bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polypharmacy and potentially inappropriate medications in older adults who use long-term care services: A cross-sectional study
Authors: Hagiwara Shotaro , Komiyama Jun , Iwagami Masao , Hamada Shota , Komuro Masato , Kobayashi Hiroyuki , Tamiya Nanako 
Published: July 2024

Abstract

Background:
Older adults requiring care often have multiple morbidities that lead to polypharmacy, including the use of potentially inappropriate medications (PIMs), leading to increased medical costs and adverse drug effects. We conducted a cross-sectional study to clarify the actual state of drug prescriptions and the background of polypharmacy and PIMs.
Methods:
Using long-term care (LTC) and medical insurance claims data in the Ibaraki Prefecture from April 2018 to March 2019, we included individuals aged ≥ 65 who used LTC services. The number of drugs prescribed for ≥ 14 days and the number of PIMs were counted. A generalized linear model was used to analyze the association between the backgrounds of individuals and the number of drugs; logistic regression analysis was used for the presence of PIMs.
Results:
Herein, 67,531 older adults who received LTC services were included. The median number of total prescribed medications and PIMs was 7(IQR 5–9) and 1(IQR 0–1), respectively. The main PIMs were loop diuretics/aldosterone antagonists, benzodiazepines/similar hypnotics, and nonsteroidal anti-inflammatory drugs. Multivariate analysis revealed that the number of medications and presence of PIMs were significantly higher in patients with comorbidities and in those visiting multiple medical institutions. However, patients requiring care level ≧ 1, nursing home residents, users of short-stay service, and senior daycare were negatively associated with polypharmacy and PIMs.
Conclusions:
Polypharmacy and PIMs are frequently observed in older adults who require LTC. This was prominent among individuals with comorbidities and at multiple consulting institutions. Therefore, a nationwide cohort study is required.
Experimental research into the injectability of cement grouts in reef limestone
Authors: Tao Yuhang , Luo Yi , wei xiaoqing , Wang Jing , Li Xinping 
Published: July 2024

Abstract

Reef limestone has special pore structures, which makes its seepage characteristics remarkably different from those of conventional terrestrial tight rocks. In this article, the microscopic structure of reef limestone and the water–cement ratio (WCR), cement fineness, and an admixture on flocculated cement particles were studied. Meanwhile, the probability analysis was adopted to evaluate the injectability for reef limestone cement grouts. The results indicate that, as the density of reef limestone increases, the pore size gradually diminishes, the thickness of the wall for cemented walls increases little by little. Generally, reef limestone has many seepage channels, indicating strong grout injectivity; when the WCR is larger and the cement fineness is smaller, the number and the size of flocculated cement particles is smaller, so the injectivity of cement grout is improved; this may be enhanced further after use of an admixture. In summary, the volume fraction of flocculated cement particles in cement grouts, as well as the relative sizes of pores and flocculated cement particles, can affect the degree of grout injectability. Injectability results calculated using the theoretical formula based on these influencing factors are found to match those arising from cement-grouting experiments, verifying the practicability and reliability of the injectability probability formula.
Experimental Characterization of VHPC Reinforced with Short Synthetic Fibers
Authors: Romanazzi Vincenzo , Micelli Francesco , Moro Sandro , Ros Pedro Serna , Aiello Maria Antonietta 
Published: July 2024

Abstract

Very-High-Performance Concrete (VHPC) are defined as concrete capable of reaching compressive strength higher than 80 MPa. These performances can be reached thanks to its compact and extremely dense microstructure, as a result of a proper mix. Together with their great durability properties, these concretes may lead to reduce cross sections of structural elements and thus save material and built volumes. The addition of synthetic fibers allows to significantly increase the toughness and crack opening resistance, beyond the tensile strength. These benefits can easily be traduced in an improved durability of the VHPC concrete. the aim of this research activity is to enlarge the experimental database of high-performances concrete reinforced with synthetic fibers having different size. In fact, contrary to the case of steel fibers, few works are reported in literature regarding the types of fibers investigated herein. In the present work three Very High-Performance Fiber Reinforced Concrete (VHPFRC) mixes have been studied and characterized in laboratory. The mixes were realized with the same VHPC concrete matrix and different types of synthetic fibers: 10mm straight polyvinyl alcohol (PVA) fibers; 30mm waved polypropylene (PP) fibers; 40mm waved polypropylene (PP) fibers. The first mix was realized using PVA fibers only, the second with 30mm PP fibers and the last one was obtained by mixing PVA fibers and 40mm PP fibers. A further VHPC mix with no fibers has been also realized and tested as reference material. Compression tests on both cylindrical and cubic specimens and modulus of elasticity tests have been performed for each mix. The VHPFRC toughness have been determined by means of three-points bending tests according to EN 14651. The bending parameters obtained from the experimental test have been compared between all the mixes and an analysis of the fracture energy has been performed. Moreover, each mix has been tested at bending with four-points setup in order to verify the efficiency of this test type for VHPC reinforced with synthetic fiber. The results provided in the paper highlight the different effects, in terms of mechanical response, caused by fibers of different size at different cracking stages of the tested materials.
Preclinical to Clinical Translation of Antibody Drug Conjugates Using a Quantitative Systems Pharmacology (QSP) Model: A Case Study with Disitamab Vedotin
Authors: Li Qiaoning , Wang Ling , Wu Baiyang , Ma Xinting , Zhao Guorui , Liu Zhihao , Wang Juncheng , Liu Huifang , Jiang Jing 
Published: July 2024

Abstract

Background: The multiscale quantitative systems pharmacology (QSP) model, which includes biomolecule, cellular and tissue data, was used for the preclinical to clinical translation of ADC efficacy. Here, we validated the feasibility of the model using the marketed drug disitamab vedotin (DV).
Methods: Model integrated pharmacokinetics (PK), in vitro tumor cell disposition data and tumor growth inhibition (TGI) data were obtained. This mechanistically explains how the ADC exerted efficacy. Based on the in vivo efficacy data, which were obtained from studies conducted using two cell-derived xenograft models (NCI-N87 and SKOV3), a QSP model was established to characterize the efficacy, and the inherent sensitivity of the ADC between patient populations with different target expression levels was further simulated. For preclinical to clinical transitioning, human PK behavior was predicted with allometric scaling using the data of the monkeys’ PK parameters. Key parameters impacting the QSP model, such as TGI, tumor volume, and target expression level of tumors, were replaced with clinically relevant data to predict the effective dose of DV in patients. The clinically approved Q2W dosing intervals were used to simulate the effective dose. Results: After continuous administration of 1.5-2 mg/kg Q2W for five months, patients with HER2-2+ and HER2-3+ tumors achieved an objective response rate (ORR), but progressive disease was observed in HER2-1+ patients, which was consistent with clinically observed efficacy outcomes.
Conclusions: The model has promising applications in ADC screening, the optimization of clinical dosing regimens and other related areas.
Accuracy of Noninvasive Indices for Diagnosing Hepatic Steatosis Compared to Controlled Attenuated Parameter (CAP) in a Lebanese Cohort.
Authors: Daniel Fady , Malak Dima , Jaafar Rola , Ibrahim Mohamad Ali , Kanso Mariam , Khalife Mohammad , Kouzi Zakaria El 
Published: July 2024

Abstract

Background
Noninvasive liver indices are valuable tools to identify patients with NAFLD in view of their simplicity and relatively low cost.
Aims
This study examined the accuracy of several published indices, including hepatic steatosis index (HSI), Framingham steatosis index (FSI), and Dallas steatosis index (DSI) in predicting steatosis compared to Transient elastography controlled attenuation parameter (CAP).
Methods
This is a retrospective study on 720 patients who underwent Fibro scan at the American University of Beirut hepatobiliary unit between 2015 and 2020. Data on demographics, comorbidities, anthropometrics, laboratory studies were obtained. The following indices: HSI, FSI, DSI were calculated. Sensitivity, specificity and C -statistics of each index was determined and compared to CAP.
Results
Out of 550 patients who met inclusion criteria ,67% were found to have hepatic steatosis with average CAP 289.5(± 70.9). Mean age 50 (± 15.6) and 70% were male. Those patients were found to have higher BMI, and higher prevalence of diabetes and HTN as well as dyslipidemia than the control group with no steatosis. The FSI out-performed the other 2 indices with fair accuracy in detecting hepatic steatosis based on the C-statistics. HSI and DSI on the other hand showed poor discriminatory ability. AUC: FSI 0.77 95%CI (0.637–0.805), HSI 0.674 95%CI (0.577–0.771), DSI 0.651 95% CI (0.543–0.759). At the cut-off where specificity was 90%, the FSI Had highest sensitivity 49.6% compared to DSI 28.6% and HSI 21.8%.
Conclusion
Our study demonstrated the accuracy of the non-invasive index FSI in diagnosing steatosis when compared to Transient elastography controlled attenuation parameter (CAP), and highlighted its superiority to other indices the HSI and DSI. Further studies with larger and more heterogeneous population are needed to confirm our results.
The Correlation between REEP6 and Prognosis and Immune Infiltration in Colorectal Cancer：A Bioinformatics Analysis
Authors: Dong Xiao-long 
Published: July 2024

Abstract

Objects:
Colorectal cancer (CRC) is the third most prevalent cancer globally and the second leading cause of cancer-related mortality. This study aims to investigate the expression of REEP6 (Receptor-expression enhancing protein 6) and its association with molecular interactions, immune infiltration, and patient survival across colorectal cancer.
Materials and methods
Data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, including datasets GSE89076, GSE37364, and GSE20916 for validation. RNA sequencing data were normalized using the DESeq2 R package, while microarray data underwent background correction and normalization via the Robust Multi-array Average method. Batch effects were corrected using the Combat method. Differentially expressed genes (DEGs) were identified based on |log2 Fold Change| > 1.5 and adjusted p-value < 0.05. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses were conducted using the Cluster Profiler R package. Correlation analyses employed Spearman's rank correlation coefficient. Kaplan-Meier survival analysis was performed to evaluate patient outcomes, and ROC (Receiver Operating Characteristic) curve analysis assessed model performance. Immune infiltration was analyzed in relation to REEP6 expression.
Results
REEP6 expression is significantly elevated in colorectal cancer samples compared to normal tissues (P < 0.001). ROC analysis revealed an area under the curve of 0.880, indicating high diagnostic potential. DEGs associated with REEP6 included UPK1A, SLC7A9, SLC22A31, and NLRP6, all positively correlated with REEP6 expression. Enrichment analyses suggested these genes are involved in nucleosome formation and DNA packaging complexes, implicating systemic lupus erythematosus and alcoholism pathways. Although Kaplan-Meier survival curves showed no significant difference in overall survival between high and low REEP6 expression groups (HR = 1.31, P = 0.133), immune infiltration analysis indicated increased NK CD56bright cell levels in high REEP6 expression samples (R = 0.333558, P < 0.001).
Conclusion
REEP6 is highly expressed in colorectal cancer and correlates with specific molecular pathways and immune cell infiltration but does not significantly impact patient survival outcomes alone. These findings highlight REEP6's potential as a diagnostic biomarker and suggest further research into its role in cancer immunology is warranted.
My virtual escape from patient life: A feasibility study on the experiences and benefits of individualized virtual reality for inpatients in palliative cancer care
Authors: Gerlach Christina , Haas Laura , Greinacher Anja , Lantelme Jonah , Guenther Melanie , Thiesbonenkamp-Maag Julia , Alt-Epping Bernd , Wrzus Cornelia 
Published: July 2024

Abstract

Background: Cancer patients benefit from Virtual Reality (VR) in burdensome situations, but evidence is scarce for palliative situations. Based on earlier work in palliative care, individualized VR interventions like seeing the patient’s home may address a patient’s wish to be at home and thus have a greater effect compared to standard VR content. Yet, some patients and relatives may be concerned about their privacy. Also, patient stakeholders raised concerns about triggering depressed mood or homesickness.
Aim: To test the feasibility and safety of individualized vs. standard 360°video VR interventions in palliative cancer inpatients.
Methods: Prospective observational study with patient-reported outcome measurement using validated instruments of well-being (MDBF), symptoms and psychosocial burden (IPOS), cybersickness (SSQ), presence experience (SPES), subjective benefit (2 items), content analysis of interviews, and field notes. Individualized VR content was recorded with action camcorder-technology to protect the patients’ privacy.
Results: Seventeen patients participated, median age 65 years (range 20-82), 9 women (53%), 8 single or widowed (47%), 4 childless (23.5%), 4 academics (23.5%), with a median length of stay of 9 days (1-75) in the hematology (10), palliative care (3), or radiotherapy (2) unit of a German university hospital. Eight patients (53.3%) chose their own home environments or family for individualized VR-content. All participants enjoyed the intervention. Compared to standard VR content the individualized VR tended to have a stronger effect on well-being and emotional touch. It was not inferior in terms of psychosocial burden and cybersickness. No subjective and relevant side effects occurred. The patients well tolerated the assessments. However, most patients demanded a lighter headset and a desire for more interactivity.
Conclusions: Individualization of VR content shows potential for enhancement of immersion, which improves the VR experience and does not harm in terms of depressed mood or worsening of symptoms. The patients’ and family desire for privacy is feasible with the support of family members who recorded the individualized videos, which is easily manageable today. We suggest a pragmatic randomized clinical trial to compare the effects of individualized vs. standard VR-content.
Trial registration: Registered at German Clinical Trials Register (Deutsches Register Klinischer Studien; DRKS); registration number: DRKS00032172; registration date: 11/07/2023
The Endoplasmic Reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells
Authors: Fernández Laura , Kong Chow-Seng , Alkhoury Majd , Tryfonos Maria , Brighton Paul J. , Rawlings Thomas M. , Muter Joanne , Gori Maria Soledad , Leirós Claudia Pérez , Lucas Emma S. , Brosens Jan J. , Ramhorst Rosanna 
Published: July 2024

Abstract

Decidualization denotes the process of inflammatory reprogramming of endometrial stromal cells (EnSC) into specialized decidual cells (DC). During this process, EnSC are subjected to endoplasmic reticulum (ER) stress as well as acute cellular senescence. Both processes contribute to the proinflammatory mid-luteal implantation window and their dysregulation has been implicated in reproductive failure. Here, we evaluated the link between ER stress, decidual differentiation and senescence. In-silico analysis identified HSPA5 gene, codifying the ER chaperone BiP, as a potentially critical regulator of cell fate divergence of decidualizing EnSC into anti-inflammatory DC and proinflammatory senescent decidual cells (snDC). Knockdown of HSPA5 in primary EnSC resulted both in decreased expression of DC marker genes and attenuated induction of senescence associated βgalactosidase activity, a marker of snDC. Stalling of the decidual reaction upon HSPA5 knockdown was apparent at 8 days of differentiation and was preceded by the upregulation of ER stress associated proteins IRE1α and PERK. Further, HSPA5 knockdown impaired colony-forming unit activity of primary EnSC, indicative of loss of cellular plasticity. Together, our results point to a key role for HSPA5/BiP in decidual transformation of EnSCs and highlight the importance of constraining ER stress levels during this process.
Parkinson’s disease-associated shifts between DNA methylation and DNA hydroxymethylation in human brain in PD-related genes, including PARK19 (DNAJC6) and PTPRN2 (IA-2β)
Authors: Choza Juliana I. , Virani Mahek , Kuhn Nathan C. , Adams Marie , Kochmanski Joseph , Bernstein Alison I. 
Published: July 2024

Abstract

Background
The majority of Parkinson’s disease (PD) cases are due to a complex interaction between aging, genetics, and environmental factors; epigenetic mechanisms are thought to act as important mediators of these risk factors. While multiple studies to date have explored the role of DNA modifications in PD, few focus on 5-hydroxymethylcytosine (5hmC). Because 5hmC occurs at its highest levels in the brain and is thought to be particularly important in the central nervous system, particularly in the response to neurotoxicants, it is important to explore the potential role of 5hmC in PD. This study expands on our previously published epigenome-wide association study (EWAS) performed on DNA isolated from neuron-enriched nuclei from human postmortem parietal cortex from the Banner Sun Health Research Institute Brain Bank. The study aimed to identify paired changes in 5hmC and 5mC in PD in enriched neuronal nuclei isolated from PD post-mortem parietal cortex and age- and sex-matched controls. We performed oxidative bisulfite (oxBS) conversion and paired it with our previously published bisulfite (BS)-based EWAS on the same samples to identify cytosines with significant shifts between these two related epigenetic marks. Interaction differentially modified cytosines (iDMCs) were identified using our recently published mixed-effects model for co-analyzing βmC and βhmC data.
Results
We identified 1,030 iDMCs with paired changes in 5mC and 5hmC (FDR < 0.05) that map to 695 genes, including PARK19 (DNAJC6), a familial PD gene, and PTPRN2 (IA-2), which has been previously implicated in PD in both epigenetic and mechanistic studies. The majority of iDMC-containing genes have not previously been implicated in PD and were not identified in our previous BS-based EWAS.
Conclusions
These data potentially link epigenetic regulation of the PARK19 and PTPRN2 loci in the pathogenesis of idiopathic PD. In addition, iDMC-containing genes have known functions in synaptic formation and function, cell cycle and senescence, neuroinflammation, and epigenetic regulation. These data suggest that there are significant shifts between 5mC and 5hmC associated with PD in genes relevant to PD pathogenesis that are not captured by analyzing BS-based data alone or by analyzing each mark as a distinct dataset.
Efficacy and Safety of Sodium Citrate and Argatroban in Continuous Renal Replacement Therapy of Patients with High Risk of Bleeding
Authors: Lan 李兰 Li , Gu Lingling , Zhang Yao , Zhuang Zhiwei , Yu Yanxia , Zhang Qian , Xu Jinhui , Xu Xiaowen , Tang Lian 
Published: July 2024

Abstract

The study was designed to evaluate the efficacy and safety of RCA versus low-dose argatroban in CRRT of critically ill patients with high risk of bleeding, so as to provide a theoretical basis for optimizing the anticoagulation mode of CRRT in critically ill patients with high risk of bleeding. 207 patients were divided into RCA group (n = 103) and Argatroban group (n = 104). After treatment, the prothrombin time, international standardized ratio, and activated partial thromboplastin time of Argatroban group were prolonged when compared with those of RCA group (P < 0.05). Compared with Argatroban group, RCA group had significantly longer filter life span (42.1 (40.9, 46.5) h vs 41.2 (38.95, 43.2) h, P = 0.009). However, there was no significant difference between the two groups in 42-day all-cause mortality (51/103 vs 46/104, P > 0.05). The cycles of filter clotting events (GRADE 0 and GRADE Ⅲ) had significant difference between the two groups(P < 0.05). Compared with argatroban group, RCA group had slightly more bleeding complications (14/103 [13.59%] vs 8/104 [7.69%], P = 0.146). Although blood transfusion volume had no significant difference, the incidence of total adverse reactions in RCA group was significantly`higher than that in argatroban group (9.62% vs 19.42%, P = 0.045). The results showed that RCA treatment improves clinical outcome of patients at high risk of bleeding after CRRT, effectively prolongs the filter life and avoids filter clotting events. Argatroban has systemic anticoagulant effect, which has a certain impact on coagulation function, but it has better safety advantages.
Gate- and flux-tunable sin(2φ) Josephson element with proximitized Ge-based junctions
Authors: De Franceschi Silvano , leblanc Axel , Tangchingchai Chotivut , Momtaz Zahra Sadre , Kiyooka Elyjah , Hartmann Jean-Michel , Gustavo Frédéric , Thomassin Jean-Luc , Brun Boris , Schmitt Vivien , Zihlmann Simon , Maurand Romain , Dumur Étienne , Lefloch François 
Published: July 2024

Abstract

Hybrid superconductor-semiconductor Josephson field-effect transistors (JoFETs) function as
Josephson junctions with a gate-tunable critical current. Additionally, they can feature a non-
sinusoidal current-phase relation (CPR) containing multiple harmonics of the superconducting phase
difference, a so-far underutilized property. In this work, we exploit this multi-harmonicity to create a
Josephson circuit element with an almost perfectly π-periodic CPR, indicative of a largely dominant
charge-4e supercurrent transport. Such a Josephson element was recently proposed as the basic
building block of a protected superconducting qubit. Here, it is realized using a superconducting
quantum interference device (SQUID) with low-inductance aluminum arms and two nominally
identical JoFETs. The latter are fabricated from a SiGe/Ge/SiGe quantum-well heterostructure
embedding a high-mobility two-dimensional hole gas. By carefully adjusting the JoFET gate voltages
and finely tuning the magnetic flux through the SQUID close to half a flux quantum, we achieve
a regime where the sin(2φ) component accounts for more than 95 % of the total supercurrent.
This result demonstrates a new promising route for the realization of superconducting qubits with
enhanced coherence properties.