bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colorectal cancer-derived small extracellular vesicles induce TGFβ1-mediated epithelial to mesenchymal transition of hepatocytes
Authors: Pucci Marzia , Moschetti Marta , Urzì Ornella , Loria Marco , Conigliaro Alice , Di Bella Maria Antonietta , Crescitelli Rossella , Olofsson Bagge Roger , Gallo Alessia , Santos Mark F. , Puglisi Caterina , Forte Stefano , Lorico Aurelio , Alessandro Riccardo , Fontana Simona 
Published: April 2023

Abstract
Background
Metastatic disease is the major cause of cancer-related deaths. Increasing evidence shows that primary tumor cells can promote metastasis by preparing the local microenvironment of distant organs, inducing the formation of the so-called “pre-metastatic niche”. In recent years, several studies have highlighted that among the tumor-derived molecular components active in pre-metastatic niche formation, small extracellular vesicles (sEVs) play a crucial role. Regarding liver metastasis, the ability of tumor-derived sEVs to affect the activities of non-parenchymal cells such as Kupffer cells and hepatic stellate cells is well described, while the effects on hepatocytes, the most conspicuous and functionally relevant hepatic cellular component, remain unknown.

Methods
sEVs isolated from SW480 and SW620 CRC cells and from clinical samples of CRC patients and healthy subjects were used to treat human healthy hepatocytes (THLE-2 cells). RT-qPCR, Western blot and confocal microscopy were applied to investigate the effects of this treatment.

Results
Our study shows for the first time that TGFβ1-carrying CRC_sEVs impair the morphological and functional properties of healthy human hepatocytes by triggering their TGFβ1/SMAD-dependent EMT. These abilities of CRC_sEVs were further confirmed by evaluating the effects elicited on hepatocytes by sEVs isolated from plasma and biopsies from CRC patients.

Conclusions
Since it is known that EMT of hepatocytes leads to the formation of a fibrotic environment, a well-known driver of metastasis, these results suggest that CRC_sEV-educated hepatocytes could have an active and until now neglected role during liver metastasis formation.
Availability of malaria diagnostic tests, anti-malarial drugs, and the correctness of treatment: a systematic review and meta-analysis
Authors: Azizi Hosein , Davtalab Esmaeili Elham , Abbasi Fariba 
Published: April 2023

Abstract
Background
Health facilities’ availability of malaria diagnostic tests and anti-malarial drugs (AMDs), and the correctness of treatment are critical for the appropriate case management, and malaria surveillance programs. It is also reliable evidence for malaria elimination certification in low-transmission settings. This meta-analysis aimed to estimate summary proportions for the availability of malaria diagnostic tests, AMDs, and the correctness of treatment.

Methods
The Web of Science, Scopus, Medline, Embase, and Malaria Journal were systematically searched up to 30th January 2023. The study searched any records reporting the availability of diagnostic tests and AMDs and the correctness of malaria treatment. Eligibility and risk of bias assessment of studies were conducted independently in a blinded way by two reviewers. For the pooling of studies, meta-analysis using random effects model were carried out to estimate summary proportions of the availability of diagnostic tests, AMDs, and correctness of malaria treatment.

Results
A total of 18 studies, incorporating 7,429 health facilities, 9,745 health workers, 41,856 febrile patients, and 15,398 malaria patients, and no study in low malaria transmission areas, were identified. The pooled proportion of the availability of malaria diagnostic tests, and the first-line AMDs in health facilities was 76% (95% CI 67–84); and 83% (95% CI 79–87), respectively. A pooled meta-analysis using random effects indicates the overall proportion of the correctness of malaria treatment 62% (95% CI 54–69). The appropriate malaria treatment was improved over time from 2009 to 2023. In the sub-group analysis, the correctness of treatment proportion was 53% (95% CI 50–63) for non-physicians health workers and 69% (95% CI 55–84) for physicians.

Conclusion
Findings of this review indicated that the correctness of malaria treatment and the availability of AMDs and diagnostic tests need improving to progress the malaria elimination stage.
Changes in life satisfaction among unaccompanied asylum-seeking and refugee minors who participated in teaching recovery techniques (TRT)
Authors: Solhaug Anne Kristine , Røysamb Espen , Oppedal Brit 
Published: April 2023

Abstract
Background
Unaccompanied asylum-seeking and refugee minors report low life satisfaction and high levels of mental health problems, nevertheless they often do not seek or receive help for their problems. Teaching Recovery Techniques (TRT) is a low-threshold, five sessions intervention developed to reduce distressing war- and disaster-related trauma reactions among children and youth. In this study, we investigate if TRT can contribute to increased life satisfaction among unaccompanied asylum-seeking and refugee minors.

Methods
Asylum-seeking and resettled unaccompanied minors participated in TRT carried out in 15 locations throughout Norway, n = 147, mean age = 16.61 (SD = 1.80), 88% boys, and 67% from Afghanistan. Life satisfaction was measured by the Cantril Ladder before the intervention, and two- and eight weeks post-intervention. We also included indices of intervention compliance and contextual variables, such as asylum status. We applied a pre- and post-intervention design with linear mixed model analyses to investigate change in life satisfaction.

Results
Life satisfaction significantly increased from pre- to post- intervention, but not for youth whose asylum application had been rejected or who were still awaiting a decision. Indices of intervention compliance were associated with an increase in life satisfaction.

Conclusions
TRT is a potential useful intervention to enhance life satisfaction among unaccompanied asylum-seeking and refugee minors and can be a measure to support positive development among youth at risk for mental health problems. However, TRT initiatives should consider the participant’s stage of asylum process, because harsh immigration policies may overburden the coping capacity. Without further adaptation, TRT seems most useful for youth granted residence. The manual has been revised to include asylum-related stressors.

Trial Registration
ClinicalTrials.gov (16/54,571, registered 30.01.2019).
Targeting the PEDV 3CL protease for identification of small molecule inhibitors: an insight from virtual screening, ADMET prediction, molecular dynamics, free energy landscape, and binding energy calculations
Authors: Pathak Rajesh Kumar , Kim Won-Il , Kim Jun-Mo 
Published: April 2023

AbstractBackgroundThe porcine epidemic diarrhea virus (PEDV) represents a major health issue for piglets worldwide and does significant damage to the pork industry. Thus, new therapeutic approaches are urgently needed to manage PEDV infections. Due to the current lack of a reliable remedy, this present study aims to identify novel compounds that inhibit the 3CL protease of the virus involved in replication and pathogenesis.ResultsTo identify potent antiviral compounds against the 3CL protease, a virtual screening of natural compounds (n = 97,999) was conducted. The top 10 compounds were selected based on the lowest binding energy and the protein-ligand interaction analyzed. Further, the top five compounds that demonstrated a strong binding affinity were subjected to drug-likeness analysis using the ADMET prediction, which was followed by molecular dynamics simulations (500 ns), free energy landscape, and binding free energy calculations using the MM-PBSA method. Based on these parameters, four putative lead (ZINC38167083, ZINC09517223, ZINC04339983, and ZINC09517238) compounds were identified that represent potentially effective inhibitors of the 3CL protease.ConclusionTherefore, these can be utilized for the development of novel antiviral drugs against PEDV. However, this requires further validation through in vitro and in vivo studies.
Insecticide resistance status of Aedes aegypti in southern and northern Ghana
Authors: Abdulai Anisa , Owusu-Asenso Christopher Mfum , Akosah-Brempong Gabriel , Mohammed Abdul Rahim , Sraku Isaac Kwame , Attah Simon Kwaku , Forson Akua Obeng , Weetman David , Afrane Yaw Asare 
Published: April 2023

Abstract
Background
Outbreaks of Aedes-borne arboviral diseases are becoming rampant in Africa. In Ghana, there is no organized arboviral control programme with interventions restricted to mitigate outbreaks. Insecticide application is a crucial part of outbreak responses and future preventative control measures. Thus, knowledge of the resistance status and underlying mechanisms of Aedes populations is required to ensure optimal insecticide choices. The present study assessed the insecticide resistance status of Aedes aegypti populations from southern Ghana (Accra, Tema and Ada Foah) and northern Ghana (Navrongo) respectively.

Methods
Phenotypic resistance was determined with WHO susceptibility tests using Ae. aegypti collected as larvae and reared into adults. Knockdown resistance (kdr) mutations were detected using allele-specific PCR. Synergist assays were performed with piperonyl butoxide (PBO) to investigate the possible involvement of metabolic mechanisms in resistance phenotypes.

Results
Resistance to DDT was moderate to high across sites (11.3 to 75.8%) and, for the pyrethroids deltamethrin and permethrin, moderate resistance was detected (62.5 to 88.8%). The 1534C kdr and 1016I kdr alleles were common in all sites (0.65 to 1) and may be on a trajectory toward fixation. In addition, a third kdr mutant, V410L, was detected at lower frequencies (0.03 to 0.31). Pre-exposure to PBO significantly increased the susceptibility of Ae. aegypti to deltamethrin and permethrin (P < 0.001). This indicates that in addition to kdr mutants, metabolic enzymes (monooxygenases) may be involved in the resistance phenotypes observed in the Ae. aegypti populations in these sites.

Conclusion
Insecticide resistance underpinned by multiple mechanisms in Ae. aegypti indicates the need for surveillance to assist in developing appropriate vector control strategies for arboviral disease control in Ghana.

Graphical Abstract
Antimicrobial use among paediatric inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program, 2017/2018
Authors: Rudnick Wallis , Conly John , Thirion Daniel J. G. , Choi Kelly , Pelude Linda , Cayen Joelle , Bautista John , Beique Lizanne , Comeau Jeannette L. , Dalton Bruce , Delport Johan , Dhami Rita , Embree Joanne , Émond Yannick , Evans Gerald , Frenette Charles , Fryters Susan , Happe Jennifer , Katz Kevin , Kibsey Pamela , Langley Joanne M. , Lee Bonita E. , Lefebvre Marie-Astrid , Leis Jerome A. , McGeer Allison , McKenna Susan , Neville Heather L. , Slayter Kathryn , Suh Kathryn N. , Tse-Chang Alena , Weiss Karl , Science Michelle ,   the Canadian Nosocomial Infection Surveillance Program
Published: April 2023

Abstract
Background
Antimicrobial resistance threatens the ability to successfully prevent and treat infections. While hospital benchmarks regarding antimicrobial use (AMU) have been well documented among adult populations, there is less information from among paediatric inpatients. This study presents benchmark rates of antimicrobial use (AMU) for paediatric inpatients in nine Canadian acute-care hospitals.

Methods
Acute-care hospitals participating in the Canadian Nosocomial Infection Surveillance Program submitted annual AMU data from paediatric inpatients from 2017 and 2018. All systemic antimicrobials were included. Data were available for neonatal intensive care units (NICUs), pediatric ICUs (PICUs), and non-ICU wards. Data were analyzed using days of therapy (DOT) per 1000 patient days (DOT/1000pd).

Results
Nine hospitals provided paediatric AMU data. Data from seven NICU and PICU wards were included. Overall AMU was 481 (95% CI 409–554) DOT/1000pd. There was high variability in AMU between hospitals. AMU was higher on PICU wards (784 DOT/1000pd) than on non-ICU (494 DOT/1000pd) or NICU wards (333 DOT/1000pd). On non-ICU wards, the antimicrobials with the highest use were cefazolin (66 DOT/1000pd), ceftriaxone (59 DOT/1000pd) and piperacillin-tazobactam (48 DOT/1000pd). On PICU wards, the antimicrobials with the highest use were ceftriaxone (115 DOT/1000pd), piperacillin-tazobactam (115 DOT/1000pd), and cefazolin (111 DOT/1000pd). On NICU wards, the antimicrobials with the highest use were ampicillin (102 DOT/1000pd), gentamicin/tobramycin (78 DOT/1000pd), and cefotaxime (38 DOT/1000pd).

Conclusions
This study represents the largest collection of antimicrobial use data among hospitalized paediatric inpatients in Canada to date. In 2017/2018, overall AMU was 481 DOT/1000pd. National surveillance of AMU among paediatric inpatients is necessary for establishing benchmarks and informing antimicrobial stewardship efforts.
Explaining the process of formation of ageism among the iranian older adults
Authors: Yaghoobzadeh Ameneh , Asgari Parvaneh , Nasrabadi Alireza Nikbakht , Mirlashari Jila , Navab Elham 
Published: April 2023

AbstractBackgroundAgeism is considered as one of the consequences of the industrialization of societies, which appears in various forms in different cultures. This study aimed to explain the process of formation of ageism among the older adults people.MethodsThe research was conducted using grounded theory method. Data were collected from 28 participants using in-depth semi-structured interviews and field notes. Data were analyzed using open, axial, and selective coding.ResultsFear of loneliness and rejection striving to tackle ageism “was identified as the core category of the study. Concepts such as “family context” and “cultural context” were relevant. After identifying the strategies used by the older adults in response to the context (“maintaining integrity”, “socio-cultural care” and “proper health care”, “striving to tackle ageism”) was the most important process in ageism by the Iranian older adults.ConclusionFindings of this study indicated that individual, family and social factors play an important role in the process of ageism among the older adults. These factors sometimes exacerbate or moderate the process of ageism. By recognizing these factors, various social institutions and organizations (including the health care system and the national media (radio and television)) can help the older adults achieve successful aging by emphasizing the issues related to the social aspect.
Analysing domain-specific problem-solving processes within authentic computer-based learning and training environments by using eye-tracking: a scoping review
Authors: Mayer Christian W. , Rausch Andreas , Seifried Jürgen 
Published: April 2023

AbstractRecently, many studies have been published on the use of eye-tracking to analyse complex problem-solving processes within authentic computer-based learning and training environments. This scoping review aims to provide a systematic report of the current state-of-the-art for related papers. Specifically, this work offers a scoping review of studies that analyse problem-solving processes by using eye-tracking (alongside additional process data such as log files, think aloud, facial expression recognition algorithms, or psychophysiological measures) within authentic technology-based learning and training environments for professional and vocational education and training (VET). A total of 12 studies were identified. The most commonly calculated measures in eye-tracking research are position measures, and these are almost exclusively position duration measures such as the proportion of fixation times or total dwell times. Count measures are also mostly related to the number or proportion of fixations and dwells. Movement measures are rarely computed and usually refer to saccade directions or a scan path. Also, latency and distance measures are almost never calculated. Eye-tracking data is most often analysed for group comparisons between experts vs. novices or high vs. low-performing groups by using common statistical methods such as t-test, (M)ANOVA, or non-parametric Mann–Whitney-U. Visual attention patterns in problem-solving are examined with heat map analyses, lag sequential analyses, and clustering. Recently, linear mixed-effects models have been applied to account for between and within-subjects differences. Also, post-hoc performance predictions are being developed for future integration into multimodal learning analytics. In most cases, self-reporting is used as an additional measurement for data triangulation. In addition to eye-tracking, log files and facial expression recognition algorithms are also used. Few studies use shimmer devices to detect electrodermal activity or practice concurrent thinking aloud. Overall, Haider and Frensch’s (1996, 1999) “information reduction hypothesis” is supported by many studies in the sample. High performers showed a higher visual accuracy, and visual attention was more focused on relevant areas, as seen by fewer fixation counts and higher fixation duration. Low performers showed significantly fewer fixation durations or substantially longer fixation durations and less selective visual attention. Performance is related to prior knowledge and differences in cognitive load. Eye-tracking, (in combination with other data sources) may be a valid method for further research on problem-solving processes in computer-based simulations, may help identify different patterns of problem-solving processes between performance groups, and may hold additional potential for individual learning support.
Modeling the impacts of projected climate change on wheat crop suitability in semi-arid regions using the AHP-based weighted climatic suitability index and CMIP6
Authors: Alsafadi Karam , Bi Shuoben , Abdo Hazem Ghassan , Almohamad Hussein , Alatrach Basma , Srivastava Amit Kumar , Al-Mutiry Motrih , Bal Santanu Kumar , Chandran M. A. Sarath , Mohammed Safwan 
Published: April 2023

AbstractDue to rapid population growth and the limitation of land resources, the sustainability of agricultural ecosystems has attracted more attention all over the world. Human activities will alter the components of the atmosphere and lead to climate change, which consequently affects crop production badly. In this context, wheat is considered an important crop and ranks as one of the top strategic crops globally. The main objective of this research is to develop a new approach (a weighted climatic suitability index) for evaluating the climate suitability for wheat production. The specific objectives are to project the impact of future climate change on wheat suitability using three models based on WCSI and CMIP6-based projections and to identify the most vulnerable area to climate change and productivity reduction. The climatic criteria for wheat production were selected and classified into eight indicators based on the Sys' scheme and the FAO framework, and then the weighted overlay approach was used in conjunction with the analytic hierarchy process. To confirm the reliability of the integrated WCSI, we determined the nonlinear curve fitting of integrated WCSI-induced wheat yields by the exponential growth equation. Finally, the CMIP6-GCMs projected from three shared socioeconomic pathways were used for WCSI mapping and predicting wheat yields in the short and long term (Southern Syria was selected as a case study). The results show that the nonlinear correlation between wheat yields and the integrated WCSI was 0.78 (R2 = 0.61) confirming the integrated WCSI's reliability in reflecting yield variation caused by climate suitability. The results indicated that WCSI for wheat will be lower over the study area during 2080–2100 compared to the current climate. During 2080–2100, the wheat yield is projected to decrease by 0.2–0.8 t. ha−1 in the western parts of the study area. The findings of this study could be used to plan and develop adaptation strategies for sustainable wheat production in the face of projected climate change. The results of the study will also help in the strategic planning of wheat production in Syria under the projected climate. The results of this research are limited to small areas as a case study, although they are not relevant to similar regions worldwide. However, the study employs novel analytical methods that can be used broadly.
Co-learning commentary: a patient partner perspective in mental health care research
Authors: Riches Linda , Ridgway Lisa , Edwards Louisa 
Published: April 2023

Abstract
Background
Although including patients as full, active members of research teams is becoming more common, there are few accounts about how to do so successfully, and almost none of these are written by patient partners themselves. Three patient partners contributed their lived experience to a three-year, multi-component mental health research project in British Columbia, Canada. As patient partners, we contributed to innovative co-learning in this project, resulting in mutual respect and wide-ranging benefits. To guide future patient partners and researchers seeking patient engagement, we outline the processes that helped our research team ‘get it right’.

Main body
From the outset, we were integrated into components of the project that we chose: thematically coding a rapid review, developing questions and engagement processes for focus groups, and shaping an economic model. Our level of engagement in each component was determined by us. Additionally, we catalyzed the use of surveys to evaluate our engagement and the perceptions of patient engagement from the wider team. At our request, we had a standing place on each monthly meeting agenda. Importantly, we broke new ground when we moved the team from using previously accepted psychiatric terminology that no longer fit the reality of patients’ experiences. We worked diligently with the team to represent the reality that was appropriate for all parties. The approach taken in this project led to meaningful and successfully integrated patient experiences, fostered a shared understanding, which positively impacted team development and cohesion. The resulting ‘lessons learned’ included engaging early, often, and with respect; carving out and creating a safe place, free from stigma; building trust within the research team; drawing on lived experience; co-creating acceptable terminology; and cultivating inclusivity throughout the entire study.

Conclusion
We believe that lived experience can and should go hand-in-hand with research, to ensure study outcomes reflect the knowledge of patients themselves. We were willing to share the truth of our lived experience. We were treated as co-researchers. Successful engagement came from the ‘lessons learned’ that can be used by other teams who wish to engage patient partners in health research.
Pre-operative intravitreal bevacizumab for tractional retinal detachment secondary to proliferative diabetic retinopathy: the Alvaro Rodriguez lecture 2023
Authors: Arevalo J. Fernando , Beatson Bradley 
Published: April 2023

AbstractThe treatment of proliferative diabetic retinopathy (PDR) has evolved significantly since the initial use of panretinal photocoagulation as a treatment in the 1950s. Vascular endothelial growth factor inhibitors have provided an effective alternative without the risk of peripheral vision loss. Despite this, the risk of complications requiring surgical intervention in PDR remains high. Intravitreal bevacizumab has shown promise as a preoperative adjuvant to vitrectomy for PDR complications, albeit with a purported risk for tractional retinal detachment (TRD) progression in eyes with significant fibrous proliferation. Here we will discuss anti-VEGF agent use in PDR and its role in surgical intervention for PDR complications including TRD.