bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of problem-based learning methodology in undergraduate medical education: a scoping review
Authors: Trullàs Joan Carles , Blay Carles , Sarri Elisabet , Pujol Ramon 
Published: February 2022

Abstract
Background
Problem-based learning (PBL) is a pedagogical approach that shifts the role of the teacher to the student (student-centered) and is based on self-directed learning. Although PBL has been adopted in undergraduate and postgraduate medical education, the effectiveness of the method is still under discussion. The author’s purpose was to appraise available international evidence concerning to the effectiveness and usefulness of PBL methodology in undergraduate medical teaching programs.

Methods
The authors applied the Arksey and O’Malley framework to undertake a scoping review. The search was carried out in February 2021 in PubMed and Web of Science including all publications in English and Spanish with no limits on publication date, study design or country of origin.

Results
The literature search identified one hundred and twenty-four publications eligible for this review. Despite the fact that this review included many studies, their design was heterogeneous and only a few provided a high scientific evidence methodology (randomized design and/or systematic reviews with meta-analysis). Furthermore, most were single-center experiences with small sample size and there were no large multi-center studies. PBL methodology obtained a high level of satisfaction, especially among students. It was more effective than other more traditional (or lecture-based methods) at improving social and communication skills, problem-solving and self-learning skills. Knowledge retention and academic performance weren’t worse (and in many studies were better) than with traditional methods. PBL was not universally widespread, probably because requires greater human resources and continuous training for its implementation.

Conclusion
PBL is an effective and satisfactory methodology for medical education. It is likely that through PBL medical students will not only acquire knowledge but also other competencies that are needed in medical professionalism.
Attitudes about withholding or withdrawing life-prolonging treatment, euthanasia, assisted suicide, and physician assisted suicide: a cross-sectional survey among the general public in Croatia
Authors: Borovecki Ana , Curkovic Marko , Nikodem Krunoslav , Oreskovic Stjepan , Novak Milivoj , Rubic Filip , Vukovic Jurica , Spoljar Diana , Gordijn Bert , Gastmans Chris 
Published: February 2022

AbstractBackgroundThere has been no in-depth research of public attitudes on withholding or withdrawing life-prolonging treatment, euthanasia, assisted suicide and physician assisted suicide in Croatia. The aim of this study was to examine these attitudes and their correlation with sociodemographic characteristics, religion, political orientation, tolerance of personal choice, trust in physicians, health status, experiences with death and caring for the seriously ill, and attitudes towards death and dying.MethodsA cross-sectional study was conducted on a three-stage random sample of adult citizens of the Republic of Croatia, stratified by regions, counties, and locations within those counties (N = 1203). In addition to descriptive statistics, ANOVA and Chi-square tests were used to determine differences, and factor analysis (component model, varimax rotation and GK dimensionality reduction criterion), correlation analysis (Bivariate correlation, Pearson’s coefficient) and multiple regression analysis for data analysis.Results38.1% of the respondents agree with granting the wishes of dying people experiencing extreme and unbearable suffering, and withholding life-prolonging treatment, and 37.8% agree with respecting the wishes of such people, and withdrawing life-prolonging treatment. 77% of respondents think that withholding and withdrawing procedures should be regulated by law because of the fear of abuse. Opinions about the practice and regulation of euthanasia are divided. Those who are younger and middle-aged, with higher levels of education, living in big cities, and who have a more liberal worldview are more open to euthanasia. Assisted suicide is not considered to be an acceptable practice, with only 18.6% of respondents agreeing with it. However, 40.1% think that physician assisted suicide should be legalised. 51.6% would support the dying person’s autonomous decisions regarding end-of-life procedures.ConclusionsThe study found low levels of acceptance of withholding or withdrawing life-prolonging treatment, euthanasia, assisted suicide and physician assisted suicide in Croatia. In addition, it found evidence that age, level of education, political orientation, and place of residence have an impact on people’s views on euthanasia. There is a need for further research into attitudes on different end-of-life practices in Croatia.
Clinical and operational insights from data-driven care pathway mapping: a systematic review
Authors: Manktelow Matthew , Iftikhar Aleeha , Bucholc Magda , McCann Michael , O’Kane Maurice 
Published: February 2022

AbstractBackgroundAccumulated electronic data from a wide variety of clinical settings has been processed using a range of informatics methods to determine the sequence of care activities experienced by patients. The “as is” or “de facto” care pathways derived can be analysed together with other data to yield clinical and operational information. It seems likely that the needs of both health systems and patients will lead to increasing application of such analyses. A comprehensive review of the literature is presented, with a focus on the study context, types of analysis undertaken, and the utility of the information gained.MethodsA systematic review was conducted of literature abstracting sequential patient care activities (“de facto” care pathways) from care records. Broad coverage was achieved by initial screening of a Scopus search term, followed by screening of citations (forward snowball) and references (backwards snowball). Previous reviews of related topics were also considered. Studies were initially classified according to the perspective captured in the derived pathways. Concept matrices were then derived, classifying studies according to additional data used and subsequent analysis undertaken, with regard for the clinical domain examined and the knowledge gleaned.Results254 publications were identified. The majority (n = 217) of these studies derived care pathways from data of an administrative/clinical type. 80% (n = 173) applied further analytical techniques, while 60% (n = 131) combined care pathways with enhancing data to gain insight into care processes.DiscussionClassification of the objectives, analyses and complementary data used in data-driven care pathway mapping illustrates areas of greater and lesser focus in the literature. The increasing tendency for these methods to find practical application in service redesign is explored across the variety of contexts and research questions identified. A limitation of our approach is that the topic is broad, limiting discussion of methodological issues.ConclusionThis review indicates that methods utilising data-driven determination of de facto patient care pathways can provide empirical information relevant to healthcare planning, management, and practice. It is clear that despite the number of publications found the topic reviewed is still in its infancy.
Diagnosis and treatment of vulnerable migrants: a retrospective study at a Doctors of the World clinic in Stockholm
Authors: Nordenskiöld Klas Ytterbrink , Olsson Jan-Eric , Bertilson Bo C 
Published: February 2022

Abstract
Background
At Doctors of the World Medical Clinic in Stockholm (DWMCS), medical care is offered to migrants who live under particularly vulnerable conditions and who lack access to subsidized care. The demographic, diagnostic and therapeutic panorama of vulnerable migrants is unknown.

Methods
A quantitative, retrospective study mapping gender, age, diagnostic group, primary diagnosis, therapeutics, referrals, and session timing (whether the care session took place in summer -April to September, or winter - October to March) by reading all patients’ electronic journals at DWMCS between 2014-04-01 and 2017-12-31. Diagnostic groups were classified according to the classification system ICPC-2 which contains six diagnostic groups: symptoms/complaints, infections, neoplasms, injuries, congenital anomalies and other diagnoses. Primary diagnosis was defined as the diagnosis that was first in the diagnosis list for the visit. Difference in median age was calculated with the Mann-Whitney test (MW), and two-group analysis of nominal data was performed with Monte Carlo simulations (MC) and chi square test´s (X2).

Results
The study included 1323 patients: 838 women and 485 men. The median age for women 37 years (29-47) was slightly lower than for men, 40 years (31-47) MW (p = 0.002). The largest diagnostic group was symptoms / complaints. The five most common primary diagnoses were cough (4%), back symptom / complaint (4%), cystitis (3%), upper respiratory infection acute (3%) and abdominal pain epigastric (2%). The most common therapeutic (55%) was pharmaceutical. Referrals accounted for 12% of the therapeutics and 25% of the referrals were to an emergency room. Tests of significance indicated an uneven distribution of diagnostic groups MC (p = 0.003), infectious primary diagnoses MC (p = 0.0001) and referrals MC (p = 0.006) between men and women and an uneven seasonal distribution among the Other diagnoses MC (0.04) and ten most common drug treatments MC (p=0.002).

Conclusions
The demographic, diagnostic and therapeutic panorama of vulnerable migrants at DWMCS was elucidated. Vulnerable migrants have differences in morbidity depending on gender and season, differences in therapeutics depending on gender and differences among their most common drug treatments depending on season. This knowledge is important when addressing the health problems of vulnerable migrants.
Empagliflozin does not reverse lipotoxicity-induced impairment in human myeloid angiogenic cell bioenergetics
Authors: Cinquegrani Gloria , Spigoni Valentina , Fantuzzi Federica , Bonadonna Riccardo C. , Dei Cas Alessandra 
Published: February 2022

Abstract
Background
Empagliflozin can curb inflammation and oxidative stress, through sodium-proton exchanger (NHE) inhibition, in a model of lipotoxicity in human myeloid angiogenic cells (MAC), which mediate endothelial repairing processes. Aim of this study is to assess in human MAC whether: (1) Stearic acid (SA) induced inflammation and increase in oxidant stress is accompanied by bioenergetic alterations; (2) empagliflozin anti-lipotoxic action is concomitant with coherent changes in bioenergetic metabolism, possibly via NHE blockade.

Methods
MAC were isolated from peripheral blood of healthy volunteers and incubated in the presence/absence of SA (100 μM for 3 h) with/without empagliflozin (EMPA 100 μM) or amiloride (Ami 100 μM) for 1 h. Cell respiration (oxygen consumption rate OCR) and anaerobic glycolysis (measured as proton production rate) were recorded in real-time by Seahorse technology, and ATP production (anaerobic glycolysis- and oxphos-derived) rates were calculated.

Results
SA, at the concentration causing inflammation and increased oxidant stress, altered cell bioenergetics of human MAC, with overall reductions in basal OCR and oxphos-derived ATP production (all p < 0.05), pointing to mitochondrial alterations. EMPA, at the concentration counteracting SA-induced lipotoxicity, both alone and in the presence of SA, caused NHE-independent extensive bioenergetic alterations (from p < 0.05 to p < 0.01), greater than those induced by SA alone.

Conclusions
In human MAC: (1) SA altered cell bioenergetics, concomitantly with inflammation and oxidant stress; (2) EMPA possibly inhibited mitochondrial respiration, (3) the protective effect of EMPA against SA-induced lipotoxicity was unlikely to be mediated through bioenergetic metabolism.
Ideational factors associated with net care behaviour: a multi-country analysis
Authors: Kumoji E. ‘Kuor , Awantang Grace N. , Toso Michael , Kamara Diarra , Bleu Thérèse , Lahai Wani , Sillah-Kanu Musa , Dosso Abdul , Achu Dorothy , Babalola Stella 
Published: February 2022

AbstractBackgroundMalaria is endemic to sub-Saharan African countries. Mass and routine distribution, promotion, and use of ITNs are critical components of malaria prevention programmes. Correct and consistent use of insecticide-treated mosquito nets (ITN) is an effective strategy for malaria prevention. To extend bed-net lifespan, the World Health Organization recommends folding or tying up ITNs when they are not in use. This study analyses factors associated with net care practices in three African countries.MethodsResearchers collected household data nationwide in Côte d’Ivoire, from the North and Far North regions of Cameroon, and from Port Loko and Bo districts in Sierra Leone, between 2018 and 2019. The dependent variable was respondents reporting that they fold or tie up their nets. The study adjusted for selected sociodemographic, ideational (psychosocial), and household variables using multilevel models. The analysis was limited to women of reproductive age and their male spouses/partners from households with at least one ITN: 2,940 respondents in Cameroon, 6,105 in Côte d’Ivoire, and 2,730 in Sierra Leone.ResultsAmong respondents, 50.2% in Cameroon, 52.0% in Côte d’Ivoire and 75.6% in Sierra Leone reported folding or tying up their net when it was not in use. In all three countries, the data showed significant clustering at both household and community levels, indicating the influence of factors operating at these levels on net-care behaviour. The odds of reporting the behaviour varied significantly by geographic unit in each country. Consistent use of nets was strongly correlated with net-care behaviour. Furthermore, five ideational variables were positively associated with the outcome behaviour in all three countries: positive attitude towards net care, perceived susceptibility for malaria, response-efficacy of ITNs, perceived self-efficacy for net use, and the perception that net use was a community norm. Additional significant ideational variables included positive attitudes towards net use (Cameroon and Côte d’Ivoire), perceived severity of malaria (Côte d’Ivoire), and interpersonal communication about malaria (Côte d’Ivoire).ConclusionsThe study identified ideational variables associated with recommended net-care practice. Programme efforts designed to promote net-care practices and extend average lifespan of ITNs may be more effective if they emphasize positive attitudes towards net care, perceived susceptibility of malaria infection, response-efficacy of ITNs, perceived self-efficacy for net use, and promote net-care behaviour as a positive community norm.
Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms
Authors: Wang Yang , Zhang Liang , Zhao Guosheng , Zhang Yuan , Zhan Fangbiao , Chen Zhiyu , He Tao , Cao Yang , Hao Lan , Wang Zhigang , Quan Zhengxue , Ou Yunsheng 
Published: February 2022

Abstract
Background
No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications.

Results
In this study, we constructed a potential theranostic nanoplatform by using (poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780 into the shell (PLGA-IR780 NPs), which were further camouflaged with human OS cell membranes from the HOS cell line (MH-PLGA-IR780 NPs). These constructed NPs showed the capacity for homologous targeting with excellent photoacoustic (PA)/fluorescence (FL) imaging ability. Benefitting from their homologous targeting capacity, MH-PLGA-IR780 NPs obviously promoted cell endocytosis in vitro and tumor accumulation in vivo, which could further improve PDT performance under near-infrared (NIR) irradiation. In addition, to their homologous targeting and PA/FL dual-mode imaging ability, MH-PLGA-IR780 NPs had advantages in penetrating deeper into tumor tissues and in real-time dynamic distribution monitoring in vivo, which laid a foundation for further clinical applications in OS. Moreover, we demonstrated that PDT guided by the constructed NPs could significantly induce HOS cells apoptosis and ferroptosis via excessive accumulation of reactive oxygen species (ROS), and further determined that the potential anticancer molecular mechanism of apoptosis was triggered by the release of cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and that ferroptosis caused the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and the inactivation of glutathione peroxidase 4 (GPX4), synergistically leading to excessive accumulation of Lipid-ROS and Lipid peroxides (LPOs). Concurrently, MH-PLGA-IR780 NPs-guided PDT also showed an obvious inhibitory effect on tumor growth in vivo.

Conclusion
These results suggest that this homologous targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and contributes a new and promising approach for OS therapy.

Graphical Abstract
Engineered a dual-targeting biomimetic nanomedicine for pancreatic cancer chemoimmunotherapy
Authors: Wang Meng , Hu Qida , Huang Junmin , Zhao Xinyu , Shao Shiyi , Zhang Fu , Yao Zhuo , Ping Yuan , Liang Tingbo 
Published: February 2022

AbstractThe therapeutic effect of chemotherapeutics such as gemcitabine against pancreatic cancer is considerably attenuated by immune-suppressive tumor microenvironment. Improvement of chemotherapeutic efficacy by targeting tumor-associated macrophage and reprograming tumor microenvironment to enhance their efficacy may become a promising strategy. To this end, we developed a biomimetic dual-targeting nanomedicine (PG@KMCM) where gemcitabine-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles are coated with a layer of bioengineered cancer cell membrane that stably expresses peptides targeting M2-like macrophages (M2pep) while reserving tumor-associated antigens (TAAs). The PG@KMCM nanomedicine enables the simultaneous targeted delivery of gemcitabine to pancreatic tumor sites and TAMs to potentiate its therapeutic effects. Furthermore, the combination of an immune checkpoint inhibitor (PD-L1 antibody) with PG@KMCM synergistically enhanced the anti-tumoral effect by reprogramming the immune-suppressive tumor microenvironment, including the elimination of PD-L1-positive macrophages and the downregulation of PD-L1 expression. Our study proved dual-targeting PG@KMCM nanomedicine in combination with PD-L1 immune checkpoint inhibitor therapy is able to effectively reprogram the tumor microenvironment and kill pancreatic cancer cells to enhance overall therapeutic potential.
Graphical Abstract
The MULTI-ACT model: the path forward for participatory and anticipatory governance in health research and care
Authors: Zaratin Paola , Bertorello Deborah , Guglielmino Roberta , Devigili Danilo , Brichetto Giampaolo , Tageo Valentina , Dati Gabriele , Kramer Stephanie , Battaglia Mario Alberto , Di Luca Monica 
Published: February 2022

AbstractThe COVID-19 pandemic has unmasked even more clearly the need for research and care to form a unique and interdependent ecosystem, a concept which has emerged in recent years. In fact, to address urgent and unexpected missions such as “fighting all together the COVID-19 pandemic”, the importance of multi-stakeholder collaboration, mission-oriented governance and flexibility has been demonstrated with great efficacy. This calls for a policy integration strategy and implementation of responsible research and innovation principles in health, promoting an effective cooperation between science and society towards a shared mission. This article describes the MULTI-ACT framework and discusses how its innovative approach, encompassing governance criteria, patient engagement and multidisciplinary impact assessment, represents a holistic management model for structuring responsible research and innovation participatory governance in brain conditions research.
Intrinsically disordered proteins play diverse roles in cell signaling
Authors: Bondos Sarah E. , Dunker A. Keith , Uversky Vladimir N. 
Published: February 2022

AbstractSignaling pathways allow cells to detect and respond to a wide variety of chemical (e.g. Ca2+or chemokine proteins) and physical stimuli (e.g., sheer stress, light). Together, these pathways form an extensive communication network that regulates basic cell activities and coordinates the function of multiple cells or tissues. The process of cell signaling imposes many demands on the proteins that comprise these pathways, including the abilities to form active and inactive states, and to engage in multiple protein interactions. Furthermore, successful signaling often requires amplifying the signal, regulating or tuning the response to the signal, combining information sourced from multiple pathways, all while ensuring fidelity of the process. This sensitivity, adaptability, and tunability are possible, in part, due to the inclusion of intrinsically disordered regions in many proteins involved in cell signaling. The goal of this collection is to highlight the many roles of intrinsic disorder in cell signaling. Following an overview of resources that can be used to study intrinsically disordered proteins, this review highlights the critical role of intrinsically disordered proteins for signaling in widely diverse organisms (animals, plants, bacteria, fungi), in every category of cell signaling pathway (autocrine, juxtacrine, intracrine, paracrine, and endocrine) and at each stage (ligand, receptor, transducer, effector, terminator) in the cell signaling process. Thus, a cell signaling pathway cannot be fully described without understanding how intrinsically disordered protein regions contribute to its function. The ubiquitous presence of intrinsic disorder in different stages of diverse cell signaling pathways suggest that more mechanisms by which disorder modulates intra- and inter-cell signals remain to be discovered.Graphical abstract