bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel cuproptosis-related gene prognostic signature in colon adenocarcinoma
Authors: Su Yongqin , Zhang Kun 
Published: September 2023

Cuproptosis is the latest cell death type caused by enhanced mitochondrial-dependent energy metabolism. This study plans to establish a survival prognosis model for colon adenocarcinoma (COAD) patients based on cuproptosis-related genes (CRGs). We investigated the genetic alterations of CRGs in COAD based on The Cancer Genome Atlas database and validated in the GSE41328 dataset. Our results showed that LIPT1, PDHA1, GLS, and CDKN2A had significantly higher expression in COAD tissues than in normal tissues, while FDX1, DLD, and MTF1 had significantly lower expression in COAD tissues than in normal tissues (|(log2(fold change))| > 2, p < 0.05). DLD (hazard ratio (HR): 0.658; 95% confidence interval (CI): 0.445, 0.974; p = 0.037) and CDKN2A (HR: 1.785; 95% CI: 1.200, 2.654; p = 0.004) expressions were linked with overall survival throughout a log-rank test. CRG prognostic scores exhibited an area under the curve of 0.737, 0.646, and 0.633 at 1, 3, and 5 years. Patients with a high-risk factor suffered from poor prognosis (HR = 1.514; 95% CI: 1.022, 2.243; p = 0.0386). An independent validation dataset (GSE41328 ( N = 20)) confirmed the above results. The CRGs’ signature may be used as a prognostic predictor for COAD patients, providing unique insights into anticancer therapy.
Signature flip in deceleration parameter: a thermodynamic phase transition?
Authors: Duary Tanima , Banerjee Narayan , Dasgupta Ananda 
Published: September 2023

AbstractUsing the Hayward–Kodama temperature for the apparent horizon, it is found that matter content in the Universe is not thermodynamically stable, and the entry to the late accelerated expansion is actually a second order phase transition. The cosmological model used for the purpose is one that imitates the $$\varLambda $$
Λ
CDM model, the favoured model for the present Universe.
Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker
Authors: Taylor Martin S. , Wu Connie , Fridy Peter C. , Zhang Stephanie J. , Senussi Yasmeen , Wolters Justina C. , Cajuso Tatiana , Cheng Wen-Chih , Heaps John D. , Miller Bryant D. , Mori Kei , Cohen Limor , Jiang Hua , Molloy Kelly R. , Chait Brian T. , Goggins Michael G. , Bhan Irun , Franses Joseph W. , Yang Xiaoyu , Taplin Mary-Ellen , Wang Xinan , Christiani David C. , Johnson Bruce E. , Meyerson Matthew , Uppaluri Ravindra , Egloff Ann Marie , Denault Elyssa N. , Spring Laura M. , Wang Tian-Li , Shih Ie-Ming , Fairman Jennifer E. , Jung Euihye , Arora Kshitij S. , Yilmaz Osman H. , Cohen Sonia , Sharova Tatyana , Chi Gary , Norden Bryanna L. , Song Yuhui , Nieman Linda T. , Pappas Leontios , Parikh Aparna R. , Strickland Matthew R. , Corcoran Ryan B. , Mustelin Tomas , Eng George , Yilmaz Ömer H. , Matulonis Ursula A. , Chan Andrew T. , Skates Steven J. , Rueda Bo R. , Drapkin Ronny , Klempner Samuel J. , Deshpande Vikram , Ting David T. , Rout Michael P. , LaCava John , Walt David R. , Burns Kathleen H. 
Published: September 2023

Abstract

Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring treatment response. Although proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity for these applications. Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is a transposable element protein overexpressed in carcinomas and high-risk precursors during carcinogenesis with negligible expression in normal tissues, suggesting ORF1p could be a highly specific cancer biomarker. To explore ORF1p as a blood-based biomarker, we engineered ultrasensitive digital immunoassays that detect mid-attomolar (10−17 mol/L) ORF1p concentrations in plasma across multiple cancers with high specificity. Plasma ORF1p shows promise for early detection of ovarian cancer, improves diagnostic performance in a multianalyte panel, provides early therapeutic response monitoring in gastroesophageal cancers, and is prognostic for overall survival in gastroesophageal and colorectal cancers. Together, these observations nominate ORF1p as a multicancer biomarker with potential utility for disease detection and monitoring.

Significance:
The LINE-1 ORF1p transposon protein is pervasively expressed in many cancers and is a highly specific biomarker of multiple common, lethal carcinomas and their high-risk precursors in tissue and blood. Ultrasensitive ORF1p assays from as little as 25 μL plasma are novel, rapid, cost-effective tools in cancer detection and monitoring.
See related commentary by Doucet and Cristofari, p. 2502.
This article is featured in Selected Articles from This Issue, p. 2489
Clinical Correlates of Venetoclax-Based Combination Sensitivities to Augment Acute Myeloid Leukemia Therapy
Authors: Eide Christopher A. , Kurtz Stephen E. , Kaempf Andy , Long Nicola , Joshi Sunil Kumar , Nechiporuk Tamilla , Huang Ariane , Dibb Charles A. , Taylor Akosha , Bottomly Daniel , McWeeney Shannon K. , Minnier Jessica , Lachowiez Curtis A. , Saultz Jennifer N. , Swords Ronan T. , Agarwal Anupriya , Chang Bill H. , Druker Brian J. , Tyner Jeffrey W. 
Published: September 2023

Abstract

The BCL2 inhibitor venetoclax combined with the hypomethylating agent azacytidine shows significant clinical benefit in a subset of patients with acute myeloid leukemia (AML); however, resistance limits response and durability. We prospectively profiled the ex vivo activity of 25 venetoclax-inclusive combinations on primary AML patient samples to identify those with improved potency and synergy compared with venetoclax + azacytidine (Ven + azacytidine). Combination sensitivities correlated with tumor cell state to discern three patterns: primitive selectivity resembling Ven + azacytidine, monocytic selectivity, and broad efficacy independent of cell state. Incorporation of immunophenotype, mutation, and cytogenetic features further stratified combination sensitivity for distinct patient subtypes. We dissect the biology underlying the broad, cell state–independent efficacy for the combination of venetoclax plus the JAK1/2 inhibitor ruxolitinib. Together, these findings support opportunities for expanding the impact of venetoclax-based drug combinations in AML by leveraging clinical and molecular biomarkers associated with ex vivo responses.

Significance:
By mapping drug sensitivity data to clinical features and tumor cell state, we identify novel venetoclax combinations targeting patient subtypes who lack sensitivity to Ven + azacytidine. This provides a framework for a taxonomy of AML informed by readily available sets of clinical and genetic features obtained as part of standard care.
See related commentary by Becker, p. 437 .
This article is featured in Selected Articles from This Issue, p. 419
СПЕКТРОФОТОМЕТРИЧНЕ ВИЗНАЧЕННЯ МЕТФОРМІНУ ГІДРОХЛОРИДУ В ТАБЛЕТКАХ ЗА РЕАКЦІЄЮ З БРОМКРЕЗОЛОВИМ ЗЕЛЕНИМ
Authors: Leleka L. H. , Vasyuk S. O. 
Published: September 2023

Мета роботи. Розробка і валідація спектрофотометричної методики кількісного визначення метформіну гідрохлориду в таблетках за реакцією з сульфофталеїновими барвниками.
Матеріали і методи. Для аналізу були використані:
- субстанція метформіну гідрохлориду фармакопейної чистоти;
- таблетки – «Метформін Астрафарм» 500 мг, «Метформін Тева» 1000 мг, «Метформін Сандоз» 850 мг, «Метформін Глюкофаж» 500 мг;
- реагенти – сульфофталеїнові барвники: бромкрезоловий зелений (Synex Pharma, Китай), бромкрезоловий пурпуровий (Шосткинський завод хімічних реактивів, Україна), бромтимоловий синій (Synex Pharma, Китай), тимоловий синій (Шосткинський завод хімічних реактивів, Україна). Всі реагенти кваліфікації «чда»;
- розчинник – ацетон кваліфікації «чда» та вода очищена;
- аналітичне обладнання – спектрофотометр «Specord-200» (Analytic Jena AG, Німеччина), ваги лабораторні електронні RADWAG XA 210. 4Y, мірний лабораторний посуд класу А.
Результати й обговорення. Розроблено нову, просту спектрофотометричну методику кількісного визначення метформіну гідрохлориду в таблетках за реакцією з бромкрезоловим зеленим (БКЗ) в 1 % водно-ацетоновому середовищі. Максимум поглинання знаходиться при 408 нм. Підпорядкування основному закону світлопоглинання перебуває в межах концентрацій 0,5–1,2 мг/100 мл. Значення межі виявлення складає 0,433×10-6 г/мл, що свідчить про високу чутливість реакції. Відповідно до вимог Державної Фармакопеї України (ДФУ) для розробленої методики були визначені деякі валідаційні характеристики, а саме, лінійність, точність, правильність та робасність. Також було проведено перевірку «зеленості» методики за допомогою інструменту AGREE (Analytical GREEnness) та аналітичної еко-шкали.
Висновки. За результатами проведеного дослідження було розроблено та валідовано спектрофотометричну методику кількісного визначення метформіну гідрохлориду. Методика є простою, доступною та відповідає вимогам ДФУ, тому може бути рекомендована для застосування в лабораторіях із контролю якості лікарських засобів.
ОСОБЛИВОСТІ ОРГАНІЗАЦІЇ ОСВІТНЬОГО ПРОЦЕСУ В ТЕРНОПІЛЬСЬКОМУ НАЦІОНАЛЬНОМУ МЕДИЧНОМУ УНІВЕРСИТЕТІ ІМЕНІ І. Я. ГОРБАЧЕВСЬКОГО МІНІСТЕРСТВА ОХОРОНИ ЗДОРОВ’Я УКРАЇНИ В ПЕРІОД ВОЄННОГО СТАНУ
Authors: Корда М. М. , Шульгай А. Г. , Машталір А. І. 
Published: September 2023

Анотація. У статті розглянуто особливості організації освітнього процесу в Тернопільському національному медичному університеті імені І. Я. Горбачевського МОЗ України у період воєнного стану. Висвітлено заходи, спрямовані на забезпечення безпечного освітнього середовища та подолання викликів сьогодення. На підставі проаналізованих даних зроблені висновки щодо забезпечення якості надання освітніх послуг, набуття здобувачами практичних навичок та безпечного середовища.
An East-Syriac Scholar in Ninth-Century Damascus
Authors: Treiger Alexander 
Published: September 2023

Abstract
The ninth-century Damascene Christian scholar, priest, and monk Bišr ibn al-Sirrī (fl. ca. 870) is known as the author of Arabic biblical translations and commentaries and Arabic festal homilies. The present contribution demonstrates that the homilies contained in Sinai ar. 431 without attribution are to be ascribed to Bišr ibn al-Sirrī. It also examines new evidence for Bišr ibn al-Sirrī’s Christology and proves that Bišr ibn al-Sirrī was an East-Syriac Christian.
Effect of high-dose intravenous ascorbic acid on microcirculation and endothelial glycocalyx during sepsis and septic shock: a double-blind, randomized, placebo-controlled study
Authors: Belousoviene Egle , Pranskuniene Zivile , Vaitkaitiene Egle , Pilvinis Vidas , Pranskunas Andrius 
Published: September 2023

AbstractPrevious studies indicate supplemental vitamin C improves microcirculation and reduces glycocalyx shedding in septic animals. Our randomized, double-blind, placebo-controlled trial aimed to investigate whether a high dose of intravenous ascorbic acid (AA) might improve microcirculation and affect glycocalyx in septic patients. In our study, 23 septic patients were supplemented with a high dose (50 mg/kg every 6 h) of intravenous AA or placebo for 96 h. Sublingual microcirculation was examined using a handheld Cytocam-incident dark field (IDF) video microscope. A sidestream dark field video microscope (SDF), connected to the GlycoCheck software (GlycoCheck ICU®; Maastricht University Medical Center, Maastricht, the Netherlands), was employed to observe glycocalyx. We found a significantly higher proportion of perfused small vessels (PPV) 6 h after the beginning of the trial in the experimental group compared with placebo. As an indicator of glycocalyx thickness, the perfused boundary region was lower in capillaries of the 5–9 μm diameter in the AA group than placebo after the first dose of AA. Our data suggest that high-dose parenteral AA tends to improve microcirculation and glycocalyx in the early period of septic shock. The study was retrospectively registered in the clinicaltrials.gov database on 26/02/2021 (registration number NCT04773717).
Comparing analytical strategies for balancing site-level characteristics in stepped-wedge cluster randomized trials: a simulation study
Authors: Ma Clement , Lee Alina , Courtney Darren , Castle David , Wang Wei 
Published: September 2023

Abstract
Background
Stepped-wedge cluster randomized trials (SWCRTs) are a type of cluster-randomized trial in which clusters are randomized to cross-over to the active intervention sequentially at regular intervals during the study period. For SWCRTs, sequential imbalances of cluster-level characteristics across the random sequence of clusters may lead to biased estimation. Our study aims to examine the effects of balancing cluster-level characteristics in SWCRTs.

Methods
To quantify the level of cluster-level imbalance, a novel imbalance index was developed based on the Spearman correlation and rank regression of the cluster-level characteristic with the cross-over timepoints. A simulation study was conducted to assess the impact of sequential cluster-level imbalances across different scenarios varying the: number of sites (clusters), sample size, number of cross-over timepoints, site-level intra-cluster correlation coefficient (ICC), and effect sizes. SWCRTs assumed either an immediate “constant” treatment effect, or a gradual “learning” treatment effect which increases over time after crossing over to the active intervention. Key performance metrics included the relative root mean square error (RRMSE) and relative mean bias.

Results
Fully-balanced designs almost always had the highest efficiency, as measured by the RRMSE, regardless of the number of sites, ICC, effect size, or sample sizes at each time for SWCRTs with learning effect. A consistent decreasing trend of efficiency was observed by increasing RRMSE as imbalance increased. For example, for a 12-site study with 20 participants per site/timepoint and ICC of 0.10, between the most balanced and least balanced designs, the RRMSE efficiency loss ranged from 52.5% to 191.9%. In addition, the RRMSE was decreased for larger sample sizes, larger number of sites, smaller ICC, and larger effect sizes. The impact of pre-balancing diminished when there was no learning effect.

Conclusion
The impact of pre-balancing on preventing efficiency loss was easily observed when there was a learning effect. This suggests benefit of pre-balancing with respect to impacting factors of treatment effects.
Dementia and Parkinson’s disease diagnoses in electronic health records vs. Medicare claims data: a study of 101,980 linked patients
Authors: Lusk Jay B. , Choi Sujung , Clark Amy G. , Johnson Kim , Ford Cassie B. , Greiner Melissa A. , Goetz Margarethe , Kaufman Brystana G. , O’Brien Richard , O’Brien Emily C. 
Published: September 2023

Abstract
Background
Medicare claims and electronic health record data are both commonly used for research and clinical practice improvement; however, it is not known how concordant diagnoses of neurodegenerative diseases (NDD, comprising dementia and Parkinson’s disease) are in these data types. Therefore, our objective was to determine the sensitivity and specificity of neurodegenerative disease (NDD) diagnoses contained in structured electronic health record (EHR) data compared to Medicare claims data.

Methods
This was a retrospective cohort study of 101,980 unique patients seen at a large North Carolina health system between 2013–2017, which were linked to 100% North and South Carolina Medicare claims data, to evaluate the accuracy of diagnoses of neurodegenerative diseases in EHRs compared to Medicare claims data. Patients age > 50 who were enrolled in fee-for-service Medicare were included in the study. Patients were classified as having or not having NDD based on the presence of validated ICD-CM-9 or ICD-CM-10 codes associated with NDD or claims for prescription drugs used to treat NDD. EHR diagnoses were compared to Medicare claims diagnoses.

Results
The specificity of any EHR diagnosis of NDD was 99.0%; sensitivity was 61.3%. Positive predictive value and negative predictive value were 90.8% and 94.1% respectively. Specificity of an EHR diagnosis of dementia was 99.0%, and sensitivity was 56.1%. Specificity of an EHR diagnosis of PD was 99.7%, while sensitivity was 76.1%.

Conclusions
More research is needed to investigate under-documentation of NDD in electronic health records relative to Medicare claims data, which has major implications for clinical practice (particularly patient safety) and research using real-world data.
The inter-prefectural regional disparity of healthcare resources and representative surgical procedures in orthopaedics and general surgery: a nationwide study in Japan during 2015–2019
Authors: Kido Masamitsu , Ikoma Kazuya , Kobayashi Yumiko , Maki Masahiro , Ohashi Suzuyo , Shoda Katsutoshi , Ichikawa Daisuke , Uehara Ritei , Takahashi Kenji 
Published: September 2023

Abstract
Background
Few reports have examined the localized regional disparity in representative surgical procedures in orthopaedics and general surgery globally. This study aimed to clarify the inter-prefectural regional disparity and relationships between healthcare resources and representative surgical procedures using a nationwide database in Japan.

Methods
The number of medical specialists in orthopaedics, general surgery, and anaesthesiology, as well as the number of hospitals, and the incidence of representative surgical procedures in orthopaedics and general surgery were evaluated annually per 100,000 inhabitants/people by prefecture in Japan during 2015–2019. Medium-sized regional disparities were evaluated using the Gini coefficient. Correlation coefficients were calculated for the defined variables and ageing rate. We also compared the urban and rural regional disparities in all study variables.

Results
The annual average number/incidence and Gini coefficients were 110.6 and 0.11 for femur fracture surgery, 106.3 and 0.09 for cholecystectomy, 14.2 and 0.11 for orthopaedic surgeon specialists, 17.6 and 0.09 for general surgeon specialists, 5.9 and 0.13 for anaesthesiology specialists, and 8.1 and 0.21 for hospitals, respectively. The correlation coefficients by the incidence of femur fracture surgery were 0.74 for orthopaedic surgeon specialists (p < 0.001), 0.63 for hospitals (p < 0.001), and 0.62 for the ageing rate (p < 0.001); those by the incidence of cholecystectomy were 0.60 for general surgeon specialists (p < 0.001) and 0.59 for hospitals (p < 0.001). The number/incidence of orthopaedic surgeon specialists, hospitals, femur fracture surgery, and cholecystectomy, as well as the ageing rate, were significantly higher in rural prefectures than in urban prefectures (p < 0.05).

Conclusions
Inter-prefectural regional disparity was small, although certain items were unevenly distributed in the rural prefectures, which is contrary to our expectations. Higher prevalence was recognised in rural prefectures due to the higher ageing rate; however, supply and demand are balanced. This study provides basic data for healthcare policy development in a medium-sized community.

Level of evidence
III.
GREM1, LRPPRC and SLC39A4 as potential biomarkers of intervertebral disc degeneration: a bioinformatics analysis based on multiple microarray and single-cell sequencing data
Authors: Zhang ZhaoLiang , Huo JianZhong , Ji XingHua , Wei LinDong , Zhang Jinfeng 
Published: September 2023

Abstract
Background
Low back pain (LBP) has drawn much widespread attention and is a major global health concern. In this field, intervertebral disc degeneration (IVDD) is frequently the focus of classic studies. However, the mechanistic foundation of IVDD is unclear and has led to conflicting outcomes.

Methods
Gene expression profiles (GSE34095, GSE147383) of IVDD patients alongside control groups were analyzed to identify differentially expressed genes (DEGs) in the GEO database. GSE23130 and GSE70362 were applied to validate the yielded key genes from DEGs by means of a best subset selection regression. Four machine-learning models were established to assess their predictive ability. Single-sample gene set enrichment analysis (ssGSEA) was used to profile the correlation between overall immune infiltration levels with Thompson grades and key genes. The upstream targeting miRNAs of key genes (GSE63492) were also analyzed. A single-cell transcriptome sequencing data (GSE160756) was used to define several cell clusters of nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplate (CEP) of human intervertebral discs and the distribution of key genes in different cell clusters was yielded.

Results
By developing appropriate p-values and logFC values, a total of 6 DEGs was obtained. 3 key genes (LRPPRC, GREM1, and SLC39A4) were validated by an externally validated predictive modeling method. The ssGSEA results indicated that key genes were correlated with the infiltration abundance of multiple immune cells, such as dendritic cells and macrophages. Accordingly, these 4 key miRNAs (miR-103a-3p, miR-484, miR-665, miR-107) were identified as upstream regulators targeting key genes using the miRNet database and external GEO datasets. Finally, the spatial distribution of key genes in AF, CEP, and NP was plotted. Pseudo-time series and GSEA analysis indicated that the expression level of GREM1 and the differentiation trajectory of NP chondrocytes are generally consistent. GREM1 may mainly exacerbate the degeneration of NP cells in IVDD.

Conclusions
Our study gives a novel perspective for identifying reliable and effective gene therapy targets in IVDD.
Prognostic value of APTT combined with fibrinogen and creatinine in predicting 28-Day mortality in patients with septic shock caused by acute enteric perforation
Authors: Fu Shuiqiao , Yu Wenqiao , Fu Qinghui , Xu Zhipeng , Zhang Shaoyang , Liang Ting-bo 
Published: September 2023

Abstract
Background
Septic shock is one of the leading causes of mortality in intensive care units. This retrospective study was carried out to evaluate the association of clinical available factors with 28-day mortality.

Patients and method
In this observational study, patients with perioperative septic shocks secondary to intra-abdominal infection caused by enteric perforation were included. A total of 328 sepsis patients were admitted to the surgical intensive care units from January 2012 to December 2016. A total of 138 patients met the enrolment criteria and were included in the study. The data of demographic, clinical and laboratory were all recorded.

Result
All these 138 patients received abdominal surgery prior to surgical intensive care units caused by acute enteric perforation. These patients were all met the diagnostic criteria of septic shock according to Sepsis-3. Statistical analysis showed that lactic acid, blood platelet, fibrinogen, creatinine and activated partial thromboplastin time were found to be associated with 28-day mortality. A combination of serum activated partial thromboplastin time combined with fibrinogen and creatinine could predict in-hospital 28-day mortality. The area under the curve of serum activated partial thromboplastin time combined with fibrinogen and creatinine is 0.875 (0.806–0.944).

Conclusion
In conclusion, this pilot study demonstrated that these factors can predict the prognosis of septic shock caused by enteric perforation. In order to reduce the mortality, surgeons and intensive care units physician may consider these data in perioperative period.