bluuebunny/crossref_metadata_2025_split huggingface dataset:
INSPIRE datahub: a pan-African integrated suite of services for harmonising longitudinal population health data using OHDSI tools
Authors: Bhattacharjee Tathagata , Kiwuwa-Muyingo Sylvia , Kanjala Chifundo , Maoyi Molulaqhooa L. , Amadi David , Ochola Michael , Kadengye Damazo , Gregory Arofan , Kiragga Agnes , Taylor Amelia , Greenfield Jay , Slaymaker Emma , Todd Jim ,   INSPIRE Network
Published: January 2024

IntroductionPopulation health data integration remains a critical challenge in low- and middle-income countries (LMIC), hindering the generation of actionable insights to inform policy and decision-making. This paper proposes a pan-African, Findable, Accessible, Interoperable, and Reusable (FAIR) research architecture and infrastructure named the INSPIRE datahub. This cloud-based Platform-as-a-Service (PaaS) and on-premises setup aims to enhance the discovery, integration, and analysis of clinical, population-based surveys, and other health data sources.MethodsThe INSPIRE datahub, part of the Implementation Network for Sharing Population Information from Research Entities (INSPIRE), employs the Observational Health Data Sciences and Informatics (OHDSI) open-source stack of tools and the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) to harmonise data from African longitudinal population studies. Operating on Microsoft Azure and Amazon Web Services cloud platforms, and on on-premises servers, the architecture offers adaptability and scalability for other cloud providers and technology infrastructure. The OHDSI-based tools enable a comprehensive suite of services for data pipeline development, profiling, mapping, extraction, transformation, loading, documentation, anonymization, and analysis.ResultsThe INSPIRE datahub's “On-ramp” services facilitate the integration of data and metadata from diverse sources into the OMOP CDM. The datahub supports the implementation of OMOP CDM across data producers, harmonizing source data semantically with standard vocabularies and structurally conforming to OMOP table structures. Leveraging OHDSI tools, the datahub performs quality assessment and analysis of the transformed data. It ensures FAIR data by establishing metadata flows, capturing provenance throughout the ETL processes, and providing accessible metadata for potential users. The ETL provenance is documented in a machine- and human-readable Implementation Guide (IG), enhancing transparency and usability.ConclusionThe pan-African INSPIRE datahub presents a scalable and systematic solution for integrating health data in LMICs. By adhering to FAIR principles and leveraging established standards like OMOP CDM, this architecture addresses the current gap in generating evidence to support policy and decision-making for improving the well-being of LMIC populations. The federated research network provisions allow data producers to maintain control over their data, fostering collaboration while respecting data privacy and security concerns. A use-case demonstrated the pipeline using OHDSI and other open-source tools.
Combined obesity- and lipid-related indices are associated with hypogonadism in Chinese male patients with type 2 diabetes: a cross-sectional study
Authors: Yu Yongzhuo , Wang Yunyang , Xu Lili , Li Wenxuan , Wang Yangang 
Published: January 2024

BackgroundThere is insufficient attention to hypogonadism in Chinese males with type 2 diabetes mellitus (T2DM). We evaluated the relationship between Combined obesity- and lipid-related indices [Visceral Adiposity Index (VAI), Chinese Visceral Adiposity Index (CVAI), Triglyceride Glucose Index (TyG) and Lipid Accumulation Product (LAP)] with total testosterone (TT) and analyzed the predictive capability of the respective cut-off values.MethodsWe recruited 958 hospitalized male patients with T2DM at the Affiliated Hospital of Qingdao University, collected baseline data and four calculated indices, and obtained their dominance ratio (OR) and corresponding 95% confidence intervals (CI) with TT by multivariate logistic regression. Receiver operating characteristic (ROC) curves were then used to determine cutoff values in predicting hypogonadism (TT&lt; 12 nmol/L), and we also analyzed the combinations between the different indices.ResultsVAI, CVAI, TyG, and LAP all have satisfactory predictive capabilities. The test capability (sensitivity and specificity) of all four indices was better or not worse than that of body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and waist circumference (WC). All four indices were effective predictors of hypogonadism at their respective cutoff values (VAI ≥ 2.284, CVAI ≥ 145.779, TyG ≥ 4.308, and LAP ≥ 59.850). Of these, LAP had the largest area under the curve (AUC, AUC = 0.852, Std. Error = 0.014, 95% CI = 0.818-0.873). However, the predictive capability of the combined indices was not significantly improved over the individual indices.ConclusionsVAI, CVAI, TyG, and LAP are sensitive indices for predicting hypogonadism in Chinese male patients with T2DM. Considering the need for concise and accurate indices in clinical practice, we suggest LAP as a commonly used index.
Evaluation of 19 years of international external proficiency testing for high-resolution HLA typing
Authors: Voorter C. E. M. , Groeneveld L. , Heidt S. , Wieten L. 
Published: January 2024

The international high-resolution external proficiency testing (EPT) started in 2004 with high-resolution typing of human leucocyte antigen (HLA) class I (HLA-A,B,C) and HLA class II (HLA-DRB1, DRB345, DQB1, and DPB1) alleles, since possibilities for such an EPT within Europe were limited and all existing EPTs at that time made use of the comparison of HLA typing results without a reference. This EPT was set up as a collaboration between the HLA laboratory of Leiden, providing DNA samples to the participants, and the laboratory of Maastricht, performing the high-resolution typing as the reference result and evaluating the results of all participants according to the prevailing European Federation for Immunogenetics (EFI) standards. Once a year, 12 samples were sent to the participating laboratories, and evaluation and certificates were provided at the end of that same year. During the years, the EPT was extended to low-resolution HLA class I and II typing, high-resolution typing including DQA1 and DPA1, and allelic resolution typing for HLA class I, the latter one being unique in this field. Evaluation of the high-resolution typing results of the last 19 years showed a clear increase in the number of loci tested by the participating laboratories and a clear change of method from Sanger sequencing with additional other techniques (SSO/SSP) to the nowadays widely used next-generation sequencing method. By strictly using the EFI rules for high-resolution HLA typing, the participants were made aware of the ambiguities within exons 2 and 3 for class I and exon 2 for class II and the presence of null alleles even in a two-field HLA typing. There was an impressive learning curve, resulting in &gt;98% correctly typed samples since 2017 and a 100% fulfillment of EFI rules for all laboratories for all loci submitted in the last 2 years. Overall, this EPT meets the need of an EPT for high-resolution typing for EFI accreditation.
An early warning indicator of mortality risk in patients with COVID-19: the neutrophil extracellular traps/neutrophilic segmented granulocyte ratio
Authors: Wang Qiong , Qin Yu , Ma Jingyun , Zhou Kehao , Xia Guiping , Li Ya , Xie Li , Afful Richmond Godwin , Lan Qian , Huo Xingyu , Zou Jian , Yang Hailin 
Published: January 2024

BackgroundNeutrophil extracellular traps (NETs) play a key role in thrombus formation in patients with coronavirus disease 2019 (COVID-19). However, the existing detection and observation methods for NETs are limited in their ability to provide quantitative, convenient, and accurate descriptions of in situ NETs. Therefore, establishing a quantitative description of the relationship between NETs and thrombosis remains a challenge.ObjectiveWe employed morphological observations of blood cells and statistical analyses to investigate the correlation between the NETs/neutrophilic segmented granulocyte ratio and mortality risk in patients with COVID-19.MethodsPeripheral blood samples were collected from 117 hospitalized patients with COVID-19 between November 2022 and February 2023, and various blood cell parameters were measured. Two types of smudge cells were observed in the blood and counted: lymphatic and neutral smudge cells. Statistical data analysis was used to establish COVID-19 mortality risk assessment indicators.ResultsMorphological observations of neutrophilic smudge cells revealed swelling, eruption, and NETs formation in the neutrophil nuclei. Subsequently, the NETs/neutrophilic segmented granulocyte ratio (NNSR) was calculated. A high concentration of NETs poses a fatal risk for thrombus formation in patients. Statistical analysis indicated that a high NNSR was more suitable for evaluating the risk of death in patients with COVID-19 compared to elevated fibrinogen (FIB) and D-dimer (DD) levels.ConclusionObserving blood cell morphology is an effective method for the detection of NETs, NNSR are important markers for revealing the mortality risk of patients with COVID-19.
An in silico modeling approach to understanding the dynamics of the post-burn immune response
Authors: Korkmaz H. Ibrahim , Sheraton Vivek M. , Bumbuc Roland V. , Li Meifang , Pijpe Anouk , Mulder Patrick P. G. , Boekema Bouke K. H. L. , de Jong Evelien , Papendorp Stephan G. F. , Brands Ruud , Middelkoop Esther , Sloot Peter M. A. , van Zuijlen Paul P. M. 
Published: January 2024

IntroductionBurns are characterized by a massive and prolonged acute inflammation, which persists for up to months after the initial trauma. Due to the complexity of the inflammatory process, Predicting the dynamics of wound healing process can be challenging for burn injuries. The aim of this study was to develop simulation models for the post-burn immune response based on (pre)clinical data.MethodsThe simulation domain was separated into blood and tissue compartments. Each of these compartments contained solutes and cell agents. Solutes comprise pro-inflammatory cytokines, anti-inflammatory cytokines and inflammation triggering factors. The solutes diffuse around the domain based on their concentration profiles. The cells include mast cells, neutrophils, and macrophages, and were modeled as independent agents. The cells are motile and exhibit chemotaxis based on concentrations gradients of the solutes. In addition, the cells secrete various solutes that in turn alter the dynamics and responses of the burn wound system.ResultsWe developed an Glazier-Graner-Hogeweg method-based model (GGH) to capture the complexities associated with the dynamics of inflammation after burn injuries, including changes in cell counts and cytokine levels. Through simulations from day 0 – 4 post-burn, we successfully identified key factors influencing the acute inflammatory response, i.e., the initial number of endothelial cells, the chemotaxis threshold, and the level of chemoattractants.ConclusionOur findings highlight the pivotal role of the initial endothelial cell count as a key parameter for intensity of inflammation and progression of acute inflammation, 0 – 4 days post-burn.
Roles of tumor necrosis factor-like ligand 1A in γδT-cell activation and psoriasis pathogenesis
Authors: Wang Shangyi , Kozai Mina , Hiraishi Masaya , Rubel Md. Zahir Uddin , Ichii Osamu , Inaba Mutsumi , Matsuo Kazuhiro , Takada Kensuke 
Published: January 2024

BackgroundInterleukin (IL)-17-producing γδT (γδT17) cells mediate inflammatory responses in barrier tissues. Dysregulated γδT17 cell activation can lead to the overproduction of IL-17 and IL-22 and the development of inflammatory diseases, including psoriasis. IL-23 and IL-1β are known to synergistically activate γδT17 cells, but the regulatory mechanisms of γδT17 cells have not been fully elucidated. This study aimed to reveal the contribution of the inflammatory cytokine tumor necrosis factor-like ligand 1A (TL1A) to γδT17 cell activation and psoriasis development.MethodsAnti-TL1A antibody was injected into an imiquimod (IMQ)-induced murine psoriasis model. TL1A receptor expression was analyzed in splenic and dermal γδT cells. γδT cells were tested for cytokine production in vitro and in vivo under stimulation with IL-23, IL-1β, and TL1A. TL1A was applied to a psoriasis model induced by intradermal IL-23 injection. Mice deficient in γδT cells were intradermally injected with IL-23 plus TL1A to verify the contribution of TL1A-dependent γδT-cell activation to psoriasis development.ResultsNeutralization of TL1A attenuated γδT17 cell activation in IMQ-treated skin. TL1A induced cytokine production by splenic γδT17 cells in synergy with IL-23. Dermal γδT17 cells constitutively expressed a TL1A receptor at high levels and vigorously produced IL-22 upon intradermal IL-23 and TL1A injection but not IL-23 alone. TL1A exacerbated the dermal symptoms induced by IL-23 injection in wild-type but not in γδT cell–deficient mice.ConclusionThese findings suggest a novel regulatory mechanism of γδT cells through TL1A and its involvement in psoriasis pathogenesis as a possible therapeutic target.
The expanding clinical spectrum of autoinflammatory diseases with NOD2 variants: a case series and literature review
Authors: Karamanakos Anastasios , Vougiouka Olga , Sapountzi Evdoxia , Venetsanopoulou Aliki I. , Tektonidou Maria G. , Germenis Anastasios E. , Sfikakis Petros P. , Laskari Katerina 
Published: January 2024

ObjectiveTo assess the impact conferred by NOD2 variants on the clinical spectrum of patients with systemic autoinflammatory diseases (SAIDs) in Greece.MethodsConsecutive patients (n=167) with confirmed SAIDs who underwent screening by next generation sequencing (NGS) targeting 26 SAID-associated genes, and carried at least one NOD2 gene variant, were retrospectively studied. The demographic, clinical and laboratory parameters were recorded.ResultsIn total, 24 rare NOD2 variants in 23/167 patients (14%) were detected. Notably, 18 patients had at least one co-existing variant in 13 genes other than NOD2. Nine patients had juvenile- and 14 adult-onset disease. All patients presented with symptoms potentially induced by the NOD2 variants. In particular, the candidate clinical diagnosis was Yao syndrome (YAOS) in 12 patients (7% of the whole SAID cohort). The clinical spectrum of patients with YAOS (mean episode duration 8 days) was fever (n=12/12), articular symptoms (n=8), gastrointestinal symptoms (n=7; abdominal pain/bloating in 7; diarrhea in 4; oral ulcers in 3), serositis (n=7), and rash (n=5), while the inflammatory markers were elevated in all but one patient. Most of these patients showed a poor response to nonsteroidal anti-inflammatory drugs (n=7/9), colchicine (n=6/8) and/or anti-TNF treatment (n=3/4), while a complete response was observed in 6/10 patients receiving steroids and 3/5 on anti-IL1 treatment. Another 8 patients were diagnosed with either FMF (n=6) or PFAPA syndrome (n=2) presenting with prominent diarrhea (n=7), oral ulcers (n=2), periorbital swelling and sicca-like symptoms (n=1), or maculopapular rash (n=1). One patient had a clinically undefined SAID, albeit characterized by oral ulcers and diarrhea. Finally, one patient presented with chronic relapsing urticaria with periorbital edema and inflammatory markers, and another one had a Crohn-like syndrome with good response to anti-IL-1 but refractory to anti-TNF treatment.ConclusionNOD2 variants were detected in 1 out of 7 SAID patients and seem to have an impact on disease phenotype and treatment response. Further studies should validate combined molecular and clinical data to better understand these distinct nosological entities.
Correlation between mismatch repair statuses and the prognosis of stage I–IV colorectal cancer
Authors: Tong Guojun , Zhang Guiyang , Hu Yan , Xu Xuting , Wang Yanyan 
Published: January 2024

BackgroundThe role of microsatellite instability (MSI) and prognosis for stage II–III colorectal cancer (CRC) has been described, but the role of MSI in stage I and IV CRC is controversial.MethodsA total of 2,540 CRC patients were collected from Huzhou Central Hospital, China, from January 2006 to 2016, and 783 cases were excluded. This retrospective study illustrates the correlation between MMR status and prognosis for 1,757 CRC patients as well as the correlation between MSI and prognosis for CRC patients. Two groups were classified as MSI-H and MSI-L&amp;MSS. If the expression of one or more mismatch repair (MMR) proteins was negative, it was considered as microsatellite instability high expression (MSI-H), whereas positive expression was considered as microsatellite instability low expression and microsatellite stability (MSI-L&amp;MSS), as assessed by correlation analyses. Overall and disease-free survival were analyzed using the Kaplan–Meier method. Univariable and multivariable analyses were conducted using Cox regression.ResultsPreoperative serum S-CEA, positive lymph, tumor size, pathologic tumor (Pt) status, node (N) stage, differentiation, chemotherapy, and the 8th Edition of the American Joint Committee on Cancer (AJCC-8) were significantly correlated with MSI (P=0.028, 0.037, 0.019, 0.007, 0.002, &lt;0.001, &lt;0.001, and &lt;0.001, respectively), whereas tumor location was not associated with MSI. Univariable and multivariable analyses showed that MSI was an independent factor for CRC. The 5-year overall survival (OS) and 5-year disease-free survival (DFS, P&lt;0.001) rates differed significantly between the two groups in stages II, III, and IV, whereas stage I did not show a significant difference (P&gt;0.05).ConclusionMSI-H was associated with a good prognosis for stages II to IV, whereas stage I did not show any significant correlation. Moreover, MSI expression was an independent prognostic factor.
Case report and literature analysis: solitary HCC- recurrence in the right maxillary sinus after curative resection
Authors: Madzikatire Tinotenda Blessing , Shan Yunfeng 
Published: January 2024

BackgroundThe primary treatment for eligible patients with hepatocellular carcinoma (HCC) is curative liver resection, offering a 5-year overall survival (OS) of 60%-80%. Despite this, the recurrence rate within five years post-resection remains notably high, ranging from 40% to 50%. Instances of recurrence in the maxillary sinus following liver resection are exceedingly uncommon. This report details a unique case of solitary maxillary sinus recurrence after the curative resection of HCC, which underwent maxillary tumor resection, along with a comprehensive review of pertinent literature. No similar cases have been documented previously.Case presentationIn 2014, an 85-year-old male patient was diagnosed with HCC and subsequently underwent left hepatectomy. Following the resection, the patient underwent a 9-year follow-up period without any evidence of intra or extrahepatic recurrence. In 2023, a computed tomography (CT) scan revealed a 1.4 cm by 1.1 cm mass in the maxillary sinus, without discernible invasion of the alveolar sinus, nasal cavity, orbital cavity, or infratemporal space. We proceeded with the resection of the maxillary sinus mass. Patho-histochemical analysis indicated that the tumor cells in the maxillary sinus were metastatic HCC cells. As of now, the patient remains in good condition with no signs of tumor recurrence.ConclusionFor patients presenting with solitary maxillary sinus metastasis, optimal liver function, and a favorable performance score, tumor resection may be the preferred treatment option. However, given the rarity of such cases, larger prospective trials are essential to determine an optimal treatment strategy that offers therapeutic benefits.
Primary vaginal cancer after hysterectomy for benign conditions: a systematic review of the literature
Authors: Qian Jing , Gracious Kaoma , Chen Li , Xu Song 
Published: January 2024

BackgroundPrimary vaginal cancer is a rare condition. Some studies have revealed an increased risk of vaginal cancer among patients who have undergone hysterectomy for premalignant and malignant cervical disease. However, there is limited literature available on primary vaginal cancer following hysterectomy for benign conditions.ObjectivesThis review aimed to investigate available evidence on clinical characteristics, treatments, and outcomes of primary vaginal cancer following hysterectomy for benign diseases. Additionally, we provide a case of a patient who developed primary vaginal cancer 10 years after undergoing hysterectomy for abnormal uterine bleeding.Search strategyWe conducted a comprehensive literature search on PubMed, Scopus, Web of Science using a combination of title and abstract represented by “hysterectomy”, and “vaginal cancer”; “vaginal neoplasm”; and “cancer of vagina”. No article type restrictions were applied.Main resultsEight studies with a total of 56 cases were included in this review. The main symptom observed was vaginal bleeding. Squamous cancer was found to be the most common type, followed by adenocarcinoma. The majority of vaginal cancer cases occurred approximately 10 years after undergoing hysterectomy. The most common location of the tumor was in the vaginal apex. The management approaches varied and details were available in 25 cases. Among these, 7 cases were treated with radiotherapy alone, 1 case received concurrent chemoradiation therapy, and the of rest of the cases underwent surgery as the primary treatment, with or without additional adjuvant therapy. Data of follow-up was available for 15 cases, with 2 cases resulting in death and 2 cases experiencing recurrence. The other cases were alive and well at the time of considered follow up.ConclusionPrimary vaginal cancer after hysterectomy for benign conditions is an extremely rare condition. It is essential to have high-level evidence to guide the screening and treatment strategy for this rare condition. A part of women who have undergone hysterectomy for benign disorders can benefit from vaginal cytology evaluation. It is reasonable to postpone the initial screening after surgery and to extend the interval between subsequent screenings. Further retrospective case-control trials are expected to determine which specific subgroups of patients mentioned above might most potentially benefit from screening. The treatment decision for vaginal cancer after hysterectomy is more favorable to radiotherapy-based management rather than surgery. Vaginal endometrioid adenocarcinoma may arise from the malignant transformation of endometriosis. More studies are expected to investigate the correlation between these two diseases.