bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of lymphocyte subsets and cytokine profiles of patients with COVID-19
Authors: Pan Pengfei , Du Xinxin , Zhou Qilong , Cui Yong , Deng Xiaochun , Liu Chao , Hu Zongjun , Chen Jianguo , Yu Xiangyou , Shi Weihua 
Published: March 2022

Abstract
Background
Abnormalities of lymphocyte subsets and cytokine profiles have been observed in most patients with coronavirus disease (COVID-19). Here, we explore the role of lymphocyte subsets and cytokines on hospital admission in predicting the severity of COVID-19.

Methods
This study included 214 patients with COVID-19 who were treated at Chongqing University Three Gorges Hospital from January 19, 2020 to April 30, 2020. Any mutants were not detected in the studied patients. Patients were divided into non-intensive care unit (ICU) (mild/moderate) group and ICU (severe/critical) group, according to the severity of the disease. Clinical and laboratory data, including peripheral lymphocyte subsets and cytokines, were analyzed and compared. Logistic regression was used to analyze the predictive factors for ICU admission. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of selected indicators for the severity of COVID-19.

Results
Of the 214 patients enrolled, 161 were non-ICU patients and 53 were ICU patients. Lymphopenia was observed in nearly all of ICU patients (96.2%) and 84.5% of non-ICU patients on hospital admission. The absolute number of lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and natural killer (NK) cells were lower in ICU group (659.00 × 106/L, 417.00 × 106/L, 261.00 × 106/L, 140.00 × 106/L, 109.00 × 106/L, 102.00 × 106/L, respectively) than in non-ICU group (1063.00 × 109/L, 717.00 × 106/L, 432.00 × 106/L, 271.00 × 106/L, 133.00 × 106/L, 143.00 × 106/L, respectively). Interleukin (IL)-6 was significantly higher in ICU patients than in non-ICU patients (18.08 pg/mL vs. 3.13 pg/mL, P < 0.001). Multivariate logistic regression analysis showed that age (odds ratio: 1.067 [1.034–1.101]), diabetes mellitus (odds ratio: 9.154 [2.710–30.926]), CD3+ T cells (odds ratio: 0.996 [0.994–0.997]), and IL-6 (odds ratio: 1.006 [1.000–1.013]) were independent predictors for the development of severe disease. ROC curve analysis showed that the area under the ROC curve (AUC) of CD3+ T cells and IL-6 was 0.806 (0.737–0.874) and 0.785 (0.705–0.864), respectively, and the cutoff values were 510.50 × 106/L (sensitivity, 71.7%; specificity, 79.5%) and 6.58 pg/mL (77.4%, 74.5%), respectively. There were no statistical differences among all tested indicators of lymphocyte subsets and cytokines between severe group (n = 38) and critical group (n = 15) on hospital admission or ICU admission, respectively.

Conclusions
The levels of lymphocyte subsets decreased and the level of IL-6 increased significantly in ICU COVID-19 patients compared with non-ICU COVID-19 patients. Therefore, the number of CD3+ T cells and the level of IL-6 on hospital admission may serve as predictive factors for identifying patients with wild-type virus infection who will have severe disease.
Indigenous farmers’ perceptions of problems in the rice field agroecosystems in the upper Baram, Malaysia
Authors: Hollaus Alexander , Schunko Christoph , Weisshaidinger Rainer , Bala Poline , Vogl Christian R. 
Published: March 2022

AbstractBackgroundRice field agroecosystems produce food for more than half of the world’s population and deliver important services supporting farmers’ livelihoods. However, traditional rice field agroecosystems are facing a variety of problems, including pests or markets that are hard to access. This research explored indigenous farmers’ perceptions of the problems, their causes and consequences, and the solutions applied to address them in the rice field agroecosystem. Furthermore, the study investigated how indigenous farmers related these problems to the surrounding landscape elements and to microzones in the fields.MethodsData were collected in two villages in the upper Baram, Sarawak using a qualitative approach that included sketch drawings and face-to-face interviews. Forty-three indigenous farmers of the Kenyah, Penan and Sa’ban ethnic groups were interviewed in their rice fields. The sketch drawings were used to identify the perceived landscape elements, while the oral interviews were employed to identify perceived microzones. Furthermore, the interviews elicited the perceived problems in the rice field agroecosystem and their relations to landscape elements and microzones.ResultsThe findings identified a total of nine environmental problems, e.g. animal disturbance, six social problems, e.g. difficult to access farm inputs, and eight agricultural technology system problems, e.g. poor soil quality, with some found to be rooted in complex causes and affecting agricultural productivity. While some problems were perceived at field level, microzones were frequently used as sub-field indicators of the problems. The surrounding landscape elements were perceived as both a source of the problems and as a means of avoiding them. To solve the problems, farmers applied preventive and reactive strategies based on traditional knowledge and scientific knowledge, resulting in a hybridisation of knowledge systems.ConclusionsBy including environmental, social, agricultural technology system problems and different spatial scales, this research contributes to addressing issues that can be overlooked when focusing on only one dimension of the problems. These results contribute to a better understanding of how indigenous farmers perceive, cope with and adapt to problems in rice field agroecosystems, which is important for landscape management.
Reduction malarplasty using a simulated surgical guide for asymmetric/prominent zygoma
Authors: Kang Sang-Hoon , Tak Hye-Jin , Kim Hak-Jin , Lee Sang-Hwy 
Published: March 2022

Abstract
Background
The present study introduces a reduction malarplasty using a three-dimensional (3D)-printed surgical guide and evaluates the guide’s technical applicability.

Methods
Twenty malarplasties were performed for 12 subjects with zygomatic asymmetry/prominency using the current method. 3D reconstruction of the craniomaxillofacial region and fine dental occlusion was made with image data from computed tomograpy and dental scanning. A computer-assisted surgical simulation was performed for reduction malarplasty and a surgical guide was designed for later 3D printing. The manufactured surgical guide was introduced to the operation field to guide the surgery; its surgical accuracy was confirmed by comparing five corresponding points from preoperative simulation and postoperative data.

Results
We successfully performed the reduction malarplasty with the surgical guide. The accuracy level of surgery fell to 0.93 mm of total median difference for the corresponding zygoma points of preoperative simulations and postoperative zygoma. The anterior and upper points showed less error level (0.59 and 0.73 mm difference, respectively) than did other points.

Conclusions
We developed a computer-assisted surgical technique using a surgical guide for asymmetrical/prominent zygoma which proved to be simple, practical, and accurate; it is expected to help surgeons perform reduction malarplasty with ease and accuracy.
Efficacy and safety of re-irradiation for locoregional esophageal squamous cell carcinoma recurrence after radiotherapy: a systematic review and meta-analysis
Authors: Lan Kuntian , Chen Jiaohong 
Published: March 2022

Abstract
Background
There is currently no standard treatment for locoregional recurrence of esophageal squamous cell carcinoma (ESCC) previously treated with radiotherapy. This study aimed to assess the efficacy and safety of re-irradiation for ESCC patients with locoregional recurrence.

Methods
The PubMed, EmBase, and Cochrane library databases were systematically searched for eligible studies published before January 2021. The pooled effect estimates were calculated using the random effects model. Subgroup analyses were conducted to assess the treatment effectiveness of re-irradiation based on specific characteristics.

Results
Nine retrospective studies including 573 ESCC patients with locoregional recurrence were selected. The pooled incidences of the 1-year, 2-year, 3-year, and 5-year survival for patients after re-irradiation were 59% (95% confidence interval [CI]: 35–83; P < 0.001), 25% (95% CI: 16–33; P < 0.001), 25% (95% CI: 4–45; P = 0.017), and 15% (95% CI: 2–27; P = 0.024), respectively. The rates of complete response and local re-recurrence after re-irradiation were 54% (95% CI: 21–88; P = 0.001) and 62% (95% CI: 55–70; P < 0.001), respectively. The median overall survival and local failure-free survival for patients after re-irradiation were 13.94 months (95% CI: 4.18–46.51; P < 0.001) and 11.01 months (95% CI: 5.99–20.22; P < 0.001), respectively. Grade ≥ 3 adverse events of esophageal perforation, tracheoesophageal fistula, and radiation pneumonitis were significantly more common after re-irradiation.

Conclusions
This study found that re-irradiation for ESCC patients with locoregional recurrence after previous radiotherapy was feasible. However, patients should be carefully observed in order to treat associated adverse events, including esophageal perforation, tracheoesophageal fistula, and radiation pneumonitis.
Anti-inflammatory effects of anemonin on acute ulcerative colitis via targeted regulation of protein kinase C-θ
Authors: Jiang Lu , Chi Chunhua , Yuan Fang , Lu Meiqi , Hu Dongqing , Wang Lin , Liu Xiaoming 
Published: March 2022

AbstractBackgroundUlcerative colitis (UC) is an inflammatory bowel disease that causes continuous mucosal inflammation. Anemonin is a natural molecule from the Ranunculaceae and Gramineae plants that exerts anti-inflammatory properties. This study aimed to explore the effects and mechanisms of anemonin on UC.MethodsC57BL/6 mice were administered dextran sulphate sodium (DSS; 3% [w/v]) to establish an animal model of UC. Mice were treated with an intraperitoneal injection of anemonin. Body weight and the disease activity index (DAI) were recorded. Haematoxylin and eosin staining, RT-qPCR, ELISA, and western blotting were performed to evaluate the histopathological changes and tissue inflammation. HT-29 cells were treated with lipopolysaccharide (LPS) and anemonin. Cell inflammation was evaluated using RT-qPCR and western blotting. The target proteins of anemonin were predicted using bioinformatics analysis and confirmed in vitro and in vivo.ResultsAnemonin improved DSS-induced body weight loss, shortened colon length, increased DAI, and induced pathological changes in the colon tissue of mice. Anemonin inhibited DSS-induced colon tissue inflammation as the release of IL-1β, TNF-α, and IL-6 was significantly suppressed. Additionally, anemonin attenuated LPS-induced cytokine production in HT-29 cells. PKC-θ was predicted as a target protein of anemonin. Anemonin did not affect PRKCQ gene transcription, but inhibited its translation. PRKCQ overexpression partially reversed the protective effects of anemonin on HT-29 cells. Adeno-associated virus delivery of the PRKCQ vector significantly reversed the protective effects of anemonin on the mouse colon.ConclusionsAnemonin has the potential to treat UC. The anti-inflammatory effects of anemonin may be mediated through targeting PKC-θ.
Nationwide comprehensive epidemiological study of rare diseases in Japan using a health insurance claims database
Authors: Ninomiya Kota , Okura Masahiro 
Published: March 2022

Abstract
Background
There are more than 7000 rare diseases, most of which have no specific treatment. Disease profiles, such as prevalence and natural history, among the population of a specific country are essential in determining for which disease to research and develop drugs. In Japan, disease profiles of fewer than 2000 rare diseases, called Nanbyo, have been investigated. However, non-Nanbyo rare diseases remain largely uninvestigated. Accordingly, we revealed the prevalence and natural history of rare diseases among the Japanese population. This cross-disease study is the first to analyze rare-disease epidemiology in Japan with high accuracy, disease coverage, and granularity.

Method
We applied for permission to use the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), which covered 99.9% of public health insurance claims from hospitals and 97.9% from clinics as of May 2015. Then, we obtained 10 years of data on the number of patients of approx. 4500 rare diseases, by sex and age. We translated disease names and established correspondences between rare diseases in NDB and those in Orphanet. Accordingly, we compared the prevalence and natural history between them.

Results
About 3000 diseases in NDB are included in Orphanet and other medical databases. The data indicates that even if the Nanbyo systems do not cover a rare disease, its patients survive in many cases. Regarding natural history, genetic diseases tend to be diagnosed later in Japan than in the West. The data shown in this research are available in the Additional file 1 and the website of NanbyoData.

Conclusions
Our research revealed the basic epidemiology and natural history of Japanese patients with some rare diseases using a health insurance claims database. The results imply that the coverage of the present Nanbyo systems is inadequate for rare diseases. Therefore, fundamental reform might be needed to reduce unfairness between rare diseases. Most diseases in Japan follow a tendency of natural history similar to those reported in Orphanet. However, some are detected later, partly because fewer clinical genetic tests are available in Japan than in the West. Finally, we hope that our data and analysis accelerate drug discovery for rare diseases in Japan.
Survival of children with rare structural congenital anomalies: a multi-registry cohort study
Authors: Coi Alessio , Santoro Michele , Pierini Anna , Rankin Judith , Glinianaia Svetlana V. , Tan Joachim , Reid Abigail-Kate , Garne Ester , Loane Maria , Given Joanne , Ballardini Elisa , Cavero-Carbonell Clara , de Walle Hermien E. K. , Gatt Miriam , García-Villodre Laura , Gissler Mika , Jordan Sue , Kiuru-Kuhlefelt Sonja , Kjaer Urhoj Stine , Klungsøyr Kari , Lelong Nathalie , Lutke L. Renée , Neville Amanda J. , Rahshenas Makan , Scanlon Ieuan , Wellesley Diana , Morris Joan K. 
Published: March 2022

AbstractBackgroundCongenital anomalies are the leading cause of perinatal, neonatal and infant mortality in developed countries. Large long-term follow-up studies investigating survival beyond the first year of life in children with rare congenital anomalies are costly and sufficiently large standardized cohorts are difficult to obtain due to the rarity of some anomalies. This study aimed to investigate the survival up to 10 years of age of children born with a rare structural congenital anomaly in the period 1995–2014 in Western Europe.MethodsLive births from thirteen EUROCAT (European network for the epidemiological surveillance of congenital anomalies) population-based registries were linked to mortality records. Survival for 12,685 live births with one of the 31 investigated rare structural congenital anomalies (CAs) was estimated at 1 week, 4 weeks and 1, 5 and 10 years of age within each registry and combined across Europe using random effects meta-analyses. Differences between registries were evaluated for the eight rare CAs with at least 500 live births.ResultsAmongst the investigated CAs, arhinencephaly/holoprosencephaly had the lowest survival at all ages (58.1%, 95% Confidence Interval (CI): 44.3–76.2% at 1 week; 47.4%, CI: 36.4–61.6% at 1 year; 35.6%, CI: 22.2–56.9% at 10 years). Overall, children with rare CAs of the digestive system had the highest survival (> 95% at 1 week, > 84% at 10 years). Most deaths occurred within the first four weeks of life, resulting in a 10-year survival conditional on surviving 4 weeks of over 95% for 17 out of 31 rare CAs. A moderate variability in survival between participating registries was observed for the eight selected rare CAs.ConclusionsPooling standardised data across 13 European CA registries and the linkage to mortality data enabled reliable survival estimates to be obtained at five ages up to ten years. Such estimates are useful for clinical practice and parental counselling.
Delineation of dual molecular diagnosis in patients with skeletal deformity
Authors: Liu Lian , Sun Liying , Chen Yujun , Wang Muchuan , Yu Chenxi , Huang Yingzhao , Zhao Sen , Du Huakang , Chen Shaoke , Fan Xin , Tian Wen , Wu Zhihong ,   Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study group, Qiu Guixing , Zhang Terry Jianguo , Wu Nan 
Published: March 2022

AbstractBackgroundSkeletal deformity is characterized by an abnormal anatomical structure of bone and cartilage. In our previous studies, we have found that a substantial proportion of patients with skeletal deformity could be explained by monogenic disorders. More recently, complex phenotypes caused by more than one genetic defect (i.e., dual molecular diagnosis) have also been reported in skeletal deformities and may complicate the diagnostic odyssey of patients. In this study, we report the molecular and phenotypic characteristics of patients with dual molecular diagnosis and variable skeletal deformities.ResultsFrom 1108 patients who underwent exome sequencing, we identified eight probands with dual molecular diagnosis and variable skeletal deformities. All eight patients had dual diagnosis consisting of two autosomal dominant diseases. A total of 16 variants in 12 genes were identified, 5 of which were of de novo origin. Patients with dual molecular diagnosis presented blended phenotypes of two genetic diseases. Mendelian disorders occurred more than once include Osteogenesis Imperfecta Type I (COL1A1, MIM:166200), Neurofibromatosis, Type I (NF1, MIM:162200) and Marfan Syndrome (FBN1, MIM:154700).ConclusionsThis study demonstrated the complicated skeletal phenotypes associated with dual molecular diagnosis. Exome sequencing represents a powerful tool to detect such complex conditions.
Multi-omics analysis dissects the genetic architecture of seed coat content in Brassica napus
Authors: Zhang Yuting , Zhang Hui , Zhao Hu , Xia Yefan , Zheng Xiangbo , Fan Ruyi , Tan Zengdong , Duan Chenhua , Fu Yansong , Li Long , Ye Jiang , Tang Shan , Hu Honghong , Xie Weibo , Yao Xuan , Guo Liang 
Published: March 2022

Abstract
Background
Brassica napus is an important vegetable oil source worldwide. Seed coat content is a complex quantitative trait that negatively correlates with the seed oil content in B. napus.

Results
Here we provide insights into the genetic basis of natural variation of seed coat content by transcriptome-wide association studies (TWAS) and genome-wide association studies (GWAS) using 382 B. napus accessions. By population transcriptomic analysis, we identify more than 700 genes and four gene modules that are significantly associated with seed coat content. We also characterize three reliable quantitative trait loci (QTLs) controlling seed coat content by GWAS. Combining TWAS and correlation networks of seed coat content-related gene modules, we find that BnaC07.CCR-LIKE (CCRL) and BnaTT8s play key roles in the determination of the trait by modulating lignin biosynthesis. By expression GWAS analysis, we identify a regulatory hotspot on chromosome A09, which is involved in controlling seed coat content through BnaC07.CCRL and BnaTT8s. We then predict the downstream genes regulated by BnaTT8s using multi-omics datasets. We further experimentally validate that BnaCCRL and BnaTT8 positively regulate seed coat content and lignin content. BnaCCRL represents a novel identified gene involved in seed coat development. Furthermore, we also predict the key genes regulating carbon allocation between phenylpropane compounds and oil during seed development in B. napus.

Conclusions
This study helps us to better understand the complex machinery of seed coat development and provides a genetic resource for genetic improvement of seed coat content in B. napus breeding.
Developing a core outcome set for assessing clinical safety outcomes of cardiovascular diseases in clinical trials of integrated traditional Chinese medicine and Western medicine: study protocol
Authors: Qiu Ruijin , Zhong Changming , Wan Siqi , Zhang Yao , Wei Xuxu , Li Min , Hu Jiayuan , Chen Shiqi , Zhao Chen , Chen Zhao , Chen Jing , Shang Hongcai 
Published: March 2022

Abstract
Background
Integrative medicine is commonly used in China. Researchers prefer to report efficacy outcomes rather than safety outcomes in clinical trials; thus, evidence regarding safety in integrative medicine is unclear. Developing a core outcome set (COS) for safety outcomes is necessary. In this study, a representative example of the methodology for developing COS to assess safety outcomes of cardiovascular diseases in clinical trials investigating integrated medicine will be developed.

Methods and analysis
Safety information will be extracted from package inserts and through systematic reviews of treatments for cardiovascular diseases (including angina pectoris, myocardial infarction, heart failure, arrhythmia, and hypertension) to develop an extensive list of safety outcomes, which will then be categorized according to whether subjective or objective outcomes. Questionnaires for clinician-reported safety outcomes and patient-reported safety outcomes will be developed. Two rounds of the Delphi survey will then be conducted for different stakeholders (traditional Chinese medicine clinicians and researchers in cardiovascular diseases, Western medicine clinicians and researchers in cardiovascular diseases, integrated medicine clinicians and researchers of cardiovascular diseases, pharmacologists, methodologists of evidence-based medicine, and patients). After round 2 of the Delphi analysis, a face-to-face consensus meeting will be held to determine the final COS for assessing safety outcomes in cardiovascular diseases.

Discussion
A COS for safety outcomes in cardiovascular diseases may improve the consistency of reporting results and will help identify potential bias of selective reporting in the future.

Trial registration
This study was registered in the Core Outcome Measures in Effectiveness Trials database as study 1564.