bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contextualised strategies to increase childhood and adolescent vaccination coverage in South Africa: a mixed-methods study
Authors: Wiysonge Charles Shey , Mahasha Phetole Walter , Ndwandwe Duduzile Edith , Ngcobo Ntombenhle , Grimmer Karen , Dizon Janine , Burnett Rosemary J , Cooper Sara 
Published: June 2020

IntroductionDespite the unparalleled success of immunisation in the control of vaccine preventable diseases, immunisation coverage in South Africa remains suboptimal. While many evidence-based interventions have successfully improved vaccination coverage in other countries, they are not necessarily appropriate to the immunisation needs, barriers and facilitators of South Africa. The aim of this research is to investigate barriers and facilitators to optimal vaccination uptake, and develop contextualised strategies and implementation plans to increase childhood and adolescent vaccination coverage in South Africa.MethodsThe study will employ a mixed-methods research design. It will be conducted over three iterative phases and use the Adopt, Contextualise or Adapt (ACA) model as an overarching conceptual framework. Phase 1 will identify, and develop a sampling frame of, immunisation stakeholders involved in the design, planning and implementation of childhood and human papillomavirus immunisation programmes in South Africa. Phase 2 will identify the main barriers and facilitators to, and solutions for, increasing vaccination coverage. This phase will comprise exploratory qualitative research with stakeholders and a review of existing systematic reviews on interventions for improving vaccination coverage. Using the findings from Phase 2 and the ACA model, Phase 3 will develop a set of proposed interventions and implementation action plans for improving immunisation coverage in South Africa. These plans will be discussed, revised and finalised through a series of participatory stakeholder workshops and an online questionnaire, conducted as part of Phase 3.EthicsEthical approval was obtained from the South African Medical Research Council (EC018-11/2018). No risks to participants are expected. Various steps will be taken to ensure the anonymity and confidentiality of participants.DisseminationThe study findings will be shared at stakeholder workshops, the website of Cochrane South Africa and academic publications and conferences.
Cholesterol and triglyceride levels in midlife and risk of heart failure in women, a longitudinal study: the prospective population study of women in Gothenburg
Authors: Halldin Anna-Karin , Lissner Lauren , Lernfelt Bodil , Björkelund Cecilia 
Published: June 2020

ObjectiveTo examine the association between triglycerides and cholesterol serum values and risk of developing heart failure in women.DesignLongitudinal observational study of four cohorts 50-year-old women examined in 1968–1969, 1980–1981, 1992–1993 and 2004–2005, and followed until 2012. S-triglycerides and s-cholesterol were measured at baseline and heart failure morbidity and mortality data collected from 1980 to 2012.SettingProspective population study Gothenburg, Sweden. Primary care.Participants1143 women 50 year old without history of heart failure or myocardial infarction.Main outcome measureAssociation among s-triglycerides, s-cholesterol and heart failure expressed as HR for heart failure, adjusted for smoking, body mass index (BMI), physical activity and age.ResultsFor 50-year-old women examined in 1968–1969, there was an independent association between level of s-triglycerides and heart failure and a significantly higher risk of developing heart failure (HR 1.8; CI 1.16 to 2.80, for each increment of 1.0 mmol/L in s-triglycerides), adjusted for smoking, BMI, physical activity and age. There was no significant association between s-cholesterol and risk of heart failure (HR 0.9; CI 0.77 to 1.15). In the cohorts of 50-year-old women examined in 1980 and 1992, there were no significant associations between neither s-triglycerides or s-cholesterol and the risk of heart failure. In the pooled analyses of the cohorts examined in 1968, 1980 and 1992, a significantly increased risk of heart failure was found (HR 1.49; CI 1.10 to 2.03) for s-triglycerides independently, but not for s-cholesterol. None of the 50-year-old women examined in 2004–2005 developed heart failure by 2012 and were excluded from further analyses.ConclusionsHigh levels of s-triglycerides but not s-cholesterol may be a risk marker for later development of heart failure in 50-year-old women.
Restoration of miR-340 controls pancreatic cancer cellCD47expression to promote macrophage phagocytosis and enhance antitumor immunity
Authors: Xi Qing , Zhang Jieyou , Yang Guangze , Zhang Lijuan , Chen Ying , Wang Chengzhi , Zhang Zimu , Guo Xiangdong , Zhao Jingyi , Xue Zhenyi , Li Yan , Zhang Qi , Da Yurong , Liu Li , Yao Zhi , Zhang Rongxin 
Published: June 2020

BackgroundImmune checkpoint blockade has emerged as a potential cancer immunotherapy. The “don’t eat me” signalCD47in cancer cells binds signal regulatory protein-α on macrophages and prevents their phagocytosis. The role of miR-340 in pancreatic ductal adenocarcinoma (PDAC), especially in tumor immunity, has not been explored. Here, we examined the clinical and biological relevance of miR-340 and the molecular pathways regulated by miR-340 in PDAC.MethodsCD47and miR-340 expression and the relationship with cancer patient survival were analyzed by bioinformatics. The mechanism of miR-340 action was explored through bioinformatics, luciferase reporter, qRT-PCR and western blot analyses. The effects of miR-340 on cancer cells were analyzed in terms of apoptosis, proliferation, migration and phagocytosis by macrophages.In vivotumorigenesis was studied in orthotopic and subcutaneous models, and immune cells from the peripheral and tumor immune microenvironments were analyzed by flow cytometry. Depletion of macrophages was used to verify the role of macrophages in impacting the function of miR-340 in tumor progression.ResultsmiR-340 directly regulates and inversely correlates withCD47,and it predicts patient survival in PDAC. The restoration of miR-340 expression in pancreatic cancer cells was sufficient to downregulateCD47and promote phagocytosis of macrophages, further inhibiting tumor growth. The overexpression of miR-340 promoted macrophages to become M1-like phenotype polarized in peripheral and tumor immune microenvironments and increased T cells, especially CD8+T cells, contributing to the antitumor effect of miR-340.ConclusionsmiR-340 is a key regulator of phagocytosis and antitumor immunity, and it could offer a new opportunity for immunotherapy for PDAC.
Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity
Authors: Reches Adi , Ophir Yael , Stein Natan , Kol Inbal , Isaacson Batya , Charpak Amikam Yoav , Elnekave Afek , Tsukerman Pinchas , Kucan Brlic Paola , Lenac Tihana , Seliger Barbara , Jonjic Stipan , Mandelboim Ofer 
Published: June 2020

BackgroundThe use of checkpoint inhibitors has revolutionized cancer therapy. Unfortunately, these therapies often cause immune-related adverse effects, largely due to a lack of tumor specificity.MethodsWe stained human natural killer cells using fusion proteins composed of the extracellular portion of various tumor markers fused to the Fc portion of human IgG1, and identified Nectin4 as a novel TIGIT ligand. Next, we generated a novel Nectin4 blocking antibody and demonstrated its efficacy as a checkpoint inhibitor in killing assays and in vivo.ResultsWe identify Nectin4 to be a novel ligand of TIGIT. We showed that, as opposed to all other known TIGIT ligands, which bind also additional receptors, Nectin4 interacts only with TIGIT. We show that the TIGIT-Nectin4 interaction inhibits natural killer cell activity, a critical part of the innate immune response. Finally, we developed blocking Nectin4 antibodies and demonstrated that they enhance tumor killing in vitro and in vivo.ConclusionWe discovered that Nectin4 is a novel ligand for TIGIT and demonstrated that specific antibodies against it enhance tumor cell killing in vitro and in vivo. Since Nectin4 is expressed almost exclusively on tumor cells, our Nectin4-blocking antibodies represent a combination of cancer specificity and immune checkpoint activity, which may prove more effective and safe for cancer immunotherapy.
Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma
Authors: Ascierto Paolo Antonio , Del Vecchio Michele , Mackiewicz Andrzej , Robert Caroline , Chiarion-Sileni Vanna , Arance Ana , Lebbé Céleste , Svane Inge Marie , McNeil Catriona , Rutkowski Piotr , Loquai Carmen , Mortier Laurent , Hamid Omid , Bastholt Lars , Dreno Brigitte , Schadendorf Dirk , Garbe Claus , Nyakas Marta , Grob Jean-Jacques , Thomas Luc , Liszkay Gabriella , Smylie Michael , Hoeller Christoph , Ferraresi Virginia , Grange Florent , Gutzmer Ralf , Pikiel Joanna , Hosein Fareeda , Simsek Burcin , Maio Michele 
Published: June 2020

BackgroundWe have previously reported significantly longer overall survival (OS) with ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with advanced melanoma, with higher incidences of adverse events (AEs) at 10 mg/kg. This follow-up analysis reports a 5-year update of OS and safety.MethodsThis randomized, multicenter, double-blind, phase III trial included patients with untreated or previously treated unresectable stage III or IV melanoma. Patients were randomly assigned (1:1) to ipilimumab 10 mg/kg or 3 mg/kg every 3 weeks for 4 doses. The primary end point was OS.ResultsAt a minimum follow-up of 61 months, median OS was 15.7 months (95% CI 11.6 to 17.8) at 10 mg/kg and 11.5 months (95% CI 9.9 to 13.3) at 3 mg/kg (HR 0.84, 95% CI 0.71 to 0.99; p=0.04). In a subgroup analysis, median OS of patients with asymptomatic brain metastasis was 7.0 months (95% CI 4.0 to 12.8) in the 10 mg/kg group and 5.7 months (95% CI 4.2 to 7.0) in the 3 mg/kg group. In patients with wild-type or mutantBRAFtumors, median OS was 13.8 months (95% CI 10.2 to 17.0) and 33.2 months (95% CI 19.4 to 45.2) in the 10 mg/kg group, and 11.2 months (95% CI 9.2 to 13.8) and 19.7 months (95% CI 11.6 to 25.3) in the 3 mg/kg group, respectively. The incidence of grade 3/4 treatment-related AEs was 36% in the 10 mg/kg group vs 20% in the 3 mg/kg group, and deaths due to treatment-related AEs occurred in four (1%) and two patients (1%), respectively.ConclusionsThis 61-month follow-up of a phase III trial showed sustained long-term survival in patients with advanced melanoma who started metastatic treatment with ipilimumab monotherapy, and confirmed the significant benefit for those who received ipilimumab 10 mg/kg vs 3 mg/kg. These results suggest the emergence of a plateau in the OS curve, consistent with previous ipilimumab studies.Trial registration numberNCT01515189.
High-precision limits on W–$$W'$$ and Z–$$Z'$$ mixing from diboson production using the full LHC Run 2 ATLAS data set
Authors: Pankov A. A. , Osland P. , Serenkova I. A. , Bednyakov V. A. 
Published: June 2020

AbstractThe full ATLAS Run 2 data set with time-integrated luminosity of $$139 \, {\text {fb}}^{-1}$$139fb-1 in the diboson channels in hadronic final states is used to probe a simple model with an extended gauge sector (EGM), proposed by Altarelli et al., and often taken as a convenient benchmark by experimentalists. This model accommodates new charged $$W'$$W′ and neutral $$Z'$$Z′ vector bosons with modified trilinear Standard Model gauge couplings, decaying into electroweak gauge boson pairs WZ or WW, where W/Z decay hadronically. Exclusion limits at the 95% CL on the $$Z'$$Z′ and $$W'$$W′ resonance production cross section times branching ratio to electroweak gauge boson pairs in the mass range of $$\sim $$∼ 1–5 TeV are here converted to constraints on W–$$W'$$W′ and Z–$$Z'$$Z′ mixing parameters and masses for the EGM. We present exclusion regions on the parameter space of the $$W'$$W′ and $$Z'$$Z′ by using the full Run 2 data set comprised of pp collisions at $$\sqrt{s}=13 \, \hbox {TeV}$$s=13TeV and recorded by the ATLAS detector at the CERN LHC. The obtained exclusion regions are significantly extended compared to those obtained from the previous analysis performed with Tevatron data as well as with LHC data collected at 7 and 8 TeV in Run 1 and are the most stringent bounds to date.
Cost-Effectiveness of Extended Electrocardiogram Monitoring for Atrial Fibrillation After Stroke
Authors: Chew Derek S. , Rennert-May Elissa , Spackman Eldon , Mark Daniel B. , Exner Derek V. 
Published: June 2020

Background and Purpose:
Management of cryptogenic stroke involves the identification of modifiable risk factors, such as atrial fibrillation (AF). Extended rhythm monitoring increases AF detection rates but at an increased device cost compared with conventional Holter monitoring. The objective of the study was to identify and synthesize the existing literature on the cost-effectiveness of prolonged rhythm monitoring devices for AF detection in cryptogenic stroke.

Methods:
We conducted a systematic review of available economic evaluations of prolonged ECG monitoring for AF detection following cryptogenic stroke compared with standard care.

Results:
Of the 530 unique citations, 8 studies assessed the cost-utility of prolonged ECG monitoring compared with standard care following cryptogenic stroke. The prolonged ECG monitoring strategies included 7-day ambulatory monitoring, 30-day external loop recorders or intermittent ECG monitoring, and implantable loop recorders. The majority of cost-utility analyses reported incremental cost-effectiveness ratios below $50 000 per QALY gained; and two studies reported a cost-savings.

Conclusions:
There is limited economic literature on the cost-effectiveness of extended ECG monitoring devices for detection of atrial fibrillation in cryptogenic stroke. In patients with cryptogenic stroke, extended ECG monitoring for AF detection may be economically attractive when traditional willingness-to-pay thresholds are adopted. However, there was substantial variation in the reported ICERs. The direct comparison of cost-effectiveness across technologies is limited by heterogeneity in modeling assumptions.
Insect evolution toward aquatic habitats; reassessment of antennal sensilla in the water bug families Ochteridae, Gelastocoridae and Aphelocheiridae (Hemiptera: Heteroptera: Nepomorpha)
Authors: Nowińska Agnieszka , Brożek Jolanta 
Published: June 2020

The first comparative morphology study on antennal sensilla of Ochteridae, Gelastocoridae and Aphelocheiridae, carried out with the use of a scanning electron microscope, is provided. Our research hypothesis was: the antennal sensilla of the studied families reflect their different adaptations for use in aquatic habitats, while maintaining a common set of sensilla similar to other water bugs (Nepomorpha). Therefore, the number and placement of antennal sensilla of several species in the mentioned families were studied using scanning electron microscopy. Nine main types of mechano- chemo- and thermo-hygroreceptive sensilla were confirmed on their surface, including sensilla trichodea, chaetica, club-like, campaniformia, basiconica, coeloconica, plate-like, ampullacea and sensilla placodea multilobated. While seven of these were already documented in other species, two of them (sensilla plate-like and placodea multilobated) were yet to be documented on the antennae of Nepomorpha. All families display differences in the shape and length of antennae as well as among sensilla types. These findings support our hypothesis regarding differences in sensillar structures among families adapted differently to suitable niches. Differences between these families and previously studied nepomorphan taxa (Nepoidea) were also documented. However, the general set of sensilla observed on the antennae of the studied species is very similar to the one documented in Nepoidea. Therefore, we confirmed our assumptions regarding similarities in antennal sensilla between the studied families and other nepomorphan insects.
Sensitivity of Convective Cell Dynamics and Microphysics to Model Resolution for the OWLeS IOP2b Lake-Effect Snowband
Authors: Jensen Anders A. , Bergmaier Philip T. , Geerts Bart , Morrison Hugh , Campbell Leah S. 
Published: June 2020

AbstractThe OWLeS IOP2b lake-effect case is simulated using the Weather Research and Forecasting (WRF) Model with a horizontal grid spacing of 148 m (WRF-LES mode). The dynamics and microphysics of the simulated high-resolution snowband and a coarser-resolution band from the parent nest (1.33-km horizontal grid spacing) are compared to radar and aircraft observations. The Ice Spheroids Habit Model with Aspect-ratio Evolution (ISHMAEL) microphysics is used, which predicts the evolution of ice particle properties including shape, maximum diameter, density, and fall speed. The microphysical changes within the band that occur when going from 1.33-km to 148-m grid spacing are explored. Improved representation of the dynamics at higher resolution leads to a better representation of the microphysics of the snowband compared to radar and aircraft observations. Stronger updrafts in the high-resolution grid produce higher ice number concentrations and produce ice particles that are more heavily rimed and thus more spherical, smaller (in terms of mean maximum diameter), and faster falling. These changes to the ice particle properties in the high-resolution grid limit the production of aggregates and improve reflectivity compared to observations. Graupel, observed in the band at the surface, is simulated in the strongest convective updrafts, but only at the higher resolution. Ultimately, the duration of heavy precipitation just onshore from the collapse of convection is better predicted in the high-resolution domain compared to surface and radar observations.
Fluoroscopic Swallowing Abnormalities in Dysphagic Patients Following Anterior Cervical Spine Surgery
Authors: Ian Dhar Shumon , Wegner Adam M. , Rodnoi Pope , Wuellner John C. , Mehdizadeh Omid Benjamin , Shen Shih C. , Nachalon Yuval , Nativ-Zeltzer Nogah , Belafsky Peter C. , Klineberg Eric O. 
Published: June 2020

Objectives: To evaluate the precise objective fluoroscopic abnormalities in persons with dysphagia following anterior cervical spine surgery (ACSS). Methods: 129 patients with dysphagia after ACSS were age and sex matched to 129 healthy controls. All individuals underwent videofluoroscopic swallow study (VFSS). VFSS parameters abstracted included upper esophageal sphincter (UES) opening, penetration aspiration scale (PAS), and pharyngeal constriction ratio (PCR). Other data collected included patient-reported outcome measures of voice and swallowing, number of levels fused, type of plate, vocal fold immobility, time from surgery to VFSS, and revision surgery status. Results: The mean age of the entire cohort was 63 (SD ± 11) years. The mean number of levels fused was 2.2 (±0.9). 11.6% (15/129) were revision surgeries. The mean time from ACSS to VFSS was 58.3 months (±63.2). The majority of patients (72.9%) had anterior cervical discectomy and fusion (ACDF). For persons with dysphagia after ACSS, 7.8% (10/129) had endoscopic evidence of vocal fold immobility. The mean UES opening was 0.84 (±0.23) cm for patients after ACSS and 0.86 (±0.22) cm for controls ( P > .0125). Mean PCR was 0.12 (±0.12) for persons after ACSS and 0.08 (±0.08) for controls, indicating significant post-surgical pharyngeal weakness ( P < .0125). The median PAS was 1 (IQR 1) for persons after ACSS as well as for controls. For ACSS patients, PCR had a weak correlation with EAT-10 ( P < .0125). Conclusion: Chronic swallowing dysfunction after ACSS appears to be secondary to pharyngeal weakness and not diminished UES opening, the presence of aspiration, vocal fold immobility, or ACSS instrumentation factors. Level of Evidence: 3b
Impact of Acamprosate on Chronic Tinnitus: A Randomized-Controlled Trial
Authors: Farhadi Mohammad , Salem Mohammad Mahdi , Asghari Alimohamad , Daneshi Ahmad , Mirsalehi Marjan , Mahmoudian Saeid 
Published: June 2020

Objectives: Tinnitus is a common and distressing otologic symptom, with various probable pathophysiologic mechanisms, such as an imbalance between excitatory and inhibitory mechanisms. Acamprosate, generally used to treat alcoholism, is a glutaminergic antagonist and GABA agonist suggested for treating tinnitus. Thus, we aimed to evaluate the efficacy and safety of acamprosate in the treatment of tinnitus. Methods: The current randomized-controlled trial study included 20 subjects with chronic tinnitus. After performing psycho-acoustic, psychometric and electrophysiological evaluations, all studied tinnitus subjects were randomly divided into two groups of acamprosate and placebo. The first group received oral acamprosate (two tablets of 333 mg/d, three times a day), whereas the second group was given placebo treatment (two tablets, three times a day). After the first 30 days, all evaluations were repeated for the studied groups just in the same manner before the study. Subsequently, the final results of each evaluation were compared together with the baseline values. Results: Nine studied subjects randomly received acamprosate, whereas eleven others received a placebo. There was no significant improvement in the psycho-acoustic tests, except a decrease was observed in the pitch match of tinnitus ( P = .039). For those subjects who were receiving acamprosate, a significant reduction was observed in tinnitus handicap inventory ( P = .006), tinnitus questionnaire scores ( P = .007), and the visual analog scores ( P = .007) compared to the placebo group. There was a significant reduction in Action Potential latency ( P = .048) as well as an increase in the amplitude of distortion product otoacoustic emissions at 4 kHz ( P = .048). Conclusions: The study results indicated a subjective relief of tinnitus as well as some degree of the electrophysiological improvement at the level of the cochlear and the distal portion of the auditory nerve among the subjects who received the acamprosate. Clinical trial registration code: IRCT2013121115751N1
Fluoxetine in the Management of Major Depressive Disorder in Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials
Authors: Reyad Ayman Antoun , Plaha Kiran , Girgis Eriny , Mishriky Raafat 
Published: June 2020

Background Fluoxetine is a serotonin-specific reuptake inhibitor antidepressant and is the only approved pharmacological treatment for major depressive disorder (MDD) in children and adolescent. Methods We searched the published randomized controlled-trials to review fluoxetine efficacy and tolerability using the databases PubMed, EudraCT, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials for fluoxetine role in managing MDD in children and adolescents. A meta-analysis was conducted using the identified 7 clinical trials to assess efficacy using the outcomes: Children's Depression Rating Scale–Revised (CDRS-R), Clinical Global Impressions–Severity of Illness (CGI-S) and Clinical Global Impressions–Improvement (CGI-I) response rate. The risk of discontinuation due to adverse effects and common side effects were examined. Results The mean difference in change from baseline for CDRS-R was −2.72 (95% confidence interval [CI], −3.96, −1.48) favoring fluoxetine treatment ( P < .001). Similarly, mean difference for CGI-S was −0.21 (95% CI, −0.36, −0.06). The risk ratio (RR) of discontinuing due to adverse events was 0.98 (95% CI, 0.54, 1.83), with RR for headache side effects 1.34 (95% CI, 1.03, 1.74) and rash 2.6 (95% CI, 1.32, 5.14). Conclusion Fluoxetine demonstrates significant improvements in symptom intensity control in young patients suffering from MDD and is considered well tolerated with similar rates of trials discontinuation; however, fluoxetine was associated with a higher risk of headache and rash side effects. These findings will guide psychiatrists and pharmacists in their clinical role for supporting the care of young mental health patients.