bluuebunny/crossref_metadata_2025_split huggingface dataset:
The temporal trend of cause-specific mortality: comparing Estonia and Lithuania, 2001 – 2019
Authors: Tran Alexander , Stoppel Relika , Jiang Huan , Kim Kawon Victoria , Lange Shannon , Petkevičienė Janina , Radišauskas Ričardas , Štelemėkas Mindaugas , Telksnys Tadas , Zafar Anush , Rehm Jürgen 
Published: October 2022

Abstract
Background
Despite being two Baltic countries with similar histories, Estonia and Lithuania have diverged in life expectancy trends in recent years. We investigated this divergence by comparing cause-specific mortality trends.

Methods
We obtained yearly mortality data for individuals 20 + years of age from 2001–2019 (19 years worth of data) through Statistics Lithuania, the Lithuanian Institute for Hygiene, and the National Institute for Health Development (Estonia). Using ICD-10 codes, we analyzed all-cause mortality rates and created eight major disease categories: ischemic heart disease, cerebrovascular disease, all other cardiovascular disease, cancers (neoplasms), digestive diseases, self-harm and interpersonal violence, unintentional injuries and related conditions, and other mortality (deaths per 100,000 population). We used joinpoint regression analysis, and analyzed the proportional contribution of each category to all-cause mortality.

Results
There was a steeper decline in all-cause mortality in Estonia (average annual percent change, AAPC = -2.55%, 95% CI: [-2.91%, -2.20%], P < .001) as compared to Lithuania (AAPC = -1.26%, 95% CI: [-2.18%, -0.57%], P = .001). For ischemic heart disease mortality Estonia exhibited a relatively larger decline over the 19-year period (AAPC = -6.61%, 95% CI: [-7.02%, -6.21%], P < .001) as compared to Lithuania (AAPC = -2.23%, 95% CI: [-3.40%, -1.04%], P < .001).

Conclusion
Estonia and Lithuania showed distinct mortality trends and distributions of major disease categories. Our findings highlight the role of ischemic heart disease mortality. Differences in public health care, management and prevention of ischemic heart disease, alcohol control policies may explain these differences.
Evaluating and rating HIV/AIDS mobile apps using the feature-based application rating method and mobile app rating scale
Authors: Raeesi Ahmad , Khajouei Reza , Ahmadian Leila 
Published: October 2022

Abstract
Background
The purpose of this study was to evaluate HIV/AIDS mobile applications using the Mobile App Rating Scale (MARS) and rate the features of these applications using the new tool called the Feature-based Application Rating Method (FARM).

Methods
In this study, all available HIV/AIDS apps in Iran from Cafe Bazaar and Google Play Store due to inclusion criteria were studied. The evaluation of the quality of applications was done using the MARS tool and the FARM tool. The FARM, which was developed in this study, was applied to rank the features of the applications.

Results
In this study, 79 applications were included. The mean score of all apps using both tools was 3.58 (SD = 0.95) out of 5. The overall mean quality score based on the MARS was 3.14 (SD = 0.84), and the mean score of features based on FARM was 3.81 (SD = 1.23). This study showed a higher than moderate correlation between the scores assigned to apps based on the MARS and FARM tools (r > 0.4).

Conclusions
The HIV/AIDS mobile applications available in Iran had the "acceptable" ranking. Also, our study results showed that to evaluate mobile apps, using a single tool may not provide good insight to evaluators about the assessed apps. However, using more than one tool may provide more details about the evaluated apps. To improve the quality of mobile health apps and help users select the most desirable app, we suggested using tools like FARM for ranking apps based on the features of each app in the app stores.
An electronic pillbox intervention designed to improve medication safety during care transitions: challenges and lessons learned regarding implementation and evaluation
Authors: Shahani Amrita , Nieva Harry Reyes , Czado Katie , Shannon Evan , Gaetani Raquel , Gresham Marcus , Garcia Jose Cruz , Ganesan Hareesh , Cerciello Emily , Dave Janan , Jain Rahul , Schnipper Jeffrey L. 
Published: October 2022

AbstractBackgroundAdverse drug events are common during transitions of care. As part of the Smart Pillbox study, a cluster-randomized controlled trial of an electronic pillbox designed to reduce medication discrepancies and improve medication adherence after hospital discharge, we explored barriers to successful implementation and evaluation of this intervention.MethodsEligible patients were those admitted to a medicine service of a large teaching hospital with a plan to be discharged home on five or more chronic medications. The intervention consisted of an electronic pillbox with pre-filled weekly blister pack medication trays given to patients prior to discharge. Pillbox features included alarms to take medications, detection of pill removal from each well, alerts to patients or caregivers by phone, email, or text if medications were not taken, and adherence reports accessible by providers. Greater than 20% missed doses for three days in a row triggered outreach from a pharmacist. To identify barriers to implementation and evaluation of the intervention, we reviewed patient exit surveys, including quantitative data on satisfaction and free-text responses regarding their experiences; technical issue logs; and team meeting minutes. Themes were derived by consensus among the study authors and organized using the Consolidated Framework for Implementation Research.ResultsBarriers to implementation included intervention characteristics such as perceived portability issues with the pillbox and time required by pharmacists to enter medication information into the software; external policies such as lack of insurance coverage for early refills and regulatory prohibitions on repackaging medications; implementation climate issues such as the incompatibility between the rushed nature of hospital discharge with the time required to deploy the intervention; and patient issues such as denial of previous problems with medication adherence. We founds several obstacles to conducting the study, including patients declining study enrollment and limited attempts by the hospital to streamline logistics by building the intervention into usual care. Several solutions to address many of these challenges were implemented or planned. Despite these challenges, many patients with the pillbox were pleased with the service and believed the intervention worked well for them.ConclusionsIn this evaluation, several barriers to implementing and conducting a study of the effectiveness of the intervention were identified. Our findings provide lessons learned for others wishing to implement and evaluate HIT-related interventions designed to improve medication safety during care transitions.Trial registrationClinicaltrials.gov NCT03475030
Dysregulation of SOX17/NRF2 axis confers chemoradiotherapy resistance and emerges as a novel therapeutic target in esophageal squamous cell carcinoma
Authors: Hsieh Chih-Hsiung , Kuan Wen-Hui , Chang Wei-Lun , Kuo I-Ying , Liu Hsun , Shieh Dar-Bin , Liu Hsuan , Tan Bertrand , Wang Yi-Ching 
Published: October 2022

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is the sixth leading cause of cancer-associated death worldwide with a dismal overall 5-year survival rate of less than 20%. The standard first-line therapy for advanced ESCC is concomitant chemo-radiation therapy (CCRT); however, patients usually develop resistance, resulting in unfavorable outcomes. Therefore, it is urgent to identify the mechanisms underlying CCRT resistance and develop effective treatment strategies.

Methods
Patients’ endoscopic biopsy tumor tissues obtained before CCRT treatment were used to perform RNA-seq and GSEA analysis. Immunohistochemical (IHC) staining, chromatin immunoprecipitation (ChIP), and promoter reporter analyses were conducted to investigate the relationship between SOX17 and NRF2. Xenograft mouse models were used to study the role of SOX17/NRF2 axis in tumor growth and the efficacy of carboxymethyl cellulose-coated zero-valent-iron (ZVI@CMC).

Results
In this study, a notable gene expression signature associated with NRF2 activation was observed in the poor CCRT responders. Further, IHC staining of endoscopic biopsy of 164 ESCC patients revealed an inverse correlation between NRF2 and SOX17, a tumor-suppressive transcription factor with low expression in ESCC due to promoter hypermethylation. Using ChIP and promoter reporter analyses, we demonstrated that SOX17 was a novel upstream transcriptional suppressor of NRF2. In particular, SOX17low/NRF2high nuclear level significantly correlated with poor CCRT response and poor survival, indicating that the dysregulation of SOX17/NRF2 axis played a pivotal role in CCRT resistance and tumor progression. Notably, the in-house developed nanoparticle ZVI@CMC functioned as an inhibitor of DNA methyltransferases to restore expression of SOX17 that downregulated NRF2, thereby overcoming the resistance in ESCC. Additionally, the combination of ZVI@CMC with radiation treatment significantly augmented anticancer efficacy to inhibit tumor growth in CCRT resistant cancer.

Conclusion
This study identifies a novel SOX17low/NRF2high signature in ESCC patients with poor prognosis, recognizes SOX17 as a transcriptional repressor of NRF2, and provides a promising strategy targeting SOX17/NRF2 axis to overcome resistance.
Economic evaluation of a leprosy innovation project in Northern Nigeria: cost-effectiveness analysis
Authors: Ezenduka Charles C. , Namadi Abudulahi , Tahir Dahiru , Nwosu Uzoma , Musa Shuaibu N. 
Published: October 2022

AbstractBackgroundThe state of leprosy in Nigeria and the realities of post elimination era underscore the need for evidence- based cost-effective approach to early case detection for enhanced control and elimination of leprosy. This study evaluated the operational cost-effectiveness of a community delivered Legacy Innovative Project implemented to enhance leprosy case detection in northern Nigeria.MethodsData were collected from an explorative cross-sectional study, undertaken in a practice setting among endemic communities in three states in northern Nigeria. Primary and secondary data were collected from the project, routine records and programme annual reports. Costs and effects were measured from both providers’ and patients’ perspectives, and outcome expressed as cost per new case detected. Incremental estimates of costs and effects of the project compared to routine practice were used to obtain the cost-effectiveness result, as incremental cost-effectiveness ratio (ICER). All costs were converted to the US Dollar at 2018exchange rate (N350 = US$1.00). Univariate sensitivity analysis was performed to evaluate uncertainties around the ICER.ResultsThe Project overall detected a total of 347 newly confirmed leprosy cases at a total annual cost of US$49,337.19, averaging US$142.18 per new case detected. Key cost drivers included routine meetings, which accounted for 28% of total expenditure, while Social Mobilization and Training/Workshop accounted for17% respectively. Findings were similar across the states. Overall, the Project dominated routine practice with ICER of US$(-17.73) per additional/new case detected, as a very cost-effective strategy. Sensitivity analysis reinforced the cost-effectiveness result.ConclusionsThe Legacy Innovative Project demonstrated a more efficient and cost-saving approach to leprosy case detection. Findings present important information to policy and programmes for enhanced control and elimination of leprosy in related settings..
How independent is the international food information council from the food and beverage industry? A content analysis of internal industry documents
Authors: Zaltz Daniel A. , Bisi Lauren E. , Ruskin Gary , Hoe Connie 
Published: October 2022

Abstract
Background
The International Food Information Council (IFIC) and its partner foundation (IFIC Foundation) widely disseminate nutrition information and participate in relevant policymaking processes. Prior research has established a connection between IFIC and large food and beverage companies, representing a potential conflict of interest. The authors reviewed public records documents to investigate the connection between IFIC and industry, and to describe how IFIC communicates policy-relevant information about nutrition science to the public.

Methods
The research team collected communications between IFIC and members of the research and policymaking communities by using state and federal transparency laws. The team analyzed the content of these documents with a commercial determinants of health framework while allowing for new themes to emerge, guided by the broad analytic questions of how and why does IFIC communicate nutrition information to policymakers and the broader public?

Results
IFIC employs self-designed research and media outreach to disseminate nutrition information. Communications from IFIC and its affiliates related to nutrition information fell within major themes of manufacturing doubt and preference shaping.

Conclusions
IFIC uses media outlets to preemptively counter information about the negative health impacts of added sugars and ultra-processed foods, and promotes a personal-responsibility narrative about dietary intake and health. IFIC and its affiliates disseminate a narrow subset of nutrition and health information consistent with corporate interests and in opposition to public health policies associated with improved population health.
Association between single-nucleotide polymorphism rs145497186 related to NDUFV2 and lumbar disc degeneration: a pilot case–control study
Authors: Wang Ziyu , Chen Lu , Li Qinghui , Zhang Hengshuo , Shan Yu , Qi Linzeng , Wang Hongliang , Chen Yunzhen 
Published: October 2022

Abstract
Objective
The association between the single-nucleotide polymorphisms (SNPs) rs28742109, rs12955018, rs987850, rs8093805, rs12965084 and rs145497186 related to gene named NADH dehydrogenase [ubiquinone] flavoprotein 2 (NDUFV2) and lumbar disc degeneration (LDD) was preliminary investigated in a small sample size.

Methods
A total of 46 patients with LDD and 45 controls were recruited at Qilu Hospital of Shandong University, and each participant provided 5 mL peripheral venous blood. NA was extracted from the blood of each participant for further genotyping. The frequency of different genotypes in the case group and control group was determined, and analysis of the risk of LDD associated with different SNP genotypes was performed. The visual analogue scale (VAS) scores of the patients’ degree of chronic low back pain were calculated, and the relationship between VAS scores and SNPs was analysed.

Results
After excluding the influence of sex, age, height, and weight on LDD, a significant association between SNP rs145497186 related to NDUFV2 and LDD persisted (P = 0.006). Simultaneously, rs145497186 was found to be associated with chronic low back pain in LDD populations.

Conclusion
NDUFV2 rs145497186 SNP could be associated with susceptibility to LDD and the degree of chronic low back pain.
Patient reported outcomes for phosphomannomutase 2 congenital disorder of glycosylation (PMM2-CDG): listening to what matters for the patients and health professionals
Authors: Pascoal C. , Ferreira I. , Teixeira C. , Almeida E. , Slade A. , Brasil S. , Francisco R. , Ligezka A. N. , Morava E. , Plotkin H. , Jaeken J. , Videira P. A. , Barros L. , dos Reis Ferreira V. 
Published: October 2022

Abstract
Background
Congenital disorders of glycosylation (CDG) are a growing group of rare genetic disorders. The most common CDG is phosphomannomutase 2 (PMM2)-CDG which often has a severe clinical presentation and life-limiting consequences. There are no approved therapies for this condition. Also, there are no validated disease-specific quality of life (QoL) scales to assess the heterogeneous clinical burden of PMM2-CDG which presents a challenge for the assessment of the disease severity and the impact of a certain treatment on the course of the disease.

Aim and methods
This study aimed to identify the most impactful clinical signs and symptoms of PMM2-CDG, and specific patient and observer reported outcome measures (PROMs and ObsROMs, respectively) that can adequately measure such impact on patients’ QoL. The most burdensome signs and symptoms were identified through input from the CDG community using a survey targeting PMM2-CDG families and experts, followed by family interviews to understand the real burden of these symptoms in daily life. The list of signs and symptoms was then verified and refined by patient representatives and medical experts in the field. Finally, a literature search for PROMs and ObsROMs used in other rare or common diseases with similar signs and symptoms to those of PMM2-CDG was performed.

Results
Twenty-four signs/symptoms were identified as the most impactful throughout PMM2-CDG patients’ lifetime. We found 239 articles that included tools to measure those community-selected PMM2-CDG symptoms. Among them, we identified 80 QoL scales that address those signs and symptoms and, subsequently, their psychometric quality was analysed. These scales could be applied directly to the PMM2-CDG population or adapted to create the first PMM2-CDG-specific QoL questionnaire.

Conclusion
Identifying the impactful clinical manifestations of PMM2-CDG, along with the collection of PROMs/ObsROMs assessing QoL using a creative and community-centric methodology are the first step towards the development of a new, tailored, and specific PMM2-CDG QoL questionnaire. These findings can be used to fill a gap in PMM2-CDG clinical development. Importantly, this methodology is transferable to other CDG and rare diseases with multiple signs and symptoms.
Preferential subcortical collateral projections of pedunculopontine nucleus-targeting cortical pyramidal neurons revealed by brain-wide single fiber tracing
Authors: Liu Qiao-Qiong , Cheng Yu-Xiao , Jing Qi , Zhang Ke-Ming , Ding Lu-Feng , Fan Xiao-Wei , Jia Chun-Hui , Xu Fang , Bi Guo-Qiang , Lau Pak-Ming 
Published: October 2022

AbstractThe pedunculopontine nucleus (PPN) is a heterogeneous midbrain structure involved in various brain functions, such as motor control, learning, reward, and sleep. Previous studies using conventional tracers have shown that the PPN receives extensive afferent inputs from various cortical areas. To examine how these cortical axons make collateral projections to other subcortical areas, we used a dual-viral injection strategy to sparsely label PPN-targeting cortical pyramidal neurons in CaMKIIα-Cre transgenic mice. Using a high-speed volumetric imaging with on-the-fly-scan and Readout (VISoR) technique, we visualized brain-wide axonal projections of individual PPN-targeting neurons from several cortical areas, including the prelimbic region (PL), anterior cingulate area (ACA) and secondary motor cortex (MOs). We found that each PPN-projecting neuron had a unique profile of collateralization, with some subcortical areas being preferential targets. In particular, PPN-projecting neurons from all three traced cortical areas exhibited common preferential collateralization to several nuclei, with most neurons targeting the striatum (STR), lateral hypothalamic area (LHA) and periaqueductal gray (PAG), and a substantial portion of neurons also targeting the zona incerta (ZI), median raphe nucleus (MRN) and substantia nigra pars reticulata (SNr). Meanwhile, very specific collateralization patterns were found for other nuclei, including the intermediate reticular nucleus (IRN), parvicellular reticular nucleus (PARN) and gigantocellular reticular nucleus (GRN), which receive collateral inputs almost exclusively from the MOs. These observations provide potential anatomical mechanisms for cortical neurons to coordinate the PPN with other subcortical areas in performing different physiological functions.
The CLOSED protocol to assess optic nerve sheath diameter using color-Doppler: a comparison study in a cohort of idiopathic normal pressure hydrocephalus patients
Authors: Aspide Raffaele , Bertolini Giacomo , Belotti Laura Maria Beatrice , Albini Riccioli Luca , Toni Francesco , Mazzatenta Diego , Palandri Giorgio , Vetrugno Luigi , Biasucci Daniele Guerino 
Published: October 2022

Abstract
Background
Sonographic assessment of the optic nerve sheath diameter represents a promising non-invasive technique for estimation of the intracranial pressure. A wide inter-observer variability, along with a lack of a standardized protocol for the optic nerve sheath diameter measurements, could lead to over- or under-estimation. The present study was aimed at evaluating feasibility of color-Doppler for better delineating optic nerve sheath borders, comparing it to B-mode imaging, using the magnetic resonance measurements as a comparison.

Methods
Optic nerve sheath diameters were evaluated using magnetic resonance by an expert radiologist in a cohort of patients with suspected idiopathic normal pressure hydrocephalus. Magnetic resonance findings were evaluated twice. In the first half of this cohort, optic nerve sheath diameters were measured using B-mode only, in the second half applying color-Doppler. Measurements obtained using these two techniques were compared to magnetic resonance imaging measurements. The Bland–Altman analysis and concordance correlation coefficient were computed to quantify the strength of agreement between the two magnetic resonance assessments. Box plots and average (± SD) were used to compare assessments by sonographic and magnetic resonance methods.

Results
Fifty patients were included. MRI assessment showed a moderate concordance correlation coefficient. Optic nerve sheath diameters measured applying color-Doppler were lower (p < 0.001) and less scattered compared to B-mode assessment, which approached more to magnetic resonance measurements.

Conclusions
In this cohort of patients, magnetic resonance showed high intra-rater variability in optic nerve sheath diameter assessments. Optic nerve sheath diameter assessments using color-Doppler yielded lower and less scattered diameters compared to B-mode only.