bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inequalities in local government spending on cultural, environmental and planning services: a time-trend analysis in England, Scotland, and Wales
Authors: Fahy Katie , Alexiou Alexandros , Mason Kate , Bennett Davara , Egan Matt , Taylor-Robinson David , Barr Ben 
Published: February 2023

Abstract
Background
Local government provides Cultural, Environmental, and Planning (CEP) services, such as parks, libraries, and waste collection, that are vital for promoting health and wellbeing. There have been significant changes to the funding of these services over the past decade, most notably due to the UK government’s austerity programme. These changes have not affected all places equally. To understand potential impacts on health inequalities, we investigated geographical patterning of recent CEP spending trends.

Methods
We conducted a time trend analysis using routinely available data on local government expenditure. We used generalised estimating equations to determine how expenditure trends varied across 378 local authorities (LAs) in Great Britain between 2009/10 and 2018/19 on the basis of country, deprivation, rurality, and local government structure. We investigated the gross expenditure per capita on CEP services, and the CEP expenditure as a proportion of total local authority budgets. We present the estimated annual percentage change in these spend measures.

Results
Expenditure per capita for CEP services reduced by 36% between 2009/10 and 2018/19. In England, the reduction in per capita spending was steepest in the most deprived quintile of areas, falling by 7.5% [95% CI: 6.0, 8.9] per year, compared to 4.5% [95% CI: 3.3, 5.6] per year in the least deprived quintile. Budget cuts in Scotland and Wales have been more equitable, with similar trends in the most and least deprived areas. Welsh LAs have reduced the proportion of total LA budget spent on CEP services the most (-4.0% per year, 95% CI: -5.0 to -2.9), followed by Scotland (-3.0% per year, 95% CI: -4.2 to -1.7) then England (-1.4% per year, 95% CI: -2.2 to -0.6). In England, rural and unitary LAs reduced their share of spending allocated to CEP more than urban and two-tier structured LAs, respectively.

Conclusion
Funding for cultural, environmental and planning services provided by local government in the UK has been cut dramatically over the last decade, with clear geographical inequalities. Local areas worst affected have been those with a higher baseline level of deprivation, those with a single-tier local government structure, and English rural local authorities. The inequalities in cuts to these services risk widening geographical inequalities in health and wellbeing.
Bicentre, randomized, parallel-arm, sham-controlled trial of transcranial direct-current stimulation (tDCS) in the treatment of palliative care patients with refractory cancer pain
Authors: Nguyen Jean-Paul , Gaillard Hélène , Suarez Alcira , Terzidis-Mallat Élie , Constant-David Diane , Van Langhenhove Aurélien , Evin Adrien , Malineau Catherine , Tan Son V. O. , Mhalla Alaa , Lefaucheur Jean-Pascal , Nizard Julien 
Published: February 2023

Abstract
Background
Pain is a common symptom in palliative care cancer patients and is often insufficiently relieved. In recent years, transcranial direct-current stimulation (tDCS) of the motor cortex has been shown to be effective to treat chronic pain, essentially neuropathic pain. We propose to test the efficacy of tDCS in patients experiencing cancer pain in the palliative care setting.

Method/design
This article describes the protocol of a bicentre, randomized, parallel-arm, sham-controlled clinical trial evaluating tDCS in the treatment of palliative care patients with refractory cancer pain. Seventy patients between the ages of 18 and 80 years experiencing refractory pain with a pain score of 4/10 on a numerical rating scale (NRS) ranging from 0 to 10 will be enrolled in this trial. The main exclusion criteria are patients unable to fill in the various rating scales and life expectancy less than 3 weeks. Treatment consists of 5 consecutive tDCS sessions targeting the motor cortex (one daily session for 5 days) on the contralateral side to the pain. After randomization (1:1 ratio), 35 patients will receive active stimulation and 35 patients will receive sham stimulation. The primary endpoint is the NRS score and the primary objective is a significant improvement of this score between the baseline score recorded between D-3 and D-1 and the score recorded 4 days after stopping treatment (D8). The secondary objectives are to evaluate whether this improvement is maintained 16 days after stopping treatment (D21) and whether the following scores are improved on D14 and D21: Brief Pain Inventory, Edmonton Symptom Assessment System, Hospital Anxiety and Depression scale, State-Trait Anxiety Inventory and Medication Quantification Scale.

Discussion
Positive results of this trial would indicate that tDCS can improve pain and quality of life of cancer patients in the palliative care setting. Reduction of analgesic consumption and improvement of activities of daily living should allow many patients to return home with a decreased workload for caregivers.
Insights into the structure-function relationship of the NorQ/NorD chaperones from Paracoccus denitrificans reveal shared principles of interacting MoxR AAA+/VWA domain proteins
Authors: Kahle Maximilian , Appelgren Sofia , Elofsson Arne , Carroni Marta , Ädelroth Pia 
Published: February 2023

Abstract
Background
NorQ, a member of the MoxR-class of AAA+ ATPases, and NorD, a protein containing a Von Willebrand Factor Type A (VWA) domain, are essential for non-heme iron (FeB) cofactor insertion into cytochrome c-dependent nitric oxide reductase (cNOR). cNOR catalyzes NO reduction, a key step of bacterial denitrification. This work aimed at elucidating the specific mechanism of NorQD-catalyzed FeB insertion, and the general mechanism of the MoxR/VWA interacting protein families.

Results
We show that NorQ-catalyzed ATP hydrolysis, an intact VWA domain in NorD, and specific surface carboxylates on cNOR are all features required for cNOR activation. Supported by BN-PAGE, low-resolution cryo-EM structures of NorQ and the NorQD complex show that NorQ forms a circular hexamer with a monomer of NorD binding both to the side and to the central pore of the NorQ ring. Guided by AlphaFold predictions, we assign the density that “plugs” the NorQ ring pore to the VWA domain of NorD with a protruding “finger” inserting through the pore and suggest this binding mode to be general for MoxR/VWA couples.

Conclusions
Based on our results, we present a tentative model for the mechanism of NorQD-catalyzed cNOR remodeling and suggest many of its features to be applicable to the whole MoxR/VWA family.
Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts
Authors: Rothwell Joseph A. , Bešević Jelena , Dimou Niki , Breeur Marie , Murphy Neil , Jenab Mazda , Wedekind Roland , Viallon Vivian , Ferrari Pietro , Achaintre David , Gicquiau Audrey , Rinaldi Sabina , Scalbert Augustin , Huybrechts Inge , Prehn Cornelia , Adamski Jerzy , Cross Amanda J. , Keun Hector , Chadeau-Hyam Marc , Boutron-Ruault Marie-Christine , Overvad Kim , Dahm Christina C. , Nøst Therese Haugdahl , Sandanger Torkjel M. , Skeie Guri , Zamora-Ros Raul , Tsilidis Kostas K. , Eichelmann Fabian , Schulze Matthias B. , van Guelpen Bethany , Vidman Linda , Sánchez Maria-José , Amiano Pilar , Ardanaz Eva , Smith-Byrne Karl , Travis Ruth , Katzke Verena , Kaaks Rudolf , Derksen Jeroen W. G. , Colorado-Yohar Sandra , Tumino Rosario , Bueno-de-Mesquita Bas , Vineis Paolo , Palli Domenico , Pasanisi Fabrizio , Eriksen Anne Kirstine , Tjønneland Anne , Severi Gianluca , Gunter Marc J. 
Published: February 2023

Abstract
Background
Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts.

Methods
Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases.

Results
Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69–0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87–0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75–0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89–1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded.

Conclusions
Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.
Systemic inflammation indicators and risk of incident arrhythmias in 478,524 individuals: evidence from the UK Biobank cohort
Authors: Yang Xiaorong , Zhao Shaohua , Wang Shaohua , Cao Xuelei , Xu Yue , Yan Meichen , Pang Mingmin , Yi Fan , Wang Hao 
Published: February 2023

Abstract
Background
The role of systemic inflammation in promoting cardiovascular diseases has attracted attention, but its correlation with various arrhythmias remains to be clarified. We aimed to comprehensively assess the association between various indicators of systemic inflammation and atrial fibrillation/flutter (AF), ventricular arrhythmia (VA), and bradyarrhythmia in the UK Biobank cohort.

Methods
After excluding ineligible participants, a total of 478,524 eligible individuals (46.75% male, aged 40–69 years) were enrolled in the study to assess the association between systemic inflammatory indicators and each type of arrhythmia.

Results
After covariates were fully adjusted, CRP levels were found to have an essentially linear positive correlation with the risk of various arrhythmias; neutrophil count, monocyte count, and NLR showed a non-linear positive correlation; and lymphocyte count, SII, PLR, and LMR showed a U-shaped association. VA showed the strongest association with systemic inflammation indicators, and it was followed sequentially by AF and bradyarrhythmia.

Conclusions
Multiple systemic inflammatory indicators showed strong associations with the onset of AF, VA, and bradyarrhythmia, of which the latter two have been rarely studied. Active systemic inflammation management might have favorable effects in reducing the arrhythmia burden and further randomized controlled studies are needed.
Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ Approach of Curamericas: 5. Mortality assessment
Authors: Perry Henry B. , Stollak Ira , Llanque Ramiro , Okari Annah , Westgate Carey C. , Shindhelm Alexis , Chou Victoria B. , Valdez Mario 
Published: February 2023

Abstract
Background
The Curamericas/Guatemala Maternal and Child Health Project, 2011–2015, implemented the Census-Based, Impact-Oriented Approach, the Care Group Approach, and the Community Birthing Center Approach. Together, this expanded set of approaches is known as CBIO+. This is the fifth of 10 papers in our supplement describing the Project and the effectiveness of the CBIO+ Approach. This paper assesses causes, levels, and risk factors for mortality along with changes in mortality.

Methods
The Project maintained Vital Events Registers and conducted verbal autopsies for all deaths of women of reproductive age and under-5 children. Mortality rates and causes of death were derived from these data. To increase the robustness of our findings, we also indirectly estimated mortality decline using the Lives Saved Tool (LiST).

Findings
The leading causes of maternal and under-5 mortality were postpartum hemorrhage and pneumonia, respectively. Home births were associated with an eight-fold increased risk of both maternal (p = 0.01) and neonatal (p = 0.00) mortality. The analysis of vital events data indicated that maternal mortality declined from 632 deaths per 100,000 live births in Years 1 and 2 to 257 deaths per 100,000 live birth in Years 3 and 4, a decline of 59.1%. The vital events data revealed no observable decline in neonatal or under-5 mortality. However, the 12–59-month mortality rate declined from 9 deaths per 1000 live births in the first three years of the Project to 2 deaths per 1000 live births in the final year. The LiST model estimated a net decline of 12, 5, and 22% for maternal, neonatal and under-5 mortality, respectively.

Conclusion
The baseline maternal mortality ratio is one of the highest in the Western hemisphere. There is strong evidence of a decline in maternal mortality in the Project Area. The evidence of a decline in neonatal and under-5 mortality is less robust. Childhood pneumonia and neonatal conditions were the leading causes of under-5 mortality. Expanding access to evidence-based community-based interventions for (1) prevention of postpartum hemorrhage, (2) home-based neonatal care, and (3) management of childhood pneumonia could help further reduce mortality in the Project Area and in similar areas of Guatemala and beyond.
Reducing inequities in maternal and child health in rural Guatemala through the CBIO+﻿ Approach of Curamericas: 10. Summary, cost effectiveness, and policy implications
Authors: Perry Henry B. , Stollak Ira , Valdez Mario 
Published: February 2023

Abstract
Background
This is the final of 10 papers that describe the implementation of the Expanded Census-Based, Impact-Oriented Approach (CBIO+) by Curamericas/Guatemala in the Cuchumatanes mountains of the Department of Huehuetenango and its effectiveness in improving the health and well-being of women and children in a population of 98,000 in three municipalities. The CBIO+ Approach consists of three components: the CBIO (Census-Based, Impact-Oriented) Approach, the Care Group Approach, and the Community Birthing Center Approach.

Methods
Each of the preceding papers was summarized. An assessment was made regarding the degree to which the initial implementation research hypotheses were confirmed. The total field cost per capita for operation of the Project was calculated. An assessment of the cost-effectiveness of the Project was made based on the estimated impact of the Project, the number of lives saved, and the number of disability-adjusted life years averted.

Results
The Project attained a number of notable achievements in terms of expanding the coverage of key maternal and child health interventions, improving the nutritional status of children, reducing the mortality of children and mothers, providing quality care for mothers at the Community Birthing Centers (Casas Maternas Rurales) that integrate traditional midwives (comadronas) into the care of women during childbirth at the birthing centers, as well as empowering women and building social capital in the communities. CBIO+ is an effective and affordable approach that is particularly notable for its capacity to engage communities in the process of improving the health of mothers and children. Overall, there is strong and consistent evidence in support of the research hypotheses. The findings did produce evidence of declines in under-5 and maternal mortality, but they were not as robust as had been hoped.

Conclusion
CBIO+ is an approach that has been effective in engaging communities in the process of improving the health of their mothers and children and in reducing health inequities in this marginalized, difficult-to-reach population of Indigenous Maya people. The CBIO+ Approach is cost-effective and merits further development and broader application in Guatemala and beyond.
Assessing the patient experience of respiratory syncytial virus infection: development of a patient-reported outcome measure
Authors: Romano Carla , Finelli Lyn , Lewis Sandy , Williams Valerie , Martin Emily , Phillips Matthew , Saretsky Todd L. , Norquist Josephine 
Published: February 2023

Abstract
Background
Respiratory syncytial virus (RSV) causes significant morbidity and mortality in older adults. Despite a number of RSV vaccine candidates in clinical trials, there are no existing disease-specific, self-reported measures that assess the symptoms and severity of RSV infection from the perspective of adult patients with acute RSV. The objective of this study was to describe the initial conceptualization and development of the RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ), a new patient-reported outcome measure.

Methods
A targeted review of the literature identified relevant existing measures, symptoms, and impacts of RSV. A draft version of the RSV-iiiQ was developed based on the Influenza Intensity and Impact Questionnaire (Flu-iiQ) with expert input. Qualitative interviews (N = 20) were conducted with participants to optimize the RSV-iiiQ conceptual model and confirm the content validity of the RSV-iiiQ. Interviews included concept elicitation and a cognitive debriefing assessment. A draft conceptual framework was developed, and the electronic clinical outcome assessment was piloted. All steps of instrument development followed Food and Drug Administration guidance for patient-reported outcomes.

Results
In-depth concept elicitation interviews followed by cognitive debriefings demonstrated that the content of the items was comprehensive, covered the breadth of RSV symptoms and impacts, and was relevant to the experiences of individuals with RSV. Both the paper and electronic versions of the RSV-iiiQ were easily completed. Minor refinements were made to some items based on participant feedback, and the draft conceptual framework was refined.

Conclusions
The RSV-iiiQ was developed for use in clinical trials to measure the symptom intensity and impact of acute RSV infection from the perspective of adult patients. The tool was developed in accordance with current regulatory guidance and is useful to support patient-focused drug development.
Regional anesthesia did not improve postoperative long-term survival of tumor patients: a systematic review and meta-analysis of randomized controlled trials
Authors: Li Tao , Meng Xiangrui , Wang Di , Wang Qiang , Ma Jiahai , Dai Zhao 
Published: February 2023

Abstract
Objective
Experimental research and clinical trials have reported a positive effect of regional anesthesia (RA) on prognosis of cancers. We systematically reviewed the efficacy of RA on recurrence-free survival (RFS) and overall survival (OS) after oncology surgeries.

Methods
PubMed, Cochrane library, and Embase were searched from inception to June 20, 2022 for RCTs in which any form of RA was initiated perioperatively. Time-to-event data (hazard ratio (HR)) were extracted independently and in duplicate. The primary outcome was the association of RA with RFS and OS, while the secondary outcomes included time to tumor progression, 5-year RFS, and 5-year OS.

Results
Fifteen RCTs with 5981 participants were included. Compared to GA, RA has no positive effect on RFS (HR, − 0.02; 95% CI, − 0.11 to 0.07), OS (HR, − 0.03; 95% CI, − 0.28 to 0.23), time to tumor progression (0.11; 95% CI, − 0.33 to 0.55), 5-year RFS (risk ratio (RR), 1.24; 95% CI, 0.88 to 1.76)), and 5-year OS (RR, 1.11; 95% CI, 0.85 to 1.44). Subgroup analysis based on study design, patient characteristics and tumor types also showed no effect of RA on RFS or OS.

Conclusions
Our results demonstrated that there is no significant evidence supporting the role of RA in improving long-term survival after oncology surgeries.
Automating iPSC generation to enable autologous photoreceptor cell replacement therapy
Authors: Bohrer Laura R. , Stone Nicholas E. , Mullin Nathaniel K. , Voigt Andrew P. , Anfinson Kristin R. , Fick Jessica L. , Luangphakdy Viviane , Hittle Bradley , Powell Kimerly , Muschler George F. , Mullins Robert F. , Stone Edwin M. , Tucker Budd A. 
Published: February 2023

Abstract
Background
Inherited retinal degeneration is a leading cause of incurable vision loss in the developed world. While autologous iPSC mediated photoreceptor cell replacement is theoretically possible, the lack of commercially available technologies designed to enable high throughput parallel production of patient specific therapeutics has hindered clinical translation.

Methods
In this study, we describe the use of the Cell X precision robotic cell culture platform to enable parallel production of clinical grade patient specific iPSCs. The Cell X is housed within an ISO Class 5 cGMP compliant closed aseptic isolator (Biospherix XVivo X2), where all procedures from fibroblast culture to iPSC generation, clonal expansion and retinal differentiation were performed.

Results
Patient iPSCs generated using the Cell X platform were determined to be pluripotent via score card analysis and genetically stable via karyotyping. As determined via immunostaining and confocal microscopy, iPSCs generated using the Cell X platform gave rise to retinal organoids that were indistinguishable from organoids derived from manually generated iPSCs. In addition, at 120 days post-differentiation, single-cell RNA sequencing analysis revealed that cells generated using the Cell X platform were comparable to those generated under manual conditions in a separate laboratory.

Conclusion
We have successfully developed a robotic iPSC generation platform and standard operating procedures for production of high-quality photoreceptor precursor cells that are compatible with current good manufacturing practices. This system will enable clinical grade production of iPSCs for autologous retinal cell replacement.