bluuebunny/crossref_metadata_2025_split huggingface dataset:
Participatory family workshops in psychosocial health and illness research: experiences from Danish health promotion projects
Authors: Grabowski Dan , Pals Regitze Anne Saurbrey , Hoeeg Didde , Ingersgaard Marianne Vie , DeCosta Patricia , Jespersen Louise Norman 
Published: February 2022

Summary
Family involvement in health and illness research is a complex matter, often characterized by unclear structural relations and contrasting needs and expectations within the family. As the family is a setting in which health and illness behaviors are developed, maintained and potentially changed, gaining knowledge about family dynamics and how to approach familial health promotion is essential. But which methodological approaches are best suited to collecting data for generating such knowledge? We propose using participatory family workshops as a method to generate in-depth data on health-related psychosocial family dynamics, the goal is to improve the field of familial health promotion. We have used family workshops in a variety of settings among various target groups in different research and development projects. In the present article, we re-visit and discuss three research projects focusing on (i) families living with type 2 diabetes, (ii) family-based prevention of childhood obesity and (iii) families with a child with type 1 diabetes. We present experiences with all phases involved in planning and facilitating research workshops. Key points are discussed in relation to implications and perspectives for practice and research. Family workshops are complex and sometimes unpredictable. However, when family workshops are successful, they provide rich and dynamic in-depth data that cannot be produced using more traditional forms of data collection. The article provides an outline of experiences as well as hands-on recommendations for working with family workshops.
Constitutive nuclear accumulation of endogenous alpha-synuclein in mice causes motor impairment and cortical dysfunction, independent of protein aggregation
Authors: Geertsma Haley M , Suk Terry R , Ricke Konrad M , Horsthuis Kyra , Parmasad Jean-Louis A , Fisk Zoe A , Callaghan Steve M , Rousseaux Maxime W C 
Published: February 2022

Abstract
A growing body of evidence suggests that nuclear alpha-synuclein (αSyn) plays a role in the pathogenesis of Parkinson’s disease (PD). However, this question has been difficult to address as controlling the localization of αSyn in experimental systems often requires protein overexpression, which affects its aggregation propensity. To overcome this, we engineered SncaNLS mice, which localize endogenous αSyn to the nucleus. We characterized these mice on a behavioral, histological and biochemical level to determine whether the increase of nuclear αSyn is sufficient to elicit PD-like phenotypes. SncaNLS mice exhibit age-dependent motor deficits and altered gastrointestinal function. We found that these phenotypes were not linked to αSyn aggregation or phosphorylation. Through histological analyses, we observed motor cortex atrophy in the absence of midbrain dopaminergic neurodegeneration. We sampled cortical proteomes of SncaNLS mice and controls to determine the molecular underpinnings of these pathologies. Interestingly, we found several dysregulated proteins involved in dopaminergic signaling, including Darpp32, Pde10a and Gng7, which we further confirmed was decreased in cortical samples of the SncaNLS mice compared with controls. These results suggest that chronic endogenous nuclear αSyn can elicit toxic phenotypes in mice, independent of its aggregation. This model raises key questions related to the mechanism of αSyn toxicity in PD and provides a new model to study an underappreciated aspect of PD pathogenesis.
The Magnitude of Crohn’s Disease Direct Costs in Health Care Systems (from Different Perspectives): A Systematic Review
Authors: Santiago Mafalda , Dias Cláudia Camila , Alves Catarina , Ministro Paula , Gonçalves Raquel , Carvalho Diana , Portela Francisco , Correia Luís , Lago Paula , Magro Fernando 
Published: February 2022

Abstract

Background
The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, causing high impact on the quality of life of patients and an increasing burden for health care systems. In this systematic review, we reviewed the literature concerning the direct costs of Crohn’s disease (CD) for health care systems from different perspectives: regional, economic, and temporal.

Methods
We searched for original real-world studies examining direct medical health care costs in Crohn’s disease. The primary outcome measure was the mean value per patient per year (PPY) of total direct health care costs for CD. Secondary outcomes comprised hospitalization, surgery, CD-related medication (including biologics), and biologics mean costs PPY.

Results
A total of 19 articles were selected for inclusion in the systematic review. The studies enrolled 179 056 CD patients in the period between 1997 and 2016. The pooled mean total cost PPY was €6295.28 (95% CI, €4660.55-€8503.41). The pooled mean hospitalization cost PPY for CD patients was €2004.83 (95% CI, €1351.68-€2973.59). The major contributors for the total health expenditure were biologics (€5554.58) and medications (€3096.53), followed by hospitalization (€2004.83) and surgery (€1883.67). No differences were found between regional or economic perspectives, as confidence intervals overlapped. However, total costs were significantly higher after 2010.

Conclusions
Our review highlighted the burden of CD for health care systems from different perspectives (regional, economic, and temporal) and analyzed the impact of the change of IBD treatment paradigm on total costs. Reducing the overall burden can depend on the increase of remission rates to further decrease hospitalizations and surgeries.
Strong tuberculin response after BCG vaccination is associated with low multiple sclerosis risk: a population-based cohort study
Authors: Nakken Ola , Holmøy Trygve , Stigum Hein , Myhr Kjell-Morten , Dahl Jesper , Heldal Einar , Meyer Haakon E 
Published: February 2022

Abstract

Background
Multiple sclerosis (MS) is characterized by inflammatory lesions in the central nervous system involving pro-inflammatory T-cells. Immune dysregulation is well described in prevalent disease, but it is not known whether this precedes disease development. Bacillus Calmette–Guérin (BCG) vaccination ameliorates MS-like disease in mice. In people vaccinated with BCG, the tuberculin skin test (TST) offers a standardized measure of a T-cell-mediated immune response. We therefore hypothesized that the strength of the TST response after BCG vaccination is associated with subsequent MS risk.

Methods
Using data from a Norwegian tuberculosis screening programme (1963–1975), we designed a population-based cohort study and related the size of TST reactions in individuals previously vaccinated with BCG to later MS disease identified through the Norwegian MS registry. We fitted Cox proportional hazard models and flexible parametric survival models to investigate the association between TST reactivity, MS risk and its temporal relationship.

Results
Among 279 891 participants (52% females), 679 (69% females) later developed MS. Larger TST reactivity was associated with decreased MS risk. The hazard ratio for MS per every 4-mm increase in skin induration size was 0.86 (95% confidence interval 0.76–0.96) and similar between sexes. The strength of the association persisted for &gt;30 years after the TST.

Conclusion
A strong in vivo vaccine response to BCG is associated with reduced MS risk &gt;30 years later. The immunological mechanisms determining TST reactivity suggest that skewed T-cell-mediated immunity precedes MS onset by many decades.
Effect of calcination on the adsorption of Chifeng zeolite on Pb2+ and Cu2+
Authors: Chen Xiaolong , Tao Jieshi , Sun Pengliang , Yu Fujia , Li Bin , Dun Linan 
Published: February 2022

Abstract
As an important non-metallic mineral resource, zeolite is widely used in many fields. In this paper, natural zeolite from Chifeng, Inner Mongolia, was selected as the experimental material, and the calcination effect of the sample was studied in detail. The zeolite sample undergoes complex changes during the calcination process. The higher the calcination temperature, the smaller the specific surface area of the sample. When calcined at 150°C for 1 h, zeolite samples with granularity ranging from 0.050 to 0.075 mm show relatively good removal of Cu2+ and Pb2+from aqueous solution. After the zeolite is calcined, the solution with an initial concentration of 100 mg/l of heavy metal ions can reduce the concentration of Pb2+ and Cu2+ to 25 mg/l and 60 mg/l, respectively, with a removal rate of 75% and 40%. In addition, this article also focuses on its removal mechanism.
Domestic Workers, the ‘Family Worker’ Exemption from Minimum Wage, and Gendered Devaluation of Women’s Work
Authors: Sedacca Natalie 
Published: February 2022

Abstract
Domestic workers, who work in private households carrying out tasks such as cooking, cleaning, and care for children and the elderly, are overwhelmingly women and often from migrant and/ or ethnic minority backgrounds. This article examines a stark example of domestic workers’ exclusion from labour law protection, regulation 57(3) of the National Minimum Wage Regulations, which exempts employers from paying the minimum wage where a worker lives in their employer’s family home and is treated ‘as a member of the family’ in relation to accommodation, meals, tasks and leisure activities. Drawing on feminist theory on the divisions between ‘productive’ work outside the home versus ‘reproductive’ work within it, it argues that the exemption’s application has reflected gendered devaluation of domestic labour, stemming from its conflation with work normally performed for free by women in the ‘private sphere’ of the home. Focusing on the December 2020 Employment Tribunal (ET) judgment in Puthenveettil v Alexander & ors, which held that the exemption was unlawful and indirectly discriminatory on the grounds of sex, the article provides timely and in-depth analysis of the prospects for challenging the devaluation of domestic work in light of the limitations of legal protections for domestic workers in the UK.
Cost-effectiveness of Respiratory Syncytial Virus Disease Prevention Strategies: Maternal Vaccine Versus Seasonal or Year-Round Monoclonal Antibody Program in Norwegian Children
Authors: Li Xiao , Bilcke Joke , Vázquez Fernández Liliana , Bont Louis , Willem Lander , Wisløff Torbjørn , Jit Mark , Beutels Philippe ,   REspiratory Syncytial virus Consortium in EUrope (RESCEU) Investigators, Beutels Philippe , Bont Louis , Nair Harish , Campbell Harry , Pollard Andrew , Openshaw Peter , Martinon-Torres Federico , Heikkinen Terho , Meijer Adam , Fischer Thea K , van den Berge Maarten , Giaquinto Carlo , Abram Michael , Swanson Kena , Rizkalla Bishoy , Vernhes Charlotte , Gallichan Scott , Aerssens Jeroen , Kumar Veena , Molero Eva 
Published: February 2022

Abstract

Background
Every winter, respiratory syncytial virus (RSV) disease results in thousands of cases in Norwegian children under 5 years of age. We aim to assess the RSV-related economic burden and the cost-effectiveness of upcoming RSV disease prevention strategies including year-round maternal immunization and year-round and seasonal monoclonal antibody (mAb) programs.

Methods
Epidemiological and cost data were obtained from Norwegian national registries, while quality-adjusted life-years (QALYs) lost and intervention characteristics were extracted from literature and phase 3 clinical trials. A static model was used and uncertainty was accounted for probabilistically. Value of information was used to assess decision uncertainty. Extensive scenario analyses were conducted, including accounting for long-term consequences of RSV disease.

Results
We estimate an annual average of 13 517 RSV cases and 1572 hospitalizations in children under 5, resulting in 79.6 million Norwegian kroner (~€8 million) treatment costs. At €51 per dose for all programs, a 4-month mAb program for neonates born in November to February is the cost-effective strategy for willingness to pay (WTP) values up to €40 000 per QALY gained. For higher WTP values, the longer 6-month mAb program that immunizes neonates from October to March becomes cost-effective. Sensitivity analyses show that year-round maternal immunization can become a cost-effective strategy if priced lower than mAb.

Conclusions
Assuming the same pricing, seasonal mAb programs are cost-effective over year-round programs in Norway. The timing and duration of the cost-effective seasonal program are sensitive to the pattern of the RSV season in a country, so continued RSV surveillance data are essential.
Longitudinal Systemic and Mucosal Immune Responses to SARS-CoV-2 Infection
Authors: Wright Peter F , Prevost-Reilly Alejandra C , Natarajan Harini , Brickley Elizabeth B , Connor Ruth I , Wieland-Alter Wendy F , Miele Anna S , Weiner Joshua A , Nerenz Robert D , Ackerman Margaret E 
Published: February 2022

Abstract

Background
A longitudinal study was performed to determine the breadth, kinetics, and correlations of systemic and mucosal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods
Twenty-six unvaccinated adults with confirmed coronavirus disease 2019 (COVID-19) were followed for 6 months with 3 collections of blood, nasal secretions, and stool. Control samples were obtained from 16 unvaccinated uninfected individuals. SARS-CoV-2 neutralizing and binding antibody responses were respectively evaluated by pseudovirus assays and multiplex bead arrays.

Results
Neutralizing antibody responses to SARS-CoV-2 were detected in serum and respiratory samples for 96% (25/26) and 54% (14/26), respectively, of infected participants. Robust binding antibody responses against SARS-CoV-2 spike protein and S1, S2, and receptor binding (RBD) domains occurred in serum and respiratory nasal secretions, but not in stool samples. Serum neutralization correlated with RBD-specific immunoglobulin (Ig)G, IgM, and IgA in serum (Spearman ρ = 0.74, 0.66, and 0.57, respectively), RBD-specific IgG in respiratory secretions (ρ = 0.52), disease severity (ρ = 0.59), and age (ρ = 0.40). Respiratory mucosal neutralization correlated with RBD-specific IgM (ρ = 0.42) and IgA (ρ = 0.63).

Conclusions
Sustained antibody responses occurred after SARS-CoV-2 infection. Notably, there was independent induction of IgM and IgA binding antibody and neutralizing responses in systemic and respiratory compartments. These observations have implications for current vaccine strategies and understanding SARS-CoV-2 reinfection and transmission.
Disulfiram enhances meropenem activity against NDM- and IMP-producing carbapenem-resistantAcinetobacter baumanniiinfections
Authors: Dubey Vineet , Devnath Kuldip , Gupta Vivek K , Kalyan Gazal , Singh Mangal , Kothari Ashish , Omar Balram Ji , Pathania Ranjana 
Published: February 2022

AbstractObjectivesTo evaluate the in vitro and in vivo efficacy of the FDA-approved drug disulfiram in combination with meropenem against MBL-expressing carbapenem-resistant Acinetobacter baumannii.MethodsChequerboard and antibiotic resistance reversal analysis were performed using 25 clinical isolates producing different MBLs. Three representative strains harbouring NDM, IMP or non-MBL genes were subjected to a time–kill assay to further evaluate this synergistic interaction. Dose-dependent inhibition by disulfiram was assessed to determine IC50 for NDM-1, IMP-7, VIM-2 and KPC-2. Further, to test the efficacy of meropenem monotherapy and meropenem in combination with disulfiram against NDM- and IMP-harbouring A. baumannii, an experimental model of systemic infection and pneumonia was developed using BALB/c female mice.ResultsChequerboard and antibiotic reversal assay displayed a synergistic interaction against MBL-expressing A. baumannii strains with 4- to 32-fold reduction in MICs of meropenem. In time–kill analysis, meropenem and disulfiram exhibited synergy against NDM- and IMP-producing carbapenem-resistant A. baumannii (CRAb) isolates. In vitro dose-dependent inhibition analysis showed that disulfiram inhibits NDM-1 and IMP-7 with IC50 values of 1.5 ± 0.6 and 16.25 ± 1.6 μM, respectively, with slight or no inhibition of VIM-2 (&lt;20%) and KPC-2. The combination performed better in the clearance of bacterial load from the liver and spleen of mice infected with IMP-expressing CRAb. In the pneumonia model, the combination significantly decreased the bacterial burden of NDM producers compared with monotherapy.ConclusionsThese results strongly suggest that the combination of disulfiram and meropenem represents an effective treatment option for NDM- and IMP-associated CRAb infections.
Vancomycin-arginine (STM-001) abrogates ESBL carrier and carbapenem-resistant Escherichia coli burden in a murine complicated urinary tract infection model
Authors: Neville Lewis F. , Shalit Itamar , Warn Peter A. , Rendell Jacob T. 
Published: February 2022

Abstract

Objectives
STM-001, a retargeted glycopeptide, is active against MDR E. coli expressing ESBLs including carbapenemases. Herein, we assessed its capability to combat E. coli complicated urinary tract infections (cUTI) in mice driven by clinically important serine (CTX-M-15) and metallo-β-lactamases (NDM-1).

Methods
Plasma and urine pharmacokinetics following IV administration of STM-001 (1–50 mg/kg) were determined in mice via LC-MS/MS. The effects on bacterial burden (kidney, bladder and urine) were determined in a 7 day mouse cUTI model whereby STM-001 was administered q12h or q24h at 2–100 mg/kg/day from Day 4. Efficacy was assessed by the change in log10 cfu/g or log10 cfu/mL from vehicle-treated infected mice.

Results
MICs of STM-001 for CTX-M-15 and NDM-1 E. coli were 8 and 16 mg/L, respectively. Blood pharmacokinetic profile was linear and dose-dependent with low clearance of 9.49 ± 0.31 mL/min/kg, V = 0.63 ± 0.02 L/kg and t½ = 1.16 ± 0.03 h. High STM-001 concentrations were recovered in urine 0–8 h post-administration, reaching up to 120-fold above its MIC. In cUTI efficacy studies, STM-001 (1–50 mg/kg, q12h) reduced CTX-M-15 burden by log10 4.31 (kidney), 3.95 (bladder) and 4.82 (urine) compared with vehicle-treated animals (P &lt; 0.0001). STM-001 also reduced NDM-1 burden by log10 3.89 (kidney), 3.76 (bladder) and 3.08 (urine) (P &lt; 0.0001), with similar inhibitory effects following q24h dosing.

Conclusions
STM-001 was highly effective in reducing E. coli burden in kidney, bladder and urine in mouse cUTI models. The observed efficacy with either dosing regimen indicates potential low humanized doses of 1–5 mg/kg. These data support further development of STM-001 as an innovative, carbapenem-sparing antibiotic to combat human cUTIs.
GARDE: a standards-based clinical decision support platform for identifying population health management cohorts
Authors: Bradshaw Richard L , Kawamoto Kensaku , Kaphingst Kimberly A , Kohlmann Wendy K , Hess Rachel , Flynn Michael C , Nanjo Claude J , Warner Phillip B , Shi Jianlin , Morgan Keaton , Kimball Kadyn , Ranade-Kharkar Pallavi , Ginsburg Ophira , Goodman Melody , Chambers Rachelle , Mann Devin , Narus Scott P , Gonzalez Javier , Loomis Shane , Chan Priscilla , Monahan Rachel , Borsato Emerson P , Shields David E , Martin Douglas K , Kessler Cecilia M , Del Fiol Guilherme 
Published: February 2022

Abstract

Population health management (PHM) is an important approach to promote wellness and deliver health care to targeted individuals who meet criteria for preventive measures or treatment. A critical component for any PHM program is a data analytics platform that can target those eligible individuals.

Objective
The aim of this study was to design and implement a scalable standards-based clinical decision support (CDS) approach to identify patient cohorts for PHM and maximize opportunities for multi-site dissemination.

Materials and Methods
An architecture was established to support bidirectional data exchanges between heterogeneous electronic health record (EHR) data sources, PHM systems, and CDS components. HL7 Fast Healthcare Interoperability Resources and CDS Hooks were used to facilitate interoperability and dissemination. The approach was validated by deploying the platform at multiple sites to identify patients who meet the criteria for genetic evaluation of familial cancer.

Results
The Genetic Cancer Risk Detector (GARDE) platform was created and is comprised of four components: (1) an open-source CDS Hooks server for computing patient eligibility for PHM cohorts, (2) an open-source Population Coordinator that processes GARDE requests and communicates results to a PHM system, (3) an EHR Patient Data Repository, and (4) EHR PHM Tools to manage patients and perform outreach functions. Site-specific deployments were performed on onsite virtual machines and cloud-based Amazon Web Services.

Discussion
GARDE’s component architecture establishes generalizable standards-based methods for computing PHM cohorts. Replicating deployments using one of the established deployment methods requires minimal local customization. Most of the deployment effort was related to obtaining site-specific information technology governance approvals.
Foot Burns in Persons With Diabetes: Outcomes From the National Trauma Data Bank
Authors: Perrault David , Cobert Jason , Gadiraju Veda , Sharma Ayushi , Gurtner Geoffrey , Pham Tam , Sheckter Clifford C 
Published: February 2022

Abstract
Diabetes mellitus (DM) complicates the treatment of burn injuries. Foot burns in diabetic patients are challenging problems with unfavorable outcomes. National-scale evaluations are needed, especially with regard to limb salvage. We aim to characterize lower-extremity burns in persons with DM and evaluate the likelihood of amputation. The National Trauma Data Bank (NTDB) was queried from 2007 to 2015 extracting encounters with primary burn injuries of the feet using International Classification of Diseases (ICD) 9th edition codes. Logistic regression modeled predictors of lower-extremity amputation. Covariables included age, sex, race/ethnicity, comorbidities including DM, % burn TBSA, mechanism, and region of burn center. Poisson regression evaluated temporal incidence rate changes in DM foot burns. Of 116,796 adult burn encounters, 7963 (7%) had foot burns. Of this group, 1308 (16%) had DM. 5.6% of encounters with DM foot burns underwent amputation compared to 1.5% of non-DM encounters (P &lt; .001). Independent predictors of lower-extremity amputation included DM (odds ratio 3.70, 95% confidence interval 2.98–4.59), alcohol use, smoking, chronic kidney disease, and burn size &gt;20%, African-American/black race, male sex, and age &gt;40 years (all P &lt; .01). The incidence of DM foot burns increased over the study period with an incidence rate ratio of 1.07 (95% confidence interval 1.05–1.10, P &lt; .001). In conclusion, DM was associated with nearly a 4-fold increase in amputation after adjusting for covariables. Furthermore, the incidence of DM foot burns is increasing. Strategies for optimizing care in persons with DM foot burns are need to improve limb salvage.
The Special Tribunal for Lebanon and its Outreach Programme
Authors: Kavran Olga 
Published: February 2022

Abstract
Not only did the Special Tribunal Lebanon face the same challenges as many other international tribunals, but arguably it was situated in a uniquely politicized context. Perhaps for this reason, the importance of outreach was recognized from the outset, as part of its legal framework. While the STL may not have concluded its operations in the manner originally envisaged, its approach to outreach and public information — including an emphasis on meta-normative truths and the importance of education — may offer valuable insights for the future, both for international and, with the increasing number of universal jurisdiction cases, also national, jurisdictions.