGD patients, lung was the most frequently infected organ, with gastrointestinal system and skin ranking second and third, respectively. Aspergillus species, Mycobacterium bovis, and Mycobacteirum tuberculosis were the most frequent pathogens to be found.

Conclusion

Phenomic analysis confirmed that XL-CGD patients have more recurrent and aggressive infections compared with AR-CGD patients. Various phenotypic differences listed out can be used as clinical handles to distinguish XL or AR-CGD based on clinical features.
Complete Replacement of Fishmeal With Plant Protein Ingredients in Gibel Carp (Carassius auratus gibelio) Diets by Supplementation With Essential Amino Acids Without Negative Impact on Growth Performance and Muscle Growth-Related Biomarkers
Authors: Cai Wanjie , Liu Haokun , Han Dong , Zhu Xiaoming , Jin Junyan , Yang Yunxia , Xie Shouqi
Published: January 2022

This study was conducted to investigate the effects of substitution of dietary fishmeal (FM) by compound plant protein supplemented with essential amino acids on growth performance, plasma physiology, and muscle growth-related genes of gibel carp (Carassius auratus gibelio). Four diets with equal digestible protein were prepared, where 30FM (control feed) contained 30% FM and land animal protein as a protein source, 10FM contained 10% FM, PMAa contained full plant meal (PM) supplemented with crystalline amino acid, and PM contained full PM feed. There was no significant difference in the specific growth rate (SGR) with 30FM, 10FM, and PMAa diets (p > 0.05); however, the SGR of PM group was the lowest with significant difference (p < 0.05). Feed efficiency of the PM group was the lowest with significant difference (p < 0.05). The whole-body crude protein content of fish in PMAa group was significantly higher than that in each group with additional FM (p < 0.05). There were no significant differences in plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C), and free amino acid profile of 30FM, 10FM, and PMAa groups (p > 0.05); however, they were significantly higher than that in PM group (p < 0.05). The expression of key genes in the TOR signaling pathway (tor, s6k1, 4e-bp2, and eif4e), autophagy (ulk1 and atg13), and ubiquitin–proteasome (trim63 and znrf2) system of the PMAa group was similar to that of the FM group (p > 0.05), indicating that the muscle growth-related biomarker genes were positively regulated by the appropriate dietary amino acid composition at the transcriptional level. These results suggest that FM in gibel carp diet can be totally replaced by PM without negative impact on growth performance and muscle growth-related biomarkers at the transcriptional level, which provided the requirement of digestible protein and balanced amino acid profile is satisfied.
Digital Medical Cannabis as Market Differentiator: Second-Generation Artificial Intelligence Systems to Improve Response
Authors: Ilan Yaron
Published: January 2022

Legalized use of cannabis products and the rising interest in their therapeutic benefits have opened up new opportunities for therapy and marketing. However, the marked variability in formulations, administration modes, therapeutic regimens, and inter- and intra-subject responses make the standardization of medical cannabis-based regimens difficult. Legalization has made the cannabis market highly competitive and lowered the revenue margins. This study reviews some of the challenges in medical cannabis use and difficulties in standardizing its therapeutic regimens that hinder maximizing its beneficial effects. The development of tolerance toward cannabis and low adherence to chronic administration further impair its long-term beneficial effects. Digital medical cannabis is a cannabis product controlled by a second-generation artificial intelligence (AI) system that improves patient responses by increasing adherence and dealing with tolerance. Second-generation AI systems focus on a single patient's outcome and deal with the inter- and intra-subject variability in responses. The use of digital medical cannabis is expected to improve product standardization, maximize therapeutic benefits, reduce health care costs, and increase the revenue of companies. Digital medical cannabis offers several market differentiators for cannabis companies. This study presents a model for promoting the use of digital medical cannabis and presents its advantages for patients, clinicians, health care authorities, insurance companies, and cannabis manufacturers. Ongoing trials and real-world data on the use of these systems further support the use of digital medical cannabis for improved global health.
Case Report: Vitreous Amyloidosis Caused by a TTR Lys55Asn Mutation With Intraoperative Suprachoroidal Hemorrhage
Authors: Xu Qing , Wang Xinting , Zhang Zhengpei , Li Jie , Liu Haiyang , Ji Sujuan , Qiao Lei , Gong Chaoju , Feng Ruifang , Li Suyan
Published: January 2022

We report a vitreous amyloidosis patient with white vitreous opacities (footplates) adhering to the posterior lens capsule. A positive Congo-red stain and transthyretin (TTR) Lys55Asn mutation confirmed the diagnosis of vitreous amyloidosis. Optical coherence tomography (OCT) revealed fern-like material adhering to the the posterior pole retinal surface in both eyes. Visual acuity significantly improved after the first vitrectomy, but vitreous opacities recurred 4 years later. The patient appeared to have aggravated sensorimotor neuropathy and severe autonomic dysfunction at the same time. He developed intraoperative suprachoroidal hemorrhage during the second vitrectomy.
Over-Expression and Prognostic Significance of FN1, Correlating With Immune Infiltrates in Thyroid Cancer
Authors: Geng Qi-Shun , Huang Tao , Li Li-Feng , Shen Zhi-Bo , Xue Wen-Hua , Zhao Jie
Published: January 2022

Background

Thyroid cancer (THCA) is a malignancy affecting the endocrine system, which currently has no effective treatment due to a limited number of suitable drugs and prognostic markers.

Methods

Three Gene Expression Omnibus (GEO) datasets were selected to identify differentially expressed genes (DEGs) between THCA and normal thyroid samples using GEO2R tools of National Center for Biotechnology Information. We identified hub gene FN1 using functional enrichment and protein-protein interaction network analyses. Subsequently, we evaluated the importance of gene expression on clinical prognosis using The Cancer Genome Atlas (TCGA) database and GEO datasets. MEXPRESS was used to investigate the correlation between gene expression and DNA methylation; the correlations between FN1 and cancer immune infiltrates were investigated using CIBERSORT. In addition, we assessed the effect of silencing FN1 expression, using an in vitro cellular model of THCA. Immunohistochemical(IHC) was used to elevate the correlation between CD276 and FN1.

Results

FN1 expression was highly correlated with progression-free survival and moderately to strongly correlated with the infiltration levels of M2 macrophages and resting memory CD4+ T cells, as well as with CD276 expression. We suggest promoter hypermethylation as the mechanism underlying the observed changes in FN1 expression, as 20 CpG sites in 507 THCA cases in TCGA database showed a negative correlation with FN1 expression. In addition, silencing FN1 expression suppressed clonogenicity, motility, invasiveness, and the expression of CD276 in vitro. The correlation between FN1 and CD276 was further confirmed by immunohistochemical.

Conclusion

Our findings show that FN1 expression levels correlate with prognosis and immune infiltration levels in THCA, suggesting that FN1 expression be used as an immunity-related biomarker and therapeutic target in THCA.
Assessment of Health-Related Quality of Life in Adult Spinal Muscular Atrophy Under Nusinersen Treatment—A Pilot Study
Authors: Thimm Andreas , Brakemeier Svenja , Kizina Kathrin , Munoz Rosales Juan , Stolte Benjamin , Totzeck Andreas , Deuschl Cornelius , Kleinschnitz Christoph , Hagenacker Tim
Published: January 2022

5q-Spinal muscular atrophy (SMA) is a severely disabling inherited neuromuscular disease that progressively reduces the motor abilities of affected individuals. The approval of the antisense oligonucleotide nusinersen, which has been shown to improve motor function in adult SMA patients, changed the treatment landscape. However, little is known about its impact on patients' quality of life (QoL), and there is still a need for adequate patient-reported outcome measures. In this study, we used the short form of the Neuro-QoL (Quality of Life in Neurological Disorders) for upper/lower extremity function to prospectively assess the health-related QoL of 17 adult SMA patients prior to initiation of nusinersen treatment and 2, 6, 10, and 14 months afterwards. At baseline, Neuro-QoL scores strongly correlated with motor function scores (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb Module, RULM), but QoL did not increase significantly during the 14-month treatment period despite significant motor improvement as measured by HFMSE. Our results underline the need for novel, disease-specific assessments of QoL in SMA.
Effects of Gaze Fixation on the Performance of a Motor Imagery-Based Brain-Computer Interface
Authors: Meng Jianjun , Wu Zehan , Li Songwei , Zhu Xiangyang
Published: January 2022

Motor imagery-based brain-computer interfaces (BCIs) have been studied without controlling subjects’ gaze fixation position previously. The effect of gaze fixation and covert attention on the behavioral performance of BCI is still unknown. This study designed a gaze fixation controlled experiment. Subjects were required to conduct a secondary task of gaze fixation when performing the primary task of motor imagination. Subjects’ performance was analyzed according to the relationship between motor imagery target and the gaze fixation position, resulting in three BCI control conditions, i.e., congruent, incongruent, and center cross trials. A group of fourteen subjects was recruited. The average group performances of three different conditions did not show statistically significant differences in terms of BCI control accuracy, feedback duration, and trajectory length. Further analysis of gaze shift response time revealed a significantly shorter response time for congruent trials compared to incongruent trials. Meanwhile, the parietal occipital cortex also showed active neural activities for congruent and incongruent trials, and this was revealed by a contrast analysis of R-square values and lateralization index. However, the lateralization index computed from the parietal and occipital areas was not correlated with the BCI behavioral performance. Subjects’ BCI behavioral performance was not affected by the position of gaze fixation and covert attention. This indicated that motor imagery-based BCI could be used freely in robotic arm control without sacrificing performance.
Potential Effectiveness of Registered Dietitian Nutritionists in Healthy Behavior Interventions for Managing Type 2 Diabetes in Older Adults: A Systematic Review
Authors: Dobrow Laurel , Estrada Isabella , Burkholder-Cooley Nasira , Miklavcic John
Published: January 2022

Purpose

A systematic review was conducted to assess how the involvement of a registered dietitian nutritionist (RDN) in healthy behavior interventions (HBIs) potentially affects outcomes in older adults with type 2 diabetes (T2D).

Methods

Literature was searched for primary research published between 2016 and 2020 on HBI involving a RDN affecting outcomes in older adults with T2D. Evaluations of hemoglobin A1c (HbA1c), blood glucose, blood pressure, cholesterol, anthropometry, body composition, medication usage, healthcare cost, and self-efficacy and/or adherence to healthy behaviors outcomes were selected for inclusion. All the literature included were summarized, evaluated for certainty of evidence criteria, and assessed for bias.

Results

A total of 12 studies were included for assessment. Involvement of a RDN in HBI was shown to reduce HbA1c, fasting blood glucose, low-density lipoprotein (LDL) cholesterol, and blood pressure and improve lean body mass, body mass index (BMI), and self-efficacy in populations of older adults with T2D. Compared to older adults with T2D receiving HBI involving RDNs, patients receiving usual care may incur higher healthcare costs or longer hospital stays. There was a high certainty of evidence for a RDN involvement in HBI with regard to reduction in HbA1c. There was a moderate certainty of evidence for a RDN involvement in HBI with regard to favorable changes in weight or body composition and cardiometabolic health outcomes. Statistically significant improvements in outcomes were usually sustained in follow-up after conclusion of HBI.

Conclusion

RDNs may play an integral role in HBIs resulting in improved glycemic control, weight management, cardiovascular outcomes, and presumably comorbidity management. RDNs are important facilitators of diet education and nutrition assessment, which are essential in T2D management and should, therefore, be considered for routine inclusion in interprofessional teams for improved outcomes in older adults with T2D.
The 2018 Japan Floods Increased the Frequency of Yokukansan Prescriptions Among Elderly: A Retrospective Cohort Study
Authors: Ishida Ryoko , Yoshida Shuhei , Kashima Saori , Okazaki Yuji , Matsumoto Masatoshi
Published: January 2022

Objective

The impact of the 2018 Japan Floods on prescriptions of Yokukansan was evaluated.

Methods

This was a retrospective cohort study based on the National Database of Health Insurance Claims which covers all the prescriptions issued in Japan. Participants were patients aged 65 or older who received any medical care at medical institutions located in the three most-severely affected prefectures between 1 year before and after the disaster. We analyzed the number of new prescriptions of Yokukansan and other Kampo drugs among those who had not been prescribed any Kampo for 1 year before the disaster. Kaplan-Meier analysis and a Cox proportional hazards model were used to evaluate the risk of the disaster for a new prescription.

Results

Subjects comprised 1,372,417 people (including 12,787 victims, 0.93%). The hazard ratio (HR) of the disaster for Yokukansan prescriptions was 1.49 [95% confidence intervals (CI): 1.25–1.78], and 1.54 (95% CI: 1.29–1.84) in the crude and age-sex adjusted model, respectively. The HR of the disaster for prescription of other Kampo drugs in the crude and adjusted model was 1.33 (95% CI: 1.27–1.39), and 1.32 (95% CI: 1.27–1.38), respectively. The magnitude of increase of victims prescribed Yokukansan (31.4%) was statistically higher than for those prescribed other Kampo drugs (19.3%) (p < 0.001).

Conclusion

The disaster increased prescriptions of both Yokukansan and other Kampo drugs among elderly victims. The increase was more remarkable in Yokukansan than other Kampo drugs. Clinicians and policymakers should be aware of the increased need for Yokukansan in times of natural disaster.
Allogeneic Stem Cell Transplantation Combined With Transfusion of Mesenchymal Stem Cells in Primary Myelofibrosis: A Multicenter Retrospective Study
Authors: Wang Qingyuan , Xu Na , Wang Yu , Zhang Xi , Liu Limin , Zhou Huifen , Wang Hong , Zhang Xiang , Tang Xiaowen , Fu Chengcheng , Miao Miao , Wu Depei
Published: January 2022

Background

Allogeneic stem cell transplantation (allo-SCT) remains the only effective curative therapy for primary myelofibrosis. Utilization and efficacy of allo-SCT are limited by lethal complications, including engraftment failure, and acute (aGVHD) and chronic graft-versus-host disease (cGVHD). Several clinical trials have explored the use of mesenchymal stem cells (MSCs) in allo-SCT to prevent hematopoietic stem cell (HSC) engraftment failure and control GVHD.

Methods

Clinical data of 17 patients with primary myelofibrosis who underwent allo-SCT combined with ex vivo expanded MSC transfusion in four centers from February 2011 to December 2018 were retrospectively analyzed.

Results

All patients received myeloablative conditioning regimen. The median number of transplanted nucleated cells (NCs) per kilogram body weight was 11.18 × 108 (range: 2.63–16.75 × 108), and the median number of CD34+ cells was 4.72 × 106 (range: 1.32–8.4 × 106). MSCs were transfused on the day of transplant or on day 7 after transplant. The median MSC infusion number was 6.5 × 106 (range: 0.011–65 × 106). None of the patients experienced primary or secondary graft failure in the study. The median time to neutrophil engraftment was 13 days (range: 11–22 days), and the median time to platelet engraftment was 21 days (range: 12–184 days). The median follow-up time was 40.3 months (range: 1.8–127.8 months). The estimated relapse-free survival (RFS) at 5 years was 79.1%, and overall survival (OS) at 5 years was 64.7%. Analysis showed that the cumulative incidence of aGVHD grade II to IV was 36% (95% CI: 8%–55%) and that of grade III to IV was 26% (95% CI: 0%–45%) at day 100. The cumulative incidence of overall cGVHD at 2 years for the entire study population was 63% (95% CI: 26%–81%). The cumulative incidence of moderate to severe cGVHD at 2 years was 17% (95% CI: 0%–42%). Seven patients died during the study, with 5 patients succumbing from non‐relapse causes and 2 from disease relapse.

Conclusion

The findings of the study indicate that allo-SCT combined with MSC transfusion may represent an effective treatment option for primary myelofibrosis.
An Integrated Pan-Cancer Analysis of 33 Human Cancers Reveals the Potential Clinical Implications and Immunotherapeutic Value of C-X-C Motif Chemokine Ligand 13
Authors: Zhang Huanyu , Yin Honghao , Chen Jing , Yuan Yuan
Published: January 2022

Background

C-X-C Motif Chemokine Ligand 13 (CXCL13) plays a crucial part in the pathogenesis of numerous lymphoproliferative disorders, inflammatory responses, and autoimmune diseases. CXCL13 also influence tumor development and prognosis, and be a potential target for cancer treatment. However, CXCL13 expression-based panoramic picture in pan-cancer remain unclear. This study focused on elucidating different expression levels, prognostic significance, immune-related characteristics, epigenetic variations, and immunotherapeutic value of CXCL13.

Methods

Based on different databases such as TCGA, GTEX, CCLE and HPA, we studied the expression of CXCL13 in different tissues at different levels. Moreover, we analyzed the correlation between CXCL13 expression and clinicopathological characteristics, prognosis, Mismatch Repair Genes (MMRs), Microsatellite Instability (MSI), tumor mutation burden (TMB), immune cells infiltration, immune-related genes, and the role in tumor immunotherapy. And the expression of CXCL13 in digestive tract cancers and the correlation between CXCL13 and immune genes were further analyzed by histological verification.

Results

CXCL13 was highly expressed in various tumor tissues and was also closely related to prognosis. CXCL13 expression levels were closely related to MSI, TMB and immune cells infiltration, including CD8+ T cells, macrophages, follicular helper T cells and B cells. CXCL13 expression levels were related to immune checkpoint genes and the efficacy of immunotherapy.

Conclusion

CXCL13 might be a useful biomarker for determining the diagnosis and prognosis of human cancers but also a biomarker for evaluating the efficacy of immunotherapy.
LncRNA SNHG1 Promotes the Progression of Pancreatic Cancer by Regulating FGFR1 Expression via Competitively Binding to miR-497
Authors: Chen Shihong , Guo Wenyi , Meng Mingyang , Wu Dong , Zhou Tao , Wang Lei , Xu Jianwei
Published: January 2022

Background

Long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) is dysregulated in a variety of tumors. However, little is known of its role in pancreatic cancer (PC).

Methods

The role of SNHG1 on PC cell proliferation, migration, invasion, apoptosis, and the epithelial-mesenchymal transition (EMT) were assessed in vitro using MTT, EDU, wound healing, and Transwell assays, as well as flow cytometry and western blotting. Luciferase reporter assay, western blotting, and qRT-PCR were used to examine SNHG1 regulation. Tumor growth in mice was also investigated.

Results

Downregulation of SNHG1 blocked cell proliferation, migration and invasion, and induced apoptosis in vitro, while also inhibiting the EMT, shown by changes in the biomarkers E-cadherin, N-cadherin, and Vimentin. The opposite results were observed on upregulation of SNHG1. In vivo experiments showed that downregulation of SNHG1 inhibited tumor development in nude mice. Furthermore, experiments investigating the regulatory mechanism of SNHG1 indicated that SNHG1 acted as a competitive endogenous RNA, positively regulating the expression of fibroblast growth factor receptor 1 (FGFR1) through sponging miR-497. Rescue experiments demonstrated that the effects of SNHG1 downregulation on PC cells were attenuated when simultaneously inhibiting the levels of miR-497.

Conclusions

SNHG1 upregulates FGFR1 expression by sponging miR-497, which promotes the progression of PC. SNHG1 may thus be a novel target for treating PC.
Syzygium jambos L. Alston: An Insight Into its Phytochemistry, Traditional Uses, and Pharmacological Properties
Authors: Ochieng Melvin Adhiambo , Ben Bakrim Widad , Bitchagno Gabin Thierry M. , Mahmoud Mona F. , Sobeh Mansour
Published: January 2022

Medicinal plants have been used since ancient times for human healthcare as drugs, spices, and food additives. The progress in technology and medicine observed, the last decades, has improved the quality of life and healthcare but with worrisome drawbacks. Side effects caused by synthetic drugs for instance originate sometimes irreversible health disorders. Natural substances, in contrast, are biologically and environmentally friendly. Syzygium jambos L. (Alston) also known as rose apple conveys a long history as essential traditional medicine with a broad spectrum of application in various cultures. The plant discloses a diverse group of secondary metabolites and extracts that displayed major susceptibilities towards various health concerns especially stress-related and inflammatory diseases. Despite a rich literature about the plant, the chemistry and biology of S. jambos have not been comprehensively reviewed yet. Accordingly, we present herein a literature survey of rose apple which aims to draw the chemical identity of the plant and establish a consistent discussion on the respective biological application of plant extracts and their corresponding traditional uses. The present work could provide a scientific basis for future studies and necessary information for further investigations of new drug discovery.
Anti-Inflammatory Efficacy of Curcumin as an Adjunct to Non-Surgical Periodontal Treatment: A Systematic Review and Meta-Analysis
Authors: Zhang Yang , Huang Lei , Zhang Jinmei , De Souza Rastelli Alessandra Nara , Yang Jingmei , Deng Dongmei
Published: January 2022

Objective: Curcumin has been used as an adjunct to non-surgical periodontal treatment. However, the efficacy of curcumin in the periodontal therapy remained controversial. This study aimed to evaluate the anti-inflammatory efficacy of curcumin as an adjunct to non-surgical periodontal treatment (NPT) by systematic review.

Methods: Databases including Embase, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched to identify relevant RCTs on the use of curcumin as an adjunct to NPT for the treatment of periodontal disease from inception to July 21, 2021. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed using Review Manager 5.3 software.

Results: A total of 18 RCTs involving 846 patients/sites were included in this meta-analysis. The results of the meta-analysis revealed that as compared to NPT alone, curcumin as an adjunct to NPT resulted in significant reduction in gingival index (GI) at the 1-week (mean differences (MD) = −0.15, 95% confidence intervals (CI) −0.26 to −0.05, p = 0.005), 2-week (MD = −0.51, 95%CI −0.74 to −0.28, p < 0.0001), 3-week (MD = −0.34, 95%CI −0.66 to −0.02, p = 0.03), 4-week (MD = −0.25, 95%CI −0.48 to −0.02, p = 0.04) or 6-week (MD = −0.33, 95%CI −0.58 to −0.08, p = 0.01) follow-ups. Similar significant reductions were also observed for sulcus bleeding index (SBI) at 1, 2, 4, and 12 weeks. However, there were no statistically significant differences in reducing bleeding on probing (BOP) between curcumin as an adjunct and NPT alone at 4, 12, and 24 weeks.

Conclusion: Based on the current evidence, curcumin demonstrates anti-inflammatory efficacies in terms of reducing GI and SBI compared with NPT alone. Moreover, curcumin is a natural herbal medicine with few side effects, and it is a good candidate as an adjunct treatment for periodontal disease.
Time and Space Resolved First Order Optical Interference Between Distinguishable Photon Paths
Authors: Fernandez-Guasti M. , García-Guerrero C.
Published: January 2022

Interference between different photons occurs and has been observed under diverse experimental conditions. A necessary condition in order to obtain interference fringes is the existence of at least two possible paths and unknown which-path information. If the photon beams have different frequencies, stability of the sources and fast spatially distributed detectors are required in order to detect the time displaced interference fringes. First order optical interference between two truly independent CW laser sources is observed. In contrast with the standard quantum criterion, interference is observed although the photon beams are distinguishable and, from quantum measurements, the path is unequivocally known for each photon beam. Segments of the continuous wave wavetrains are selected with an acousto-optic modulator. Temporal and spatial interference are integrated in a single combined phenomenon via streak camera detection. The displacement of the fringes in the time versus space interferograms evince the trajectories of the labeled photons. These results suggest that in non-degenerate frequency schemes, the ontology has to be refined and the which-path criterion must be precisely formulated. On the one hand, if the query refers to the frequency labeled photons, the path of each red or blue photon is known, whereas on the other hand, if the query is performed in terms of the detected photons, the path is unknown.
The Loss of Function of the NODULE INCEPTION-Like PROTEIN 7 Enhances Salt Stress Tolerance in Arabidopsis Seedlings
Authors: Le Quang Tri , Lee Won Je , Choi Jun Ho , Nguyen Dinh Thanh , Truong Hai An , Lee Sang-A , Hong Suk-Whan , Lee Hojoung
Published: January 2022

Plants acquire nitrogen, an essential macronutrient, from the soil as nitrate. Since nitrogen availability is a major determinant of crop productivity, the soil is amended with nitrogenous fertilizers. Extensive use of irrigation can lead to the accumulation of salt in the soil, which compromises crop productivity. Our characterization of NODULE INCEPTION (NIN)-like PROTEIN 7 (NLP7), a transcription factor regulating the primary response to nitrate, revealed an intersection of salt stress and nitrate metabolism. The growth of loss-of-function mutant nlp7 was tolerant to high salinity that normally reduces the fresh weight and chlorophyll and protein content of wild type (Col-0). On a medium with high salinity, the nlp7 experienced less stress, accumulating less proline, producing less nitric oxide (NO) and reactive oxygen species (ROS), and expressing lower transcript levels of marker genes, such as RD29A and COR47, than Col-0. Nevertheless, more sodium ions were translocated to and accumulated in the shoots of nlp7 than that of Col-0. Since nlp7 also expressed less nitrate reductase (NR) activity, nitrate accumulated to abnormally high levels with or without salinity. We attributed the enhanced salt tolerance of nlp7 to the balanced accumulation of nitrate anions and sodium cations. Our results suggest that nitrate metabolism and signaling might be targeted to improve salt tolerance.
Molecular Mapping of Quantitative Trait Loci for Fusarium Head Blight Resistance in the Brazilian Spring Wheat Cultivar “Surpresa”
Authors: Poudel Bikash , Mullins Joseph , Puri Krishna D. , Leng Yueqiang , Karmacharya Anil , Liu Yuan , Hegstad Justin , Li Xuehui , Zhong Shaobin
Published: January 2022

Fusarium head blight (FHB) is a devastating disease in wheat. The use of resistant germplasm from diverse sources can significantly improve resistance to the disease. “Surpresa” is a Brazilian spring wheat cultivar with moderate FHB resistance, different from currently used sources. In this study, we aimed to identify and map the genetic loci for FHB resistance in Surpresa. A mapping population consisting of 187 recombinant inbred lines (RILs) was developed from a cross between Surpresa and a susceptible spring wheat cultivar, “Wheaton.” The population was evaluated for FHB by the point-inoculation method in three greenhouse experiments and four field trials between 2016 and 2018. Mean disease severity for Surpresa and Wheaton was 41.2 and 84.9% across the 3 years of experiments, ranging from 30.3 to 59.1% and 74.3 to 91.4%, respectively. The mean FHB severity of the NILs was 57%, with an overall range from 7 to 100%, suggesting transgressive segregation in the population. The population was genotyped using a two-enzyme genotyping-by-sequencing approach, and a genetic map was constructed with 5,431 single nucleotide polymorphism (SNP) markers. Four QTL for type II resistance were detected on chromosomes 3A, 5A, 6A, and 7A, explaining 10.4–14.4% of the total phenotypic variation. The largest effect QTL was mapped on chromosome 7A and explained 14.4% of the phenotypic variation; however, it co-localized with a QTL governing the days to anthesis trait. A QTL for mycotoxin accumulation was also detected on chromosome 1B, explaining 18.8% of the total phenotypic variation. The QTL for FHB resistance identified in the study may diversify the FHB resistance gene pool and increase overall resistance to the disease in wheat.
Minimum Leaf Conductance (gmin) Is Higher in the Treeline of Pinus uncinata Ram. in the Pyrenees: Michaelis’ Hypothesis Revisited
Authors: Bueno Amauri , Alonso-Forn David , Peguero-Pina José Javier , de Souza Aline Xavier , Ferrio Juan Pedro , Sancho-Knapik Domingo , Gil-Pelegrín Eustaquio
Published: January 2022

The search for a universal explanation of the altitudinal limit determined by the alpine treeline has given rise to different hypotheses. In this study, we revisited Michaelis’ hypothesis which proposed that an inadequate “ripening” of the cuticle caused a greater transpiration rate during winter in the treeline. However, few studies with different explanations have investigated the role of passive mechanisms of needles for protecting against water loss during winter in conifers at the treeline. To shed light on this, the cuticular transpiration barrier was studied in the transition from subalpine Pinus uncinata forests to alpine tundra at the upper limit of the species in the Pyrenees. This upper limit of P. uncinata was selected here as an example of the ecotones formed by conifers in the temperate mountains of the northern hemisphere. Our study showed that minimum leaf conductance in needles from upper limit specimens was higher than those measured in specimens living in the lower levels of the sub-alpine forest and also displayed lower cuticle thickness values, which should reinforce the seminal hypothesis by Michaelis. Our study showed clear evidence that supports the inadequate development of needle cuticles as one of the factors that lead to increased transpirational water losses during winter and, consequently, a higher risk of suffering frost drought.
Influence of Streamer's Social Capital on Purchase Intention in Live Streaming E-Commerce
Authors: Xu Ping , Cui Bang-jun , Lyu Bei
Published: January 2022

The virtual display of products in e-commerce brings new problems of information asymmetry, and the overload of digital information also increases the difficulty of consumers' purchasing decisions. The real-time interaction between the streamer and the consumer during live streaming e-commerce will promote consumers' understanding of the product, reduce information asymmetry, and increase consumers' purchase intention. However, why do people trust the untouchable and unfamiliar streamers from live streaming e-commerce to purchase online? To understand this phenomenon, based on the perspective of the information asymmetry theory and parasocial relationship theory, this research identified how social capital affected purchase intention in live streaming e-commerce. Through a questionnaire survey of live viewers, the purchase intention model constructed by empirical testing was used. The findings showed that the streamer's professionalism, the reciprocal expectation of live streaming, and the viewer's parasocial relationship could effectively increase the viewer's purchase intention. The occurrence of a streamer's negative public events could significantly reduce the viewer's purchase intention. The scale of live streaming and the streamer's commitment had no significant impact on the viewer's purchase intention. Trust played an intermediary role between the streamer's professionalism and parasocial relationship and the viewer's purchase intention.