bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Analysis of Clinical Outcomes Between Neoadjuvant Chemoimmunotherapy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Retrospective Study
Authors: Yan Xue , Peng Ying , Mo Peng , Li Liuyu , Jiang Weijing , Zhang Wenzhen , Xu Yuanji , Su Miaoyi , Shen Yongshi , Fu Zhichao 
Published: January 2025

Abstract

Background
Patients with locally advanced esophageal squamous-cell carcinoma (LA-ESCC) generally experience poor prognosis after surgery. Neoadjuvant therapy has shown potential to improve survival outcomes. This study aimed to compare the long-term efficacy and safety of neoadjuvant chemoimmunotherapy (nCIT) versus neoadjuvant chemoradiotherapy (nCRT) in patients with LA-ESCC.
Methods
This multicenter study included patients with LA-ESCC treated at three hospitals in China between November 2015 and January 2024. Patients underwent either nCIT or nCRT followed by surgical resection. The primary endpoint was the 3-year overall survival (OS) rate. Secondary outcomes included objective response rate (ORR), pathologic complete response (pCR) rate, major pathologic response, disease-free survival (DFS), OS, and treatment-related adverse events. Propensity score matching was employed to adjust for baseline differences.
Results
A total of 225 LA-ESCC patients were included in this study, with 87 patients receiving nCRT and 138 patients receiving nCIT. After propensity score matching adjustment, each group have 87 patients included. The nCRT group demonstrated significantly superior outcomes to nCIT group in terms of ORR (85.06% vs. 45.98%, p < 0.001), T stage down rate (78.16% vs. 58.62%, p = 0.006), N stage down rate (85.06% vs. 45.98%, p < 0.001) and pCR rate (37.90% vs 14.90%, p < 0.001). The median follow-up duration was 44.5 months for the nCIT group and 35.1 months for the nCRT group. The nCIT group exhibited better 3-year OS (75.90% vs 55.60%, P < 0.05) andDFS (66.40% vs. 47.30%, P = 0.009) compared to the nCRT group. Subgroup analysis indicated that LA-ESCC patient with N + or non cT4 stage who received neoadjuvant chemoradiotherapy followed by esophagectomy had better OS and DFS. Univariate and multivariate Cox regression analyses identified clinical N stage as an independent prognostic factor for both OS and disease-free survival across both cohorts.
Conclusion
Neoadjuvant chemoimmunotherapy followed by esophagectomy is a promising treatment strategy for locally advanced resectable esophageal squamous cell carcinoma. nCRT may provide greater benefits in patients with N + or non-cT4 stage disease.
S100A9 Promotes Resistance to Anti-PD-1 Immunotherapy in Hepatocellular Carcinoma by Degrading PARP1 and Activating the STAT3/PD-L1 Pathway
Authors: Zhou Xianwei , Qiao Chu , Chu Xuehui , Man Haoran , Liu Jingxin , Li Yunzheng , Li Huan , Shan Xiaodong , Wang Weihong , Lian Zaowu , Lu Yanjun , Yu Decai , Sun Xitai , Li Binghua 
Published: January 2025

Abstract

Background
Immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 (PD-1) immunotherapy, have emerged as promising treatments for advanced hepatocellular carcinoma (HCC), significantly improving clinical outcomes. However, resistance to ICIs remains a major challenge, and the underlying mechanisms of this resistance are not yet fully understood. This study aimed to investigate the role of S100 calcium-binding protein A9 (S100A9) in mediating resistance to anti-PD-1 therapy.
Approach and Results:
We conducted RNA sequencing (RNA-seq) on tumor samples from anti-PD-1 responders and non-responders in HCC patients. Differential expression analysis identified S100A9 as a potential driver gene of resistance to anti-PD-1 therapy. Subcutaneous tumor models and an orthotopic HCC model established via hydrodynamic transfection were utilized to evaluate the impact of S100A9 on the efficacy of PD-1 therapy. Our findings revealed that S100A9 promotes resistance to anti-PD-1 therapy in HCC. Mechanistically, S100A9 directly interacted with PARP1 and induced its degradation via the ubiquitin-proteasome pathway. This process increased STAT3 phosphorylation at Tyr705, thereby enhancing PD-L1 transcription. Notably, treatment with the S100A9 inhibitor Tasquinimod significantly improved the efficacy of anti-PD-1 therapy in HCC.
Conclusions
Our study reveals that S100A9 facilitates immune evasion in HCC by enhancing PARP1 ubiquitination, STAT3 phosphorylation, and PD-L1 expression. Furthermore, combining S100A9 inhibitors with anti-PD-1 antibodies markedly enhances the therapeutic efficacy of ICIs in HCC. These findings highlight S100A9 as a potential therapeutic target for overcoming resistance to immunotherapy in HCC.
Nomogram Prediction Model on hospital mortality in patients after surgery with non-traumatic intracerebral hemorrhage: a retrospective analysis of the MIMIC-IV database
Authors: Wang Yu-Mei , Lu Jiaqi , Zhou Yi-Min , Tian Ying , Shi Guangzhi , Lv Yi 
Published: January 2025

Abstract

Background
The study aimed to investigate the association of clinical data in intensive care unit (ICU) with the hospital mortality, and constructed a prediction model on the prognosis in patients with non-traumatic intracerebral hemorrhage (ICH).
Methods
We extracted all clinical information in ICU of patients with non-traumatic ICH from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Logistic regression analysis was used to analyzing the risk factors. A nomogram for predicting the hospital mortality was constructed with R software and validated. Afterwards, the effectiveness and accuracy of the model were tested and evaluated.
Results
In the MIMIC IV database, 2004 patients with non-traumatic ICH were included in the study, with 1403 in training cohort and 601 in validation cohort. The mortality of hospital was 20.0% and 20.1% in the training and validation cohort, respectively. Age, Sequential Organ Failure Assessment Score (SOFA score), maximal mean blood pressure (Mbp), maximal temperature, glumbg and white blood cell count(WBC) were independent risk factors. The patients with higher glumbg and WBC were more likely to have poor prognosis (glumbg: p < 0.001, OR 1.018, 95% CI 1.010–1.025; WBC: p = 0.006, OR 1.057, 95% CI 1.016–1.099). The nomogram for predicting model exhibited a good performance and calibration. The AUC was 0.8022(0.7741–0.8303). The calibration curve indicated a satisfactory level of fit.
Conclusion
Non-traumatic ICH was associated with high rate of mortality (20%). The nomogram constructed in the study included age, SOFA score, maximal Mbp, maximal temperature, glumbg and WBC. Therefore, dynamic monitoring of these factors may be beneficial in assessing the risk and predicting the prognosis of the patients admitted to ICU with non-traumatic ICH.
Measurement Invariance of the CESD-R-10 Among Adolescents over the Transition from Paper to Online Administration
Authors: Gohari Mahmood R , Ferro Mark A. , Patte Karen , MacKillop James , Leatherdale Scott T 
Published: January 2025

Abstract

Despite the prevalence of online surveys, research validating paper-based scale measurement properties for online use is lacking. We assessed the measurement invariance of the 10-item CESD-R-10 scale in adolescents transitioning from paper to online administration. We analyzed 2-year linked data from 2,831 Canadian secondary school students during 2019/20 and 2020/21. Using structural equation modeling, we examined measurement invariance across configural, metric, scalar, and strict stages due to the COVID-19 pandemic shift to online surveys. Baseline mean depression score was 8.2 (SD = 5.9), with 33.7% (N = 953) reporting clinically relevant symptoms. We found measurement invariance between paper and online administration. The results support measurement invariance in males, while partial scalar invariance for females when thresholds of items 6 (I felt fearful) and item 9 (I felt lonely) are freely estimated between the two administrations. Our findings demonstrate that the CESD-R-10 remains invariant even with a shift in data collection mode from paper to online surveys. This study supports the validity of conducting meaningful comparisons of depression symptoms when changing the mode of data collection in survey research among adolescent samples.
Educação em saúde sobre complicações crônicas do Diabetes Mellitus
Authors: CRUZ Aline Ribeiro da , FONSECA Beatriz Gonçalves Barbosa da , GOMES Graziela Gama da Conceição , SODELLI Júlia Vinhati , COSTA Safira Pontes de Almeida , COSTA Sueli de Souza 
Published: January 2025

Ações de educação em saúde são fundamentais ao considerar-se a promoção de informação à população, no que diz respeito ao controle, prevenção e retardamento de questões inerentes às doenças presentes, como o Diabetes Mellitus (DM). Nesse sentido, o presente relato tem como objetivo descrever a experiência dos autores na elaboração e na efetivação de uma ação educativa realizada por meio de palestra, oferta de material informativo gratuito e criação de espaço para diálogo, sobre as complicações crônicas do DM, com foco na conscientização dos cidadãos presentes no local. A ação foi desenvolvida por meio da metodologia da problematização com o uso das cinco etapas do Arco de Maguerez. O planejamento desse evento ampliou a habilidade de interação com o público, além da capacitação da população acerca de medidas para melhora de hábitos de vida e identificação de sintomas, essenciais ao tema proposto, implicando no melhor prognóstico e na menor sobrecarga do sistema de saúde.
Design, Synthesis, Biological Evaluation and Docking Studies of 2-hydroxy-4-benzyloxy Chalcone Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease
Authors: Li Wei , Huang Jing , Chen Zhixin , Zhang Dan , He Lin , Guo Yan , Zhong Lei , Yang Chenwu , Yang Chunyan , Zeng Mei , Zhu Jiang , Cao Zhongcheng 
Published: January 2025

Objectives:
Alzheimer's disease (AD) is the most prevalent neurodegenerative
disorder, but no drugs can cure this disease. Chalcones possess good antioxidant activity,
anti-neuroinflammatory activity, neuroprotective effects, inhibitory effects on Aβ
aggregation, and Aβ disaggregation ability. Therefore, chalcones are ideal lead compounds,
and the discovery of novel anti-AD agent-based chalcones is necessary.

Methods:
Hydroxy groups and aryl benzyl ether groups were introduced into chalcone
scaffolds to obtain a series of 2-hydroxyl-4-benzyloxy chalcone derivatives. These derivatives
were further synthesized, biologically evaluated, and docked.

Results:
Most target derivatives exhibited good anti-AD activities. In particular, compound
11d had excellent inhibitory effects on self-induced Aβ1-42 aggregation (90.8% inhibition
rate at 25 μM) and Cu2+ induced Aβ1-42 aggregation (93.4% inhibition rate at 25
μM). In addition, it also exhibited good Aβ1-42 fibril disaggregation ability (64.7% at 25
μM), significant antioxidative activity (ORAC = 2.03 Trolox equivalent), moderate
MAO-B inhibition (IC50 = 4.81 μM), selective metal chelation, appropriate BBB permeation,
and dramatic anti-neuroinflammatory ability. In addition, compound 11d relieved
AD symptoms and protected hippocampal neurons in vivo.

Conclusion:
Compound 11d is a promising multifunctional anti-Aβ agent.
Combinatorial Synthesis of Tetrasubstituted Alkenes and Related Compounds with Potential Anticancer Activity
Authors: Nováčková Kateřina , Drož Ladislav , Kořínek Marek , Sedlák David , Bartůněk Petr , Eigner Václav , Havránek Miroslav 
Published: January 2025

Objective:
In search of efficient anticancer agents, we aimed at the design and synthesis
of a library of tetrasubstituted alkenes. These are structural analogues of tamoxifen, one of
the widely used anticancer therapeutics.

Methods:
Our small organic compound library was prepared via a chemical synthesis in the solution
using the Larock three-component coupling reaction, which is known to tolerate diverse
functional groups. Further, we have integrated this synthetic approach to four- and fivecomponent
alkene assembly by using Sonogashira coupling, A3 and AHA reactions. The final
products were isolated through preparative LC/MS station and characterized by NMR, MS, and
X-ray crystallography. The biological activity of all novel compounds was tested by luciferase
reporter assays against estrogen receptor (ER) and androgen receptor (AR).

Results and Discussion:
Our combinatorial synthetic approach was based on structurally diverse
internal alkynes, arylboronic acids and aryl halides. After experiment optimization a "one-pot"
single synthetic procedure was developed. This allowed us to prepare a small-sized screening library
of novel tetrasubstituted alkenes quickly and efficiently without laborious intermediate isolation.
In most cases, we isolated the final product as a single isomer, and in selected cases, we
confirmed their chemical structure via X-ray crystallography. High throughput screening of the
novel tetrasubstituted alkenes revealed a dozen hits with predominant agonistic ERα- and antagonistic
AR-activity in the micromolar range.

Conclusion:
The proposed combinatorial approach is applicable for the synthesis of diversified
organic compound libraries and for the discovery of new tamoxifen analogues with an improved
therapeutic profile.
Traditional Chinese Medicine for Liver Cancer Treatment: Network Pharmacology Research
Authors: Zheng Shihao , Gu Yixiao , Qi Wenying , Wang Wei , Li Xiaoke , Zao Xiaobin , Li Size , Liu Shaoyu , Xue Tianyu , Ye Yongan , Liu Aimin 
Published: January 2025

Background:
As one of the common malignant tumors nowadays, liver cancer has more
risk factors for its development and is characterized by a high recurrence rate, high mortality rate,
and poor prognosis, which poses a great threat to people's health. The specific efficacy of traditional
Chinese medicine is based on clinical practice, which is a high degree of generalization of
the characteristics and scope of the clinical effects of prescription medicines and a special form of
expression of the medical effects of the human body within the scope of traditional Chinese medicine.
Because of its multi-ingredient, multi-target, and multi-pathway characteristics, it has a great
advantage in the treatment of liver cancer. Still, at present, its specific molecular mechanism of
action has not yet been clarified.

Aim:
This study reviews the current status and characteristics of network pharmacology research
in the treatment of liver cancer, aiming to provide new ideas and methods for traditional Chinese
medicine treatment of the disease.

Methods:
This study was searched on the Web of Science and PubMed using keywords, such as
"traditional Chinese medicine", "liver cancer," and "network pharmacology." The citation dates of
the literature cited in this review are from 2000 to 2024.

Results:
The discovery of the key molecular mechanisms of traditional Chinese medicine in the
treatment of liver cancer through the network pharmacology approach and the in-depth study of
the related signaling pathways are conducive to a more in-depth exploration of traditional Chinese
medicine.

Conclusion:
Network pharmacology research plays a key role in the treatment and prevention of
liver cancer and deserves deeper exploration in the future.
Synthesis, Characterization, and Docking Studies of 1,4-dien as a Potential Impurity in Bimatoprost Drug
Authors: Guttikonda Nagarjuna Reddy , Venkatanarayana Muvvala , Haridasyam Sharath Babu 
Published: January 2025

Introduction:
Bimatoprost synthesis, novel diene impurity, Pd/C, Docking studies, IFD calculations, prostaglandin.

Methods:
This impurity was controlled by employing 30% Pd/C, and the impurity level was brought to the permissible level, i.e., 0.03% (ICH guidelines) in the final drug preparation of Bimatoprost.

Results:
Finally, induced-fit docking calculations were performed to theoretically evaluate the binding efficiencies of these inhibitors in the crystal structure of Prostaglandin F syn-thase (PGFS).

Conclusion:
There are negligible differences in RMSD and docking scores between the two ligands, which amount to only 0.18 Å and 0.313 kcal/mol, respectively. These findings strongly indicate that both ligands are likely to exhibit similar biological functions and effi-ciencies.
Trends in Total Antioxidant Status and Other Biochemical Parameters in Type 2 Diabetes Mellitus: A Case-control Study
Authors: Al-Salman Remah Salih , Al-Ahmad Mohammad M. , Alameri Hiba 
Published: January 2025

Objectives:
Owing to the existing evidence of the implication of oxidative stress in the
pathophysiology of type 2 diabetes mellitus (T2DM), the present study aims to investigate the correlation
of serum total antioxidant status (TAS) with comorbidities, various biochemical parameters,
and duration of T2DM. Various factors contributing to disease prevalence and trends in other
biochemical parameters are assessed.

Methods:
A retrospective observational study of 246 patients with T2DM whose data were retrieved
from the Proficiency Health Diagnostic Lab System in Al Ain. Data were analyzed using
the Statistical Package for the Social Sciences (SPSS) program.

Results:
The prevalence of T2DM was found to be higher in gender (male), age (≥45 years), ethnicity
(Middle Eastern), BMI (≥25), family history, and metabolic syndrome (hypertension and
dyslipidemia). TAS was found to be significantly higher in patients with comorbidities, than in
those without, particularly dyslipidemia and micro-albuminuria (p<0.05). TAS was weakly positively
correlated with various T2DM biochemical parameters (p<0.05), except for Fasting blood
glucose (FBG) (p=0.061). TAS was weakly negatively correlated with BMI (≥25) (p=0.042). Albumin-
to-creatinine ratio (ACR) was statistically higher in hypertensives than normotensives
(p=0.049). Duration of disease was only significantly correlated with ACR (r=0.325, p=0.001).
Uric acid levels were statistically higher in patients with microalbuminuria than in patients without
microalbuminuria (p=0.001).

Conclusion:
TAS was higher in patients with dyslipidemia and microalbuminuria, suggesting the
influence of other factors such as uric acid and lipid-lowering agents. TAS could be an important
factor in the management of T2DM cases. This needs to be further investigated in future studies to
fill the gap found in the literature.
Health Literacy and Numeracy in Self-monitoring of Capillary Glycemia: A Systematic Review of Mixed Methods
Authors: Medina Luis Angel Cendejas , Brandão Maria Girlane Sousa Albuquerque , Lima Glaubervania Alves , Zanetti Maria Lucia , Pace Ana Emília , Gallardo Maria del Pilar Serrano , Valverde Juana Mercedes Gutierrez , Oliveira Brena Shellem Bessa de , Lima Francisca Elisangela Teixeira , Teixeira Carla Regina de Souza 
Published: January 2025

Objective:
The aim of this study was to synthesize scientific evidence on the influence
of health literacy and numerical knowledge on self-monitoring of capillary blood glucose.

Methods:
Adhering to the PRISMA guidelines and the principles of the Joanna Briggs Institute, a
comprehensive search was conducted across multiple databases, including CINAHL, Cochrane,
Embase, LILACS, PubMed, Scopus, Web of Science, Google Scholar, OPENGREY, and
NDLTD. The review included studies published in any language that examined the relationship between
HL, numeracy, and SMBG.

Results:
A total of 12 studies met the inclusion criteria. These studies utilized various assessment
tools, such as the Brief Test of Functional Health Literacy in Adults (B-TOFHLA) and the Diabetes
Numeracy Test (DNT-15), to evaluate health literacy and numeracy levels. The findings revealed
a significant association between adequate HL and numeracy and improved SMBG practices.
Specifically, individuals with sufficient health literacy were more likely to monitor their
blood glucose levels regularly and make appropriate treatment adjustments based on their readings.

Conclusion:
The results indicated that numeracy skills and health literacy are critical determinants
of effective SMBG, influencing the frequency and accuracy of self-care practices in diabetes
management. These findings highlight the urgent need for educational interventions tailored to enhance
these skills, which could lead to improved health outcomes for individuals with diabetes.
Synthesis and Biological Evaluation of Cyclohexane-1,2,3,5-Tetrol Analogs as Potential Lead Candidates for Cancer Therapy
Authors: Jayaraj Sujaritha , K Hemalatha 
Published: January 2025

Introduction:
A preliminary biological evaluation of ten synthesized analogs, 5a-5j
{[5-(E)-benzylidene amino]-1,3,4-thiadiazol-2-yl} cyclohexane-1,2,3,5-tetrol, revealed promising
results, positioning these compounds as potential lead candidates for further optimization and
preclinical exploration in cancer therapy. Incorporating the 1,3,4-thiadiazol moiety into the structure
of the produced analogs considerably improved their anticancer activities, revealing the
compound's high potential for cancer treatment. Spectroscopic approaches and structural analysis,
such as elemental analysis, IR, ¹H NMR, ¹³C NMR, and MS, were crucial for properly establishing
the molecular structures of these analogs and evaluating their anticancer activity. These methodologies
laid a solid platform for rationally developing new anticancer medications with increased
efficacy and fewer adverse effects. Furthermore, computational tools like molecular
docking, ADMET prediction, and drug-likeness evaluation have accelerated the drug development
by finding the most promising lead candidates for preclinical and clinical trials. This technique
not only saves time and costs, but also raises the chances of producing successful anticancer
drugs.

Method:
The main aim of the current study is to develop, synthesize, in-silico, in-vitro potentials
of {5-[(E)-benzylidene amino]-1,3,4-thiadiazol-2-yl} cyclohexane-1,2,3,5-tetrol for a possible
anticancer drug to improve their efficiency and selectivity against cancer cells, computational
approaches aided in the rational design of these chemicals. Spectroscopic methods verified the
chemical structures of the target compounds. The structures show the presence of 1,3,4, thiadiazol
also responsible for anticancer activity. The 10 analogs were synthesized and showed encouraging
anticancer efficacy in preliminary biological evaluation, suggesting they might be suitable
lead candidates for more optimization and preclinical exploration

Results:
{5-[(E)-benzylidene amino]-1,3,4-thiadiazol-2-yl} cyclohexane-1,2,3,5-tetrol derivatives
5a-5j showed optimum IC50 values in invitro activity by SRB assay using MCF-7 as a strain, the
few selected analogs.

Conclusion:
The study synthesized cyclohexane-1,2,3,5-tetrol analogs and evaluated their potential
for cancer therapy. The compounds showed promising cytotoxic activity against various cancer
cell lines, with 5c, 5f, 5g, and 5j showing the most potent anti-proliferative effects. These
compounds induce apoptosis via mitochondrial dysfunction and cell cycle arrest. Further preclinical
investigations are needed to establish their therapeutic potential.