bluuebunny/crossref_metadata_2025 huggingface dataset:
Palliative and end of life care in undergraduate medical education: a survey of New Zealand medical schools
Authors: Heath Lis , Egan Richard , Iosua Ella , Walker Robert , Ross Jean , MacLeod Rod
Published: July 2022

Background

In New Zealand, 34% of deaths occur in the hospital setting where junior doctors are at the frontline of patient care. The death rate in New Zealand is expected to double by 2068 due to the aging population, but many studies report that graduates feel unprepared to care for people near the end of life and find this to be one of the most stressful parts of their work. International guidelines recommend that palliative and end of life care should be a mandatory component of undergraduate medical education, yet teaching varies widely and remains optional in many countries. Little is known about how medical students in New Zealand learn about this important area of clinical practice. The purpose of this study was to investigate the organisation, structure and provision of formal teaching, assessment and clinical learning opportunities in palliative and end of life care for undergraduate medical students in New Zealand.

Methods

Quantitative descriptive, cross-sectional survey of module conveners in New Zealand medical schools.

Results

Palliative and end of life care is included in undergraduate teaching in all medical schools. However, there are gaps in content, minimal formal assessment and limited contact with specialist palliative care services. Lack of teaching staff and pressure on curriculum time are the main barriers to further curriculum development.

Conclusions

This article reports the findings of the first national survey of formal teaching, assessment and clinical learning opportunities in palliative and end of life care in undergraduate medical education in New Zealand. There has been significant progress towards integrating this content into the curriculum, although further development is needed to address barriers and maximise learning opportunities to ensure graduates are as well prepared as possible.
Use of digital technologies to combat loneliness and social isolation: a cross-sectional study in Swiss outpatient care during COVID-19 pandemic
Authors: Stängle Sabrina , Benedetti Franzisca Domeisen , Hediger Hannele , Bonmarin Mathias , Loeser Martin , Fringer André
Published: July 2022

Background

There is limited data on the use of digital technologies in outpatient care in Switzerland. Our objectives were therefore to determine which digital technologies are used and whether they had an impact on loneliness and social isolation in the wake of the COVID-19 pandemic.

Methods

A cross-sectional survey design was used with a convenience sample of 1272 outpatient care providers in Switzerland. The questionnaire used is based on an unsystematic literature review and a previous qualitative study with six outpatient caregivers and two caring relatives, based on which the 30 items for this questionnaire were developed. Data were analyzed descriptively, and group comparisons were made using the Kruskal Wallis test. Changes over time were measured using Friedman test with Bonferroni post hoc tests and Wilcoxon test for paired samples.

Results

The impact of the COVID-19 pandemic was evident both on the part of the health care system, e.g., inadequate protective equipment; on the part of health care providers, e.g., increasing fatigue in keeping abreast of the virus as the pandemic progressed; and on the part of clients, who reduced services of care, e.g., out of fear of infection. According to the assessment of the outpatient caregivers, loneliness and social isolation of the clients was high in spring 2020 and increased strongly in the following winter. Alternative solutions, such as digital technologies, were hardly used or not used at all by the clients.

Conclusions

The results suggest that the pandemic is dramatically impacting clients. This highlights the urgent need to invest in the development of appropriate digital technologies reducing the impact of social isolation and loneliness and the associated long-term costs to the healthcare system.
Implementing ethical aspects in the development of a robotic system for nursing care: a qualitative approach
Authors: Nielsen Svenja , Langensiepen Sina , Madi Murielle , Elissen Maurice , Stephan Astrid , Meyer Gabriele
Published: July 2022

Background

As robotics in nursing care is still in an early explorative research phase, it is not clear which changes robotic systems will ultimately bring about in the long term. According to the approach of “Responsible Research and Innovation”, the research project “PfleKoRo” aims to anticipate and mitigate ethical risks that might be expected when starting to develop a robot. The robot under investigation is intended to be a hands-on support in nursing care in due course. Therefore, the question is which ethical risks and requirements must be considered when developing the robot.

Methods

Guided by the British Standard for the design of robotic systems, ethical risks related to the robot’s use were identified at the outset (Step 1). This was followed by the definition of the requirements needed to mitigate ethical risks (Step 2). Professional nurses, patients and relatives were involved in focus groups and interviews in Step 1. The transcribed interviews and focus groups were then analysed using content analysis. The available literature and expert guidance were taken into account in both steps. Finally, validation and verification methods were defined (Step 3).

Results

Sixteen professional nurses participated in three focus groups. Individual interviews were held with a total of eight patients and relatives. Ethical risks and requirements could be defined in the context of dignity, autonomy, privacy, human relationships and safety in the project. Professional nurses feared most issues relating to safety and that the robot would lead to more workload instead of relief, whereas patients and relatives frequently raised the issue of the staffing ratio. Despite the focus on possible negative consequences, participants also made uncritical or optimistic comments regarding the robot’s use in the future.

Conclusion

Focus groups, individual interviews and existing literature revealed to some extent different ethical issues. Along with identified risks, the results suggest a general open-mindedness of nurses, patients and relatives towards the introduced robot. When investigating the ethical implications of robots for nursing care, one should include multiple perspectives and, in particular, potentially affected individuals.
You are exactly my type! The traits of a good doctor: a factor analysis study on public's perspectives
Authors: Grundnig Julia S. , Steiner-Hofbauer Verena , Drexler Viktoria , Holzinger Anita
Published: July 2022

Background

A multiplicity of qualities and behaviours are considered essential in a good doctor and are identified in various medical profession frameworks. However, there is no consensus as to their meaning or even agreement on fundamental qualities. The authors wanted to examine the importance placed by the Austrian public on the professional and personal traits of ideal physicians. Competencies were used to create different types of ‘good doctor’ and then examined to discover how these can be integrated into existing medical professionalism frameworks.

Methods

A 69-item Likert scale-based questionnaire was developed and administered via telephone interview to 1,000 subjects. Computer-assisted telephone interviews (CATI) were carried out by the Austrian GALLUP-Institute. An explorative factor analysis with promax rotation was undertaken to summarise the interrelationships among variables.

Results

Factor analysis identified six interpretable factors which we define as six different types of doctors: the dutiful doctor, the online health-celebrity, the medical expert, the service physician, the medical altruist, and the ethical agent. The items perceived as most important were ‘takes time’, ‘listens’, and ‘makes correct diagnoses’. Outcome measures of internal consistency and reliability estimates (Cronbach´s alpha, 0.69–0.86) for each element.

Conclusions

The six types of physicians may be a step toward recognizing the professional behaviour of all physicians, their actions as healers, and their commitment to moral concepts, values, and needs of their patients, and society. According to our results, the public has expectations of good doctors that go beyond the scope within the medical professionalism frameworks. Therefore, these guidelines should be adapted in light of the changing expectations and needs of the general population.
Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis
Authors: Strzebonska Karolina , Blukacz Mateusz , Wasylewski Mateusz T. , Polak Maciej , Gyawali Bishal , Waligora Marcin
Published: July 2022

Background

Umbrella clinical trials in precision oncology are designed to tailor therapies to the specific genetic changes within a tumor. Little is known about the risk/benefit ratio for umbrella clinical trials. The aim of our systematic review with meta-analysis was to evaluate the efficacy and safety profiles in cancer umbrella trials testing targeted drugs or a combination of targeted therapy with chemotherapy.

Methods

Our study was prospectively registered in PROSPERO (CRD42020171494). We searched Embase and PubMed for cancer umbrella trials testing targeted agents or a combination of targeted therapies with chemotherapy. We included solid tumor studies published between 1 January 2006 and 7 October 2019. We measured the risk using drug-related grade 3 or higher adverse events (AEs), and the benefit by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). When possible, data were meta-analyzed.

Results

Of the 6207 records identified, we included 31 sub-trials or arms of nine umbrella trials (N = 1637). The pooled overall ORR was 17.7% (95% confidence interval [CI] 9.5–25.9). The ORR for targeted therapies in the experimental arms was significantly lower than the ORR for a combination of targeted therapy drugs with chemotherapy: 13.3% vs 39.0%; p = 0.005. The median PFS was 2.4 months (95% CI 1.9–2.9), and the median OS was 7.1 months (95% CI 6.1–8.4). The overall drug-related death rate (drug-related grade 5 AEs rate) was 0.8% (95% CI 0.3–1.4), and the average drug-related grade 3/4 AE rate per person was 0.45 (95% CI 0.40–0.50).

Conclusions

Our findings suggest that, on average, one in five cancer patients in umbrella trials published between 1 January 2006 and 7 October 2019 responded to a given therapy, while one in 125 died due to drug toxicity. Our findings do not support the expectation of increased patient benefit in cancer umbrella trials. Further studies should investigate whether umbrella trial design and the precision oncology approach improve patient outcomes.
Exome sequencing contributes to identify comorbidities in a rare case of infant ARDS induced by the CD40LG mutation
Authors: Gong Xue , He Yunru , Lu Guoyan , Zhang Yulin , Qiu Yu , Qiao Lina , Li Yifei
Published: July 2022

Background

Acute respiratory distress syndrome (ARDS) causes significant mortality in young children with certain diseases. Early diagnosis and treatment can reduce infant mortality. Here, we report a rare case of exome sequencing in the early diagnosis of immunodeficiency in an infant.

Case presentation

A four-month-old full-term male infant presented with severe shortness of breath, hypoxemia, and unexplained parenchymal lung lesions. A series of examinations were performed to search for potential culprit viruses but negative results were obtained with the only exception being the rhinovirus that tested positive. The child’s family history revealed he had a brother who died of severe infection at the age of two years. We performed an exome sequencing analysis and a mutation analysis of CD40LG to obtain genetic data on the patient. Besides, we used flow cytometry to measure the CD40LG expression levels of activated T cells. A retrospective review of all the CD40LG mutant-induced X-linked hyper IgM syndromes (XHIGM) had been conducted to assess the differences between clinical and genetic molecular features. Finally, a regular intravenous immunoglobulin (IVIG) regimen led to steady breathing, the correction of hypoxemia, and a progressive improvement of lung CT scans. During follow-up, the patient received an IVIG regimen and his CT images improved. Moreover, his parents took advantage of pre-implantation genetic testing with in vitro fertilization to have a healthy twin offspring who did not carry such a mutation according to the early exome sequencing for the proband. Compared with other CD40LG mutant cases in our center, this proband displayed a normal plasma immunoglobulin level and he should be the youngest infant to have a molecular diagnosis of XHIGM.

Conclusion

Usually, XHIGM would not be suspected with a normal plasma immunoglobulin concentration. However, as we could not identify a potential comorbidity or risk factor, exome sequencing helps target this patient's real facts. Thus, this case report calls for exome sequencing to be performed in the case of unexplained infections when immunodeficiency is suspected after general immunological tests, especially for cases with a contributive family history among infants as the maternal transfused immunoglobulin might mask immune deficiency.
A signature of immune-related gene pairs (IRGPs) for risk stratification and prognosis of oral cancer patients
Authors: Yu Yanling , Tian Jing , Hou Yanni , Zhang Xinxin , Li Linhua , Cong Peifu , Ji Lei , Wang Xuri
Published: July 2022

Background

With low response to present immunotherapy, it is imperative to identify new immune-related biomarkers for more effective immunotherapies for oral cancer.

Methods

RNA profiles for 390 oral cancer patients and 32 normal samples were downloaded from The Cancer Genome Atlas (TCGA) database and differentially expressed genes (DEGs) were analyzed. Immune genesets from ImmPort repository were overlapped with DEGs. After implementing univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, key immune-related gene pairs (IRGPs) among the overlapped DEGs for predicting the survival risk were obtained. Then, the cutoff of risk score was calculated by the receiver operating characteristic (ROC) curve to stratify oral cancer patients into high and low-risk groups. Multivariate Cox analysis was used to analyze independent prognostic indicators for oral cancer. Besides, infiltration of immune cells, functional annotation, and mutation analysis of IRGPs were conducted. Biological functions correlated with IRGPs were enriched by Gene Set Enrichment Analysis (GSEA) method.

Results

We identified 698 differentially expressed genes (DEGs) in response to oral cancer. 17 IRGPs among the DEGs were identified and integrated into a risk score model. Patients in the high-risk group have a significantly worse prognosis than those in the low-risk group in both training (P<0.001) and test (P=0.019) cohorts. Meanwhile, the IRGP model was identified as an independent prognostic factor for oral cancer. Different infiltration patterns of immune cells were found between the high- and low-risk groups that more types of T and B cells were enriched in the low-risk group. More immune-related signaling pathways were highly enriched in the low-risk group and Tenascin C (TNC) was the most frequently mutated gene. We have developed a novel 17-IRGPs signature for risk stratification and prognostic prediction of oral cancer.

Conclusion

Our study provides a foundation for improved immunotherapy and prognosis and is beneficial to the individualized management of oral cancer patients.
Barriers and enablers for deprescribing benzodiazepine receptor agonists in older adults: a systematic review of qualitative and quantitative studies using the theoretical domains framework
Authors: Evrard Perrine , Pétein Catherine , Beuscart Jean-Baptiste , Spinewine Anne
Published: July 2022

Background

Many strategies aimed at deprescribing benzodiazepine receptor agonists (BZRA) in older adults have already been evaluated with various success rates. There is so far no consensus on which strategy components increase deprescribing the most. Yet, despite an unfavourable benefit-to-risk ratio, BZRA use among older adults remains high. We systematically reviewed barriers and enablers for BZRA deprescribing in older adults.

Methods

Two reviewers independently screened records identified from five electronic databases—Medline, Embase, PsycINFO, CINAHL and the Cochrane library—and published before October 2020. They searched for grey literature using Google Scholar. Qualitative and quantitative records reporting data on the attitudes of older adults, caregivers and healthcare providers towards BZRA deprescribing were included. Populations at the end of life or with specific psychiatric illness, except for dementia, were excluded. The two reviewers independently assessed the quality of the included studies using the mixed-methods appraisal tool. Barriers and enablers were identified and then coded into domains of the theoretical domains framework (TDF) using a combination of deductive and inductive qualitative analysis. The most relevant TDF domains for BZRA deprescribing were then identified.

Results

Twenty-three studies were included 13 quantitative, 8 qualitative and 2 mixed-method studies. The points of view of older adults, general practitioners and nurses were reported in 19, 9 and 3 records, respectively. We identified barriers and enablers in the majority of TDF domains and in two additional themes: “patient characteristics” and “BZRA prescribing patterns”. Overall, the most relevant TDF domains were “beliefs about capabilities”, “beliefs about consequences”, “environmental context and resources”, “intention”, “goals”, “social influences”, “memory, attention and decision processes”. Perceived barriers and enablers within domains differed across settings and across stakeholders.

Conclusion

The relevant TDF domains we identified can now be linked to behavioural change techniques to help in the design of future strategies and health policies. Future studies should also assess barriers and enablers perceived by under-evaluated stakeholders (such as pharmacists, psychiatrists and health care professionals in the hospital setting).

Trial registration

This work was registered on PROSPERO under the title “Barriers and enablers to benzodiazepine receptor agonists deprescribing”. Registration number:CRD42020213035
Hypertensive disorders in pregnancy complicated by liver rupture or hematoma: a systematic review of 391 reported cases
Authors: Augustin Goran , Hadzic Matija , Juras Josip , Oreskovic Slavko
Published: July 2022

Background

Spontaneous liver rupture in pregnancy is often unrecognized, highly lethal, and not completely understood. The goal was to summarize and define the etiology, risk factors, clinical presentation, appropriate diagnostic methods, and therapeutic options for spontaneous hepatic rupture during pregnancy/puerperium (SHRP) complicated by the hypertensive disorder.

Methods

Literature search of all full-text articles included PubMed (1946–2021), PubMed Central (1900–2021), and Google Scholar. Case reports of a spontaneous hepatic rupture or liver hematoma during pregnancy or puerperium as a complication of hypertensive disorders (preeclampsia, eclampsia, HELLP syndrome) were searched. There was no restriction of language to collect the cases. Additional cases were identified by reviewing references of retrieved studies. PRISMA guidelines for the data extraction and quality assessment were applied.

Results

Three hundred and ninety-one cases were collected. The median maternal age was 31 (range 17–48) years; 36.6% were nulliparous. Most (83.4%) occurred in the third trimester. Maternal and fetal mortality was 22.1% and 37.2%, respectively. Maternal and fetal mortality was significantly higher 1) before the year 1990, 2) with maternal hemodynamic instability, and 3) eclampsia. The most important risk factors for SHRP were preeclampsia and HELLP syndrome. Most women had right lobe affected (70.9%), followed by both lobes in 22.1% and left lobe in 6.9%. The most common surgical procedure was liver packing. Liver transplantation was performed in 4.7% with 100% survival. Maternal mortality with liver embolization was 3.0%. Higher gestational age increases fetal survival.

Conclusion

The diagnosis and treatment of SHRP are often delayed, leading to high maternal and fetal mortality. SHRP should be excluded in hemodynamically unstable patients with preeclampsia/eclampsia or HELLP syndrome and right upper abdominal pain. Liver embolization and liver transplantation contribute to maternal survival. Maternal and fetal mortality was significantly higher before the year 1990. Hemodynamic instability, preeclampsia, and eclampsia have a significant negative influence on maternal survival.

Level of evidence

Level V
Program characteristics of cardiothoracic surgery departments versus divisions
Authors: Soler Lisa M. , Lopez Raymond A. , Hornbuckle Kyle J. , Dabal Robert J. , Chen Herbert , Xie Rongbing , Vardas Panos N.
Published: July 2022

Background

The organizational structure of cardiothoracic surgery practices varies among different programs throughout the United States (U.S.). We aimed to investigate the characteristics of the top ranked programs within the specialty and the surgeons practicing within each.

Methods

The top 50 hospitals for adult cardiology and heart surgery were identified using the US News and World Report 2019–20 ranking. There were 590 hospitals reported on, with 50 top rated programs. Data was collected from each hospital’s website, analyses conducted using SAS 9.4 with statistical significance set at p ≤ 0.05.

Results

When comparing cardiothoracic surgery program organizational structures, 21 of the top 50 ranked programs were departments and 24 were divisions within their respective Department of Surgery. Mean number of surgeons was 11 with no statistical difference when analyzed by division versus department. Overall, 9% of practicing cardiothoracic surgeons were female. Between programs that are a department versus division, general thoracic surgery was included in 58% of divisions and 52% of departments (p = ns). Among programs that were departments, approximately 6% of surgeons had attained a Ph.D., while in divisions approximately 4% of surgeons had attained a Ph.D.

Conclusions

The top 50 Cardiothoracic Surgery programs in the U.S. have approximately the same number of surgeons within the group and are organized similarly. This study group had a slightly higher percentage of female surgeons than has previously been noted in cardiothoracic surgery, with general thoracic surgery trending toward higher gender diversity. The presence of physician scientists was low, though similar amongst the study groups.
HTA decision-making for drugs for rare diseases: comparison of processes across countries
Authors: Stafinski Tania , Glennie Judith , Young Andrea , Menon Devidas
Published: July 2022

Introduction

Drugs for rare diseases (DRDs) offer important health benefits, but challenge traditional health technology assessment, reimbursement, and pricing processes due to limited effectiveness evidence. Recently, modified processes to address these challenges while improving patient access have been proposed in Canada. This review examined processes in 12 jurisdictions to develop recommendations for consideration during formal government-led multi-sectoral discussions currently taking place in Canada.

Methods

(i) A scoping review of DRD reimbursement processes, (ii) key informant interviews, (iii) a case study of evaluations for and the reimbursement status of a set of 7 DRDs, and (iv) a virtual, multi-stakeholder consultation retreat were conducted.

Results

Only NHS England has a process specifically for DRDs, while Italy, Scotland, and Australia have modified processes for eligible DRDs. Almost all consider economic evaluations, budget impact analyses, and patient-reported outcomes; but less than half accept surrogate measures. Disease severity, lack of alternatives, therapeutic value, quality of evidence, and value for money are factors used in all decision-making process; only NICE England uses a cost-effectiveness threshold. Budget impact is considered in all jurisdictions except Sweden. In Italy, France, Germany, Spain, and the United Kingdom, specific factors are considered for DRDs. However, in all jurisdictions opportunities for clinician/patient input are the same as those for other drugs. Of the 7 DRDs included in the case study, the number that received a positive reimbursement recommendation was highest in Germany and France, followed by Spain and Italy. No relationship between recommendation type and specific elements of the pricing and reimbursement process was found.

Conclusions

Based on the collective findings from all components of the project, seven recommendations for possible action in Canada are proposed. These focus on defining “appropriate access”, determining when a “full” HTA may not be needed, improving coordination among stakeholder groups, developing a Canadian framework for Managed Access Plans, creating a pan-Canadian DRD/rare disease data infrastructure, genuine and continued engagement of patient groups and clinicians, and further research on different decision and financing options, including MAPs.
A characterization of trauma laparotomies in a scandinavian setting: an observational study
Authors: Bentin Jakob Mejdahl , Possfelt-Møller Emma , Svenningsen Peter , Rudolph Søren Steemann , Sillesen Martin
Published: July 2022

Background

Despite treatment advances, trauma laparotomy continuous to be associated with significant morbidity and mortality. Most of the literature originates from high volume centers, whereas patient characteristics and outcomes in a Scandinavian setting is not well described. The objective of this study is to characterize treatments and outcomes of patients undergoing trauma laparotomy in a Scandinavian setting and compare this to international reports.

Methods

A retrospective study was performed in the Copenhagen University Hospital, Rigshospitalet (CUHR). All patients undergoing a trauma laparotomy within the first 24 h of admission between January 1st 2019 and December 31st 2020 were included. Collected data included demographics, trauma mechanism, injuries, procedures performed and outcomes.

Results

A total of 1713 trauma patients were admitted to CUHR of which 98 patients underwent trauma laparotomy. Penetrating trauma accounted for 16.6% of the trauma population and 66.3% of trauma laparotomies. Median time to surgery after arrival at the trauma center (TC) was 12 min for surgeries performed in the Emergency Department (ED) and 103 min for surgeries performed in the operating room (OR). A total of 14.3% of the procedures were performed in the ED. A damage control strategy (DCS) approach was chosen in 18.4% of cases. Our rate of negative laparotomies was 17.3%. We found a mortality rate of 8.2%. The total median length of stay was 6.1 days.

Conclusion

The overall rates, findings, and outcomes of trauma laparotomies in this Danish cohort is comparable to reports from similar Western European trauma systems.
Evaluation of a mobile mammography unit: concepts and randomized cluster trial protocol of a population health intervention research to reduce breast cancer screening inequalities
Authors: Guillaume Elodie , Rollet Quentin , Launay Ludivine , Beuriot Séverine , Dejardin Olivier , Notari Annick , Crevel Elodie , Benhammouda Ahmed , Verzaux Laurent , Quertier Marie-Christine , Launoy Guy
Published: July 2022

Background

Breast cancer is the leading cancer in women in France both in incidence and mortality. Organized breast cancer screening (OBCS) has been implemented nationwide since 2004, but the participation rate remains low (48%) and inequalities in participation have been reported. Facilities such as mobile mammography units could be effective to increase participation in OBCS and reduce inequalities, especially areas underserved in screening. Our main objective is to evaluate the impact of a mobile unit and to establish how it could be used to tackle territorial inequalities in OBCS participation.

Methods

A collaborative project will be conducted as a randomized controlled cluster trial in 2022–2024 in remote areas of four French departments. Small geographic areas were constructed by clustering women eligible to OBCS, according to distance to the nearest radiology centre, until an expected sample of eligible women was attained, as determined by logistic and financial constraints. Intervention areas were then selected by randomization in parallel groups. The main intervention is to propose an appointment at the mobile unit in addition to current OBCS in these remote areas according to the principle of proportionate universalism. A few weeks before the intervention, OBCS will be promoted with a specific information campaign and corresponding tools, applying the principle of multilevel, intersectoral and community empowerment to tackle inequalities.

Discussion

This randomized controlled trial will provide a high level of evidence in assessing the effects of mobile unit on participation and inequalities. Contextual factors impacting the intervention will be a key focus in this evaluation. Quantitative analyses will be complemented by qualitative analyses to investigate the causal mechanisms affecting the effectiveness of the intervention and to establish how the findings can be applied at national level.

Trial registration

Registered on ClinicalTrials.gov, December 21, 2021: NCT05164874.
Eimeria falciformis secretes extracellular vesicles to modulate proinflammatory response during interaction with mouse intestinal epithelial cells
Authors: Olajide Joshua Seun , Xiong Ling , Yang Shunli , Qu Zigang , Xu Xiao , Yang Bin , Wang Jing , Liu Baohong , Ma Xueting , Cai Jianping
Published: July 2022

Background

Protozoan parasite secretions can be triggered by various modified media and diverse physicochemical stressors. Equally, host-parasite interactions are known to co-opt the exchange and secretion of soluble biochemical components. Analysis of Eimeria falciformis sporozoite secretions in response to interaction with mouse intestinal epithelial cells (MIECs) may reveal parasite secretory motifs, protein composition and inflammatory activities of E. falciformis extracellular vesicles (EVs).

Methods

Eimeria falciformis sporozoites were allowed to interact with inactivated MIECs. Parasite secretions were separated into EV and vesicle-free (VF) fractions by discontinuous centrifugation and ultracentrifugation. Secreted EVs were purified in an iodixanol density gradient medium and the protein composition of both EV and VF fractions were analyzed by liquid chromatoraphy-tandem mass spectroscopy. The inflammatory activities of E. falciformis sporozoite EV on MIECs were then investigated.

Results

During the interaction of E. falciformis sporozoites with inactivated MIECs, the parasite secreted VF and vesicle-bound molecules. Eimeria falciformis vesicles are typical pathogenic protozoan EVs with a mean diameter of 264 ± 2 nm, and enclosed heat shock protein (Hsp) 70 as classical EV marker. Refractile body-associated aspartyl proteinase (or eimepsin), GAP45 and aminopeptidase were the main components of E. falciformis sporozoite EVs, while VF proteins include Hsp90, actin, Vps54 and kinases, among others. Proteomic data revealed that E. falciformis EV and VF proteins are aggregates of bioactive, antigenic and immunogenic molecules which act in concert for E. falciformis sporozoite motility, pathogenesis and survival. Moreover, in MIECs, E. falciformis EVs induced upregulation of gene expression and secretion of IL-1β, IL-6, IL-17, IL-18, MCP1 as well as pyroptosis-dependent caspase 11 and NLRP6 inflammasomes with the concomitant secretion of lactate dehydrogenase.

Conclusions

Eimeria falciformis sporozoite interaction with MIECs triggered the secretion of immunogenic and antigenic proteins. In addition, E. falciformis sporozoite EVs constitute parasite-associated molecular pattern that induced inflammatory response and cell death. This study offers additional insight in the secretion and protein composition of E. falciformis secretomes as well as the proinflammatory functions of E. falciformis sporozoite EVs.

Graphical Abstract
Autism traits outweigh alexithymia traits in the explanation of mentalising performance in adults with autism but not in adults with rejected autism diagnosis
Authors: Falter-Wagner Christine M. , Bloch Carola , Burghof Lana , Lehnhardt Fritz-Georg , Vogeley Kai
Published: July 2022

Background

Pronounced alexithymia traits have been found in autism spectrum disorder (ASD) and recent research has been carving out the impact alexithymia traits might have on mentalising deficits associated with ASD.

Method

In this cross-sectional study, a large representative referral population for diagnostic examination for possible ASD (n = 400) was screened for clinical alexithymia with a German version of the Reading the Mind in the Eyes test (RME). In contrast to previous attempts to carve out the impact of alexithymia traits on mentalising deficits though, we employed dominance analysis to account for the correlation between predictors. Therelativerelationship between alexithymia traits and autism traits with RME performance was investigated in the group of individuals with confirmed ASD diagnosis (N = 281) and compared to the clinical referral sample in which ASD was ruled out (N = 119).

Results

Dominance analysis revealed autism traits to be the strongest predictor for reduced mentalising skills in the ASD sample, whereas alexithymia contributed significantly less. In the sample of individuals with ruled out diagnosis, autism traits were the strongest predictor, but alexithymia traits were in sum equally associated to mentalising, with theExternal-Oriented Thinkingsubscale as an important predictor of this association.

Limitations

It needs to be considered that the cross-sectional study design does not allow for causal inference. Furthermore, mentalising is a highly facetted capacity and measurements need to reduce this complexity into simple quantities which limits the generalizability of results.

Discussion

While alexithymia traits should be considered for their mental health importance, they do not dominate the explanation of reduced mentalising skills in individuals with ASD, but they might do to a larger degree in individuals with ruled out ASD.
Improving efficiency of knowledge and technology diffusion using community seed banks and farmer-to-farmer extension: experiences from Malawi
Authors: Okori Patrick , Munthali Wills , Msere Harry , Charlie Harvey , Chitaya Soka , Sichali Felix , Chilumpha Ethel , Chirwa Teddie , Seetha Anitha , Chinyamuyamu Betty , Monyo Emmanuel , Siambi Moses , Chirwa Rowland
Published: July 2022

Background

Agri-innovations are mostly delivered to farmers through private and public sector-led institutions around the world, with various degrees of success in Malawi. These distribution systems, on the other hand, do not meet everyone's production and productivity needs, particularly those of smallholder farmers. Alternative gap-filling systems are therefore required. Over the course of 7 years, we performed two studies in Malawi to assess the efficiency of integrated farmer led agri-innovation delivery mechanisms, in order to advise programming and delivery improvements. The first study looked at the impact of farmer-led technology delivery on agricultural output and productivity. It was split into two phases: learning (2010–2015) and scaling-out (2016–2019). The second study looked at how smallholder farmers changed their behaviour, after receiving instruction during the scaling-out phase. A farmer-led social network, community seed banks, was used as the research platform.

Results

The number of farmers who had access to improved seed increased by 35-fold from 2.4% in the baseline year. Groundnut, the major study crop, had a 1.8-fold increase in productivity. In sorghum, and common bean, the difference in grain yield between beneficiaries and control populations was 19% and 30%, respectively. The lowest aflatoxin contamination was found in groundnut grain samples from trained farmers, showing that learning had occurred, with three training sessions sufficient for initiating and sustaining adoption of agri-innovations.

Conclusions

Many developing country economies have limited investments in agricultural extension and advisory services, and as well as inefficient agri-input delivery systems, limiting access to science solutions needed to boost productivity. The farmer-led technology and knowledge dissemination systems examined in this research, are appropriate for a variety farming contexts, especially for crops underinvested by private sector, and where public extension and advisory services are poorly funded.
Mechanisms of processing speed training and transfer effects across the adult lifespan: protocol of a multi-site cognitive training study
Authors: von Bastian Claudia C. , Reinhartz Alice , Udale Robert C. , Grégoire Stéphanie , Essounni Mehdi , Belleville Sylvie , Strobach Tilo
Published: July 2022

Background

In recent years, cognitive training has gained popularity as a cost-effective and accessible intervention aiming at compensating for or even counteracting age-related cognitive declines during adulthood. Whereas the evidence for the effectiveness of cognitive training in general is inconsistent, processing speed training has been a notable successful exception, showing promising generalized benefits in untrained tasks and everyday cognitive functioning. The goal of this study is to investigate why and when processing speed training can lead to transfer across the adult lifespan. Specifically, we will test (1) whether training-induced changes in the rate of evidence accumulation underpin transfer to cognitive performance in untrained contexts, and (2) whether these transfer effects increase with stronger attentional control demands of the training tasks.

Methods

We will employ a multi-site, longitudinal, double-blinded and actively controlled study design with a target sample size of N = 400 adult participants between 18 and 85 years old. Participants will be randomly assigned to one of three processing speed training interventions with varying attentional control demands (choice reaction time, switching, or dual tasks) which will be compared to an active control group training simple reaction time tasks with minimal attentional control demands. All groups will complete 10 home-based training sessions comprising three tasks. Training gains, near transfer to the untrained tasks of the other groups, and far transfer to working memory, inhibitory control, reasoning, and everyday cognitive functioning will be assessed in the laboratory directly before, immediately after, and three months after training (i.e., pretest, posttest, and follow-up, respectively). We will estimate the rate of evidence accumulation (drift rate) with diffusion modeling and conduct latent-change score modeling for hypothesis testing.

Discussion

This study will contribute to identifying the cognitive processes that change when training speeded tasks with varying attentional control demands across the adult lifespan. A better understanding of how processing speed training affects specific cognitive mechanisms will enable researchers to maximize the effectiveness of cognitive training in producing broad transfer to psychologically meaningful everyday life outcomes.

Trial registration Open Science Framework Registries, registration https://doi.org/10.17605/OSF.IO/J5G7E; date of registration: 9 May 2022.
Applying multimodal learning analytics to examine the immediate and delayed effects of instructor scaffoldings on small groups’ collaborative programming
Authors: Ouyang Fan , Dai Xinyu , Chen Si
Published: July 2022

Background

Instructor scaffolding is proved to be an effective means to improve collaborative learning quality, but empirical research indicates discrepancies about the effect of instructor scaffoldings on collaborative programming. Few studies have used multimodal learning analytics (MMLA) to comprehensively analyze the collaborative programming processes from a process-oriented perspective. This research conducts a MMLA research to examine the immediate and delayed effects of instructor scaffoldings on small groups’ collaborative programming in K-12 education context with an aim to provide research, analytics, and pedagogical implications.

Results

The results indicated that the instructor provided five types of scaffoldings from the social, cognitive, and metacognitive dimensions, and groups had seven types of responses (i.e., immediate uptake and delayed use) to five instructor scaffoldings, ranging from the low-to-medium and high level of cognitive engagement. After the scaffolding was faded, groups used the content from the high-control cognitive scaffolding frequently to solve problems in a delayed way, but groups did not use the instructor’s scaffolding content from the social and low-control cognitive scaffoldings from the pedagogical perspective, instructors should consider scaffolding types, group states and characteristics, as well as the timing of scaffolding to better design and facilitate collaborative programming. From an analytical perspective, MMLA was proved to be conducive to understand collaborative learning from social, cognitive, behavioral, and micro-level dimensions, such that instructors can better understand and reflect on the process of collaborative learning, and use scaffoldings more skillfully to support collaborative learning.

Conclusions

Collaborative programming is encouraged to be integrated in STEM education to transform education from the instructor-directed lecturing to the learner-centered learning. Using MMLA methods, this research provided a deep understanding of the immediate and delayed effects of instructor scaffoldings on small groups’ collaborative programming in K-12 STEM education from a process-oriented perspective. The results showed that various instructor scaffoldings have been used to promote groups’ social and cognitive engagement. Instructor scaffoldings have delayed effects on promoting collaborative programming qualities. It is highly suggested that instructors should integrate scaffoldings to facilitate computer programming education and relevant research should apply MMLA to reveal details of the process of collaboration.
Coupling metal and whole-cell catalysis to synthesize chiral alcohols
Authors: Yin Hang , Luan Peng-Qian , Cao Yu-Fei , Ge Jun , Lou Wen-Yong
Published: July 2022

Background

The combination of metal-catalyzed reactions and enzyme catalysis has been an essential tool for synthesizing chiral pharmaceutical intermediates in the field of drug synthesis. Metal catalysis commonly enables the highly efficient synthesis of molecular scaffolds under harsh organic conditions, whereas enzymes usually catalyze reactions in mild aqueous medium to obtain high selectivity. Since the incompatibility between metal and enzyme catalysis, there are limitations on the compatibility of reaction conditions that must be overcome.

Findings

We report a chemoenzymatic cascade reaction involved Palladium (Pd) catalyzed Suzuki–Miyaura coupling and whole-cell catalyzed C = O asymmetric reduction for enantioselective synthesis of value-added chiral alcohol. The cell membrane serves as a natural barrier can protect intracellular enzymes from organic solvents.

Conclusions

With dual advantages of cascade catalysis and biocompatibility, our work provides a rational strategy to harvest chiral alcohols in high yield and excellent enantioselectivity, as a channel to establish chemoenzymatic catalysis.
Optimizing acquisition times for total-body positron emission tomography/computed tomography with half-dose 18F-fluorodeoxyglucose in oncology patients
Authors: He Yibo , Gu Yushen , Yu Haojun , Wu Bing , Wang Siyang , Tan Hui , Cao Yanyan , Chen Shuguang , Sui Xiuli , Zhang Yiqiu , Shi Hongcheng
Published: July 2022

Background

The present study aimed to explore the boundary of acquisition time and propose an optimized acquisition time range for total-body positron emission tomography (PET)/computed tomography (CT) oncological imaging using half-dose (1.85 MBq/kg) 18F-fluorodeoxyglucose activity based on diagnostic needs.

Methods

In this retrospective study based on a total-body PET system (uEXPLORER), an exploration cohort (October 2019–December 2019) of 46 oncology patients was first studied. The acquisition time for all patients was 15 min, and the acquired images were reconstructed and further split into 15-, 8-, 5-, 3-, 2-, and 1-min duration groups (abbreviated as G15, G8, G5, G3, G2, and G1). The image quality and lesion detectability of reconstructed PET images with different acquisition times were evaluated subjectively (5-point scale, lesion detection rate) and objectively (standardized uptake values, tumor-to-background ratio). In the same way, the initial optimized acquisition times were further validated in a cohort of 147 oncology patients (December 2019–June 2021) by using the Gs images (the images obtained using the 15- and 10-min acquisition times) as controls.

Results

In the exploration cohort, the subjective scores for G1, G2, G3, G5, and G8 images were 2.0 ± 0.2, 2.9 ± 0.3, 3.0 ± 0.0, 3.9 ± 0.2, and 4.2 ± 0.4, respectively. Two cases in G1 were rated as 1 point. No significant difference in scores was observed between G5 and G8 (p > 0.99). In general, groups with a longer acquisition time showed lower background uptake and lesion conspicuity. Compared with G15, lesion detection rate significantly reduced to 85.3% in G1 (p < 0.05). In the validation cohort, the subjective score was 3.0 ± 0.2 for G2, 3.0 ± 0.1 for G3, 3.6 ± 0.5 for G5, 4.0 ± 0.3 for G8, and 4.4 ± 0.5 for Gs. Only the scores between G2 and G3 were not significantly different (p > 0.99). The detection rates (204 lesions) significantly reduced to 94.1–90.2% in G3 and G2 (all p < 0.05).

Conclusion

A 2-min acquisition time provided acceptable performance in certain groups and specific medical situations. And protocols with acquisition times ≥ 5 min could provide comparable lesion detectability as regular protocols, showing better compatibility and feasibility with clinical practice.