bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomechanical properties of different anterior and posterior techniques for atlantoaxial fixation: a finite element analysis
Authors: Li Jie , Cao Shuai , Guo Dong , Lu Teng , Zang Quanjin 
Published: June 2023

AbstractBackgroundMany techniques for atlantoaxial fixation have been developed. However, the biomechanical differences among various atlantoaxial fixation methods remain unclear. This study aimed to evaluate the biomechanical influence of anterior and posterior atlantoaxial fixation techniques on fixed and nonfixed segments.MethodsAn occiput-C7 cervical finite element model was used to construct 6 surgical models including a Harms plate, a transoral atlantoaxial reduction plate (TARP), an anterior transarticular screw (ATS), a Magerl screw, a posterior screw-plate, and a screw-rod system. Range of motion (ROM), facet joint force (FJF), disc stress, screw stress, and bone-screw interface stress were calculated.ResultsThe C1/2 ROMs were relatively small in the ATS and Magerl screw models under all loading directions except for extension (0.1°–1.0°). The posterior screw-plate system and screw-rod system generated greater stresses on the screws (77.6–1018.1 MPa) and bone-screw interfaces (58.3–499.0 MPa). The Harms plate and TARP models had relatively small ROMs (3.2°–17.6°), disc stress (1.3–7.6 MPa), and FJF (3.3–106.8 N) at the nonfixed segments. Changes in disc stress and FJF of the cervical segments were not consistent with changes in ROM.ConclusionsATS and Magerl screws may provide good atlantoaxial stability. The posterior screw-rod system and screw-plate system may have higher risks of screw loosening and breakage. The Harms plate and TARP model may more effectively relieve nonfixed segment degeneration than other techniques. The C0/1 or C2/3 segment may not be more susceptible to degeneration than other nonfixed segments after C1/2 fixation.
Ultrasound guided versus blinded injection in trigger finger treatment: a prospective controlled study
Authors: Tunçez Mahmut , Turan Kaya , Aydın Özgür Doğan , Çetin Tunçez Hülya 
Published: June 2023

Abstract
Background
Trigger finger is a common disease with a lifetime prevalence of 2%. One of the frequently preferred non-surgical treatments is blinded injection around the A1 pulley. This study aims to compare the clinical results of ultrasound-guided and blinded corticosteroid injection in the trigger finger.

Methods
In this prospective clinical study, 66 patients who had persistent symptoms of a single trigger finger were included. Patients with similar baseline characteristics such as age, gender, triggering period, and comorbidities were randomized. 34 patients had ultrasound-guided (UG), and 32 had blinded injections (BG). QDASH, VAS, time to return to work, and complications were compared between the groups.

Results
The mean age was 52,66 (29–73) years. There were 18 male and 48 female patients. In the UG, the triggering resolved faster, returning to work was earlier, and the medication period was shorter (p < 0.05). A total of 17 patients who had diabetes mellitus received re-injections, 11 of which were in BG and 6 in UG (p < 0.05). Although statistically significantly lower scores were obtained in UG at the 1st and 4th weeks in the QDASH and VAS scores (p < 0.05), at the 12th and 24 weeks, there was no significant difference (p > 0.05).

Conclusion
Using ultrasound guidance for corticosteroid injections is more effective for treating trigger fingers than the blinded method, leading to better results and a faster return to work in the early stages of treatment.
Real-world evidence in achondroplasia: considerations for a standardized data set
Authors: Alanay Yasemin , Mohnike Klaus , Nilsson Ola , Alves Inês , AlSayed Moeenaldeen , Appelman-Dijkstra Natasha M. , Baujat Genevieve , Ben-Omran Tawfeg , Breyer Sandra , Cormier-Daire Valerie , Gregersen Pernille Axél , Guillén-Navarro Encarna , Högler Wolfgang , Maghnie Mohamad , Mukherjee Swati , Cohen Shelda , Pimenta Jeanne , Selicorni Angelo , Semler J. Oliver , Sigaudy Sabine , Popkov Dmitry , Sabir Ian , Noval Susana , Sessa Marco , Irving Melita 
Published: June 2023

AbstractBackgroundCollection of real-world evidence (RWE) is important in achondroplasia. Development of a prospective, shared, international resource that follows the principles of findability, accessibility, interoperability, and reuse of digital assets, and that captures long-term, high-quality data, would improve understanding of the natural history of achondroplasia, quality of life, and related outcomes.MethodsThe Europe, Middle East, and Africa (EMEA) Achondroplasia Steering Committee comprises a multidisciplinary team of 17 clinical experts and 3 advocacy organization representatives. The committee undertook an exercise to identify essential data elements for a standardized prospective registry to study the natural history of achondroplasia and related outcomes.ResultsA range of RWE on achondroplasia is being collected at EMEA centres. Whereas commonalities exist, the data elements, methods used to collect and store them, and frequency of collection vary. The topics considered most important for collection were auxological measures, sleep studies, quality of life, and neurological manifestations. Data considered essential for a prospective registry were grouped into six categories: demographics; diagnosis and patient measurements; medical issues; investigations and surgical events; medications; and outcomes possibly associated with achondroplasia treatments.ConclusionsLong-term, high-quality data are needed for this rare, multifaceted condition. Establishing registries that collect predefined data elements across age spans will provide contemporaneous prospective and longitudinal information and will be useful to improve clinical decision-making and management. It should be feasible to collect a minimum dataset with the flexibility to include country-specific criteria and pool data across countries to examine clinical outcomes associated with achondroplasia and different therapeutic approaches.
The association of hypoglycemia with outcome of critically ill children in relation to nutritional and blood glucose control strategies
Authors: Gunst Jan , De Bruyn Astrid , Jacobs An , Langouche Lies , Derese Inge , Dulfer Karolijn , Güiza Fabian , Garcia Guerra Gonzalo , Wouters Pieter J. , Joosten Koen F. , Verbruggen Sascha C. , Vanhorebeek Ilse , Van den Berghe Greet 
Published: June 2023

Abstract
Background
Withholding parenteral nutrition (PN) until one week after PICU admission facilitated recovery from critical illness and protected against emotional and behavioral problems 4 years later. However, the intervention increased the risk of hypoglycemia, which may have counteracted part of the benefit. Previously, hypoglycemia occurring under tight glucose control in critically ill children receiving early PN did not associate with long-term harm. We investigated whether hypoglycemia in PICU differentially associates with outcome in the context of withholding early PN, and whether any potential association with outcome may depend on the applied glucose control protocol.

Methods
In this secondary analysis of the multicenter PEPaNIC RCT, we studied whether hypoglycemia in PICU associated with mortality (N = 1440) and 4-years neurodevelopmental outcome (N = 674) through univariable comparison and multivariable regression analyses adjusting for potential confounders. In patients with available blood samples (N = 556), multivariable models were additionally adjusted for baseline serum NSE and S100B concentrations as biomarkers of neuronal, respectively, astrocytic damage. To study whether an association of hypoglycemia with outcome may be affected by the nutritional strategy or center-specific glucose control protocol, we further adjusted the models for the interaction between hypoglycemia and the randomized nutritional strategy, respectively, treatment center. In sensitivity analyses, we studied whether any association with outcome was different in patients with iatrogenic or spontaneous/recurrent hypoglycemia.

Results
Hypoglycemia univariably associated with higher mortality in PICU, at 90 days and 4 years after randomization, but not when adjusted for risk factors. After 4 years, critically ill children with hypoglycemia scored significantly worse for certain parent/caregiver-reported executive functions (working memory, planning and organization, metacognition) than patients without hypoglycemia, also when adjusted for risk factors including baseline NSE and S100B. Further adjustment for the interaction of hypoglycemia with the randomized intervention or treatment center revealed a potential interaction, whereby tight glucose control and withholding early PN may be protective. Impaired executive functions were most pronounced in patients with spontaneous or recurrent hypoglycemia.

Conclusion
Critically ill children exposed to hypoglycemia in PICU were at higher risk of impaired executive functions after 4 years, especially in cases of spontaneous/recurrent hypoglycemia.
Detrimental effects of PCSK9 loss-of-function in the pediatric host response to sepsis are mediated through independent influence on Angiopoietin-1
Authors: Atreya Mihir R. , Cvijanovich Natalie Z. , Fitzgerald Julie C. , Weiss Scott L. , Bigham Michael T. , Jain Parag N. , Schwarz Adam J. , Lutfi Riad , Nowak Jeffrey , Allen Geoffrey L. , Thomas Neal J. , Grunwell Jocelyn R. , Baines Torrey , Quasney Michael , Haileselassie Bereketeab , Alder Matthew N. , Lahni Patrick , Ripberger Scarlett , Ekunwe Adesuwa , Campbell Kyle R. , Walley Keith R. , Standage Stephen W. 
Published: June 2023

Abstract
Background
Sepsis is associated with significant mortality. Yet, there are no efficacious therapies beyond antibiotics. PCSK9 loss-of-function (LOF) and inhibition, through enhanced low-density lipoprotein receptor (LDLR) mediated endotoxin clearance, holds promise as a potential therapeutic approach among adults. In contrast, we have previously demonstrated higher mortality in the juvenile host. Given the potential pleiotropic effects of PCSK9 on the endothelium, beyond canonical effects on serum lipoproteins, both of which may influence sepsis outcomes, we sought to test the influence of PCSK9 LOF genotype on endothelial dysfunction.

Methods
Secondary analyses of a prospective observational cohort of pediatric septic shock. Genetic variants of PCSK9 and LDLR genes, serum PCSK9, and lipoprotein concentrations were determined previously. Endothelial dysfunction markers were measured in day 1 serum. We conducted multivariable linear regression to test the influence of PCSK9 LOF genotype on endothelial markers, adjusted for age, complicated course, and low- and high-density lipoproteins (LDL and HDL). Causal mediation analyses to test impact of select endothelial markers on the association between PCSK9 LOF genotype and mortality. Juvenile Pcsk9 null and wildtype mice were subject to cecal slurry sepsis and endothelial markers were quantified.

Results
A total of 474 patients were included. PCSK9 LOF was associated with several markers of endothelial dysfunction, with strengthening of associations after exclusion of those homozygous for the rs688 LDLR variant that renders it insensitive to PCSK9. Serum PCSK9 was not correlated with endothelial dysfunction. PCSK9 LOF influenced concentrations of Angiopoietin-1 (Angpt-1) upon adjusting for potential confounders including lipoprotein concentrations, with false discovery adjusted p value of 0.042 and 0.013 for models that included LDL and HDL, respectively. Causal mediation analysis demonstrated that the effect of PCSK9 LOF on mortality was mediated by Angpt-1 (p = 0.0008). Murine data corroborated these results with lower Angpt-1 and higher soluble thrombomodulin among knockout mice with sepsis relative to the wildtype.

Conclusions
We present genetic and biomarker association data that suggest a potential direct role of the PCSK9-LDLR pathway on Angpt-1 in the developing host with septic shock and warrant external validation. Further, mechanistic studies on the role of PCSK9-LDLR pathway on vascular homeostasis may lead to the development of pediatric-specific sepsis therapies.

Graphical abstract
Transcriptionally regulated miR-26a-5p may act as BRCAness in Triple-Negative Breast Cancer
Authors: Zhang Yue , Lv Lianqiu , Zheng Renjing , Xie Rong , Yu Yuanhang , Liao Han , Chen Jianying , Zhang Bo 
Published: June 2023

AbstractBackgroundDNA damage and DNA damage repair (DDR) are important therapeutic targets for triple-negative breast cancer (TNBC), a subtype with limited chemotherapy efficiency and poor outcome. However, the role of microRNAs in the therapy is emerging. In this study, we explored whether miR-26a-5p could act as BRCAness and enhance chemotherapy sensitivity in TNBC.MethodsQuantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-26a-5p in breast cancer tissues and cell lines. CCK-8 was used to measure drug sensitivity in concentration gradient and time gradient. Comet assay was used to detect DNA damage. Flow cytometry was performed to examine apoptosis. Moreover, we used western blot and immunofluorescence to detect biomarkers. Luciferase reporter assay was performed to verify the combination of miR-26a-5p and 3’UTR of target gene. Hormone deprivation and stimulation assay were used to validate the effect of hormone receptors on the expression of miR-26a-5p. Chromatin immunoprecipitation (ChIP) assays were used to verify the binding sites of ER-a or PR with the promoter of miR-26a-5p. Animal experiments were performed to the effect of miR-26a-5p on Cisplatin treatment.ResultsThe expression of miR-26a-5p was significantly downregulated in TNBC. Overexpressing miR-26a-5p enhanced the Cisplatin-induced DNA damage and following apoptosis. Interestingly, miR-26a-5p promoted the expression of Fas without Cisplatin stimulating. It suggested that miR-26a-5p provided a hypersensitivity state of death receptor apoptosis and promoted the Cisplatin sensitivity of TNBC cells in vitro and in vivo. Besides, miR-26a-5p negatively regulated the expression of BARD1 and NABP1 and resulted in homologous recombination repair defect (HRD). Notably, overexpressing miR-26a-5p not only facilitated the Olaparib sensitivity of TNBC cells but also the combination of Cisplatin and Olaparib. Furthermore, hormone receptors functioned as transcription factors in the expression of miR-26a-5p, which explained the reasons that miR-26a-5p expressed lowest in TNBC.ConclusionsTaken together, we reveal the important role of miR-26a-5p in Cisplatin sensitivity and highlight its new mechanism in DNA damage and synthetic lethal.
Human papillomavirus integration transforms chromatin to drive oncogenesis
Authors: Karimzadeh Mehran , Arlidge Christopher , Rostami Ariana , Lupien Mathieu , Bratman Scott V. , Hoffman Michael M. 
Published: June 2023

AbstractBackgroundHuman papillomavirus (HPV) drives almost all cervical cancers and up to 70% of head and neck cancers. Frequent integration into the host genome occurs predominantly in tumorigenic types of HPV. We hypothesize that changes in chromatin state at the location of integration can result in changes in gene expression that contribute to the tumorigenicity of HPV.ResultsWe find that viral integration events often occur along with changes in chromatin state and expression of genes near the integration site. We investigate whether introduction of new transcription factor binding sites due to HPV integration could invoke these changes. Some regions within the HPV genome, particularly the position of a conserved CTCF binding site, show enriched chromatin accessibility signal. ChIP-seq reveals that the conserved CTCF binding site within the HPV genome binds CTCF in 4 HPV﻿+cancer cell lines. Significant changes in CTCF binding pattern and increases in chromatin accessibility occur exclusively within 100 kbp of HPV integration sites. The chromatin changes co-occur with out-sized changes in transcription and alternative splicing of local genes. Analysis of The Cancer Genome Atlas (TCGA) HPV+tumors indicates that HPV integration upregulates genes which have significantly higher essentiality scores compared to randomly selected upregulated genes from the same tumors.ConclusionsOur results suggest that introduction of a new CTCF binding site due to HPV integration reorganizes chromatin state and upregulates genes essential for tumor viability in some HPV+tumors. These findings emphasize a newly recognized role of HPV integration in oncogenesis.
DCATS: differential composition analysis for flexible single-cell experimental designs
Authors: Lin Xinyi , Chau Chuen , Ma Kun , Huang Yuanhua , Ho Joshua W. K. 
Published: June 2023

AbstractDifferential composition analysis — the identification of cell types that have statistically significant changes in abundance between multiple experimental conditions — is one of the most common tasks in single cell omic data analysis. However, it remains challenging to perform differential composition analysis in the presence of flexible experimental designs and uncertainty in cell type assignment. Here, we introduce a statistical model and an open source R package, DCATS, for differential composition analysis based on a beta-binomial regression framework that addresses these challenges. Our empirical evaluation shows that DCATS consistently maintains high sensitivity and specificity compared to state-of-the-art methods.
Transcriptome- and proteome-wide association studies nominate determinants of kidney function and damage
Authors: Schlosser Pascal , Zhang Jingning , Liu Hongbo , Surapaneni Aditya L. , Rhee Eugene P. , Arking Dan E. , Yu Bing , Boerwinkle Eric , Welling Paul A. , Chatterjee Nilanjan , Susztak Katalin , Coresh Josef , Grams Morgan E. 
Published: June 2023

AbstractBackgroundThe pathophysiological causes of kidney disease are not fully understood. Here we show that the integration of genome-wide genetic, transcriptomic, and proteomic association studies can nominate causal determinants of kidney function and damage.ResultsThrough transcriptome-wide association studies (TWAS) in kidney cortex, kidney tubule, liver, and whole blood and proteome-wide association studies (PWAS) in plasma, we assess for effects of 12,893 genes and 1342 proteins on kidney filtration (glomerular filtration rate (GFR) estimated by creatinine; GFR estimated by cystatin C; and blood urea nitrogen) and kidney damage (albuminuria). We find 1561 associations distributed among 260 genomic regions that are supported as putatively causal. We then prioritize 153 of these genomic regions using additional colocalization analyses. Our genome-wide findings are supported by existing knowledge (animal models forMANBA,DACH1,SH3YL1, INHBB), exceed the underlying GWAS signals (28 region-trait combinations without significant GWAS hit), identify independent gene/protein-trait associations within the same genomic region (INHBC,SPRYD4), nominate tissues underlying the associations (tubule expression ofNRBP1), and distinguish markers of kidney filtration from those with a role in creatinine and cystatin C metabolism.Furthermore, we follow up on members of the TGF-beta superfamily of proteins and find a prognostic value of INHBC for kidney disease progression even after adjustment for measured glomerular filtration rate (GFR).ConclusionIn summary, this study combines multimodal, genome-wide association studies to generate a catalog of putatively causal target genes and proteins relevant to kidney function and damage which can guide follow-up studies in physiology, basic science, and clinical medicine.
Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives
Authors: Firoozpour Loghman , Moghimi Setareh , Salarinejad Somayeh , Toolabi Mahsa , Rafsanjani Mahdi , Pakrad Roya , Salmani Farzaneh , Shokrolahi Seyed Mohammad , Sadat Ebrahimi Seyed Esmail , Karima Saeed , Foroumadi Alireza 
Published: June 2023

AbstractIn this work, a novel series of pyridazine-triazole hybrid molecules were prepared and evaluated as inhibitors of rat intestinalα-glucosidase enzyme. Amongst all newly synthesized compounds,10kshowed good inhibition in the series with IC50value of 1.7 µM which is 100 folds stronger than positive control, acarbose. The cytotoxicity revealed that this compound is not toxic against normal cell line, HDF. The docking studies showed that triazole ring plays an important role in the binding interactions with the active site. The insertion of compound10kinto the active pocket ofα-glucosidase and formation of hydrogen bonds with Leu677 was observed from docking studies. The kinetic studies revealed that this compound has uncompetitive mode of inhibition againstα-glucosidase enzyme.
Comparison of fasting and random lipid profiles among subjects with type 2 diabetes mellitus: an outpatient-based cross-sectional study in Bangladesh
Authors: Kamrul-Hasan A. B. M. , Talukder Samir Kumar , Kabir Md Ahamedul , Mustari Marufa , Un Nabi Md Masud , Gaffar Abu Jar , Hossain Md Firoj , Alam Muhammad Shah , Islam Md Rashedul , Hannan Mohammad Abdul , Zarin Nusrat , Paul Ajit Kumar , Akter Farhana , Ahammed Afsar , Kabir Md Lutful , Rahman Mohammad Motiur , Asaduzzaman Md , Saifuddin Mohammad , Chanda Palash Kumar , Rafi Md Abdur , Hasan Mohammad Jahid , Selim Shahjada 
Published: June 2023

Abstract
Background
Despite the wide acceptability of fasting lipid profiles in practice, emerging evidence suggests that random lipid profiles might be a convenient alternative for lipid measurement. The objective of the present study was to compare the fasting and random lipid profile among subjects with type 2 diabetes mellitus (T2DM).

Methods
The present cross-sectional study included 1543 subjects with T2DM visiting several endocrinology outpatient clinics throughout Bangladesh from January to December 2021. The fasting lipid profile was measured in the morning following 8–10 h of overnight fasting, and the random lipid profile was measured at any time of the day, irrespective of the last meal. The values of fasting and random lipids were compared using the Wilcoxon signed-rank test and Spearman rank correlation coefficients.

Results
In this study, a good level of correlation was observed between fasting and random lipid levels [r = 0.793, p < 0.001 for triglyceride (TG); r = 0.873, p < 0.001 for low-density lipoprotein cholesterol (LDL-C); r = 0.609, p < 0.001 for high-density lipoprotein cholesterol (HDL-C); and r = 0.780, p < 0.001 for total cholesterol (TC)]. In addition, TG and TC levels increased by 14% and 0.51%, respectively, in the random state compared to the fasting state (p- <0.05), while LDL-C levels decreased by 0.71% (p-value 0.42). No change was noticed in the HDL-C level. The difference between fasting and random lipid profiles was similar irrespective of patients’ age, sex, BMI, glucose-lowering drug(s), and lipid-lowering therapy.

Conclusions
Random lipid profile correlates significantly with fasting lipid profile with little difference. Hence, it might be a reliable alternative for fasting lipid profile in patients with T2DM.