bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacteriophages of Mycobacterium tuberculosis, their diversity, and potential therapeutic uses: a review
Authors: Zeynali kelishomi Fatemeh , Khanjani Susan , Fardsanei Fatemeh , Saghi Sarabi Hediyeh , Nikkhahi Farhad , Dehghani Behzad
Published: December 2022

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) is a highly infectious disease and worldwide health problem. Based on the WHO TB report, 9 million active TB cases are emerging, leading to 2 million deaths each year. The recent emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains emphasizes the necessity to improve novel therapeutic plans. Among the various developing antibacterial approaches, phage therapy is thought to be a precise hopeful resolution. Mycobacteriophages are viruses that infect bacteria such as Mycobacterium spp., containing the M. tuberculosis complex. Phages and phage-derived proteins can act as promising antimicrobial agents. Also, phage cocktails can broaden the spectrum of lysis activity against bacteria. Recent researches have also shown the effective combination of antibiotics and phages to defeat the infective bacteria. There are limitations and concerns about phage therapy. For example, human immune response to phage therapy, transferring antibiotic resistance genes, emerging resistance to phages, and safety issues. So, in the present study, we introduced mycobacteriophages, their use as therapeutic agents, and their advantages and limitations as therapeutic applications.
Pre-hospital and intrahospital workflow optimization for patients with suspected ischemic stroke due to large vessel occlusion - findings from a tertiary care facility
Authors: Krebs Stefan , Ferrari Julia , Schürer Alice , Chiari Astrid , Neumann Christian , Lang Wilfried , Sykora Marek
Published: December 2022

Background

The efficacy of recanalization treatment in patients with ischemic stroke due to large vessel occlusion (LVO) is highly time dependent. We aimed to investigate the effects of an optimization of prehospital and intrahospital pathways on time metrics and efficacy of endovascular treatment in ischemic stroke due to LVO.

Methods

Patients treated with mechanical thrombectomy (MT) at the Hospital of St. John of God Vienna, Austria, between 2013 and 2020 were extracted from the Austrian Stroke Unit Registry. Study endpoints including time metrics, early neurological improvement and functional outcome measured by modified Rankin Scale (mRS) at 3 months were compared before and after optimization of prehospital and intrahospital pathways.

Results

Two hundred ninety-nine patients were treated with MT during the study period, 94 before and 205 after the workflow optimization. Workflow optimization was significantly associated with time metrics improvement (door to groin puncture time 45 versus 31 min; p < 0.001), rates of neurological improvement (NIHSS ≥ 8: 30 (35%) vs. 70 (47%), p = 0.04) and radiological outcome (TICI ≥ 2b: 71 (75%) versus 153 (87%); p = 0.013). Functional outcome (mRS 0–2: 17 (18%) versus 57 (28%); p = 0.067) and mortality (34 (37%) versus 54 (32%); p = 0.450) at 3 months showed a non-significant trend in the later time period group.

Conclusion

The implementation of workflow optimization was associated a significant reduction of intrahospital time delays and improvement of neurological and radiological outcomes.
Dads in Distress: symptoms of depression and traumatic stress in fathers following poor fetal, neonatal, and maternal outcomes
Authors: Kothari A. , Bruxner G. , Dulhunty J. M. , Ballard E. , Callaway L.
Published: December 2022

Background

This study aims to explore the prevalence of symptoms of depression and traumatic stress in fathers in the setting of poor fetal, neonatal, and maternal outcomes.

Methods

A prospective mixed-methods study was conducted at an outer metropolitan public teaching hospital in Brisbane, Australia, with quantitative results presented here. Subjects included 28 fathers whose partners had experienced pregnancy or childbirth complicated by a significant congenital abnormality or aneuploidy, termination of pregnancy, fetal death in-utero, stillbirth, admission to the neonatal intensive care unit or special care nursery or significant maternal morbidity, such as a postpartum haemorrhage or an emergency postpartum hysterectomy. These experiences were classified into two groups: anticipatory (time to prepare) and sudden (no warning). The fathers were screened using the Edinburgh Postnatal Depression Scale (EPDS) and the Impact of Events Scale-Revised (IES-R) to assess subjective distress at 2-3 weeks (timepoint 1) and 3-4 months (timepoint 2) after the event.

Results

Data for both the EPDS and IES-R scales was available for 26 fathers (92.9%) at timepoint 1 and for 15 fathers (53.6%) at timepoint 2. High overall EPDS scores (≥10) were noted in 16/27 (59.3%) fathers at timepoint 1 and 6/15 fathers (40.0%) at timepoint 2. High overall IES-R scores ≥33 were noted in 12/26 (46.2%) fathers at timepoint 1 and 4/15 fathers (26.7%) at timepoint 2. A higher percentage of fathers who experienced anticipatory events had EPDS and IES-R score above these cut-offs at timepoint 1 (8/13 or 61.5%) compared to those experiencing sudden events (8/14 or 57.1%), however, percentages were similar between groups at time point 2 (2/7 or 28.6%% and 4/8 or 50.0%, respectively). More fathers who experienced anticipatory events had IES-R scores ≥33 at timepoint 1 (7/13 or 53.8%) compared to those experiencing sudden events (5/14 or 38.0%).

Conclusion

Our study indicates high rates of distress in fathers exposed to poor fetal, neonatal, and maternal outcomes, which can persist for months after the event. Increased support for fathers in this setting may be required to prevent poor mental health. Further research on the long-term effects of these adverse events is warranted.
Unilateral surgery for pediatric sensory exotropia: clinical characteristics and surgical results
Authors: Shafik Heba M. , Eldesouky Mohamed Ashraf , Elbakary Molham A. , Elbedewy Hazem A.
Published: December 2022

Background

To delineate the clinical characteristics and surgical outcomes of large angle sensory exotropia in pediatric patients.

Methods

The medical records of 54 large angle exotropia ≥40 PD patients aged from 1 to 18 years who were operated on between 2018 and 2021 and were followed up for 1 year were reviewed and contacted. Clinical characteristics and surgical outcomes were analyzed retrospectively. Patients were divided into two groups, group S patients had supermaximum recession resection and group E had augmented recession by lateral rectus muscle elongation with an autograft from the resected medial rectus muscle in the same eye. The clinical characteristics and results of both groups were compared.

Results

The mean age of the studied patients with sensory exodeviation at the time of surgery was 8.3 ± 4.2 years. Mean of the duration of exotropia was 6.9 ± 2.2 years, and the mean of postoperative follow-up was 14.3 ± 4.2 months. Surgical success was achieved in 73.07% of group S and 82.14% of group E. Recurrence was more common with anterior segment pathology. Larger post-operative distant angles were strongly related to poorer visual acuities P = 0.001 and not related to the age of onset or the duration. Narrowing of the palpebral fissure improved in both groups at the last follow up P = 0.336. The limitation of abduction in both groups improved in the last follow up P = 0.145.

Conclusion

The outcome of monocular surgery for sensory exotropia in children is satisfactory with no significant differences in results between lateral rectus muscle tendon autograft elongation technique and supermaximum recession resection. Recurrence is more common with anterior segment pathology. Larger post-operative distant angle of deviation is strongly related to poorer visual acuity.

Clinical trial registration

This study was retrospectively registered at clinicaltrials.gov (ID: NCT04286945) on 25-2-2020.
Behavioral responses for facemask use messages to prevent COVID-19 among residents of Bahir Dar City, Ethiopia: an application of extended parallel process model
Authors: Eseyneh Tenagnework , Wondiye Habtamu , Fentaw Zinabu , Eseyneh Netsanet , Bogale Eyob Ketema , Gutema Hordofa
Published: December 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic causes major morbidity and mortality in the world. Timely behavioral response assessment of the community is important to shape the next effective interventions and risk communication strategies to adopt preventive behavior. Hence, this study aimed to assess behavioral responses for facemask-use messages to prevent COVID-19 and its predictors among residents of Bahir Dar City, Ethiopia, 2021 by using the Extended Parallel Process Model. 

Methods

A community-based cross-sectional study was conducted with the guide of the Extended Parallel Process Model in Bahir Dar city from March 9 to April 9, 2021. A multistage sampling technique was used, and data was collected through a face-to-face interviewer-administered questionnaire using Epicollect5. Descriptive statistics and Binary logistic regression were computed using SPSS V.25. Variable with P < 0.25 in the bivariable analysis was a candidate for multivariable analysis to control confounding effect. In multivariable analysis, variables with P < 0.05 were considered statistically significant and the result was presented using an adjusted odd ratio (AOR) with a 95% confidence interval (CI).

Results

A total of 616 participants with a response rate of 97.1% were included. Of the total participants, 229(37.2%) were in the danger control response. The behavioral response was affected by Occupational status [AOR (95%CI) 3.53(1.67–7.46)], the number of people living together [AOR (95%CI) 2.62(1.28–5.39)], self-control [AOR (95%CI) 1.14(1.05–1.25)], a friend for the preferred source of information [AOR (95%CI) 5.18(3.22–8.33)] and printed materials for the preferred channel [AOR (95%CI) 2.14(1.35–3.43)].

Conclusion

Above one-third of the participants were in the danger control response. Occupational status, number of people living together, self-control, a friend for the preferred source of information, and printed materials for the preferred channel were independent predictors of resident behavioral response to the use of facemasks. Policymakers should consider students and people who live alone. Message developers should use a friendly person to transmit messages and should prepare printed materials. Activities and strategies should also focus on self-control and perceived efficacy without ignoring the perceived threat.
Clinical and radiologic outcomes of biportal endoscopic lumbar discectomy in obese patients: a retrospective case-control study
Authors: Park Hyun-Jin , Choi Jun-Young , You Ki-Han , Kang Min-Seok , Lee Woo-Myung , Hyun Jin-Tak , Park Sang-Min
Published: December 2022

Background

Obese patients have a higher risk of complications during spinal surgery than non-obese patients. To the best of our knowledge, no studies have examined the differences in clinical and radiological outcomes after biportal endoscopic lumbar discectomy (BELD) between obese and non-obese patients. The study evaluated the association between obesity and outcomes after BELD in patients with lumbar disc herniation.

Methods

This was a retrospective case-control study conducted from March 2017 to March 2021 at two hospitals with 360 patients who underwent BELD after showing no improvement with conservative treatment. Clinical and radiologic outcomes were retrospectively analyzed after BELD in the non-obese (body mass index [BMI] < 30 kg/m2) and obese (BMI ≥ 30 kg/m2) groups. Demographic data and surgery-related factors were compared between the two groups. Clinical outcomes were followed up for 12 months after surgery and analyzed for differences.

Results

A total of 211 patients were enrolled in this study, and through case-control matching, the data of 115 patients (29, obese group; 86, non-obese group) were analyzed. The two groups showed no significant differences in Oswestry Disability Index, European Quality of Life-5 Dimensions (EQ-5D), and visual analog scale scores measured immediately after BELD and 12 months after surgery. After surgery, back pain, radiating leg pain, and EQ-5D scores improved. However, there was no significant difference in improvement, residual herniated disc, hematoma, or recurrence between the groups.

Conclusions

Obese patients who underwent BELD for lumbar disc herniation showed no significant difference in clinical and radiologic outcomes compared with non-obese patients.
Transverse differences between cleft lip and palate and non-cleft palate with skeletal Class III malocclusion using buccolingual inclination: a cone-beam computed tomography retrospective study
Authors: He Jiabei , Jiang Lihua , Song Shaohua , Mo Shuixue
Published: December 2022

Background

The purpose of this study was to evaluate the differences between buccolingual inclination (BI) of maxillary posterior teeth in patients with cleft lip and palate (CLP) and non-cleft palate with skeletal Class III malocclusion. We propose a method of maxillary expansion which is more suitable for patients with CLP.

Methods

For this retrospective study, 40 patients with CLP and 21 patients with skeletal Class III malocclusion were selected. The CLP group was divided into the unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) groups. The BI of the maxillary first premolar (BI4), maxillary second premolar (BI5) and first molar (BI6) were measured using cone-beam computed tomography, and the differences between them were compared and analyzed by Student’s t-test.

Results

There were significant differences between cleft side BI4 and non-cleft side BI4 in the UCLP group, BI5 in the BCLP group, BI4 and BI5 in all CLP groups and the skeletal Class III malocclusion group. BI6 was similar across all three groups.

Conclusions

The premolars of patients with CLP do not exhibit the same regularity as those with Class III malocclusion; this may be related to surgical scarring of the cleft palate. Greater attention should be paid to the correction of BI in the maxillary expansion of patients with CLP.
LiSA: an assisted literature search pipeline for detecting serious adverse drug events with deep learning
Authors: Martenot Vincent , Masdeu Valentin , Cupe Jean , Gehin Faustine , Blanchon Margot , Dauriat Julien , Horst Alexander , Renaudin Michael , Girard Philippe , Zucker Jean-Daniel
Published: December 2022

Introduction

Detecting safety signals attributed to a drug in scientific literature is a fundamental issue in pharmacovigilance. The constant increase in the volume of publications requires the automation of this tedious task, in order to find and extract relevant articles from the pack. This task is critical, as serious Adverse Drug Reactions (ADRs) still account for a large number of hospital admissions each year.

Objectives

The aim of this study is to develop an augmented intelligence methodology for automatically identifying relevant publications mentioning an established link between a Drug and a Serious Adverse Event, according to the European Medicines Agency (EMA) definition of seriousness.

Methods

The proposed pipeline, called LiSA (for Literature Search Application), is based on three independent deep learning models supporting a precise detection of safety signals in the biomedical literature. By combining a Bidirectional Encoder Representations from Transformers (BERT) algorithms and a modular architecture, the pipeline achieves a precision of 0.81 and a recall of 0.89 at sentences level in articles extracted from PubMed (either abstract or full-text). We also measured that by using LiSA, a medical reviewer increases by a factor of 2.5 the number of relevant documents it can collect and evaluate compared to a simple keyword search. In the interest of re-usability, emphasis was placed on building a modular pipeline allowing the insertion of other NLP modules to enrich the results provided by the system, and extend it to other use cases. In addition, a lightweight visualization tool was developed to analyze and monitor safety signal results.

Conclusions

Overall, the generic pipeline and the visualization tool proposed in this article allows for efficient and accurate monitoring of serious adverse drug reactions from the literature and can easily be adapted to similar pharmacovigilance use cases. To facilitate reproducibility and benefit other research studies, we also shared a first benchmark dataset for Serious Adverse Drug Events detection.
Exploring the experiences of the team members in the interprofessional socialization process for becoming an interprofessional collaborator
Authors: Keshmiri Fatemeh
Published: December 2022

Background

The current study aimed to explore the team members’ experiences in the socialization process for becoming a collaborator in an interprofessional team.

Method

This qualitative study is conducted using an inductive qualitative content analysis approach. Participants consisted of 32 physicians (n = 16) and nurses (n = 16) who participated by purposeful sampling. Data were collected through in-depth semi-structured interviews and analyzed by Graneheim and Lundman approach.

Results

In the study, “the perceived confrontation between interprofessional professionalism and uni-professionalism in the interprofessional socialization process” is explored as the theme, including two categories: “interprofessional professionalism commitment” as a facilitator and “uni-professional centrism” as a barrier.

Conclusion

A reciprocal dimension in interprofessional socialization was explored. Interprofessional professionalism adherence and team-centered accountability among team members were explored as a facilitator. The uni-professional culture and immature interprofessional collaboration competencies of team members disrupted the interprofessional socialization process.
A comparative study of positive and negative electronic word-of-mouth on the SERVQUAL scale during the COVID-19 epidemic - taking a regional teaching hospital in Taiwan as an example
Authors: Lee Po-Chun , Liang Li-Lin , Huang Min-Hsin , Huang Ching-Yuan
Published: December 2022

Background

In recent years, studies have shown that electronic WOM (eWOM) directly reflects consumers’ post-purchase psychological perception and directly affects repurchase behavior. This information is valued by institutions in various fields. Within the scope of the evaluation of service characteristics, medical service is the least visible and most difficult service attribute to evaluate. Service organizations must have high trust attributes. Therefore, an eWOM review significantly influences people’s decision-making process when choosing a healthcare provider. The purpose of this research is to combine eWOM reviews with the SERVQUAL scale in a comparative study of positive and negative eWOM reviews of a regional teaching hospital in Taiwan.

Methods

This research obtained data from publicly available eWOM reviews on Google Maps of a regional teaching hospital in Taiwan over the past 10 years (from June 24, 2011, to December 31, 2021) using website scraping technology. The semantic content analysis method was used in this study to classify eWOM reviews according to the revised PZB SERVQUAL scale.

Results

Statistical analysis was conducted. During the COVID-19 pandemic, positive reviews showed a downward trend. Among the five determinants of the SERVQUAL of PZB, positive eWOM reviews performed best in “assurance” with a positive review rate of 60.00%, followed by 42.11% for “reliability”. For negative eWOM reviews, “assurance” performed the worst with a positive rate of 72.34%, followed by “responsiveness” at 28.37% and “reliability” at 26.95%.

Conclusion

Since the onset of COVID-19 in 2020, negative eWOM has increased significantly and exceeded the amount of positive eWOM. Regardless of positive and negative reviews, what patients care most about is “assurance” of the professional attitude and skills of medical staff, which urgently needs to be strengthened. In addition, good “reliability” will help to develop positive eWOM. However, “responsiveness” as indicated by poor service waiting time can easily lead to the spread of negative eWOM. Hospital management should focus on these service-oriented qualities.
Malaria transmission in Nepal under climate change: anticipated shifts in extent and season, and comparison with risk definitions for intervention
Authors: Bhattarai Shreejana , Blackburn Jason K. , Ryan Sadie J.
Published: December 2022

Background

Climate and climate change affect the spatial pattern and seasonality of malaria risk. Season lengths and spatial extents of mapped current and future malaria transmission suitability predictions for Nepal were assessed for a combination of malaria vector and parasites:Anopheles stephensiandPlasmodium falciparum(ASPF) andAn. stephensiandPlasmodium vivax(ASPV) and compared with observed estimates of malaria risk in Nepal.

Methods

Thermal bounds of malaria transmission suitability for baseline (1960–1990) and future climate projections (RCP 4.5 and RCP 8.5 in 2030 and 2050) were extracted from global climate models and mapped for Nepal. Season length and spatial extent of suitability between baseline and future climate scenarios for ASPF and ASPV were compared using the Warren’s I metric. Official 2010 DoHS risk districts (DRDs) and 2021 DoHS risk wards (DRWs), and spatiotemporal incidence trend clusters (ITCs) were overlaid on suitability season length and extent maps to assess agreement, and potential mismatches.

Results

Shifts in season length and extent of malaria transmission suitability in Nepal are anticipated under both RCP 4.5 and RCP 8.5 scenarios in 2030 and 2050, compared to baseline climate. The changes are broadly consistent across both future climate scenarios for ASPF and ASPV. There will be emergence of suitability and increasing length of season for both ASPF and ASPV and decreasing length of season for ASPV by 2050. The emergence of suitability will occur in low and no-risk DRDs and outside of high and moderate-risk DRWs, season length increase will occur across all DRD categories, and outside of high and moderate-risk DRWs. The high and moderate risk DRWs of 2021 fall into ITCs with decreasing trend.

Conclusions

The study identified areas of Nepal where malaria transmission suitability will emerge, disappear, increase, and decrease in the future. However, most of these areas are anticipated outside of the government’s current and previously designated high and moderate-risk areas, and thus outside the focus of vector control interventions. Public health officials could use these anticipated changing areas of malaria risk to inform vector control interventions for eliminating malaria from the country, and to prevent malaria resurgence.
Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis
Authors: Nallasamy Palanisamy , Nimmakayala Rama Krishna , Parte Seema , Are Abhirup C. , Batra Surinder K. , Ponnusamy Moorthy P.
Published: December 2022

Cancer divergence has many facets other than being considered a genetic term. It is a tremendous challenge to understand the metastasis and therapy response in cancer biology; however, it postulates the opportunity to explore the possible mechanism in the surrounding tumor environment. Most deadly solid malignancies are distinctly characterized by their tumor microenvironment (TME). TME consists of stromal components such as immune, inflammatory, endothelial, adipocytes, and fibroblast cells. Cancer stem cells (CSCs) or cancer stem-like cells are a small sub-set of the population within cancer cells believed to be a responsible player in the self-renewal, metastasis, and therapy response of cancer cells. The correlation between TME and CSCs remains an enigma in understanding the events of metastasis and therapy resistance in cancer biology. Recent evidence suggests that TME dictates the CSCs maintenance to arbitrate cancer progression and metastasis. The immune, inflammatory, endothelial, adipocyte, and fibroblast cells in the TME release growth factors, cytokines, chemokines, microRNAs, and exosomes that provide cues for the gain and maintenance of CSC features. These intricate cross-talks are fueled to evolve into aggressive, invasive, migratory phenotypes for cancer development. In this review, we have abridged the recent developments in the role of the TME factors in CSC maintenance and how these events influence the transition of tumor progression to further translate into metastasis and therapy resistance in cancer.
Hospitalization, death, and probable reinfection in Peruvian healthcare workers infected with SARS-CoV-2: a national retrospective cohort study
Authors: Ramos Willy , Guerrero Nadia , Napanga-Saldaña Edwin Omar , Medina José , Loayza Manuel , De La Cruz-Vargas Jhony A. , Vargas María , Ordóñez Luis , Seclén-Ubillús Yovanna , Álvarez-Antonio Carlos , Arrasco Juan
Published: December 2022

Background

Peru has some of the worst outcomes worldwide as a result of the SARS-CoV-2 pandemic; it is presumed that this has also affected healthcare workers. This study aimed to establish whether occupation and other non-occupational variables were risk factors for possible reinfection, hospitalization, and mortality from COVID-19 in cohorts of Peruvian healthcare workers infected with SARS-CoV-2.

Methods

Retrospective cohort study. Healthcare workers who presented SARS-CoV-2 infection between March 1, 2020, and August 6, 2021, were included. Occupational cohorts were reconstructed from the following sources of information: National Epidemiological Surveillance System, molecular tests (NETLAB), results of serology and antigen tests (SICOVID-19), National Registry of Health Personnel (INFORHUS), and National Information System of Deaths (SINADEF). The incidence of probable reinfection, hospitalization, and death from COVID-19 was obtained in the cohorts of technicians and health assistants, nursing staff, midwives, dentists, doctors, and other healthcare workers. We evaluated whether the occupation and other non-occupational variables were risk factors for probable reinfection, hospitalization, and death from COVID-19 using log-binomial and probit binomial models, obtaining the adjusted relative risk (RRAJ).

Results

90,398 healthcare workers were included in the study. Most cases were seen in technicians and health assistants (38.6%), and nursing staff (25.6%). 8.1% required hospitalization, 1.7% died from COVID-19, and 1.8% had probable reinfection. A similar incidence of probable reinfection was found in the six cohorts (1.7–1.9%). Doctors had a higher incidence of hospitalization (13.2%) and death (2.6%); however, they were also those who presented greater susceptibility linked to non-occupational variables (age and comorbidities). The multivariate analysis found that doctors (RRAJ = 1.720; CI 95: 1.569–1.886) had a higher risk of hospitalization and that the occupation of technician and health assistant was the only one that constituted a risk factor for mortality from COVID-19 (RRAJ = 1.256; 95% CI: 1.043–1.512).

Conclusions

Peruvian technicians and health assistants would have a higher risk of death from COVID-19 than other healthcare workers, while doctors have a higher incidence of death probably linked to the high frequency of non-occupational risk factors. Doctors present a higher risk of hospitalization independent of comorbidities and age; likewise, all occupations show a similar risk of probable reinfection.
Identification of biological pathways and processes regulated by NEK5 in breast epithelial cells via an integrated proteomic approach
Authors: de Castro Ferezin Camila , Lim Kam Sian Terry C. C. , Wu Yunjian , Ma Xiuquan , Chüeh Anderly C. , Huang Cheng , Schittenhelm Ralf B. , Kobarg Jörg , Daly Roger J.
Published: December 2022

Specific members of the Nima-Related Kinase (NEK) family have been linked to cancer development and progression, and a role for NEK5, one of the least studied members, in breast cancer has recently been proposed. However, while NEK5 is known to regulate centrosome separation and mitotic spindle assembly, NEK5 signalling mechanisms and function in this malignancy require further characterization. To this end, we established a model system featuring overexpression of NEK5 in the immortalized breast epithelial cell line MCF-10A. MCF-10A cells overexpressing NEK5 exhibited an increase in clonogenicity under monolayer conditions and enhanced acinar size and abnormal morphology in 3D Matrigel culture. Interestingly, they also exhibited a marked reduction in Src activation and downstream signalling. To interrogate NEK5 signalling and function in an unbiased manner, we applied a variety of MS-based proteomic approaches. Determination of the NEK5 interactome by Bio-ID identified a variety of protein classes including the kinesins KIF2C and KIF22, the mitochondrial proteins TFAM, TFB2M and MFN2, RhoH effectors and the negative regulator of Src, CSK. Characterization of proteins and phosphosites modulated upon NEK5 overexpression by global MS-based (phospho)proteomic profiling revealed impact on the cell cycle, DNA synthesis and repair, Rho GTPase signalling, the microtubule cytoskeleton and hemidesmosome assembly. Overall, the study indicates that NEK5 impacts diverse pathways and processes in breast epithelial cells, and likely plays a multifaceted role in breast cancer development and progression.
Incentivising public transport use for physical activity gain: process evaluation of the COVID-19 disrupted trips4health randomised controlled trial
Authors: Jose K. A. , Sharman M. J. , Stanesby O. , Greaves S. , Venn A. J. , Blizzard L. , Palmer A. , Cooper K. , Williams J. , Cleland V. J.
Published: December 2022

Background

Partnering with a public transport (PT) provider, state government, and local government, the single-blinded randomised controlled trial, trips4health, investigated the impact of PT use incentives on transport-related physical activity (PA) in Tasmania, Australia. The intervention involved 16-weeks of incentives (bus trip credits) for achieving weekly PT use targets, supported by weekly text messages. This study objective was to conduct a process evaluation of the COVID-19 disrupted trips4health study.

Methods

The Medical Research Council UK’s framework for complex public health interventions guided the process evaluation. Participant reach, acceptability, fidelity and feasibility were evaluated. Administrative and post-intervention survey data were analysed descriptively. Semi-structured interviews with intervention participants (n = 7) and PT provider staff (n = 4) were analysed thematically.

Results

Due to COVID-19, trips4health was placed on hold (March 2020) then stopped (May 2020) as social restrictions impacted PT use. At study cessation, 116 participants (approximately one third of target sample) had completed baseline measures, 110 were randomised, and 64 (n = 29 in the intervention group; n = 35 in the control group) completed post-intervention measures. Participants were 18 – 80 years (average 44.5 years) with females (69%) and those with tertiary education (55%) over-represented. The intervention was delivered with high fidelity with 96% of bus trip credits and 99% of behavioural text messages sent as intended. Interviewed PT staff said implementation was highly feasible. Intervention participant acceptability was high with 90% reporting bus trip incentives were helpful and 59% reporting the incentives motivated them to use PT more. From a total of 666 possible bus trip targets, 56% were met with 38% of intervention participants agreeing and 41% disagreeing that ‘Meeting the bus trip targets was easy’. Interviews and open-ended survey responses from intervention participants revealed incentives motivated bus use but social (e.g., household member commitments) and systemic (e.g., bus availability) factors made meeting bus trip targets challenging.

Conclusions

trips4health demonstrated good acceptability and strong fidelity and feasibility. Future intervention studies incentivising PT use will need to ensure a broader demographic is reached and include more supports to meet PT targets.

Trial registration

ACTRN12619001136190.
The impact of interventions in the built environment on physical activity levels: a systematic umbrella review
Authors: Zhang Yufang , Koene Marijke , Reijneveld Sijmen A. , Tuinstra Jolanda , Broekhuis Manda , van der Spek Stefan , Wagenaar Cor
Published: December 2022

Physical activity is good for people’s health. The relationship between the built environment and physical activity has been well documented. However, evidence is both scarce and scattered on specific urban interventions, i.e., intentional redesigns of the built environment that promote physical activity accompanied by pre- and post-effect measurement. This umbrella review aims to synthesize the findings of systematic reviews focused on these urban interventions. We followed the PRISMA 2020 and JBI umbrella review protocol guidelines and searched seven databases covering the period between Jan 2010 and April 2022 using keywords relating to the built environment, health, physical activity, and interventions. This yielded seven systematic reviews, in which we identified several urban interventions that can promote physical activity. We found positive effects of urban interventions on physical activity regarding park renovations, adding exercise equipment, introducing a (new) pocket park, improving cycling environments, improving walking & cycling environments, as well as multi-component initiatives for active travel and enhancing the availability & accessibility of destinations. The findings suggest that the urban environment can effectively promote physical activity, especially by adding various facilities and destinations and by making the environment better suitable for active use.
Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease
Authors: Ito Fuyu , Oharaseki Toshiaki , Tsukui Daisuke , Kimura Yoshitaka , Yanagida Tamiko , Kishi Fukuko , Yamakawa Yoshio , Kameoka Yosuke , Suzuki Shoichi , Uno Kazuko , Suzuki Osamu , Miura Noriko N. , Ohno Naohito , Takahashi Kei , Kono Hajime , Suzuki Kazuo
Published: December 2022

Background

Kawasaki disease (KD) is usually treated with high-dose intravenous immunoglobulin (IVIg) as severe infectious and other diseases. Due to issues that are associated with immunoglobulin preparation, such as the risk of possible contamination by infectious agents and limited blood banking resources, recombinant immunoglobulins are required.

We developed a novel recombinant antibody drug candidate, “VasSF,” based on the therapeutic effects it exerted on a mouse spontaneous crescentic glomerulonephritis model (SCG/Kj). Apolipoprotein A-2 (ApoA2) has been identified as one of VasSF’s target molecules.

Methods

Here, we tested the potential of anti-apolipoprotein A-2 antibodies (anti-ApoA2) as a new therapeutic drug against KD by examining its effect on a mouse model, in which KD was induced via Candida albicans water-soluble fraction (CAWS). CAWS (2 mg/mouse) was injected intraperitoneally into C57BL/6NCrSlc mice for five consecutive days. The incidence and histological severity of vasculitis in CAWS-induced coronary arteritis in mice administered anti-ApoA2 was examined. The following experimental groups were tested: solvent (only PBS (−) injection); anti-ApoA2 antibodies at dosages of 0.05 mg, 0.1 mg, and 0.5 mg/kg/day; human IgG at 0.1 mg/kg/day.

Results

The group treated with anti-ApoA2 0.5 mg/kg/day showed a lower incidence of panvasculitis induced by CAWS, less inflammation of the coronary arteries and aortic roots, and lower levels of serum IL-6, M-CSF, and MIP-1α and 32 cytokines/chemokines compared with those in the solvent group.

Conclusions

The anti-ApoA2 treatment suppressed the development of coronary arteritis in an animal KD model and anti-ApoA2 shows potential as an effective therapeutic candidate for the treatment of KD vasculitis. The use of specific antibodies that display higher vasculitis-suppressing effects, such as anti-ApoA2, may attenuate KD as well as other infectious diseases, with less severe adverse side effects than treatment with IVIg.
Obesity-induced neuroinflammation and cognitive impairment in young adult versus middle-aged mice
Authors: Henn Rosemary E. , Elzinga Sarah E. , Glass Emily , Parent Rachel , Guo Kai , Allouch Adam M. , Mendelson Faye E. , Hayes John , Webber-Davis Ian , Murphy Geoffery G. , Hur Junguk , Feldman Eva L.
Published: December 2022

Background

Obesity rates are increasing worldwide. Obesity leads to many complications, including predisposing individuals to the development of cognitive impairment as they age. Immune dysregulation, including inflammaging (e.g., increased circulating cytokines) and immunosenescence (declining immune system function), commonly occur in obesity and aging and may impact cognitive impairment. As such, immune system changes across the lifespan may impact the effects of obesity on neuroinflammation and associated cognitive impairment. However, the role of age in obesity-induced neuroinflammation and cognitive impairment is unclear. To further define this putative relationship, the current study examined metabolic and inflammatory profiles, along with cognitive changes using a high-fat diet (HFD) mouse model of obesity.

Results

First, HFD promoted age-related changes in hippocampal gene expression. Given this early HFD-induced aging phenotype, we fed HFD to young adult and middle-aged mice to determine the effect of age on inflammatory responses, metabolic profile, and cognitive function. As anticipated, HFD caused a dysmetabolic phenotype in both age groups. However, older age exacerbated HFD cognitive and neuroinflammatory changes, with a bi-directional regulation of hippocampal inflammatory gene expression.

Conclusions

Collectively, these data indicate that HFD promotes an early aging phenotype in the brain, which is suggestive of inflammaging and immunosenescence. Furthermore, age significantly compounded the impact of HFD on cognitive outcomes and on the regulation of neuroinflammatory programs in the brain.
ADAR1p110 promotes Enterovirus D68 replication through its deaminase domain and inhibition of PKR pathway
Authors: Zhang Kehan , Wang Siyuan , Chen Tingting , Tu Zeng , Huang Xia , Zang Guangchao , Wu Chun , Fan Xinyue , Liu Jia , Tian Yunbo , Cheng Yong , Lu Nan , Zhang Guangyuan
Published: December 2022

Background

Severe respiratory and neurological diseases caused by human enterovirus D68 (EV-D68) pose a serious threat to public health, and there are currently no effective drugs and vaccines. Adenosine deaminase acting on RNA1 (ADAR1) has diverse biological functions in various viral infections, but its role in EV-D68 infections remains undetermined.

Methods

Rhabdomyosarcoma (RD) and human embryonic kidney 293 T (293 T) cells, and HeLa cells were used to evaluate the expression level of ADAR1 upon EV-D68 (Fermon strain) and human parainfluenza virus type 3 (HPIV3; NIH47885) infection, respectively. Knockdown through silencing RNA (siRNA) and overexpression of either ADAR1p110 or ADAR1p150 in cells were used to determine the function of the two proteins after viral infection. ADAR1p110 double-stranded RNA binding domains (dsRBDs) deletion mutation was generated using a seamless clone kit. The expression of ADAR1, EV-D68 VP1, and HPIV3 hemagglutinin–neuraminidase (HN) proteins was identified using western blotting. The median tissue culture infectious dose (TCID50) was applied to detect viral titers. The transcription level of EV-D68 mRNA was analyzed using reverse transcription-quantitative PCR (RT-qPCR) and the viral 5′-untranslated region (5′-UTR)-mediated translation was analyzed using a dual luciferase reporter system.

Conclusion

We found that the transcription and expression of ADAR1 was inhibited upon EV-D68 infection. RNA interference of endogenous ADAR1 decreased VP1 protein expression and viral titers, while overexpression of ADAR1p110, but not ADAR1p150, facilitated viral replication. Immunofluorescence assays showed that ADAR1p110 migrated from the nucleus to the cytoplasm after EV-D68 infection. Further, ADAR1p110 lost its pro-viral ability after mutations of the active sites in the deaminase domain, and 5′-UTR sequencing of the viral genome revealed that ADAR1p110 likely plays a role in EV-D68 RNA editing. In addition, after ADAR1 knockdown, the levels of both phosphorylated double-stranded RNA dependent protein kinase (p-PKR) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α) increased. Attenuated translation activity of the viral genome 5′-UTR was also observed in the dual-luciferase reporter assay. Lastly, the deletion of ADAR1p110 dsRBDs increased the level of p-PKR, which correlated with a decreased VP1 expression, indicating that the promotion of EV-D68 replication by ADAR1p110 is also related to the inhibition of PKR activation by its dsRBDs. Our study illustrates that ADAR1p110 is a novel pro-viral factor of EV-D68 replication and provides a theoretical basis for EV-D68 antiviral research.
Non-interventional follow-up versus fluid bolus in RESPONSE to oliguria in hemodynamically stable critically ill patients: a randomized controlled pilot trial
Authors: Inkinen Nina , Pettilä Ville , Valkonen Miia , Serlo Maija , Bäcklund Minna , Hästbacka Johanna , Pulkkinen Anni , Selander Tuomas , Vaara Suvi T.
Published: December 2022

Background

Fluid bolus therapy is a common intervention to improve urine output. Data concerning the effect of a fluid bolus on oliguria originate mainly from observational studies and remain controversial regarding the actual benefit of such therapy. We compared the effect of a follow-up approach without fluid bolus to a 500 mL fluid bolus on urine output in hemodynamically stable critically ill patients with oliguria at least for 2 h (urine output < 0.5 mL/kg/h) in randomized setting.

Methods

We randomized 130 patients in 1:1 fashion to receive either (1) non-interventional follow-up (FU) for 2 h or (2) 500 mL crystalloid fluid bolus (FB) administered over 30 min. The primary outcome was the proportion of patients who doubled their urine output, defined as 2-h urine output post-randomization divided by urine output 2 h pre-randomization. The outcomes were adjusted for the stratification variables (presence of sepsis or AKI) using two-tailed regression. Obtained odds ratios were converted to risk ratios (RR) with 95% confidence intervals (CI). The between-group difference in the continuous variables was compared using mean or median regression and expressed with 95% CIs.

Results

Altogether 10 (15.9%) of 63 patients in the FU group and 22 (32.8%) of 67 patients in FB group doubled their urine output during the 2-h period, RR (95% CI) 0.49 (0.23–0.71), P = 0.026. Median [IQR] change in individual urine output 2 h post-randomization compared to 2 h pre-randomization was − 7 [− 19 to 17] mL in the FU group and 19[0–53] mL in the FB group, median difference (95% CI) − 23 (− 36 to − 10) mL, P = 0.001. Median [IQR] duration of oliguria in the FU group was 4 [2–8] h and in the FB group 2 [0–6] h, median difference (95%CI) 2 (0–4) h, P = 0.038. Median [IQR] cumulative fluid balance on study day was lower in the FU group compared to FB group, 678 [518–1029] mL versus 1071 [822–1505] mL, respectively, median difference (95%CI) − 387 (− 635 to − 213) mL, P < 0.001.

Conclusions

Follow-up approach to oliguria compared to administering a fluid bolus of 500 mL crystalloid in oliguric patients improved urine output less frequently but lead to lower cumulative fluid balance.

Trial registration clinical.trials.gov, NCT02860572. Registered 9 August 2016.

Graphical Abstract
Can we hit prenatal depression and anxiety through HIIT? The effectiveness of online high intensity interval training in pregnant women during the COVID-19 pandemic: a randomized controlled trial
Authors: Wilczyńska Dominika , Walczak-Kozłowska Tamara , Radzimiński Łukasz , Oviedo-Caro Miguel Ángel , Santos-Rocha Rita , Szumilewicz Anna
Published: December 2022

Background

In recent years high intensity interval training (HIIT) has grown in popularity. However, it rarely represents training interventions in experimental studies in pregnant populations. Therefore, in this study we aimed to assess changes in depressive symptoms, fear of childbirth, fear of Covid-19 and quality of life after an 8-week supervised online HIIT program, compared to an educational (self-performed physical activity) program.

Methods

We conducted a randomized control trial among 54 Caucasian women in uncomplicated, singleton pregnancy (age 32 ± 4 years, 22 ± 4 week of gestation; mean ± SD). There were 34 women in the experimental group, who participated in an 8-week high intensity interval training program (HIIT group). The comparative group was constituted of 20 pregnant women who attended 8-week educational program (EDU group).

Results

The most important finding was that mental health improved somewhat in both groups after the intervention, but only the HIIT group improved statistically significantly. The positive trends in lowering the severity of depressive symptoms, fear of childbirth, and fear of Covid-19 were observed in both groups. However, the positive response to the intervention was stronger in the EDU group. As a secondary outcome, there was a significant decrease in cardiorespiratory fitness level in the EDU group, while the HIIT group maintained unchanged level of maximal oxygen uptake.

Conclusions

HIIT seems to be beneficial for women with uncomplicated pregnancies to maintain adequate quality of life and mental health. However, more research is needed to determine the effectiveness of prenatal HIIT in pregnant women in various psychological conditions.

Trial registration: We conducted this study in Poland, in 2021. It was approved by the Bioethics Commission at the District Medical Chamber in Gdansk (KB-8/21). The full study protocol was registered in ClinicalTrials.gov (NCT05009433).
Malnutrition screening and treatment in pediatric oncology: a scoping review
Authors: Franke Jessica , Bishop Chris , Runco Daniel V.
Published: December 2022

Background

Malnutrition and cachexia during pediatric cancer treatment worsen toxicity and quality-of-life. Clinical practice varies with lack of standard malnutrition definition and nutrition interventions. This scoping review highlights available malnutrition screening and intervention data in childhood cancer and the need for standardizing assessment and treatment.

Methods

Ovid Medline, CINAHL, and Cochrane Library were searched for studies containing malnutrition as the primary outcome with anthropometric, radiographic, or biochemical measurements. Secondary outcomes included validated nutritional assessment or screening tools. Two authors reviewed full manuscripts for inclusion. Narrative analysis was chosen over statistical analysis due to study heterogeneity.

Results

The search yielded 234 articles and 17 articles identified from reference searching. Nine met inclusion criteria with six nutritional intervention studies (examining appetite stimulants, nutrition supplementation, and proactive feeding tubes) and three nutritional screening studies (algorithms or nutrition support teams) each with variable measures and outcomes. Both laboratory evaluations (albumin, prealbumin, total protein) and body measurement (weight loss, mid-upper arm circumference) were used. Studies demonstrated improved weight, without difference between formula or appetite stimulant used. Screening studies yielded mixed results on preventing weight loss, weight gain, and survival.

Conclusion

Our review demonstrated a paucity of evidence for malnutrition screening and intervention in pediatric cancer treatment. While a variety of malnutrition outcomes, interventions, and screening tools exist, nutritional interventions increased weight and decreased complications. Screening tools decreased malnutrition risk and may improve weight gain. Potential age- and disease-specific nutritional benefits and toxicities also exist, further highlighting the benefit of standardizing malnutrition definitions, screening, and interventions.