bluuebunny/crossref_metadata_2025 huggingface dataset:
MBNL1 Suppressed Cancer Metastatic of Skin Squamous Cell Carcinoma Via by TIAL1/MYOD1/Caspase-9/3 Signaling Pathways
Authors: Chen Jiaorong , Wang Jiaqi , Qian Jingyi , Bao Mengying , Zhang Xin , Huang Zheng
Published: April 2021

Objective:

The incidence of skin squamous cell carcinoma (SSCC) has recently been increasing, with diverse clinical manifestations.SSCC could metastasize to lymph nodes or other organs, posing a great threat to life. The present study was designed to investigate the function and underlying mechanism of muscleblind-like protein 1 (MBNL1) in skin squamous cell carcinoma.

Methods:

SCL-1 cell was used for vitro model and transfected with MBNL1 or siMBNL1 plasmids. MTT Assays, LDH activity ELISA, and Transwell chamber migration experiment were used to confirm the effects of MBNL1 on cell growth of SCL-1 cell. Western blot analysis was used to analyze the mechanism of MBNL1 in SCL-1 cell.

Results:

Down-regulation of MBNL1 promoted cell metastasis of SSCC, while up-regulation of MBNL1 reduced cell metastasis of SSCC in vitro. Down-regulation of MBNL1 suppressed the protein expression of T cell intracellular antigen (TIAL1), myogenic determinant 1 (MyoD1) and Caspase-3 in vitro. Consistent with these observations, inhibition of TIAL1 or MYOD1 expression attenuated the effects of MBNL1 in SSCC.

Conclusion:

The present study revealed that MBNL1 suppressed thecancer metastatic capacity of SSCC via by TIAL1/MYOD1/Caspase-3 signaling pathways.
Paediatric admissions to a district general hospital adult intensive care unit over a six year period: A single centre retrospective case series, with review of practitioner confidence and competence in paediatric critical care
Authors: Spencer Stephen A , Gumley Joanna S , Pachucki Marcin
Published: April 2021

Background

Critically ill children presenting to district general hospitals (DGH) are admitted to adult intensive care units (AICUs) for stabilisation prior to transfer to paediatric intensive care units (PICUs). Current training in PICU for adult intensive care physicians is only three months. This single centre retrospective case series examines the case mix of children presenting to a DGH AICU and a multidisciplinary survey assesses confidence and previous experience, highlighting continued training needs for DGH AICU staff.

Methods

all paediatric admissions to AICU and paediatric retrievals were reviewed over a 6-year period (2014-2019). Cases were identified from the Electronic Patient Record (EPR) and from data provided by the regional paediatric retrieval service. A questionnaire survey was sent to AICU doctors and nurses to assess confidence and competence in paediatric critical care.

Results

Between 2014-2019, 284 children were managed by AICU. In total 35% of cases were <1 y, 48% of cases were <2 y and 64% of cases were <5 y, and 166/284 (58%) children were retrieved. Retrieval reduced with increasing age (OR 0.49 [0.40-0.60], p < 0.0001). The survey had an 82% response rate, and highlighted that only 13% of AICU nurses and 50% of doctors had received prior PICU training.

Conclusion

At least one critically unwell child presents to the AICU each week. Assessment, stabilisation and management of critically unwell children are vital skills for DGH AICU staff, but confidence and competence are lacking. Formalised strategies are required to develop and maintain paediatric competencies for AICU doctors and nurses.
Video Visits Using the Zoom for Healthcare Platform for People Receiving Maintenance Hemodialysis and Nephrologists: A Feasibility Study in Alberta, Canada
Authors: Lunney Meaghan , Thomas Chandra , Rabi Doreen , Bello Aminu K. , Tonelli Marcello
Published: April 2021

Background:

Demand for virtual visits (an online synchronous medical appointment between a health care provider and patient) is increasing due to the COVID-19 pandemic. There may be additional benefits of virtual visits as they appear to be convenient and potentially cost-saving to patients. People receiving maintenance hemodialysis require ongoing care from their nephrologist and may benefit from virtual visits; however, the optimal model for a virtual kidney clinic is unknown.

Objective:

To codesign and assess the feasibility of a virtual (video) kidney clinic model with clinic staff, nephrologists, and patients receiving maintenance hemodialysis, to be used for routine follow-up visits.

Design:

Mixed-methods study.

Setting:

Two main kidney clinics in central Calgary, Alberta.

Participants:

Adults with kidney failure receiving maintenance hemodialysis, nephrologists, and clinic staff.

Methods:

First, we individually interviewed clinic staff and nephrologists to assess the needs of the clinic to deliver virtual visits. Then, we used participant observation with patients and nephrologists to codesign the virtual visit model. Finally, we used structured surveys to evaluate the patients’ and nephrologists’ experiences when using the virtual model.

Results:

Eight video visits (8 patients; 6 nephrologists) were scheduled between October 2019 and February 2020 and 7 were successfully completed. Among completed visits, all participants reported high satisfaction with the service, were willing to use it again, and would recommend it to others. Three main themes were identified with respect to factors influencing visit success: IT infrastructure, administration, and process.

Limitations:

Patients received training on how to use the videoconference platform by the PhD student, whom also set up the technical components of the visit for the nephrologist. This may have overestimated the feasibility of virtual visits if this level of support is not available in future. Second, interviews were not audio-recorded and thematic analysis relied on field notes.

Conclusions:

Video visits for routine follow-up care between people receiving hemodialysis and nephrologists were acceptable to patients and nephrologists. Video visits appear to be feasible if clinics are equipped with appropriate equipment and IT infrastructure, physicians are remunerated appropriately, and patients receive training on how to use software as needed.
Bystander Intoxication and Appraisal of Sexual Assault Risk: A Field Study of Emerging Adult Bargoers
Authors: Ham Lindsay S. , Hurd Lauren E. , Wolkowicz Noah R. , Wiersma-Mosley Jacquelyn D. , Bridges Ana J. , Jozkowski Kristen N.
Published: April 2021

Emerging adults are especially vulnerable to experiencing alcohol-related sexual assault. While bystanders play a critical role in preventing sexual assault, little is known about how bystander alcohol intoxication affects the intervention process—particularly in naturalistic settings. We recruited 315 emerging adult bargoers ages 21–29 (46% women; 28% non-college attending; 81% White) from a high-density bar area to provide responses to a sexual assault vignette and complete a breath alcohol concentration test. In this field-based study, we found a negative direct association between intoxication and appraisal of risk in the hypothetical sexual assault situation. We also found a negative indirect relation of intoxication on perceptions of personal responsibility to intervene and confidence in the ability to intervene, statistically mediated through reduced risk appraisal. Findings add to the limited literature in laboratory-based settings suggesting that bystander intoxication interferes with sexual assault intervention and help inform effective bystander intervention programming for emerging adults.
Performance-based assessment of students’ communication skills
Authors: Braun Edith
Published: April 2021

Higher education is a fundamental social institution that supports the latest theoretical developments and builds advanced skills. All institutions of higher education require that undergraduate and postgraduate students acquire performance skills as communication. Despite the fact that nearly every higher education program and discipline includes such skills among their learning outcomes, there are few instruments available with which to assess such complex competences. This article presents the findings of a study in which an instrument to measure communication skills was operationalized according to Habermas’ theory of communication, which distinguishes between strategic and understanding-oriented communication. The instrument introduced and used was based on role-plays that included standardised instructions and standardised observation forms. In addition to the empirical investigation into the theoretical dimensions of strategic and understanding-orientated communication, this study also examined two correlations: the correlation between performance-based testing and self-assessments and the correlation between performance-based testing and non-verbal communication. Two dimensions can be found in confirmatory factors analysis. Furthermore, the study found a medium correlation with non-verbal skills, but low correlation with self-assessments. Following a presentation of the study, the article concludes with a discussion of the benefits as well as limitations of such an instrument.
Does the Common Core Have a Common Effect? An Exploration of Effects on Academically Vulnerable Students
Authors: Bleiberg Joshua
Published: April 2021

Policymakers have long sought to raise expectations for students through standards-based reform. I examine the extent to which the Common Core State Content Standards (CC) affected student achievement and the size of achievement gaps. I merge together data on preparation for and implementation of the CC with the National Assessment of Educational Progress student-level data. To identify the effect of CC on student outcomes, I compare early implementors of the CC to late implementors of the CC in a difference-in-differences framework. I find the initial effect of the CC on math scores was positive. The CC had a large positive initial effect on economically advantaged students but no detectable initial effect on economically disadvantaged students. Raising state expectations without addressing the structural issues burdening economically disadvantaged students may result in unintended consequences.
Adherence to prenatal iron–folic acid supplementation and associated factors among pregnant women attending antenatal care services in Dilla town, South Ethiopia
Authors: Mamo Tizalegn Tesfaye , Ashenafi Eden , Gube Addisu Alemayehu , Bekele Tesfanew
Published: April 2021

Background:

During pregnancy, due to the physiological and hormonal change, the requirement of iron–folic acid is enhanced. Therefore, the occurrence of iron/folic acid deficiency is relatively high and it is responsible for 95% of anemia during pregnancy.

Objectives:

The aim of this study was to assess adherence to prenatal iron–folic acid supplementation (IFAS) and associated factors among pregnant women attending antenatal care services at public health facilities of Dilla town.

Methods:

Facility-based cross-sectional study design was employed selecting 403 pregnant women attending antenatal care services in three public health institutions of Dilla town. The women were included in the study by simple random sampling. Data were collected by interview and document review. Then it was entered into EPI Data version 3.1 and exported to SPSS version 20 for analysis. Bivariate and multivariate binary logistic regression techniques were used to identify independent predictors. A p-value <0.05 was taken as indication of statistical significance.

Results:

From the total of planned 403 pregnant women, 396 participated in the study, with a response rate of 98.2%. Of these, 172 (43.4%) pregnant women were adhered to IFAS. The study also revealed that history of previous anemia (adjusted odds ratio (AOR) = 1.87; 95% confidence interval (CI): (1.01–3.47); p = 0.04), frequency of antenatal care center (ANC) visits (AOR = 2.51; 95% CI: (1.17–5.37); p = 0.01), knowledge of IFA supplement (AOR = 2.28; 95% CI: (1.36–3.82); p = 0.002), and knowledge of anemia (AOR = 2.30; 95% CI: (1.40–3.77); p = 0.001) were independent predictors of adherence to IFAS.

Conclusion:

The finding of this study showed that less than half of the pregnant women were adhered to IFAS. History of previous anemia, frequency of ANC visits, knowledge of IFA supplement, and knowledge of anemia were the factors associated with adherence to IFA supplement.
Book Review: Ashok. K. Pankaj and Ajit. K. Pankaj (eds.), Dalits, Subalternity and Social Change in India
Authors: Gorringe Hugo
Published: April 2021

Ashok. K. Pankaj and Ajit. K. Pankaj (eds.), Dalits, Subalternity and Social Change in India. Abingdon: Routledge, 2019, HB. pp xv + 207. £115.00.
Patient Use of Dietary Supplements, Home Monitoring, or Genetic Testing for Nonneovascular Age-Related Macular Degeneration
Authors: Tsou Brittany C. , Liu T.Y. Alvin , Kong Jun , Bressler Susan B. , Arevalo J. Fernando , Brady Christopher J. , Handa James T. , Meyerle Catherine B. , Scott Adrienne W. , Wenick Adam S. , Bressler Neil M.
Published: April 2021

Purpose:

This work evaluated the use and type of dietary supplements and home monitoring for nonneovascular age-related macular degeneration (AMD), as well as the prevalence of genetic testing among patients with AMD.

Methods:

A cross-sectional study was conducted of 129 participants older than 50 years who completed self-administered questionnaires regarding usage and type of dietary supplements and home monitoring, as well as the participants’ use of genetic testing for AMD.

Results:

Of 91 participants with AMD, 83 (91.2%) took vitamins, including 55 (60.4%) who used an Age-Related Eye Disease Study (AREDS) or AREDS2 formulation. Of 38 without AMD, 31 (81.6%) took vitamins (difference from participants with AMD = 9.6% [95% CI, 0%-23.2%]), including 2 on an AREDS formulation. Among 82 participants with AMD who were AREDS candidates (intermediate or advanced AMD in 1 or both eyes), 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS or AREDS2 formulation, and 31 (37.8%) did not (5 were unsure). Additionally, 50 (61.0%; 95% CI, 50.4%-71.6%) AREDS candidates did some type of home monitoring. Only 1 (1.2%; 95% CI, 0%-3.6%) underwent genetic testing for AMD. Among 9 with AMD who were not AREDS candidates, 4 (44.4%) used an AREDS formulation, 4 (44.4%) did not, and 1 (11.1%) was unsure; only 1 (11.1%) of these 9 performed home monitoring.

Conclusions:

Despite similar results from past surveys and AREDS2 data supporting supplement use in 2013 and home monitoring in 2014, these findings suggest about one-third of AREDS candidates do not do so, providing further support for improving education regarding appropriate supplement and home monitoring usage. Genetic testing for AMD also appears infrequent.
Potential Osteoinductive Effects of Hydroxyapatite Nanoparticles on Mesenchymal Stem Cells by Endothelial Cell Interaction
Authors: Wang Zhongyi , Han Tianlei , Zhu Haoqi , Tang Jinxin , Guo Yanyang , Jin Yabing , Wang Yu , Chen Guilan , Gu Ning , Wang Chen
Published: April 2021

Nano-hydroxyapatite (nano-HA) has attracted substantial attention in the field of regenerative medicine. Endothelial cell (EC)-mesenchymal stem cell (MSC) interactions are necessary for bone reconstruction, but the manner in which nano-HA interacts in this process remains unknown. Herein, we investigated the cytotoxicity and osteoinductive effects of HA nanoparticles (HANPs) on MSCs using an indirect co-culture model mediated by ECs and highlighted the underlying mechanisms. It was found that at a subcytotoxic dose, HANPs increased the viability and expression of osteoblast genes, as well as mineralized nodules and alkaline phosphatase production of MSCs. These phenomena relied on HIF-1α secreted by ECs, which triggered the ERK1/2 signaling cascade. In addition, a two-stage cell-lineage mathematical model was established to quantitatively analyze the impact of HIF-1α on the osteogenic differentiation of MSCs. It demonstrated that HIF-1α exerted a dose-dependent stimulatory effect on the osteogenic differentiation rate of MSCs up to 1500 pg/mL, which was in agreement with the above results. Our data implied that cooperative interactions between HANPs, ECs, and MSCs likely serve to stimulate bone regeneration. Furthermore, the two-stage cell-lineage model is helpful in vitro system for assessing the potential influence of effector molecules in bone tissue engineering.
Genome sequence, transcriptome, and annotation of rodent malaria parasite Plasmodium yoelii nigeriensis N67
Authors: Zhang Cui , Oguz Cihan , Huse Sue , Xia Lu , Wu Jian , Peng Yu-Chih , Smith Margaret , Chen Jack , Long Carole A. , Lack Justin , Su Xin-zhuan
Published: April 2021

Background

Rodent malaria parasites are important models for studying host-malaria parasite interactions such as host immune response, mechanisms of parasite evasion of host killing, and vaccine development. One of the rodent malaria parasites is Plasmodium yoelii, and multiple P. yoelii strains or subspecies that cause different disease phenotypes have been widely employed in various studies. The genomes and transcriptomes of several P. yoelii strains have been analyzed and annotated, including the lethal strains of P. y. yoelii YM (or 17XL) and non-lethal strains of P. y. yoelii 17XNL/17X. Genomic DNA sequences and cDNA reads from another subspecies P. y. nigeriensis N67 have been reported for studies of genetic polymorphisms and parasite response to drugs, but its genome has not been assembled and annotated.

Results

We performed genome sequencing of the N67 parasite using the PacBio long-read sequencing technology, de novo assembled its genome and transcriptome, and predicted 5383 genes with high overall annotation quality. Comparison of the annotated genome of the N67 parasite with those of YM and 17X parasites revealed a set of genes with N67-specific orthology, expansion of gene families, particularly the homologs of the Plasmodium chabaudi erythrocyte membrane antigen, large numbers of SNPs and indels, and proteins predicted to interact with host immune responses based on their functional domains.

Conclusions

The genomes of N67 and 17X parasites are highly diverse, having approximately one polymorphic site per 50 base pairs of DNA. The annotated N67 genome and transcriptome provide searchable databases for fast retrieval of genes and proteins, which will greatly facilitate our efforts in studying the parasite biology and gene function and in developing effective control measures against malaria.
Characteristics and variation of fecal bacterial communities and functions in isolated systolic and diastolic hypertensive patients
Authors: Wang Pan , Dong Ying , Zuo Kun , Han Chunming , Jiao Jie , Yang Xinchun , Li Jing
Published: April 2021

Background

Hypertension (HTN) is one of the major cardiovascular risk factors, which contributes to increasing target organ damages and cardiovascular morbidity and mortality worldwide. Isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) are two important subtypes of HTN. Previous researches have demonstrated the alteration of fecal bacteria in HTN, but not down to these two sub-types. In order to identify whether the composition of bacterial taxa and functional modules shift in ISH and IDH, we performed a metagenomic sequencing analysis of fecal samples from 15 controls, 14 ISH, and 11 IDH.

Results

Compared with control and ISH, IDH patients showed decreased gene number, bacterial richness, and evenness, although the bacterial alterations did not reach statistical significance in the Shannon index. Also, at the genus level, the β-diversity for intestinal flora in IDH was distinguishable from those with ISH. Furthermore, the taxonomic composition of ISH or IDH was different from that of healthy control at genus and species levels. Patients with IDH or ISH were confirmed to be enriched with Rothia mucilaginosa, along with reduced Clostridium sp. ASBs410. Lastly, the altered KEGG modules were significantly decreased in IDH compared with the control group, such as sodium transport system; while for ISH, functions relevant to biotin biosynthesis were decreased.

Conclusions

Overall, our results showed the disordered fecal bacteria profiles in subjects with ISH and especially IDH, emphasizing the significance of early intervention for IDH.
A short-term musical training affects implicit emotion regulation only in behaviour but not in brain activity
Authors: Berthold-Losleben M. , Papalini S. , Habel U. , Losleben K. , Schneider F. , Amunts K. , Kohn N.
Published: April 2021

Background

In everyday life, negative emotions can be implicitly regulated by positive stimuli, without any conscious cognitive engagement; however, the effects of such implicit regulation on mood and related neuro-mechanisms, remain poorly investigated in literature. Yet, improving implicit emotional regulation could reduce psychological burden and therefore be clinically relevant for treating psychiatric disorders with strong affective symptomatology.

Results

Music training reduced the negative emotional state elicited by negative odours. However, such change was not reflected at the brain level.

Conclusions

In a context of affective rivalry a musical training enhances implicit regulatory processes. Our findings offer a first base for future studies on implicit emotion regulation in clinical populations.
Development of a temporally harmonized asset index: evidence from across 50 years of follow up of a birth cohort in Guatemala
Authors: Varghese Jithin Sam , Maluccio John A. , Cunningham Solveig A. , Ramirez-Zea Manuel , Stein Aryeh D.
Published: April 2021

Background

Asset-based indices are widely-used proxy measures of wealth in low and middle-income countries (LMIC). The stability of these indices within households over time is not known.

Methods

We develop a harmonized household asset index using Principal Component Analysis for the participants (n = 2392) of INCAP Longitudinal Study, Guatemala using data from six waves of follow-up over the period of 1965–2018. We estimate its cross-sectional association with parental schooling (in 1967–75) and attained schooling (in 2015–18) of cohort members. We study how patterns of cross-sectional loadings change over time and between urban-rural settings. We assess its robustness to omission of assets or study waves and alternate specifications of factor extraction procedure (exploratory factor analysis, multiple correspondence analysis).

Results

The harmonized index constructed using 8 assets and 11 housing characteristics explained 32.4% of the variance. Most households increased in absolute wealth over time with median wealth (25th percentile, 75th percentile; households) increasing from − 3.74 (− 4.42, − 3.07; 547) in 1967 to 2.08 (1.41, 2.67; 1145) in 2017–18. Ownership of television, electricity, quality of flooring and sanitary installation explained the largest proportion of variance. The index is positively associated with measures of schooling (maternal: r = 0.16; paternal: r = 0.10; attained: r = 0.35, all p < 0.001). In 2015–18, house ownership versus housing characteristics and ownership of electronic goods differentiate households in urban and rural areas respectively. The index is robust for omission of assets or study waves, indicator categorization and factor extraction method.

Conclusion

A temporally harmonized asset index constructed from consistently administered surveys in a cohort setting over time may allow study of associations of life-course social mobility with human capital outcomes in LMIC contexts. The approach permits exploration of trends in household wealth of the sample over a follow-up period against repeated cross-sectional surveys which permit the estimation of only the mean trajectory.
Antibiotic resistance among the Lahu hill tribe people, northern Thailand: a cross-sectional study
Authors: Intahphuak Sophaphan , Apidechkul Tawatchai , Kuipiaphum Patita
Published: April 2021

Background

Antibiotic resistance is often reported and great concerned as one of public health problems especially people living with poverty in developing countries including Thailand. The hill tribe people is defined as vulnerable population for antibiotic resistance in Thailand due to poor economic and education status particularly the Lahu people who is the second greatest group of the hill tribe people in Thailand. The study aimed to estimate the prevalence, factors associated with, and typing major species of bacteria with antibiotic drugs resistance among the Lahu hill tribe people in northern Thailand.

Methods

A cross-sectional study was conducted to gather the information from the participants. A validated questionnaire was used for data collection. Participants who presented an illness related to infectious diseases were eligible to participate the study and were asked to obtain specific specimen; sputum, urine or stool. Antibiotic susceptibility was tested by Kirbey Bauer’s disc diffusion test. Chi-square and logistic regression were used to detect the associations between variables at the significant level of α = 0.05.

Results

A total of 240 participants were recruited into the study. The majority had urinary tract infection (67.9%) with two major pathogenic species of the infection; Escherichia coli (12.8%), and Enterobacter cloacae (8.0%). The prevalence of antibiotic resistance was 16.0%. Escherichia coli and Klebsiella pneumoniae species were found to have multidrug resistance that was greater than that of other species, while ampicillin was found to have the greatest drug resistance. It was found that those who had poor knowledge of antibiotic use had a 2.56-fold greater chance (95% CI = 1.09–5.32) of having antibiotic resistance than did those who had good knowledge of antibiotic use, and those who had poor antibiotic use behaviors had a 1.79-fold greater chance (95% CI = 1.06–4.80) of having antibiotic resistance than did those who had good antibiotic use behaviors.

Conclusion

Effective public health interventions are urgently needed to reduce antibiotic drug resistance among the Lahu people by improving their knowledge and skills regarding the proper use of antibiotics and eventually minimizing antibiotic resistance. Moreover, health care professionals should strictly follow the standard guideline to prescribe antibiotics.
Trastuzumab administration during pregnancy: an update
Authors: Andrikopoulou Angeliki , Apostolidou Kleoniki , Chatzinikolaou Spyridoula , Bletsa Garyfalia , Zografos Eleni , Dimopoulos Meletios-Athanasios , Zagouri Flora
Published: April 2021

Background

Over than one third (28–58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2) expression. Trastuzumab anti-HER2 monoclonal antibody is still the benchmark treatment of HER2-positive breast tumors. However, FDA has categorized Trastuzumab as a category D drug for pregnant patients with breast cancer. This systemic review aims to synthesize all currently available data of trastuzumab administration during pregnancy and provide an updated view of the effect of trastuzumab on fetal and maternal outcome.

Methods

Eligible articles were identified by a search of MEDLINE bibliographic database and ClinicalTrials.gov for the period up to 01/09/2020; The algorithm consisted of a predefined combination of the words “breast”, “cancer”, “trastuzumab” and “pregnancy”. This study was performed in accordance with the PRISMA guidelines.

Results

A total of 28 eligible studies were identified (30 patients, 32 fetuses). In more than half of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration during gestation was 15.7 weeks (SD: 10.8; median: 17.5; range: 1–32). Oligohydramnios or anhydramnios was the most common (58.1%) adverse event reported in all cases. There was a statistically significant decrease in oligohydramnios/anhydramnios incidence in patients receiving trastuzumab only during the first trimester (P = 0.026, Fisher’s exact test). In 43.3% of cases a completely healthy neonate was born. 41.7% of fetuses exposed to trastuzumab during the second and/or third trimester were born completely healthy versus 75.0% of fetuses exposed exclusively in the first trimester. All mothers were alive at a median follow-up of 47.0 months (ranging between 9 and 100 months). Of note, there were three cases (10%) of cardiotoxicity and decreased ejection fraction during pregnancy.

Conclusions

Overall, treatment with trastuzumab should be postponed until after delivery, otherwise pregnancy should be closely monitored.
Neurocognitive function among HIV-infected children on protease inhibitor -based versus non-protease inhibitor based antiretroviral therapy in Uganda: a pilot study
Authors: Nalwanga Damalie , Musiime Victor , Bangirana Paul , Nishiguchi Erika Phelps , Kiggwe Andrew , Ssesanga Titus , Ssenkusu John M. , Musoke Philippa , Cusick Sarah E.
Published: April 2021

Background

HIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children’s neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes. We compared the neurocognitive function between children living with HIV receiving PI-based and non PI-based ART.

Methods

We recruited a consecutive sample of clinically stable Ugandan children living with HIV aged 5–12 years who received PI-based or non PI-based ART for ≥ 1 year (viral load < 1000 copies). Neurocognitive function was assessed using the Kaufman Assessment Battery for Children, the Test of Variables of Attention, and Bruininks-Oseretsky Test of Motor Proficiency. Age-adjusted neurocognitive z-scores for the two groups were compared using linear regression models in STATA version 13. The Hommel’s method was used to adjust for multiple testing.

Results

We enrolled 76 children living with HIV; 34 on PI ART and 42 on non-PI ART. Mean (±SD) age was greater in the non-PI vs. PI group (9.5 ± 1.9 vs. 8.5 ± 2.0) years (p = 0.03). Children in the non-PI group had lower socioeconomic scores (5.7 ± 3.3 vs. 7.4 ± 2.8, p = 0.02). There was no difference in neurocognitive function between the groups (adjusted p > 0.05) for KABC and TOVA. Children in the PI group had better total BOT scores than their counterparts (46.07 ± 1.40) vs. 40.51 (1.24), p = 0.03).

Conclusions

We detected no difference in neurocognitive function among children on PI and non PI-based ART therapy based on KABC and TOVA tests. Children on PI based ART had better motor function than their counterparts. We recommend a prospective study with a larger sample size.
Correction to: Combining targeted instrument-assisted soft tissue mobilization applications and neuromuscular exercises can correct forward head posture and improve the functionality of patients with mechanical neck pain: a randomized control study
Authors: Mylonas Konstantinos , Angelopoulos Pavlos , Billis Evdokia , Tsepis Elias , Fousekis Konstantinos
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Laparoscopic infrapyloric lymph nodes dissection through the right bursa omentalis approach for gastric cancer
Authors: Yang Kun , Zhang Wei-Han , Liu Kai , Chen Xin-Zu , Chen Xiao-Long , Zhou Zong-Guang , Hu Jian-Kun
Published: April 2021

Background

A complete dissection of infrapyloric lymph nodes is the key to a curative gastrectomy, which can be sometimes technically challenging in laparoscopic surgery.

Methods

One hundred and eighteen patients with gastric cancer undergoing laparoscopic gastrectomy with D2 lymphadenectomy in which the infrapyloric lymph nodes were dissected through the right bursa omentalis approach were included. The clinicopathologic characteristics and surgical outcomes were analyzed retrospectively.

Results

The laparoscopic gastrectomy with D2 lymphadenectomy was successful in all 118 patients with no open conversion. The mean operation time was 246.6 ± 45.7 min. The mean estimated blood loss was 87.0 ± 35.9 mL. Postoperative complications occurred in 17.8% of the patients, which were treated successfully with conservative therapy or aspiration in all. There were no No.6 lymphadenectomy-associated complications, such as injury of transverse colon, vessels of mesocolon, pancreas or duodenum, no pancreatitis, pancreatic leakage or postoperative hemorrhage. The mean postoperative hospital stay was 9.6 ± 3.7 days. On average, the total lymph nodes harvested were 36.8 ± 12.9, in which the ones from the infrapyloric area were 5.1 ± 3.1.

Conclusion

Laparoscopic dissection of infrapyloric lymph nodes through the right bursa omentalis approach seems to be feasible and safe, facilitating a more complete No.6 lymphadenectomy for gastric cancer.
Survey-based experiential learning as a new approach to strengthening non-technical skills in LMIC health care settings
Authors: Hodza-Beganovic Ruhija , Berggren Peter , Hugelius Karin , Edelbring Samuel
Published: April 2021

Background

This study outlines key aspects of professional development among health professionals in low- and middle-income countries (LMIC). LMICs need support in developing their continuing medical education, and non-technical skills (NTS) that have been neglected in this respect. Given the nature of NTS, educational methods should be used experientially. This study aims to explore an interactive educational approach to increase NTS among health care professionals in an LMIC setting.

Methods

A design-based research approach was applied to develop an educational method. Key NTS concepts were identified, which directed the selection of research-based surveys. A series of workshops was designed in which a survey-based experiential approach was developed. The educational process followed a pattern of individual reflection, small group discussion and relating the concepts to the local practice in a wider group.

Results

An approach to increase NTS in LMIC settings emerged in iterative development through conducting workshops with health care teams in the Balkans. The topics could be grouped into individual, team, and organisational dimensions. The approach can be described as survey-based experiential learning involving steps in recurring interaction with participants. The steps include identifying concepts in individual, team and organization dimensions and contextualising them using experiential learning on the individual and group levels.

Conclusion

An overarching approach has been developed that addresses NTS in an LMIC setting. The survey-based experiential learning approach can be beneficial for raising professional awareness and the development of sustainable healthcare settings in LMICs.
The impact of lean management on frontline healthcare professionals: a scoping review of the literature
Authors: Mahmoud Zeyad , Angelé-Halgand Nathalie , Churruca Kate , Ellis Louise A. , Braithwaite Jeffrey
Published: April 2021

Background

Lean management practices are increasingly used in hospitals. However, their impacts on staff have not been systematically synthesised. This scoping review aims to synthesise the evidence on the effects of Lean Management practices on frontline healthcare professionals.

Methods

A search was conducted in February 2020 on multiple databases to identify relevant sources. Studies had to satisfy the following inclusion criteria to be considered: published in English or French, peer-reviewed, empirical, studied the use of Lean in a healthcare setting and focused on its impacts on frontline workers. The studies included were heterogeneous in terms of participants. Findings were coded and classified using a thematic analysis. The quality and methodological rigour of the reviewed articles were assessed to establish a level of confidence in their findings.

Results

Of 998 identified articles, 17 were included in the review. The findings were coded into four themes: (1) Morale, motivation and job satisfaction (n = 9, 2) work intensification, job strain, anxiety, stress and dehumanisation (n = 7, 3) teamwork, communication and coordination (n = 6); and (4) learning, innovation and personal development (n = 3). Overall, the articles reported positive (n = 11), negative (n = 3) and mixed (n = 3) impacts of Lean on frontline healthcare professionals.

Conclusion

This review is the first to synthesise and highlight the gaps in the existing literature examining the impacts of Lean on frontline health professionals. The review revealed a range of both positive, negative and mixed effects, and points to the need for more empirical research to identify the underlying reasons leading to these outcomes.
Integrating Patient Reported Outcome Measures (PROMs) into routine nurse-led primary care for patients with multimorbidity: a feasibility and acceptability study
Authors: Porter Ian , Davey Antoinette , Gangannagaripalli Jaheeda , Evans Jonathan , Bramwell Charlotte , Evans Philip , Gibbons Chris , Valderas Jose M.
Published: April 2021

Background

The use of Patient Reported Outcome Measures (PROMS) in clinical practice has the potential to promote patient-centred care and improve patients’ quality of life. Individualized PROMs may be particularly helpful in identifying, prioritizing and monitoring health problems of patients with multimorbidity. We aimed to develop an intervention centred around PROMs feedback as part of Primary Care annual reviews for patients with multimorbidity and evaluate its feasibility and acceptability.

Methods

We developed a nurse-oriented intervention including (a) training of nurses on PROMs; (b) administration to patients with multimorbidity of individualized and standardized PROMS; and (c) feedback to both patients and nurses of PROMs scores and interpretation guidance. We then tailored the intervention to patients with two or more highly prevalent conditions (asthma, COPD, diabetes, heart failure, depression, and hip/knee osteoarthritis) and designed a non-controlled feasibility and acceptability evaluation in a convenience sample of primary care practices (5). PROMs were administered and scores fed back immediately ahead of scheduled annual reviews with nurses. Patients and nurses rated the acceptability of the intervention using with a brief survey including optional free comments. Thematic analysis of qualitative interviews with a sample of participating patients (10) and nurses (4) and of survey free comments was conducted for further in-depth evaluation of acceptability. Feasibility was estimated based on rates of participation and completion.

Results

Out of 68 recruited patients (mean age 70; 47% female), 68 completed the PROMs (100%), received feedback (100%) and confirmed nurse awareness of their scores (100%). Most patients (83%) “agreed”/”strongly agreed” that the PROMs feedback had been useful, a view supported by nurses in 89% of reviews. Thematic analysis of rich qualitative data on PROMS administration, feedback and role in annual reviews indicated that both patients and nurses perceived the intervention as acceptable and promising, emphasizing its comprehensiveness and patient-centredness.

Conclusions

We have developed and tested an intervention focusing on routine PROM assessment of patients with multimorbidity in Primary Care. Preliminary findings support its feasibility and a high degree of acceptability from both patients and nurses. The next step is to conduct a full-scale trial for evaluating the effectiveness of the proposed intervention.
Peptide targeting of lysophosphatidylinositol-sensing GPR55 for osteoclastogenesis tuning
Authors: Mosca Maria Giovanna , Mangini Maria , Cioffi Stefania , Barba Pasquale , Mariggiò Stefania
Published: April 2021

Background

The G-protein-coupled receptor GPR55 has been implicated in multiple biological activities, which has fuelled interest in its functional targeting. Its controversial pharmacology and often species-dependent regulation have impacted upon the potential translation of preclinical data involving GPR55.

Results

With the aim to identify novel GPR55 regulators, we have investigated lysophosphatidylinositol (LPI)-induced GPR55-mediated signal transduction. The expression system for wild-type and mutated GPR55 was HeLa cells silenced for their endogenous receptor by stable expression of a short-hairpin RNA specific forGPR555′-UTR, which allowed definition of the requirement of GPR55 Lys80for LPI-induced MAPK activation and receptor internalisation. In RAW264.7 macrophages, GPR55 pathways were investigated byGpr55silencing using small-interfering RNAs, which demonstrated that LPI increased intracellular Ca2+levels and induced actin filopodium formation through GPR55 activation. Furthermore, the LPI/GPR55 axis was shown to have an active role in osteoclastogenesis of precursor RAW264.7 cells induced by ‘receptor-activator of nuclear factor kappa-β ligand’ (RANKL). Indeed, this differentiation into mature osteoclasts was associated with a 14-fold increase inGpr55mRNA levels. Moreover, GPR55 silencing and antagonism impaired RANKL-induced transcription of the osteoclastogenesis markers: ‘nuclear factor of activated T-cells, cytoplasmic 1′, matrix metalloproteinase-9, cathepsin-K, tartrate-resistant acid phosphatase, and the calcitonin receptor, as evaluated by real-time PCR. Phage display was previously used to identify peptides that bind to GPR55. Here, the GPR55-specific peptide-P1 strongly inhibited osteoclast maturation of RAW264.7 macrophages, confirming its activity as a blocker of GPR55-mediated functions. Although osteoclast syncytium formation was not affected by pharmacological regulation of GPR55, osteoclast activity was dependent on GPR55 signalling, as shown with resorption assays on bone slices, where LPI stimulated and GPR55 antagonists inhibited bone erosion.

Conclusions

Our data indicate that GPR55 represents a target for development of novel therapeutic approaches for treatment of pathological conditions caused by osteoclast-exacerbated bone degradation, such as in osteoporosis or during establishment of bone metastases.
COVID-19 related mortality in post-operative cardiac surgical patients
Authors: Hussain Azhar , Khalil Amina , Kolvekar Priyanka , Gupta Prity , Kolvekar Shyamsunder
Published: April 2021

Background

COVID-19 has caused a global pandemic of unprecedented proportions. Elective cardiac surgery has been universally postponed with only urgent and emergency cardiac operations being performed. The National Health Service in the United Kingdom introduced national measures to conserve intensive care beds and significantly limit elective activity shortly after lockdown.

Case presentation

We report two cases of early post-operative mortality secondary to COVID-19 infection immediately prior to the implementation of these widespread measures.

Conclusion

The role of cardiac surgery in the presence of COVID-19 is still very unpredictable and further studies on both short term and long term outcomes are warranted.
A multi-stakeholder multicriteria decision analysis for the reimbursement of orphan drugs (FinMHU-MCDA study)
Authors:   the FinMHU-MCDA Group, de Andrés-Nogales Fernando , Cruz Encarnación , Calleja Miguel Ángel , Delgado Olga , Gorgas Maria Queralt , Espín Jaime , Mestre-Ferrándiz Jorge , Palau Francesc , Ancochea Alba , Arce Rosabel , Domínguez-Hernández Raquel , Casado Miguel Ángel
Published: April 2021

Background

Patient access to orphan medicinal products (OMPs) is limited and varies between countries, reimbursement decisions on OMPs are complex, and there is a need for more transparent processes to know which criteria should be considered to inform these decisions. This study aimed to determine the most relevant criteria for the reimbursement of OMPs in Spain, from a multi-stakeholder perspective, and using multicriteria decision analysis (MCDA).

Methods

An MCDA was developed in 3 phases and included 28 stakeholders closely related to the field of rare diseases (6 physicians, 5 hospital pharmacists, 7 health economists, 4 patient representatives and 6 members from national and regional health authorities). Initially [phase A], a bibliographic review was conducted to identify the potential reimbursement criteria. Then, a reduced advisory board (8 members) proposed, selected, and defined the final list of criteria that could be relevant for reimbursement. A discrete choice experiment (DCE) [phase B] was developed to determine the relevance and relative importance weight of such criteria according to the stakeholders’ preferences by choosing between pairs of hypothetical financing scenarios. A multinomial logit model was fitted to analyze the DCE responses. Finally [phase C], the advisory board review the results using a deliberative process.

Results

Thirteen criteria were selected, related to 4 dimensions: patient population, disease, treatment, and economic evaluation. Nine criteria were deemed relevant for decision-making and associated with a higher relative importance: Health-related quality of life (HRQL) (23.53%), treatment efficacy (14.64%), availability of treatment alternatives (13.51%), disease severity (12.62%), avoided costs (11.21%), age of target population (7.75%), safety (seriousness of adverse events) (4.72%), quality of evidence (3.82%) and size of target population (3.12%). The remaining criteria had a < 3% relative importance: economic burden of disease (2.50%), cost of treatment (1.73%), cost-effectiveness (0.83%) and safety (frequency of adverse events) (0.03%).

Conclusion

The reimbursement of OMPs in Spain should be determined by its effect on patient’s HRQL, the extent of its therapeutic benefit from efficacy and the availability of other therapeutic options. Furthermore, the severity of the rare disease should also influence the decision along with the potential of the treatment to avoid associated costs.
Inhibition of retinoic acid receptor α phosphorylation represses the progression of triple-negative breast cancer via transactivating miR-3074-5p to target DHRS3
Authors: Lou Siyue , Gao Hang , Hong Huanwu , Zhu Zhihui , Zhao Huajun
Published: April 2021

Background

Retinoids are promising agents in the treatment of different types of neoplasia including estrogen receptor-positive breast cancers, whereas refractoriness/low sensitivity is observed in triple-negative breast cancer (TNBC) subtype. However, the reason for these diverse retinoid-sensitivity remains elusive.

Methods

Determinants of retinoid sensitivity were investigated using immunohistochemistry of primary patient samples, and identified retinoic acid receptor α (RARα) as a putative factor. The anti-tumor activity of hypo-phosphorylated RARα was investigated in TNBC cell models and a xenograft mouse model. Next, miRNA sequencing analysis was performed to identify the target miRNA of RARα, and luciferase reporter was used to confirm the direct target gene of miR-3074-5p.

Results

We discovered that serine-77 residue of RARα was constantly phosphorylated, which correlated with TNBC’s resistance to retinoids. Overexpression of a phosphorylation-defective mutant RARαS77A mimicked activated RARα and repressed TNBC cell progression both in vitro and in vivo, via activating cell cycle arrest, apoptosis, and cytotoxic autophagy, independent of RARα agonists. We further revealed that the anti-tumor action of RARαS77A was, at least in part, mediated by the up-regulation of miR-3074-5p, which directly targeted DHRS3, a reductase negatively associated with TNBC patient survival. Our results suggest that the inhibition of RARαS77 phosphorylation by either expressing RARαS77A or inhibiting RARα’s phosphokinase CDK7, can bypass RA stimuli to transactivate tumor-suppressive miR-3074-5p and reduce oncogenic DHRS3, thus overcoming the RA-resistance of TNBC.

Conclusion

The novel regulatory network, involving RARαS77 phosphorylation, miR-3074-5p, and DHRS3, emerges as a new target for TNBC treatment.