bluuebunny/crossref_metadata_2025_split huggingface dataset:
National Rare Diseases Registry System (NRDRS): China’s first nation-wide rare diseases demographic analyses
Authors: Guo Jian , Liu Peng , Chen Limeng , Lv Haohan , Li Jie , Yu Weichao , Xu Kaifeng , Zhu Yicheng , Wu Zhihong , Tian Zhuang , Jin Ye , Yang Rachel , Gu Weihong , Zhang Shuyang ,   the Administrative Group of National Rare Diseases Registry System of China
Published: December 2021

Abstract
Background
China has made tremendous progresses in serving the needs of its people living with rare diseases in the past decade, especially over the last 5 years. The Chinese government’s systematic approach included a series of coordinated initiatives, amongst these are: forming the Rare Disease Expert Committee (2016), funding the “Rare Diseases Cohort Study” (2016–2020), and publishing its first “Rare Disease Catalog” (2018). Herein, we present the National Rare Diseases Registry System (NRDRS)—China’s first national rare diseases registry, and the analysis of cases registered in the first 5 years ending Dec 31, 2020.

Results
The total 62,590 cases covered 166 disease/disease types, forming 183 disease cohorts. The data from nearly 22% of them (13,947 cases) is also linked to valuable biological samples. The average age of definitive diagnosis was 30.88 years; 36.07% of cases were under 18 years of age. Regional distribution analysis showed 60% of cases were from the more developed, wealthier East and North China, suggesting the local availability of quality care and patients’ financial status were key access factors. Finally, 82.04% of cases were registered from the five clinical departments: Neurology, Endocrine, Hematology, Cardiovascular, and Nephrology, suggesting that either these are most affected by rare diseases, or that there were disease non-specific ascertainment factors.

Conclusions
The preliminary analysis of the first 5-year’s data provides unique and valuable insight on rare disease distribution in China, and higlights the directions for enhancing equity, scale and utility.
Current status of newborn screening for Pompe disease in Japan
Authors: Sawada Takaaki , Kido Jun , Sugawara Keishin , Momosaki Ken , Yoshida Shinichiro , Kojima-Ishii Kanako , Inoue Takahito , Matsumoto Shirou , Endo Fumio , Ohga Shouichi , Hirose Shinichi , Nakamura Kimitoshi 
Published: December 2021

Abstract
Background
Pompe disease is an autosomal recessive inherited metabolic disorder caused by a deficiency of the acid α-glucosidase (GAA). Pompe disease manifests as an accumulation of lysosomal glycogen in the skeletal and heart muscle. We conducted newborn screening (NBS) for Pompe disease in Japan from April 2013 to October 2020 to determine the feasibility and utility of NBS for Pompe disease.

Results
From the 296,759 newborns whose enzyme activity was measured, 107 of which underwent GAA analysis, we found one patient with infantile-onset Pompe disease (IOPD) and seven with potential late-onset Pompe disease (LOPD). We identified 34 pseudodeficient individuals and 65 carriers or potential carriers. The frequency of patients with IOPD was similar to that in the United States, but significantly lower than that in Taiwan. One patient with IOPD underwent early enzyme replacement therapy within a month after birth before presenting exacerbated manifestations, whereas those with potential LOPD showed no manifestations during the follow-up period of six years.

Conclusions
The frequency of IOPD in Japan was similar to that in the United States, where NBS for Pompe disease is recommended. This indicates that NBS for Pompe disease may also be useful in Japan. Therefore, it should be used over a wider region in Japan.
BacMam virus-based surface display for HCV E2 glycoprotein induces strong cross-neutralizing antibodies and cellular immune responses in vaccinated mice
Authors: Kord Ebrahim , Roohvand Farzin , Dubuisson Jean , Vausselin Thibaut , Nasr Azadani Hosein , Keshavarz Abolfazl , Nejati Ahmad , Samimi-Rad Katayoun 
Published: December 2021

Abstract
Background
Despite recent advancements, limitations in the treatment and control of hepatitis C virus (HCV) infection reprioritized the studies for invention of an efficient HCV vaccine to elicit strong neutralizing antibodies (NAbs) and cellular responses.

Methods
Herein, we report molecular construction of a BacMam virus-based surface display for a subtype-1a HCV gpE2 (Bac-CMV-E2-gp64; Bac) that both expressed and displayed gpE2 in mammalian cells and bacouloviral envelope, respectively.

Results
Assessments by western blotting, Immunofluorescence and Immunogold-electron microscopy indicated the proper expression and incorporation in insect cell and baculovirus envelope, respectively. Mice immunized in three different prime-boost immunization groups of: Bac/Bac, Bac/Pro (bacoulovirus-derived gpE2) and Bac/DNA (plasmid DNA (pCDNA)-encoding gpE2) developed high levels of IgG and IFN-γ (highest for Bac/Bac group) indicating the induction of both humeral and cellular immune responses. Calculation of the IgG2a/IgG1 and IFN-γ/IL-4 ratios indicated a Th1 polarization of immune responses in the Bac/Bac and Bac/DNA groups but a balanced Th1-Th2 phenotype in the Bac/Pro group. Sera of the mice in the Bac/Bac group provided the highest percentage of cross-NAbs against a subtype-2a HCVcc (JFH1) compared to Bac/Pro and Bac/DNA groups (62% versus 41% and 6%).

Conclusions
Results indicated that BacMam virus-based surface display for gpE2 might act as both subunit and DNA vaccine and offers a promising strategy for development of HCV vaccine for concurrent induction of strong humoral and cellular immune responses.
Anorexia nervosa, conduct disorder, and the juvenile justice system: a case of applying traditional treatment modalities in a non-traditional setting
Authors: Robinovitz Miriam L. , Montalto Gregg Joseph , Afzal Khalid I. , Lichtor Stephanie , Palepu Sandeep , Oaklander Dena , Carollo Sarah , Tutko Jonathan , Wildes Jennifer E. 
Published: December 2021

Abstract
Background
Anorexia Nervosa is highly comorbid with depressive, anxiety, and obsessive-compulsive spectrum disorders. However, it has not previously been reported as comorbid with antisocial personality traits, except when substance use disorder is also identified. We present an unusual case of a patient with resistant anorexia nervosa and comorbid conduct disorder. This case was also unique in that the juvenile justice system was involved during treatment.

Case presentation
A 13-year-old female was admitted to our pediatric hospital for the treatment of anorexia nervosa. She had a history of violent behaviors toward family members, often jeopardizing her care. During hospitalization, she physically attacked a physician on her care team shortly before she transitioned to an eating disorders treatment program. She was diagnosed with conduct disorder, and following discharge, she attacked her father in a premeditated act. This led to her entry into the juvenile justice system. While under the custody of the juvenile justice system, she was readmitted to our hospital for further treatment of anorexia nervosa. Our treatment strategy included psychotropics, positive reinforcement, close interdisciplinary coordination among the various hospital teams, and the juvenile justice system. Following discharge from her second hospitalization back to the juvenile detention system, our patient maintained a healthy weight and appeared to show improvements in the cognitive distortions related to her eating disorder.

Conclusions
To our knowledge, this is the first reported successful treatment of an individual with resistant anorexia nervosa and conduct disorder. It was likely a combination of weight gain, psychotropic medications, and the structured milieu provided by the juvenile justice system that led to the effective treatment of our patient. This case illustrates that a non-traditional healthcare setting can be an asset to treatment through persistence and close collaboration across institutions.
Quantitative single-cell analysis of immunofluorescence protein multiplex images illustrates biomarker spatial heterogeneity within breast cancer subtypes
Authors: Cheung Alison Min-Yan , Wang Dan , Liu Kela , Hope Tyna , Murray Mayan , Ginty Fiona , Nofech-Mozes Sharon , Martel Anne Louise , Yaffe Martin Joel 
Published: December 2021

Abstract
Background
The extent of cellular heterogeneity in breast cancer could have potential impact on diagnosis and long-term outcome. However, pathology evaluation is limited to biomarker immunohistochemical staining and morphology of the bulk cancer. Inter-cellular heterogeneity of biomarkers is not usually assessed. As an initial evaluation of the extent of breast cancer cellular heterogeneity, we conducted quantitative and spatial imaging of Estrogen Receptor (ER), Progesterone Receptor (PR), Epidermal Growth Factor Receptor-2 (HER2), Ki67, TP53, CDKN1A (P21/WAF1), CDKN2A (P16INK4A), CD8 and CD20 of a tissue microarray (TMA) representing subtypes defined by St. Gallen surrogate classification.

Methods
Quantitative, single cell-based imaging was conducted using an Immunofluorescence protein multiplexing platform (MxIF) to study protein co-expression signatures and their spatial localization patterns. The range of MxIF intensity values of each protein marker was compared to the respective IHC score for the TMA core. Extent of heterogeneity in spatial neighborhoods was analyzed using co-occurrence matrix and Diversity Index measures.

Results
On the 101 cores from 59 cases studied, diverse expression levels and distributions were observed in MxIF measures of ER and PR among the hormonal receptor-positive tumor cores. As expected, Luminal A-like cancers exhibit higher proportions of cell groups that co-express ER and PR, while Luminal B-like (HER2-negative) cancers were composed of ER+, PR- groups. Proliferating cells defined by Ki67 positivity were mainly found in groups with PR-negative cells. Triple-Negative Breast Cancer (TNBC) exhibited the highest proliferative fraction and incidence of abnormal P53 and P16 expression. Among the tumors exhibiting P53 overexpression by immunohistochemistry, a group of TNBC was found with much higher MxIF-measured P53 signal intensity compared to HER2+, Luminal B-like and other TNBC cases. Densities of CD8 and CD20 cells were highest in HER2+ cancers. Spatial analysis demonstrated variability in heterogeneity in cellular neighborhoods in the cancer and the tumor microenvironment.

Conclusions
Protein marker multiplexing and quantitative image analysis demonstrated marked heterogeneity in protein co-expression signatures and cellular arrangement within each breast cancer subtype. These refined descriptors of biomarker expressions and spatial patterns could be valuable in the development of more informative tools to guide diagnosis and treatment.
Long noncoding RNA PVT1 promotes breast cancer proliferation and metastasis by binding miR-128-3p and UPF1
Authors: Liu Shuiyi , Chen Weiqun , Hu Hui , Zhang Tianzhu , Wu Tangwei , Li Xiaoyi , Li Yong , Kong Qinzhi , Lu Hongda , Lu Zhongxin 
Published: December 2021

Abstract
Background
Mounting evidence supports that long noncoding RNAs (lncRNAs) have critical roles during cancer initiation and progression. In this study, we report that the plasmacytoma variant translocation 1 (PVT1) lncRNA is involved in breast cancer progression.

Methods
qRT-PCR and western blot were performed to detect the gene and protein expression. Colony formation would healing and transwell assays were used to detect cell function. Dual-luciferase reporter assay and RNA pull-down experiments were used to examine the mechanisms interaction between molecules. Orthotopic mouse models were established to evaluate the influence of PVT1 on tumor growth and metastasis in vivo.

Results
PVT1 is significant upregulated in breast cancer patients’ plasma and cell lines. PVT1 promotes breast cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, PVT1 upregulates FOXQ1 via miR-128-3p and promotes epithelial–mesenchymal transition. In addition, PVT1 binds to the UPF1 protein, thereby inducing epithelial–mesenchymal transition, proliferation and metastasis in breast cancer cells.

Conclusion
PVT1 may act as an oncogene in breast cancer through binding miR-128-3p and UPF1 and represents a potential target for BC therapeutic development.
SmartFeeding4Kids, an online self-guided parenting intervention to promote positive feeding practices and healthy diet in young children: study protocol for a randomized controlled trial
Authors: Gomes Ana Isabel , Pereira Ana Isabel , Guerreiro Tiago , Branco Diogo , Roberto Magda Sofia , Pires Ana , Sousa Joana , Baranowski Tom , Barros Luísa 
Published: December 2021

Abstract
Background
Caregivers’ influence on young children’s eating behaviors is widely recognized. Nutritional interventions that focus on the promotion of children’s healthy diet should actively involve parents, focusing on their feeding behaviors and practices.

Methods
This work aims to describe the development and study protocol of the SmartFeeding4Kids (SF4K) program, an online self-guided 7-session intervention for parents of young (2–6 years old) children. The program is informed by social cognitive, self-regulation, and habit formation theoretical models and uses self-regulatory techniques as self-monitoring, goal setting, and feedback to promote behavior change. We propose to examine the intervention efficacy on children’s intake of fruit, vegetables, and added sugars, and parental feeding practices with a two-arm randomized controlled with four times repeated measures design (baseline, immediately, 3 and 6 months after intervention). Parental perceived barriers about food and feeding, food parenting self-efficacy, and motivation to change will be analyzed as secondary outcomes. The study of the predictors of parents’ dropout rates and the trajectories of parents’ and children’s outcomes are also objectives of this work.

Discussion
The SmartFeeding4Kids program relies on technological resources to deliver parents’ self-regulation techniques that proved effective in promoting health behaviors. The study design can enhance the knowledge about the most effective methodologies to change parental feeding practices and children’s food intake. As a self-guided online program, SmartFeeding4Kids might overcome parents’ attrition more effectively, besides being easy to disseminate and cost-effective.

Trial registration
The study was registered in ClinicalTrials.gov (NCT04591496) on October 19, 2020.
Association of Helicobacter pylori infection with the risk of metabolic syndrome and insulin resistance: an updated systematic review and meta-analysis
Authors: Azami Mobin , Baradaran Hamid Reza , Dehghanbanadaki Hojat , Kohnepoushi Parisa , Saed Lotfolah , Moradkhani Asra , Moradpour Farhad , Moradi Yousef 
Published: December 2021

Abstract
Background
Conflicting results of recent studies on the association between Helicobacter pylori (H. pylori) infection and the risk of insulin resistance and metabolic syndrome explored the need for updated meta-analysis on this issue. Therefore, this systematic review aimed to estimate the pooled effect of H. pylori infection on the risk of insulin resistance and metabolic syndrome.

Methods
To identify case–control studies and cohort studies evaluating the association of H. pylori infection with insulin resistance and metabolic syndrome, a comprehensive literature search was performed from international databases including Medline (PubMed), Web of Sciences, Scopus, EMBASE, and CINHAL from January 1990 until January 2021. We used odds ratio with its 95% confidence interval to quantify the effect of case–control studies and risk ratio with its 95% CI for the effect of cohort studies.

Results
22 studies with 206,911 participants were included for meta-analysis. The pooled estimate of odds ratio between H. pylori infection and metabolic syndrome in case–control studies was 1.19 (95% CI 1.05–1.35; I2 = 0%), and in cohort studies, the pooled risk ratio was 1.31 (95% CI 1.13–1.51; I2 = 0%). Besides, case–control studies showed the pooled odds ratio of 1.54 (95% CI 1.19–1.98; I2 = 6.88%) for the association between H. pylori infection and insulin resistance.

Conclusion
In this meta-analysis, the results showed that there was a possibility of metabolic syndrome and insulin resistance in case of H. pylori infection.
Transcriptome-wide association study identified candidate genes associated with gut microbiota
Authors: Pan Chuyu , Ning Yujie , Jia Yumeng , Cheng Shiqiang , Wen Yan , Yang Xuena , Meng Peilin , Li Chun’e , Zhang Huijie , Chen Yujing , Zhang Jingxi , Zhang Zhen , Zhang Feng 
Published: December 2021

Abstract
Background
Gut microbiota is closely associated with host health and disease occurrence. Host genetic factor plays an important role in shaping gut microbial communities. The specific mechanism of host-regulated gene expression affecting gut microbiota has not been elucidated yet. Here we conducted a transcriptome-wide association study (TWAS) for gut microbiota by leveraging expression imputation from large-scale GWAS data sets.

Results
TWAS detected multiple tissue-specific candidate genes for gut microbiota, such as FUT2 for genus Bifidobacterium in transverse colon (PPERM.ANL = 1.68 × 10–3) and SFTPD for an unclassified genus of Proteobacteria in transverse colon (PPERM.ANL = 5.69 × 10–3). Fine mapping replicated 3 candidate genes in TWAS, such as HELLS for Streptococcus (PIP = 0.685) in sigmoid colon, ANO7 for Erysipelotrichaceae (PIP = 0.449) in sigmoid colon. Functional analyses detected 94 significant GO terms and 11 pathways for various taxa in total, such as GO_NUCLEOSIDE_DIPHOSPHATASE_ACTIVITY for Butyrivibrio (FDR P = 1.30 × 10–4), KEGG_RENIN_ANGIOTENSIN_SYSTEM for Anaerostipes (FDR P = 3.16 × 10–2). Literature search results showed 12 genes prioritized by TWAS were associated with 12 diseases. For instance, SFTPD for an unclassified genus of Proteobacteria was related to atherosclerosis, and FUT2 for Bifidobacterium was associated with Crohn’s disease.

Conclusions
Our study results provided novel insights for understanding the genetic mechanism of gut microbiota, and attempted to provide clues for revealing the influence of genetic factors on gut microbiota for the occurrence and development of diseases.
Identification of muscle weakness in older adults from normalized upper and lower limbs strength: a cross-sectional study
Authors: Abdalla Pedro Pugliesi , Bohn Lucimere , da Silva Leonardo Santos Lopes , dos Santos André Pereira , Tasinafo Junior Marcio Fernando , Venturini Ana Claudia Rossini , dos Santos Carvalho Anderson , Gomez David Martinez , Mota Jorge , Machado Dalmo Roberto Lopes 
Published: December 2021

Abstract
Background
To propose cut-off points for older adults’ weakness for upper and lower limbs muscle strength normalized by body size with the ratio standard/muscle quality and allometric scaling.

Methods
Ninety-four community-dwelling older adults (69.1% women) were assessed for 49 body-size variables (anthropometry, body composition and body indexes), handgrip strength (HGS), one maximum repetition measurement for knee extensors (1RM), isokinetic knee extension peak torque at 60°/s (PT), and six-minute walk test (6MWT). Ratio standard or muscle quality (muscle strength/body size) and allometric scaling (muscle strength/body sizeb; when b is the allometric exponent) were applied for body-size variables significantly correlated with HGS, 1RM and PT. Cut-off points were computed according to sex based on mobility limitation (6MWT < 400 m) with ROC curve and Youden index.

Results
Absolute HGS, 1RM and PT cut-off points were not adequate because they were associated with body size (r > 0.30). But it was corrected with muscle strength normalization according to body size-variables: HGS (n = 1); 1RM (n = 24) and PT (n = 24). The best cut-off points, with the highest area under the curve (AUC), were found after normalization for men: HGS/forearm circumference (1.33 kg/cm, AUC = 0.74), 1RM/triceps skinfold (4.22 kg/mm, AUC = 0.81), and PT/body mass*height0.43 (13.0 Nm/kg*m0.43, AUC = 0.94); and for women: HGS/forearm circumference (1.04 kg/cm, AUC = 0.70), 1RM/body mass (0.54 kg/kg, AUC = 0.76); and PT/body mass0.72 (3.14 Nm/kg0.72; AUC = 0.82).

Conclusions
Upper and lower limbs muscle weakness cut-off points standardized according to body size were proposed for older adults of both sexes. Normalization removes the effect of extreme body size on muscle strength (both sexes) and improves the accuracy to identify weakness at population level (for women, but not in men), reducing the risk of false-negative/positive cases.
Bixin and fucoxanthin sensitize human lung cancer and cervical cancer cell to cisplatin in vitro
Authors: Nurcahyanti Agustina Dwi Retno , Kusmita Lia , Wink Michael 
Published: December 2021

Abstract
Objective
Cisplatin is a conventional anticancer drug that generates reactive oxygen species and causes apoptosis. However, many cancer cells develop alterations in the ATP binding cassette transporter responsible for the uptake and efflux process, which leads to resistance. Many natural products have shown potential to compete with ATP binding cassette transporter and may sensitize resistant cells to cisplatin. Studies have shown pro-oxidant effect of carotenoids that promote apoptosis of cancer cells. Bixin and fucoxanthin are well-known carotenoids with known antioxidant properties, however their bioactivity in lung cancer cells, clinically known to develop resistance due to ATP binding cassette transporter, has been minimally studied. This study is the first to investigate the potential of bixin and fucoxanthin to sensitize human lung cancer cell line, A549 and cervical cancer cell line, HeLa, to cisplatin. Drug combination method developed by Chou and Talalay theorem was employed.

Result
Employing the best combination ratio, this study shows selective sensitization of cancer cells to cisplatin after bixin and fucoxanthin treatment. Further study on the mechanism of action in specific types of cancer cells is warranted. It may improve cisplatin sensitivity in tumors and rational use of cancer drugs.

Graphical Abstract
Promoter methylation-mediated repression of UNC5 receptors and the associated clinical significance in human colorectal cancer
Authors: Dong Dong , Zhang Runshi , Shao Jie , Zhang Aimin , Wang Yichao , Zhou Yunli , Li Yueguo 
Published: December 2021

Abstract
Background
Deregulated methylation of tumor suppressor genes is a hallmark event in colorectal cancer (CRC) carcinogenesis. UNC5 receptors, down-regulated in various human malignancies due to epigenetic alterations, have been proposed as putative tumor suppressor genes. In this study, we focused on the methylation-mediated inhibition of UNC5 receptors and the associated clinical significance in CRC.

Methods
Methylation and expression analysis was performed in TCGA datasets. And the results were confirmed in vitro in CRC cell lines treated with 5-aza-deoxycytidine. Then, the expression and epigenetic alterations of UNC5 receptors were evaluated in clinical specimens. Moreover, the diagnostic and prognostic values of the methylation alterations were also analyzed.

Results
Methylation-mediated repression was observed in UNC5C and UNC5D, but not in UNC5A and UNC5B, which was confirmed in CRC cell lines. Except for UNC5B, significantly elevated methylation was observed in UNC5A, UNC5C, and UNC5D in CRC. The discrimination efficiency of the three receptors was comparable with that of SEPT9. Kaplan–Meier curve survival analysis showed that hypermethylation of UNC5A, UNC5C and UNC5D was associated with poor progression-free and overall survival. Moreover, methylation levels of UNC5C and UNC5D were independent predictors of CRC progression-free (P = 0.001, P = 0.003, respectively) and overall survival (P = 0.008, P = 0.004, respectively).

Conclusions
Hypermethylation of UNC5C and UNC5D mediates the repression and has promising diagnostic and prognostic values in CRC.