bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studying human nociceptors: from fundamentals to clinic
Authors: Middleton Steven J , Barry Allison M , Comini Maddalena , Li Yan , Ray Pradipta R , Shiers Stephanie , Themistocleous Andreas C , Uhelski Megan L , Yang Xun , Dougherty Patrick M , Price Theodore J , Bennett David L 
Published: February 2021

AbstractChronic pain affects one in five of the general population and is the third most important cause of disability-adjusted life-years globally. Unfortunately, treatment remains inadequate due to poor efficacy and tolerability. There has been a failure in translating promising preclinical drug targets into clinic use. This reflects challenges across the whole drug development pathway, from preclinical models to trial design. Nociceptors remain an attractive therapeutic target: their sensitization makes an important contribution to many chronic pain states, they are located outside the blood–brain barrier, and they are relatively specific. The past decade has seen significant advances in the techniques available to study human nociceptors, including: the use of corneal confocal microscopy and biopsy samples to observe nociceptor morphology, the culture of human nociceptors (either from surgical or post-mortem tissue or using human induced pluripotent stem cell derived nociceptors), the application of high throughput technologies such as transcriptomics, the in vitro and in vivo electrophysiological characterization through microneurography, and the correlation with pain percepts provided by quantitative sensory testing. Genome editing in human induced pluripotent stem cell-derived nociceptors enables the interrogation of the causal role of genes in the regulation of nociceptor function. Both human and rodent nociceptors are more heterogeneous at a molecular level than previously appreciated, and while we find that there are broad similarities between human and rodent nociceptors there are also important differences involving ion channel function, expression, and cellular excitability. These technological advances have emphasized the maladaptive plastic changes occurring in human nociceptors following injury that contribute to chronic pain. Studying human nociceptors has revealed new therapeutic targets for the suppression of chronic pain and enhanced repair. Cellular models of human nociceptors have enabled the screening of small molecule and gene therapy approaches on nociceptor function, and in some cases have enabled correlation with clinical outcomes. Undoubtedly, challenges remain. Many of these techniques are difficult to implement at scale, current induced pluripotent stem cell differentiation protocols do not generate the full diversity of nociceptor populations, and we still have a relatively poor understanding of inter-individual variation in nociceptors due to factors such as age, sex, or ethnicity. We hope our ability to directly investigate human nociceptors will not only aid our understanding of the fundamental neurobiology underlying acute and chronic pain but also help bridge the translational gap.
The Critical Need for Pooled Data on Coronavirus Disease 2019 in African Children: An AFREhealth Call for Action Through Multicountry Research Collaboration
Authors: Sam-Agudu Nadia A , Rabie Helena , Pipo Michel Tshiasuma , Byamungu Liliane Nsuli , Masekela Refiloe , van der Zalm Marieke M , Redfern Andrew , Dramowski Angela , Mukalay Abdon , Gachuno Onesmus W , Mongweli Nancy , Kinuthia John , Ishoso Daniel Katuashi , Amoako Emmanuella , Agyare Elizabeth , Agbeno Evans K , Mohammed Jibril Aishatu , Abdullahi Asara M , Amadi Oma , Mohammed Umar Umar , Ayele Birhanu T , Machekano Rhoderick N , Nyasulu Peter S , Hermans Michel P , Otshudiema John Otokoye , Bongo-Pasi Nswe Christian , Kayembe Jean-Marie N , Mbala-Kingebeni Placide , Muyembe-Tamfum Jean-Jacques , Aanyu Hellen Tukamuhebwa , Musoke Philippa , Fowler Mary Glenn , Sewankambo Nelson , Suleman Fatima , Adejumo Prisca , Tsegaye Aster , Mteta Alfred , Noormahomed Emilia V , Deckelbaum Richard J , Zumla Alimuddin , Mavungu Landu Don Jethro , Tshilolo Léon , Zigabe Serge , Goga Ameena , Mills Edward J , Umar Lawal W , Kruger Mariana , Mofenson Lynne M , Nachega Jean B ,   Investigators in the AFREhealth COVID-19 Research Collaboration on Children and Adolescents, Dasoberi Ireneous N , Sam-Woode Clara , Yeboah Georgina 
Published: February 2021

Abstract
Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children and adolescents; and these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of coronavirus disease 2019 (COVID-19) among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and coinfections such as human immunodeficiency virus (HIV), tuberculosis, malaria, sickle cell disease, and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policy-making for COVID-19 while concurrently addressing other major diseases affecting children in African countries.
Visuospatial and Tactile Working Memory in Individuals with Congenital Deafness
Authors: Heled Eyal , Ohayon Maayan 
Published: February 2021

Abstract
Studies examining visuospatial working memory (WM) in individuals with congenital deafness have yielded inconsistent results, and tactile WM has rarely been examined. The current study examined WM span tasks in the two modalities among 20 individuals with congenital deafness and 20 participants with typical hearing. The congenital deafness group had longer forward and backward spans than typical hearing participants in a computerized Corsi block-tapping test (Visuospatial Span), whereas no such difference was found in the Tactual Span (tactile WM). In the congenital deafness group, age of sign language acquisition was not correlated with either condition of the visuospatial task, and Tactual and Visuospatial Spans scores were correlated in the backward but not the forward condition. The typical hearing group showed no correlation between the tasks. The findings suggest that early deafness leads to visuospatial but not tactile superiority in WM, specifically with respect to the storage component. More broadly, it appears that deafness-related compensation mechanisms in WM do not affect the other modalities in a uniform manner.
The Burden of Inflammatory Bowel Disease in Europe in 2020
Authors: Zhao Mirabella , Gönczi Lóránt , Lakatos Peter L , Burisch Johan 
Published: February 2021

Abstract
New data suggest that incidence and prevalence of inflammatory bowel diseases [IBD] are still increasing worldwide, and approximately 0.2% of the European population suffer from IBD at the present time. Medical therapy and disease management have evolved significantly in recent decades, with an emphasis on tight objective monitoring of disease progression and a treat-to-target approach in Europe and also worldwide, aiming to prevent early bowel damage and disability. Surgery rate declined over time in Europe, with 10–30% of CD and 5–10% of UC patients requiring a surgery within 5 years. The health economic burden associated with IBD is high in Europe. Direct health care costs [approximately €3500 in CD and €2000 in UC per patient per year] have shifted from hospitalisation and surgery towards drug-related expenditures with the increasing use of biologic therapy and other novel agents, and substantial indirect costs arise from work productivity loss [approximately €1900 per patient yearly]. The aim of this paper is to provide an updated review of the burden of IBD in Europe by discussing current data on epidemiology, disease course, risk for surgery, hospitalisation, and mortality and cancer risks, as well as the economic aspects, patient disability, and work impairment, by discussing the latest population-based studies from the region.
The Production of Inequalities within Families and across Generations: The Intergenerational Effects of Birth Order on Educational Attainment
Authors: Barclay Kieron J , Lyngstad Torkild H , Conley Dalton C 
Published: February 2021

Abstract
There has long been interest in the extent to which effects of social stratification extend and persist across generations. We take a novel approach to this question by asking whether birth order in the parental generation influences the educational attainment of their children. To address this question, we use Swedish population data on cohorts born 1960–1982. To study the effects of parental birth order, we use cousin fixed effects comparisons. In analyses where we compare cousins who share the same biological grandparents to adjust for unobserved factors in the extended family, we find that having a later-born parent reduces educational attainment to a small extent. For example, a second- or fifth-born mother reduces educational attainment by 0.09 and 0.18 years, respectively, while having a second- or fifth-born father reduces educational attainment by 0.04 and 0.11 years, respectively. After adjusting for attained parental education and social class, the parental birth order effect is practically attenuated to zero. Overall our results suggest that parental birth order influences offspring educational and socioeconomic outcomes through the parents own educational and socioeconomic attainment. We cautiously suggest that parental birth order may have potential as an instrument for parental socioeconomic status in social stratification research more generally.
A cohort study and meta-analysis of isolated diastolic hypertension: searching for a threshold to guide treatment
Authors: Jacobsen Alan P , Al Rifai Mahmoud , Arps Kelly , Whelton Seamus P , Budoff Matthew J , Nasir Khurram , Blaha Michael J , Psaty Bruce M , Blumenthal Roger S , Post Wendy S , McEvoy John W 
Published: February 2021

Abstract

Aims
Whether isolated diastolic hypertension (IDH), as defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline, is associated with cardiovascular disease (CVD) has been disputed. We aimed to further study the associations of IDH with (i) subclinical CVD in the form of coronary artery calcium (CAC), (ii) incident systolic hypertension, and (iii) CVD events.

Methods and results
We used multivariable-adjusted logistic and Cox regression to test whether IDH by 2017 ACC/AHA criteria (i.e. systolic blood pressure &lt;130 mmHg and diastolic blood pressure ≥80 mmHg) was associated with the above outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA). In a random-effects meta-analysis of the association between IDH and CVD events, we combined the MESA results with those from seven other previously published cohort studies. Among the 5104 MESA participants studied, 7.5% had IDH by the 2017 ACC/AHA criteria. There was no association between IDH and CAC [e.g. adjusted prevalence odds ratio for CAC &gt;0 of 0.88 (95% CI 0.66, 1.17)]. Similarly, while IDH was associated with incident systolic hypertension, there was no statistically significant associations with incident CVD [hazard ratio 1.19 (95% CI 0.77, 1.84)] or death [hazard ratio 0.94 (95% CI 0.65, 1.36)] over 13 years in MESA. In a stratified meta-analysis of eight cohort studies (10 037 843 participants), the 2017 IDH definition was also not consistently associated with CVD and the relative magnitude of any potential association was noted to be numerically small [e.g. depending on inclusion criteria applied in the stratification, the adjusted hazard ratios ranged from 1.04 (95% CI 0.98, 1.10) to 1.09 (95% 1.03, 1.15)].

Conclusion
The lack of consistent excess in CAC or CVD suggests that emphasis on healthy lifestyle rather than drug therapy is sufficient among the millions of middle-aged or older adults who now meet the 2017 ACC/AHA criteria for IDH, though they require follow-up for incident systolic hypertension. These findings may not extrapolate to adults younger than 40 years, motivating further study in this age group.
Discovery of three loci increasing resistance to charcoal rot caused by Macrophomina phaseolina in octoploid strawberry
Authors: Nelson Jonathan R , Verma Sujeet , Bassil Nahla V , Finn Chad E , Hancock James F , Cole Glenn S , Knapp Steven J , Whitaker Vance M 
Published: February 2021

Abstract
Charcoal rot caused by Macrophomina phaseolinais an increasing economic problem in annualized strawberry production systems around the world. Currently there are no effective postfumigation chemical controls for managing charcoal rot, and no information is available on the genetic architecture of resistance to M. phaseolina in strawberry (Fragaria ×ananassa). In this study, three multiparental discovery populations and two validation populations were inoculated at planting and evaluated for mortality in three consecutive growing seasons. Genome-wide SNP genotyping and pedigree-based analysis with FlexQTL™ software were performed. Two large-effect quantitative trait loci (QTL) increasing charcoal rot resistance were discovered and validated in cultivated germplasm. FaRMp1 was located on linkage group 2A in the interval 20.4to 24.9 cM, while FaRMp2 was located on linkage group 4B in the interval 41.1to 61.2 cM. Together these QTLs explained 27% and 17% of the phenotypic variance in two discovery populations consisting of elite breeding germplasm. For both QTLs, the resistant allele showed some evidence of partial dominance, but no significant interaction was detected between the two loci. As the dosage of resistant alleles increased from 0 to 4 across the two QTLs, mortality decreased regardless of the combination of alleles.A third locus, FaRMp3 on 4D, was discovered in FVC 11–58, a reconstituted F.×ananassa originating from diverse F. virginiana and F. chiloensis accessions. This locus accounted for 44% of phenotypic variation in four segregating crosses. These findings will form the basis for DNA-informed breeding for resistance to charcoal rot in cultivated strawberry.
Of Mice and Men: Impacts of Calorie Restriction on Metabolomics of the Cerebellum
Authors: García-Flores Libia Alejandra , Green Cara L 
Published: February 2021

AbstractThe main purpose of research in mice is to explore metabolic changes in animal models and then predict or propose potential translational benefits in humans. Although some researchers in the brain research field have mentioned that the mouse experiments results still lack the complex neuroanatomy of humans, caution is required to interpret the findings. In mice, we observed in article seventeenth of the series of the effects of graded levels of calorie restriction, metabolomic changes in the cerebellum indicated activation of hypothalamocerebellar connections driven by hunger responses. Therefore, the purpose of the current perspective is to set this latest paper into a wider context of the physiological, behavioral, and molecular changes seen in these mice and to compare and contrast them with previous human studies.
The needs-based health workforce planning method: a systematic scoping review of analytical applications
Authors: Asamani James Avoka , Christmals Christmal Dela , Reitsma Gerda Marie 
Published: February 2021

Abstract
Although the theoretical underpinnings and analytical framework for needs-based health workforce planning are well developed and tested, its uptake in national planning processes is still limited. Towards the development of open-access needs-based planning model for national workforce planning, we conducted a systematic scoping review of analytical applications of needs-based health workforce models. Guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses—extension for Scoping Reviews (PRISMA-ScR) checklist, a systematic scoping review was conducted. A systematic search of peer-reviewed literature published in English was undertaken across several databases. Papers retrieved were assessed against predefined inclusion criteria, critically appraised, extracted and synthesized. Twenty-five papers were included, which showed increasing uptake of the needs-based health workforce modelling, with 84% of the studies published within the last decade (2010–20). Three countries (Canada, Australia and England) accounted for 48% of the publications included whilst four studies (16%) were based on low-and-middle-income countries. Only three of the studies were conducted in sub-Saharan Africa. Most of the studies (36%) reported analytical applications for specific disease areas/programs at sub-national levels; 20% focused on the health system need for particular categories of health workers, and only two (8%) reported the analytical application of the needs-based health workforce approach at the level of a national health system across several disease areas/programs. Amongst the studies that conducted long-term projections, the time horizon of the projection was an average of 17 years, ranging from 3 to 33 years. Most of these studies had a minimum time horizon of 10 years. Across the studies, we synthesized six typical methodological considerations for advancing needs-based health workforce modelling. As countries aspire to align health workforce investments with population health needs, the need for some level of methodological harmonization, open-access needs-based models and guidelines for policy-oriented country-level use is not only imperative but urgent.
Social determinants of quality of life among PLHIV in Australia: implications for health promotion
Authors: Mikołajczak Gosia , Brown Graham , Power Jennifer , Lyons Anthony , Howard Chris , Drummond Fraser 
Published: February 2021

SummaryA cascade of care model is central to contemporary approaches to HIV prevention. The model prioritizes strategies to increase rates of HIV testing and promote early and sustained uptake of antiretroviral treatment (ART) among people living with HIV (PLHIV). The model aims to prevent new HIV transmissions by increasing the number of PLHIV who have achieved HIV viral suppression. However, good quality of life (QoL) among PLHIV has been proposed as an additional goal. This prioritizes the basic right of PLHIV to lead meaningful lives and acknowledges the relationship between better QoL and consistent ART use. A better understanding of factors associated with the QoL can thus inform health promotion programmes for PLHIV. In this study, N=465 Australian participants, recruited through social media and various HIV community organizations, completed an online survey that included a measure of QoL and a range of demographic, health-related and social variables. Overall, social factors accounted uniquely for the most variance in QoL (18%), followed by health-related (11%) and demographic factors (2%). Social support, HIV-related discrimination and treatment convenience were among the strongest determinants of QoL. These findings reinforce the importance of a more holistic approach to health promotion among PLHIV. Specifically, our results indicate that to improve the QoL of PLHIV and to boost related public health benefits, community advocates and healthcare professionals must be responsive to the broader psychological, social and functional needs of PLHIV.
Promoting healthy eating in the community sport setting: a scoping review
Authors: Westberg Kate , Stavros Constantino , Parker Lukas , Powell Ashleigh , Martin Diane M , Worsley Anthony , Reid Mike , Fouvy David 
Published: February 2021

Summary
Community sport organizations promote beneficial health outcomes such as social connection and physical activity, yet they can also facilitate the consumption of unhealthy food and beverages. To provide a foundation for future research and to inform intervention efforts in this context, this scoping review summarizes existing knowledge of the factors that contribute to unhealthy food and beverage consumption in the community sport setting and explores the interventions to promote healthier choices. Using a qualitative process aligned with the nature of our aims, 228 articles were initially identified and subjected to a systemized appraisal, resulting in 45 articles pertinent to the review. The findings identify that the two key factors contributing to unhealthy food choices are the limited availability of healthy options within the sport setting and the presence of unhealthy food and beverage sponsorship. These factors contribute to the normalization of unhealthy eating in this context and health promotion interventions have had limited success. Barriers to change primarily stem from the revenue implications of removing unhealthy food sponsors, lack of organizational capabilities and resources, and consumer preference for unhealthy options. Public health practitioners seeking to intervene in this setting should consider adopting practices used in other settings outside of the sport environment, including the use of technology, the role of peers and mentors and the co-production of impactful material. Community sport plays a vital role in delivering health benefits but must do more to stem its facilitation of a potentially unhealthy consumptive environment.
Integrin-directed antibody-based immunotherapy: focus on VLA-4
Authors: Savino Wilson , Chaves Beatriz , Bonomo Adriana Cesar , Cotta-de-Almeida Vinicius 
Published: February 2021

SummaryOne major finding of chronic inflammatory diseases of various origins is the establishment of inflammatory infiltrates, bearing different leukocyte subpopulations, including activated T lymphocytes. Integrins are among the large series of molecular interactions that have been implicated as players in both triggering and maintenance of leukocyte influx from the blood into a given organ parenchyme. Accordingly, blocking the interaction between VLA-6 integrin and laminin, experimentally abrogates heart graft rejection. Many reports have shown that VLA-4 is used by T cells to cross endothelial barriers, as well as to migrate within target tissues. In this respect, a humanized IgG4 anti-VLA-4 monoclonal antibody (specific to the α4-integrin chain of VLA-4) has been successfully applied to treat multiple sclerosis as well as inflammatory bowel disease. Anti-VLA-4 monoclonal antibody has also been applied to block transendothelial passage in other autoimmune diseases, such as rheumatoid arthritis. On this same vein is the action of such a reagent in impairing in vitro transendothial and fibronectin-driven migration of CD4+ and CD8+ T cells expressing high densities of VLA-4 from Duchenne muscular dystrophy patients, thus potentially enlarging the use of this strategy to other diseases. Yet, in a small number of patients, the use of Natalizumab has been correlated with the progressive multifocal leukoencephalopathy, a serious brain infection caused by the John Cunningham virus. This issue restricted the use of the reagent. In this respect, the development of smaller and more specific antibody reagents should be envisioned as a next-generation promising strategy.