bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of lncRNA Expression Pattern and Potential Role in Heart Failure Pathology
Authors: Chen Xiatian , Shi Chengzhen , Gao Jinning , Jumbo Juan Carlos Cueva , Wang Yin , Li Xin , Zhao Cheng , Yu Hua , Li Peifeng , Aung Lynn Htet Htet
Published: July 2023

During the last few decades, the morbidity and mortality of heart failure (HF) have remained on an upward trend. Despite the advances in therapeutic and diagnostic measures, there are still many aspects requiring further research. This study is aimed at finding potential long noncoding RNAs (lncRNAs) that could aid with the diagnosis and treatment of HF. We performed RNA sequencing on the peripheral blood of healthy controls as well as HF patients. The expression of lncRNAs was validated by RT-qPCR. Bioinformatic analysis was performed to investigate the possible mechanism of differentially expressed lncRNAs and mRNAs. The diagnostic value of lncRNAs was analysed by ROC analysis. Finally, a total of 207 mRNAs and 422 lncRNAs were identified. GO and KEGG pathway analyses revealed that biological pathways such as immune response, regulation of cell membrane, and transcriptional regulatory process were associated with the pathological progress of HF. The lncRNA-mRNA coexpression network was conducted, and several mRNAs were identified as key potential pathological targets, while lncRNA CHST11, MIR29B2CHG, CR381653.1, and FP236383.2 presented a potential diagnostic value for HF. These findings provide novel insights for the underlying mechanisms and possible therapeutic targets for HF.
Monitoring of Tidal Variation and Temperature Change-Induced Movements of an Immersed Tunnel Using Distributed Optical Fiber Sensors (DOFSs)
Authors: Zhang Xuehui , Broere Wout
Published: July 2023

The short-term deformation behavior of immersed tunnels due to daily or monthly temperature changes and tidal variations is often not monitored but forms important input for a structural health assessment of the tunnel. In this study, distributed optical fiber sensors (DOFSs) are used to monitor the short-term (daily and monthly) deformation behavior of an immersed tunnel. Joint opening and the relative settlement differences between tunnel elements are monitored simultaneously at subhour intervals. Measurements show that the variation in the joint opening is strongly correlated with temperature change, and the joint gap has a tendency to open at low temperatures and to close at increasing temperatures. Simultaneously, the entire immersed section behaves more like a rigid body and moves upwards and downwards periodically due to tidal fluctuations in the river, with an observed vertical movement of slightly less than one millimeter. The tide also causes local tilting of tunnel segments, and this tilting behavior differs between winter and summer, which implies that the (seasonal) temperature-induced joint deformations affect the robustness of the tunnel to tidal loads. A soil-tunnel structure interaction analysis reveals that the cyclic vertical movement of the tunnel is driven by retardation of the tidal wave in deeper soil layers, which can be captured by a coupled flow model. This study provides new insights into the short-term deformation behavior of immersed tunnels.
Different Scenarios for Reducing Carbon Emissions, Optimal Sizing, and Design of a Stand-Alone Hybrid Renewable Energy System for Irrigation Purposes
Authors: Al-Rawashdeh Hani , Al-Khashman Omar Ali , Arrfou Laith M. , Gomaa Mohamed R. , Rezk Hegazy , Shalby Mohammad , Al Bdour Jehad T. , Louzazni Mohamed
Published: July 2023

Irrigation systems to supply water to agricultural land are essential in remote and isolated areas. However, these areas often face challenges and obstacles in obtaining energy for use in irrigation since many depend on diesel generators (DGs) to produce electricity. A farm located in a remote area in Al-Jafr, Jordan, uses a 100 kW DG to supply its need for electric energy for irrigation purposes. Its energy consumption is 500 kWh/day at $0.29/kWh. This paper designs a new hybrid renewable energy system (HRES) for this farm by conducting simulations using the HOMER (Hybrid Optimization of Multiple Energy Resources) software. This new system consists of solar photovoltaics (PVs), batteries, an inverter, and a 100 kW DG. The results showed a clear difference between the baseline DG-only system and the hybrid system regarding energy cost and carbon emissions. The energy price for the HRES is $0.107/kWh, and carbon dioxide emissions are reduced to 27,378 kg/yr from 184,917 kg/yr for the DG-only system. In addition, simulations and comparisons for an alternative HRES with a 60 kW DG were conducted. Based on the simulation results, the energy price was $0.091 instead of $0.19, and carbon dioxide (CO2) emissions were 15,847 kg/yr instead of 115,090 kg/yr. It was concluded that using hybrid renewable energy systems to power the irrigation of remote areas successfully reduced the energy cost, fuel consumption, emissions, and overall cost. The HOMER program makes an accurate comparison over extended periods between the four strategies (load following, cycle charging, combined dispatch, and predictive dispatch) and selects the optimal system based on the cost, emissions, fuel consumption, and percentage of renewable energy from the system.
Sustainable Flue Gas Treatment System Assessment for Iron and Steel Sector: Spherical Fuzzy MCDM-Based Innovative Multistage Approach
Authors: Abdel-Basset Mohamed , Gamal Abduallah , Sallam Karam M. , Hezam Ibrahim M. , Alshamrani Ahmad M.
Published: July 2023

The emission crisis in the iron and steel sector prompted the search for modern systems that contribute to reducing the resulting emissions to alleviate the growing concerns about global warming. This research evaluates four flue gas treatment systems in the iron and steel sector through a case study in Egypt. A comprehensive approach is presented through which experts can use linguistic terms and their corresponding spherical fuzzy numbers (SFNs) to express their views on identifying aspects and indicators that affect the sustainability of flue gas treatment systems. Also, determining the optimal system for dealing with emissions is a necessary task, which requires consideration of many aspects of sustainability, including economic, environmental, and technological aspects and their subindicators. This paper presents a new hybrid approach to multicriteria decision-making (MCDM) under a spherical fuzzy (SF) environment that takes into account several incompatible indicators. The SF-CRiteria Importance through Intercriteria Correlation (SF-CRITIC) has been used to assess and prioritize the main aspects and subindicators. The SF-COmbinative Distance-based ASsessment (SF-CODAS) has been applied to evaluate and rank the selected systems. A sensitivity analysis has been implemented to confirm the effectiveness of the recommended hybrid approach and the stability of its results by changing the weights of the indicators used. Also, a comparative analysis has been fulfilled with MARCOS and WASPAS methods under an SF environment to validate the proposed approach. The findings show that the environmental aspect is the highest evaluated with a weight of 0.431, followed by the technological aspect with a weight of 0.326, and they are the basis for enhancing the sustainability of low-emission systems in the iron and steel sector. Furthermore, the conclusions advise optimizing low-emission systems for sintering flue gas in the iron and steel sector to improve sustainability.
Epidemiology and Evolutionary Dynamics of High Pathogenicity Avian Influenza (HPAI) H5N1 in Bangladesh
Authors: Islam Ariful , Ara Tasnim , Amin Emama , Islam Shariful , Sayeed Md. Abu , Shirin Tahmina , Hassan Mohammad Mahmudul , Klaassen Marcel , Epstein Jonathan H.
Published: July 2023

Understanding disease clustering and transmission patterns improves the prevention and control of disease. Herein, we described the epizootic characteristics and spatiotemporal dynamics of High Pathogenicity Avian Influenza (HPAI) H5N1 outbreaks as well as clade diversity and phylodynamics of H5N1 over time and across host species in Bangladesh. We used Moran’s I, Geary’s C, Getis-Ord Gi∗, and a space-time permutation model to analyze the spatiotemporal patterns of H5N1 outbreaks. We used Bayesian phylogenetic analysis to generate a time-scaled maximum clade credibility (MCC) tree. Our study revealed nine HPAI H5N1 epizootic waves between 2007 and 2020 that invariably peaked in the wintertime. After vaccination of poultry against H5N1 was introduced in 2012, the incidence of HPAI H5N1 outbreaks and poultry mortality decreased significantly over time. Nonetheless, our research revealed that the virus continued circulating unabatedly in Bangladesh. The various spatiotemporal analyses were identified up to nine space-time clusters across Bangladesh, with the most significant clustering and hotspots of H5N1 outbreaks in and around the district of Dhaka. Since 2007, four H5N1 clades have been detected in Bangladesh, with only clade 2.3.2.1a continuing to circulate since 2011, which was followed up by the reassorted clade 2.3.2.1a in 2012. The HA gene of the H5N1 clade 2.3.2.1a has been reassorted into at least nine subgroups (R1–R9). After 2016, the first eight groups disappeared, with only the R9 group remaining. Spatiotemporal patterns and phylodynamics of H5N1 outbreaks are crucial for developing targeted and appropriate HPAI control and prevention measures. We recommended intensive monitoring of biosecurity measures and disease records in high-priority areas, along with assessing vaccine efficacy to better control HPAI outbreaks in Bangladesh.
Design of Miniaturized FSS with High Angular Stability Utilizing a Novel Closed Loop
Authors: Li Wei , Zhang Fengshuo , Suo Ying , Jiang Zhe , Qiu Jinghui
Published: July 2023

In this paper, we propose a miniaturized 2.5-dimensional (2.5D) frequency selective surface (FSS) structure with high angular stability. A novel closed-loop FSS is formed by combining the Jerusalem cross (JC) structure with the conventional rectangular closed loop using vias. This approach further enhances the coupling performance of the FSS and thus achieves miniaturized design. The unit cell size of the proposed FSS is 0.019λ0 × 0.019λ0 at the resonant frequency, and the metal is printed on a dielectric substrate with a thickness of 0.003λ0. The proposed FSS has a resonant frequency of 850 MHz and exhibits band-stop characteristics. It is insensitive to the incident angle with a good operating performance in both the TE and TM wave modes. Therefore, it can be well used as an electromagnetic shield for the GSM 850 band. In order to facilitate the rapid analysis and design of the FSS, the equivalent circuit model is further analyzed and established, and values of the corresponding lumped components are derived. In addition, a prototype FSS is fabricated using printed circuit board technology and is tested in a microwave anechoic chamber. The full-wave analysis simulation, equivalent circuit model simulation, and practical measurement results reflect a high level of consistency.
Edaravone Improves Streptozotocin-Induced Memory Impairment via Alleviation of Behavioral Dysfunction, Oxidative Stress, Inflammation, and Histopathological Parameters
Authors: Anoush Mahdieh , Bijani Soroush , Moslemifar Fatemeh , Jahanpour Fatemeh , Kalantari-Hesari Ali , Hosseini Mir-Jamal
Published: July 2023

Alzheimer’s disease (AD), as the main cause of dementia, has a progressive and neurodegenerative pattern with number of cases increasing over the next decades. Therefore, discovering an effective treatment with the ability to invert memory impairment and pathophysiological events of AD seems to be required. The present study performed to investigate the probable effects of Edaravone (EDV) in AD-like disorder induced by intracerebroventricular streptozotocin (ICV-STZ) administration in mice. This study also compares the two different methods of ICV-STZ in the memory impairment induction. NMRI male mice were administrated with 3 mg/kg of STZ for two times during 48 hours span, and after 24 hours, animals were treated with EDV (5 and 10 mg/kg), Donepezil, and Memantine for 14 days. After behavioral tests regarding memory and cognitive function, animals were sacrificed, and the hippocampi were utilized for further analyses. Our results demonstrated that administration of STZ induced memory impairment in the Morris water maze (MWM) test and decreased the discriminative factor in novel object recognition (NOR). The biochemical output shows a significant decrease in ferric reducing antioxidant power (FRAP) and glutathione (GSH) levels followed by increase in malondialdehyde (MDA) and protein carbonylation (PCO) levels. The output showed no difference between the patterns of AD-like disorder induction. Following our treatment groups, administration of EDV (5 and 10 mg/kg), Donepezil, and Memantine significantly improved memory performance and discriminatory behavior. Aforementioned treatments managed to improve FRAP and GSH content of hippocampus, while significantly attenuating MDA, PCO, and nitric oxide overproduction. In addition, no significant difference has been observed between the effect of 5 and 10 mg/kg EDV application. It was supposed that EDV managed to ameliorate memory dysfunction, discriminatory behavior, oxidative stress, and cellular antioxidant power in a dose-independent pattern in mice.
Supplementary Figure 2 from Sources of Disparities in Surveillance Mammography Performance and Risk-Guided Recommendations for Supplemental Breast Imaging: A Simulation Study
Authors: Hubbard Rebecca A. , Pujol Toyya A. , Alhajjar Elie , Edoh Kossi , Martin Melissa L.
Published: July 2023

Supplementary Figure 2. Simulation results for surveillance mammography cancer detection rates overall and stratified by race and ethnicity in simulated populations of women with a personal history of breast cancer
Supplementary Table S3 from Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization
Authors: King Sontoria D. , Veliginti Swathi , Brouwers Martijn C.G.J. , Ren Zhewen , Zheng Wei , Setiawan Veronica W. , Wilkens Lynne R. , Shu Xiao-Ou , Arslan Alan A. , Beane Freeman Laura E. , Bracci Paige M. , Canzian Federico , Du Mengmeng , Gallinger Steven J. , Giles Graham G. , Goodman Phyllis J. , Haiman Christopher A. , Kogevinas Manolis , Kooperberg Charles , LeMarchand Loic , Neale Rachel E. , Visvanathan Kala , White Emily , Albanes Demetrius , Andreotti Gabriella , Babic Ana , Berndt Sonja I. , Brais Lauren K. , Brennan Paul , Buring Julie E. , Rabe Kari G. , Bamlet William R. , Chanock Stephen J. , Fuchs Charles S. , Gaziano J. Michael , Giovannucci Edward L. , Hackert Thilo , Hassan Manal M. , Katzke Verena , Kurtz Robert C. , Lee I.-Min , Malats Núria , Murphy Neil , Oberg Ann L. , Orlow Irene , Porta Miquel , Real Francisco X. , Rothman Nathaniel , Sesso Howard D. , Silverman Debra T. , Thompson Ian M. , Wactawski-Wende Jean , Wang Xiaoliang , Wentzensen Nicolas , Yu Herbert , Zeleniuch-Jacquotte Anne , Yu Kai , Wolpin Brian M. , Duell Eric J. , Li Donghui , Hung Rayjean J. , Perdomo Sandra , McCullough Marjorie L. , Freedman Neal D. , Patel Alpa V. , Peters Ulrike , Riboli Elio , Sund Malin , Tjønneland Anne , Zhong Jun , Van Den Eeden Stephen K. , Kraft Peter , Risch Harvey A. , Amundadottir Laufey T. , Klein Alison P. , Stolzenberg-Solomon Rachael Z. , Antwi Samuel O.
Published: July 2023

Supplementary Table S3 shows results of univariate analysis for 36 biopsy-confirmed nonalcoholic fatty liver disease SNPs in the PanScan sample
Data from Association Between Sleep Duration and Colorectal Adenomas: Findings from a Case-Control Study in Vietnam
Authors: Tran Chi Thi-Du. , Paragomi Pedram , Tran Mo Thi. , Nguyen Mai Vu-Tuyet. , Tuong Thuy Thi-Van. , Tran Quang Hong. , Le Linh Cu. , Pham Huong Thi-Thu. , Ha Hien Thi-Thu. , Bui Nam Chi. , Vu Hien Huy. , Ta Phuong Que. , Shrubsole Martha J. , Cai Qiuyin , Ye Fei , Le Song Huu. , Vu Khien Van. , Tran Huong TT. , Tran Thuan V. , Boffetta Paolo , Shu Xiao-Ou , Luu Hung N.
Published: July 2023

Abstract
Background. Colorectal cancer (CRC) is one of the leading cancers worldwide and in Vietnam. Adenomas are important precursors of CRC. Study on the association between sleep duration and development of colorectal adenoma (CRA) is limited, particularly among Vietnamese population.
Methods. We conducted an individually matched case-control study of 870 CRA cases and 870 controls in a large-scale colorectal screening program involving 103,542 individuals aged ≥40 years old in Hanoi, Vietnam. Sleep duration was categorized in three groups: short: <6 hours/day, normal: 7-8 hours/day, and long: >8 hours/day. Conditional logistic regression was used to evaluate the association between sleep duration and adenomas risk after controlling for potential confounders.
Results. Overall, short-sleep duration was associated with increased risk of having CRA compared to normal duration (Odds Ratio-OR=1.48, 95% confidence interval-CI: 1.12-1.97). This pattern was present in both females (OR=1.58, 95% CI: 1.14-2.18) and males (OR=1.45, 95% CI: 1.08-1.93), with advanced adenomas (OR=1.61, 95% CI: 1.09-2.38) and non-advanced adenomas (OR=1.66, 95% CI: 1.19-2.32). Furthermore, the association between CRA development and short sleep duration was more apparent among females who were non-drinker, non-obese, physically active, with proximal or both sided adenomas and with cardiometabolic disorder. Among males, the short sleep duration was associated with CRA risk among never-smoking, cardiometabolic disorders and obese.
Conclusions. Short sleep duration was associated with increased prevalence of both advanced and non-advanced CRAs among Vietnamese population.
Impact. Findings from the current study showed that maintaining an adequate sleep duration may have an important implication for CRC prevention and control.
Data from Elevated EVL methylation level in the normal colon mucosa is a potential risk biomarker for developing recurrent adenomas
Authors: Yu Ming , Carter Kelly T. , Baker Kelsey K. , Redman Mary W. , Wang Ting , Vickers Kathy , Li Christopher I. , Cohen Stacey A. , Krane Mukta , Ose Jennifer , Gigic Biljana , Figueiredo Jane C. , Toriola Adetunji T. , Siegel Erin M. , Shibata David , Schneider Martin , Ulrich Cornelia M. , Dzubinski Lynda Ann. , Schoen Robert E. , Grady William M.
Published: July 2023

Abstract
Background: Individuals with adenomatous colorectal polyps undergo repeated
colonoscopy surveillance to identify and remove metachronous adenomas. However, many patients with adenomas do not develop recurrent adenomas. Better methods to evaluate who benefits from increased surveillance are needed. We evaluated the use of altered EVL methylation as a potential biomarker for risk of recurrent adenomas.
Methods: Patients with ≥1 colonoscopy had EVL methylation (mEVL) measured with an ultra-accurate methylation-specific droplet digital PCR assay on normal colon mucosa. The association between EVL methylation levels and adenoma or colorectal cancer (CRC) was evaluated using three case/control definitions in three models: unadjusted (model 1), adjusting for baseline characteristics (model 2), and an adjusted model excluding patients with CRC at baseline (model 3).
Results: Between 2001 and 2020, 136 patients were included; 74 healthy patients and 62 patients with a history of CRC. Older age, never smoking and baseline CRC were associated with higher levels of mEVL (p≤0.05). Each log10 difference in mEVL was associated with an increased risk of adenoma(s) or cancer at/after baseline for model 1(OR: 2.64 95% CI: 1.09-6.36), and adenoma(s) or cancer after baseline for models 1(OR: 2.01, 95% CI: 1.04-3.90) and model 2 (OR: 3.17, 95% CI: 1.30-7.72).
Conclusion: Our results suggest that EVL methylation level detected in the normal colon mucosa has the potential to be a biomarker for monitoring the risk for recurrent adenomas.
Impact: These findings support the potential utility of EVL methylation for improving the accuracy for assigning risk for recurrent colorectal adenomas and cancer.
Data from Sources of disparities in surveillance mammography performance and risk-guided recommendations for supplemental breast imaging: A simulation study
Authors: Hubbard Rebecca A. , Pujol Toyya A. , Alhajjar Elie , Edoh Kossi , Martin Melissa L.
Published: July 2023

Abstract
Background: Surveillance mammography is recommended for all women with a history of breast cancer.

Risk-guided surveillance incorporating advanced imaging modalities based on individual risk of a second cancer could improve cancer detection. However, personalized surveillance may also amplify disparities.

Methods: In simulated populations using inputs from the Breast Cancer Surveillance Consortium (BCSC), we investigated race- and ethnicity-based disparities. Disparities were decomposed into those due to primary breast cancer and treatment characteristics, social determinants of health (SDOH) and differential error in second cancer ascertainment by modeling populations with or without variation across race and ethnicity in the distribution of these characteristics. We estimated effects of disparities on mammography performance and supplemental imaging recommendations stratified by race and ethnicity.

Results: In simulated cohorts based on 65,446 BCSC surveillance mammograms, when only cancer characteristics varied by race and ethnicity, mammograms for Black women had lower sensitivity compared to the overall population (64.1% vs 71.1%). Differences between Black women and the overall population were larger when both cancer characteristics and SDOH varied by race and ethnicity (53.8% vs 71.1%). Basing supplemental imaging recommendations on high predicted second cancer risk resulted in less frequent recommendations for Hispanic (6.7%) and Asian/Pacific Islander women (6.4%) compared to the overall population (10.0%).

Conclusions: Variation in cancer characteristics and SDOH led to disparities in surveillance mammography performance and recommendations for supplemental imaging.

Impact: Risk-guided surveillance imaging may exacerbate disparities. Decision-makers should consider implications for equity in cancer outcomes resulting from implementing risk-guided screening programs.
Data from Development of a breast cancer risk prediction model incorporating polygenic risk scores and non-genetic risk factors for Korean women
Authors: Choi Jihye , Ha Tae-woong , Choi Hye-Mi , Lee Han-Byoel , Shin Hee-Chul , Chung Woosung , Han Wonshik
Published: July 2023

Abstract
Background:To develop a breast cancer prediction model for Korean women using published polygenic risk scores (PRSs) combined with non-genetic risk factors (NGRFs).

Methods:Thirteen PRS models generated from single or multiple combinations of the Asian and European PRSs were evaluated among 20,434 Korean women. The area under the curve (AUC) and increase in odds ratio (OR) per standard deviation (SD) were compared for each PRS. The PRSs with the highest predictive power were combined with NGRFs; then, an integrated prediction model was established using the iCARE tool. The absolute breast cancer risk was stratified for 18,142 women with available follow-up data.

Results:PRS38_ASN+PRS190_EB, a combination of Asian and European PRSs, had the highest AUC (0.621) among PRSs, with an OR per SD increase of 1.45 (95% CI: 1.31-1.61). Compared with the average risk group (35-65%), women in the top 5% had a 2.5-fold higher risk of breast cancer. Incorporating NGRFs yielded a modest increase in the AUC of women aged >50 years. For PRS38_ASN+PRS190_EB+NGRF, the average absolute risk was 5.06%. The lifetime absolute risk at age 80 years for women in the top 5% was 9.93%, whereas that of women in the lowest 5% was 2.22%. Women at higher risks were more sensitive to NGRF incorporation.

Conclusions:Combined Asian and European PRSs were predictive of breast cancer in Korean women. Our findings support the use of these models for personalized screening and prevention of breast cancer.

Impact:Our study provides insights into genetic susceptibility and NGRFs for predicting breast cancer in Korean women.
Data from Diabetes and prostate cancer outcomes in men with nonmetastatic castrate-resistant prostate cancer: Results from the SEARCH Cohort
Authors: Sergeyev Andrei , Gu Lin , De Hoedt Amanda M. , Amling Christopher L. , Aronson William J. , Cooperberg Matthew R. , Kane Christopher J. , Klaassen Zachary , Terris Martha K. , Guerrios-Rivera Lourdes , Freedland Stephen J. , Csizmadi Ilona
Published: July 2023

Abstract
Background: The prognosis of diabetic men with advanced prostate cancer (PC) is poorly understood and understudied. Hence, we studied associations between diabetes and progression to metastases, PC-specific mortality (PCSM) and all-cause mortality (ACM) in men with non-metastatic castrate-resistant PC (nmCRPC).
Methods: Data from men diagnosed with nmCRPC between 2000 and 2017 at 8 Veterans Affairs Health Care Centers were analyzed using Cox regression to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between diabetes and outcomes. Men with diabetes were classified according to (i) ICD-9/10 codes only, (ii) two HbA1c values > 6.4% (missing ICD-9/10 codes), and (iii) all diabetic men ((i) and (ii) combined).
Results: Of 976 men (median age: 76 years), 304 (31%) had diabetes at nmCRPC diagnosis, of whom 51% had ICD-9/10 codes. During a median follow-up of 6.5 years, 613 men were diagnosed with metastases, and 482 PCSM and 741 ACM events occurred. In multivariable-adjusted models, ICD-9/10 code-identified diabetes was inversely associated with PCSM (HR= 0.67; 95%CI: 0.48-0.92) while diabetes identified by high HbA1c values (no ICD-9/10 codes) was associated with an increase in ACM (HR=1.41; 95%CI: 1.16-1.72). Duration of diabetes, prior to CRPC diagnosis was inversely associated with PCSM among men identified by ICD-9/10 codes and/or HbA1c values (HR=0.93; 95%CI: 0.88-0.98).
Conclusion: In men with late-stage PC, ICD-9/10 code identified diabetes is associated with better overall survival than ‘undiagnosed’ diabetes identified by high HbA1c values only.
Impact: Our data suggest that better diabetes detection and management may improve survival in late-stage PC.
Data from Intake of Proton-Pump Inhibitors and Gastric Cancer Within the Stomach cancer Pooling (StoP) Project
Authors: Sassano Michele , Mariani Marco , Pelucchi Claudio , Lunet Nuno , Morais Samantha , Martín Vicente , Moreno Victor , Curado Maria Paula. , Dias-Neto Emmanuel , Leja Marcis , Gašenko Evita , La Vecchia Carlo , Boccia Stefania , Pastorino Roberta
Published: July 2023

Abstract
Background: A potential association between proton-pump inhibitors (PPIs) and gastric cancer (GC) remains undefined. Thus, we aimed to evaluate such association within the Stomach cancer Pooling (StoP) Project.

Methods: Data from five case-control studies of the StoP Project were included (1,889 cases, 6,517 controls). We assessed the impact of different exposure definitions, specifically any reported use of PPIs and exposure definitions based on the duration of PPI intake. Additionally, we modelled the dose-response relationship between cumulative duration of PPI intake and GC.

Results: Significant associations between PPI intake and GC, both overall and in the stratified analyses, were limited to exposure definitions based on short durations of intake. The overall OR for any reported PPI intake was 1.78 (95% CI: 0.76, 4.14). In the dose-response analysis, the ORs of GC were found to be higher for short durations of PPI intake (six months: OR 3.26 [95% CI: 2.40, 4.42], one year: OR 2.14 [95% CI: 1.69, 2.70], two years: OR 1.50 [95% CI: 1.22, 1.85], three years: OR 1.27 [95% CI: 1.03, 1.56]), with the association becoming not significant for durations longer than three years.

Conclusions: Our findings suggest that the observed association between PPIs and GC might be mainly due to reverse causality.

Impact: The results of this study suggest that PPIs are a safe therapeutic choice regarding their effect on the occurrence of GC.
Data from An Open-label Phase I Study of GDC-0927 in Postmenopausal Women with Locally Advanced or Metastatic Estrogen Receptor–Positive Breast Cancer
Authors: Chandarlapaty Sarat , Dickler Maura N. , Perez Fidalgo Jose Alejandro , Villanueva-Vázquez Rafael , Giltnane Jennifer , Gates Mary , Chang Ching-Wei , Cheeti Sravanthi , Fredrickson Jill , Wang Xiaojing , Collier Ann , Moore Heather M. , Metcalfe Ciara , Lauchle Jennifer , Humke Eric W. , Bardia Aditya
Published: July 2023

AbstractPurpose:
GDC-0927 is a novel, potent, nonsteroidal, orally bioavailable, selective estrogen receptor (ER) degrader that induces tumor regression in ER+ breast cancer xenograft models.
Patients and Methods:
This phase I dose-escalation multicenter study enrolled postmenopausal women with ER+/HER2− metastatic breast cancer to determine the safety, pharmacokinetics, and recommended phase II dose of GDC-0927. Pharmacodynamics was assessed with [18F]-fluoroestradiol (FES) PET scans.
Results:
Forty-two patients received GDC-0927 once daily. The MTD was not reached. The most common adverse events (AE) regardless of causality were nausea, constipation, diarrhea, arthralgia, fatigue, hot flush, back pain, and vomiting. There were no deaths, grade 4/5 AEs, or treatment-related serious AEs. Two patients experienced grade 2 AEs of special interest of deep vein thrombosis and jugular vein thrombosis, both considered unrelated to GDC-0927. Following dosing, approximately 1.6-fold accumulation was observed, consistent with the observed half-life and dosing frequency. There were no complete or partial responses. Pharmacodynamics was supported by >90% reduction in FES uptake and an approximately 40% reduction in ER expression, suggesting ER degradation is not the mechanistic driver of ER antagonism. Twelve patients (29%) achieved clinical benefit; 17 patients (41%) showed a confirmed best overall response of stable disease. Baseline levels of ER and progesterone receptor protein and mutant ESR1 circulating tumor DNA did not correlate with clinical benefit.
Conclusions:
GDC-0927 appeared to be well tolerated with pharmacokinetics supporting once-daily dosing. There was evidence of target engagement and preliminary evidence of antitumor activity in heavily pretreated patients with advanced/metastatic ER+/HER2− breast cancer with and without ESR1 mutations.
Data from Targeting the ATF6-mediated ER stress response and autophagy blocks integrin-driven prostate cancer progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: July 2023

Abstract
Prostate cancer (PCa) progression to the lethal metastatic castration-resistant phenotype (mCRPC) is driven by αv integrins and is associated with Golgi disorganization and activation of the ATF6 branch of unfolded protein response (UPR). Overexpression of integrins requires N-acetylglucosaminyltransferase-V (MGAT5)-mediated glycosylation and subsequent cluster formation with Galectin-3 (Gal-3). However, the mechanism underlying this altered glycosylation is missing. For the first time, using HALO analysis of immunohistochemistry, we found a strong association of Integrin αv and Gal-3 at the plasma membrane (PM) in primary PCa and mCRPC samples. We discovered that MGAT5 activation is caused by Golgi fragmentation and mislocalization of its competitor, N-acetylglucosaminyltransferase-III, MGAT3, from Golgi to the endoplasmic reticulum (ER). This was validated in an ethanol-induced model of ER stress, where alcohol treatment in androgen-refractory PC-3 and DU145 cells or alcohol consumption in PCa patient samples aggravates Golgi scattering, activates MGAT5, and enhances integrin expression at PM. This explains known link between alcohol consumption and PCa mortality. ATF6 depletion significantly blocks UPR and reduces the number of Golgi fragments in both PC-3 and DU145 cells. Inhibition of autophagy by hydroxychloroquine (HCQ) restores compact Golgi, rescues MGAT3 intra-Golgi localization, blocks glycan modification via MGAT5, and abrogates delivery of Gal-3 to the cell surface. Importantly, the loss of Gal-3 leads to reduced integrins at PM and their accelerated internalization. ATF6 depletion and HCQ treatment synergistically decrease Integrin αv and Gal-3 expression and temper orthotopic tumor growth and metastasis.

Implications: Combined ablation of ATF6 and autophagy can serve as new mCRPC therapeutic.
Data from Targeting c-Jun is a potential therapy for luminal breast cancer bone metastasis
Authors: Han Yuxuan , Katayama Shota , Futakuchi Mitsuru , Nakamichi Kazuya , Wakabayashi Yutaro , Sakamoto Mai , Nakayama Jun , Semba Kentaro
Published: July 2023

Abstract
Luminal breast cancer has the highest bone metastasis frequency among all breast cancer subtypes; however, its metastatic mechanism has not been elucidated because of a lack of appropriate models. We have previously developed useful bone metastatic cell lines of luminal breast cancer using MCF7 cells. In this study, we characterized bone metastatic MCF7-BM cell lines and identified c-Jun as a novel bone metastasis marker of luminal breast cancer. The protein level of c-Jun was upregulated in MCF7-BM cells compared with that in parental cells, and its deficiency resulted in the suppression of tumor cell migration, transformation, and reduced osteolytic ability. In vivo, dominant-negative c-Jun exhibited smaller bone metastatic lesions and a lower metastatic frequency. Histological analysis revealed that c-Jun expression was heterogeneous in bone metastatic lesions, whereas c-Jun overexpression mediated a vicious cycle between MCF7-BM cells and osteoclasts by enhancing calcium-induced migration and releasing the osteoclast activator BMP5. Pharmacological inhibition of c-Jun by the Jun amino-terminal kinase (JNK) inhibitor JNK-IN-8 effectively suppressed tumorigenesis and bone metastasis in MCF7-BM cells. Furthermore, c-Jun downstream signals were specifically correlated with the clinical prognosis of patients with the luminal subtype of breast cancer. Our results illustrate the potential benefits of a therapy that targets c-Jun to prevent bone metastasis in luminal breast cancer.

Implications: c-Jun expression mediates bone metastasis in luminal breast cancer by forming a vicious cycle in the bone microenvironment, which reveals potential strategies for subtype-specific bone metastasis therapy.
Data from Targeting c-Jun Is a Potential Therapy for Luminal Breast Cancer Bone Metastasis
Authors: Han Yuxuan , Katayama Shota , Futakuchi Mitsuru , Nakamichi Kazuya , Wakabayashi Yutaro , Sakamoto Mai , Nakayama Jun , Semba Kentaro
Published: July 2023

Abstract
Luminal breast cancer has the highest bone metastasis frequency among all breast cancer subtypes; however, its metastatic mechanism has not been elucidated because of a lack of appropriate models. We have previously developed useful bone metastatic cell lines of luminal breast cancer using MCF7 cells. In this study, we characterized bone metastatic MCF7-BM cell lines and identified c-Jun as a novel bone metastasis marker of luminal breast cancer. The protein level of c-Jun was upregulated in MCF7-BM cells compared with that in parental cells, and its deficiency resulted in the suppression of tumor cell migration, transformation, and reduced osteolytic ability. In vivo, dominant-negative c-Jun exhibited smaller bone metastatic lesions and a lower metastatic frequency. Histologic analysis revealed that c-Jun expression was heterogeneous in bone metastatic lesions, whereas c-Jun overexpression mediated a vicious cycle between MCF7-BM cells and osteoclasts by enhancing calcium-induced migration and releasing the osteoclast activator BMP5. Pharmacological inhibition of c-Jun by the Jun amino-terminal kinase (JNK) inhibitor JNK-IN-8 effectively suppressed tumorigenesis and bone metastasis in MCF7-BM cells. Furthermore, c-Jun downstream signals were specifically correlated with the clinical prognosis of patients with the luminal subtype of breast cancer. Our results illustrate the potential benefits of a therapy that targets c-Jun to prevent bone metastasis in luminal breast cancer.
Implications:
c-Jun expression mediates bone metastasis in luminal breast cancer by forming a vicious cycle in the bone microenvironment, which reveals potential strategies for subtype-specific bone metastasis therapy.
Data from Simultaneous targeting of DNA polymerase theta and PARP1 or RAD52 triggers dual synthetic lethality in homologous recombination-deficient leukemia cells
Authors: Sullivan-Reed Katherine , Toma Monika M. , Drzewiecka Malgorzata , Nieborowska-Skorska Margaret , Nejati Reza , Karami Adam , Wasik Mariusz A. , Sliwinski Tomasz , Skorski Tomasz
Published: July 2023

Abstract
DNA polymerase theta (Poltheta, encoded by POLQ gene) plays an essential role in Poltheta-mediated end-joining (TMEJ) of DNA double-strand breaks (DSBs). Inhibition of Poltheta is synthetic lethal in homologous recombination (HR)-deficient tumor cells. However, DSBs can be also repaired by PARP1 and RAD52 -mediated mechanisms. Since leukemia cells accumulate spontaneous DSBs, we tested if simultaneous targeting of Pol and PARP1 or RAD52 enhance the synthetic lethal effect in HR-deficient leukemia cells. Transformation potential of the oncogenes inducing BRCA1/2-deficiency (BCR-ABL1 and AML1-ETO) was severely limited in Polq-/-;Parp1-/- and Polq-/-;Rad52-/- cells when compared to single knockouts, which was associated with accumulation of DSBs. Small molecule inhibitor of Poltheta (Polthetai) when combined with PARP or RAD52 inhibitors (PARPi, RAD52i) caused accumulation of DSBs and exerted increased effect against HR-deficient leukemia and myeloproliferative neoplasm cells.

Implications: In conclusion, we show that PARPi or RAD52i might improve therapeutic effect of Polthetai against HR-deficient leukemias.
ПОРІВНЯЛЬНИЙ АНАЛІЗ ОРГАНІЗАЦІЙНИХ ФОРМ І МОДЕЛЕЙ УПРАВЛІННЯ ІМУНІЗАЦІЄЮ НАСЕЛЕННЯ У СВІТІ ТА В УКРАЇНІ
Authors: Трущенкова Л. В. , Теренда Н. О. , Солтис І. С.
Published: July 2023

Мета: порівняти актуальні аспекти програм імунопрофілактики у світі та в Україні.

Матеріали і методи. Використано бібліографічний метод, методи системного підходу та системного аналізу при вивченні основних міжнародних та національних нормативно-правових актів щодо імунізації населення.

Результати. У більшості країн світу розроблені та працюють національні програми вакцинації за рахунок державних інвестицій. Стратегічний курс і політичні кроки в контексті вакцинації варіюють серед країн світу з різними внутрішніми процесами та результатами в кожній з них. Вони відображають різну епідеміологію, а також різницю в системах охорони здоров’я, рівень фактичних даних, які доводять необхідність вакцинації, сприйнятність вакцин у суспільстві та їх фінансування.

У світі існують різні підходи до збільшення прищеплення населення, застосовуються заходи різного характеру від заохочення тих, хто вакцинується, до покарання щеплень, що відмовляються. В Австралії, де імунізація є добровільною та безкоштовною, держава заохочує тих, хто отримав своєчасну вакцинацію, можливістю отримання різних пільг та допомоги, які недоступні для нещеплених громадян. У США вакцинація де-юре обов’язкова і наявність всіх щеплень є необхідною умовою для вступу в освітні та виховні установи. У Франції профілактичні щеплення від певних хвороб є обов’язковими (дифтерія, поліомієліт, правець), і за відмову передбачається покарання у вигляді штрафу або навіть ув’язнення до 6 місяців для людей, які перешкоджають проведенню вакцинації, в тому числі і для батьків. У Пакистані також можливий арешт за відмову вакцинуватися проти поліомієліту.

В Україні імунізація вакцинами в рамках національного календаря профілактичних щеплень проводиться населенню безкоштовно та на добровільній основі, передбачено і відмову від вакцинації.

Висновки. У різних країнах склалися різні моделі здійснення вакцинації, які зумовлені величиною охоплення профілактичними щепленнями, рівнем захворюваності, колективним імунітетом. Для України є актуальним питання перегляду норм Українського законодавства в галузі імунопрофілактики для забезпечення повноти охоплення щепленнями населення та посилення відповідальності громадян за відмови та несвоєчасність їх проведення.
Clinical Outcomes of Surgical Crown Reattachment as Treatment for Complicated Crown-Root Fractures: A Retrospective Study
Authors: Zhang Xin , Xue Liang , Zhou Weiwei , Zhang Lili , Gao Zhenhua , Wang Songlin
Published: July 2023

This retrospective study evaluated the clinical outcomes of surgical crown reattachment in the treatment of complicated crown-root fractures in permanent teeth in 35 patients. Treatments were defined as follows: surgical crown reattachment combined with internal fixation with a fiberreinforced core post, ostectomy, and reattachment of the original crown fragment. Patients were examined to record the periodontal pocket depth (PD), marginal bone loss, tooth migration, and coronal fragment looseness or loss. In most cases, the fracture lines on the palatal aspect were located below the alveolar crest. About 20% to 30% of teeth had periodontal pockets ≥ 3 mm present at least 1 year after surgery. Significant PD differences were observed between the traumatized teeth and adjacent untraumatized teeth at 6 months. The available evidence suggests that surgical crown reattachment is a feasible and effective technique for managing complicated crown-root fractures in permanent teeth.
Sharing the Knowledge at Habsburg Medical Faculties in the Baroque Era: The Case of Jan František Löw’s Reading List for Medical Students in Prague (1693)
Authors: Černý Karel
Published: July 2023

In 1693, professor Jan František Löw von Erlsfeld published a reading list for the students of medicine at Charles-Ferdinand University in Prague. The list records over 350 authorities from Aristotle to Johann Zwelfer and offers a unique insight into the structure of medicine and knowledge-sharing. It also points towards the fact that the Prague faculty was developing intellectual connections with other schools within the Habsburg domain. This paper will provide an analysis of the list, discuss the context in which it was created, and compare it with contemporary examples of the same genre from Copenhagen and Leiden. Additionally, it will explain how Prague university drew inspiration, first from Vienna and later from Innsbruck, to inform and modernize its medical curriculum during the Baroque period.
La Luce (1698) by Giovanni Michele Milani – A Final Attempt at Reconciling Atomism and Religion in Seventeenth-Century Rome?
Authors: Iovine Maria Fiammetta
Published: July 2023

In the poem La Luce, composed in 1685 and dedicated to Christina of Sweden, Giovanni Michele Milani propounds a mechanical and vitalist (meta-)physics of light that complies with Christian tenets by adopting a peculiar version of Democritean atomism. His lecture for the Roman Simposiaci Academy indicates the extent of Milani’s dissatisfaction with Aristotelian philosophy. While he attended the Physico-mathematical Academy and the heterodox Congresso medico romano, he nevertheless, signed La Luce – published posthumously in 1698 with a preface by Francesco Redi – as “Accademico Umorista.” When we examine La Luce together with some excerpts of the unpublished work of Milani’s friend and fellow member of this literary institution – the Dialoghi eruditi by Giuseppe Giusto Guaccimanni – we are presented with an interesting cultural scenario. It would seem that some Umoristi might have joined the Queen in the effort to devise a Christian experimental philosophy which was open to alchemy. The posthumous publication of the poem may well have been triggered by the rivalry between the Umoristi and the Academy of the Arcadia.
Aesthetics, Culture, Dialogue
Authors: Patella Giuseppe
Published: July 2023

What is the relevance of organizing knowledge in distinct conceptual fields when everything has become cultural with no distinct areas anymore? Is, for example, Western traditional aesthetics as an autonomous cognitive discipline always relevant in the age of multiculturalism? This essay argues, albeit controversially, that the perspective of socalled cultural studies has opened new doors by adopting a more radically pluralistic and inclusive approach – one whereby aesthetic categories are thought in terms of cultural practices. Despite the many defects of such culture-related studies – such as their eclecticism, lack of scientific rigor, or methodological unreliability – the challenges of today’s multicultural society demand that we pay more attention at all levels to the roles played by difference and dialogue with otherness. This includes overcoming any form of ethnocentricity in our cognitive cultural disciplines; incorporating new topical horizons, whether economic, political or social; and rethinking the very nature of value, meaning and way of life.
Karadenizia, a new monospecific pachyiuline genus (Diplopoda: Julida: Julidae) from Turkey
Authors: ANTIĆ DRAGAN
Published: July 2023

The present paper is dedicated to the description of the monospecific pachyiuline genus Karadenizia gen. nov. with the type species K. merti sp. nov. from Erçek Cave near the southern coast of the Black Sea in Turkey. In addition to the diagnosis and detailed description, brief notes on the locality and known ecology of this taxon are given. The relationship of this genus with some other pachyiulines is discussed based on the structure of the gonopods and some somatic features. The interesting colouration of the new taxon allows a brief discussion and hypothesis on the possible defensive role of such a colour pattern, which is also known in some other millipedes.