bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deteksi Dini Diabetes Mellitus Tipe 2 Terhadap Kegawatdaruratan Hiperglikemia Dan Hipoglikemia Melalui Screening GDS
Authors: Rahmawati Rahmawati , Hasanuddin Fitria , Purqan Nur Muhammad , Samudra Hijriah. S , Maiyo Nurlinda Maiyo 
Published: November 2024

tar Belakang: IDF melaporkan prevalensi diabetes secara global sebanyak 537 juta pada tahun 2021, diperkirakan akan meningkat menjadi 643 juta pada tahun 2030 dan 783 juta pada tahun 2045. Angka kematian di atas 6,7 juta pada tahun 2021, 1 kematian setiap 5 detik. Indonesia menempati urutan kelima dengan 19,5 juta pada tahun 2021. Lebih dari 90% menderita T2D akibat faktor sosial ekonomi, demografi, lingkungan, dan genetik. Kegawatdaruratan hipoglikemia dan hiperglikemia dapat menyebabkan Ketoasidosis Diabetikum dan Status Hiperosmolar Hiperglikemi yang mengancam jiwa, sehingga perlu deteksi dini melalui screening GDS. Tujuan: Mengetahui adanya kegawatdaruratan hiperglikemia dan Hipoglikemia melalui Screening GDS. Metode: Penelitian menggunakan desain analisis deksriptif dengan pendekatan cross sectional study. Pengumpulan data dilakukan secara survey observasional retrospektif pada 343 sampel. Hasil: Berdasarkan screening GDS menunjukkan hipoglikemia ringan 3,8%, sedang (0,6%) dan hiperglikemia ringan (23,9%), sedang 34,7%) dan berat (24,4%). Analisis korelasi Pearson menunjukkan terdapat korelasi positif yang signifikan antara nilai GDS dan kegawatdaruratan hiperglikemia (r=0,308, p=0,000). Namun, tidak terdapat korelasi antara GDS dan kegawatdaruratan hipoglikemia (r=0,022, p=0,682).Kesimpulan: Screening GDS dapat digunakan untuk deteksi dini kegawatdaruratan hiperglikemia dan hipoglikemia, dimana penderita telah teridentifikasi mengalami gejala kegawatdaruratan hiperglikemia dan hipoglikemia.
Comparison of uremic toxin removal between expanded hemodialysis and high volume online hemodiafiltrations in different modes
Authors: Biedunkiewicz Jan , Zakrzewska Agnieszka , Małgorzewicz Sylwia , Komorniczak Michał , Jasiulewicz Katarzyna , Płonka Natalia , Tarasewicz Agnieszka , Jankowska Magdalena , Biedunkiewicz Bogdan , Dębska‐Ślizień Alicja , Tylicki Leszek 
Published: November 2024

Various high-efficiency hemodialysis techniques exist, including different online high- volume hemodiafiltration (HDF) modes and expanded hemodialysis (HDx) utilizing dialyzers with medium cut-off (MCO) membranes. This study aimed to evaluate the efficacy of uremic toxin removal among four modalities: (I) HDx, (II) pre-dilution HDF (PRE-HDF), (III) mixed-dilution HDF (MIX-HDF), and (IV) post-dilution HDF (POST-HDF), each applied for 1 week in a randomized order. This research was a single-center, prospective, open-label, exploratory crossover study. The reduction ratio (RR) for small molecular toxins (urea and phosphate), a middle molecular toxin (beta-2-microglobulin, β2M), a large-middle molecular toxin (Chitinase-3-like protein 1, YKL-40), and a protein- bound uremic toxin (indoxyl sulfate, IS) was evaluated during a single mid-week dialysis session. Twelve patients were included, with an average age of 52.5 ± 15.47 years and an average dialysis duration of 42.05 ± 31.04 months. The dialysis parameters, including; post-dialysis weight, session duration, dialysate composition, blood and dialysate flow; rates, dialysate temperature, and anticoagulation dosage, were maintained consistently across all modalities. No significant differences in RR for urea, phosphate, β2M, YKL-40, and IS were observed between the treatments. Although the highest IS clearance, though not statistically significant, was observed with POST-HDF and HDx, the differences were not substantial enough to favor any particular modality as the most effective.
Serum exocrine pancreas enzymes are biomarkers of immunotherapy response in new-onset type 1 diabetes
Authors: Bruggeman Brittany Sorensen , Gornisiewicz Savanna , Bacher Rhonda , McGrail Kieran , Campbell-Thompson Martha , Wasserfall Clive , Jacobsen Laura M. , Atkinson Mark , Haller Michael J. , Schatz Desmond A. 
Published: November 2024

IntroductionThe immune-mediated destruction of insulin-producing β-cells characterizes type 1 diabetes. Nevertheless, exocrine pancreatic enzymes, including amylase, lipase, and trypsin, are also significantly reduced in type 1 diabetes. With an immunotherapy now approved to treat early-stage type 1 diabetes, biomarkers to delineate response to treatment are needed. No study has yet evaluated whether serum exocrine pancreatic enzymes could delineate immunotherapy responders and non-responders.MethodsIn this novel study, we sought to identify longitudinal trends in the most commonly measured circulating exocrine enzymes before and after treatment with anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) in individuals with new-onset type 1 diabetes (n=34). We defined response to immunotherapy as participants with at least 60% of baseline area under the curve (AUC) C-peptide levels after a 2-hour mixed meal tolerance test (MMTT) at two years post-treatment. In the overall study (n=89), 42% of treated and 17% of placebo participants met this definition. Due to constraints of sample availability, we compared longitudinal serum amylase, lipase, and trypsin levels in a subset of responders to therapy (n=4-6), placebo “responders” (n=2), treated non-responders (n=16), and placebo non-responders (n=10).ResultsThere were no differences in amylase levels between groups at baseline or six months post-treatment. Baseline levels of lipase and trypsin tended to be lower in responders; however, these variations were not significant in this small study sample. Lipase and trypsin improved to 115% of baseline in responders to immunotherapy six months after treatment and declined to 80-90% of baseline in non-responders and placebo participants (p=0.03). This difference was not present before the six-month time point.DiscussionOur findings provide preliminary evidence that the exocrine pancreatic enzymes lipase and trypsin may be useful biomarkers of response to immunotherapy in type 1 diabetes. Further studies with larger numbers of participants are warranted.
Detection of gene variants associated with recessive limb–girdle muscular weakness and Pompe disease in a global cohort of patients through the application of next-generation sequencing analysis
Authors: Bevilacqua Jorge Alfredo , Al-Salti Abdullah Mohammed , Al Madani Abubaker , Alves da Fonseca Armando , Durmus Hacer , Chai Josiah , Alshehri Ali , Ribeiro Márcia Gonçalves , Sgobbi Paulo , Nikitin Sergey S. , Vargas Steven , Furtado Adriana , Thibault Nathan , Araujo Roberto , Daba Nadia 
Published: November 2024

IntroductionHereditary myopathies arise due to numerous pathogenic variants occurring in distinct genes, which amount to several hundred. Limb–girdle muscular dystrophies (LGMDs) constitute a heterogeneous group of neuromuscular disorders involving more than 30 genes. Clinically, LGMD is characterized by limb–girdle muscular weakness (LGMW). Late-onset Pompe disease is an important disorder with a differential diagnosis for LGMD, where next-generation sequencing (NGS) plays a crucial role in accurate and prompt diagnosis. The sensitivity and specificity of a 10-gene NGS panel have been previously evaluated for the prevalent forms of recessive LGMD (LGMD-R) and Pompe disease in Latin American patients with LGMW of unknown cause. This project aims to identify the regional relative prevalence of frequent LGMD-R subtypes and Pompe disease in a larger geographic area and to diagnose patients with LGMW by identifying genetic variants of LGMD-R and Pompe disease.Methods and ResultsThis 21-country multicentric analysis enrolled 2,372 patients with LGMW from 2017 to 2018. Sequencing analysis was performed using the Illumina NextSeq 500 system, and variant interpretation was performed according to the American College of Medical Genetics and Genomics guidelines. Pathogenic or likely pathogenic variants were seen in 11% of patients (n = 261). Among the positive cases, NGS effectively diagnosed 86.2% and 13.8% of patients with LGMD and Pompe disease, respectively. The most prevalent pathogenic acid α-glucosidase (GAA) variant identified was c.-32-13T &gt; G.ConclusionThe study adds to the knowledge of the relative occurrence of various subtypes of LGMD worldwide. The inclusion of GAA in the NGS panel to investigate patients with LGMW is a powerful diagnostic approach to screen for late-onset Pompe disease.
Exome sequencing in 90 children with developmental delay: a single-center experience
Authors: Boyarchuk Oksana , Volianska Liubov , Smashna Olena , Makukh Halyna 
Published: November 2024

IntroductionDevelopmental delay (DD) in children is often caused by genetic abnormalities, which are challenging to diagnose due to the vast genetic variability.MethodsThis study presents a detailed analysis of whole-exome sequencing (WES) on 90 children with DD at a single clinical center.ResultsWe identified pathogenic or likely pathogenic variants in 27.8% of cases, with 7.8% revealing variants of uncertain significance (VUS). Among the positive findings, 21 (84.0%) corresponded to the main clinical manifestations in patients, and 4 (16.0%) secondary findings provided new insights into the patient’s conditions. Positive and inconclusive cases led to a revision of the diagnosis or management plan in 34.4% of cases. The positive genetic result in children with Developmental delay was higher in the presence of epilepsy or seizures (odds ratio – 5.4444; 95% CI 2.0176 to 14.6918; p = 0.0008) and more than 3 dysmorphic features (odds ratio – 7.1739; 95% CI 1.7791 to 28.9282; p = 0.0056). Variants compatible with the clinical manifestations were identified in 11.9% of children with autistic spectrum disorders.ConclusionOur findings emphasize the utility of WES in clinical diagnostics, offering significant insights into patient management and potentially guiding therapeutic decisions.
Effective inhibition of dengue virus replication using 3′UTR-targeted Vivo-Morpholinos
Authors: Niu Mengwei , Yi Wenyanbo , Dong Zhuofan , Li Xiaofeng , Dong Xue , Yu Lifang , Han Yao , Zhang Oujia , Sheng Ziyang , An Jing , Li Hao , Sun Yansong 
Published: November 2024

IntroductionDue to the impact of antibody-dependent enhancement and viral variation, effective vaccines or antiviral therapies remain lacking for the dengue virus (DENV). Nucleic acid drugs, particularly Vivo-Morpholinos (MOs), have emerged as a promising avenue for antiviral treatment due to their programmability and precise targeting, as well as their safety and stability.MethodIn this study, we designed and developed 10 morpho-modified (octa-guanidine dendrimer) vivo-MO molecules that target each coding gene of DENV. Subsequently, we assessed the inhibitory impact of vivo-MOs on dengue viral RNA load utilizing qRT-PCR. Furthermore, we examined the inhibitory effect on the live virus through a plaque assay and the TCID50 assay.ResultsWe found that the vivo-3′UTR molecule targeting the 3′ untranslated region of the dengue virus exhibited the highest inhibitory rate against viral load. The vivo-3′UTR demonstrated 99% inhibition of dengue virus RNA and the inhibition of up to 98% of the live virus. Additionally, the targeted sequence was conserved among all four DENV serotypes, and treatment with 10 μM of vivo-3′UTR resulted in a reduction of viral titers for all four DENV serotypes by over 99.99%. Additionally, we revealed that pre-treatment with vivo-3′UTR had a notable preventive effect against viral infection.ConclusionThis study screened an effective vivo-MO target drug for the treatment of dengue virus infection, demonstrating low toxicity in mammalian cell lines, and proposed a novel preventive antiviral approach.
Beach erosion and typhoons reduce green turtle nesting grounds on the Xisha Islands, South China Sea
Authors: Zhang Ting , Zhang Chenglong , Li Yupei , Yu Yangfei , An Xiaoyu , Jiang Yongkang , Wang Jichao , Lin Liu , Shi Hai-Tao 
Published: November 2024

IntroductionSea turtles are ideal flagship and umbrella species for marine biodiversity conservation. The quality of nesting grounds is crucial for the successful reproduction of sea turtles, as it determines whether they can successfully nest and hatch. The Xisha Islands represent the largest remaining nesting grounds for green turtles in China. However, they face numerous threats and lack management guidelines for nesting ground restoration.MethodsIn this study, we continuously monitored the beach changes and coastal erosion on North Island, which is located in the northern region of the Xisha Islands, from 2019 to 2022.ResultsFrom 2020 to 2022, the beach area on North Island decreased annually by 11,800 m2, accounting for 24.39% of the beach area in 2020. The proportion of suitable nesting sand types (including coarse and medium sands) also decreased annually, with a reduction of 40–70% on the southern beach of North Island. The peak nesting period of green turtles on North Island coincides with the frequent occurrence of typhoons in the South China Sea, causing tidal surges that inundate green turtle nests, resulting in an average nest loss rate of 35.25%.DiscussionBased on the above threats, it is recommended to promptly initiate habitat restoration in severely eroded areas of green turtle nesting grounds to prevent further declines in nesting area and quality. Additionally, measures such as nest relocation should be implemented to enhance green turtle reproductive success.
The triglyceride-glucose index and risk of cognitive impairment: a systematic review and meta-analysis with inclusion of two national databases
Authors: Yang Ying , Peng Pai , Huang Huadong , Zhao Yanan , Li Yating , Xu Xiao , Jiang Shixie , Yang Yanrong , Pan Gaofeng , Wen Yanting , Wu Dan , Chen Shanping , Feng Lei , Peng Tangming , Wang Jiang , Li Zheng 
Published: November 2024

BackgroundTo investigate the relationship between the triglyceride and glucose (TyG) index and cognitive impairment (CI).MethodsFive authoritative databases were systematically searched for potentially relevant studies on ‘TyG index’ and ‘CI’ from inception to 27 April 2024. Two representative databases from the United Kingdom and United States were also included. We used the PICOS criteria to select available articles. All data was combined to compute Odd Ratios (ORs).Results15 studies were included in the meta-analysis (participants: 5604303). The pooled effect sizes demonstrate that individuals with a high TyG index exhibit a significantly elevated risk of CI compared to those with a low TyG index (OR = 2.16, 95%CI: 1.51; 3.08, p &lt; 0.001). The subgroup analysis showed that inpatients with a high TyG index exhibited an increased risk of CI (OR = 4.56, 95%CI: 3.09; 6.74, p &lt; 0.001). Furthermore, the risk of developing distinct types of CI differed significantly [CI: OR = 1.64, 95% CI: 1.29; 2.07, p &lt; 0.001; Vascular Cognitive Impairment (VCI): OR = 5.39, 95% CI: 3.33; 8.70, p &lt; 0.001].ConclusionA positive correlation exists between the TyG index and risk of CI, which has potential value in optimizing CI risk stratification among elderly people, especially those hospitalized.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023450336.
Medical history of thyroid cancer does not impair prognosis in non-metastatic breast cancer patients: an analysis study based on SEER database and external cohort
Authors: Li Shuai , Chen Xiaosong , Shen Kunwei 
Published: November 2024

BackgroundNon-metastatic breast cancer patients who had a medical history of skin or cervix cancers were presently eligible for clinical trials while few data were available regarding thyroid gland cancer. The study estimated the rate of prior thyroid gland cancer and evaluated its impact on survivals among breast cancer patients.MethodsNon-metastatic invasive breast cancer patients from the SEER database (SEER cohort) between 2010 and 2019 and Ruijin Hospital (Ruijin cohort) during 2009 and 2019 were retrospectively analyzed. Ascian or Pacific Island patients in the SEER cohort (SEER API cohort) were analyzed separately. Chi-square test and multivariate logistic regression analysis were performed to describe the clinical features. Kaplan-Meier analysis and Cox proportional hazards model were used to compare the overall survival (OS) and breast cancer specific survival (BCSS).ResultsA total of 136,441 patients from the SEER cohort, 17,183 from the SEER API cohort, and 8,079 from the Ruijin cohort were enrolled, of whom 0.68%, 0.81%, and 1.06% had a medical history of thyroid gland cancer, respectively. Patients with prior thyroid gland cancers were significantly older (51-60 years: OR 1.84, 95% CI 1.46-2.30, P &lt; 0.001; 61-70 years: OR 2.00, 95% CI 1.61-2.50, P &lt; 0.001; &gt; 70 years: OR 1.51, 95% CI 1.18-1.92, P = 0.001) and more likely to be API (OR 1.23, 95% CI 1.03-1.48, P = 0.026) versus other races. Multivariate analysis demonstrated that patients with a history of thyroid gland cancer had comparable OS (SEER: HR 0.87, 95% CI 0.68-1.11, P = 0.257; SEER API: HR 0.53, 95% CI 0.22-1.28, P = 0.159; Ruijin: HR 1.07, 95% CI 0.26-4.29, P = 0.811) and BCSS (SEER: HR 0.72, 95% CI 0.49-1.08, P = 0.117; SEER API: HR ∞, 95% CI ∞-∞, P = 0.878; Ruijin: HR 0.70, 95% CI 0.10-4.98, P = 0.750) versus those without primary malignancies in the three cohorts.ConclusionThere were of a sizable of non-metastatic breast cancer patients with medical history of thyroid gland cancer, which was related with different races. Prior thyroid gland cancer had no adverse impact on clinical outcomes, indicating possible eligible in further clinical trials.
Development and validation of an individualized nomogram for predicting distant metastases in gastric cancer using a CT radiomics-clinical model
Authors: Xue Hui-Bin , Liang Mei-Li , Xu Huang-Zhen , Wang Chen-Yu , Xu Tian-Wen , Zhao Ai-Yue 
Published: November 2024

PurposeThis study aimed to develop and validate a model for accurately assessing the risk of distant metastases in patients with gastric cancer (GC).MethodsA total of 301 patients (training cohort, n = 210; testing cohort, n = 91) with GC were retrospectively collected. Relevant clinical predictors were determined through the application of univariate and multivariate logistic regression analyses. Then the clinical model was established. Venous phase computed tomography (VPCT) images were utilized to extract radiomic features, and relevant features were selected using univariate analysis, Spearman correlation coefficient, and the least absolute shrinkage and selection operator (Lasso) regression. Subsequently, radiomics scores were calculated based on the selected features. Radiomics models were constructed using five machine learning algorithms according to the screened features. Furthermore, separate joint models incorporating radiomic features and clinically independent predictors were established using traditional logistic regression algorithms and machine learning algorithms, respectively. All models were comprehensively assessed through discrimination, calibration, reclassification, and clinical benefit analysis.ResultsThe multivariate logistic regression analysis revealed that age, histological grade, and N stage were independent predictors of distant metastases. The radiomics score was derived from 15 selected features out of a total of 944 radiomic features. The predictive performance of the joint model 1 [AUC (95% CI) 0.880 (0.811-0.949)] constructed using logistic regression is superior to that of the joint model 2 [AUC (95% CI) 0.834 (0.736-0.931)] constructed using SVM algorithm. The joint model 1 [AUC(95% CI) 0.880(0.811-0.949)], demonstrated superior performance compared to the clinical model [AUC(95% CI) 0.781(0.689-0.873)] and radiomics model [AUC(95% CI) 0.740(0.626-0.855), using LR algorithm]. The NRI and IDI values for the joint model 1 and clinical model were 0.115 (95% CI 0.014 -0.216) and 0.132 (95% CI 0.093-0.171), respectively; whereas for the joint model 1 and LR model, they were found to be 0.130 (95% CI 0.018-0.243) and 0.116 (95% CI 0.072-0.160), respectively. Decision curve analysis indicated that the joint model 1 exhibited a higher clinical net benefit than other models.ConclusionsThe nomogram of the joint model, integrating radiomic features and clinically independent predictors, exhibits robust predictive capability for early identification of high-risk patients with a propensity for distant metastases of GC.
Pharmacokinetics, pharmacodynamics and bioavailability of dexmedetomidine nasal spray in healthy Chinese adults: A phase I clinical trial
Authors: Li Yan , Qi Lu , Wang Zhenyu , Wang Wan , Zhang Langxi , Yang Leting , Liu Chen , Zhong Wenjing , Wang Xinghe 
Published: November 2024

BackgroundIntranasal administration is a convenient route for drug delivery that can be applied for procedural sedation. However, there is currently limited exploration into fixed dosing regimens. This study was to investigate the pharmacokinetics (PK), pharmacodynamics (PD), bioavailability (BA) and safety of dexmedetomidine after fixed doses of intranasal and intravenous administration in healthy male and female subjects.MethodsGroup A subjects received intranasal or intravenous administration in two periods (12 subjects received intranasal dexmedetomidine (Dex) or the intravenous formulation, and four received the corresponding placebo). Groups B to F underwent single-period dose ascending, receiving only the intranasal Dex formulation or the corresponding placebo (the number of subjects receiving the drug/placebo in groups B to F were 12/2, 12/2, 12/2, 10/2, 10/2, respectively), with doses of 75 μg, 125 μg, 150 μg, 175 μg, and 200 μg, respectively. After administration of each group, blood samples were collected to investigate the plasma concentration of dexmedetomidine, adrenaline and noradrenaline using a HPLC-MS/MS method. Ramsay score, blood pressure and heart rate were collected for safety evaluation. Pharmacokinetic parameters (Cmax, Tmax, AUC0-24h, AUC0–∞, and t1/2) of dexmedetomidine were calculated.ResultsA total of 82 subjects were randomized. One subject withdrew for personal reasons before administration and the other subjects completed the entire study process. At a dose of 25 μg, the absolute bioavailability was 59%. Across the dose range of 25 to 200 μg, the median Tmax was similar (0.5–1 h), and the mean elimination half-life was comparable (3.09–4.28 h), with exposure (Cmax and AUC0-t) increasing with dose. The pharmacokinetics after intranasal spray administration exhibited linear characteristics, although Cmax was similar in the higher dose groups (175 μg and 200 μg). PD results showed that ideal sedation effects (Ramsay score of 3 or higher in at least 90% of subjects) could be achieved within 30 min following intranasal administration of 75 μg or higher doses. All the subjects were well tolerated without any serious adverse events (SAEs).ConclusionDexmedetomidine nasal spray was well tolerated and achieved satisfactory sedation in the dose range of 25–200 μg in Chinese healthy male and female subjects.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/, identifier CTR20201650