bluuebunny/crossref_metadata_2025 huggingface dataset:
Care for caregivers- a mission for primary care
Authors: Biderman Aya , Carmel Sara , Amar Shimon , Bachner Yaacov G.
Published: November 2021

Background

The number of elderly people living in the community who are limited in daily activities is increasing worldwide. This generates prolonged care, which usually falls on one family member, the family caregiver. Caregivers are prone to develop psychosocial and physical symptoms. As a result, the World Health Organization (WHO) issued a clear directive to assess and support these caregivers.

The main goals of this study were to assess primary care physicians’ (PCP) awareness to caregivers’ health risks and the extent that they recommended preventive measures to maintain the health of the caregivers. As no suitable instrument existed, a secondary goal was to develop a scale to measure physicians’ awareness to caregivers’ health and preventive treatment and test it’s psychometric properties.

Methods

Data were collected from a convenience sample of 201 PCP interviewed with structured questionnaires.

Results

The participants’ mean age was 48.5 ± 11.2 years and 53.5% were female. Only 48.5% were Israel medical graduates and 72% were board-certified family physicians. Nearly 34% had been primary caregivers of family members.

Most physicians (83.6%) were aware of the primary caregiver’s high-risk for morbidity and mortality, and recommended preventive care. On a multivariate regression, PCP's higher level of risk awareness, their country of medical school and board certification were significant for explaining recommendations for preventive care. However, being a primary caregiver for a sick family member neither contributed significantly to the physicians’ awareness to caregiving risks nor to their preventive care.

Conclusion

Although a high percentage of physicians were aware and concerned about caregivers’ health, their preventive care activities were relatively passive. PCPs should take a more active and preventive role for maintaining caregivers’ health.
The PREvention Program for Alzheimer’s RElated Delirium (PREPARED) cluster randomized trial: a study protocol
Authors: Wilchesky Machelle , Ballard Stephanie A. , Voyer Philippe , McCusker Jane , Lungu Ovidiu , Champoux Nathalie , Vu T. T. Minh , Cole Martin G. , Monette Johanne , Ciampi Antonio , Belzile Eric , Carmichael Pierre-Hugues , McConnell Ted
Published: November 2021

Background

Delirium is a significant cause of morbidity and mortality among older people admitted to both acute and long-term care facilities (LTCFs). Multicomponent interventions have been shown to reduce delirium incidence in the acute care setting (30–73%) by acting on modifiable risk factors. Little work, however, has focused on using this approach to reduce delirium incidence in LTCFs.

Methods

The objective is to assess the effectiveness of the multicomponent PREPARED Trial intervention in reducing the following primary outcomes: incidence, severity, duration, and frequency of delirium episodes in cognitively impaired residents. This 4-year, parallel-design, cluster randomized study will involve nursing staff and residents in 45–50 LTCFs in Montreal, Canada. Participating public and private LTCFs (clusters) that provide 24-h nursing care will be assigned to either the PREPARED Trial intervention or the control (usual care) arm of the study using a covariate constrained randomization procedure. Approximately 400–600 LTC residents aged 65 and older with dementia and/or cognitive impairment will be enrolled in the study and followed for 18 weeks. Residents must be at risk of delirium, delirium-free at baseline and have resided at the facility for at least 2 weeks. Residents who are unable to communicate verbally, have a history of specific psychiatric conditions, or are receiving end-of-life care will be excluded. The PREPARED Trial intervention consists of four main components: a decision tree, an instruction manual, a training package, and a toolkit. Primary study outcomes will be assessed weekly. Functional autonomy and cognitive levels will be assessed at the beginning and end of follow-up, while information pertaining to modifiable delirium risk factors, medical consultations, and facility transfers will be collected retrospectively for the duration of the follow-up period. Primary outcomes will be reported at the level of intervention assignment. All researchers analyzing the data will be blinded to group allocation.

Discussion

This large-scale intervention study will contribute significantly to the development of evidence-based clinical guidelines for delirium prevention in this frail elderly population, as it will be the first to evaluate the efficacy of a multicomponent delirium prevention program translated into LTC clinical practice on a large scale.

Trial registration

NCT03718156,ClinicalTrials.gov.
A complex intervention to promote prevention of delirium in older adults by targeting caregiver’s participation during and after hospital discharge – study protocol of the TRAnsport and DElirium in older people (TRADE) project
Authors: Leinert Christoph , Brefka Simone , Braisch Ulrike , Denninger Natascha , Mueller Martin , Benzinger Petra , Bauer Juergen , Bahrmann Anke , Frey Norbert , Katus Hugo A. , Geisler Tobias , Eschweiler Gerhard , Klaus Jochen , Seufferlein Thomas , Schuetze Konrad , Gebhard Florian , Dreyhaupt Jens , Muche Rainer , Pahmeier Kathrin , Biermann-Stallwitz Janine , Wasem Juergen , Flagmeier Lena , Dallmeier Dhayana , Denkinger Michael
Published: November 2021

Background

Among potentially modifiable risk factors for delirium, transfers between wards, hospitals and other facilities have been mentioned with low evidence. TRADE (TRAnsport and DElirium in older people) was set up to investigate i) the impact of transfer and/or discharge on the onset of delirium in older adults and ii) feasibility and acceptance of a developed complex intervention targeting caregiver’s participation during and after hospital discharge or transfer on cognition and the onset of delirium in older adults.

Methods

The study is designed according to the guidelines of the UK Medical Research Council (MRC) for development and evaluation of complex interventions and comprises two steps: development and feasibility/piloting. The development phase includes i) a multicenter observational prospective cohort study to assess delirium incidence and cognitive decline associated with transfer and discharge, ii) a systematic review of the literature, iii) stakeholder focus group interviews and iv) an expert workshop followed by a Delphi survey. Based on this information, a complex intervention to better and systematically involve family caregivers in discharge and transport was developed. The intervention will be tested in a pilot study using a stepped wedge design with a detailed process and health economic evaluation. The study is conducted at four acute care hospitals in southwest Germany. Primary endpoints are the delirium incidence and cognitive function. Secondary endpoints include prevalence of caregiver companionship, functional decline, cost and cost effectiveness, quality of discharge management and quality of admission management in admitting hospitals or nursing homes. Data will be collected prior to discharge as well as after 3, 7 and 90 days.

Discussion

TRADE will help to evaluate transfer and discharge as a possible risk factor for delirium. In addition, TRADE evaluates the impact and modifiability of caregiver’s participation during patient’s transfer or discharge on delirium incidence and cognitive decline providing the foundation for a confirmatory implementation study.

Trial registration

DRKS (Deutsches Register für klinische Studien) DRKS00017828. Registered on 17th September 2019. Retrospectively registered.
Impact of cocreation training capsules for preschool teachers on children’s healthy habits: a pilot study conducted in Barcelona, Spain
Authors: Violant-Holz Verónica , Rodríguez-Silva Carlota , Carol María , Rodríguez Manuel J.
Published: November 2021

Background

Healthy habits are essential for preschoolers to have a healthy lifestyle. The promotion of these healthy habits from a holistic approach by preschool teachers guarantees a better quality of life and a healthier society. Using cocreation, we designed training for healthy habit promotion for preschool teachers (all@once). Then, we implemented the training and evaluated its impact on classroom teaching strategies.

Methods

This study presents the all@once training design and its implementation and evaluation during 2019. The cocreation process involved 8 parents, 9 preschool teachers and 9 health professionals (selected by a nonprobabilistic sampling system according to quotas) to design training from a holistic perspective. To evaluate the all@once impact in classroom practice, a pilot study was undertaken in four public schools in Barcelona (Spain). All@once was implemented with 16 volunteer teachers selected by convenience sampling and 328 children. A mixed methods approach was chosen to collect data based on direct nonparticipating naturalist systematic observations in June and October 2019. After qualitative data categorization, changes in health routines and actions at school were assessed by either contingency table analysis of frequency distributions or nonparametric comparisons of two related samples.

Results

The cocreation process provided training organized into online capsules with a holistic view of health in four main dimensions (nutrition, hygiene, physical activity and emotional health). Of these dimensions, the emotional health dimension comprised half of the training content. Pilot testing of the impact of all@once on classroom health-related activities evidenced an increase in the likelihood of observing fruit consumption by children, healthy habit promotion and hand washing. The most significant all@once-induced changes that we observed were related to teaching strategies concerning the emotional health dimension of the training.

Conclusions

This pilot study provides evidence of cocreation being a productive way to design training for preschool teachers regarding inclusive education in integral health. This approach collects the needs of the school community, provides training with a holistic concept of health and effectively impacts classroom routines and family health habits in the short term.
Protective effect of Palmijihwanghwan in a mouse model of cigarette smoke and lipopolysaccharide-induced chronic obstructive pulmonary disease
Authors: Baek Eun Bok , Rho Jin-hyung , Jung Eunhye , Seo Chang-Seob , Kim Jin-Hee , Kwun Hyo-Jung
Published: November 2021

Background

Palmijihwanghwan (PJH) is a traditional medicine and eight constituents derived from PJH possess anti-inflammatory activities. However, the scientific evidence for its potential as a therapeutic agent for inflammatory lung disease has not yet been studied. In this study, we examined the protective effect of PJH in a mouse model of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS) with lipopolysaccharide (LPS).

Methods

Mice received CS exposure for 8 weeks and intranasal instillation of LPS on weeks 1, 3, 5 and 7. PJH (100 and 200 mg/kg) was administrated daily 1 h before CS treatment for the last 4 weeks.

Results

Compared with CS plus LPS-exposed mice, mice in the PJH-treated group showed significantly decreased inflammatory cells count and reduced inflammatory cytokines including interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) levels in broncho-alveolar lavage fluid (BALF) and lung tissue. PJH also suppressed the phosphorylation of nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase1/2 (ERK1/2) caused by CS plus LPS exposure. Furthermore, CS plus LPS induced increases in matrix metallopeptidase (MMP)-7, MMP-9, and transforming growth factor-β (TGF-β) expression and collagen deposition that were inhibited in PJH-treated mice.

Conclusions

This study demonstrates that PJH prevents respiratory inflammation and airway remodeling caused by CS with LPS exposure suggesting potential therapy for the treatment of COPD.
Observations from the emergency management of dialysis patients evacuated from the US Virgin Islands to Puerto Rico following hurricane Irma
Authors: Avilés Mendoza Guillermo J. , Finne Kristen P. , Torre Leon Francisco , Burke Lisandro Montalvo , Cabrera-Marquez Jessica , Mercado Casillas Ana M. , Malave Grasiela , Brown Christopher , Kelman Jeffrey , Kopp Jeffrey B.
Published: November 2021

Two category 5 hurricanes, Irma and Maria, arrived in the Caribbean in September 2017 in rapid succession. On September 6, Irma devastated the islands of St. Thomas and St. John, in the Virgin Islands of the United States (USVI). Most medical infrastructure was damaged, including hemodialysis facilities, paralyzing dialysis operations. After Irma’s landfall, Puerto Rico served as a safehaven for thousands of displaced and repatriated persons from the impacted islands. These included a cohort of 129 hemodialysis patients evacuated from St. Thomas, USVI to San Juan, Puerto Rico from September 9−11, 2017. The hemodialysis patients arrived first at hotels in San Juan and were then transferred to a Special Needs Shelter, run by the Commonwealth of Puerto Rico and located in the Puerto Rico Convention Center. With the imminent arrival of Hurricane Maria, most patients were evacuated on September 19 to a special needs shelter on the campus of the Florida International University, in Miami, Florida. While in San Juan, hemodialysis treatments were provided by local nephrologists working with local hemodialysis centers. Here, we describe the challenges and the emergency management actions taken to ensure continuity of care, including providing dialysis, general medical care, shelter, food and transportation for USVI dialysis patients during their stay in San Juan, Puerto Rico. We describe here the experiences of federal and host state/territorial officials in the special needs shelter, in the context of the state/territorial and federal response to disasters, in order to provide ideas about challenges, solutions, and approaches to coordinating care for dialysis patients evacuated from a disaster.
Functional apoptosis profiling identifies MCL-1 and BCL-xL as prognostic markers and therapeutic targets in advanced thymomas and thymic carcinomas
Authors: Müller Denise , Mazzeo Paolo , Koch Raphael , Bösherz Mark-Sebastian , Welter Stefan , von Hammerstein-Equord Alexander , Hinterthaner Marc , Cordes Lucia , Belharazem Djeda , Marx Alexander , Ströbel Philipp , Küffer Stefan
Published: November 2021

Background

Multi-omics studies have shown a high and lack of common driver mutations in most thymomas (TH) and thymic carcinomas (TC) that hamper the development of novel treatment approaches. However, deregulation of apoptosis has been proposed as a common hallmark of TH and TC. BH3 profiling can be utilized to study the readiness of living cancer cells to undergo apoptosis and their dependency on pro-survival BCL-2 family proteins.

Methods

We screened a cohort of 62 TH and TC patient samples for expression of BCL-2 family proteins and used the TC cell line 1889c and native TH for dynamic BH3 profiling and treatment with BH3 mimetics.

Results

Immunohistochemical overexpression of MCL-1 and BCL-xL was a strong prognostic marker of TH and TC, and BH3 profiling indicated a strong dependency on MCL-1 and BCL-xL in TH. Single inhibition of MCL-1 resulted in increased binding of BIM to BCL-xL as an escape mechanism that the combined inhibition of both factors could overcome. Indeed, the inhibition of MCL-1 and BCL-xL in combination induced apoptosis in a caspase-dependent manner in untreated and MCL-1-resistant 1889c cells.

Conclusion

TH and TC are exquisitely dependent on the pro-survival factors MCL-1 and BCL-xL, making them ideal candidates for co-inhibition by BH3 mimetics. Since TH show a heterogeneous dependency on BCL-2 family proteins, upfront BH3 profiling could select patients and tailor the optimal therapy with the least possible toxicity.
COVID-19 and risk of subsequent life-threatening secondary infections: a matched cohort study in UK Biobank
Authors: Hou Can , Hu Yihan , Yang Huazhen , Chen Wenwen , Zeng Yu , Ying Zhiye , Hu Yao , Sun Yajing , Qu Yuanyuan , Gottfreðsson Magnús , Valdimarsdóttir Unnur A. , Song Huan
Published: November 2021

Background

With the increasing number of people infected with and recovered from coronavirus disease 2019 (COVID-19), the extent of major health consequences of COVID-19 is unclear, including risks of severe secondary infections.

Methods

Based on 445,845 UK Biobank participants registered in England, we conducted a matched cohort study where 5151 individuals with a positive test result or hospitalized with a diagnosis of COVID-19 were included in the exposed group. We then randomly selected up to 10 matched individuals without COVID-19 diagnosis for each exposed individual (n = 51,402). The life-threatening secondary infections were defined as diagnoses of severe secondary infections with high mortality rates (i.e., sepsis, endocarditis, and central nervous system infections) from the UK Biobank inpatient hospital data, or deaths from these infections from mortality data. The follow-up period was limited to 3 months after the initial COVID-19 diagnosis. Using a similar study design, we additionally constructed a matched cohort where exposed individuals were diagnosed with seasonal influenza from either inpatient hospital or primary care data between 2010 and 2019 (6169 exposed and 61,555 unexposed individuals). After controlling for multiple confounders, Cox models were used to estimate hazard ratios (HRs) of life-threatening secondary infections after COVID-19 or seasonal influenza.

Results

In the matched cohort for COVID-19, 50.22% of participants were male, and the median age at the index date was 66 years. During a median follow-up of 12.71 weeks, the incidence rate of life-threatening secondary infections was 2.23 (123/55.15) and 0.25 (151/600.55) per 1000 person-weeks for all patients with COVID-19 and their matched individuals, respectively, which corresponded to a fully adjusted HR of 8.19 (95% confidence interval [CI] 6.33–10.59). The corresponding HR of life-threatening secondary infections among all patients with seasonal influenza diagnosis was 4.50, 95% CI 3.34–6.08 (p for difference < 0.01). Also, elevated HRs were observed among hospitalized individuals for life-threatening secondary infections following hospital discharge, both in the COVID-19 (HR = 6.28 [95% CI 4.05–9.75]) and seasonal influenza (6.01 [95% CI 3.53–10.26], p for difference = 0.902) cohorts.

Conclusion

COVID-19 patients have increased subsequent risks of life-threatening secondary infections, to an equal extent or beyond risk elevations observed for patients with seasonal influenza.
Engineered microbial consortia: strategies and applications
Authors: Duncker Katherine E. , Holmes Zachary A. , You Lingchong
Published: November 2021

Many applications of microbial synthetic biology, such as metabolic engineering and biocomputing, are increasing in design complexity. Implementing complex tasks in single populations can be a challenge because large genetic circuits can be burdensome and difficult to optimize. To overcome these limitations, microbial consortia can be engineered to distribute complex tasks among multiple populations. Recent studies have made substantial progress in programming microbial consortia for both basic understanding and potential applications. Microbial consortia have been designed through diverse strategies, including programming mutualistic interactions, using programmed population control to prevent overgrowth of individual populations, and spatial segregation to reduce competition. Here, we highlight the role of microbial consortia in the advances of metabolic engineering, biofilm production for engineered living materials, biocomputing, and biosensing. Additionally, we discuss the challenges for future research in microbial consortia.
The possible role of SRMS in colorectal cancer by bioinformatics analysis
Authors: Zhang Jie , Liu Weidong , Feng Sisi , Zhong Baiyun
Published: November 2021

Background

Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (SRMS) is a non-receptor tyrosine kinase that has been found to be overexpressed in various tumors. However, the role of SRMS in colorectal cancer (CRC) has not been well established.

Methods

We evaluated the expression levels of SRMS in CRC using GEPIA, Oncomine, and HPA datasets. Survival information and gene expression data of CRC were obtained from The Cancer Genome Atlas (TCGA). Then, the association between SRMS and clinicopathological features was analyzed using UALCAN dataset. LinkedOmics was used to determine co-expression and functional networks associated with SRMS. Besides, we used TISIDB to assess the correlation between SRMS and immune signatures, including tumor-infiltrating immune cells and immunomodulators. Lastly, protein-protein interaction network (PPI) was established and the function enrichment analysis of the SRMS-associated immunomodulators and immune cell marker genes were performed using the STRING portal.

Results

Compared to normal colorectal tissues, SRMS was found to be overexpressed in CRC tissues, which was correlated with a poor prognosis. In colon adenocarcinoma (COAD), the expression levels of SRMS are significantly correlated with pathological stages and nodal metastasis status. Functional network analysis suggested that SRMS regulates intermediate filament-based processes, protein autophosphorylation, translational initiation, and elongation signaling through pathways involving ribosomes, proteasomes, oxidative phosphorylation, and DNA replication. In addition, SRMS expression was correlated with infiltrating levels of CD4+ T cells, CD56dim, MEM B, Neutrophils, Th2, Th17, and Act DC. The gene ontology (GO) analysis of SRMS-associated immunomodulators and immune cell marker genes showed that they were mainly enriched in the immune microenvironment molecule-related signals. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of these genes indicated that they are involved in multiple cancer-related pathways.

Conclusions

SRMS is a promising prognostic biomarker and potential therapeutic target for CRC patients. In particular, SRMS regulates CRC progression by modulating cytokine-cytokine receptor interaction, chemokines, IL-17, and intestinal immune networks for IgA production signaling pathways among others. However, more studies are needed to validate these findings.
Knowledge and perceptions of preconception care among health workers and women of reproductive age in Mzuzu City, Malawi: a cross-sectional study
Authors: Munthali Mtondera , Chiumia Isabel Kazanga , Mandiwa Chrispin , Mwale Saul
Published: November 2021

Background

Preconception care is one of the preventive strategies in maternal and new-born health as recommended by WHO. However, in sub-Saharan Africa there is poor preconception care practices. This study examined knowledge and perceptions of preconception care among health workers and women of reproductive age group in Mzuzu City, Malawi.

Methods

A descriptive cross-sectional study was conducted using a mixed methods approach. Selection of respondents was done through a multistage and purposive sampling techniques respectively. A total of 253 women of reproductive age from nine townships of Mzuzu City responded to the questionnaire and 20 health workers were interviewed.

Results

A total of 136 (54%) respondents had heard of preconception care. About 57.7% (n = 146) demonstrated a good level of knowledge of preconception care while 42.3% (n = 107) had poor knowledge. About 72% (n = 105) of those with good of knowledge of preconception care, lacked awareness on possibilities of talking to a health care provider on intentions of getting pregnant. About 74.7% (n = 189) of women had a positive perception towards preconception care. Knowledge of preconception care was a good predictor of positive perception (AOR = 2.5; 95% CI 1.2–5.0), however its predictability was influenced by the academic level attained. Those with secondary (AOR = 10.2; 95% CI 3.2–26.2) and tertiary (AOR = 2.3; 95% CI 1.1–4.9) were more likely to have good knowledge of preconception care than those with primary school education level. About 95% (n = 19) of health workers lacked details about preconception care but they admitted their role in preconception care.

Conclusion

Preconception care practice among health workers and women of reproductive age in Mzuzu City was low. However there was positive perception towards preconception care in both parties. There is an opportunity in existing platforms for implementation of interventions targeting identified predictors for increased knowledge and uptake of preconception care.
Omitting surgery in esophageal cancer patients with complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis
Authors: Park Jaehyeon , Yea Ji Woon , Oh Se An , Park Jae Won
Published: November 2021

Background

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is a standard treatment modality for locally-advanced esophageal cancer. However, patients who achieve clinical complete response (cCR) after nCRT have been reported to have better prognosis. Further, the role of surgery in these patients is controversial. Thus, this meta-analysis aimed to evaluate whether surgery is still useful in patients with cCR after nCRT.

Methods

We systematically reviewed the MEDLINE, PubMed, Embase, Cochrane library, and Scopus databases for studies on surgical efficacy in complete responders after concurrent chemoradiotherapy for esophageal cancer. The publication date was set to January 1, 2010–January 31, 2020. The hazard ratio (HR) and risk ratio were used to compare the 2-year overall survival (OS), disease-free survival (DFS), incidence of locoregional failure, distant metastasis, and treatment mortality between the nCRT and nCRT plus surgery groups.

Results

Six articles involving 609 patients were included. There was a significant benefit of nCRT for OS (HR = 0.80, 95% confidence interval [CI] 0.64–0.99, p = 0.04), but not for DFS (HR = 1.55, 95% CI 0.35–6.86, p = 0.56). The nCRT group tended to have lower mortality than the nCRT plus surgery group (risk ratio = 0.15, 95% CI 0.02–1.18, p = 0.07).

Conclusion

Omitting surgery provides better OS in complete responders after nCRT. Adding surgery could increase the morbidity and mortality and decrease the quality of life. Thus, nCRT alone could be a feasible approach for patients with cCR.
NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome
Authors: Kurosaki Tatsuaki , Sakano Hitomi , Pröschel Christoph , Wheeler Jason , Hewko Alexander , Maquat Lynne E.
Published: November 2021

Background

Fragile X syndrome (FXS) is an intellectual disability attributable to loss of fragile X protein (FMRP). We previously demonstrated that FMRP binds mRNAs targeted for nonsense-mediated mRNA decay (NMD) and that FMRP loss results in hyperactivated NMD and inhibition of neuronal differentiation in human stem cells.

Results

We show here that NMD is hyperactivated during the development of the cerebral cortex, hippocampus, and cerebellum in theFmr1-knockout (KO) mouse during embryonic and early postnatal periods. Our findings demonstrate that NMD regulates many neuronal mRNAs that are important for mouse brain development.

Conclusions

We reveal the abnormal regulation of these mRNAs in theFmr1-KO mouse, a model of FXS, and highlight the importance of early intervention.
A community approach of pathogens and their arthropod vectors (ticks and fleas) in dogs of African Sub-Sahara
Authors: Heylen Dieter , Day Michael , Schunack Bettina , Fourie Josephus , Labuschange Michel , Johnson Sherry , Githigia Samuel Maina , Akande Foluke Adedayo , Nzalawahe Jahashi Saidi , Tayebwa Dickson Stuart , Aschenborn Ortwin , Marcondes Mary , Madder Maxime
Published: November 2021

Background

Arthropod-borne pathogens and their vectors are present throughout Africa. They have been well-studied in livestock of sub-Saharan Africa, but poorly in companion animals. Given the socio-economic importance of companion animals, the African Small Companion Animal Network (AFSCAN), as part of the WSAVA Foundation, initiated a standardized multi-country surveillance study.

Methods

Macro-geographic variation in ectoparasite (ticks and fleas) and pathogen communities in dogs was assessed through molecular screening of approximately 100 infested dogs in each of six countries (Ghana, Kenya, Nigeria, Tanzania, Uganda and Namibia), both in rural and urban settings. The most important intrinsic and extrinsic risk factors within the subpopulation of infested dogs were evaluated.

Results

Despite the large macro-geographic variation in the dogs screened, there was no consistent difference between East and West Africa in terms of the diversity and numbers of ticks. The highest and lowest numbers of ticks were found in Nigeria and Namibia, respectively. Most often, there was a higher diversity of ticks in rural habitats than in urban habitats, although the highest diversity was observed in an urban Uganda setting. With the exception of Namibia, more fleas were collected in rural areas. We identified tick species (including Haemaphysalis spinulosa) as well as zoonotic pathogens (Coxiella burnetti, Trypanosoma spp.) that are not classically associated with companion animals. Rhipicephalus sanguineus was the most abundant tick, with a preference for urban areas. Exophilic ticks, such as Haemaphysalis spp., were more often found in rural areas. Several multi-host ticks occurred in urban areas. For R. sanguineus, housing conditions and additional pets were relevant factors in terms of infestation, while for a rural tick species (Haemaphysalis elliptica), free-roaming dogs were more often infested. Tick occurrence was associated to the use of endoparasiticide, but not to the use of ectoparasiticide. The most prevalent tick-borne pathogen was Hepatozoon canis followed by Ehrlichia canis. High levels of co-parasitism were observed in all countries and habitats.

Conclusions

As dogs share a common environment with people, they have the potential to extend the network of pathogen transmission to humans. Our study will help epidemiologists to provide recommendations for surveillance and prevention of pathogens in dogs and humans.

Graphical abstract
Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling
Authors: Zhang Lixia , Kirkwood Cameron L. , Sohn Jiho , Lau Ashley , Bayers-Thering Mary , Bali Supinder Kour , Rachala Sridhar , Marzo John M. , Anders Mark J. , Beier Frank , Kirkwood Keith L.
Published: November 2021

Background

Osteoarthritis (OA) subsequent to acute joint injury accounts for a significant proportion of all arthropathies. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells classically known for potent immune-suppressive activity; however, MDSCs can also differentiate into osteoclasts. In addition, this population is known to be expanded during metabolic disease. The objective of this study was to determine the role of MDSCs in the context of OA pathophysiology.

Methods

In this study, we examined the differentiation and functional capacity of MDSCs to become osteoclasts in vitro and in vivo using mouse models of OA and in MDSC quantitation in humans with OA pathology relative to obesity status.

Results

We observed that MDSCs are expanded in mice and humans during obesity. MDSCs were expanded in peripheral blood of OA subjects relative to body mass index and in mice fed a high-fat diet (HFD) compared to mice fed a low-fat diet (LFD). In mice, monocytic MDSC (M-MDSC) was expanded in diet-induced obesity (DIO) with a further expansion after destabilization of the medial meniscus (DMM) surgery to induce post-traumatic OA (PTOA) (compared to sham-operated controls). M-MDSCs from DIO mice had a greater capacity to form osteoclasts in culture with increased subchondral bone osteoclast number. In humans, we observed an expansion of M-MDSCs in peripheral blood and synovial fluid of obese subjects compared to lean subjects with OA.

Conclusion

These data suggest that MDSCs are reprogrammed in metabolic disease, with the potential to contribute towards OA progression and severity.
Insights from patients screened but not randomised in the HYPERION trial
Authors: Lascarrou J. B. , Muller Gregoire , Quenot Jean-Pierre , Massart Nicolas , Landais Mickael , Asfar Pierre , Frat Jean-Pierre , Chakarian Jean-Charles , Sirodot Michel , Francois Bruno , Grillet Guillaume , Vimeux Sylvie , Delahaye Arnaud , Legriel Stéphane , Thevenin Didier , Reignier Jean , Colin Gwenhael ,   for the AfterROSC Network
Published: November 2021

Background

Few data are available about outcomes of patients screened for, but not enrolled in, randomised clinical trials.

Methods

We retrospectively reviewed patients who had non-inclusion criteria for the HYPERION trial comparing 33 °C to 37 °C in patients comatose after cardiac arrest in non-shockable rhythm, due to any cause. A good neurological outcome was defined as a day-90 Cerebral Performance Category score of 1 or 2.

Results

Of the 1144 patients with non-inclusion criteria, 1130 had day-90 information and, among these, 158 (14%) had good functional outcomes, compared to 7.9% overall in the HYPERION trial (10.2% with and 5.7% without hypothermia). Considerable centre-to-centre variability was found in the proportion of non-included patients who received hypothermia (0% to 83.8%) and who had good day-90 functional outcomes (0% to 31.3%). The proportion of patients with a good day-90 functional outcome was significantly higher with than without hypothermia (18.5% vs. 11.9%, P = 0.003).

Conclusion

Our finding of better functional outcomes without than with inclusion in the HYPERION trial, despite most non-inclusion criteria being of adverse prognostic significance (e.g., long no-flow and low-flow times and haemodynamic instability), raises important questions about the choice of patient selection criteria and the applicability of trial results to everyday practice. At present, reserving hypothermia for patients without predictors of poor prognosis seems open to criticism.
Spectral line extraction based on ant-colony algorithm
Authors: Cheng Yusheng , Ma Kai , Li Haitao , Sun Shilin , Wang Yichuan
Published: November 2021

A spectral-line-extraction algorithm based on the ant-colony algorithm is proposed to address the difficulty of extracting spectral lines in low signal-to-noise ratio conditions, and the problem that results from the optimal path algorithm falls into local optimization. The algorithm applies the ant-colony path-optimization strategy to detect a spectral line and constructs a corresponding mathematical model using the grid method. A new cost function is proposed to replace path length as the optimization standard in the conventional ant-colony algorithm. At the same time, the roulette rule is used to determine the direction of the next step. This algorithm improves the traditional heuristic function, increases the attraction of the target spectral line to the route search, and improves the convergence rate. Sea-trial data show that the algorithm performs better in extracting spectral lines with a low signal-to-noise ratio than the optimal path algorithm.
Existence of solutions for a class of nonlinear boundary value problems on the hexasilinane graph
Authors: Turab Ali , Mitrović Zoran D. , Savić Ana
Published: November 2021

Chemical graph theory is a field of mathematics that studies ramifications of chemical network interactions. Using the concept of star graphs, several investigators have looked into the solutions to certain boundary value problems. Their choice to utilize star graphs was based on including a common point connected to other nodes. Our aim is to expand the range of the method by incorporating the graph of hexasilinane compound, which has a chemical formula $\mathrm{H}_{12} \mathrm{Si}_{6}$

H
12

Si
6

. In this paper, we examine the existence of solutions to fractional boundary value problems on such graphs, where the fractional derivative is in the Caputo sense. Finally, we include an example to support our significant findings.
The rights (and responsibilities) of the public to advance health through research
Authors: Jotterand Fabrice , Spellecy Ryan , Shaker Reza
Published: November 2021

In this commentary we assert that the rights and responsibilities of the community at large as an important key stakeholder in the effort of advancing health through research and discovery have not been carefully examined and delineated. The time has come to investigate the nature of the rights and responsibilities of the public in advancing health through research and discovery. We argue that the public has the right not merely to participate in research and have their rights protected, but that they have a right to engage in and take ownership in research.
Electric vehicle charging and end-user motivation for flexibility: a case study from Norway
Authors: Henriksen Ida Marie , Throndsen William , Ryghaug Marianne , Skjølsvold Tomas Moe
Published: November 2021

Background

Norway is currently in the process of replacing internal combustion engine (ICE) vehicles with electric vehicles (EVs). A steadily increasing number of EVs being charged in the evening when the demand peaks are already high has added to the strain on local electricity grids. Smart charging is proposed as a solution to peak-load challenges of this kind, as it can delay charging until evenings and nights when demand peaks are generally low. However, current knowledge of the preferences and motivations of EV owners regarding the installation and use of smart chargers is lacking. Accordingly, the study aims to contribute an improved understanding in this respect.

Methods

The authors conducted a qualitative study based on semi-structured interviews, in which they gained information on householder’s experiences following their participation in a pilot project to test smart charging of EVs. The interviews explored the interviewees’ motivation for participating in the project, their experiences of using and charging EVs, and their thoughts on flexibility in the timing of EV charging. Interviews were recorded and transcribed verbatim, after which a domestication theory approach was employed to perform an in-depth analysis of the interview data.

Results

The analysis of the interviews revealed that the study participants had four motivations for participating in the smart charging demonstration project and engaging in the further use of smart charging: (1) the fire-safety aspect and speed of charging devices for EVs was better than charging from a socket; (2) they derived a broader interest in and more joy from using smart home technology; (3) attractive practical and economic benefits; and (4) the flexibility offered by smart charging had the potential to have a positive impact on physical comfort.

Conclusions

The study revealed key domestication processes unfolding in the Norwegian energy transition with the increasing numbers of EVs and the corresponding grid peaks. The findings clearly indicate that users’ motivations go much further than simple economic rationalization, which should be of interest to policymakers, smart home developers, and all others that work with end-user flexibility in the grid.
Vascular pythiosis caused by Pythium aphanidermatum: the first case report in Asia
Authors: Thongsuk Pannaporn , Plongla Rongpong , Thammahong Arsa , Tiewsurin Jaruwan , Worasilchai Navaporn , Chindamporn Ariya , Suankratay Chusana
Published: November 2021

Background

Pythium, soil-borne plant pathogens, are in the class Oomycetes. They are not true fungi, but are related to diatom and algae. There are two human pathogens includingP. insidiosumandP. aphanidermatum. To date, only one case of pythiosis caused byP. aphanidermatumhas been reported. We present herein the first case ofP. aphanidermatumvascular pythiosis in Asia.

Case presentation

A 47-year-old Thai woman, living in North Thailand, with ß thalassemia/hemoglobin E presented with acute recurrent arterial insufficiency of both legs. Emergent embolectomy with clot removal was performed. The pathology of the clot exhibited noncaseous granulomatous inflammation with many fungal hyphal elements. PCR identifiedP. aphanidermatumwith 100% identity. Final diagnosis is vascular pythiosis. Unfortunately, the patient eventually expired after treatment with itraconazole, terbinafine, azithromycin, and doxycycline.

Conclusions

To date, only one case of pythiosis caused byP. aphanidermatumhas been reported. We present herein the first case ofP. aphanidermatumvascular pythiosis in Asia.
In vitro growth inhibitory activity of Medicines for Malaria Venture pathogen box compounds against Leishmania aethiopica
Authors: Tadele Markos , Abay Solomon M. , Asaga Peter , Makonnen Eyasu , Hailu Asrat
Published: November 2021

Introduction

Leishmania aethiopica (L. aethiopica) is responsible for different forms of cutaneous leishmaniasis (CL) in Ethiopia. Treatment heavily depends on limited drugs, together with drawbacks like toxicity and microbial resistance. The current research aimed to investigate in vitro growth inhibitory activity of Medicines for Malaria Ventures - Pathogen Box (MMV - PB) compounds against L. aethiopica clinical isolate.

Methodology

Four hundred MMV – PB compounds were screened against L. aethiopica using resazurin based colourimetric assay. Compounds with > 70% inhibition were further tested using macrophage based intracellular amastigote assay. Cytotoxic and hemolytic activity of candidate hits were assessed on THP1- cells and sheep red blood cells (RBCs), respectively. In vitro drug interaction study was also conducted for the most potent hit using the combination index method.

Results

At the test concentration of 1 μM, twenty-three compounds showed > 50% inhibition of promastigotes parasite growth, of which 11 compounds showed > 70% inhibition. The 50% growth inhibition (IC50) of the 11 compounds was ranged from 0.024 to 0.483 μM in anti-promastigote assay and from 0.064 to 0.899 μM in intracellular amastigote assay. Candidate compounds demonstrated good safety on sheep RBCs and THP-1 cell lines. MMV688415 demonstrated a slight hemolytic activity on sheep RBC (5.3% at 25 μM) and THP-1 cell line (CC20 = 25 μM) while MMV690102 inhibited half of THP-1 cells at 36.5 μM (selectivity index = 478). No synergistic activity was observed from the combinations of MMV690102 and amphotericin B (CI > 1), and MMV690102 and Pentamidine (CI > 1) at lower and higher combination points.

Conclusion

The present study identified a panel of compounds that can be used as a novel starting point for lead optimization. MMV690102 appears to be the most potent inhibitor against L. aethiopica promastigotes and amastigotes. Future works should investigate the antileishmanial mechanism of action and in vivo antileishmanial activities of identified hits.
A billion-dollar donation: estimating the cost of researchers’ time spent on peer review
Authors: Aczel Balazs , Szaszi Barnabas , Holcombe Alex O.
Published: November 2021

Background

The amount and value of researchers’ peer review work is critical for academia and journal publishing. However, this labor is under-recognized, its magnitude is unknown, and alternative ways of organizing peer review labor are rarely considered.

Methods

Using publicly available data, we provide an estimate of researchers’ time and the salary-based contribution to the journal peer review system.

Results

We found that the total time reviewers globally worked on peer reviews was over 100 million hours in 2020, equivalent to over 15 thousand years. The estimated monetary value of the time US-based reviewers spent on reviews was over 1.5 billion USD in 2020. For China-based reviewers, the estimate is over 600 million USD, and for UK-based, close to 400 million USD.

Conclusions

By design, our results are very likely to be under-estimates as they reflect only a portion of the total number of journals worldwide. The numbers highlight the enormous amount of work and time that researchers provide to the publication system, and the importance of considering alternative ways of structuring, and paying for, peer review. We foster this process by discussing some alternative models that aim to boost the benefits of peer review, thus improving its cost-benefit ratio.
Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging
Authors: Favaretto C. , Talip Z. , Borgna F. , Grundler P. V. , Dellepiane G. , Sommerhalder A. , Zhang H. , Schibli R. , Braccini S. , Müller C. , van der Meulen N. P.
Published: November 2021

Background

Terbium-155 [T1/2 = 5.32 d, Eγ = 87 keV (32%) 105 keV (25%)] is an interesting radionuclide suitable for single photon emission computed tomography (SPECT) imaging with potential application in the diagnosis of oncological disease. It shows similar decay characteristics to the clinically established indium-111 and would be a useful substitute for the diagnosis and prospective dosimetry with biomolecules that are afterwards labeled with therapeutic radiolanthanides and pseudo-radiolanthanides, such as lutetium-177 and yttrium-90. Moreover, terbium-155 could form part of the perfect “matched pair” with the therapeutic radionuclide terbium-161, making the concept of true radiotheragnostics a reality. The aim of this study was the investigation of the production of terbium-155 via the155Gd(p,n)155Tb and156Gd(p,2n)155Tb nuclear reactions and its subsequent purification, in order to obtain a final product in quantity and quality sufficient for preclinical application. The156Gd(p,2n)155Tb nuclear reaction was performed with 72 MeV protons (degraded to ~ 23 MeV), while the155Gd(p,n)155Tb reaction was degraded further to ~ 10 MeV, as well as performed at an 18 MeV medical cyclotron, to demonstrate its feasibility of production.

Result

The156Gd(p,2n)155Tb nuclear reaction demonstrated higher production yields of up to 1.7 GBq, however, lower radionuclidic purity when compared to the final product (~ 200 MBq) of the155Gd(p,n)155Tb nuclear reaction. In particular, other radioisotopes of terbium were produced as side products. The radiochemical purification of terbium-155 from the target material was developed to provide up to 1.0 GBq product in a small volume (~ 1 mL 0.05 M HCl), suitable for radiolabeling purposes. The high chemical purity of terbium-155 was proven by radiolabeling experiments at molar activities up to 100 MBq/nmol. SPECT/CT experiments were performed in tumor-bearing mice using [155Tb]Tb-DOTATOC.

Conclusion

This study demonstrated two possible production routes for high activities of terbium-155 using a cyclotron, indicating that the radionuclide is more accessible than the exclusive mass-separated method previously demonstrated. The developed radiochemical purification of terbium-155 from the target material yielded [155Tb]TbCl3in high chemical purity. As a result, initial cell uptake investigations, as well as SPECT/CT in vivo studies with [155Tb]Tb-DOTATOC, were successfully performed, indicating that the chemical separation produced a product with suitable quality for preclinical studies.