bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of host gene-microbiome associations in colorectal cancer patients using mendelian randomization
Authors: Xiang Yaoxian , Zhang Chan , Wang Jing , Cheng Yurong , Wang Li , Tong Yingying , Yan Dong 
Published: August 2023

Abstract
Background
There are many studies indicating that alterations in the abundance of certain gut microbiota are associated with colorectal cancer (CRC). However, a causal relationship has not been identified due to confounding factors such as lifestyle, environmental, and possible reverse causal associations between the two. Furthermore, certain host gene mutations can also contribute to the development of CRC. However, the association between genes and gut microbes in patients with CRC has not been extensively studied.

Methods
We conducted a two-sample Mendelian randomization (MR) study to reveal the causal relationship between gut microbiota and CRC. We obtained SNPs associated with gut microbiome abundance as instrumental variables (IVs) from a large-scale, multi-ethnic GWAS study, and extracted CRC-related datasets from an East Asian Population genetic consortia GWAS (AGWAS) study and FinnGen consortium, respectively. We analyzed a total of 166 bacterial features at four taxonomic levels, including order, family, genus, and species. The inverse-variance-weighted (IVW), weighted median, MR-Egger, and simple median methods were applied to the MR analysis, and the robustness of the results were tested using a series of sensitivity analyses. We extracted IVs of gut microbiota with direct causal association with CRC for SNP annotation to identify the genes in which these genetic variants were located to reveal the possible host gene-microbiome associations in CRC patients.

Results
The findings from our MR analysis based on CRC-associated GWAS datasets from AGWAS revealed causal relationships between 6 bacterial taxa and CRC at a locus-wide significance level (P < 1 × 10–5). The IVW method found that family Porphyromonadaceae, genera Anaerotruncus, Intestinibacter, Slackia, and Ruminococcaceae UCG004, and species Eubacterium coprostanoligenes group were positively associated with CRC risk, which was generally consistent with the results of other complementary analyses. The results of a meta-analysis of the MR estimates from the AGWAS and the FinnGen datasets showed that family Porphyromonadaceae and genera Slackia, Anaerotruncus, and Intestinibacter replicated the same causal association. Sensitivity analysis of all causal associations did not indicate significant heterogeneity, horizontal pleiotropy, or reverse causal associations. We annotated the SNPs at a locus-wide significance level of the above intestinal flora and identified 24 host genes that may be related to pathogenic intestinal microflora in CRC patients.

Conclusion
This study supported the causal relationship of gut microbiota on CRC and revealed a possible correlation between genes and pathogenic microbiota in CRC. These findings suggested that the study of the gut microbiome and its further multi-omics analysis was important for the prevention and treatment of CRC.
Transmitted/founder SHIV.D replicates in the brain, causes neuropathogenesis, and persists on combination antiretroviral therapy in rhesus macaques
Authors: Podgorski Rachel M. , Robinson Jake A. , Smith Mandy D. , Mallick Suvadip , Zhao Huaqing , Veazey Ronald S. , Kolson Dennis L. , Bar Katharine J. , Burdo Tricia H. 
Published: August 2023

AbstractA biologically relevant non-human primate (NHP) model of HIV persistence in the central nervous system (CNS) is necessary. Most current NHP/SIV models of HIV infection fail to recapitulate viral persistence in the CNS without encephalitis or fail to employ viruses that authentically represent the ongoing HIV-1 pandemic. Here, we demonstrate viral replication in the brain and neuropathogenesis after combination antiretroviral therapy (ART) in rhesus macaques (RMs) using novel macrophage-tropic transmitted/founder (TF) simian-human immunodeficiency virus SHIV.D.191,859 (SHIV.D). Quantitative immunohistochemistry (IHC) and DNA/RNAscope in situ hybridization (ISH) were performed on three brain regions from six SHIV.D-infected RMs; two necropsied while viremic, two during analytical treatment interruptions, and two on suppressive ART. We demonstrated myeloid-mediated neuroinflammation, viral replication, and proviral DNA in the brain in all animals. These results demonstrate that TF SHIV.D models native HIV-1 CNS replication, pathogenesis, and persistence on ART in rhesus macaques.
Classification of multi-year and multi-variety pumpkin seeds using hyperspectral imaging technology and three-dimensional convolutional neural network
Authors: Li Xiyao , Feng Xuping , Fang Hui , Yang Ningyuan , Yang Guofeng , Yu Zeyu , Shen Jia , Geng Wei , He Yong 
Published: August 2023

Abstract
Background
Pumpkin seeds are major oil crops with high nutritional value and high oil content. The collection and identification of different pumpkin germplasm resources play a significant role in the realization of precision breeding and variety improvement. In this research, we collected 75 species of pumpkin from the Zhejiang Province of China. 35,927 near-infrared hyperspectral images of 75 types of pumpkin seeds were used as the research object.

Results
To realize the rapid classification of pumpkin seed varieties, position attention embedded three-dimensional convolutional neural network (PA-3DCNN) was designed based on hyperspectral image technology. The experimental results showed that PA-3DCNN had the best classification effect than other classical machine learning technology. The classification accuracy of 99.14% and 95.20% were severally reached on the training and test sets. We also demonstrated that the PA-3DCNN model performed well in next year’s classification with fine-tuning and met with 94.8% accuracy.

Conclusions
The model performance improved by introducing double convolution and pooling structure and position attention module. Meanwhile, the generalization performance of the model was verified, which can be adopted for the classification of pumpkin seeds in multiple years. This study provided a new strategy and a feasible technical approach for identifying germplasm resources of pumpkin seeds.
Joint manifestations revealing inborn metabolic diseases in adults: a narrative review
Authors: Loret Amaury , Jacob Claire , Mammou Saloua , Bigot Adrien , Blasco Hélène , Audemard-Verger Alexandra , Schwartz Ida VD , Mulleman Denis , Maillot François 
Published: August 2023

AbstractInborn metabolic diseases (IMD) are rare conditions that can be diagnosed during adulthood. Patients with IMD may have joint symptoms and the challenge is to establish an early diagnosis in order to institute appropriate treatment and prevent irreversible damage. This review describes the joint manifestations of IMD that may be encountered in adults. The clinical settings considered were arthralgia and joint stiffness as well as arthritis. Unspecific arthralgias are often the first symptoms of hereditary hemochromatosis, chronic low back pain may reveal an intervertebral disc calcification in relation with alkaptonuria, and progressive joint stiffness may correspond to a mucopolysaccharidosis or mucolipidosis. Gaucher disease is initially revealed by painful acute attacks mimicking joint pain described as “bone crises”. Some IMD may induce microcrystalline arthropathy. Beyond classical gout, there are also gouts in connection with purine metabolism disorders known as “enzymopathic gouts”. Pyrophosphate arthropathy can also be part of the clinical spectrum of Gitelman syndrome or hypophosphatasia. Oxalate crystals arthritis can reveal a primary hyperoxaluria. Destructive arthritis may be indicative of Wilson’s disease. Non-destructive arthritis may be seen in mevalonate kinase deficiency and familial hypercholesterolemia.
Childhood cerebral adrenoleukodystrophy (CCALD) in France: epidemiology, natural history, and burden of disease - A population-based study
Authors: Sevin Caroline , Hatteb Samira , Clément Aurore , Bignami Fabrizia , Chillotti Louis , Bugnard Françoise , Bénard Stève , Boespflug-Tanguy Odile 
Published: August 2023

Abstract
Background
X-linked adrenoleukodystrophy (ALD) is a rare metabolic and neurodegenerative disorder belonging to the group of leukodystrophies, with an estimated incidence around 1:25 000 newborns worldwide, mostly among men. Childhood Cerebral ALD (CCALD) is the most severe form with a poor prognosis if not properly treated during the first years of life. Currently, only allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely available for CCALD treatment. To date, there is a lack of data regarding CCALD epidemiology, natural history, and current management in France. This knowledge is crucial for the development of new therapies such as gene therapies. In this context, the French National Health Data System (SNDS) is a particularly indicated database to collect information meeting these needs. A non-interventional, national, real-life, retrospective study was performed using secondary data from the national ALD registry (LEUKOFRANCE) and SNDS. CCALD patients detected between 2009 and 2018 and successfully matched between LEUKOFRANCE and SNDS were included in this study. Index date was defined as the first CCALD event detected during study period. Subgroups of patients with sufficient follow-up (6 months) and history (1 year) available around index date were analyzed to assess CCALD burden and natural history.

Results
52 patients were included into the matched cohort. Median annual incidence of CCALD was estimated at 4 patients. Median age at CCALD diagnosis was 7.0 years. Among patients without allo-HSCT, five-year overall survival was 66.6%, with 93.3% of them presenting at least one CCALD symptom and 62.1% presenting a least one major functional disability (MFD). Among patients with allo-HSCT, five-year overall survival was 94.4%, with only 11.1% of patients presenting CCALD symptoms, and 16.7% of presenting a MFD. Mean annualized costs were almost twice as important among patients without allo-HSCT, with 49,211€, 23,117€, respectively. Costs were almost exclusively represented by hospitalizations.

Conclusions
To the best of our knowledge, this is the most up to date study analyzing CCALD epidemiology, clinical and economic burden in France. The necessity of a precocious management with HSCT highlight the potential benefits of including an expanded screening program among newborns, coupled with family screenings when a mutation is detected.
Physicians’ use and perceptions of genetic testing for rare diseases in China: a nationwide cross-sectional study
Authors: Liu Weida , Liu Peng , Guo Dan , Jin Ye , Zhao Kun , Zheng Jiayin , Li Kexin , Li Linkang , Zhang Shuyang 
Published: August 2023

Abstract
Background
Genetic testing can facilitate the diagnosis and subsequent therapeutic management of rare diseases. However, there is a lack of data on the use of genetic testing for rare diseases. This study aims to describe the utilization rate and troubles encountered by clinicians in treating rare diseases with genetic testing.

Methods
A cross-sectional electronic questionnaire survey was conducted between June and October 2022 among the medical staff from the hospitals covering all provinces, municipalities, and autonomous regions of China. The survey on genetic testing focused on whether genetic testing was used in the diagnosis and treatment of rare diseases, the specific methods of genetic testing, and the problems encountered when using genetic testing.

Results
A total of 20,132 physicians who had treated rare diseases were included, of whom 35.5% were from the central region, 36.7% were from the eastern region, and 27.8% were from the western region. The total utilization rate of genetic testing for rare diseases was 76.0% (95%CI: 75.4–76.6). The use of genetic testing was highest in the Eastern region (79.2% [95% CI: 78.3–80.1]), followed by the Central (75.9% [95% CI: 74.9–76.9]) and Western regions (71.9% [95% CI: 70.7–73.1]). More than 90% (94.1% [95%CI: 93.4–94.8]) of pediatricians had used genetic testing to treat rare diseases, with surgeons having the lowest use of genetic testing (58.3% [95% CI: 56.6–60.0]). Physicians’ departments and education levels affect the use of genetic testing. Most physicians have used a variety of genetic tests in the management of rare diseases, the most popular methods were “Whole-exome sequencing (Proband)” and “Whole-exome sequencing (families of three or more)”. Doctors have encountered many problems with the use of genetic testing in the diagnosis and treatment of rare diseases, among which the high price was the main concern of medical workers.

Conclusion
Three-quarters of physicians used genetic testing in rare disease practice, and there were regional differences in the use of genetic testing. Recognition of the utilization of genetic testing can help identify patterns of resource utilization in different regions and provide a more comprehensive picture of the epidemiology of rare diseases in jurisdictions.
Adult mortality patterns in Yemen before and during armed conflict: evidence from a web survey of the global diaspora
Authors: McGowan Catherine R. , Alhaffar Mervat , Ekoriko Promise , Al-Refai Sawsan , Badr Jamal , Bell Lucy , Checchi Francesco 
Published: August 2023

Abstract
Background
The ongoing war in Yemen has created a severe and protracted crisis that has left nearly three-quarters of the population in need of urgent humanitarian assistance. Despite eight years of conflict there exist few robust estimates of how the conflict (and the conflict combined with the COVID-19 pandemic) have affected mortality in Yemen. As the security situation has limited access to affected populations we have designed a novel alternative to local mortality surveys.

Methods
We used a web-based, respondent-driven sampling method to disseminate a mortality survey amongst the global Yemeni diaspora. We used Cox proportional hazards survival models to estimate the association between the exposure (i.e. between the pre-conflict, conflict, and conflict/pandemic periods) and mortality risk, adjusted for gender and birth cohort.

Results
Eighty-nine eligible respondents completed the survey. Respondents provided data on the status of 1704 individuals of whom 85 (5%) had died; of these 65 (3.8%) were reported to have died in Yemen. An analysis of survivorship of respondents’ parents after their 50th birthday (adjusted for gender and birth cohort) provided weak evidence that the war and pandemic periods were associated with higher mortality when compared to the pre-war period. Analysis of the subset of individuals who died in Yemen also suggested an increased, but non-significant hazard of dying during the war/pandemic period: this association tended towards significance when allowing for varying degrees of out-migration from Yemen across the cohort. The number of deaths amongst respondents’ siblings and children under five in Yemen were too low to allow meaningful analysis.

Conclusions
Our data suggest increased mortality during the war/pandemic period, compared to the pre-war period, among older Yemeni adults. However, our findings require careful interpretation as our study design cannot establish causation, and as our small and non-representative sample appeared skewed towards higher-income, urban communities. Surveys of diaspora populations offer a promising means of describing mortality patterns in crisis-affected populations; though, large numbers of respondents are likely required to achieve accurate mortality estimates and to adjust for selection bias.
Mother–child interactions in adolescents with borderline personality disorder traits and the impact of early life maltreatment
Authors: Williams Katharina , Fleck Leonie , Fuchs Anna , Koenig Julian , Kaess Michael 
Published: August 2023

Abstract
Background
Early detection and intervention of borderline personality disorder (BPD) in adolescence has become a public health priority. Theoretical models emphasize the role of social interactions and transgenerational mechanisms in the development of the disorder suggesting a closer look at caregiver-child relationships.

Methods
The current study investigated mother-adolescent interactions and their association with adolescent BPD traits by using a case–control design. Thirty-eight adolescent patients with ≥ 3 BPD traits and their mothers (BPD-G) were investigated in contrast to 35 healthy control dyads (HC-G). Maternal, adolescent and dyadic behavior was coded using the Coding Interactive Behavior Manual (CIB) during two interactions: a fun day planning and a stress paradigm. Additional effects of maternal and/or adolescent early life maltreatment (ELM) on behavior were also explored.

Results
BPD-G displayed a significantly lower quality of maternal, adolescent and dyadic behavior than the HC-G during both interactions. Maternal and adolescent behavior was predicted by BPD traits alone, whilst dyadic behavior was also influenced by general adolescent psychopathology. Exploratory analyses of CIB subscales showed that whilst HC-G increased their reciprocal behavior during stress compared to the fun day planning, BPD-G dyads decreased it. Maternal ELM did not differ between groups or have any effect on behavior. Adolescent ELM was correlated with behavioral outcome variables, but did not explain behavioral outcomes above and beyond the effect of clinical status.

Discussion/Conclusion
Our data suggest a stronger focus on parent–child interactions in BPD-specific therapies to enhance long-term treatment outcomes in adolescent BPD patients. Further research employing study designs that allow the analyses of bidirectional transactions (e.g. longitudinal design, behavioral microcoding) is needed.
CIS deletion by CRISPR/Cas9 enhances human primary natural killer cell functions against allogeneic glioblastoma
Authors: Nakazawa Tsutomu , Morimoto Takayuki , Maeoka Ryosuke , Matsuda Ryosuke , Nakamura Mitsutoshi , Nishimura Fumihiko , Ouji Noriko , Yamada Shuichi , Nakagawa Ichiro , Park Young Soo , Ito Toshihiro , Nakase Hiroyuki , Tsujimura Takahiro 
Published: August 2023

Abstract
Background
Glioblastoma (GBM) is the most common malignant brain tumor and has “immunologically cold” features. Changing GBM to an “immunologically hot” tumor requires a strong trigger that induces initial immune responses in GBM. Allogeneic natural killer cells (NKCs) have gained considerable attention as promising immunotherapeutic tools against cancer, where gene-edited NKCs would result in effective anti-cancer treatment. The present study focused on the immune checkpoint molecule cytokine-inducible SH2-containing protein (CISH, or CIS) as a critical negative regulator in NKCs.

Methods
The GBM tumor environment featured with immunological aspect was analyzed with Cancer immunogram and GlioVis. We generated human primary CIS-deleted NKCs (NK dCIS) using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) with single guide RNA targeting genome sites on CIS coding exons. The genome-edited NKCs underwent microarray with differential expression analysis and gene set enrichment analysis (GSEA). The anti-GBM activity of the genome-edited NKCs was evaluated by apoptosis induction effects against allogeneic GBM cells and spheroids. We further detected in vivo antitumor effects using xenograft brain tumor mice.

Results
We successfully induced human CIS-deleted NKCs (NK dCIS) by combining our specific human NKC expansion method available for clinical application and genome editing technology. CIS gene-specific guide RNA/Cas9 protein complex suppressed CIS expression in the expanded NKCs with high expansion efficacy. Comprehensive gene expression analysis demonstrated increased expression of 265 genes and decreased expression of 86 genes in the NK dCIS. Gene set enrichment analysis revealed that the enriched genes were involved in NKC effector functions. Functional analysis revealed that the NK dCIS had increased interferon (IFN)ɤ and tumor necrosis factor (TNF) production. CIS deletion enhanced NKC-mediated apoptosis induction against allogeneic GBM cells and spheroids. Intracranial administration of the allogeneic NKCs prolonged the overall survival of xenograft brain tumor mice. Furthermore, the NK dCIS extended the overall survival of the mice.

Conclusion
The findings demonstrated the successful induction of human primary NK dCIS with CRISPR/Cas9 with efficient expansion. CIS deletion enhanced the NKC-mediated anti-tumor effects in allogeneic GBM and could be a promising immunotherapeutic alternative for patients with GBM.
AR antagonists develop drug resistance through TOMM20 autophagic degradation-promoted transformation to neuroendocrine prostate cancer
Authors: Yin Linglong , Ye Yubing , Zou Ling , Lin Jinli , Dai Yi , Fu Yongming , Liu Youhong , Peng Yuchong , Gao Yingxue , Fu Yuxin , Qi Xuli , Deng Tanggang , Zhang Songwei , Li Xiong 
Published: August 2023

Abstract
Background
Prostate cancer(PCa) is the most commonly occurring male cancer in the USA. Abiraterone or Enzalutamide have been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC). However, the treatment-emergent neuroendocrine PCa (t-NEPC) may develop, resulting in drug resistance in about 10–17% CRPC patients. The detailed mechanisms remain unclear..

Methods
The expression correlation of TOMM20 and AR in PCa was determined by analyzing publicly available datasets, or by IHC staining in tumor specimens. The protein interaction of TOMM20 and AR was validated by co-immunoprecipitation or GST pull-down assay. The impact of TOMM20 depletion on drug sensitivity were elucidated by assays of cell proliferation, invasion, sphere formation, xenograft growth and intravenous metastasis. The intracellular ROS level was measured by flow cytometry, and the NEPC transdifferentiation and characteristics of cancer stem-like cells were validated by RNA-seq, RT-PCR and western blotting.

Results
The protein level of TOMM20 is positively correlated with AR in PCa cells and specimens. TOMM20 protein physically interacts with AR. AR antagonists induced the protein degradation of TOMM20 through autophagy-lysosomal pathway, thereby elevating the intracellular ROS level and activating PI3K/AKT signaling pathway. When TOMM20 was depleted, PCa cells underwent EMT, acquired the characteristics of cancer stem-like cells, and developed resistance to AR antagonists. The stable depletion of TOMM20 promoted the transdifferentiation of PCa adenocarcinoma into NEPC and metastasis. Conversely, the rescue of TOMM20 re-sensitized the resistant PCa cells to AR antagonists.

Conclusions
TOMM20 protein degradation induced by AR antagonists promoted the transdifferentiation of PCa to NEPC, thereby revealing a novel molecular mechanism by which AR antagonists develop drug resistance through mitochondrial outer membrane-mediated signaling pathway. These findings suggested that the decreasing or loss of TOMM20 expression in PCa tissues might become a useful predictor of PCa resistance to AR antagonists.