bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can positive expectations help to improve the learning of risk literacy? A cluster-randomized study in undergraduate medical students
Authors: Benson Sven , Schmidt Katharina , Kleine-Borgmann Julian , Herbstreit Stephanie , Schedlowski Manfred , Hollinderbäumer Anke 
Published: May 2022

Abstract
Background
Risk literacy, i.e., the ability to calculate and apply risk parameters, represents a key competence for risk communication and medical decision making. However, risk literacy is reportedly low in medical students. The successful acquisition of statistical competencies is often difficult, and can be hampered by emotional learning obstacles, calling for interventions to support learning. In this cluster-randomized study, we aimed to translate findings from placebo research to medical education. Specifically, we tested if the acquisition of risk literacy during a seminar unit can be facilitated by positive expectations, induced by a positive and non-threatening framing of the content and learning goals.

Methods
The study took place during a mandatory 2.5-h seminar on “risk literacy” for 2nd year medical students. The seminar teaches both statistical knowledge and its application in patient communication. To test the effects of expectations on risk literacy acquisition, the (otherwise identical) seminar was framed either as “communication training” (positive framing condition) or “statistics seminar” (negative framing condition). All N = 200 students of the semester were invited to participate, and cluster-randomized to the positive or negative framing condition (4 seminar groups each condition). Risk literacy was assessed with the “Quick Risk Test” (QRT) at the beginning and end of the seminar, along with statistics anxiety and subjective learning success using questionnaires.

Results
Data from N = 192 students were included. At the end of the seminar, risk literacy was increased in both framing conditions, with a significantly greater increase in QRT scores in the positive framing condition. Statistics anxiety was significantly decreased in both framing conditions, with no evidence of group differences. Subjective learning success was overall high and comparable between groups.

Conclusions
Supporting our hypothesis, positive framing led to a significantly greater increase in risk literacy (i.e., in QRT scores). Our data offer first support that positive framing of learning goals may help to facilitate the acquisition of statistical knowledge. Expectation-orientated interventions may thus offer a feasible tool to optimize learning settings and framing of learning objectives in medical statistics courses.
Effectiveness of instructional videos for enhancing healthcare provider competencies for hypertension management – a pre-post study in primary healthcare settings, Tanzania
Authors: Edward Anbrasi , Kagaruki Gibson B. , Manase Frank , Appel Lawrence J. , Matsushita Kunihiro 
Published: May 2022

Abstract
Background
Inadequate adherence to hypertension (HT) clinical standards by healthcare providers is one of the major barriers for HT management. We examined the effectiveness of four short instructional training videos on HT management.

Methods
Eighteen primary health care facilities were randomly selected using systematic sampling from five districts in the Dar es Salaam region, Tanzania. Pre-post provider knowledge assessments were conducted six months after training and provider performance was measured using patient observations on 8-10 consecutive adult patients per facility. A Screening Quality Index (SQI), comprised of ten HT screening standards, was used to measure adherence.

Results
Pre-post knowledge scores improved significantly, for, time between blood pressure (BP) readings (28.1% to 72.7%, p=0.01), BP threshold for patients with complications (21.2% to 97.0%, p<0.001), and lifestyle/dietary counseling (from 36.4% to 97.0%, p<0.001). SQI was significantly higher following the training for all provider groups; Nurses (3.0±3.5 to 8.4±1.0, p<0.001), Assistant Medical Officers and Medical Officers (3.5±4.1 to 7.6±2.4, p<0.001), and Assistant Clinical Officers and Clinical Officers (5.4±3.8 to 8.4±2.0, p<0.001). After training, significantly higher adherence was evident for key aspects of managing patients with HT: e.g., counseling on medication (62.1% to 92.7%, p=0.002), side effects (41.4% to 56.1%, p=0.009), reducing caloric intake (69.0 % to 95.1%, p=0.003), reducing cooking salt (65.5% to 97.6%, p<0.01), increasing physical activity (55.2% to 92.7% p<0.001), stopping/reducing cigarette smoking (24.1% to 63.4%, p=0.001), and reducing alcohol consumption (24.1% to 68.3%, p<0.001). SQI was significantly associated with number of years of provider experience (more than 2 years), type of primary healthcare facility (public facility), and exposure to the training intervention.

Conclusion
Training with short instructional videos can improve provider competency and clinical performance for HT management. The strategy has the potential to enhance effective implementation of HT control strategies in primary care clinics in Tanzania and elsewhere.
Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy/internal irradiation combination therapy
Authors: Wang Congcong , Li Ning , Li Yutian , Hou Shasha , Zhang Wenxin , Meng Zhaowei , Wang Shen , Jia Qiang , Tan Jian , Wang Renfei , Zhang Ruiguo 
Published: May 2022

AbstractExosomes are nanoscale monolayer membrane vesicles that are actively endogenously secreted by mammalian cells. Currently, multifunctional exosomes with tumor-targeted imaging and therapeutic potential have aroused widespread interest in cancer research. Herein, we developed a multifunctional HEK-293T exosome-based targeted delivery platform by engineering HEK-293T cells to express a well-characterized exosomal membrane protein (Lamp2b) fused to the αv integrin-specific iRGD peptide and tyrosine fragments. This platform was loaded with doxorubicin (Dox) and labeled with radioiodine-131 (131I) using the chloramine-T method. iRGD exosomes showed highly efficient targeting and Dox delivery to integrin αvβ3-positive anaplastic thyroid carcinoma (ATC) cells as demonstrated by confocal imaging and flow cytometry in vitro and an excellent tumor-targeting capacity confirmed by single-photon emission computed tomography-computed tomography after labeling with 131I in vivo. In addition, intravenous injection of this vehicle delivered Dox and 131I specifically to tumor tissues, leading to significant tumor growth inhibition in an 8505C xenograft mouse model, while showing biosafety and no side effects. These as-developed multifunctional exosomes (denoted as Dox@iRGD-Exos-131I) provide novel insight into the current treatment of ATC and hold great potential for improving therapeutic efficacy against a wide range of integrin αvβ3-overexpressing tumors.
Graphical Abstract
Platinum-induced mitochondrial OXPHOS contributes to cancer stem cell enrichment in ovarian cancer
Authors: Sriramkumar Shruthi , Sood Riddhi , Huntington Thomas D. , Ghobashi Ahmed H. , Vuong Truc T. , Metcalfe Tara X. , Wang Weini , Nephew Kenneth P. , O’Hagan Heather M. 
Published: May 2022

Abstract
Background
Platinum based agents—cisplatin and carboplatin in combination with taxanes are used for the treatment of ovarian cancer (OC) patients. However, the majority of OC patients develop recurrent, platinum resistant disease that is uniformly fatal. Platinum treatment enriches for chemoresistant aldehyde dehydrogenase (ALDH) + ovarian cancer stem cells (OCSCs), which contribute to tumor recurrence and disease relapse. Acquired platinum resistance also includes metabolic reprograming and switching to oxidative phosphorylation (OXPHOS). Chemosensitive cells rely on glycolysis while chemoresistant cells have the ability to switch between glycolysis and OXPHOS, depending on which pathway drives a selective advantage for growth and chemoresistance. High expression of genes involved in OXPHOS and high production of mitochondrial ROS are characteristics of OCSCs, suggesting that OCSCs favor OXPHOS over glycolysis. Based on connections between OCSCs, chemoresistance and OXPHOS, we hypothesize that platinum treatment induces changes in metabolism that contribute to platinum-induced enrichment of OCSCs.

Methods
The effect of cisplatin on mitochondrial activity was assessed by JC1 staining and expression of OXPHOS genes by RT-qPCR. Cisplatin-induced changes in Sirtuin 1 (SIRT1) levels and activity were assessed by western blot. Small molecule inhibitors of mitochondrial complex I and SIRT1 were used to determine if their enzymatic activity contributes to the platinum-induced enrichment of OCSCs. The percentage of ALDH + OCSCs in OC cells and tumor tissue from xenograft models across different treatment conditions was analyzed using ALDEFLUOR assay and flow cytometry.

Results
We demonstrate that platinum treatment increases mitochondrial activity. Combined treatment of platinum agents and OXPHOS inhibitors blocks the platinum-induced enrichment of ALDH + OCSCs in vitro and in vivo. Furthermore, platinum treatment increases SIRT1 levels and subsequent deacetylase activity, which likely contributes to the increase in platinum-induced mitochondrial activity.

Conclusions
These findings on metabolic pathways altered by platinum-based chemotherapy have uncovered key targets that can be exploited therapeutically to block the platinum-induced enrichment of OCSCs, ultimately improving the survival of OC patients.
Pentoxifylline alleviates ischemic white matter injury through up-regulating Mertk-mediated myelin clearance
Authors: Zheng Lili , Jia Junqiu , Chen Yan , Liu Renyuan , Cao Runjing , Duan Manlin , Zhang Meijuan , Xu Yun 
Published: May 2022

Abstract
Background
Vascular dementia (VAD) is the second most common type of dementia lacking effective treatments. Pentoxifylline (PTX), a nonselective phosphodiesterase inhibitor, displays protective effects in multiple cerebral diseases. In this study, we aimed to investigate the therapeutic effects and potential mechanisms of PTX in VAD.

Methods
Bilateral common carotid artery stenosis (BCAS) mouse model was established to mimic VAD. Mouse behavior was tested by open field test, novel object recognition test, Y-maze and Morris water maze (MWM) tests. Histological staining, magnetic resonance imaging (MRI) and electron microscopy were used to define white matter integrity. The impact of PTX on microglia phagocytosis, peroxisome proliferator-activated receptors-γ (PPAR-γ) activation and Mer receptor tyrosine kinase (Mertk) expression was assessed by immunofluorescence, western blotting and flow cytometry with the application of microglia-specific Mertk knockout mice, Mertk inhibitor and PPAR-γ inhibitor.

Results
Here, we found that PTX treatment alleviated cognitive impairment in novel object recognition test, Y-maze and Morris water maze tests. Furthermore, PTX alleviated white matter injury in corpus callosum (CC) and internal capsule (IC) areas as shown by histological staining and MRI analysis. PTX-treatment group presented thicker myelin sheath than vehicle group by electron microscopy. Mechanistically, PTX facilitated microglial phagocytosis of myelin debris by up-regulating the expression of Mertk in BCAS model and primary cultured microglia. Importantly, microglia-specific Mertk knockout blocked the therapeutic effects of PTX in BCAS model. Moreover, Mertk expression was regulated by the nuclear translocation of PPAR-γ. Through modulating PPAR-γ, PTX enhanced Mertk expression.

Conclusions
Collectively, our results demonstrated that PTX showed therapeutic potentials in VAD and alleviated ischemic white matter injury via modulating Mertk-mediated myelin clearance in microglia.
Anti-inflammatory effects of recreational marijuana in virally suppressed youth with HIV-1 are reversed by use of tobacco products in combination with marijuana
Authors: Yin Li , Dinasarapu Ashok R. , Borkar Samiksha A. , Chang Kai-Fen , De Paris Kristina , Kim-Chang Julie J. , Sleasman John W. , Goodenow Maureen M. 
Published: May 2022

Abstract
Background
Marijuana’s putative anti-inflammatory properties may benefit HIV-associated comorbidities. How recreational marijuana use affects gene expression in peripheral blood cells (PBC) among youth with HIV-1 (YWH) is unknown.

Approach
YWH with defined substance use (n = 54) receiving similar antiretroviral therapy (ART) were assigned to one of four analysis groups: YWH with detectable plasma HIV-1 (> 50 RNA copies/ml) who did not use substances (H+V+S−), and YWH with undetectable plasma HIV-1 who did not use substances (H+V−S−), or used marijuana alone (H+V−S+[M]), or marijuana in combination with tobacco (H+V−S+[M/T]). Non-substance using youth without HIV infection (H−S−, n = 25) provided a reference group. PBC mRNA was profiled by Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Differentially expressed genes (DEG) within outcome groups were identified by Significance Analysis of Microarrays and used for Hierarchical Clustering, Principal Component Analysis, and Ingenuity Pathways Analysis.

Results
HIV-1 replication resulted in > 3000 DEG involving 27 perturbed pathways. Viral suppression reduced DEG to 313, normalized all 27 pathways, and down-regulated two additional pathways, while marijuana use among virally suppressed YWH resulted in 434 DEG and no perturbed pathways. Relative to H+V−S−, multiple DEG normalized in H+V−S+[M]. In contrast, H+V−S+[M/T] had 1140 DEG and 10 dysregulated pathways, including multiple proinflammatory genes and six pathways shared by H+V+S−.

Conclusions
YWH receiving ART display unique transcriptome bioprofiles based on viral replication and substance use. In the context of HIV suppression, marijuana use, alone or combined with tobacco, has opposing effects on inflammatory gene expression.
Effect of catheter ablation combined with left appendage occlusion for non-valvular atrial fibrillation: a meta-analysis
Authors: Qu Jun , Wang Zhen , Wang Shuhao 
Published: May 2022

Abstract
Objective
To estimate the effect of catheter ablation combined with left appendage occlusion in the treatment of non-valvular atrial fibrillation (NVAF) by a method of meta-analysis.

Methods
Pubmed, Embase, and Cochrane Library were searched for the studies about catheter ablation combined with left appendage occlusion in treating NVAF. The data analysis was performed using R 4.0.5 software. The retrieval time was from inception to May 12, 2021.

Results
A total of 18 published studies were identified in the meta-analysis, including 1385 participants. During the perioperative period of catheter ablation combined with left appendage occlusion in treating NVAF, the pooled incidences of pericardial effusion, major or minor bleeding events, and residual flow documented were 0.5%(95%CI 0.0002–0.0099), 1.42%(95% CI 0.00–0.04), 7.24%(95% CI 0.0447–0.0975), respectively. During the follow-up, the incidences of all-cause mortality, embolism events, and bleeding events were 0.32%(95%CI 0.0000–0.0071), 1.29%(95%CI 0.0037–0.0222), 2.07%(95% CI 0.0075–0.0339), respectively. In the follow-up period of the transesophageal echocardiography, the most complication was residual flow event with an incident rate of 10.80%(95% CI 0.054–0.1620). The maximum occurrence probability of residual flow events was 17.92% (95% CI 0.1133–0.2452). Moreover, the incident rate of NVAF recurrence was 29.23% (95% CI 0.2222–0.3623).

Conclusion
The meta-analysis suggests that the “one-stop” procedure is effective for those patients undergoing NVAF. However, Patients with more residual blood flow have a higher incidence of bleeding complications. More studies are warranted to verify the safety and efficacy of catheter ablation combined with left appendage occlusion in terms of the “one-stop” procedure.
Prompting endogenous repair of brain injury: science fiction or reality?
Authors: de Rus Jacquet Aurelie , Cicchetti Francesca 
Published: May 2022

AbstractDrug-refractory forms of neurological diseases could find their next breakthrough therapy in non-pharmacological approaches to brain repair. Lentini et al. present the potential of in situ brain regeneration to address neurodegeneration in the epileptic brain.
Depletion of Toxoplasma adenine nucleotide translocator leads to defects in mitochondrial morphology
Authors: Wu Yihan , Ying Zhu , Liu Jing , Sun Zhepeng , Li Shuang , Liu Qun 
Published: May 2022

Abstract
Background
Adenine nucleotide translocase (ANT) is a protein that catalyzes the exchange of ADP/ATP across the inner mitochondrial membrane. Beyond this, ANT is closely associated with cell death pathways and mitochondrial dysfunction. It is a potential therapeutic target for many diseases. The function of the ANT in Toxoplasma gondii is poorly understood.

Methods
The CRISPR/CAS9 gene editing tool was used to identify and study the function of the ANT protein in T. gondii. We constructed T. gondii ANT transgenic parasite lines, including endogenous tag strain, knockout strain and gene complement strain, to clarify the function and location of TgANT. Mitochondrial morphology was observed by immunofluorescence and transmission electron microscopy.

Results
Toxoplasma gondii was found to encode an ANT protein, which was designated TgANT. TgANT localized to the inner mitochondrial membrane. The proliferation of the Δant strain was significantly reduced. More important, depletion of TgANT resulted in significant changes in the morphology and ultrastructure of mitochondria, abnormal apicoplast division and abnormal cytoskeletal daughter budding. In addition, the pathogenicity of the Δant strain to mice was significantly reduced.

Conclusions
Altogether, we identified and characterized the ANT protein of T. gondii. Depletion of TgANT inhibited parasite growth and impaired apicoplast and mitochondrial biogenesis, as well as abnormal parasite division, suggesting TgANT is important for parasite growth.
Physical optimization of cell proliferation and differentiation using spinner flask and microcarriers
Authors: Yang Feng , Wang Shouwei , Li Yingying , Li Shilei , Liu Wenting , Li Yushuang , Hu Haijuan 
Published: May 2022

Abstract
The traditional breeding industry has been increasingly saturated and caused environmental pollution, disease transmission, excessive resource use, and methane emission; however, it still cannot meet the needs of the growing population. To explore other alternatives, researchers focused on cell agriculture and cell-based meat, especially large-scale cell culture. As a prerequisite for production, large-scale culture technology has become an important bottleneck restricting cell-based meat industrialization. In this study, the single-factor variable method was adopted to examine the influence of Cytodex1 microcarrier pretreatment, spinner flask reaction vessel, cell culture medium, serum and cell incubation, and other influencing factors on large-scale cell cultures to identify the optimization parameters suitable for 3D culture environment. Collagen and 3D culture were also prospectively explored to promote myogenesis and cultivate tissue-like muscle fibers that contract spontaneously. This research lays a theoretical foundation and an exploratory practice for large-scale cell cultures and provides a study reference for the microenvironment of myoblast culture in vitro, a feasible direction for the cell therapy of muscular dystrophy, and prerequisites for the industrialized manufacturing of cell-based meat.

Graphical Abstract
Host-dependent impairment of parasite development and reproduction in the acanthocephalan model
Authors: Schmidt Hanno , Mauer Katharina , Hankeln Thomas , Herlyn Holger 
Published: May 2022

AbstractBackgroundA central question in parasitology is why parasites mature and reproduce in some host species but not in others. Yet, a better understanding of the inability of parasites to complete their life cycles in less suitable hosts may hold clues for their control. To shed light on the molecular basis of parasite (non-)maturation, we analyzed transcriptomes of thorny-headed worms (Acanthocephala:Pomphorhynchus laevis), and compared developmentally arrested worms excised from European eel (Anguilla anguilla) to developmentally unrestricted worms from barbel (Barbus barbus).ResultsBased on 20 RNA-Seq datasets, we demonstrate that transcriptomic profiles are more similar betweenP. laevismales and females from eel than between their counterparts from barbel. Impairment of sexual phenotype development was reflected in gene ontology enrichment analyses of genes having differential transcript abundances. Genes having reproduction- and energy-related annotations were found to be affected by parasitizing either eel or barbel. According to this, the molecular machinery of male and female acanthocephalans from the eel is less tailored to reproduction and more to coping with the less suitable environment provided by this host. The pattern was reversed in their counterparts from the definitive host, barbel.ConclusionsComparative analysis of transcriptomes of developmentally arrested and reproducing parasites elucidates the challenges parasites encounter in hosts which are unsuitable for maturation and reproduction. By studying a gonochoric species, we were also able to highlight sex-specific traits. In fact, transcriptomic evidence for energy shortage in female acanthocephalans associates with their larger body size. Thus, energy metabolism and glycolysis should be promising targets for the treatment of acanthocephaliasis. Although inherently enabling a higher resolution in heterosexuals, the comparison of parasites from definitive hosts and less suitable hosts, in which the parasites merely survive, should be applicable to hermaphroditic helminths. This may open new perspectives in the control of other helminth pathogens of humans and livestock.