bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous Treatment Effects of Intensive Glycemic Control on Kidney Microvascular Outcomes and Mortality in ACCORD
Authors: Charu Vivek , Liang Jane W. , Chertow Glenn M. , Li June , Montez-Rath Maria E. , Geldsetzer Pascal , de Boer Ian H. , Tian Lu , Tamura Manjula Kurella 
Published: December 2023

Significance Statement
Identifying and quantifying treatment effect variation across patients is the fundamental challenge of precision medicine. Here we quantify heterogeneous treatment effects of intensive glycemic control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, considering three outcomes of interest—a composite kidney outcome (driven by macroalbuminuria), all-cause mortality, and first assisted hypoglycemic event. We demonstrate that the effects of intensive glycemic control vary with risk of kidney failure, as predicted by the kidney failure risk equation (KFRE). Participants at highest risk of kidney failure gain the largest absolute kidney benefit of intensive glycemic control but also experience the largest absolute risk of death and hypoglycemic events. Our findings illustrate the value of identifying clinically meaningful treatment heterogeneity, particularly when treatments have different effects on multiple end points.

Objective
Clear criteria to individualize glycemic targets in patients with type II diabetes are lacking. In this post hoc analysis of the ACCORD, we evaluate whether the KFRE can identify patients for whom intensive glycemic control confers more benefit in preventing kidney microvascular outcomes.

Research Design and Methods
We divided the ACCORD trial population into quartiles on the basis of 5-year kidney failure risk using the KFRE. We estimated conditional treatment effects within each quartile and compared them with the average treatment effect in the trial. The treatment effects of interest were the 7-year restricted mean survival time (RMST) differences between intensive and standard glycemic control arms on (1) time-to-first development of severely elevated albuminuria or kidney failure and (2) all-cause mortality.

Results
We found evidence that the effect of intensive glycemic control on kidney microvascular outcomes and all-cause mortality varies with baseline risk of kidney failure. Patients with elevated baseline risk of kidney failure derived the most from intensive glycemic control in reducing kidney microvascular outcomes (7-year RMST difference of 114.8 [95% confidence interval 58.1 to 176.4] versus 48.4 [25.3 to 69.6] days in the entire trial population) However, this same patient group also experienced a shorter time to death (7-year RMST difference of −56.7 [−100.2 to −17.5] v. −23.6 [−42.2 to −6.6] days).

Conclusions
We found evidence of heterogenous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD as a function of predicted baseline risk of kidney failure. Patients with higher kidney failure risk experienced the most pronounced reduction in kidney microvascular outcomes but also experienced the highest risk of all-cause mortality.
Applying Customer-Oriented Approach in the System of Strategic Management of Territorial Development of the Municipalities in the Republic of Armenia
Authors: Martirosyan Goharik 
Published: December 2023

Today a citizen is considered as a «client» and he evaluates municipal services provided. The evaluation of such services can be done using such criteria as: compliance with quality standards, information support, time costs, financial costs, accessibility, customer focus of local governments, providing feedback, accessibility for all population groups and the «impression» of municipal services. We analyzed the relevance of «Customer Relationship Management» (CRM) that can be identified as a strategy that is used to learn more about the needs and behavior of the population to local governance. The purpose of our research was to prove the necessity of using the customer-oriented approach while providing municipal services in the Republic of Armenia. The use of that managerial model will make it possible to increase the efficiency of local authorities’ activity and the loyalty of citizens. The research methodology is based on practical developments of the Management theories, originally created for commercial organizations. The study found necessary conditions to implement those developments in the field of public administration of the Republic of Armenia with the aim of improving relations between local authorities and citizens. The information and empirical basis of the study was statistical reports and summary data of the municipal development programs in the Republic of Armenia. The object of research were large municipalities in the Republic of Armenia with a population of more than 100 000 people. The scientific novelty lies in the development and adaptation of the «Customer Relationship Management» — model’s elements that could be used by local authorities in large municipalities of the Republic of Armenia.
Comparative role of tumor marker CA 242 and CA 19.9 in various pancreatic lesions
Authors: Khandvi Akash , Chauhan Akshar M , Dave Neeru D , Dave Darshan D 
Published: December 2023

The pancreas has important endocrine and exocrine function and diseases of it causes significant morbidity and mortality. Diseases of the pancreas thus remain a continuing source of frustration in modern medicine. Clinical parameters have their limitations in diagnosing such lesions. Radiological evaluation also helps in diagnosing these lesions but to a certain extent. A good tumor marker is the answer to these problems. There are two tumor markers CA 242 and CA 19.9 which will not only help in early diagnosis of various pancreatic lesions, but also in differentiating them into neoplastic & non-neoplastic lesions. 100 patients of various pancreatic lesions were evaluated prospectively having USG confirmed pancreatic lesions, unexplained pancreatitis, pancreatic mass or pancreatic cystic lesion or worrisome clinical, imaging (CECT/USG) or laboratory findings.Serum tumor marker CA 242 is more specific (100%) than CA 19.9(75%) and CA 19.9(71.9%) is more sensitive than CA 242(70.1%) in patients of various pancreatic lesions. While combined serum tumor marker CA 19.9 and CA 242 was more sensitive (70.5%) and specific (100%) than CA 19.9 and CA 242 alone. For detection of various pancreatic lesions by serum tumor marker CA 19.9 and CA 242, the sensitivity, specificity and positive predictive value increases if markers are used in combination (serum tumor marker CA 19.9 and CA 242).
Histopathological spectrum of ovarian neoplasms - A 3 year hospital based study
Authors: Das V Shruthi , Kathireshan Charumathy , Bhushan V Prarthana 
Published: December 2023

: Ovarian neoplasms are the fifth leading cause of cancer mortality among females worldwide. It is associated with poor survival due to late clinical presentation with most cases presenting at stage III or stage IV.: The present study was undertaken to assess the histopathological spectrum of ovarian neoplasms according to the World Health Organization classification (2020) and to determine the frequency and age distribution of these neoplasms in a tertiary care hospital. : This observational study was conducted over a period of 3 years (August 2016 to July 2019) in the Department of Pathology, Gandhi Medical College, Telangana, India. All ovarian neoplasm specimens were routinely processed and histopathological examination was done for each specimen.: A total of 115 cases were included in the study out of which 97 (84.34%) cases were benign, 6 (5.22%) cases were borderline and 12 (10.44%) cases were malignant. Surface epithelial tumours were the most common, followed by germ cell tumours and sex cord-stromal tumours. The age group of 31-40 years showed the largest percentage of ovarian neoplasms.: Ovaries are a common site for tumours. Most patients present at late stages due to non-specific symptoms. Ovarian neoplasms are associated with a variety of clinical and morphological features and hence a correct histopathological diagnosis is required to institute appropriate therapy.
Clinicopathological and flowcytometric analysis of platelet function in patients presenting with thrombocytopenia
Authors: Singh Lal Panay , Bhandari Sandeep , Singrol Meena , Verma Priyanka 
Published: December 2023

Platelet function disorders are highly heterogeneous; those may be inherited/ acquired. Patients with these may have inadequate platelet count with impaired function, but may also have both. Early detection of platelet dysfunction also helps in better patient management and improve outcome. Prospective study done in 50 cases, Patient’s details history of thrombocytopenia. Complete blood count with peripheral smear is done and various parameters are analysed with respect to the platelet count, PDW, P-LCR. On EDTA preserved blood sample four monoclonal antibodies CD41, CD42b, CD61 and CD62p are applied and analysed by flow cytometer. In 50 thrombocytopenia cases out of which 06(12%) were immunological thrombocytopenia & 44 (88%) were non-immunological thrombocytopenia.
Nandai Boteba dan Tabligh Musibah: Komparasi Upacara Kematian Tradisional Masyarakat Serawai dan Kematian Warga Muhammadiyah Bengkulu
Authors: Hardiansyah Hardiansyah , Rasman Rasman , Susiyanto Susiyanto 
Published: December 2023

Penelitian ini mengkaji komparasi antara upacara kematian tradisional masyarakat suku Serawai dan upacara kematian golongan warga Muhammadiyah. Urgensi kajian ini berkaitan dengan Muhamma-diyah yang lekat dengan ciri kemodernan. Cara beragama Muhammadiyah yang mengusung jargon anti takhayul, Bid’ah dan Khurafat (TBC) dinilai kering dan sangat sederhana dibandingkan dengan kaum tradisionalis. Namun pada kenyataanya, warga Muhamadiyah sendiri membentuk sebuah budaya dalam malam kematian dengan sebuah acara yang dinamakan Tabligh Musibah, di mana penyelenggaraan acara ini memiliki kesamaan tujuan dengan upacara tradisional masyrakat serawai. Alih-alih mengirim doa untuk orang yang sudah mati sebagaimana tradisi tradisionalis Islam, kedua acara ini justru berfokus menghibur keluarga yang ditinggalkan serta berisi nasehat bagi para hadirin. Dengan menggunakan jenis penelitian adalah studi pustaka berkaitan dengan catatan atau arsip tentang Nandai Boteba dan studi lapangan dengan melakukan wawancara terkait dengan Tabligh Musibah, hasil penelitian menunjukkan bahwa terdapat perbedaan dan persamaan antara upacara tardisional kematian suku Serawai baik berkaitan dengan ritual maupun rangkaian acara. Selain itu, Nandai Boteba dan Tabligh Musibah memiliki kemiripan di mana tujuannya adalah menghibur keluarga yang ditinggalkan.
High circulating MIF levels indicate the association with atypical antipsychotic-induced metabolic adverse effects
Authors: Qi Dake , Chen Xi , Gao Pingyi , Qi Yadan , Li Zezhi , Huang Hongna , Shi Yuan , Wang Lijun , Cui Donghong 
Published: December 2023

Abstract

Atypical antipsychotics (AAPs) are first-line medications for schizophrenia (SZ). However, their use is frequently associated with the development of metabolic adverse effects, and the mechanisms behind these negative effects remain inadequately elucidated. To investigate the role of macrophage migration inhibitory factor (MIF) in regulating antipsychotic-induced metabolic abnormalities, we recruited 142 healthy individuals and 388 SZ patients who had been receiving either typical antipsychotic (TAP) or AAP treatments. Subsequently, we conducted assessments of metabolic indices and measured plasma MIF levels, followed by a comprehensive statistical analysis to investigate the connection between MIF levels and metabolic dysfunction. A significant increase in plasma MIF levels was observed in groups receiving monotherapies with five major AAPs in comparison to healthy controls (all p < 0.0001). There was no such increase shown in the group receiving TAP treatment (p > 0.05). Elevated plasma MIF levels displayed a notable correlation with insulin resistance (β = 0.024, p = 0.020), as well as with the levels of triglycerides (β = 0.019, p = 0.001) and total cholesterol (β = 0.012, p = 0.038) in the groups receiving AAPs. However, while the TAP group also displayed some degree of metabolic dysfunction compared to healthy controls, no significant association was evident with plasma MIF levels (all p > 0.05). In conclusion, Plasma MIF levels exhibit a distinctive correlation with metabolic abnormalities triggered by AAPs. Thus, MIF could be further developed as a unique marker to monitor AAP-induced metabolic adverse effects in clinical settings.
TRPML1 ion channel promote HepaRG cells differentiation under simulated microgravity conditions
Authors: Gao Ming , Fan Huancai , Lü Dongyuan , Lu Zheng , Li Hangyu , Qi Zijuan , Sun Shujin , Guan Dongshi , Long Mian , Liu Sijin 
Published: December 2023

Abstract
Stem cell differentiation must be regulated by intricate and complex interactions between cells and their surrounding environment, ensuring normal organ and tissue morphology such as the liver 1. Though it is well acknowledged that microgravity provides necessary mechanical force signals for cells fate 2, how microgravity affects growth, differentiation, and communication is still largely unknown due to the lack of real experimental scenarios and reproducibility tools. Here, we used Rotating Flat Chamber (RFC) to simulate ground-based microgravity effects to study how microgravity affects the differentiation of HepaRG (hepatic progenitor cells) cells. Unexpectedly, we found that simulated microgravity could promote HepaRG cells differentiation which was exhibited as increased expression of Alpha-fetoprotein (AFP), albumin (ALB), and Recombinant Cytokeratin 18 (CK18). Through screening a series of mechanical receptors, we identified that ion channel TRPML1 was critical for the differentiation promotion effect of microgravity. Once TRPML1 was activated by microgravity, the concentration of lysosomal calcium ions was increased to activate the Wnt/β-catenin signaling pathway, which finally led to the enhanced cell differentiation of HepaRG cells. In addition, the cytoskeleton was remodeled under microgravity conditions and then influenced the expression of PI (3,5) P2, which is the best-known activator of TRPML1. In summary, our findings have established a mechanism by which microgravity promotes the differentiation of HepaRG cells through the TRPML1 signaling pathway, which may provide a potential target for the regulation of hepatic stem/progenitor cells differentiation and embryonic liver development under microgravity conditions.
A novel neuroprotective derived peptide of erythropoietin improved cognitive function in vascular dementia mice
Authors: Zhou Zhiyuan , Ma Yuanyuan , Wu Tingting , Xu Tongtong , Wu Shengju , Yang Guo-Yuan , Ding Jing , Wang Xin 
Published: December 2023

Abstract

Background: The effective therapeutics for vascular dementia are still lacking. Here, we designed a novel derived peptide of erythropoietin-DEPO and evaluated its safety, erythropoiesis effect and neuroprotective effects in mice of vascular dementia.
Methods: DEPO was injected to C57BL6 mice (n=5) for 4-8 weeks, venous blood was collected at 1, 2, and 4 weeks after DEPO treatment for evaluating the safety of DEPO. Neuroprotective effects of DEPO were studied in both cultured neurons and vascular dementia mice (n=10/group). After 4-week DEPO administration, neurobehavioral tests and histology were applied to evaluate cognitive function and brain tissue damage of mice, respectively. Molecule docking, western blotting, pharmacological or genetic interference with EPOR and JAK/STAT/AKT pathway were used to determine the mechanism of neuroprotective effects of DEPO.
Results: DEPO did not increase the hemoglobin concentration or red blood cell number in mice after 4-week treatment compared to the vehicle group (p>0.05). DEPO treatment alleviated spatial reference memory impairment and the anxiety level in mice. Both gray and white matter injuries were significantly alleviated by DEPO treatment (p<0.05). DEPO activated JAK2/STAT5/AKT pathway in cultured neurons and protected neurons against chronic ischemia (p<0.05). Pharmacological or genetic interference with JAK2 signaling or EPOR inhibited the pro-survival effect of DEPO on chronic ischemia neurons (p<0.05).
Conclusions: DEPO is a novel safe erythropoietin-derived peptide and exerted its neuroprotective effects in vascular dementia mice through activating EPOR and its downstream JAK2/STAT5/AKT signaling pathway. DEPO is a potential alternative agent for treatment of vascular dementia or chronic cerebral ischemia.
Computationally Efficient and Stable Real-World Synthetic Emergency Room EHR Data Generation: High Similarity and Privacy Preserving Diffusion Model Approach
Authors: Aguirre Javier , Yu Jae Yong , Jung Kyu-Hwan , Yoon Jinsung , Cha Won Chul 
Published: December 2023

Abstract
Objective: This study aims to develop real-world synthetic electronic health record (EHR) for emergency departments using computationally efficient and stable diffusion probabilistic models.
Materials and Methods: In this research, we compare the performance of diffusion models and state-of-the-art generative adversarial networks (GANs) in terms of statistical similarity, privacy, medical usefulness, and the feasibility of using the synthetic data for machine learning purposes.
Results: Our results demonstrate that diffusion models are significantly more computationally efficient than GANs and perform comparably or slightly better in terms of similarity, privacy, and utility. We also found that the data quality of the diffusion model is statistically very similar for both categorical and continuous values and can address class imbalance precisely. Moreover, the machine learning usefulness of the synthetic data is almost identical to real EHR data. Our privacy analysis shows that the synthetic data generated by diffusion models is private.
Discussion: These findings have significant implications for improving the efficiency of emergency settings such as disasters and enabling real-time emergency room data modeling. Therefore, it demonstrates the potential of diffusion models to generate computationally efficient high-quality synthetic data.
Conclusion: The study concludes that diffusion models can generate real-world synthetic EHRs that are computationally efficient, private, and high-quality, which can be used for machine learning purposes in emergency settings.
CXCL13 determines superior prognosis and immunoactive tumor microenvironment in patients with colorectal cancer
Authors: Guo Fangfang , Chen Weiwei , Yan Yuqing , Cheng Yao , Zhang Rui , Shen Chaoqing , Cui Yun , Peng Yanshen , Hong Jie , Chen Haoyan , Ji Linhua , Xuan Baoqin , Zhu Xiaoqiang 
Published: December 2023

Abstract
Immunotherapy yields limited results in patients with colorectal cancer (CRC), emphasizing the need for a deeper comprehension of the immune landscape within the tumor microenvironment (TME). The precise immune function and prognostic significance of chemokine (C-X-C motif) ligand 13 (CXCL13) in CRC have remained uncertain, despite its known ability to attract B cells and contribute to tertiary lymphoid structures (TLS). Our study uncovered a positive correlation between CXCL13 expression and improved survival among CRC patients. Heightened levels of CXCL13, along with CXCL13+CD8+ T cells, were linked to a favorable immune contexture that impeded tumor growth in CRC. Moreover, CXCL13 expression was more prevalent in MSI-H/MMRd tumors, demonstrating potential in enhancing the response to anti-PD-L1 treatment. These findings emphasize the crucial role of CXCL13 in shaping the tumor microenvironment. Nevertheless, further investigation is required to fully elucidate the mechanisms through which CXCL13 regulates CD8+ T cells within the antitumor immune microenvironment.
Evaluation of Biaxial Flexural Strength and Shear Bond Strength of a Novel Chair-Side Cad/Cam Pre-crystalized Zirconia Reinforced Lithium Silicate (In-Vitro Study)
Authors: AlShahalii AbdulRahman A. , Kader Sanaa H. Abel , AboElhassan Rewaa G. 
Published: December 2023

Abstract
Statement of problem.
Lithium disilicate has been the gold standard for esthetic restorations, however several materials have been introduced to improve the strength without compromising esthetics.
Purpose.
The objective of this study was to perform a comparison between a newly introduced chair-side pre-crystalized zirconia reinforced lithium silicate material containing virgilite crystals (CEREC Tessera) and lithium disilicate ceramic material (LDS) regarding biaxial flexural strength and shear bond strength.
Materials and Methods.
For biaxial flexural strength, Twenty disc-shaped specimens, measuring 10 mm in diameter and 1.5 mm in thickness, were manufactured from both Tessera and LDS, with each group consisting of 10 specimens (n = 10The biaxial flexural strength was evaluated using the piston-on-ring method on a universal testing machine. For Shear Bond Strength, 20 cuboid specimens (3x3mm and 5 mm thickness) were fabricated from Tessera and LDS (n = 10). Specimens of both groups were bonded to natural human teeth with dual cured resin cement after appropriate surface treatment for both human natural teeth and specimen discs. The shear bond strength was assessed using a universal testing machine, and the testing was conducted at a cross-head speed of 1 mm/min.
Results.
The data obtained was statistically analyzed using appropriate tests. As for BFS, difference in results was statistically significant. The mean BFS value was higher for Tessera group (274.58 ± 22.26) compared to the LDS group (243.31 ± 24.98), however the difference in SBS values were not statistically significant between Tessera group (20.97 ± 1.59), although slightly higher, and LDS group (19.18 ± 2.99). The independent t test was used as the test of significance among the groups.
Conclusion.
Tessera material (zirconia reinforced lithium silicate material containing virgilite crystals) performed better overall than the more time-consuming e.max material ( lithium disilicate ceramic).
Bivariate Extreme Value Analysis of Extreme Temperature and Mortality in Canada, 2000-2020
Authors: Zhang Yuqing , Wang Kai , Ren Junjie , Liu Yixuan , Ma Fei , Li Tenglong , Chen Ying , Ling Chengxiu 
Published: December 2023

Abstract
Climate change increases the risk of illness through rising temperature,severe precipitation and worst air pollution. This paper investigates howmonthly excess mortality rate is associated with the increasing frequencyand severity of extreme temperature in Canada during 2000–2020. Theextreme associations were compared among four age groups across fivesub-blocks of Canada based on the datasets of monthly T90 and T10,the two most representative indices of severe weather monitoring mea-sures developed by the actuarial associations in Canada and US. Weutilize a combined seasonal Auto-regressive Integrated Moving Average(ARIMA) and bivariate Peaks-Over-Threshold (POT) method to inves-tigate the extreme association via the extreme tail index χ and Pickandsdependence function plots. It turns out that it is likely (more than 10%) to occur with excess mortality if there are unusual low temperature withextreme intensity (all χ > 0.1 except Northeast Atlantic (NEA), North-ern Plains (NPL) and Northwest Pacific (NWP) for age group 0–44),while extreme frequent high temperature seems not to affect health signif-icantly (all χ ≤ 0.001 except NWP). Particular attention should be paidto NWP and Central Arctic (CAR) since population health therein ishighly associated with both extreme frequent high and low temperatures(both χ = 0.3182 for all age groups). The revealed extreme depen-dence is expected to help stakeholders avoid significant ramifications withtargeted health protection strategies from unexpected consequences ofextreme weather events. The novel extremal dependence methodology ispromisingly applied in further studies of the interplay between extrememeteorological exposures, social-economic factors and health outcomes.