bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving oncology first-in-human and Window of opportunity informed consent forms through participant feedback
Authors: Avinger Anna M. , Sibold Hannah Claire , Campbell Gavin , Abernethy Eli , Bourgeois John , McClary Tekiah , Blee Shannon , Dixon Margie , Harvey R. Donald , Pentz Rebecca D. 
Published: February 2023

AbstractBackgroundAlthough patient advocates have developed templates for standard consent forms, evaluating patient preferences for first in human (FIH) and window of opportunity (Window) trial consent forms is critical due to their unique risks. FIH trials are the initial use of a novel compound in study participants. In contrast, Window trials give an investigational agent over a fixed duration to treatment naïve patients in the time between diagnosis and standard of care (SOC) surgery. Our goal was to determine the patient-preferred presentation of important information in consent forms for these trials.MethodsThe study consisted of two phases: (1) analyses of oncology FIH and Window consents; (2) interviews of trial participants. FIH consent forms were analyzed for the location(s) of information stating that the study drug has not been tested in humans (FIH information); Window consents were analyzed for the location(s) of information stating the trial may delay SOC surgery (delay information). Participants were asked about their preferred placement of the information in their own trial’s consent form. The location of information in the consent forms was compared to the participants’ suggestions for placement.Results34 [17 FIH; 17 Window] of 42(81%) cancer patients approached participated. 25 consents [20 FIH; 5 Window] were analyzed. 19/20 FIH consent forms included FIH information, and 4/5 Window consent forms included delay information. 19/20(95%) FIH consent forms contained FIH information in the risks section 12/17(71%) patients preferred the same. Fourteen (82%) patients wanted FIH information in the purpose, but only 5(25%) consents mentioned it there. 9/17(53%) Window patients preferred delay information to be located early in the consent, before the “Risks” section. 3/5(60%) consents did this.ConclusionsDesigning consents that reflect patient preferences more accurately is essential for ethical informed consent; however, a one-size fits all approach will not accurately capture patient preferences. We found that preferences differed for FIH and Window trial consents, though for both, patients preferred key risk information early in the consent. Next steps include determining if FIH and Window consent templates improve understanding.
ER ribosomal-binding protein 1 regulates blood pressure and potassium homeostasis by modulating intracellular renin trafficking
Authors: Chiu Chu-Hsuan , Hsuan Chin-Feng , Lin Shih-Hua , Hung Yi-Jen , Hwu Chii-Min , Hee Siow-Wey , Lin Shu-Wha , Fong Sitt-Wai , Hsieh Patrick Ching-Ho , Yang Wei-Shun , Lin Wei-Chou , Lee Hsiao-Lin , Hsieh Meng-Lun , Li Wen-Yi , Lin Jou-Wei , Hsu Chih-Neng , Wu Vin-Cent , Chuang Gwo-Tsann , Chang Yi-Cheng , Chuang Lee-Ming 
Published: February 2023

Abstract
Background
Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown.

Methods
To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia–Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model.

Results
In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion.

Conclusions
RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.

Graphical Abstract
Assessment of artemisinin tolerance in Plasmodium falciparum clinical isolates in children with uncomplicated malaria in Ghana
Authors: Ahorhorlu Samuel Yao , Quashie Neils Ben , Jensen Rasmus Weisel , Kudzi William , Nartey Edmund Tetteh , Duah-Quashie Nancy Odurowah , Zoiku Felix , Dzudzor Bartholomew , Wang Christian William , Hansson Helle , Alifrangis Michael , Adjei George Obeng 
Published: February 2023

Abstract
Background
Artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria in Ghana. Artemisinin (ART) tolerance in Plasmodium falciparum has arisen in Southeast Asia and recently, in parts of East Africa. This is ascribed to the survival of ring-stage parasites post treatment. The present study sought to assess and characterize correlates of potential ART tolerance based on post-treatment parasite clearance, ex vivo and in vitro drug sensitivity, and molecular markers of drug resistance in P. falciparum isolates from children with uncomplicated malaria in Ghana.

Methods
Six months to fourteen years old children presenting with acute uncomplicated malaria (n = 115) were enrolled in two hospitals and a Health Centre in Ghana’s Greater Accra region and treated with artemether-lumefantrine (AL) according to body weight. Pre- and post-treatment parasitaemia (day 0 and day 3) was confirmed by microscopy. The ex vivo ring-stage survival assay (RSA) was used to detect percent ring survival while the 72 h SYBR Green I assay was used to measure the 50% inhibition concentration (IC50s) of ART and its derivatives and partner drugs. Genetic markers of drug tolerance /resistance were evaluated using selective whole genome sequencing.

Results
Of the total of 115 participants, 85 were successfully followed up on day 3 post-treatment and 2/85 (2.4%) had parasitaemia. The IC50 values of ART, artesunate (AS), artemether (AM), dihydroartemisinin (DHA), amodiaquine (AQ), and lumefantrine (LUM) were not indicative of drug tolerance. However, 7/90 (7.8%) pre-treatment isolates had > 10% ring survival rates against DHA. Of the four isolates (2 RSA positive and 2 RSA negative) with high genomic coverage, P. falciparum (Pf) kelch 13 K188* and Pfcoronin V424I mutations were only present in the two RSA positive isolates with > 10% ring survival rates.

Conclusions
The observed low proportion of participants with day-3 post-treatment parasitaemia is consistent with rapid ART clearance. However, the increased rates of survival observed in the ex vivo RSA against DHA, maybe a pointer of an early start of ART tolerance. Furthermore, the role of two novel mutations in PfK13 and Pfcoronin genes, harboured by the two RSA positive isolates that had high ring survival in the present study, remains to be elucidated.
‘I’m not going to leave someone to die’: carriage of naloxone by police in Scotland within a public health framework: a qualitative study of acceptability and experiences
Authors: Speakman Elizabeth M. , Hillen Peter , Heyman Inga , Murray Jennifer , Dougall Nadine , Aston Elizabeth V. , McAuley Andrew 
Published: February 2023

Abstract
Background
Scotland has one of the highest rates of drug-related deaths (DRDs) per capita in Europe, the majority of which involve opioids. Naloxone is a medication used to reverse opioid-related overdoses. In efforts to tackle escalating DRDs in many countries, naloxone is increasingly being provided to people who are likely first responders in overdose situations. This includes non-healthcare professionals, such as police officers. A pilot exercise to test the carriage and administration of naloxone by police officers was conducted in selected areas of Scotland between March and October 2021. The aim of the study was to explore the acceptability and experiences of naloxone carriage and administration by police in Scotland.

Methods
The study comprised of two stages. Stage 1 involved in-depth one-to-one qualitative interviews with 19 community stakeholders (people with lived experience, family members, support workers). Stage 2 involved a mixture of in-depth one-to-one interviews and focus groups with 41 police officers. Data were analysed thematically, and the findings from the two stages were triangulated to develop overarching themes and subthemes.

Results
By the end of the pilot, 808 police officers had been trained in the use of intranasal naloxone. Voluntary uptake of naloxone kits among police officers who completed training was 81%. There were 51 naloxone administration incidents recorded by police officers at suspected opioid-related overdose incidents during the pilot. Most officers shared positive experiences of naloxone administration. Naloxone as a first aid tool suited their role as first responders and their duty and desire to preserve life. Perceived barriers included concerns about police undertaking health-related work, potential legal liabilities and stigmatising attitudes. The majority of participants (and all community stakeholders) were supportive of the pilot and for it to be expanded across Scotland.

Conclusions
Police carriage of naloxone is an acceptable and potentially valuable harm reduction tool to help tackle the DRDs crisis in Scotland. However, it requires appropriate integration with existing health and social care systems. The intervention lies at the intersection between public health and policing and implies a more explicit public health approach to policing.
A head-to-head comparison of the EQ-5D-5L and 15D descriptive systems and index values in a general population sample
Authors: Nikl Anna , Janssen Mathieu F. , Brodszky Valentin , Rencz Fanni 
Published: February 2023

Abstract
Background
The EQ-5D-5L and 15D are generic preference-accompanied health status measures with similar dimensions. In this study, we aim to compare the measurement properties of the EQ-5D-5L and 15D descriptive systems and index values in a general population sample.

Methods
In August 2021, an online cross-sectional survey was conducted in a representative adult general population sample (n = 1887). The EQ-5D-5L and 15D descriptive systems and index values were compared in terms of ceiling and floor, informativity (Shannon’s Evenness index), agreement, convergent and known-groups validity for 41 chronic physical and mental health conditions. Danish value sets were used to compute index values for both instruments. As a sensitivity analysis, index values were also estimated using the Hungarian EQ-5D-5L and Norwegian 15D value sets.

Results
Overall, 270 (8.6%) and 1030 (3.4*10−6%) unique profiles occurred on the EQ-5D-5L and 15D. The EQ-5D-5L dimensions (0.51–0.70) demonstrated better informativity than those of 15D (0.44–0.69). EQ-5D-5L and 15D dimensions capturing similar areas of health showed moderate or strong correlations (0.558–0.690). The vision, hearing, eating, speech, excretion and mental function 15D dimensions demonstrated very weak or weak correlations with all EQ-5D-5L dimensions, which may indicate potential room for EQ-5D-5L bolt-ons. The 15D index values showed lower ceiling than the EQ-5D-5L (21% vs. 36%). The mean index values were 0.86 for the Danish EQ-5D-5L, 0.87 for the Hungarian EQ-5D-5L, 0.91 for the Danish 15D and 0.81 for the Norwegian 15D. Strong correlations were found between the index values (Danish EQ-5D-5L vs. Danish 15D 0.671, Hungarian EQ-5D-5L vs. Norwegian 15D 0.638). Both instruments were able to discriminate between all chronic condition groups with moderate or large effect sizes (Danish EQ-5D-5L 0.688–3.810, Hungarian EQ-5D-5L 1.233–4.360, Danish 15D 0.623–3.018 and Norwegian 15D 1.064–3.816). Compared to the 15D, effect sizes were larger for the EQ-5D-5L in 88–93% of chronic condition groups.

Conclusions
This is the first study to compare the measurement properties of the EQ-5D-5L and 15D in a general population sample. Despite having 10 fewer dimensions, the EQ-5D-5L performed better than the 15D in many aspects. Our findings help to understand the differences between generic preference-accompanied measures and support resource allocation decisions.
Soluble low-density lipoprotein receptor-related protein 1 as a surrogate marker of carotid plaque inflammation assessed by 18F-FDG PET in patients with a recent ischemic stroke
Authors: Garcia Eduardo , Camps-Renom Pol , Puig Núria , Fernández-Leon Alejandro , Aguilera-Simón Ana , Benitez-Amaro Aleyda , Solé Arnau , Vilades David , Sanchez-Quesada José Luis , Martí-Fàbregas Joan , Jiménez-Xarrié Elena , Benitez Sonia , Llorente-Cortés Vicenta 
Published: February 2023

Abstract
Background
18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) identifies carotid plaque inflammation and predicts stroke recurrence.

Aim
Our aim was to evaluate the performance of soluble low-density lipoprotein receptor-related protein 1 (sLRP1) as an indicator of carotid plaque inflammation.

Methods
A prospective study was conducted among adult patients with recent (< 7 days) anterior circulation ischemic stroke and at least one atherosclerotic plaque in the ipsilateral internal carotid artery. Patients underwent an early (< 15 days from inclusion) 18F-FDG PET, and the maximum standardized uptake value (SUVmax) within the plaque was measured. sLRP1 levels were measured in plasma samples by ELISA. The association of sLRP1 with SUVmax was assessed using bivariate and multivariable linear regression analyses. Hazard ratios (HR) were estimated with Cox regression to evaluate the association between circulating sLRP1 and stroke recurrence.

Results
The study was conducted with 64 participants, of which 57.8% had ≥ 50% carotid stenosis. The multivariable linear and logistic regression analyses showed that sLRP1 was independently associated with (i) SUVmax within the plaque (β = 0.159, 95% CI 0.062–0.257, p = 0.002) and (ii) a probability of presenting SUVmax ≥ 2.85 g/mL (OR = 1.31, 95% CI 1.00–1.01, p = 0.046), respectively. Participants with stroke recurrence showed higher sLRP1 levels at baseline [6447 ng/mL (4897–11163) vs. 3713 ng/mL (2793–4730); p = 0.018].

Conclusions
sLRP1 was independently associated with carotid plaque inflammation as measured by 18F-FDG PET in patients with recent ischemic stroke and carotid atherosclerosis.
The effectiveness of virtual reality, augmented reality, and mixed reality training in total hip arthroplasty: a systematic review and meta-analysis
Authors: Su Shilong , Wang Ruideng , Zhou Rubing , Chen Zhengyang , Zhou Fang 
Published: February 2023

Abstract
Background
Extended reality (XR), including virtual reality (VR), augmented reality (AR), and mixed reality (MR), has been used in the training of total hip arthroplasty (THA). This study aims to examine the effectiveness of XR training in THA.

Methods
In this systematic review and meta-analysis, we searched PubMed (MEDLINE), EMBASE (OVID), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and clinicaltrials.gov from inception to September 2022 for eligible studies. The Review Manager 5.4 software was applied to compare accuracy of inclination and anteversion, and surgical duration between XR training and conventional methods.

Results
We identified 213 articles, of which 4 randomized clinical trials and 1 prospective controlled study including 106 participants met inclusion criteria. The pooled data indicated the XR training had better accuracy of inclination and shorter surgical duration than conventional methods (MD = −2.07, 95% CI [− 4.02 to −0.11], P = 0.04; SMD = −1.30, 95% CI [− 2.01 to −0.60], P = 0.0003), but the accuracy of anteversion was similar in the two groups.

Conclusions
This systematic review and meta-analysis found XR training had better accuracy of inclination and shorter surgical duration than conventional methods in THA, but the accuracy of anteversion was similar. Based on the pooled results, we suggested that XR training can better improve trainees’ surgical skills than conventional methods in THA.
Assessing Epstein–Barr virus in gastric cancer: clinicopathological features and prognostic implications
Authors: Li Guanghua , Zhou Zhihao , Wang Zhixiong , Wang Zhao 
Published: February 2023

AbstractBackgroundEpstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) was a unique molecular subtype of gastric cancer (GC). However, the clinicopathological characteristics and prognostic role of EBV infection remains unclear. We aimed to evaluate the clinicopathological features of EBVaGC and its role on prognosis.MethodsEBV-encoded RNA (EBER) in situ hybridization method was used to evaluate the EBV status in GC. The serum tumor markers AFP, CEA, CA19-9 and CA125 of patients were detected before treatment. HER2 expression and microsatellite instability (MSI) status was evaluated according to established criteria. The relationship between EBV infection and clinicopathological factors as well as its role on prognosis were investigated.Results420 patients were enrolled in the study and of 53 patients (12.62%) were identified as EBVaGC. EBVaGC was more common in males (p = 0.001) and related to early T stage (p = 0.045), early TNM stage (p = 0.001) and lower level of serum CEA (p = 0.039). No association could be found between EBV infection and HER2 expression, MSI status and other factors (pall > 0.05). Kaplan–Meier analysis revealed that both the overall survival and disease-free survival of EBVaGC patients were similar to that of EBV-negative GC (EBVnGC) patients (p = 0.309 andp = 0.264, respectively).ConclusionEBVaGC was more common in males and in patients with the early T stage and TNM stage as well as patients with lower serum CEA level. Difference in overall survival and disease-free survival between EBVaGC and EBVnGC patients cannot be detected.
The trend of schistosomiasis related bladder cancer in the lake zone, Tanzania: a retrospective review over 10 years period
Authors: Yohana Coletha , Bakuza Jared S. , Kinung’hi Safari M. , Nyundo Bruno A. , Rambau Peter F. 
Published: February 2023

Abstract
Introduction
Bladder cancer is a possible outcome of chronic urinary schistosomiasis in many endemic countries. In Tanzania, the Lake Victoria area is one of the areas with the highest prevalence of urinary schistosomiasis and higher incidences of squamous cell carcinoma (SCC) of the urinary bladder. A previous study in the area over one decade (2001–2010) showed SCC to be common in patients aged below 50 years. With various prevention and intervention programs there are likely to be notable changes in schistosomiasis-related urinary bladder cancer, which is currently unknown. Updated information on the status of SCC in this area will be useful for giving an insights into efficacy of control interventions implemented and help guide the initiation of new ones. Therefore, this study was done to determine the current trend of schistosomiasis-related bladder cancer in lake zone, Tanzania.

Methods
This was a descriptive retrospective study of histologically confirmed urinary bladder cancer cases diagnosed at the Pathology Department of Bugando Medical Centre over 10 years period. The patient files and histopathology reports were retrieved and information was extracted. Data were analyzed using Chi-square and student t-test.

Results
A total of 481 patients were diagnosed with urinary bladder cancer during the study period whereby, 52.6% were males and 47.4% were females. The mean age regardless of histological type of cancer was 55 ± 14.2 years. The SCC was the commonest histological type accounting for 57.0%, followed by transitional cell carcinoma 37.6%, and 5.4% were adenocarcinomas. The Schistosoma haematobium eggs were observed in 25.2% and were commonly associated with SCC (p = 0.001). Poorly differentiated cancers were observed mostly in females (58.6%) compared to males (41.4%) (p = 0.003). Muscular invasion of the urinary bladder by cancer was observed in 11.4% of the patients, and this was significantly higher in non-squamous than in squamous cancers (p = 0.034).

Conclusion
Schistosomiasis-related cancers of the urinary bladder in the Lake zone of Tanzania is still a problem. Schistosoma haematobium eggs were associated with SCC type indicating the persistence of infection in the area. This calls for more efforts on preventive and intervention programs to reduce the burden of urinary bladder cancer in the lake zone.
Ensuring equity in mental health and psychosocial support during the COVID-19 pandemic and beyond
Authors: Armijos Andrea , Bonz Annie G. , Brown Felicity L. , Charlet Danielle , Cohen Flora , Greene M. Claire , Hermosilla Sabrina , James Leah E. , Le Roch Karine ,   MHPSS Implementation Science Learning Collaborative
Published: February 2023

AbstractPopulations affected by armed conflict and other humanitarian crises are at elevated risk for mental health problems. While the COVID-19 pandemic has had broadly deleterious effects on livelihoods, economic well-being, and population health worldwide, vulnerable groups have been disproportionately impacted by the pandemic. Providing mental health and psychosocial support (MHPSS) services during these times to vulnerable groups, especially in low- and middle-income countries and humanitarian settings, is essential. In an effort to comply with the public health response to the pandemic and mitigate COVID-19 transmission, significant implementation adaptations were made to service delivery during the pandemic. This short report describes several strategies to ensure that equity was central to these adaptations and public health responses, and provides recommendations for ensuring continuity of this progress post-pandemic. Examples and key lessons learned are given related to strategies to increase access to MHPSS services, improve meaningful stakeholder engagement, develop and support community networks, and implement community-based psychosocial support groups. They come from diverse settings of Bangladesh, Colombia, Ecuador, and Lebanon. The COVID-19 pandemic has highlighted the importance of preventing and treating MHPSS issues. It also has created opportunities for innovative programming to address overlooked problems, improve the quality of services provided, and increase focus on equity. It is vital that we use the momentum and attention generated around MHPSS services during the COVID-19 pandemic to continue to build and improve existing MHPSS services in more equitable ways for vulnerable populations.