bluuebunny/crossref_metadata_2025 huggingface dataset:
A qualitative study exploring contributors to the success of a community of practice in rehabilitation
Authors: Moore Jennifer L. , Bjørkli Cato , Havdahl Richard Tidemann , Lømo Linn Lien , Midthaug Mari , Skjuve Marita , Klokkerud Mari , Nordvik Jan E.
Published: May 2021

Background

Communities of Practice (CoPs) focus on learning, knowledge sharing, and creation, and research indicates they can improve healthcare performance. This article describes the development of a CoP that focused on synthesizing and adapting evidence in Physical Medicine and Rehabilitation (PM&R). This study aimed to investigate the CoP members’ experiences and perceived barriers and enablers of CoP success in the early phase of a CoP.

Methods

Physical therapists and a physician (n = 10) volunteered for a CoP that synthesized literature of PM&R evidence. CoP members participated in education and training on critical appraisal and knowledge synthesis, practiced critical appraisal skills, and summarized literature. Three months after CoP initiation, semi-structured interviews were conducted to understand the CoP members’ experiences and reflections. Members also completed an online survey that included the Evidence-Based Practice Confidence scale (EPIC), questions related to CoP activities, and demographics before CoP initiation. We utilized the Capability, Opportunity, and Motivation Model of Behaviour (COM-B) to explore how these experiences related to the behavioral adaptation and participation.

Results

Ten themes related to the potential contributors to CoP success and failure were identified. These included project management, technological solutions, efficacy, organizational support, interaction, the bigger picture, self-development, time, and motivation.

Conclusions

Contributors to CoP success may include clearly articulated project goals and participant expectations, education and training, reliable technology solutions, organizational support, face-to-face communication, and good project management. Importantly, CoP members need time to participate in activities.
A mixed methods evaluation of a 4-week geriatrics curriculum in strengthening knowledge and comfort among orthopaedic surgery residents
Authors: Chan Adrian C H , Chuen Victoria , Perrella Andrew , Limfat Guillaume , Ng Karen , Chau Vicky
Published: May 2021

Background

In 2014, the University of Toronto Faculty of Medicine implemented a 4-week “Orthogeriatrics” rotation for orthopaedic surgery residents. We sought to assess the rotation’s impact on trainees’ knowledge, attitudes, and behaviours toward caring for older adults, and explore areas for improvement.

Methods

We used a mixed methods concurrent triangulation design. The Geriatrics Clinical Decision-Making Assessment (GCDMA) and Geriatric Attitudes Scale (GAS) compared knowledge, attitudes, and behaviours between trainees who were or were not exposed to the curriculum. Rotation evaluations and semi-structured interviews with trainees and key informants explored learning experiences and the curriculum’s impact on resident physician growth and development in geriatric competencies.

Results

Among trainees who completed the GCDMA (n = 19), those exposed to the rotation scored higher in knowledge compared to the unexposed cohort (14.4 ± 2.1 vs. 11.3 ± 2.0, p < 0.01). The following themes emerged from the qualitative analysis of 29 stakeholders: Increased awareness and comfort regarding geriatric medicine competencies, appreciation of the value of orthogeriatric collaboration, and suggestions for curriculum improvement.

Conclusions

These results suggest that the Orthogeriatrics curriculum strengthens knowledge, behaviour, and comfort towards caring for older adults. Our study aims to inform further curriculum development and facilitate dissemination of geriatric education in surgical training programs across Canada and the world.
On intimate relationships between healthcare professionals and patients: a nationwide cohort analysis of medical tribunal decisions in the Netherlands
Authors: Rietdijk Wim , Renes Sander
Published: May 2021

Background

We examine the incidence of medical tribunal decisions and disciplinary actions (DAs) against healthcare professionals (HCPs). In addition, we studied whether an intimate relationship between an HCP and patient as part of the medical tribunal decision is associated with an increased likelihood of disciplinary actions.

Methods

We conducted a nationwide cohort analysis on the downloadable medical tribunal decisions from a medical disciplinary tribunal in the Netherlands from 2010 to 2017.

Results

We found that 117 (2.8%) of the 4,046 medical tribunal decisions involved an alleged intimate relationship between an HCP and patient. In these medical tribunal decisions the likelihood of a disciplinary action was significantly increased (odds ratio [OR] 12.97, 95% Confidence Interval [95% CI] 7.11–23.64). In addition, we found that nurses and psychiatrists are more frequently accused of and receive disciplinary actions due to intimate relationships than other HCP groups.

Conclusions

We found a limited number of medical tribunal decisions involving an intimate relationship. Especially given the total number of medical tribunal decisions and the number of yearly HCP-patient interactions, the number appears small. Furthermore, an alleged intimate relationship or inappropriate sexual conduct is associated with an increased likelihood of disciplinary action. Future research should obtain statistics on the number of intimate relationships that actually start between HCPs and patients.
An OMOP-CDM based pharmacovigilance data-processing pipeline (PDP) providing active surveillance for ADR signal detection from real-world data sources
Authors: Shin Hyunah , Lee Suehyun
Published: May 2021

Background

Adverse drug reactions (ADRs) are regarded as a major cause of death and a major contributor to public health costs. For the active surveillance of drug safety, the use of real-world data and real-world evidence as part of the overall pharmacovigilance process is important. In this regard, many studies apply the data-driven approaches to support pharmacovigilance. We developed a pharmacovigilance data-processing pipeline (PDP) that utilized electronic health records (EHR) and spontaneous reporting system (SRS) data to explore pharmacovigilance signals.

Methods

To this end, we integrated two medical data sources: Konyang University Hospital (KYUH) EHR and the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). As part of the presented PDP, we converted EHR data on the Observation Medical Outcomes Partnership (OMOP) data model. To evaluate the ability of using the proposed PDP for pharmacovigilance purposes, we performed a statistical validation using drugs that induce ear disorders.

Results

To validate the presented PDP, we extracted six drugs from the EHR that were significantly involved in ADRs causing ear disorders: nortriptyline, (hazard ratio [HR] 8.06, 95% CI 2.41–26.91); metoclopramide (HR 3.35, 95% CI 3.01–3.74); doxycycline (HR 1.73, 95% CI 1.14–2.62); digoxin (HR 1.60, 95% CI 1.08–2.38); acetaminophen (HR 1.59, 95% CI 1.47–1.72); and sucralfate (HR 1.21, 95% CI 1.06–1.38). In FAERS, the strongest associations were found for nortriptyline (reporting odds ratio [ROR] 1.94, 95% CI 1.73–2.16), sucralfate (ROR 1.22, 95% CI 1.01–1.45), doxycycline (ROR 1.30, 95% CI 1.20–1.40), and hydroxyzine (ROR 1.17, 95% CI 1.06–1.29). We confirmed the results in a meta-analysis using random and fixed models for doxycycline, hydroxyzine, metoclopramide, nortriptyline, and sucralfate.

Conclusions

The proposed PDP could support active surveillance and the strengthening of potential ADR signals via real-world data sources. In addition, the PDP was able to generate real-world evidence for drug safety.
Factors influencing risk perception and nosocomial infection prevention practices of frontline nurses during the COVID-19 pandemic
Authors: Lyu Xiaoguang , Hu Jiming , Xu Xin , Xianyu Yunyan , Dong Weiguo
Published: May 2021

Background

During the coronavirus disease 2019 (COVID-19) pandemic, exploring factors influencing nosocomial infection among frontline nurses may provide evidence to optimize prevention strategies in hospitals.

Method

A large-scale online questionnaire survey of nurses’ state-trait anxiety, job burnout, risk perception, workplace safety perception, knowledge about nosocomial infection, and preventive practices was conducted with 2795 frontline nurses working in the COVID-19 wards of six hospitals in Hubei Province, China, from February 1 to April 1, 2020. The questionnaire data were analyzed using the structural equation modeling (SEM) method to reveal the mechanisms influencing nurses’ risk perception and preventive practices related to nosocomial COVID-19 infection.

Results

A model of the factors that influence nurses’ risk perception and preventive practices regarding nosocomial COVID-19 infection was established. The model verified hypotheses regarding the impact of nurses’ risk perception and preventive practices. Notably, the hypothesis that risk perception has an impact on nurses’ preventive practices regarding nosocomial infection is not valid. Moreover, different marital and educational conditions are associated with significant differences in the impact of state anxiety on the execution of preventive practices, the impact of workplace safety perceptions on risk perception, and the impact of workplace safety perceptions on the execution of preventive practices. The effect of state anxiety on preventive practices differed significantly with different durations of work experience.

Conclusions

According to the results of the influencing factor model, promoting the quality of training on nosocomial infection, meliorating workplace safety, and conducting timely and effective psychological interventions would aid in improving nurses’ preventive practices. Meliorating workplace safety and easing state anxiety would be beneficial to reduce nurses’ risk perception. These strategies are conducive to the optimization of policies for preventing nosocomial COVID-19 infections and similar infectious diseases.
Measuring and modeling energy and power consumption in living microbial cells with a synthetic ATP reporter
Authors: Deng Yijie , Beahm Douglas Raymond , Ionov Steven , Sarpeshkar Rahul
Published: May 2021

Background

Adenosine triphosphate (ATP) is the main energy carrier in living organisms, critical for metabolism and essential physiological processes. In humans, abnormal regulation of energy levels (ATP concentration) and power consumption (ATP consumption flux) in cells is associated with numerous diseases from cancer, to viral infection and immune dysfunction, while in microbes it influences their responses to drugs and other stresses. The measurement and modeling of ATP dynamics in cells is therefore a critical component in understanding fundamental physiology and its role in pathology. Despite the importance of ATP, our current understanding of energy dynamics and homeostasis in living cells has been limited by the lack of easy-to-use ATP sensors and the lack of models that enable accurate estimates of energy and power consumption related to these ATP dynamics. Here we describe a dynamic model and an ATP reporter that tracks ATP in E. coli over different growth phases.

Results

The reporter is made by fusing an ATP-sensing rrnB P1 promoter with a fast-folding and fast-degrading GFP. Good correlations between reporter GFP and cellular ATP were obtained in E. coli growing in both minimal and rich media and in various strains. The ATP reporter can reliably monitor bacterial ATP dynamics in response to nutrient availability. Fitting the dynamics of experimental data corresponding to cell growth, glucose, acetate, dissolved oxygen, and ATP yielded a mathematical and circuit model. This model can accurately predict cellular energy and power consumption under various conditions. We found that cellular power consumption varies significantly from approximately 0.8 and 0.2 million ATP/s for a tested strain during lag and stationary phases to 6.4 million ATP/s during exponential phase, indicating ~ 8–30-fold changes of metabolic rates among different growth phases. Bacteria turn over their cellular ATP pool a few times per second during the exponential phase and slow this rate by ~ 2–5-fold in lag and stationary phases.

Conclusion

Our rrnB P1-GFP reporter and kinetic circuit model provide a fast and simple way to monitor and predict energy and power consumption dynamics in bacterial cells, which can impact fundamental scientific studies and applied medical treatments in the future.
A novel autophagy-related genes prognostic risk model and validation of autophagy-related oncogene VPS35 in breast cancer
Authors: Li Xiaoying , Cao Yu , Yu Xinmiao , Jin Feng , Li Yang
Published: May 2021

Background

Accumulating evidence implies that autophagy plays a critical role in breast cancer development and progression. It is crucial to screen out autophagy-related encoding genes (ARGs) with prognostic value in breast cancer and reveal their biological properties in the aggressiveness of breast cancer.

Methods

Univariate and multivariate Cox proportional hazards analyses were used to identify a prognostic risk model of ARGs from The Cancer Genome Atlas (TCGA). Kaplan–Meier analysis, univariate and multivariate Cox regression analyses and receiver operating characteristic (ROC) curve analysis were performed to validate the risk model. Western blot and immunohistochemistry (IHC) were conducted to assess the expression of VPS35 (one of ARGs in risk model). CCK8, Colony formation assay, Transwell migration/invasion assays and autophagy flux assay were used to confirm biological function of VPS35 in breast cancer.

Results

In this study, the prognostic risk model consisting of six ARGs (VPS35, TRIM21, PRKAB2, RUFY4, MAP1LC3A and LARP1) in breast cancer were identified. The risk model was further verified as a novel independent prognostic factor for breast cancer patients. We also clarified that vacuolar protein sorting-associated protein 35 (VPS35), one of ARGs in the risk model, was upregulated in breast cancer samples and cell lines. VPS35 overexpression was correlated with more aggressive phenotype of breast cancer and indicated worse prognosis in both progression-free survival and overall survival analyses. Meanwhile, VPS35 knockdown inhibited breast cancer cell proliferation, migration and invasion, suggesting that VPS35 promoted the progression of breast cancer. VPS35 silence also influenced autophagy process, indicating that VPS35 was essential for autophagy completion.

Conclusion

Taken together, the six ARGs risk model has a remarkably prognostic value for breast cancer. Among them, VPS35 might exert as a significant oncogenic and prognostic factor for breast cancer and could be a promising autophagy-related therapeutic target in clinical practice.
Effect and significance of incorporating access in estimating the number of required physicians: focus on differences in population density in the target area
Authors: Suzuki Tatsuya , Koike Soichi , Matsumoto Masatoshi
Published: May 2021

Background

Geographical imbalances in the health workforce, particularly the shortage of health care workers in rural areas, is an issue of social and political concern in most countries. Estimating the number of required doctors is essential for evidence-based health policy planning. In this study, we propose two methods for estimating the number of required doctors using a simple method. One is counting by unit and the other is incorporating access to medical institutions. The purpose of this study is to verify the need to incorporate access to medical institutions when estimating the number of required physicians in a region by comparing both estimation methods from the viewpoint of regional population density.

Methods

We calculated the ratio of outpatients who can access medical institutions and the number of required physicians using the travel time by car and the number of patients who can be treated per doctor per day (estimation method for the number of physicians based on the access simulation, hereinafter referred to as EAS). We compared the results of this estimation with those of a conventional method, such as the number of doctors per population (estimation method for the number of physicians based on the number of patients, hereinafter referred to as ENP) to show how important it is to incorporate the element of accessibility in such a simulation analysis. Based on the results, we discussed the applicability of the proposed method.

Results

ENP estimated that 38,685 outpatient primary care (PC) physicians were required and EAS estimated that 46,378 were required. There was a difference of about 8000. A comparison of the EAS-estimated number of physicians and the ENP-estimated number of physicians showed that the ENP-estimated number was small, particularly in areas with low population density.

Conclusions

The results showed that it is effective to use the proposed EAS method for the estimation of PC physicians, particularly in areas with low population density. We showed that the method of allocating the number of physicians in proportion to the number of patients in a certain unit requires paying attention to the setting of the unit.
Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons
Authors: Guo Lin , Huang Zhixuan , Huang Lijuan , Liang Jia , Wang Peng , Zhao Liang , Shi Yijie
Published: May 2021

Background

The incidence of ischemic stroke in the context of vascular disease is high, and the expression of growth-associated protein-43 (GAP43) increases when neurons are damaged or stimulated, especially in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R).

Experimental

design

We bioengineered neuron-targeting exosomes (Exo) conjugated to a monoclonal antibody against GAP43 (mAb GAP43) to promote the targeted delivery of quercetin (Que) to ischemic neurons with high GAP43 expression and investigated the ability of Exo to treat cerebral ischemia by scavenging reactive oxygen species (ROS).

Results

Our results suggested that Que loaded mAb GAP43 conjugated exosomes (Que/mAb GAP43-Exo) can specifically target damaged neurons through the interaction between Exo-delivered mAb GAP43 and GAP43 expressed in damaged neurons and improve survival of neurons by inhibiting ROS production through the activation of the Nrf2/HO-1 pathway. The brain infarct volume is smaller, and neurological recovery is more markedly improved following Que/mAb GAP43-Exo treatment than following free Que or Que-carrying exosome (Que-Exo) treatment in a rat induced by MCAO/R.

Conclusions

Que/mAb GAP43-Exo may serve a promising dual targeting and therapeutic drug delivery system for alleviating cerebral ischemia/reperfusion injury.
Relationship between symptoms and both stage of change in adopting a healthy life style and quality of life in patients with liver cirrhosis: a cross-sectional study
Authors: Lee Myung Kyung , Chung Woo Jin
Published: May 2021

Background

Previous studies of patients with liver cirrhosis have not considered the broad range of symptoms or the association between healthy behavior and quality of life. The purposes of this study were to examine the association between symptoms and adopting exercise and consuming fruits and vegetables and to identify factors associated with quality of life in patients with liver cirrhosis.

Methods

This cross-sectional study enrolled 91 consecutive patients with liver cirrhosis in one tertiary general hospital in South Korea between February 2016 and January 2017. Each study participant completed a self-administered questionnaire that measured symptom, stage of change in engaging in exercise and consumption of fruits and vegetables, and the Korean version of the 36-item Short-Form Health Survey. Multivariate ordinal logistic regression analysis and multiple regression models was used, respectively, to examine the association between each symptom with stage of change in engaging in exercise and consumption of fruits and vegetables and to evaluate factors affecting quality of life.

Results

Experiencing nausea was associated with more readiness for change in engaging in exercise, but experiencing shortness of breath was associated with less readiness for change in engaging in exercise. Experiencing right upper quadrant pain was associated with more readiness for change in engaging in consumption of fruits and vegetables. Muscle cramps, anorexia, right upper quadrant pain and body pain, itching, ascites or edema, bruising, and change in appearance negatively affected quality of life.

Conclusions

The results suggest that the types of symptoms experienced by a patient with liver cirrhosis hinder or promote the patient’s adoption of exercise and dietary behavior. Experiencing symptoms may negatively affect quality of life. Caregivers should provide supportive care to patients with liver cirrhosis, which includes assessing and managing symptoms to improve quality of life.
Neoadjuvant chemotherapy followed by hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastasis: a retrospective study of its safety and efficacy
Authors: Zhou Sicheng , Jiang Yujuan , Liang Jianwei , Pei Wei , Zhou Zhixiang
Published: May 2021

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective routine treatments for colorectal peritoneal metastasis (PM). However, the safety and efficacy of neoadjuvant chemotherapy (NAC) before CRS+HIPEC are poorly understood. Therefore, this study aimed to assess the perioperative safety and long-term efficacy of NAC prior to CRS+HIPEC for patients with synchronous colorectal PM.

Methods

Patients with synchronous colorectal PM who received NAC prior to CRS+HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. The clinicopathologic characteristics, perioperative parameters, and survival rates of patients who underwent CRS+HIPEC with NAC (NAC group) and patients who underwent CRS+HIPEC without NAC (non-NAC group) were compared.

Results

The study enrolled 52 patients, with 20 patients in the NAC group and 32 in the non-NAC group. In the NAC group, the proportion of patients with a peritoneal carcinomatosis index (PCI) score < 12 was significantly higher than that in the non-NAC group (80.0% vs 50.0%, P = 0.031), and more patients achieved complete cytoreduction (80.0% vs 46.9%, P = 0.018). The two groups had comparable grade III/IV complications and similar reoperation and mortality rates (P > 0.05). However, patients who received NAC had lower platelet counts (151.9 vs 197.7 × 109/L, P = 0.036) and neutrophil counts (4.7 vs 7.2 × 109/L, P = 0.030) on postoperative day 1. More patients survived for 2 years in the NAC group than in the non-NAC group (67.4% vs 32.2%, respectively, P = 0.044). However, the completeness of cytoreduction score (HR, 2.99; 95% CI, 1.14–7.84; P = 0.026), rather than NAC, was independently associated with overall survival (OS) in the multivariate analysis after controlling for confounding factors.

Conclusion

NAC administration before CRS+HIPEC can be regarded as safe and feasible for patients with colorectal PM with comparably low mortality rates and acceptable morbidity rates. Nevertheless, large-sample randomized controlled studies are needed to confirm whether the administration of NAC before CRS+HIPEC confers a survival benefit to patients.
PRICKLE1, a Wnt/PCP signaling component, is overexpressed and associated with inferior prognosis in acute myeloid leukemia
Authors: Jiang Duanfeng , He Yanjuan , Mo Qiuyu , Liu Enyi , Li Xin , Huang Lihua , Zhang Qin , Chen Fangping , Li Yan , Shao Haigang
Published: May 2021

Background

Prickle planar cell polarity protein 1 (PRICKLE1), a core component of the non-canonical Wnt/planar cell polarity (PCP) pathway, was recently reported to be upregulated and correlated with poor prognosis in solid cancers. However, the effect of PRICKLE1 on acute myeloid leukemia (AML) remains unknown. This study aims to characterize the prognostic significance of PRICKLE1 expression in patients with AML.

Methods

RNA-seq was performed to compare mRNA expression profiles of AML patients and healthy controls. qRT-PCR and western blotting were used to analyze the expression of PRICKLE1 in AML patients and cell lines, and two independent datasets (TCGA-LAML and TARGET-AML) online were used to validate the expression results. The correlations between the expression of PRICKLE1 and clinical features were further analyzed.

Results

Our data showed that PRICKLE1 expression levels were markedly high in AML patients at the time of diagnosis, decreased after complete remission and increased again at relapse. Of note, PRICKLE1 was highly expressed in drug resistant AML cells and monocytic-AML patients. High PRICKLE1 expression was found in FLT3/DNMT3A/IDH1/IDH2-mutant AML and associated with poor prognosis. Furthermore, high expression of PRICKLE1 may be correlated with migration and invasion components upregulation in AML patients.

Conclusions

These results indicated that high PRICKLE1 expression may be a poor prognostic biomarker and therapeutic target of AML.
Gene alterations as predictors of radiation-induced toxicity in head and neck squamous cell carcinoma
Authors: Sumner Whitney , Ray Xenia , Sutton Leisa , Rebibo Daniel , Marincola Francesco , Sanghvi Parag , Moiseenko Vitali , Deichaite Ida
Published: May 2021

Background

Optimizing the therapeutic ratio for radiation therapy (RT) in head and neck squamous cell carcinoma (HNSCC) is uniquely challenging owing to high rates of early and late toxicity involving nearby organs at risk. These toxicities have a profound impact on treatment compliance and quality of life. Emerging evidence suggests that RT dose alone cannot fully account for the variable severity of RT-related adverse events (rtAEs) observed in HNSCC patients. Next-generation sequencing has become an increasingly valuable tool with widespread use in the oncology field and is being robustly explored for predicting rtAEs beyond dosimetric data.

Methods

Patients who had Foundation Medicine sequencing data and received RT for primary or locally recurrent HNSCC were selected for this study. Early and late toxicity data were collected and reported based on Common Terminology Criteria for Adverse Events version 5.0. Dosimetric parameters were collected for pertinent structures.

Results

A total of HNSCC 37 patients were analyzed in this study. Genetic alterations in BRCA2, ERBB3, NOTCH1 and CCND1 were all associated with higher mean grade of toxicity with BRCA2 alteration implicated in all toxicity parameters evaluated including mucositis, early dysphagia, xerostomia and to a lesser extent, late dysphagia. Interestingly, patients who exhibited alterations in both BRCA2 and ERBB3 experienced a twofold or greater increase in early dysphagia, early xerostomia and late dysphagia compared to ERBB3 alteration alone. Furthermore, several gene alterations were associated with improved toxicity outcomes. Within an RT supersensitive patient subset, alterations were found in TNFAIP3, HNF1A, SPTA1 and CASP8. All of these alterations were not found in the RT insensitive patient subset. We found 17 gene alterations in the RT insensitive patient subset that were not found in the RT supersensitive patient subset.

Conclusion

Despite consistent RT dosimetric parameters, patients with HNSCC experience heterogeneous patterns of rtAEs. Identifying factors associated with toxicity outcomes offers a new avenue for personalized precision RT therapy and prophylactic management. Here, next-generation sequencing in a population of HNSCC patients correlates several genetic alterations with severity of rtAEs. Further analysis is urgently needed to identify genetic patterns associated with rtAEs in order to reduce harmful outcomes in this challenging population.
Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies
Authors: Hayashida Kei , Takegawa Ryosuke , Shoaib Muhammad , Aoki Tomoaki , Choudhary Rishabh C. , Kuschner Cyrus E. , Nishikimi Mitsuaki , Miyara Santiago J. , Rolston Daniel M. , Guevara Sara , Kim Junhwan , Shinozaki Koichiro , Molmenti Ernesto P. , Becker Lance B.
Published: May 2021

Background

Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation.

Methods

We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis.

Results

Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery.

Conclusion

The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation.

Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.
Monitoring the patterns of submission and presence of tick-borne pathogens in Ixodes scapularis collected from humans and companion animals in Ontario, Canada (2011–2017)
Authors: Nelder Mark P. , Russell Curtis B. , Dibernardo Antonia , Clow Katie M. , Johnson Steven , Cronin Kirby , Patel Samir N. , Lindsay L. Robbin
Published: May 2021

Background

The universal nature of the human–companion animal relationship and their shared ticks and tick-borne pathogens offers an opportunity for improving public and veterinary health surveillance. With this in mind, we describe the spatiotemporal trends for blacklegged tick (Ixodes scapularis) submissions from humans and companion animals in Ontario, along with pathogen prevalence.

Methods

We tested tick samples submitted through passive surveillance (2011–2017) from humans and companion animals for Borrelia burgdorferi, Borrelia miyamotoi, Anaplasma phagocytophilum and Babesia microti. We describe pathogen prevalence in ticks from humans and from companion animals and constructed univariable Poisson and negative binomial regression models to explore the spatiotemporal relationship between the rates of tick submissions by host type.

Results

During the study, there were 17,230 blacklegged tick samples submitted from humans and 4375 from companion animals. Tick submission rates from companion animals were higher than expected in several public health units (PHUs) lacking established tick populations, potentially indicating newly emerging populations. Pathogen prevalence in ticks was higher in PHUs where established blacklegged tick populations exist. Borrelia burgdorferi prevalence was higher in ticks collected from humans (maximum likelihood estimate, MLE = 17.5%; 95% confidence interval, CI 16.97–18.09%) than from companion animals (9.9%, 95% CI 9.15–10.78%). There was no difference in pathogen prevalence in ticks by host type for the remaining pathogens, which were found in less than 1% of tested ticks. The most common co-infection B. burgdorferi + B. miyamotoi occurred in 0.11% of blacklegged ticks from humans and animals combined. Borrelia burgdorferi prevalence was higher in unengorged (21.9%, 95% CI 21.12–22.65%) than engorged ticks (10.0%, 95% CI 9.45–10.56%). There were no consistent and significant spatiotemporal relationships detected via regression models between the annual rates of submission of each host type.

Conclusions

While B. burgdorferi has been present in blacklegged ticks in Ontario for several decades, other tick-borne pathogens are also present at low prevalence. Blacklegged tick and pathogen surveillance data can be used to monitor risk in human and companion animal populations, and efforts are under consideration to unite surveillance efforts for the different target populations.

Graphical Abstract
Effectiveness of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) for the treatment of larval and immature adult stages of Ancylostoma caninum in experimentally infected dogs
Authors: Snyder Daniel E. , Wiseman Scott , Crawley Elizabeth , Wallace Kim , Bowman Dwight D. , Reinemeyer Craig R.
Published: May 2021

Background

The hookworm,Ancylostoma caninum, is a common and important zoonotic intestinal nematode parasite that infects dogs globally. Both the immature and adult stages ofA. caninumingest large volumes of blood during the feeding process and can cause severe anemia and death in young dogs, even before patent infections can be diagnosed using routine faecal examination methods. Thus, effective treatment of any pre-patent stages of immature hookworms can reduce or eliminate the risk of clinical disease in infected dogs and additionally reduce environmental contamination of eggs and infective larvae. Two randomized, blinded, GCP-compliant, pivotal laboratory dose confirmation studies were conducted to evaluate the effectiveness and safety of a new novel combination of lotilaner and milbemycin oxime tablets (Credelio Plus®) administered orally to dogs experimentally infected with immature (L4 and immature adult [L5]) stages ofA. caninum.

Methods

Treatments using the intended global commercial tablet formulation of Credelio Plus were administered in a time frame relative to inoculation with infective larvae so that effectiveness could be assessed against each specific immature stage ofA. caninum. In each study, dogs were randomized to one of six (study 1) or four (study 2) treatment groups. Each treatment group contained 8 (study 1) or 10 (study 2) dogs that had been experimentally inoculated with infectiveA. caninumlarvae on day 0 and were dosed once on day 7 or day 11. Enrolled subjects were administered placebo tablets, Credelio Plus tablets, or lotilaner mono tablets to provide minimum dosages of 0.75 mg/kg of milbemycin oxime and 20 mg/kg of lotilaner. All dogs were necropsied 5 days after their respective treatment. All nematodes recovered from the gastrointestinal tract at necropsy were counted by species and stage.

Results

For both dose confirmation studies and based on geometric mean worm counts, efficacy of Credelio Plus was ≥ 97.3% against L4 larval stage ofA. caninumand ≥ 98.7% against immature adult (L5)A. caninum.

Conclusions

These studies demonstrated that the orally administered Credelio Plus combination tablet was highly efficacious in treating immature (L4 and immature adult [L5]) stages ofA. caninumin experimentally infected dogs.

Graphical Abstract
Leveraging epigenetics to enhance the efficacy of immunotherapy
Authors: Licht Jonathan D. , Bennett Richard L.
Published: May 2021

Background

Epigenetic mechanisms regulate chromatin accessibility patterns that govern interaction of transcription machinery with genes and their cis-regulatory elements. Mutations that affect epigenetic mechanisms are common in cancer. Because epigenetic modifications are reversible many anticancer strategies targeting these mechanisms are currently under development and in clinical trials.

Main body

Here we review evidence suggesting that epigenetic therapeutics can deactivate immunosuppressive gene expression or reprogram tumor cells to activate antigen presentation mechanisms. In addition, the dysregulation of epigenetic mechanisms commonly observed in cancer may alter the immunogenicity of tumor cells and effectiveness of immunotherapies.

Conclusions

Therapeutics targeting epigenetic mechanisms may be helpful to counter immune evasion and improve the effectiveness of immunotherapies.
The Comprehensive Autistic Trait Inventory (CATI): development and validation of a new measure of autistic traits in the general population
Authors: English Michael C. W. , Gignac Gilles E. , Visser Troy A. W. , Whitehouse Andrew J. O. , Enns James T. , Maybery Murray T.
Published: May 2021

Background

Traits and characteristics qualitatively similar to those seen in diagnosed autism spectrum disorder can be found to varying degrees in the general population. To measure these traits and facilitate their use in autism research, several questionnaires have been developed that provide broad measures of autistic traits [e.g. Autism-Spectrum Quotient (AQ), Broad Autism Phenotype Questionnaire (BAPQ)]. However, since their development, our understanding of autism has grown considerably, and it is arguable that existing measures do not provide an ideal representation of the trait dimensions currently associated with autism. Our aim was to create a new measure of autistic traits that reflects our current understanding of autism, the Comprehensive Autism Trait Inventory (CATI).

Methods

In Study 1, 107 pilot items were administered to 1166 individuals in the general population and exploratory factor analysis of responses used to create the 42-item CATI comprising six subscales: Social Interactions, Communication, Social Camouflage, Repetitive Behaviours, Cognitive Rigidity, and Sensory Sensitivity. In Study 2, the CATI was administered to 1119 new individuals and confirmatory factor analysis used to verify the factor structure. The AQ and BAPQ were administered to validate the CATI, and additional autistic participants were recruited to compare the predictive ability of the measures. In Study 3, to validate the CATI subscales, the CATI was administered to 202 new individuals along with existing valid measures qualitatively similar to each CATI subscale.

Results

The CATI showed convergent validity at both the total-scale (r ≥ .79) and subscale level (r ≥ .68). The CATI also showed superior internal reliability for total-scale scores (α = .95) relative to the AQ (α = .90) and BAPQ (α = .94), consistently high reliability for subscales (α > .81), greater predictive ability for classifying autism (Youden’s Index = .62 vs .56–.59), and demonstrated measurement invariance for sex.

Limitations

Analyses of predictive ability for classifying autism depended upon self-reported diagnosis or identification of autism. The autistic sample was not large enough to test measurement invariance of autism diagnosis.

Conclusions

The CATI is a reliable and economical new measure that provides observations across a wide range of trait dimensions associated with autism, potentially precluding the need to administer multiple measures, and to our knowledge, the CATI is also the first broad measure of autistic traits to have dedicated subscales for social camouflage and sensory sensitivity.
The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation
Authors: Sun Yuanxiu , Yuan Yu , Wu Wei , Lei Le , Zhang Lingli
Published: May 2021

Bone marrow mesenchymal stem cells (BMSCs) refer to a heterogeneous population of cells with the capacity for self-renewal. BMSCs have multi-directional differentiation potential and can differentiate into chondrocytes, osteoblasts, and adipocytes under specific microenvironment or mechanical regulation. The activities of BMSCs are closely related to bone quality. Previous studies have shown that BMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. Thus, a goal of this review is to discuss how these ubiquious signals arising from mechanical stimulation are perceived by BMSCs and then how the cells respond to them. Studies in recent years reported a significant effect of locomotion on the migration, proliferation and differentiation of BMSCs, thus, contributing to our bone mass. This regulation is realized by the various intersecting signaling pathways including RhoA/Rock, IFG, BMP and Wnt signalling. The mechanoresponse of BMSCs also provides guidance for maintaining bone health by taking appropriate exercises. This review will summarize the regulatory effects of locomotion/mechanical loading on BMSCs activities. Besides, a number of signalling pathways govern MSC fate towards osteogenic or adipocytic differentiation will be discussed. The understanding of mechanoresponse of BMSCs makes the foundation for translational medicine.
The autonomic nervous system in septic shock and its role as a future therapeutic target: a narrative review
Authors: Carrara Marta , Ferrario Manuela , Bollen Pinto Bernardo , Herpain Antoine
Published: May 2021

The autonomic nervous system (ANS) regulates the cardiovascular system. A growing body of experimental and clinical evidence confirms significant dysfunction of this regulation during sepsis and septic shock. Clinical guidelines do not currently include any evaluation of ANS function during the resuscitation phase of septic shock despite the fact that the severity and persistence of ANS dysfunction are correlated with worse clinical outcomes. In the critical care setting, the clinical use of ANS-related hemodynamic indices is currently limited to preliminary investigations trying to predict and anticipate imminent clinical deterioration. In this review, we discuss the evidence supporting the concept that, in septic shock, restoration of ANS-mediated control of the cardiovascular system or alleviation of the clinical consequences induced by its dysfunction (e.g., excessive tachycardia, etc.), may be an important therapeutic goal, in combination with traditional resuscitation targets. Recent studies, which have used standard and advanced monitoring methods and mathematical models to investigate the ANS-mediated mechanisms of physiological regulation, have shown the feasibility and importance of monitoring ANS hemodynamic indices at the bedside, based on the acquisition of simple signals, such as heart rate and arterial blood pressure fluctuations. During the early phase of septic shock, experimental and/or clinical studies have shown the efficacy of negative-chronotropic agents (i.e., beta-blockers or ivabradine) in controlling persistent tachycardia despite adequate resuscitation. Central α-2 agonists have been shown to prevent peripheral adrenergic receptor desensitization by reducing catecholamine exposure. Whether these new therapeutic approaches can safely improve clinical outcomes remains to be confirmed in larger clinical trials. New technological solutions are now available to non-invasively modulate ANS outflow, such as transcutaneous vagal stimulation, with initial pre-clinical studies showing promising results and paving the way for ANS modulation to be considered as a new potential therapeutic target in patients with septic shock.
Boosting CNN-based primary quantization matrix estimation of double JPEG images via a classification-like architecture
Authors: Tondi Benedetta , Costanzo Andrea , Huang Dequ , Li Bin
Published: May 2021

Estimating the primary quantization matrix of double JPEG compressed images is a problem of relevant importance in image forensics since it allows to infer important information about the past history of an image. In addition, the inconsistencies of the primary quantization matrices across different image regions can be used to localize splicing in double JPEG tampered images. Traditional model-based approaches work under specific assumptions on the relationship between the first and second compression qualities and on the alignment of the JPEG grid. Recently, a deep learning-based estimator capable to work under a wide variety of conditions has been proposed that outperforms tailored existing methods in most of the cases. The method is based on a convolutional neural network (CNN) that is trained to solve the estimation as a standard regression problem. By exploiting the integer nature of the quantization coefficients, in this paper, we propose a deep learning technique that performs the estimation by resorting to a simil-classification architecture. The CNN is trained with a loss function that takes into account both the accuracy and the mean square error (MSE) of the estimation. Results confirm the superior performance of the proposed technique, compared to the state-of-the art methods based on statistical analysis and, in particular, deep learning regression. Moreover, the capability of the method to work under general operative conditions, regarding the alignment of the second compression grid with the one of first compression and the combinations of the JPEG qualities of former and second compression, is very relevant in practical applications, where these information are unknown a priori.