bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining optimal implementation packages for delivering community-wide mass drug administration for soil-transmitted helminths with high coverage
Authors: Gwayi-Chore Marie-Claire , Aruldas Kumudha , Avokpaho Euripide , Chirambo Chawanangwa Maherebe , Kaliappan Saravanakumar Puthupalayam , Houngbégnon Parfait , Togbevi Comlanvi Innocent , Chabi Félicien , Nindi Providence , Simwanza James , Johnson Jabaselvi , Miech Edward J. , Kalua Khumbo , Ibikounlé Moudachirou , Ajjampur Sitara S. R. , Weiner Bryan J. , Walson Judd L. , Means Arianna Rubin 
Published: June 2022

Abstract
Background
Recent evidence suggests that community-wide mass drug administration (MDA) may interrupt the transmission of soil-transmitted helminths (STH), a group of intestinal worms that infect 1.5 billion individuals globally. Although current operational guidelines provide best practices for effective MDA delivery, they do not describe which activities are most essential for achieving high coverage or how they work together to produce effective intervention delivery. We aimed to identify the various packages of influential intervention delivery activities that result in high coverage of community-wide MDA for STH in Benin, India, and Malawi.

Methods
We applied coincidence analysis (CNA), a novel cross-case analytical method, to process mapping data as part of the implementation science research of the DeWorm3 Project, a Hybrid Type 1 cluster randomized controlled trial assessing the feasibility of interrupting the transmission of STH using bi-annual community-wide MDA in Benin, India, and Malawi. Our analysis aimed to identify any necessary and/or sufficient combinations of intervention delivery activities (i.e., implementation pathways) that resulted in high MDA coverage. Activities were related to drug supply chain, implementer training, community sensitization strategy, intervention duration, and implementation context. We used pooled implementation data from three sites and six intervention rounds, with study clusters serving as analytical cases (N = 360). Secondary analyses assessed differences in pathways across sites and over intervention rounds.

Results
Across all three sites and six intervention rounds, efficient duration of MDA delivery (within ten days) singularly emerged as a common and fundamental component for achieving high MDA coverage when combined with other particular activities, including a conducive implementation context, early arrival of albendazole before the planned start of MDA, or a flexible community sensitization strategy. No individual activity proved sufficient by itself for producing high MDA coverage. We observed four possible overall models that could explain effective MDA delivery strategies, all which included efficient duration of MDA delivery as an integral component.

Conclusion
Efficient duration of MDA delivery uniquely stood out as a highly influential implementation activity for producing high coverage of community-wide MDA for STH. Effective MDA delivery can be achieved with flexible implementation strategies that include various combinations of influential intervention components.
Cisplatin-associated ototoxicity: perspectives from a single institution cervical cancer cohort and implications for developing a locally responsive monitoring programme in a public healthcare setting
Authors: Paken Jessica , Govender Cyril D. , Pillay Mershen , Sewram Vikash 
Published: June 2022

AbstractBackgroundOtotoxicity monitoring is uncommon in South Africa, despite the increased use of ototoxic medication to manage the burden of disease in the country. The successful implementation of such a protocol requires cognisance of contextual realities and multiple dimensions for consideration from both patients and service providers. As part of an ongoing cohort study on cisplatin-associated ototoxicity and efforts to better inform the implementation of such programmes, the perspectives of cervical cancer patients and healthcare workers towards ototoxicity monitoring were assessed.MethodsThis concurrent-triangulation mixed-methods study was conducted at a tertiary hospital in South Africa. Self-reported questionnaires from patients (n = 80) and healthcare personnel comprising clinicians, oncology nurses, pharmacists, and radiotherapists (n = 32), results of audiological evaluations, researcher field notes, and estimated patient and service provider costs contributed to data for this study. Data analysis included descriptive statistics, comparison of test characteristics and deductive thematic analysis.ResultsThe ototoxicity monitoring programme was positively received by the participants, with 90.6% of healthcare personnel and 89% of patients reporting it to be beneficial. The clinicians (76.6%) were identified as the main providers of information on the effects of chemotherapy medication and made the necessary referrals for audiological evaluation. The approximate cost of setting up such a programme included purchase of equipment (US56 700) and the appointment of an audiologist (US 26 250). The approximate costs to patients included transport costs (US$ 38) and the loss of income for the day (US 60), calculated at the minimum wage per hour, if employed. Creative appointment scheduling, easy facility access and detailed locally comprehensible couselling improved patient compliance to the programme. Whilst the sequential use of American Speech-Language-Hearing Association (ASHA) and National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria aided in an evidence-informed approach to aural rehabilitation, DPOAEs and speech discrimination displayed low sensitivity (range 1.45% – 22.39%) but high specificity (range 77.78% – 100%) when identifying ototoxic change.ConclusionThis novel study, through a ‘real-world’ experience, has revealed that an ototoxicity monitoring programme is feasible in South Africa, through meaningful engagements with- and considerations from- patients and service providers regarding planning, delineation of responsibilities and cost implications. The findings can potentially serve as a roadmap for other limited resource environments.
Ordering of computed tomography scans for head and cervical spine: a qualitative study exploring influences on doctors’ decision-making
Authors: Hattingh H. Laetitia , Michaleff Zoe Alexandra , Fawzy Peter , Du Leanne , Willcocks Karlene , Tan K. Meng , Keijzers Gerben 
Published: June 2022

Abstract
Background
Ordering of computed tomography (CT) scans needs to consideration of diagnostic utility as well as resource utilisation and radiation exposure. Several factors influence ordering decisions, including evidence-based clinical decision support tools to rule out serious disease. The aim of this qualitative study was to explore factors influencing Emergency Department (ED) doctors’ decisions to order CT of the head or cervical spine.

Methods
In-depth semi-structured interviews were conducted with purposively selected ED doctors from two affiliated public hospitals. An interview tool with 10 questions, including three hypothetical scenarios, was developed and validated to guide discussions. Interviews were audio recorded, transcribed verbatim, and compared with field notes. Transcribed data were imported into NVivo Release 1.3 to facilitate coding and thematic analysis.

Results
In total 21 doctors participated in semi-structured interviews between February and December 2020; mean interview duration was 35 min. Data saturation was reached. Participants ranged from first-year interns to experienced consultants. Five overarching emerging themes were: 1) health system and local context, 2) work structure and support, 3) professional practices and responsibility, 4) reliable patient information, and 5) holistic patient-centred care. Mapping of themes and sub-themes against a behaviour change model provided a basis for future interventions.

Conclusions
CT ordering is complex and multifaceted. Multiple factors are considered by ED doctors during decisions to order CT scans for head or c-spine injuries. Increased education on the use of clinical decision support tools and an overall strategy to improve awareness of low-value care is needed. Strategies to reduce low-yield CT ordering will need to be sustainable, sophisticated and supportive to achieve lasting change.
Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomics
Authors: Hsu Yu-Wen , Wong Henry Sung-Ching , Huang Wan-Chen , Yeh Yi-Hung , Hsiao Chwan-Deng , Chang Wei-Chiao , Hsieh Shie-Liang 
Published: June 2022

AbstractBackgroundHuman traits, diseases susceptibility, and clinical outcomes vary hugely among individuals. Despite a fundamental understanding of genetic (or environmental) contributions, the detailed mechanisms of how genetic variation impacts molecular or cellular behaviours of a gene, and subsequently leads to such variability remain poorly understood.MethodsHere, in addition to phenome-wide correlations, we leveraged multiomics to exploit mechanistic links, from genetic polymorphism to protein structural or functional changes and a cross-omics perturbation landscape of a germline variant.ResultsWe identified a missensecis-acting expression quantitative trait locus inCLEC18A(rs75776403) in which the altered residue (T151→M151) disrupts the lipid-binding ability of the protein domain. The altered allele carriage led to a metabolic and proliferative shift, as well as immune deactivation, therefore determines human anthropometrics (body height), kidney, and hematological traits.ConclusionsCollectively, we uncovered genetic pleiotropy in human complex traits and diseases viaCLEC18Ars75776403-regulated pathways.
Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials
Authors: Wijkman Magnus O. , Claggett Brian , Vaduganathan Muthiah , Cunningham Jonathan W. , Rørth Rasmus , Jackson Alice , Packer Milton , Zile Michael , Rouleau Jean , Swedberg Karl , Lefkowitz Martin , Shah Sanjiv J. , Pfeffer Marc A. , McMurray John J. V. , Solomon Scott D. 
Published: June 2022

Abstract
Background
Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes.

Methods
We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF.

Results
Among 2395 patients with HFpEF and diabetes in PARAGON-HF, sacubitril/valsartan compared with valsartan reduced HbA1c (baseline-adjusted between-group difference in HbA1c change at 48 weeks: − 0.24%, 95% CI − 0.33 to − 0.16%, P < 0.001). Numerically, new insulin treatment was initiated less often in the sacubitril/valsartan group than in the valsartan group, but the difference was not statistically significant (12.8% vs. 16.1%; HR: 0.80, 95% CI 0.62–1.02, P = 0.07). Hypoglycemia adverse event reports were low, but more frequent in those receiving sacubitril/valsartan than in the valsartan group (4.2% vs. 2.6%; HR: 1.64, 95% CI 1.05–2.56, P = 0.030). In a pooled analysis of PARAGON-HF and PARADIGM-HF, the effect of sacubitril/valsartan on change in HbA1c was not significantly modified by LVEF (Pinteraction = 0.56). Across the spectrum of LVEF, sacubitril/valsartan reduced new insulin therapy (HR: 0.75, 95% CI 0.63–0.89, P = 0.001), compared with enalapril or valsartan.

Conclusions
Sacubitril/valsartan reduced HbA1c and new insulin therapy in patients with heart failure and diabetes across the spectrum of LVEF but may be associated with a slightly higher risk for hypoglycemia.
Trial registration ClinicalTrials.gov NCT01920711
The dual interaction of antimicrobial peptides on bacteria and cancer cells; mechanism of action and therapeutic strategies of nanostructures
Authors: Parchebafi Atefeh , Tamanaee Farzaneh , Ehteram Hassan , Ahmad Ejaz , Nikzad Hossein , Haddad Kashani Hamed 
Published: June 2022

AbstractMicrobial infection and cancer are two leading causes of global mortality. Discovering and developing new therapeutics with better specificity having minimal side-effects and no drug resistance are of an immense need. In this regard, cationic antimicrobial peptides (AMP) with dual antimicrobial and anticancer activities are the ultimate choice. For better efficacy and improved stability, the AMPs available for treatment still required to be modified. There are several strategies in which AMPs can be enhanced through, for instance, nano-carrier application with high selectivity and specificity enables researchers to estimate the rate of drug delivery to a particular tissue. In this review we present the biology and modes of action of AMPs for both anticancer and antimicrobial activities as well as some modification strategies to improve the efficacy and selectivity of these AMPs.
Graphical Abstract
Validity and reliability of a food frequency questionnaire for community dwelling older adults in a Mediterranean country: Lebanon
Authors: Yaghi Nathalie , Boulos Christa , Baddoura Rafic , Abifadel Marianne , Yaghi Cesar 
Published: June 2022

Abstract
Background
Food frequency questionnaires (FFQ) is an easy and inexpensive tool that can be used to evaluate nutrient and dietary trends of groups and individuals. Few studies in the East Mediterranean region tailored FFQs to describe dietary intakes of older adults. The purpose of the study is therefore to assess the validity and reproducibility of a FFQ, designed for use with older adults living in a Mediterranean Arabic speaking country, Lebanon.

Methods
The FFQ is composed of a list of 90 food items, commonly consumed by adults above 60 years of age. Validity of the FFQ was tested using the mean of two 24-hours dietary recalls (24HDR), and reproducibility, by repeating the questionnaire within a one-month period, along the second dietary recall. Our study included 42 and 76 participants, for the repoducibility and validity analysis respectively. Subjects were randomly selected from 2 of the 8 governorates in the country.

Results
FFQ reproducibility showed a mean relative difference of 1.03% without any significant difference between all paired components of nutrients. Intra class correlation (ICC) showed good and excellent reliability for caloric intake and all macronutrients, moderate to good reliability for all remaining nutrients, except for poly-unsaturated fatty acids, vitamins A, B12 and fibers. Correlation coefficients for all nutrients were fair to strong. Both administrations of the FFQ showed good internal validity. Validation of FFQ showed a mean relative difference between FFQ and mean 24HDR at 19.5%. Agreements between the 2 methods, for classifying individuals in the same or adjacent quartile, for nutrient intake and nutrient adequacy, were 80 and 78.2% respectively. Mean Kappa coefficient was 0.56 and energy-adjusted correlations were within the recommended values for all items except for vitamin A and B12. Adjusting for nutrient-dense food intake improved the agreement for theses 2 vitamins to 0.49 and 0.56, respectively.

Conclusion
The proposed FFQ can be considered a valid tool to help describe nutrient intake of older individuals in an Arabic speaking Mediterranean country. It could serve for possible use in the East Mediterranean region for the evaluation of regular dietary intake of community-dwelling older adults.
Healthy U.S.-style dietary patterns can be modified to provide increased energy from protein
Authors: Murphy Mary M. , Barraj Leila M. , Higgins Kelly A. 
Published: June 2022

AbstractBackgroundDietary patterns developed by the USDA provide modest levels of protein (14–18% energy) within the Acceptable Macronutrient Distribution Range (AMDR) of 10–35% for adults, though diets providing a higher percentage of energy may be beneficial for some individuals. The purpose of this study was to determine if it is feasible to modify the Healthy U.S.-Style Eating Pattern (“HEP”) to provide a higher percentage of energy from protein.MethodsUsing the framework implemented by the USDA in developing the HEP, energy from protein was set at 20%, 25%, and 30%. Amounts of protein foods were proportionally increased while amounts of other foods were adjusted iteratively within specified parameters. The models also disaggregated total meat/poultry into fresh and processed forms to develop patterns maintaining current proportions, current levels, reduced, or no processed meat/poultry. Nutrient intakes were compared with nutrient goals for representative U.S. populations with 2,000 kcal needs (females 19–30 years, males 51–70 years), with 90% of the Recommended Dietary Allowance or Adequate Intake regarded as sufficient.ResultsDietary patterns with 20% energy from protein were constructed with minor deviations from the current 2,000 kcal HEP. Dietary patterns with 25% energy from protein were constructed for all levels of processed meat/poultry excluding the current proportion model, though relative to the current HEP the constructed patterns reflect substantial reductions in amounts of refined grains and starchy vegetables, and substantial increases in protein foods consumed as beans and peas, seafood, and soy products. It was not possible to develop a pattern with 30% energy from protein without reducing the percentage of energy from carbohydrate below the AMDR or non-compliance with other modeling constraints. Stepwise reductions in processed meat/poultry reduced sodium intake.ConclusionsIt is feasible to develop dietary patterns in a 2,000 kcal diet while mirroring the HEP that meet recommended intakes of nutrients with 20% or 25% energy from protein, though the pattern with 25% energy from protein may be more idealistic than realistic. Reduced levels of processed meat/poultry may translate to lower sodium intake.
Comprehensive characterization of the prostate tumor microenvironment identifies CXCR4/CXCL12 crosstalk as a novel antiangiogenic therapeutic target in prostate cancer
Authors: Heidegger Isabel , Fotakis Georgios , Offermann Anne , Goveia Jermaine , Daum Sophia , Salcher Stefan , Noureen Asma , Timmer-Bosscha Hetty , Schäfer Georg , Walenkamp Annemiek , Perner Sven , Beatovic Aleksandar , Moisse Matthieu , Plattner Christina , Krogsdam Anne , Haybaeck Johannes , Sopper Sieghart , Thaler Stefanie , Keller Markus A. , Klocker Helmut , Trajanoski Zlatko , Wolf Dominik , Pircher Andreas 
Published: June 2022

Abstract
Background
Crosstalk between neoplastic and stromal cells fosters prostate cancer (PCa) progression and dissemination. Insight in cell-to-cell communication networks provides new therapeutic avenues to mold processes that contribute to PCa tumor microenvironment (TME) alterations. Here we performed a detailed characterization of PCa tumor endothelial cells (TEC) to delineate intercellular crosstalk between TEC and the PCa TME.

Methods
TEC isolated from 67 fresh radical prostatectomy (RP) specimens underwent multi-omic ex vivo characterization as well as orthogonal validation of both TEC functions and key markers by immunohistochemistry (IHC) and immunofluorescence (IF). To identify cell–cell interaction targets in TEC, we performed single-cell RNA sequencing (scRNA-seq) in four PCa patients who underwent a RP to catalogue cellular TME composition. Targets were cross-validated using IHC, publicly available datasets, cell culture expriments as well as a PCa xenograft mouse model.

Results
Compared to adjacent normal endothelial cells (NEC) bulk RNA-seq analysis revealed upregulation of genes associated with tumor vasculature, collagen modification and extracellular matrix remodeling in TEC. PTGIR, PLAC9, CXCL12 and VDR were identified as TEC markers and confirmed by IF and IHC in an independent patient cohort. By scRNA-seq we identified 27 cell (sub)types, including endothelial cells (EC) with arterial, venous and immature signatures, as well as angiogenic tip EC. A focused molecular analysis revealed that arterial TEC displayed highest CXCL12 mRNA expression levels when compared to all other TME cell (sub)populations and showed a negative prognostic role. Receptor-ligand interaction analysis predicted interactions between arterial TEC derived CXCL12 and its cognate receptor CXCR4 on angiogenic tip EC. CXCL12 was in vitro and in vivo validated as actionable TEC target by highlighting the vessel number- and density- reducing activity of the CXCR4-inhibitor AMD3100 in murine PCa as well as by inhibition of TEC proliferation and migration in vitro.

Conclusions
Overall, our comprehensive analysis identified novel PCa TEC targets and highlights CXCR4/CXCL12 interaction as a potential novel target to interfere with tumor angiogenesis in PCa.

Graphical Abstract
An IFI6-based hydrogel promotes the healing of radiation-induced skin injury through regulation of the HSF1 activity
Authors: Hao Jie , Sun Mengyi , Li Dong , Zhang Tao , Li Jianjun , Zhou Daijun 
Published: June 2022

AbstractRadiation-induced skin injury (RISI) is a common complication of radiotherapy. Interferon-alpha inducible protein 6 (IFI6) significantly reduces the radiation sensitivity of HaCaT cells. Sodium alginate (SA) has substantial moisturizing properties. Graphene oxide (GO) is a suitable substrate with physical antibacterial properties. Therefore, we designed materials to modify IFI6 using the biogule of polydopamine (PDA) connected to GO/SA. The structure, size, morphology, and elemental compositions of IFI6-PDA@GO/SA were analyzed. Cytological studies suggested that IFI6-PDA@GO/SA is non-toxic to HaCaT cells, with antibacterial properties. It promotes migration and vascularization and inhibits apoptosis. These cells express IFI6 after irradiation. The mouse model suggested that IFI6-PDA@GO/SA promotes wound healing and reduces reactive oxygen species expression. IFI6-PDA@GO/SA accelerates RISI healing, possibly by initiating the SSBP1/HSF1 signaling pathway. In addition, IFI6-PDA@GO/SA improves the immune microenvironment. This study constitutes the first use of IFI6 as a RISI wound-healing material.
Who is using take-home naloxone? An examination of supersavers
Authors: Eide Desiree , Lobmaier Philipp , Clausen Thomas 
Published: June 2022

Abstract
Background
As the opioid overdose crisis persists and take-home naloxone (THN) programmes expand, it is important that the intervention is targeted towards those most likely to use it. We examined THN program participants to 1) describe those that return for refills, specifically those that reported multiple use (supersavers), and 2) to examine what rescuer characteristics were associated with higher rates of THN use.

Methods
This study included a cohort of consenting THN recipients from June 2014–June 2021 who completed initial and refill questionnaires from a widespread program in Norway. Age, gender, number of witnessed and experienced overdoses were assessed for associations with higher reported rates of THN use. ‘Supersavers’ reported 3 or more THN uses.

Results
A total of 1054 participants returned for a THN refill during the study period. Of these, 558 reported their last THN to have been used on an overdose. Supersavers (those that reported 3 or more THN uses) were younger, primarily reported current opioid use, and had witnessed higher rates of overdoses at the time of initial training when compared to non-supersavers (those that reported 0–2 THN uses).

Conclusions
THN programs should continue to emphasize and prioritize THN for people actively using drugs, particularly those who have witnessed overdoses previously.