bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous Chromatographic Estimation of Vildagliptin and Dapagliflozin Using Hybrid Principles of White Analytical Chemistry and Analytical Quality by Design
Authors: Prajapati Pintu , Rana Bageshree , Pulusu Veera Shakar , Shah Shailesh 
Published: September 2023

Abstract

Background
The fixed-dose combination of vildagliptin (VDG) and dapagliflozin (DGZ) is used in the treatment of type 2 diabetes mellitus. According to the literature survey, RP-HPLC and HPTLC methods have been reported for routine analysis of VDG and DGZ. These chromatographic methods have been developed using potentially neurotoxic and teratogenic solvents, which are unsafe for human and aquatic animal life and hazardous to the environment. These types of organic solvents shall be replaced or reduced during chromatographic analysis of drugs for the safety of human and aquatic animal life and the protection of the environment. The novel white analytical chemistry (WAC) approach has been introduced, which emphasizes robust, green, user-friendly, economical, and rapid analysis of drug samples.

Objective
Hence, the WAC-based RP-HPLC method has been developed for the estimation of VDG and DGZ using lower toxic and economical solvents.

Method
The development of the RP-HPLC method includes the implementation of the analytical quality by design approach using principles of design of experiments to reduce organic waste generation and regulatory compliance of analytical method. The central composite design was applied for response surface modeling (RSM) and optimization of the RP-HPLC method. The method validation was carried out according to ICH Q2 (R1) guidelines.

Results
The fixed-dose combinations of VDG and DGZ were assayed, and results were found in compliance with their labeled claim. The published and proposed RP-HPLC methods were assessed for chromatographic analysis of VDG and DGZ using the Red-Green-Blue (RGB) model, AGREE calculator, Eco-Scale Assessment tool, GAPI software, and NEMI standards.

Conclusions
The proposed method was found to be robust, green, economical, and user-friendly for chromatographic analysis of VDG and DGZ. The proposed method can be an economical and eco-friendly analytical tool in the pharmaceutical industry for quality control and routine analysis of fixed-dose combinations of VDG and DGZ.

Highlights
Hybrid principles of WAC and analytical quality by design to RP-HPLC method for simultaneous estimation of VDG and DGZ in their fixed-dose combinations.
An investigation on the evolution of strain localization zone in metallic materials based on tensile tests and a 1-D nonlocal model
Authors: Chen Wei , Xia Lizhi , Yao Yin 
Published: September 2023

Abstract
Metallic materials exhibit pronounced strain localization during damage and failure, posing a challenge in damage mechanics when predicting the change in the size of the strain localization zone. In this study, uniaxial tensile tests were carried out to observe changes in the size of the strain localization zone during the loading of aluminum and low-carbon steel. The initial and final states of the two metallic materials during deformation localization were compared. The strain localization zone shrank gradually with the increase in the load, which agrees with existing electronic speckle pattern interferometry (ESPI) results. This experimental phenomenon was further analyzed theoretically. By establishing the relationship between the material characteristic length and the damage, the variation of the material characteristic length was revealed, and the form of the nonlocal kernel function with a varying characteristic length was determined. The results demonstrated that within the framework of nonlocal damage theory, the nonlocal kernel function with a varying characteristic length can be used to satisfactorily simulate the gradual shrinkage of the strain localization zone of metallic materials with the damage evolution. Therefore, this study provides an effective theoretical tool for predicting the size of the strain localization zone.
Current status and issues with the dosimetric assay of iodine-125 seed sources at medical facilities in Japan: a questionnaire-based survey
Authors: Kojima Toru , Kawamura Shinji , Otani Yuki , Hanada Takashi , Wakitani Yuichiro , Naniwa Kenta , Yorozu Atsunori , Ikushima Hitoshi , Dokiya Takushi 
Published: September 2023

Abstract
In conducting dosimetric assays of seed sources containing iodine-125 (125I), several major guidelines require the medical physicist to verify the source strength before patient treatment. Japanese guidelines do not mandate dosimetric assays at medical facilities, but since 2017, three incidents have occurred in Japan wherein seeds with incorrect strengths were delivered to medical facilities. Therefore, this study aimed to survey the current situation and any barriers to conducting the dosimetric assay of iodine-125 seeds at medical facilities in Japan. We conducted a questionnaire-based survey from December 2020 to April 2021, to examine whether seed assay and verification of the number of seeds delivered were being performed. We found that only 9 facilities (16%) performed seed assay and 28 (52%) verified the number of seeds. None of the facilities used an assay method that ensured traceability. The reasons for not performing an assay were divided into two categories: lack of resources and legal issues. Lack of resources included lack of instruments, lack of knowledge of assay methods, shorthand, or all of the above, whereas legal issues included the inability to resterilize iodine-125 seeds distributed in Japan and/or purchase seeds dedicated to the assay. Dosimetric assays, including simple methods, are effective in detecting calibration date errors and non-radioactive seeds. The study findings suggest that familiarization of medical personnel with these assay methods and investigation of the associated costs of labor and equipment should be recommended, as these measures will lead to medical reimbursement for quality assurance.
The Devil’s Ransom and Christology in Origen and the Cappadocians
Authors: Heinze Ky 
Published: September 2023

Abstract
This article identifies a relationship between third- and fourth-century Christology and the idea that Christ’s blood ransomed sinners from the devil. The thesis is that the ‘devil’s ransom’ was a natural conclusion for patristic exegetes but that those who accepted it had to navigate around the outrageous possibility that Christ’s divinity had been offered to the devil. Origen, depending on what some would call a dualistic Christology, solved the problem by saying that the ransom price (Christ’s blood or soul) had not included his divinity; but Gregory of Nazianzus, for whom Christ’s blood was in some real sense ‘the blood of God’, could not say this, which is one of the reasons that he rejected the whole idea of a ransom to the devil. In contrast, Gregory of Nyssa’s emphasis on the concealment of Christ’s divinity within the ransom prevented it from having been part of the agreed-upon price and so saved the devil’s ransom from scandal. This theological manoeuvring shows that the ransom stories should be read within a broader theological context. The recent scholarly recognition that the ransom is one among many colourful and sometimes incompatible soteriological metaphors should not lead us to ignore the degree to which patristic authors treated it with theological seriousness.
Phase II trial of concurrent sunitinib, temozolomide, and radiotherapy with adjuvant temozolomide for newly diagnosed MGMT unmethylated glioblastoma
Authors: Faye Mame Daro , Easaw Jacob , De Robles Paula , Agnihotram Raman , Torres-Vasquez Alexander , Lamonde Frederic , Petrecca Kevin , Owen Scott , Panet-Raymond Valerie , Shenouda George , Souhami Luis , Azam Maryam , Hossain Bushra , Alkass Jad , Sabri Siham , Abdulkarim Bassam 
Published: September 2023

AbstractBackgroundThe overall prognosis of glioblastoma (GBM) remains dismal, particularly for patients with unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter. In this phase II trial, we tested the combination of the antiangiogenic agent sunitinib with radiotherapy and temozolomide (TMZ) for newly diagnosed unmethylated MGMT GBM patients.MethodsWe enrolled 37 patients with unmethylated MGMT promoter GBM, age 18–70, and KPS ≥70. Patients received 12.5 mg of daily sunitinib for 7 days, followed by concurrent chemoradiation plus 12.5 mg sunitinib, then adjuvant TMZ. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), safety, and neutrophil-to-lymphocyte ratio (NLR) biomarker.ResultsAt a median follow-up time of 15.3 months (range: 3.1–71.3 months), the median PFS was 7.15 months (95% CI: 5.4–10.5) and the 6-month PFS was 54.0%. Median OS was 15.0 months (95% CI: 13.8–19.4) and 2-year OS rate was 17.1%. Patients receiving &gt;3 cycles of adjuvant TMZ, undergoing surgery at progression, and presenting a post-concurrent NLR ≤6 experienced a significant improved OS with hazard ratios of 0.197 (P = .001), 0.46 (P = .049), and 0.38 (P = .021), respectively, on multivariable analysis. Age &gt;65 years predicted for worse OS with hazard ratio of 3.92 (P = .037). Grade ≥3 thrombocytopenia occurred in 22.9%, grade ≥3 neutropenia in 20%, and grade ≥3 thromboembolic events in 14.3% of patients. There were no grade 5 events.ConclusionOur findings suggest a potential benefit of combining sunitinib with chemoradiation in newly diagnosed GBM patients with unmethylated MGMT status and provide a strong rationale to test this combination in future studies.
MRI-guided focused ultrasound blood–brain barrier opening increases drug delivery and efficacy in a diffuse midline glioma mouse model
Authors: Martinez Payton , Nault Genna , Steiner Jenna , Wempe Michael F , Pierce Angela , Brunt Breauna , Slade Mathew , Song Jane J , Mongin Andrew , Song Kang-Ho , Ellens Nicholas , Serkova Natalie , Green Adam L , Borden Mark 
Published: September 2023

Abstract

Background
Diffuse intrinsic pontine glioma (DIPG) is the most common and deadliest pediatric brainstem tumor and is difficult to treat with chemotherapy in part due to the blood–brain barrier (BBB). Focused ultrasound (FUS) and microbubbles (MBs) have been shown to cause BBB opening, allowing larger chemotherapeutics to enter the parenchyma. Panobinostat is an example of a promising in vitro agent in DIPG with poor clinical efficacy due to low BBB penetrance. In this study, we hypothesized that using FUS to disrupt the BBB allows higher concentrations of panobinostat to accumulate in the tumor, providing a therapeutic effect.

Methods
Mice were orthotopically injected with a patient-derived diffuse midline glioma (DMG) cell line, BT245. MRI was used to guide FUS/MB (1.5 MHz, 0.615 MPa peak negative pressure, 1 Hz pulse repetition frequency, 10-ms pulse length, 3 min treatment time)/(25 µL/kg, i.v.) targeting to the tumor location.

Results
In animals receiving panobinostat (10 mg/kg, i.p.) in combination with FUS/MB, a 3-fold increase in tumor panobinostat concentration was observed, without significant increase of the drug in the forebrain. In mice receiving 3 weekly treatments, the combination of panobinostat and FUS/MB led to a 71% reduction of tumor volumes (P = .01). Furthermore, we showed the first survival benefit from FUS/MB improved delivery increasing the mean survival from 21 to 31 days (P &lt; .0001).

Conclusions
Our study demonstrates that FUS-mediated BBB disruption can increase the delivery of panobinostat to an orthotopic DMG tumor, providing a strong therapeutic effect and increased survival.
Spontaneous oesophageal perforation secondary to renal colic
Authors: Zhang Jinghong , Yang Xinglin , Jiang Hui , Liu Jihai , Wang Jiangshan , Zhu Huadong 
Published: September 2023

Abstract
Boerhaave syndrome is a rare but potentially life-threatening condition that involves a full-thickness tear of the oesophagus. It accounts for around 15% of all cases of oesophageal perforations and is associated with up to 40% of mortality. Vomiting has been found to be associated with the development of Boerhaave syndrome. However, the aetiology of vomiting varies broadly in the available literatures from alcohol indulgence to marathon running, and from panic attack to radiotherapy for cancer. We present here an unusual case of Boerhaave syndrome where the patient developed spontaneous oesophageal perforation in the setting of renal colic.
Standardized image-based polysomnography database and deep learning algorithm for sleep-stage classification
Authors: Jeong Jaemin , Yoon Wonhyuck , Lee Jeong-Gun , Kim Dongyoung , Woo Yunhee , Kim Dong-Kyu , Shin Hyun-Woo 
Published: September 2023

Abstract

Study Objectives
Polysomnography (PSG) scoring is labor-intensive, subjective, and often ambiguous. Recently several deep learning (DL) models for automated sleep scoring have been developed, they are tied to a fixed amount of input channels and resolution. In this study, we constructed a standardized image-based PSG dataset in order to overcome the heterogeneity of raw signal data obtained from various PSG devices and various sleep laboratory environments.

Methods
All individually exported European data format files containing raw signals were converted into images with an annotation file, which contained the demographics, diagnoses, and sleep statistics. An image-based DL model for automatic sleep staging was developed, compared with a signal-based model, and validated in an external dataset

Results
We constructed 10253 image-based PSG datasets using a standardized format. Among these, 7745 diagnostic PSG data were used to develop our DL model. The DL model using the image dataset showed similar performance to the signal-based dataset for the same subject. The overall DL accuracy was greater than 80%, even with severe obstructive sleep apnea. Moreover, for the first time, we showed explainable DL in the field of sleep medicine as visualized key inference regions using Eigen-class activation maps. Furthermore, when a DL model for sleep scoring performs external validation, we achieved a relatively good performance.

Conclusions
Our main contribution demonstrates the availability of a standardized image-based dataset, and highlights that changing the data sampling rate or number of sensors may not require retraining, although performance decreases slightly as the number of sensors decreases.
Shared and distinct abnormalities of brain magnetization transfer ratio in schizophrenia and major depressive disorder: a comparative voxel-based meta-analysis
Authors: Lan Huan , Suo Xueling , Zuo Chao , Ni Weishi , Wang Song , Kemp Graham J. , Gong Qiyong 
Published: September 2023

Abstract

Background:
Patients with schizophrenia (SCZ) and major depressive disorder (MDD) share significant clinical overlap, although it remains unknown to what extent this overlap reflects shared neural profiles. To identify the shared and specific abnormalities in SCZ and MDD, we performed a whole-brain voxel-based meta-analysis using magnetization transfer imaging, a technique that characterizes the macromolecular structural integrity of brain tissue in terms of the magnetization transfer ratio (MTR).

Methods:
A systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in PubMed, EMBASE, International Scientific Index (ISI) Web of Science, and MEDLINE for relevant studies up to March 2022. Two researchers independently screened the articles. Rigorous scrutiny and data extraction were performed for the studies that met the inclusion criteria. Voxel-wise meta-analyses were conducted using anisotropic effect size-signed differential mapping with a unified template. Meta-regression was used to explore the potential effects of demographic and clinical characteristics.

Results:
A total of 15 studies with 17 datasets describing 365 SCZ patients, 224 MDD patients, and 550 healthy controls (HC) were identified. The conjunction analysis showed that both disorders shared higher MTR than HC in the left cerebellum (P=0.0006) and left fusiform gyrus (P=0.0004). Additionally, SCZ patients showed disorder-specific lower MTR in the anterior cingulate/paracingulate gyrus, right superior temporal gyrus, and right superior frontal gyrus, and higher MTR in the left thalamus, precuneus/cuneus, posterior cingulate gyrus, and paracentral lobule; and MDD patients showed higher MTR in the left middle occipital region. Meta-regression showed no statistical significance in either group.

Conclusions:
The results revealed a structural neural basis shared between SCZ and MDD patients, emphasizing the importance of shared neural substrates across psychopathology. Meanwhile, distinct disease-specific characteristics could have implications for future differential diagnosis and targeted treatment.
Global, regional, and national burden of hypertensive heart disease among older adults in 204 countries and territories between 1990 and 2019: a trend analysis
Authors: Yang Ruixue , Zhang Xun , Bai Jingjing , Wang Lu , Wang Wenjie , Cai Jun 
Published: September 2023

Abstract

Background:
Hypertensive heart disease (HHD) poses a public health challenge, but data on its burden and trends among older adults are scarce. This study aimed to identify trends in the burden of HHD among older adults between 1990 and 2019 at the global, regional, and national levels.

Methods:
Using the Global Burden of Diseases study 2019 data, we assessed HHD prevalence, death, and disability-adjusted life-year (DALY) rates for individuals aged 60–89 years at the global, regional, and national levels and estimated their average annual percentage changes (AAPCs) between 1990 and 2019 using joinpoint regression analysis.

Results:
In 2019, there were 14.35 million HHD prevalent cases, 0.85 million deaths, and 14.56 million DALYs in older adults. Between 1990 and 2019, the prevalence of HHD increased globally {AAPC, 0.38 (95% confidence interval [CI], 0.36, 0.41)} with decreases observed in mortality (AAPC, –0.83 [95% CI, –0.99, –0.66]) and the DALY rate (AAPC, –1.03 [95% CI, –1.19, –0.87]). This overall global trend pattern was essentially maintained for sex, age group, and sociodemographic index (SDI) quintile except for non-significant changes in the prevalence of HHD in those aged 70–74 years and in the middle SDI quintile. Notably, males had a higher HHD prevalence rate. However, HHD-related mortality and the DALY rate were higher in females. The middle SDI quintile experienced the largest decreases in mortality and the DALY rate, with a non-significant decline in prevalence between 1990 and 2019. There were significant discrepancies in the HHD burden and its trends across regions and countries.

Conclusions:
In the past three decades, there has been an overall increasing trend in the prevalence of HHD among older adults worldwide despite decreasing trends in mortality and the DALY rate. Better management of hypertension, and prevention and control of HHD are needed in older adults.
Diagnostic Accuracy of a Trauma Risk Assessment Tool Among Geriatric Patients With Crash Injuries
Authors: Adeyemi Oluwaseun John , Gibbons Kester , Schwartz Luke B. , Meltzer-Bruhn Ariana T. , Esper Garrett W. , Grudzen Corita , DiMaggio Charles , Chodosh Joshua , Egol Kenneth A. , Konda Sanjit R. 
Published: September 2023

ABSTRACT
The Score for Trauma Triage in the Geriatric and Middle-Aged (STTGMA) is a risk stratification tool. We evaluated the STTGMA's accuracy in predicting 30-day mortality and the odds of unfavorable clinical trajectories among crash-related trauma patients. This retrospective cohort study (n = 912) pooled adults aged 55 years and older from a single institutional trauma database. The data were split into training and test data sets (70:30 ratio) for the receiver operating curve analysis and internal validation, respectively. The outcome variables were 30-day mortality and measures of clinical trajectory. The predictor variable was the high-energy STTGMA score (STTGMAHE). We adjusted for the American Society of Anesthesiologists Physical Status. Using the training and test data sets, STTGMAHE exhibited 82% (95% CI: 65.5–98.3) and 96% (90.7–100.0) accuracies in predicting 30-day mortality, respectively. The STTGMA risk categories significantly stratified the proportions of orthopedic trauma patients who required intensive care unit (ICU) admissions, major and minor complications, and the length of stay (LOS). The odds of ICU admissions, major and minor complications, and the median difference in the LOS increased across the risk categories in a dose–response pattern. STTGMAHE exhibited an excellent level of accuracy in identifying middle-aged and geriatric trauma patients at risk of 30-day mortality and unfavorable clinical trajectories.
A Study on Vascular Regulators as Early Biomarkers of Hand Arm Vibration Syndrome
Authors: Yang Hongyu , Chen Ziyu , Hu Xiuwen , Wei Nuoyan , Li Jiajie , Wei Yuan , Chen Qingsong 
Published: September 2023

Objectives
Purposes of this study are to study the changes in expression of vascular regulators after vibration exposure and during the onset of vibration-induced white finger (VWF) and to screen for vascular regulatory factors that could be used as early biomarkers of HAVS.

Methods
Using judgmental sampling from a Chinese factory, workers with VWF and hand-transmitted vibration exposure but without VWF were selected for research. Blood samples were taken from all subjects, and the levels of nine of the vascular regulators were measured using ELISA.

Results
Receiver operating characteristic curve analysis was performed on nine vascular regulators to assess their diagnostic sensitivity for VWF with the following area under the curve results: PGI2 = 0.861, ANP = 0.840.

Conclusions
Collectively, PGI2 and ANP exhibited the most potential for the early diagnosis of HAVS.
Antimitochondrial antibody-negative primary biliary cirrhosis with secondary Sjogren syndrome: a case report
Authors: Acharya Suman , Shrestha Suraj , Poddar Elisha , Neupane Ashru , Khadayat Ramesh , Magar Sagar R. , Lamsal Manoj , Pathak Rahul 
Published: September 2023

Introduction and importance:
Primary biliary cholangitis (PBC) is a rare immune-mediated liver disease characterized by the destruction of intrahepatic bile ducts and a positive antimitochondrial antibody (AMA), which is considered a serological hallmark for the diagnosis. Rarely, AMA can be absent/nondetectable in a few cases and is referred to as ‘AMA-negative’.

Case presentation:
The authors present such an uncommon case of AMA-negative PBC in a 39-year-female with Sjogren’s syndrome who presented with fatigue, pruritus, and dry eyes.

Clinical discussion:
Previously published studies state that approximately only about 5% of patients with PBC are ‘AMA-negative’. For patients negative for AMA, the diagnosis has to be based on typical pathological features of this disease. Once a diagnosis of PBC is established, regardless of whether it is positive or negative for AMAs, ursodeoxycholic acid is a widely accepted treatment.

Conclusion:
The presence/absence of AMAs is associated with similar clinical, biochemical, and histopathological characteristics in PBC. The identification of AMAs alone should not impact the diagnosis or treatment of PBC.