bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients’ recovery of mobility and return to original residence after hip fracture are associated with multiple modifiable components of hospital service organisation: the REDUCE record-linkage cohort study in England and Wales
Authors: Patel Rita , Judge Andrew , Johansen Antony , Marques Elsa M. R. , Chesser Tim , Griffin Xavier L. , Javaid Muhammad K. ,   REDUCE Study Group, Ben-Shlomo Yoav , Gregson Celia L. 
Published: July 2023

Abstract
Background
Hip fractures are devastating injuries causing disability, dependence, and institutionalisation, yet hospital care is highly variable. This study aimed to determine hospital organisational factors associated with recovery of mobility and change in patient residence after hip fracture.

Methods
A cohort of patients aged 60 + years in England and Wales, who sustained a hip fracture from 2016 to 2019 was examined. Patient-level Hospital Episodes Statistics, National Hip Fracture Database, and mortality records were linked to 101 factors derived from 18 hospital-level organisational metrics. After adjustment for patient case-mix, multilevel models were used to identify organisational factors associated with patient residence at discharge, and mobility and residence at 120 days after hip fracture.

Results
Across 172 hospitals, 165,350 patients survived to discharge, of whom 163,230 (99%) had post-hospital discharge destination recorded. 18,323 (11%) died within 120 days. Among 147,027 survivors, 58,344 (40%) across 143 hospitals had their residence recorded, and 56,959 (39%) across 140 hospitals had their mobility recorded, at 120 days. Nineteen organisational factors independently predicted residence on hospital discharge e.g., return to original residence was 31% (95% confidence interval, CI:17–43%) more likely if the anaesthetic lead for hip fracture had time allocated in their job plan, and 8–13% more likely if hip fracture service clinical governance meetings were attended by an orthopaedic surgeon, physiotherapist or anaesthetist. Seven organisational factors independently predicted residence at 120 days. Patients returning to their pre-fracture residence was 26% (95%CI:4–42%) more likely if hospitals had a dedicated hip fracture ward, and 20% (95%CI:8–30%) more likely if treatment plans were proactively discussed with patients and families on admission. Seventeen organisational factors predicted mobility at 120 days. More patients re-attained their pre-fracture mobility in hospitals where (i) care involved an orthogeriatrician (15% [95%CI:1-28%] improvement), (ii) general anaesthesia was usually accompanied by a nerve block (7% [95%CI:1-12%], and (iii) bedside haemoglobin testing was routine in theatre recovery (13% [95%CI:6-20%]).

Conclusions
Multiple, potentially modifiable, organisational factors are associated with patient outcomes up to 120 days after a hip fracture, these factors if causal should be targeted by service improvement initiatives to reduce variability, improve hospital hip fracture care, and maximise patient independence.
Design, validation and implementation of an automated e-alert for acute kidney injury: 6-month pilot study shows increased awareness
Authors: Niemantsverdriet Michael S.A. , Tiel Groenestege Wouter M. , Khairoun M. , Hoefer Imo E. , van Solinge Wouter W. , Bellomo Domenico , van Vliet Martin H. , Kaasjager Karin A.H. , Haitjema Saskia 
Published: July 2023

Abstract
Background
Acute kidney injury (AKI) is defined as a sudden episode of kidney failure but is known to be under-recognized by healthcare professionals. The Kidney Disease Improving Global Outcome (KDIGO) guidelines have formulated criteria to facilitate AKI diagnosis by comparing changes in plasma creatinine measurements (PCr). To improve AKI awareness, we implemented these criteria as an electronic alert (e-alert), in our electronic health record (EHR) system.

Methods
For every new PCr measurement measured in the University Medical Center Utrecht that triggered the e-alert, we provided the physician with actionable insights in the form of a memo, to improve or stabilize kidney function. Since e-alerts qualify for software as a medical device (SaMD), we designed, implemented and validated the e-alert according to the European Union In Vitro Diagnostic Regulation (IVDR).

Results
We evaluated the impact of the e-alert using pilot data six months before and after implementation. 2,053 e-alerts of 866 patients were triggered in the before implementation, and 1,970 e-alerts of 853 patients were triggered after implementation. We found improvements in AKI awareness as measured by (1) 2 days PCr follow up (56.6–65.8%, p-value: 0.003), and (2) stop of nephrotoxic medication within 7 days of the e-alert (59.2–63.2%, p-value: 0.002).

Conclusion
Here, we describe the design and implementation of the e-alert in line with the IVDR, leveraging a multi-disciplinary team consisting of physicians, clinical chemists, data managers and data scientists, and share our firsts results that indicate an improved awareness among treating physicians.
Role of pelitinib in the regulation of migration and invasion of hepatocellular carcinoma cells via inhibition of Twist1
Authors: Lee Sewoong , Kang Eunjeong , Lee Unju , Cho Sayeon 
Published: July 2023

AbstractBackgroundOverexpression of Twist1, one of the epithelial-mesenchymal transition-transcription factors (EMT-TFs), is associated with hepatocellular carcinoma (HCC) metastasis. Pelitinib is known to be an irreversible epidermal growth factor receptor tyrosine kinase inhibitor that is used in clinical trials for colorectal and lung cancers, but the role of pelitinib in cancer metastasis has not been studied. This study aimed to investigate the anti-migration and anti-invasion activities of pelitinib in HCC cell lines.MethodsUsing three HCC cell lines (Huh7, Hep3B, and SNU449 cells), the effects of pelitinib on cell cytotoxicity, invasion, and migration were determined by cell viability, wound healing, transwell invasion, and spheroid invasion assays. The activities of MMP-2 and -9 were examined through gelatin zymography. Through immunoblotting analyses, the expression levels of EMT-TFs (Snail1, Twist1, and ZEB1) and EMT-related signaling pathways such as mitogen-activated protein kinases (MAPKs) and Akt signaling pathways were measured. The activity and expression levels of target genes were analyzed by reporter assay, RT-PCR, quantitative RT-PCR, and immunoblotting analysis. Statistical analysis was performed using one-way ANOVA with Dunnett's Multiple comparison tests in Prism 3.0 to assess differences between experimental conditions.ResultsIn this study, pelitinib treatment significantly inhibited wound closure in various HCC cell lines, including Huh7, Hep3B, and SNU449. Additionally, pelitinib was found to inhibit multicellular cancer spheroid invasion and metalloprotease activities in Huh7 cells. Further investigation revealed that pelitinib treatment inhibited the migration and invasion of Huh7 cells by inducing Twist1 degradation through the inhibition of MAPK and Akt signaling pathways. We also confirmed that the inhibition of cell motility by Twist1 siRNA was similar to that observed in pelitinib-treated group. Furthermore, pelitinib treatment regulated the expression of target genes associated with EMT, as demonstrated by the upregulation of E-cadherin and downregulation of N-cadherin.ConclusionBased on our novel finding of pelitinib from the perspective of EMT, pelitinib has the ability to inhibit EMT activity of HCC cells via inhibition of Twist1, and this may be the potential mechanism of pelitinib on the suppression of migration and invasion of HCC cells. Therefore, pelitinib could be developed as a potential anti-cancer drug for HCC.
Safety and efficacy of topical interferon alpha 2B and mitomycin C for localized conjunctival intraepithelial neoplasia: long-term report of their pharmacological safety and efficacy
Authors: Alvarado-Castillo Beatriz , Santa Cruz-Pavlovich Francisco J. , Gonzalez-Castillo Celia , Vidal-Paredes Isaac Alejandro , Garcia-Benavides Leonel , Rosales-Gradilla Maria Elena , Navarro-Partida Jose 
Published: July 2023

Abstract
Purpose
Ocular surface squamous neoplasia (OSSN) comprises a wide spectrum of squamous tumors, from which corneal/conjunctival intraepithelial neoplasia (CIN) is the most common one. The classic treatment is complete excision, but recurrence rates are high. Antineoplastic drugs such as mitomycin C (MMC) and interferon alpha 2b (IFNα2b) have been used as adjuvants or as primary treatment. To evaluate the efficacy and safety of topical IFNα2b and MMC in patients with CIN, a phase IIb double-blind clinical trial was performed.

Methods
Patients diagnosed with localized CIN were evaluated by slit lamp and impression cytology and were randomly given MMC 0.04% or INF2b (1 million IU/mL) 4 times daily until neoplasia resolution. Time of resolution and frequency of adverse effects were analyzed to determine the pharmacological efficacy and safety of both medications.

Results
Seventeen patients were included. Nine patients were treated with MMC and 8 with IFNα2b. All patients responded to treatment. The resolution time in days was 59.11 ± 24.02 in patients treated with MMC and 143.50 ± 47.181 in those treated with IFNα2b (p < 0.001). In the MMC group, one recurrence was reported (11%). There were no recurrences at 2 years of follow-up in the IFNα2b group. Regarding adverse effects, one or more mild adverse reaction occurred in 77% of patients managed with MMC and in 50% of patients managed with IFNα2b (p > 0.05). No serious adverse effects were reported.

Conclusions
Topical chemotherapy with MMC and IFNα2b demonstrate pharmacological safety and efficacy. Therefore, these drugs could be considered as primary therapies for localized CIN .
Using a theory-informed approach to guide the initial development of a post-tuberculosis care package in British Columbia, Canada
Authors: Romanowski Kamila , Cook Victoria Jane , Gilbert Mark , Johnston James Cameron 
Published: July 2023

Abstract
Background
The importance of addressing the long-term needs of tuberculosis (TB) survivors is gaining increasing attention. One promising approach to improving post-TB care is implementing a post-TB care package. With a specific focus on the perspectives of healthcare providers in British Columbia, Canada, this study aimed to (1) determine a set of components to be included in a post-TB care package, (2) explore barriers and facilitators influencing their implementation, and (3) propose potential solutions to overcome identified challenges.

Methods
Employing a multi-method approach guided by the Theoretical Domains Framework, we first conducted virtual workshops with TB care providers and utilized a modified Delphi process to establish a preliminary list of care package components. Then, we surveyed healthcare providers using closed-ended, Likert-scale questions to identify implementation barriers and enablers. Lastly, we mapped the identified barriers and enablers to establish behaviour change techniques to identify possible solutions to overcome the challenges identified.

Results
Eleven participants attended virtual workshops, and 23 of 51 (45.1%) healthcare providers completed questionnaires. Identified components of the post-TB care package included:
1. Linking people with TB to a primary care provider if they do not have one.
2. Referring people with pulmonary TB for an end-of-treatment chest x-ray and pulmonary function testing.
3. Referring people with TB who smoke to a smoking cessation specialist.
4. Sharing a one-page post-TB information sheet with the patient's primary care provider, including a summary of post-TB health concerns, complications, and recommendations to prioritize age-appropriate screening for cardiovascular disease, lung cancer, and depression.
Survey results indicated that domain scores for ‘environment, context, and resources’ were the lowest, suggesting potential implementation barriers. Care navigation services to help individuals overcome health system barriers while transitioning from TB care, information leaflets, and checklists summarizing key post-TB health concerns for patients and healthcare providers to help facilitate discussions may help overcome the identified barriers.

Conclusion
Healthcare providers in British Columbia acknowledge that post-TB care is integral to comprehensive health care but are limited by time and resources. Care navigation services, a post-TB checklist, and patient information leaflets may help resolve some of these barriers.
vamos: variable-number tandem repeats annotation using efficient motif sets
Authors: Ren Jingwen , Gu Bida , Chaisson Mark J. P. 
Published: July 2023

AbstractRoughly 3% of the human genome is composed of variable-number tandem repeats (VNTRs): arrays of motifs at least six bases. These loci are highly polymorphic, yet current approaches that define and merge variants based on alignment breakpoints do not capture their full diversity. Here we present a method vamos:VNTRAnnotation using efficientMotifSets that instead annotates VNTR using repeat composition under different levels of motif diversity. Using vamos we estimate 7.4–16.7 alleles per locus when applied to 74 haplotype-resolved human assemblies, compared to breakpoint-based approaches that estimate 4.0–5.5 alleles per locus.
Significance of methylation-related genes in diagnosis and subtype classification of renal interstitial fibrosis
Authors: Zhang Hanchao , Yang Yue , Liu Zhengdao , Xu Hong , Zhu Han , Wang Peirui , Liang Guobiao 
Published: July 2023

Abstract
Background
RNA methylation modifications, such as N1-methyladenosine/N6-methyladenosine /N5-methylcytosine (m1A/m6A/m5C), are the most common RNA modifications and are crucial for a number of biological processes. Nonetheless, the role of RNA methylation modifications of m1A/m6A/m5C in the pathogenesis of renal interstitial fibrosis (RIF) remains incompletely understood.

Methods
Firstly, we downloaded 2 expression datasets from the GEO database, namely GSE22459 and GSE76882. In a differential analysis of these datasets between patients with and without RIF, we selected 33 methylation-related genes (MRGs). We then applied a PPI network, LASSO analysis, SVM-RFE algorithm, and RF algorithm to identify key MRGs.

Results
We eventually obtained five candidate MRGs (WTAP, ALKBH5, YTHDF2, RBMX, and ELAVL1) to forecast the risk of RIF. We created a nomogram model derived from five key MRGs, which revealed that the nomogram model may be advantageous to patients. Based on the selected five significant MRGs, patients with RIF were classified into two MRG patterns using consensus clustering, and the correlation between the five MRGs, the two MRG patterns, and the genetic pattern with immune cell infiltration was shown. Moreover, we conducted GO and KEGG analyses on 768 DEGs between MRG clusters A and B to look into their different involvement in RIF. To measure the MRG patterns, a PCA algorithm was developed to determine MRG scores for each sample. The MRG scores of the patients in cluster B were higher than those in cluster A.

Conclusions
Ultimately, we concluded that cluster A in the two MRG patterns identified on these five key m1A/m6A/m5C regulators may be associated with RIF.
Visit-to-Visit Glucose Variability, Cognition, and Global Cognitive Decline: The Multi-Ethnic Study of Atherosclerosis
Authors: Schaich Christopher L , Bancks Michael P , Hayden Kathleen M , Ding Jingzhong , Rapp Stephen R , Bertoni Alain G , Heckbert Susan R , Hughes Timothy M , Mongraw-Chaffin Morgana 
Published: July 2023

Abstract

Context
Higher visit-to-visit glucose variability (GV) is associated with dysglycemia and type 2 diabetes (T2D), key risk factors for cognitive decline.

Objective
Evaluate the association of GV with cognitive performance and decline in racially/ethnically diverse older populations with and without T2D.

Methods
We calculated the standard deviation of glucose (SDG), average real variability (ARV), and variability independent of the mean (VIM) among 4367 Multi-Ethnic Study of Atherosclerosis participants over 6 clinical examinations. Participants completed a cognitive assessment at the fifth examination, and a subset completed a second assessment 6 years later. We used multivariable linear regression to estimate the association of intraindividual GV with cognitive test scores after adjustments for cardiovascular risk factors and mean glucose level over the study period.

Results
Two-fold increments in the VIM and SDG were associated with worse Cognitive Abilities Screening Instrument (CASI) performance, while two-fold increments in VIM and ARV were associated with worse Digit Symbol Coding test score. GV measures were not associated with change in CASI performance among 1834 participants with repeat CASI data 6 years later. However, among 229 participants with incident T2D, the SDG and VIM were associated with decline in CASI (−1.7 [95% CI: −3.1, −0.3] and −2.1 [−3.7, −0.5] points, respectively). In contrast, single-timepoint glucose and HbA1c were not associated with CASI decline among participants with or without incident T2D.

Conclusion
Higher visit-to-visit GV over 16 to 18 years is associated with worse cognitive performance in the general population, and with modest global cognitive decline in participants with T2D.
Intergenerational plasticity to cycling high temperature and hypoxia affects offspring stress responsiveness and tolerance in zebrafish
Authors: Lim Michael Y.-T. , Bernier Nicholas J. 
Published: July 2023

ABSTRACT
Predicted climate change-induced increases in heat waves and hypoxic events will have profound effects on fishes, yet the capacity of parents to alter offspring phenotype via non-genetic inheritance and buffer against these combined stressors is not clear. This study tested how prolonged adult zebrafish exposure to combined diel cycles of thermal stress and hypoxia affect offspring early survival and development, parental investment of cortisol and heat shock proteins (HSPs), larval offspring stress responses, and both parental and offspring heat and hypoxia tolerance. Parental exposure to the combined stressor did not affect fecundity, but increased mortality, produced smaller embryos and delayed hatching. The combined treatment also reduced maternal deposition of cortisol and increased embryo hsf1, hsp70a, HSP70, hsp90aa and HSP90 levels. In larvae, basal cortisol levels did not differ between treatments, but acute exposure to combined heat stress and hypoxia increased cortisol levels in control larvae with no effect on larvae from exposed parents. In contrast, whereas larval basal hsf1, hsp70a and hsp90aa levels differed between parental treatments, the combined acute stressor elicited similar transcriptional responses across treatments. Moreover, the combined acute stressor only induced a marked increase in HSP47 levels in the larvae derived from exposed parents. Finally, combined hypoxia and elevated temperatures increased both thermal and hypoxia tolerance in adults and conferred an increase in offspring thermal but not hypoxia tolerance. These results demonstrate that intergenerational acclimation to combined thermal stress and hypoxia elicit complex carryover effects on stress responsiveness and offspring tolerance with potential consequences for resilience.
Safety and Efficacy of Oxaliplatin Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Colorectal and Appendiceal Cancer with Peritoneal Metastases: Results of a Multicenter Phase I Trial in the USA
Authors: Raoof Mustafa , Whelan Richard L. , Sullivan Kevin M. , Ruel Christopher , Frankel Paul H. , Cole Sarah E. , Tinsley Raechelle , Eng Melissa , Fakih Marwan , Chao Joseph , Lim Dean , Woo Yanghee , Paz Isaac Benjamin , Lew Michael , Cristea Michaela , Rodriguez-Rodriguez Lorna , Fong Yuman , Thomas Rebecca Meera , Chang Sue , Deperalta Danielle , Merchea Amit , Dellinger Thanh H. 
Published: July 2023

Abstract
Background
Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a laparoscopic locoregional treatment for peritoneal metastases (PM) from colorectal cancer (CRC) or appendiceal cancer (AC) in patients who cannot undergo cytoreductive surgery (CRS). While PIPAC has been studied in Europe and Asia, it has not been investigated in the USA.

Patients and Methods
We evaluated PIPAC with 90 mg/m2 oxaliplatin alone (cycle 1) and preceded by systemic chemotherapy with fluorouracil (5-FU) and leucovorin (LV) (cycle 2–3) as a multicenter prospective phase I clinical trial (NCT04329494). The primary endpoint was treatment-related adverse events (AEs). Secondary endpoints included survival and laparoscopic, histologic, and radiographic response.

Results
12 patients were included: 8 with CRC and 4 with AC. Median prior chemotherapy cycles was 2 (interquartile range (IQR) 2–3). All patients were refractory to systemic oxaliplatin-based chemotherapy. Median peritoneal carcinomatosis index (PCI) was 28 (IQR 19–32). Six (50%) of twelve patients completed three PIPAC cycles. No surgical complications or dose-limiting toxicities were observed. Two patients developed grade 3 treatment-related toxicities (one abdominal pain and one anemia). Median overall survival (OS) was 12.0 months, and median progression-free survival (PFS) was 2.9 months. OS was correlated with stable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria but not with laparoscopic response by PCI or histologic response by peritoneal regression grading system (PRGS).

Conclusions
This phase I trial in the USA demonstrated safety, feasibility, and early efficacy signal of PIPAC with oxaliplatin and chemotherapy in patients with PM from AC or CRC who are refractory to standard lines of systemic chemotherapy.
Searching for the Best Yardstick: Cost of Quality Improvements in the U.S. Hospital Industry
Authors: Lim Jong Myeong , Moon Ken , Savin Sergei 
Published: July 2023

The Hospital Value-Based Purchasing (VBP) Program is Medicare’s implementation of yardstick incentives applied to hospitals in the United States. Under the VBP Program, 2% of all Medicare payments to hospitals, estimated to be U.S. $1.9 billion in fiscal year 2021, are withheld and redistributed based on their relative performance in the quality of delivered care. We develop a dynamic mean-field equilibrium model in which hospitals are engaged in repeated competition under yardstick incentives. Using structural estimation methods, we recover key parameters that govern hospitals’ decisions to invest in quality improvement, including the financial and nonfinancial costs and uncertain outcomes of investment. By dynamically solving for hospitals’ individually optimal investment policies, we estimate the trajectory of quality improvements for each hospital, including its investment decisions and quality levels throughout the implementation of the VBP Program. Our counterfactual analyses explore the benefits, on the one hand, of modifying the overall size of the yardstick incentives and on the other hand, of implementing a more focused program tailored to hospital type. We find that increasing the size of the incentives from 2% to 4% would have resulted in an additional quality investment of U.S. $1.2 billion from 2011 to 2018, leading to a 3.3% reduction in the average rate of central line-associated bloodstream infections (CLABSIs). Applying yardstick incentives to the tailored hospital peer groups, even without changing the size of the incentives, can lead to an average reduction of 1.4% in the rate of CLABSI among groups of hospitals associated with the highest costs of quality investment. This paper was accepted by Stefan Scholtes, healthcare management. Funding: K. Moon acknowledges support from the Wharton School [Claude Marion Endowed Faculty Scholar Award]. Supplemental Material: The data files and online appendix are available at https://doi.org/10.1287/mnsc.2023.4875 .