bluuebunny/crossref_metadata_2025_split huggingface dataset:
46 An integrated pathway to access medicines for the palliative care patient in crisis in the out-of-hours period
Authors: Donovan Gemma , Foster Stephen , Herscovitz Marc , Griffiths Andrew , Slark Denise 
Published: May 2024

IntroductionIt is recognised that community rapid response services can face difficulties in sourcing medicines to support end-of-life care (Butler and Holdsworth, 2013). Medicines used in the out-of-hours (OOH) period cannot usually be dispensed directly to the patient due to community pharmacies being closed. This can prevent the setup of syringe drivers and/or administration of prescribed stat doses. Here, an on-call pharmacy service was commissioned but not well integrated into pathways of care.AimTo optimise the treatment of palliative care patients in crisis, using an integrated pathway.MethodA Rapid Process Improvement Workshop (RPIW) was used to map the process of managing a patient in crisis, and plan a more efficient pathway to access medicines across nursing, medical and pharmacy services.ResultsAn integrated pathway was developed to facilitate best use of healthcare professional time to deliver palliative care (see below). An on-call pharmacy service is key to its delivery. In 2015/16, palliative care nurses were coordinating medicines supply for 95% pharmacy call-outs (n=38), since implementation of the new pathway in 2016/17 this has reduced to 42% (n=31). At baseline, it was estimated that sourcing medicines by nurses took four to five hours, the new service takes an average 49 min from call-out to patient delivery of required medicines.ConclusionCommissioning an on-call pharmacy service using an integrated pathway for patients in crisis enables efficient supply of medicines during the OOH period, optimising use of nursing, pharmacist and medical time to facilitate timely access to medicines for symptom management.Reference. Butler, C. and Holdsworth, L. (2013) ‘Setting up a new evidence-based hospice-at-home service in England’, International Journal of Palliative Nursing, 19(7), pp. 355–359
Allysine-Targeted Molecular MRI Enables Early Prediction of Chemotherapy Response in Pancreatic Cancer
Authors: Ma Hua , Esfahani Shadi A. , Krishna Shriya , Ataeinia Bahar , Zhou Iris Y. , Rotile Nicholas J. , Weigand-Whittier Jonah , Boice Avery T. , Liss Andrew S. , Tanabe Kenneth K. , Caravan Peter 
Published: May 2024

Abstract
Neoadjuvant therapy is routinely used in pancreatic ductal adenocarcinoma (PDAC), but not all tumors respond to this treatment. Current clinical imaging techniques are not able to precisely evaluate and predict the response to neoadjuvant therapies over several weeks. A strong fibrotic reaction is a hallmark of a positive response, and during fibrogenesis, allysine residues are formed on collagen proteins by the action of lysyl oxidases. Here, we report the application of an allysine-targeted molecular MRI probe, MnL3, to provide an early, noninvasive assessment of treatment response in PDAC. Allysine increased 2- to 3-fold after one dose of neoadjuvant therapy with FOLFIRINOX in sensitive human PDAC xenografts in mice. Molecular MRI with MnL3 could specifically detect and quantify fibrogenesis in PDAC xenografts. Comparing the MnL3 signal before and 3 days after one dose of FOLFIRINOX predicted subsequent treatment response. The MnL3 tumor signal increased by 70% from day 0 to day 3 in mice that responded to subsequent doses of FOLFIRINOX, whereas no signal increase was observed in FOLFIRINOX-resistant tumors. This study indicates the promise of allysine-targeted molecular MRI as a noninvasive tool to predict chemotherapy outcomes.
Significance: Allysine-targeted molecular MRI can quantify fibrogenesis in pancreatic tumors and predict response to chemotherapy, which could guide rapid clinical management decisions by differentiating responders from nonresponders after treatment initiation.
Abstract A025: Integrating genomic alterations and histopathological features for enhanced risk stratification in non-muscle invasive bladder cancer
Authors: Lillesand Melinda , Kvikstad Vebjørn , Gudlaugsson Einar , Skaland Ivar , Johannessen Aida Slewa , Tesfahun Almaz Nigatu , Sperstad Sigmund Vegard , Janssen Emiel A.M. , Austdal Marie 
Published: May 2024

Abstract
Urothelial carcinoma is the most prevalent type of bladder cancer, where non-muscle invasive bladder cancer (NMIBC) accounts for about 75% of the initial diagnosis. Recognizing the limitations of current WHO04/16 grading and TNM staging systems, this study investigates genomic alterations, mitotic activity index (MAI) and immunohistochemical (IHC) markers CK20, p53, and CD25 to identify better prognostic biomarkers in NMIBC. In this retrospective population-based study of NMIBC patients (n=287), a targeted next-generation sequencing (NGS) panel analysis was performed using Oncomine™ Focus Assay on Ion GeneStudio S5 platform to identify genomic changes, including single nucleotide variations (SNVs) and copy number variations (CNVs) across 52 genes. The results revealed that the most frequent gene variants were identified in FGFR3 (n=183, 45%) and PIK3CA (n=98, 24%), while AKT1 (n=39, 20%), ERBB2 (n=24, 12%), MYCN (n=23, 12%) and CCND1 (n=22, 11%) were among the most amplified genes. Distinct genetic associations were observed among Ta, T1, low-grade (LG), and high-grade (HG) tumors. Ta tumors were significantly associated with FGFR3 and PIK3CA mutations, while T1 tumors were linked to ERBB2 mutations (p&lt;0.001). Additionally, LG tumors were enriched with FGFR3 mutations, while HG tumors were significantly associated with FGFR1, CCND1, and ERBB2 mutations (p&lt;0.001). In the analysis of tumor recurrence, patients with FGFR3 mutations had significantly shorter recurrence-free survival (RFS) (p=0.033). Analysis of stage progression revealed a significant association between FGFR3 mutations and improved PFS (p&lt;0.001), while MYC, ERBB2 (p&lt;0.001), and MYCN (p=0.011) were linked to shorter PFS. In gene set enrichment analysis, gene sets like PIK3CA and ERBB2 (p=0.003), and PIK3CA and MYC (p=0.005), were inversely associated with progression-free survival (PFS). In the multivariate Cox regression analysis, MAI was the strongest predictor for PFS (p&lt;0.001). The study emphasizes the potential of combining genomic alterations with histopathological features for enhanced risk stratification in NMIBC patients.
Citation Format: Melinda Lillesand, Vebjørn Kvikstad, Einar Gudlaugsson, Ivar Skaland, Aida Slewa Johannessen, Almaz Nigatu Tesfahun, Sigmund Vegard Sperstad, Emiel A.M. Janssen, Marie Austdal. Integrating genomic alterations and histopathological features for enhanced risk stratification in non-muscle invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A025.
Hemangiosarcoma Cells Promote Conserved Host-derived Hematopoietic Expansion
Authors: Kim Jong Hyuk , Schulte Ashley J. , Sarver Aaron L. , Lee Donghee , Angelos Mathew G. , Frantz Aric M. , Forster Colleen L. , O'Brien Timothy D. , Cornax Ingrid , O'Sullivan M. Gerard , Cheng Nuojin , Lewellen Mitzi , Oseth LeAnn , Kumar Sunil , Bullman Susan , Pedamallu Chandra Sekhar , Goyal Sagar M. , Meyerson Matthew , Lund Troy C. , Breen Matthew , Lindblad-Toh Kerstin , Dickerson Erin B. , Kaufman Dan S. , Modiano Jaime F. 
Published: May 2024

Abstract

Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel–forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells. In a series of xenografts, we observed that the transplanted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. Our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. Furthermore, gene expression profiling data revealed hemangiosarcoma cells expressed a repertoire of hematopoietic cytokines capable of regulating the surrounding stromal cells. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, maintain molecular properties that provide hematopoietic support and facilitate stromal reactions, suggesting their potential involvement in promoting the growth of hematopoietic tumors.

Significance:
We demonstrate that hemangiosarcomas regulate molecular programs supporting hematopoietic expansion and differentiation, providing insights into their potential roles in creating a permissive stromal-immune environment for tumor progression.
Ablating Myocardium Using Nanosecond Pulsed Electric Fields: Preclinical Assessment of Feasibility, Safety, and Durability
Authors: Nies Moritz , Watanabe Keita , Kawamura Iwanari , Wang Bingyan J. , Litt Jeffrey , Turovskiy Roman , Danitz David J. , Uecker Darrin R. , Linder Keith E. , Maejima Yasuhiro , Sasano Tetsuo , Reddy Vivek Y. , Koruth Jacob S. 
Published: May 2024

BACKGROUND:
Unlike conventional microsecond pulsed electrical fields that primarily target the cell membranes, nanosecond pulses are thought to primarily electroporate intracellular organelles. We conducted a comprehensive preclinical assessment of catheter-based endocardial nanosecond pulsed field ablation in swine.

METHODS:
A novel endocardial nanosecond pulsed field ablation system was evaluated in a total of 25 swine. Using either a low-dose (5-second duration) or high-dose (15-second duration) strategy, thoracic veins and discrete atrial and ventricular sites were ablated. Predetermined survival periods were <1 (n=1), ≈2 (n=7), ≈7 (n=6), 14 (n=2), or ≈28 (n=9) days, and venous isolation was assessed before euthanasia. Safety assessments included evaluation of esophageal effects, phrenic nerve function, and changes in venous caliber. All tissues were subject to careful gross pathological and histopathologic examination.

RESULTS:

All (100%) veins (13 low-dose, 34 high-dose) were acutely isolated, and all reassessed veins (6 low-dose, 15 high-dose) were durably isolated. All examined vein lesions (10 low-dose, 22 high-dose) were transmural. Vein diameters (n=15) were not significantly changed. Of the animals assessed for phrenic palsy (n=9), 3 (33%) demonstrated only transient palsy. There were no differences between dosing strategies. Thirteen mitral isthmus lesions were analyzed, and all 13 (100%) were transmural (depth, 6.4±0.4 mm). Ventricular lesions were 14.7±4.5 mm wide and 7.1±1.3 mm deep, with high-dose lesions deeper than low-dose (7.9±1.2 versus 6.2±0.8 mm;
P
=0.007). The esophagus revealed nontransmural adventitial surface lesions in 5 of 5 (100%) animals euthanized early (2 days) post-ablation. In the 10 animals euthanized later (14–28 days), all animals demonstrated significant esophageal healing—8 with complete resolution, and 2 with only trace fibrosis.

CONCLUSIONS:
A novel, endocardial nanosecond pulsed field ablation system provides acute and durable venous isolation and linear lesions. Transient phrenic injury and nontransmural esophageal lesions can occur with worst-case assessments suggesting limits to pulsed field ablation tissue selectivity and the need for dedicated assessments during clinical studies.
Ocean Heat Convergence and North Atlantic Multidecadal Heat Content Variability
Authors: Moat B. I. , Sinha B. , Berry David I. , Drijfhout S. S. , Fraser N. , Hermanson L. , Jones D. C. , Josey S. A. , King B. , Macintosh C. , Megann A. , Oltmanns M. , Sanders R. , Williams S. 
Published: May 2024

Abstract
We construct an upper ocean (0–1000 m) North Atlantic heat budget (26°–67°N) for the period 1950–2020 using multiple observational datasets and an eddy-permitting global ocean model. On multidecadal time scales, ocean heat transport convergence controls ocean heat content (OHC) tendency in most regions of the North Atlantic with little role for diffusive processes. In the subpolar North Atlantic (45°–67°N), heat transport convergence is explained by geostrophic currents, whereas ageostrophic currents make a significant contribution in the subtropics (26°–45°N). The geostrophic contribution in all regions is dominated by anomalous advection across the time-mean temperature gradient although other processes make a significant contribution, particularly in the subtropics. The time scale and spatial distribution of the anomalous geostrophic currents are consistent with a simple model of basin-scale thermal Rossby waves propagating westward/northwestward in the subpolar gyre, and multidecadal variations in regional OHC are explained by geostrophic currents periodically coming into alignment with the mean temperature gradient as the Rossby wave passes through. The global ocean model simulation shows that multidecadal variations in the Atlantic meridional overturning circulation are synchronized with the ocean heat transport convergence consistent with modulation of the west–east pressure gradient by the propagating Rossby wave.

Significance Statement
The purpose of the work is to understand why the North Atlantic Ocean warms up and cools down on time scales of about 40 years. The key finding is that the temperature fluctuations are caused by an oceanic wave pushing the ocean surface up and down and causing ocean currents to change direction, pushing heat into and out of different parts of the ocean, and drawing down or emitting heat to the atmosphere. The findings matter because the warm and cool periods affect the climate of the countries surrounding the North Atlantic. Climate models need to account for this oceanic wave process to correctly predict how it will change in the future and affect the large-scale climate in a warming world.
Nerolidol Alleviates Oxidative Stress and Inflammation in Diabetic Retinopathy Mediated by High Glucose through Ameliorating Nrf2/HO-1 Pathway
Authors: Li Changhong , Shi Buchao , Li Dong , Li Hui 
Published: May 2024

Background Diabetic retinopathy (DR) is the foremost microvascular problem that causes drastic visual impairment in diabetes patients. Hyperglycemia-triggered reaction cascade of inflammation and oxidative stress constitute the DR pathogenesis. The existing treatment options are not completely satisfactory. Materials and Methods We investigated the cell viability by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, inflammatory mediators, lactate dehydrogenase (LDH), superoxide dismutase, glutathione, and malonaldehyde (MDA) levels by ELISA and qRT-PCR assay, protein expression of Nrf2 and heme oxygenase-1 (HO-1) by western blotting assay were analyzed. Results According to our research, nerolidol (NRD) increases the proliferation and antioxidant activity of human retinal endothelial cells (HRECs) by inducing Nrf2/HO-1 signaling, while attenuating MDA, an oxidative stress marker, LDH, and inflammatory mediators. These outcomes suggest that a substantial reaction of inflammation and oxidative stress injury happened in DR, which might be correlated to the instigation of the signaling Nrf2/HO-1. Conclusion NRD effectively suppresses oxidative stress and inflammation in HG-induced HRECs. The primary mechanism of NRD on DR may be linked to the activation of the Nrf2/HO-1 pathway and may give a useful medicine for DR treatment.
Using Artificial Intelligence to Improve the Accuracy of a Wrist-Worn, Noninvasive Glucose Monitor: A Pilot Study
Authors: Qureshi Muhammad Rafaqat Ali , Bain Stephen Charles , Luzio Stephen , Handy Consuelo , Fowles Daniel J. , Love Bradley , Wareham Kathie , Barlow Lucy , Dunseath Gareth J. , Crane Joel , Masso Isamar Carrillo , Ryan Julia A. M. , Chaudhry Mohamed Sabih 
Published: May 2024

Background: Self-monitoring of glucose is important to the successful management of diabetes; however, existing monitoring methods require a degree of invasive measurement which can be unpleasant for users. This study investigates the accuracy of a noninvasive glucose monitoring system that analyses spectral variations in microwave signals. Methods: An open-label, pilot design study was conducted with four cohorts (N = 5/cohort). In each session, a dial-resonating sensor (DRS) attached to the wrist automatically collected data every 60 seconds, with a novel artificial intelligence (AI) model converting signal resonance output to a glucose prediction. Plasma glucose was measured in venous blood samples every 5 minutes for Cohorts 1 to 3 and every 10 minutes for Cohort 4. Accuracy was evaluated by calculating the mean absolute relative difference (MARD) between the DRS and plasma glucose values. Results: Accurate plasma glucose predictions were obtained across all four cohorts using a random sampling procedure applied to the full four-cohort data set, with an average MARD of 10.3%. A statistical analysis demonstrates the quality of these predictions, with a surveillance error grid (SEG) plot indicating no data pairs falling into the high-risk zones. Conclusions: These findings show that MARD values approaching accuracies comparable to current commercial alternatives can be obtained from a multiparticipant pilot study with the application of AI. Microwave biosensors and AI models show promise for improving the accuracy and convenience of glucose monitoring systems for people with diabetes.
Prevalence of cervical intraepithelial lesions and associated factors among women attending a cervical cancer clinic in Western Uganda; results based on Pap smear cytology
Authors: Ssedyabane Frank , Niyonzima Nixon , Nambi Najjuma Josephine , Birungi Abraham , Atwine Raymond , Tusubira Deusdedit , Randall Thomas C , Castro Cesar M , Lee Hakho , Ngonzi Joseph 
Published: May 2024

Introduction: There are high incidence and mortality rates of cervical cancer among females in East Africa. This is exacerbated by limited up-to-date data on premalignant lesions and associated factors in this setting. In this study, we determined the prevalence of cervical intraepithelial lesions and associated factors among women attending the Mbarara Regional Referral Hospital cervical cancer clinic in Southwestern Uganda. Methods: In this cross-sectional study, 364 participants were recruited from among women attending the Mbarara Regional Referral Hospital cervical cancer clinic from 1 April to 30 June 2023. On consent, the study nurse collected demographic data and Pap smears, which were microscopically examined and reported by a laboratory scientist and a pathologist following the Bethesda grading system (2014). Statistical analyses were done in STATA version 17, using proportions, Chi-square, bivariate, and multivariate logistic regression analysis to determine associated factors at ⩽0.05 significance level. Results: The mean age of participants was 41.9 years. A third of all study participants (37.6%, 132/351) were contraceptive users, mostly hormonal contraceptives (87.1%, 115/132). Almost 88% (307/351) had an unknown Human Papilloma Virus status. The prevalence of cervical intraepithelial lesions among our study participants was 6.6% (23/351), of which 73.9% (17/23) were low-grade squamous intraepithelial lesions. More than half (9/17, 52.9%) of low-grade squamous intraepithelial lesions were active hormonal contraceptive users. Use of hormonal contraceptives (OR: 3.032, p: 0.0253), use of intrauterine devices (OR: 6.284, p: 0.039), and any family history of cervical cancer (OR: 4.144, p: 0.049) were significantly associated with cervical intraepithelial lesions. Conclusion: The prevalence of cervical intraepithelial lesions was 6.6%, lower than global estimates. Use of hormonal and intrauterine device contraceptives, as well as family history of cervical cancer, were significantly associated with cervical intraepithelial lesions among our study population. Prospective studies are recommended to further understand associations between different types of intrauterine devices and hormonal contraceptives, and cervical lesions.
Recommendations of Clinical Practice Guidelines for the treatment of urinary incontinence in women: A methodological survey
Authors: Moura Mariana Del Grossi , Sorrilha Flávia Blaseck , Magnusson Gabriela , Barberato-Filho Silvio , Lopes Luciane Cruz , Pereira Glasiela Isabele Camargo , Bergamaschi Cristiane de Cássia 
Published: May 2024

Objective: This study described and analysed key recommendations from Clinical Practice Guidelines (CPGs) concerning urinary incontinence (UI) treatment in women. Materials and methods: We carried out searches in the following databases: MEDLINE, EMBASE, Web of Science, Virtual Health Library, among others. The reviewers, in duplicate and independently, selected the documents and extracted the data. The quality assessment of the guidelines was carried out, in triplicate, using the Appraisal of Guidelines REsearch and Evaluation (AGREE II) instrument. Results: Six CPGs were selected for analysis. Pelvic Floor Muscle Training (PFMT) is the primary treatment for UI, with adjunctive therapies (biofeedback, vaginal cones, dynamic lumbopelvic stabilisation, and electrical stimulation) recommended alongside PFMT. Discrepancies among CPG were noted in recommendations for drug treatments and invasive procedures, suggesting the need for individualised approaches. When conservative non-pharmacological treatments failed, drugs are recommended. Mid-urethral slings were endorsed, with alternatives like colposuspension or autologous rectus fascial slings considered when mid-urethral slings were unsuitable. Botulinum toxin type A was suggested for urge UI patients unresponsive to conservative therapy. Conclusion: UI treatment must prioritise the conservative non-pharmacological therapies and progressing to invasive options, as necessary. These evidence-based findings aim to guide patients, healthcare professionals, and policy managers in effectively managing UI. Level of evidence: Not applicable