bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparedness for and impact of COVID-19 on primary health care delivery in urban and rural Malawi: a mixed methods study
Authors: Phiri Mackwellings Maganizo , MacPherson Eleanor Elizabeth , Panulo Mindy , Chidziwisano Kondwani , Kalua Khumbo , Chirambo Chawanangwa Mahebere , Kawalazira Gift , Gundah Zaziwe , Chunda Penjani , Morse Tracy 
Published: June 2022

ObjectiveAcross Africa, the impact of COVID-19 continues to be acutely felt. This includes Malawi, where a key component of health service delivery to mitigate against COVID-19 are the primary healthcare facilities, strategically placed throughout districts to offer primary and maternal healthcare. These facilities have limited infrastructure and capacity but are the most accessible and play a crucial role in responding to the COVID-19 pandemic. This study assessed health facility preparedness for COVID-19 and the impact of the pandemic on health service delivery and frontline workers.SettingPrimary and maternal healthcare in Blantyre District, Malawi.ParticipantsWe conducted regular visits to 31 healthcare facilities and a series of telephone-based qualitative interviews with frontline workers (n=81 with 38 participants) between August 2020 and May 2021.ResultsDespite significant financial and infrastructural constraints, health centres continued to remain open. The majority of frontline health workers received training and access to preventative COVID-19 materials. Nevertheless, we found disruptions to key services and a reduction in clients attending facilities. Key barriers to implementing COVID-19 prevention measures included periodic shortages of resources (soap, hand sanitiser, water, masks and staff). Frontline workers reported challenges in managing physical distancing and in handling suspected COVID-19 cases. We found discrepancies between reported behaviour and practice, particularly with consistent use of masks, despite being provided. Frontline workers felt COVID-19 had negatively impacted their lives. They experienced fatigue and stress due to heavy workloads, stigma in the community and worries about becoming infected with and transmitting COVID-19.ConclusionResource (human and material) inadequacy shaped the health facility capacity for support and response to COVID-19, and frontline workers may require psychosocial support to manage the impacts of the COVID-19 pandemic.
Therapy of genomic unstable solid tumours (WHO grade 3/4）in clinical stage III/IV using individualised neoantigen tumour peptides-INP trial (individualised neoantigen tumour peptides immunotherapy): study protocol for an open-label, non-randomised, prospective, single-arm trial
Authors: Wang Ling , Tang Jiaxi , Chen Xia , Zhao Juan , Tang Wanyan , Liao Bin , Nian Weiqi 
Published: June 2022

IntroductionNeoantigens derived from tumour somatic mutations are recognised as ideal vaccine targets. Tumour neoantigens have been studied in a wide range of tumours. Most of research on neoantigens has focused just on a unique tumour and a single mutated gene. Currently, a few studies have reported using a mixture of neoantigen peptides derived from multiple genetic mutation sites in the treatment of genomic unstable advanced solid malignancies. The trial aims to evaluate the safety and efficacy of individualised tumour neoantigen peptide mixtures in the treatment of genomic unstable advanced solid malignant tumours.Methods and analysisThis is a prospective, non-randomised, open, single-centre, single-arm, phase I trial. Patients with genomic unstable advanced solid malignancies are eligible for study participations. 20 patients will be included in the trial. Through the whole exome and transcriptome sequencing analysis of the fresh blood and tumour tissues of the enrolled patients, the 20 25-33aa antigen peptides with the highest mutation scores of the patients will be screened out, and the corresponding new antigen peptides will be synthesised and prepared. Patients will be treated with their own individualised neoantigen polypeptide combined with a polypeptide adjuvant (human granulocyte-macrophage colony-stimulating factor). The primary endpoint is safety indicators, including general and specific adverse events which will be monitored continuously. Secondary endpoints are progression-free survival, objective response rate, objective duration of remission, 1-year survival rate and overall survival.Ethics and disseminationThis study has received approval from the Ethics Committee of Chongqing University Cancer Hospital on 21 November 2019 (207/2019). The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications.Trial registration numberChiCTR1900025364.
Development and design validation of a novel network meta-analysis presentation tool for multiple outcomes: a qualitative descriptive study
Authors: Phillips Mark R , Sadeghirad Behnam , Busse Jason W , Brignardello-Petersen Romina , Cuello-Garcia Carlos A , Kenji Nampo Fernando , Guo Yu Jia , Bzovsky Sofia , Bannuru Raveendhara R , Thabane Lehana , Bhandari Mohit , Guyatt Gordon H 
Published: June 2022

ObjectiveThe Grades of Recommendations, Assessment, Development and Evaluation working group recently developed an innovative approach to interpreting results from network meta-analyses (NMA) through minimally and partially contextualised methods; however, the optimal method for presenting results for multiple outcomes using this approach remains uncertain. We; therefore, developed and iteratively modified a presentation method that effectively summarises NMA results of multiple outcomes for clinicians using this new interpretation approach.DesignQualitative descriptive study.SettingA steering group of seven individuals with experience in NMA and design validation studies developed two colour-coded presentation formats for evaluation. Through an iterative process, we assessed the validity of both formats to maximise their clarity and ease of interpretation.Participants26 participants including 20 clinicians who routinely provide patient care, 3 research staff/research methodologists and 3 residents.Main outcome measuresTwo team members used qualitative content analysis to independently analyse transcripts of all interviews. The steering group reviewed the analyses and responded with serial modifications of the presentation format.ResultsTo ensure that readers could easily discern the benefits and safety of each included treatment across all assessed outcomes, participants primarily focused on simple information presentations, with intuitive organisational decisions and colour coding. Feedback ultimately resulted in two presentation versions, each preferred by a substantial group of participants, and development of a legend to facilitate interpretation.ConclusionIterative design validation facilitated the development of two novel formats for presenting minimally or partially contextualised NMA results for multiple outcomes. These presentation approaches appeal to audiences that include clinicians with limited familiarity with NMAs.
Treatment and prescribing trends of antihypertensive drugs in 2.7 million UK primary care patients over 31 years: a population-based cohort study
Authors: Rouette Julie , McDonald Emily G. , Schuster Tibor , Brophy James M. , Azoulay Laurent 
Published: June 2022

ObjectivesTo describe the prescribing trends of antihypertensive drugs in primary care patients and assess the trajectory of antihypertensive drug prescriptions, from first-line to third-line, in patients with hypertension according to changes to the United Kingdom (UK) hypertension management guidelines.DesignPopulation-based cohort study.Setting and participantsWe used the UK Clinical Practice Research Datalink, an electronic primary care database representative of the UK population. Between 1988 and 2018, we identified all adult patients with at least one prescription for a thiazide diuretic, angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker, beta-blocker or calcium channel blocker (CCB).Primary and secondary outcome measuresWe estimated the period prevalence of patients with antihypertensive drug prescriptions for each calendar year over a 31-year period. Treatment trajectory was assessed by identifying patients with hypertension newly initiating an antihypertensive drug, and treatment changes were defined by a switch or add-on of a new class. This cohort was stratified before and after 2007, the year following important changes to UK hypertension management guidelines.ResultsThe cohort included 2 709 241 patients. The prevalence of primary care patients with antihypertensive drug prescriptions increased from 7.8% (1988) to 21.9% (2018) and was observed for all major classes except thiazide diuretics. Patients with hypertension initiated thiazide diuretics (36.8%) and beta-blockers (23.6%) as first-line drugs before 2007, and ACE inhibitors (39.9%) and CCBs (31.8%) after 2007. After 2007, 17.3% were not prescribed guideline-recommended first-line agents. Overall, patients were prescribed a median of 2 classes (IQR 1–2) after first-line treatment.ConclusionNearly one-quarter of primary care patients were prescribed antihypertensive drugs by the end of the study period. Most patients with hypertension initiated guideline-recommended first-line agents. Not all patients, particularly females, were prescribed recommended agents however, potentially leading to suboptimal cardiovascular outcomes. Future research should aim to better understand the implication of this finding.
Combinations of Toll-like receptor 8 agonist TL8-506 activate human tumor-derived dendritic cells
Authors: He Mi , Soni Bhavesh , Schwalie Petra C , Hüsser Tamara , Waltzinger Caroline , De Silva Duvini , Prinz Ylva , Krümpelmann Laura , Calabro Samuele , Matos Ines , Trumpfheller Christine , Bacac Marina , Umaña Pablo , Levesque Mitchell P , Dummer Reinhard , van den Broek Maries , Gasser Stephan 
Published: June 2022

BackgroundDendritic cells (DCs) are professional antigen presenting cells that initiate immune defense to pathogens and tumor cells. Human tumors contain only few DCs that mostly display a non-activated phenotype. Hence, activation of tumor-associated DCs may improve efficacy of cancer immunotherapies. Toll-like receptor (TLR) agonists and interferons are known to promote DC maturation. However, it is unclear if DCs in human tumors respond to activation signals and which stimuli induce the optimal activation of human tumor DCs.MethodsWe first screened combinations of TLR agonists, a STING agonist and interferons (IFNs) for their ability to activate human conventional DCs (cDCs). Two combinations: TL8-506 (a TLR8 agonist)+IFN-γ and TL8-506+Poly(I:C) (a TLR3 agonist) were studied in more detail. cDC1s and cDC2s derived from cord blood stem cells, blood or patient tumor samples were stimulated with either TL8-506+IFN-γ or TL8-506+Poly(I:C). Different activation markers were analyzed by ELISA, flow cytometry, NanoString nCounter Technology or single-cell RNA-sequencing. T cell activation and migration assays were performed to assess functional consequences of cDC activation.ResultsWe show that TL8-506 synergized with IFN-γ or Poly(I:C) to induce high expression of different chemokines and cytokines including interleukin (IL)-12p70 in human cord blood and blood cDC subsets in a combination-specific manner. Importantly, both combinations induced the activation of cDC subsets in patient tumor samples ex vivo. The expression of immunostimulatory genes important for anticancer responses includingCD40,IFNB1,IFNL1,IL12AandIL12Bwere upregulated on stimulation. Furthermore, chemokines associated with CD8+T cell recruitment were induced in tumor-derived cDCs in response to TL8-506 combinations. In vitro activation and migration assays confirmed that stimulated cDCs induce T cell activation and migration.ConclusionsOur data suggest that cord blood-derived and blood-derived cDCs are a good surrogate to study treatment responses in human tumor cDCs. While most cDCs in human tumors display a non-activated phenotype, TL8-506 combinations drive human tumor cDCs towards an immunostimulatory phenotype associated with Th1 responses on stimulation. Hence, TL8-506-based combinations may be promising candidates to initiate or boost antitumor responses in patients with cancer.
A novel diagnostic approach for patients with adult-onset dystonia
Authors: van Egmond Martje E , Lagrand Tjerk J , Lizaitiene Gintaute , Smit Marenka , Tijssen Marina A J 
Published: June 2022

Adult-onset dystonia can be acquired, inherited or idiopathic. The dystonia is usually focal or segmental and for a limited number of cases causal treatment is available. In recent years, rapid developments in neuroimmunology have led to increased knowledge on autoantibody-related dystonias. At the same time, genetic diagnostics in sequencing technology have evolved and revealed several new genes associated with adult-onset dystonia. Furthermore, new phenotype–genotype correlations have been elucidated. Consequently, clinicians face the dilemma of which additional investigations should be performed and whether to perform genetic testing or not. To ensure early diagnosis and to prevent unnecessary investigations, integration of new diagnostic strategies is needed.We designed a new five-step diagnostic approach for adult-onset dystonia. The first four steps are based on a broad literature search and expert opinion, the fifth step, on when to perform genetic testing, is based on a detailed systematic literature review up to 1 December 2021.The basic principle of the algorithm is that genetic testing is unlikely to lead to changes in management in three groups: (1) patients with an acquired form of adult-onset dystonia; (2) patients with neurodegenerative disorders, presenting with a combined movement disorder including dystonic symptoms and (3) patients with adult-onset isolated focal or segmental dystonia. Throughout the approach, focus lies on early identification of treatable forms of dystonia, either acquired or genetic.This novel diagnostic approach for adult-onset dystonia can help clinicians to decide when to perform additional tests, including genetic testing and facilitates early aetiological diagnosis, to enable timely treatment.
Use of permethrin and other pyrethroids and mortality in the Agricultural Health Study
Authors: Shrestha Srishti , Parks Christine G , Umbach David M , Hofmann Jonathan N , Beane Freeman Laura E , Blair Aaron , Sandler Dale P 
Published: June 2022

ObjectivesPyrethroid insecticides have been linked with multiple health outcomes. One study reported an association with increased all-cause and cardiovascular mortality. Given the widespread use of pyrethroids, these findings warrant confirmation. We explored associations of permethrin/pyrethroid use with overall and cause-specific mortality among 50 665 licensed pesticide applicators in the Agricultural Health Study.MethodsAt enrolment (1993–1997), participants self-reported information on permethrin/pyrethroid use. Information on causes of death came from linkage with death registries through 2016. We used Cox proportional hazards models to estimate HRs and 95% CIs with adjustment for potential confounders.ResultsOver an average 21 years of follow-up, 19.6% (9,955) of the cohort died. We found no clear evidence that ever-use of permethrin/pyrethroid was associated with elevated overall mortality or with mortality from most causes examined. There was suggestive evidence, based on a small number of deaths among those exposed, for elevated pyrethroid-associated mortality from some neurological, respiratory and genitourinary diseases in the overall sample and from lung cancer among never-smokers.ConclusionAlthough based on mortality, which is also affected by survival, rather than incidence, these findings are biologically plausible, and future investigations in other populations may be warranted.
Tilt grain boundary energy in 〈0001〉/φ bicrystals of pure ice
Authors: Di Prinzio C.L. , Stoler D. , Varela Aguirre , Druetta E. 
Published: June 2022

This work presents measurements of the relative energy ( γgb/ γs) of the tilt grain boundary (GB) in pure ice bicrystals with crystalline misorientation 〈0001〉/ φ. The GBs had different inclinations and were annealed at −5 °C and −18 °C. A GB structure model called the facet model (FM) was applied. The FM assumes that the GB is composed of facets. The facets are oriented with the principal faces of the cell primitive of the coincident site lattice (CSL). The CSL is associated with the bicrystalline misorientation. In general, ( γgb/ γs) varies by more than one order of magnitude between temperatures −5 °C ( γgb/ γs ~ 0.03) and −18 °C ( γgb/ γs ~ 0.35), so GB structural changes are very noticeable with temperature. The GB energy does not depend on the inclination at temperatures near 0 °C, while the dependence on inclination presents a slight significance at −18 °C. Finally, it was observed that the GB relative energy ( γgb/ γs) for bicrystalline 〈0001〉/ φ samples is lower than the relative energy at other crystalline misorientations. These experimental data are unique and could explain the slow GB migration in 〈0001〉/ φ bicrystals and they could help to understand grain growth in polar ice where the most frequent crystalline misorientation is 〈0001〉/ φ.
Effects of hunting pressure and timing of harvest on bighorn sheep (Ovis canadensis) horn size
Authors: Lassis Roxane , Festa-Bianchet Marco , Pelletier Fanie 
Published: June 2022

Trophy hunting can affect weapon size of wild animals through both demographic and evolutionary changes. In bighorn sheep ( Ovis canadensis Shaw, 1804), intense harvest of young males with fast-growing horns may have partly driven long-term decreases in horn size. These selective effects could be dampened if migrants from protected areas, not subject to artificial selection, survived and reproduced within hunted populations. Bighorn rams undertake long-distance breeding migrations in the weeks preceding the late-November rut. We analysed records of >7800 trophy bighorn rams shot from 1974 to 2019 in Alberta, Canada, to test the hypothesis that high harvest pressure during breeding migrations was correlated with a greater decrease in horn size. We compared areas with and without a pronounced harvest peak in late October, when male breeding migrations begin. Areas without a pronounced harvest peak in late October, which likely experienced a lower harvest rate, showed a similar temporal decline in horn size, but no increase in age at harvest suggesting a possibly weaker decline in horn growth. Our study suggests that unselected immigrants from protected areas could partly buffer the effects of intense trophy hunting only if harvest pressure was reduced when breeding migrations commence.
Adherence to the AICR Cancer Prevention Recommendations and Subsequent Morbidity and Mortality in the Iowa Women's Health Study Cohort
Authors: Cerhan James R. , Potter John D. , Gilmore Julie M.E. , Janney Carol A. , Kushi Larry H. , Lazovich DeAnn , Anderson Kristin E. , Sellers Thomas A. , Folsom Aaron R. 
Published: June 2022

Abstract
In 1997, the American Institute for Cancer Research (AICR) published 14 recommendations related to diet for individuals to reduce cancer incidence on a global basis; smoking was also discouraged. We operationalized these into nine recommendations that are particularly relevant to western populations in a cohort of 29,564 women ages 55 to 69 years at baseline in 1986 who had no history of cancer or heart disease. The cohort was followed through 1998 for cancer incidence (n = 4,379), cancer mortality (n = 1,434), cardiovascular disease (CVD) mortality (n = 1,124), and total mortality (n = 3,398). The median number (range) of recommendations followed was 4 (0-8), and 33% of the cohort had ever smoked. Women who followed no or one recommendation compared with six to nine recommendations were at an increased risk of cancer incidence [relative risk (RR) 1.35, 95% confidence interval (CI) 1.15-1.58] and cancer mortality (RR 1.43, 95% CI 1.11-1.85), but there was no association with CVD mortality (RR 1.06, 95% CI 0.78-1.43). We calculated the population attributable risk (PAR) to estimate the proportion of cancer incidence, cancer mortality, and CVD mortality that theoretically would have been avoidable if the entire cohort had never smoked, had followed six to nine recommendations, or had done both. The PARs for smoking were 11% (95% CI 10-13) for cancer incidence, 21% (95% CI 17-24) for cancer mortality, and 20% (95% CI 16-23) for CVD mortality. The PARs for not following six to nine recommendations were 22% (95% CI 12-30) for cancer incidence, 11% (95% CI −5 to 24) for cancer mortality, and 4% (95% CI −20 to 19) for CVD mortality. When smoking and the operationalized AICR recommendations were combined together, the PARs were 31% (95% CI 19-37) for cancer incidence, 30% (95% CI 15-40) for cancer mortality, and 22% (95% CI 4-36) for CVD mortality. These data suggest that the adherence to the AICR recommendations, independently and in conjunction with not smoking, is likely to have a substantial public health impact on reducing cancer incidence and, to a lesser degree, cancer mortality at the population level.
A Prospective Study of Body Size in Different Periods of Life and Risk of Premenopausal Breast Cancer
Authors: Weiderpass Elisabete , Braaten Tonje , Magnusson Cecilia , Kumle Merethe , Vainio Harri , Lund Eiliv , Adami Hans-Olov 
Published: June 2022

Abstract
The prevalence of obesity at all ages is increasing epidemically worldwide. Information on the association between premenopausal breast cancer and body size during childhood and teenage years is scarce. In 1991 to 1992, a prospective cohort study was assembled in Norway and Sweden. We included in the analysis presented here 99,717 premenopausal women. During the follow-up period, which ended in December 1999, 733 of these women developed a primary invasive breast cancer. Overweight and obesity [body mass index (BMI) &gt; 25 kg/m2] at enrolment was associated with a decreased risk of premenopausal breast cancer (P for linear trend = 0.007). Apparent associations between perceived body shape at age 7 and BMI at age 18, with heavier builds at both ages seemingly being protective for premenopausal breast cancer risk, lost their statistical significance after adjustment for BMI at cohort enrolment. Body size at age 7 was correlated with BMI at age 18 (r = 0.43); BMI at age 18 was correlated with adult BMI (r = 0.48). Changes in body size from age 7 or 18 to adulthood did not affect per se risk of premenopausal breast cancer risk. Height was related to risk, with a statistically significantly 30% reduced risk only in women shorter than 160 cm as compared with taller ones. The decreased risk of premenopausal breast cancer was observed in overweight and obese women without, but not in those with, a family history of breast cancer.