bluuebunny/crossref_metadata_2025 huggingface dataset:
Carboxymethyl cellulose/sulfur-functionalized Ti-based MOF composite: synthesis, characterization, antimicrobial, antiviral and anticancer potentiality
Authors: Abdelhameed Reda M. , Hasanin Mohamed S. , Hashem Amr H.
Published: May 2023

Microbial resistance is the first morbidity and mortality cause for patients as usually a secondary infection. Additionally, the MOF is a promising material that shows a nice activity in this field. However, these materials need a good formulation to enhance biocompatibility and sustainability. Cellulose and its derivatives are well as filers for this gap. In this presented work, a novel green active system based on carboxymethyl cellulose and Ti-MOF (MIL-125-NH2@CMC) modified with thiophene (Thio@MIL-125-NH2@CMC) was prepared by a post-synthetic modification (PSM) route based. FTIR, SEM and PXRD were utilized to characterize nanocomposites. In addition, transmission electron microscopy (TEM) was used to corroborate the nanocomposites' particle size and diffraction pattern as well as the DLS affirmed the size as 50 and 35 nm for MIL-125-NH2@CMC and Thio@MIL-125-NH2@CMC, respectively. The formulation of the nanocomposites was validated by physicochemical characterization techniques, while morphological analysis confirmed the nanoform of the prepared composites. The antimicrobial, antiviral and antitumor properties of MIL-125-NH2@CMC and Thio@MIL-125-NH2@CMC were assessed. Antimicrobial testing revealed that Thio@MIL-125-NH2@CMC possesses greater antimicrobial activity than MIL-125-NH2@CMC. Additionally, Thio@MIL-125-NH2@CMC demonstrated promising antifungal activity againstC. albicansandA. nigerwhere MICs were 31.25 and 0.97 µg/mL, respectively. Also, Thio@MIL-125-NH2@CMC exhibited antibacterial activity againstE. coliandS. aureuswhere MICs were 1000 and 250 µg/mL, respectively. In addition, the results demonstrated that Thio@MIL-125-NH2@CMC displayed promising antiviral activity against both HSV1 and COX B4, with antiviral activities of 68.89% and 39.60%, respectively. Furthermore, Thio@MIL-125-NH2@CMC exhibited potential anticancer activity against MCF7 and PC3 cancerous cell lines, where IC50was 93.16 and 88.45%, respectively. In conclusion, carboxymethyl cellulose/sulfur-functionalized Ti-based MOF composite was successfully synthesized which had antimicrobial, antiviral and anticancer activities.
Bayesian compositional regression with microbiome features via variational inference
Authors: Scott Darren A. V. , Benavente Ernest , Libiseller-Egger Julian , Fedorov Dmitry , Phelan Jody , Ilina Elena , Tikhonova Polina , Kudryavstev Alexander , Galeeva Julia , Clark Taane , Lewin Alex
Published: May 2023

The microbiome plays a key role in the health of the human body. Interest often lies in finding features of the microbiome, alongside other covariates, which are associated with a phenotype of interest. One important property of microbiome data, which is often overlooked, is its compositionality as it can only provide information about the relative abundance of its constituting components. Typically, these proportions vary by several orders of magnitude in datasets of high dimensions. To address these challenges we develop a Bayesian hierarchical linear log-contrast model which is estimated by mean field Monte-Carlo co-ordinate ascent variational inference (CAVI-MC) and easily scales to high dimensional data. We use novel priors which account for the large differences in scale and constrained parameter space associated with the compositional covariates. A reversible jump Monte Carlo Markov chain guided by the data through univariate approximations of the variational posterior probability of inclusion, with proposal parameters informed by approximating variational densities via auxiliary parameters, is used to estimate intractable marginal expectations. We demonstrate that our proposed Bayesian method performs favourably against existing frequentist state of the art compositional data analysis methods. We then apply the CAVI-MC to the analysis of real data exploring the relationship of the gut microbiome to body mass index.
Neighbourhood greenness moderates the association between physical activity and geriatric-relevant health outcomes: an analysis of the CLSA
Authors: Putman Andrew , Klicnik Irmina , Dogra Shilpa
Published: May 2023

Background

The purpose of this analysis was to evaluate the relationship between baseline physical activity levels of older adults and geriatric-relevant health outcomes at 3-year follow-up, and to determine whether baseline neighbourhood characteristics alter this association.

Methods

Data from the Canadian Longitudinal Study on Aging (CLSA) were used to assess geriatric-relevant outcomes of physical impairment, medication use, severity of daily pain, and depressive symptoms. Data from the Canadian Active Living Environments (Can-ALE) and the Normalized Difference Vegetative Index (NDVI) were used to determine neighbourhood walkability and greenness, respectively. The analytic sample included adults who were 65 years or older at baseline$$(n=\text{16,735}, age=73\pm 5.6, 50\% female)$$. Adjusted odds ratios and 95% confidence intervals for the base relationships were calculated using proportional odds logistic regression (physical impairment, pain, medication use), and linear regression (depressive symptoms). Moderation effects of environmental factors were assessed using greenness and walkability.

Results

The base relationships showed protective associations between each additional hour per week of total physical activity and physical impairment$$\left(OR=0.95, 95\%CI=\text{0.94,0.96}; p<.001\right),$$daily pain severity$$\left(OR=0.98, 95\%CI=0.98, 0.99; p<.001\right),$$medication use$$(OR=0.98, 95\%CI= 0.97, 0.99; p< .001)$$, and depressive symptoms$$(OR=0.95, 95\%CI=\text{0.94,0.96}; p<.001)$$. Additive moderation effects were seen when greenness was added to physical impairment$$(\beta =0.022, p=.04)$$, daily pain severity$$(\beta =0.019, p<.01)$$, and depressive symptoms$$(\beta =0.032, p=.01)$$but no moderation was seen with walkability. Sex differences were observed. For example, greenness moderation was found in severity of daily pain in males but not in females.

Conclusion

Future research investigating geriatric-relevant health outcomes and physical activity should consider neighbourhood greenness as a potential moderator.
Factors associated with the unsuccessful TB treatment outcomes in the northern regions of Namibia: a mixed methods study
Authors: Amkongo Mondjila , Mitonga Honoré K. , Alfeus Anna , Shipingana Loide Ndelimona Ndapandula , Keendjele Tuwilika , Eelu Hilja , Nashihanga Tunelago
Published: May 2023

Background

Tuberculosis (TB) is among the leading causes of death globally. The disease has a huge burden in Namibia, with a case notification rate of at least 442 per 100,000. To date, Namibia is among the countries with the highest global TB burden, despite all efforts to reduce it. This study aimed to determine the factors associated with the unsuccessful treatment outcomes of the Directly Observed Therapy Short course (DOTS) programme in the Kunene and Oshana regions.

Methods

The study utilised a mixed-methods explanatory-sequential design to collect data from all TB patient records and healthcare workers who work directly with the DOTS strategy for TB patients. The relationship between independent and dependent variables was analysed using multiple logistic regression analysis, while interviews were analysed using inductive thematic analysis.

Results

The overall treatment success rates of the Kunene and Oshana regions throughout the review period were 50.6% and 49.4%, respectively. The logistic regression analyses showed that in the Kunene region, the type of DOT used (Community-based DOTS) (aOR = 0.356, 95% CI: 0.835–2.768, p = 0.006) was statistically significant with the unsuccessful treatment outcomes. While in the Oshana region, age groups 21–30 years old (aOR = 1.643, 95% CI = 1.005–2.686, p = 0.048), 31–40 years old (aOR = 1.725, 95% CI = 11.026–2.9, p = 0.040), 41–50 years old (aOR = 2.003, 95% CI = 1.155–3.476, p = 0.013) and 51–60 years old (aOR = 2.106, 95% CI = 1.228–3.612, p = 0.007) had statistically significant associations with the poor TB-TO. Inductive thematic analysis revealed that patients in the Kunene region were challenging to reach owing to their nomadic lifestyle and the vastness of the area, adversely affecting their ability to observe TB therapy directly. In the Oshana region, it was found that stigma and poor TB awareness among adult patients, as well as mixing anti-TB medication with alcohol and tobacco products among adult patients, was a prevalent issue affecting TB therapy.

Conclusion

The study recommends that regional health directorates embark on rigorous community health education about TB treatment and risk factors and establish a robust patient observation and monitoring system to enhance inclusive access to all health services and ensure treatment adherence.
Delay in diagnosis and associated factors among children with cancer admitted at pediatric oncology ward, University of Gondar comprehensive specialized hospital, Ethiopia: a retrospective cross-sectional study
Authors: Gardie Yimenu , Wassie Mulugeta , Wodajo Seid , Giza Mastewal , Ayalew Mulugeta , Sewale Yihenew , Feleke Zelalem , Dessie Melkamu Tilahun
Published: May 2023

Background

Delay in the diagnosis of childhood cancer is one of the major health problem that contribute to decreased survival rates of children particularly in developing nations. Despite advances in the field of pediatric oncology, cancer remains a leading cause of death in children. Diagnosis of childhood cancer as early as possible is crucial to reduce mortality. Therefore, the aim of this study was to assess delay in diagnosis and associated factors among children with cancer admitted to pediatric oncology ward, University of Gondar comprehensive specialized hospital, Ethiopia 2022.

Method

Institutional-based retrospective cross-sectional study design was conducted from January1, 2019 to December 31, 2021 at University of Gondar comprehensive specialized hospital. All 200 children were included in the study and Data were extracted through structured check-list. The data were entered using EPI DATA version 4.6 and exported to STATA version 14.0 for data analysis.

Results

From the total of two hundred pediatric patients 44% had delayed diagnosis and the median delay diagnosis was 68 days. Rural residence (AOR = 1.96; 95%CI = 1.08–3.58), absence of health insurance (AOR = 2.21; 95%CI = 1.21–4.04), Hodgkin lymphoma (AOR = 9.36; 95%CI = 2.1-41.72), Retinoblastoma (AOR = 4.09; 95%CI = 1.29–13.02), no referral (AOR = 6.3; 95%CI = 2.15–18.55) and absence of comorbid disease (AOR = 2.14; 95%CI = 1.17–3.94) were significant factors associated with delay in diagnosis.

Conclusion and recommendation

Delayed in diagnosis of childhood cancer was relatively lower than previous studies and most influenced by the child’s residency, health insurance, type of cancer and comorbid disease. Thus; every effort should be made to promote public and parental understanding of childhood cancer, promote health insurance and referral.
Cancer incidence and mortality in Brunei Darussalam, 2011 to 2020
Authors: Leong Elvynna , Ong Sok King , Si-Ramlee Khairil Azhar , Naing Lin
Published: May 2023

This study presents the trends of age-standardised incidence and mortality rates of common cancers in Brunei Darussalam from 2011 to 2020. All cancer cases diagnosed among Brunei Darussalam citizens and permanent residents in the period 2011 to 2020 were included in the study. De-identified data were provided by the CanReg5 based BDCR, Ministry of Health Brunei Darussalam. The annual age-standardised incidence and mortality rates per 100,000 persons were standardised by the direct method using the World Health Organization (WHO) world standard population distribution. Joinpoint regression analyses were used to study the incidence and mortality trends of cancer in Brunei Darussalam over the 2011–2020 period. Trends were expressed as average annual percent change (AAPC) over 2011 to 2020, or annual percent change (APC) for a given time period. There were a total of 6,495 new cancer cases diagnosed and 3,359 death cases recorded from 2011 to 2020, in Brunei Darussalam. The five common cancers for males were colorectal, lung and bronchus, prostate, liver, and non-Hodgkin lymphoma. Among females, the five most common cancers were breast, colorectal, lung and bronchus, corpus uteri and cervix uteri. The five leading cancer deaths for males were lung and bronchus, colorectal, liver, prostate, and stomach, while for females, the five leading cancer deaths were breast, lung and bronchus, colorectal, ovary, and cervix uteri. There was a significant increase in the incidence trend of corpus uteri (AAPC$$:13.3$$

:
13.3

) and a significant decline in the incidence trend for cervical cancer (AAPC$$:-4.5$$

:
-
4.5

) from 2011 to 2020. There was a significant increase in the mortality trend of female breast cancer from 2011 to 2015 (APC$$:16.3$$

:
16.3

), but the trend significantly declined from 2015 to 2020 (APC$$:-12.5$$

:
-
12.5

). We also found a significant decrease in mortality trends for stomach cancer (AAPC$$:-4.7$$

:
-
4.7

) from 2011 to 2020 for both genders combined. The burden of common cancers is expected to continue to grow with ageing population, effective public health interventions targeting high burden cancers and high-risk groups, and control of modifiable risk factors will continue to be the essential approaches in reducing cancer burden.
A comparative study on two methods of ocular surface microbial sampling
Authors: Shen Xinyi , Xu Yi , Huang Jinzhi , Wu Peiyu , Zhou Weihe , Chen Yanyan
Published: May 2023

Purpose

To compare the effect of traditional conjunctival sac swab sampling (A) with aerosolization ocular surface microorganism sampling (B),a novel microbial sampling method, in detecting ocular microbial infection.

Methods

The study included 61 participants (122 eyes) enrolled at the Eye Hospital, Wenzhou Medical University from December, 2021 to March, 2023. Each eye of the participants underwent sampling first with method A then B.Before aerosolization sampling, the air environment was disinfected and sampled as blank air control sample. Subsequently, the air pulses impinging the ocular surface causes dehiscence of the tear film covering the ocular surface and aerosols are formed.The microorganisms from the ocular surface attach to the aerosols generated as aerosolization ocular surface microorganism and be sampled as subject sample by bio-aerosol sampler.The samples were collected and incubated at 25℃ for 3–5 days and 37℃ for 24–48 h.The colonies were counted and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Results

The accuracy in Group B was higher than that in Group A (45.8% vs. 38.3%, P = 0.289). There was a slight level of agreement between the results from both the sampling methods (k = 0.031, P = 0.730). The sensitivity in Group B was higher than that in Group A (57.1% vs. 35.7%, P = 0.453). The specificity results in Group B was higher than that in Group A (44.3% vs. 38.7%, P = 0.480). There were 12 and 37 types of microbes detected in Groups A and B, respectively.

Conclusions

Compared with traditional swab sampling, the novel aerosolization sampling method shows higher accuracy and more comprehensive detection of microbes; however, it cannot completely replace swab sampling. The novel method can be a novel conducive strategy and supplement swab sampling to auxiliary diagnose ocular surface infection.
Depression after stoma surgery: a systematic review and meta-analysis
Authors: Kovoor Joshua G. , Jacobsen Jonathan Henry W. , Stretton Brandon , Bacchi Stephen , Gupta Aashray K. , Claridge Brayden , Steen Matthew V. , Bhanushali Ameya , Bartholomeusz Lorenz , Edwards Suzanne , Asokan Gayatri P. , Asokan Gopika , McGee Amanda , Ovenden Christopher D. , Hewitt Joseph N. , Trochsler Markus I. , Padbury Robert T. , Perry Seth W. , Wong Ma-Li , Licinio Julio , Maddern Guy J. , Hewett Peter J.
Published: May 2023

Background

Depression is the leading cause of global disability and can develop following the change in body image and functional capacity associated with stoma surgery. However, reported prevalence across the literature is unknown. Accordingly, we performed a systematic review and meta-analysis aiming to characterise depressive symptoms after stoma surgery and potential predictive factors.

Methods

PubMed/MEDLINE, Embase, CINAHL and Cochrane Library were searched from respective database inception to 6 March 2023 for studies reporting rates of depressive symptoms after stoma surgery. Risk of bias was assessed using the Downs and Black checklist for non-randomised studies of interventions (NRSIs), and Cochrane RoB2 tool for randomised controlled trials (RCTs). Meta-analysis incorporated meta-regressions and a random-effects model. Registration: PROSPERO, CRD42021262345.

Results

From 5,742 records, 68 studies were included. According to Downs and Black checklist, the 65 NRSIs were of low to moderate methodological quality. According to Cochrane RoB2, the three RCTs ranged from low risk of bias to some concerns of bias. Thirty-eight studies reported rates of depressive symptoms after stoma surgery as a proportion of the respective study populations, and from these, the median rate across all timepoints was 42.9% 42.9% (IQR: 24.2–58.9%). Pooled scores for respective validated depression measures (Hospital Anxiety and Depression Score (HADS), Beck Depression Inventory (BDI), and Patient Health Questionnaire-9 (PHQ-9)) across studies reporting those scores were below clinical thresholds for major depressive disorder according to severity criteria of the respective scores. In the three studies that used the HADS to compare non-stoma versus stoma surgical populations, depressive symptoms were 58% less frequent in non-stoma populations. Region (Asia–Pacific; Europe; Middle East/Africa; North America) was significantly associated with postoperative depressive symptoms (p = 0.002), whereas age (p = 0.592) and sex (p = 0.069) were not.

Conclusions

Depressive symptoms occur in almost half of stoma surgery patients, which is higher than the general population, and many inflammatory bowel disease and colorectal cancer populations outlined in the literature. However, validated measures suggest this is mostly at a level of clinical severity below major depressive disorder. Stoma patient outcomes and postoperative psychosocial adjustment may be enhanced by increased psychological evaluation and care in the perioperative period.
Circulating eosinophils associated with responsiveness to COVID-19 vaccine and the disease severity in patients with SARS-CoV-2 omicron variant infection
Authors: Zhu Zhuxian , Cai Jixu , Tang Qiang , Mo Yin-yuan , Deng Tiantian , Zhang Xiaoyu , Xu Ke , Wu Beishou , Tang Haicheng , Zhang Ziqiang
Published: May 2023

Objective

This study aimed to investigate the longitudinal circulating eosinophil (EOS) data impacted by the COVID-19 vaccine, the predictive role of circulating EOS in the disease severity, and its association with T cell immunity in patients with SARS-CoV-2 Omicron BA.2 variant infection in Shanghai, China.

Methods

We collected a cohort of 1,157 patients infected with SARS-CoV-2 Omicron/BA.2 variant in Shanghai, China. These patients were diagnosed or admitted between Feb 20, 2022, and May 10, 2022, and were classified as asymptomatic (n = 705), mild (n = 286) and severe (n = 166) groups. We compiled and analyzed data of patients’ clinical demographic characteristics, laboratory findings, and clinical outcomes.

Results

COVID-19 vaccine reduced the incidence of severe cases. Severe patients were shown to have declined peripheral blood EOS. Both the 2 doses and 3 doses of inactivated COVID-19 vaccines promoted the circulating EOS levels. In particular, the 3rd booster shot of inactivated COVID-19 vaccine was shown to have a sustained promoting effect on circulating EOS. Univariate analysis showed that there was a significant difference in age, underlying comorbidities, EOS, lymphocytes, CRP, CD4, and CD8 T cell counts between the mild and the severe patients. Multivariate logistic regression analysis and ROC curve analysis indicate that circulating EOS (AUC = 0.828, p = 0.025), the combination of EOS and CD4 T cell (AUC = 0.920, p = 0.017) can predict the risk of disease severity in patients with SARS-CoV-2 Omicron BA.2 variant infection.

Conclusions

COVID-19 vaccine promotes circulating EOS and reduces the risk of severe illness, and particularly the 3rd booster dose of COVID-19 vaccine sustainedly promotes EOS. Circulating EOS, along with T cell immunity, may have a predictive value for the disease severity in SARS-CoV-2 Omicron infected patients.
Analysis of clinical characteristics of thyroid disorders in patients with chronic hepatitis B treated with pegylated-interferon alpha
Authors: Liu Yisi , Zheng Yanhong , Lin Xiao , Cao Zhenhuan , Lu Junfeng , Ma Lina , Ren Shan , Zheng Sujun , Hu Zhongjie , Xu Bin , Chen Xinyue
Published: May 2023

Background

Thyroid disorders (TD) is a common complication of pegylated-interferon alpha (Peg-IFNα) therapy. Few studies have investigated the relationship between TD and the efficacy of interferon therapy for chronic hepatitis B (CHB). Therefore, we analyzed the clinical characteristics of TD in patients with CHB treated with Peg-IFNα, and evaluated the correlation between TD and Peg-IFNα treatment efficacy.

Methods

In this retrospective study, the clinical data of 146 patients with CHB receiving Peg-IFNα therapy were collected and analyzed.

Results

During the course of Peg-IFNα therapy, positive conversion of thyroid autoantibodies and TD occurred in 7.3% (85/1158) and 8.8% (105/1187) patients, respectively, and was diagnosed more often in women. The most common thyroid disorder was hyperthyroidism (53.3%), followed by subclinical hypothyroidism (34.3%). We found that thyroid function returned to normal in 78.7% of patients with CHB, and thyroid antibody levels returned to the negative range in approximately 50% of patients after interferon treatment cessation. Only 25% of patients with clinical TD required treatment. Compared with patients with hypothyroidism/subclinical hypothyroidism, patients with hyperthyroidism/subclinical hyperthyroidism showed greater reduction and seroclearance of hepatitis B surface antigen (HBsAg) levels.

Conclusions

TD are not an absolute contraindication for interferon therapy; however, patients should be monitored closely during interferon therapy. In pursuit of functional cure, a balance between efficacy and safety must be achieved.
Influence of buccal and palatal bone thickness on post-surgical marginal bone changes around implants placed in posterior maxilla: a multi-centre prospective study
Authors: Cicciù Marco , Pratella Umberto , Fiorillo Luca , Bernardello Fabio , Perillo Francesco , Rapani Antonio , Stacchi Claudio , Lombardi Teresa
Published: May 2023

Background

Numerous clinical variables may influence early marginal bone loss (EMBL), including surgical, prosthetic and host-related factors. Among them, bone crest width plays a crucial role: an adequate peri-implant bone envelope has a protective effect against the influence of the aforementioned factors on marginal bone stability. The aim of the present study was to investigate the influence of buccal and palatal bone thickness at the time of implant placement on EMBL during the submerged healing period.

Methods

Patients presenting a single edentulism in the upper premolar area and requiring implant-supported rehabilitation were enrolled following inclusion and exclusion criteria. Internal connection implants (Twinfit, Dentaurum, Ispringen, Germany) were inserted after piezoelectric implant site preparation. Mid-facial and mid-palatal thickness and height of the peri-implant bone were measured immediately after implant placement (T0) with a periodontal probe and recorded to the nearest 0.5 mm. After 3 months of submerged healing (T1), implants were uncovered and measurements were repeated with the same protocol. Kruskal-Wallis test for independent samples was used to compare bone changes from T0 to T1. Multivariate linear regression models were built to assess the influence of different variables on buccal and palatal EMBL.

Results

Ninety patients (50 females, 40 males, mean age 42.9 ± 15.1 years), treated with the insertion of 90 implants in maxillary premolar area, were included in the final analysis. Mean buccal and palatal bone thickness at T0 were 2.42 ± 0.64 mm and 1.31 ± 0.38 mm, respectively. Mean buccal and palatal bone thickness at T1 were 1.92 ± 0.71 mm and 0.87 ± 0.49 mm, respectively. Changes in both buccal and palatal thickness from T0 to T1 resulted statistically significant (p = 0.000). Changes in vertical bone levels from T0 to T1 resulted not significant both on buccal (mean vertical resorption 0.04 ± 0.14 mm; p = 0.479) and palatal side (mean vertical resorption 0.03 ± 0.11 mm; p = 0.737). Multivariate linear regression analysis showed a significant negative correlation between vertical bone resorption and bone thickness at T0 on both buccal and palatal side.

Conclusion

The present findings suggest that a bone envelope > 2 mm on the buccal side and > 1 mm on the palatal side may effectively prevent peri-implant vertical bone resorption following surgical trauma.

Trial Registration

The present study was retrospectively recorded in a public register of clinical trials (www.clinicaltrials.gov - NCT05632172) on 30/11/2022.
Evaluation of registered nurses’ interprofessional emergency care competence through the gamification of cardiopulmonary resuscitation training: a cross-sectional study
Authors: Chen Tzu-Sang , Hsieh Pei-Lun , Tung Chien Chien , Wu Chao-Hsin , Cheng Yu-Chieh
Published: May 2023

Backgrounds

Cardiopulmonary resuscitation (CPR) training is generally led by instructors in a classroom; thus, conventional teaching materials used in CPR training are often constrained by spatiotemporal factors, limiting learners’ interest and sense of achievement in learning and preventing them from effectively applying what they learn in practice. For greater effectiveness and more flexible application, clinical nursing education has increasingly emphasized contextualization, individualization, and interprofessional learning. This study determined the self-assessed emergency care competencies of nurses who received gamified emergency care training and explored the factors associated with those competencies.

Methods

Quota sampling of nurses working at a certain regional hospital in central Taiwan was conducted, and a structured questionnaire was administered to the recruited nurses. A total of 194 valid responses were collected. The research tool was a scale measuring the participants’ emergency care competencies after they received gamified emergency care training. The data were analyzed using descriptive and inferential statistics and multiple regression.

Results

Of the recruited participants, 50.52% were ≤ 30 years old; 48.45% worked in the internal medicine department; 54.64% graduated from 2-year university technical programs; 54.12% were N2 registered nurses; 35.57% and 21.13% had ≥ 10 and 1–3 years of work experience, respectively; and 48.45% worked in general wards. User need (r = 0.52, p = 0.000), perceived usefulness (r = 0.54, p = 0.000), perceived ease of use (r = 0.51, p = 0.000), and usage attitude (r = 0.41, p = 0.000) were positively correlated with emergency care competencies. Furthermore, the multiple regression analysis revealed that perceived usefulness was the primary factor associated with the participants’ emergency care competencies.

Conclusions

The results of this study may serve as a reference for acute care facility authorities in designing advanced nursing competency standards and emergency care training programs for nurses.
Evaluation of a dementia awareness game for undergraduate nursing students in Northern Ireland: a Pre-/Post-Test study
Authors: Craig Stephanie , Stark Patrick , Wilson Christine Brown , Carter Gillian , Clarke Sonya , Mitchell Gary
Published: May 2023

Introduction

Although it is possible to live well with dementia and many individuals with dementia lead active lives with the help of family, friends, and communities, the general impression of dementia is frequently negative. Dementia is a global health issue. Despite this, little research has been done on the effects of innovative dementia education strategies among undergraduate nursing students. The aim of this study was therefore to assess if this serious digital game, originally intended for the public, could increase knowledge about dementia in first-year nursing students.

Methods

The intervention was a digital serious game called “The Dementia Game”, which was available to students throughout February 2021, to a convenience sample of first-year undergraduate nursing students (n = 560) completing a BSc Honours Nursing Degree programme in one university in Northern Ireland. The game was evaluated using a pretest-posttest design. The questionnaire comprised of a 30- item true- false Alzheimer’s Disease Knowledge Scale (ADKS), which covers risk factors, assessment and diagnosis, symptoms, course, life impact, caregiving and treatment and management. Data were analysed using paired t-tests and descriptive statistics.

Results

Overall dementia knowledge increased significantly after playing the game. Pre-test to post-test increases were observed across a range of seven categories of dementia knowledge (life impact, risk factors, symptoms, treatment, assessment, caregiving and trajectory), with particularly large increases in knowledge of trajectory and risk factors, as shown using paired t-tests. All pre-test to post-test comparisons were significant at the p < 0.001 level.

Conclusions

A short serious digital game on dementia improved first-year student’s knowledge about dementia. Undergraduate students also expressed that this approach to dementia education was effective in improving their knowledge about the disease.
Chinese Intelligence Prescription System improves prescription accuracy while decreasing labor and drug costs
Authors: Huang Ting-Yu , Huang Wei-Te , Lin Yu-Chuan , Hung Hao-Hsiu , Ou Shi-Chen , Chang Chin-Wei , Lin Hung-En , Lin Ting-Yen , Chang Ching-Wen , Hung Hui-Chun , Huang Sheng-Teng
Published: May 2023

Background and Aim

The traditional method of taking Chinese Medicine involves creating a decoction by cooking medicinal Chinese herbs. However, this method has become less popular, being replaced by the more convenient method of consuming concentrated Chinese herbal extracts, which creates challenges related to the complexity of stacking multiple formulas.

Methods

We developed the Chinese Intelligence Prescription System (CIPS) to simplify the prescription process. In this study, we used data from our institutions pharmacy to calculate the number of reductions, average dispensing time, and resulting cost savings.

Results

The mean number of prescriptions was reduced from 8.19 ± 3.65 to 7.37 ± 3.34 ($$p=2.46\;\times10^{-8}$$

p
=
2.46

×

10

-
8

). The reduction in the number of prescriptions directly resulted in decreased dispensing time, reducing it from 1.79 ± 0.25 to 1.63 ± 0.66 min ($$p=1.88\;\times10^{-14}$$

p
=
1.88

×

10

-
14

). The reduced dispensing time totaled 3.75 h per month per pharmacist, equivalent to an annual labor cost savings of $15,488 NTD per pharmacist. In addition, drug loss was reduced during the prescription process, with a mean savings of $4,517 NTD per year. The combined savings adds up to a not insignificant $20,005 NTD per year per pharmacist. When taking all TCM clinics/hospitals in Taiwan into account, the total annual savings would be $77 million NTD.

Conclusion

CIPS assists clinicians and pharmacists to formulate precise prescriptions in a clinical setting to simplify the dispensing process while reducing medical resource waste and labor costs.
Familial 5.29 Mb deletion in chromosome Xq22.1–q22.3 with a normal phenotype: a rare pedigree and literature review
Authors: Xu Hui-Hui , Zhang Yang , He Zhe-Hang , Di Xing-Hong , Pan Fei-Yan , Shi Wei-Wu
Published: May 2023

Background

Xq22.1–q22.3 deletion is a rare chromosome aberration. The purpose of this study was to identify the correlation between the phenotype and genotype of chromosome Xq22.1–q22.3 deletions.

Methods

Chromosome aberrations were identified by copy number variation sequencing (CNV-seq) technology and karyotype analysis. Furthermore, we reviewed patients with Xq22.1–q22.3 deletions or a deletion partially overlapping this region to highlight the rare condition and analyse the genotype–phenotype correlations.

Results

We described a female foetus who is the “proband” of a Chinese pedigree and carries a heterozygous 5.29 Mb deletion (GRCh37: chrX: 100,460,000–105,740,000) in chromosome Xq22.1–q22.3, which may affect 98 genes from DRP2 to NAP1L4P2. This deletion encompasses 7 known morbid genes: TIMM8A, BTK, GLA, HNRNPH2, GPRASP2, PLP1, and SERPINA7. In addition, the parents have a normal phenotype and are of normal intelligence. The paternal genotype is normal. The mother carries the same deletion in the X chromosome. These results indicate that the foetus inherited this CNV from her mother. Moreover, two more healthy female family members were identified to carry the same CNV deletion through pedigree analysis according to the next-generation sequencing (NGS) results. To our knowledge, this family is the first pedigree to have the largest reported deletion of Xq22.1–q22.3 but to have a normal phenotype with normal intelligence.

Conclusions

Our findings further improve the understanding of the genotype–phenotype correlations of chromosome Xq22.1–q22.3 deletions.This report may provide novel information for prenatal diagnosis and genetic counselling for patients who carry similar chromosome abnormalities.
Targeting unfolded protein response reverts ER stress and ER Ca2+ homeostasis in cardiomyocytes expressing the pathogenic variant of Lamin A/C R321X
Authors: Pietrafesa Giusy , De Zio Roberta , Scorza Simona Ida , Armentano Maria Francesca , Pepe Martino , Forleo Cinzia , Procino Giuseppe , Gerbino Andrea , Svelto Maria , Carmosino Monica
Published: May 2023

Background

We previously demonstrated that an Italian family affected by a severe dilated cardiomyopathy (DCM) with history of sudden deaths at young age, carried a mutation in the Lmna gene encoding for a truncated variant of the Lamin A/C protein (LMNA), R321X. When expressed in heterologous systems, such variant accumulates into the endoplasmic reticulum (ER), inducing the activation of the PERK-CHOP pathway of the unfolded protein response (UPR), ER dysfunction and increased rate of apoptosis. The aim of this work was to analyze whether targeting the UPR can be used to revert the ER dysfunction associated with LMNA R321X expression in HL-1 cardiac cells.

Methods

HL-1 cardiomyocytes stably expressing LMNA R321X were used to assess the ability of 3 different drugs targeting the UPR, salubrinal, guanabenz and empagliflozin to rescue ER stress and dysfunction. In these cells, the state of activation of both the UPR and the pro-apoptotic pathway were analyzed monitoring the expression levels of phospho-PERK, phospho-eIF2α, ATF4, CHOP and PARP-CL. In addition, we measured ER-dependent intracellular Ca2+ dynamics as indicator of proper ER functionality.

Results

We found that salubrinal and guanabenz increased the expression levels of phospho-eIF2α and downregulated the apoptosis markers CHOP and PARP-CL in LMNA R321X-cardiomyocytes, maintaining the so-called adaptive UPR. These drugs also restored ER ability to handle Ca2+ in these cardiomyocytes. Interestingly, we found that empagliflozin downregulated the apoptosis markers CHOP and PARP-CL shutting down the UPR itself through the inhibition of PERK phosphorylation in LMNA R321X-cardiomyocytes. Furthermore, upon empagliflozin treatment, ER homeostasis, in terms of ER ability to store and release intracellular Ca2+ was also restored in these cardiomyocytes.

Conclusions

We provided evidence that the different drugs, although interfering with different steps of the UPR, were able to counteract pro-apoptotic processes and to preserve the ER homeostasis in R321X LMNA-cardiomyocytes. Of note, two of the tested drugs, guanabenz and empagliflozin, are already used in the clinical practice, thus providing preclinical evidence for ready-to-use therapies in patients affected by the LMNA R321X associated cardiomyocytes.
Predicting response and toxicity to immune checkpoint inhibitors in lung cancer using antibodies to frameshift neoantigens
Authors: Shen Luhui , Brown Justin R. , Johnston Stephen Albert , Altan Mehmet , Sykes Kathryn F.
Published: May 2023

Purpose

To evaluate a new class of blood-based biomarkers, anti-frameshift peptide antibodies, for predicting both tumor responses and adverse immune events to immune checkpoint inhibitor (ICI) therapies in advanced lung cancer patients.

Experimental design

Serum samples were obtained from 74 lung cancer patients prior to palliative PD-(L)1 therapies with subsequently recorded tumor responses and immune adverse events (irAEs). Pretreatment samples were assayed on microarrays of frameshift peptides (FSPs), representing ~ 375,000 variant peptides that tumor cells can be informatically predicted to produce from translated mRNA processing errors. Serum-antibodies specifically recognizing these ligands were measured. Binding activities preferentially associated with best-response and adverse-event outcomes were determined. These antibody bound FSPs were used in iterative resampling analyses to develop predictive models of tumor response and immune toxicity.

Results

Lung cancer serum samples were classified based on predictive models of ICI treatment outcomes. Disease progression was predicted pretreatment with ~ 98% accuracy in the full cohort of all response categories, though ~ 30% of the samples were indeterminate. This model was built with a heterogeneous sample cohort from patients that (i) would show either clear response or stable outcomes, (ii) would be administered either single or combination therapies and (iii) were diagnosed with different lung cancer subtypes. Removing the stable disease, combination therapy or SCLC groups from model building increased the proportion of samples classified while performance remained high. Informatic analyses showed that several of the FSPs in the all-response model mapped to translations of variant mRNAs from the same genes. In the predictive model for treatment toxicities, binding to irAE-associated FSPs provided 90% accuracy pretreatment, with no indeterminates. Several of the classifying FSPs displayed sequence similarity to self-proteins.

Conclusions

Anti-FSP antibodies may serve as biomarkers for predicting ICI outcomes when tested against ligands corresponding to mRNA-error derived FSPs. Model performances suggest this approach might provide a single test to predict treatment response to ICI and identify patients at high risk for immunotherapy toxicities.
An ocular Th1 immune response promotes corneal nerve damage independently of the development of corneal epitheliopathy
Authors: Vereertbrugghen Alexia , Pizzano Manuela , Sabbione Florencia , Keitelman Irene Angelica , Shiromizu Carolina Maiumi , Aguilar Douglas Vera , Fuentes Federico , de Paiva Cintia S. , Giordano Mirta , Trevani Analía , Galletti Jeremías G.
Published: May 2023

Proper sight is not possible without a smooth, transparent cornea, which is highly exposed to environmental threats. The abundant corneal nerves are interspersed with epithelial cells in the anterior corneal surface and are instrumental to corneal integrity and immunoregulation. Conversely, corneal neuropathy is commonly observed in some immune-mediated corneal disorders but not in others, and its pathogenesis is poorly understood. Here we hypothesized that the type of adaptive immune response may influence the development of corneal neuropathy. To test this, we first immunized OT-II mice with different adjuvants that favor T helper (Th)1 or Th2 responses. Both Th1-skewed mice (measured by interferon-γ production) and Th2-skewed (measured by interleukin-4 production) developed comparable ocular surface inflammation and conjunctival CD4+ T cell recruitment but no appreciable corneal epithelial changes upon repeated local antigenic challenge. Th1-skewed mice showed decreased corneal mechanical sensitivity and altered corneal nerve morphology (signs of corneal neuropathy) upon antigenic challenge. However, Th2-skewed mice also developed milder corneal neuropathy immediately after immunization and independently of ocular challenge, suggestive of adjuvant-induced neurotoxicity. All these findings were confirmed in wild-type mice. To circumvent unwanted neurotoxicity, CD4+ T cells from immunized mice were adoptively transferred to T cell-deficient mice. In this setup, only Th1-transferred mice developed corneal neuropathy upon antigenic challenge. To further delineate the contribution of each profile, CD4+ T cells were polarized in vitro to either Th1, Th2, or Th17 cells and transferred to T cell-deficient mice. Upon local antigenic challenge, all groups had commensurate conjunctival CD4+ T cell recruitment and macroscopic ocular inflammation. However, none of the groups developed corneal epithelial changes and only Th1-transferred mice showed signs of corneal neuropathy. Altogether, the data show that corneal nerves, as opposed to corneal epithelial cells, are sensitive to immune-driven damage mediated by Th1 CD4+ T cells in the absence of other pathogenic factors. These findings have potential therapeutic implications for ocular surface disorders.
The BET PROTAC inhibitor dBET6 protects against retinal degeneration and inhibits the cGAS-STING in response to light damage
Authors: Zhu Xingfei , Liu Wei , Tang Xiangcheng , Chen Yulin , Ge Xiangyu , Ke Qin , Liang Xingmiao , Gan Yuwen , Zheng Yingfeng , Zou Ming , Deng Mi , Liu Yizhi , Li David Wan-Cheng , Gong Lili
Published: May 2023

Background

Chronic inflammation significantly contributes to photoreceptor death in blinding retinal diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that act as key proinflammatory factors. We recently found the first-generation BET inhibitor JQ1 alleviated sodium iodate-induced retinal degeneration by suppressing cGAS-STING innate immunity. Here, we investigated the effects and mechanism of dBET6, a proteolysis‑targeting chimera (PROTAC) small molecule that selectively degrades BET by the ubiquitin‒proteasome system, in light-induced retinal degeneration.

Methods

Mice were exposed to bright light to induce retinal degeneration, and the activation of cGAS-STING was determined by RNA-sequencing and molecular biology. Retinal function, morphology, photoreceptor viability and retinal inflammation were examined in the presence and absence of dBET6 treatment.

Results

Intraperitoneal injection of dBET6 led to the rapid degradation of BET protein in the retina without detectable toxicity. dBET6 improved retinal responsiveness and visual acuity after light damage (LD). dBET6 also repressed LD-induced retinal macrophages/microglia activation, Müller cell gliosis, photoreceptor death and retinal degeneration. Analysis of single-cell RNA-sequencing results revealed cGAS-STING components were expressed in retinal microglia. LD led to dramatic activation of the cGAS-STING pathway, whereas dBET6 suppressed LD-induced STING expression in reactive macrophages/microglia and the related inflammatory response.

Conclusions

This study indicates targeted degradation of BET by dBET6 exerts neuroprotective effects by inhibiting cGAS-STING in reactive retinal macrophages/microglia, and is expected to become a new strategy for treatment of retinal degeneration.
A Nano-QSTR model to predict nano-cytotoxicity: an approach using human lung cells data
Authors: Meneses João , González-Durruthy Michael , Fernandez-de-Gortari Eli , Toropova Alla P. , Toropov Andrey A. , Alfaro-Moreno Ernesto
Published: May 2023

Background

The widespread use of new engineered nanomaterials (ENMs) in industries such as cosmetics, electronics, and diagnostic nanodevices, has been revolutionizing our society. However, emerging studies suggest that ENMs present potentially toxic effects on the human lung. In this regard, we developed a machine learning (ML) nano-quantitative-structure-toxicity relationship (QSTR) model to predict the potential human lung nano-cytotoxicity induced by exposure to ENMs based on metal oxide nanoparticles.

Results

Tree-based learning algorithms (e.g., decision tree (DT), random forest (RF), and extra-trees (ET)) were able to predict ENMs’ cytotoxic risk in an efficient, robust, and interpretable way. The best-ranked ET nano-QSTR model showed excellent statistical performance with R2 and Q2-based metrics of 0.95, 0.80, and 0.79 for training, internal validation, and external validation subsets, respectively. Several nano-descriptors linked to the core-type and surface coating reactivity properties were identified as the most relevant characteristics to predict human lung nano-cytotoxicity.

Conclusions

The proposed model suggests that a decrease in the ENMs diameter could significantly increase their potential ability to access lung subcellular compartments (e.g., mitochondria and nuclei), promoting strong nano-cytotoxicity and epithelial barrier dysfunction. Additionally, the presence of polyethylene glycol (PEG) as a surface coating could prevent the potential release of cytotoxic metal ions, promoting lung cytoprotection. Overall, the current work could pave the way for efficient decision-making, prediction, and mitigation of the potential occupational and environmental ENMs risks.
Transtendon technique versus repair after completion of the tear for articular-sided partial rotator cuff tear: a meta-analysis of comparative studies
Authors: Yang Yimeng , Hu Dan , Chen Shiyi , Guan Shibing , Shang Xiliang
Published: May 2023

Background

Transtendon repair and repair after completion of the tear have been widely used to treat partial-thickness rotator cuff tears (PT-RCTs). The present study was aimed to compare the clinical outcomes and tendon integrity following arthroscopic repair of articular PT-RCTs using transtendon repair or repair after completion of the tear.

Methods

We performed a systematic electronic database search on Cochrane Central Register of Controlled Trials, PubMed and Embase to identify articles equating articular-sided PT-RCTs repair. The randomized controlled clinical trials that met our criteria were evaluated for quality of methodology. The results obtained were further analyzed and correlated to present the benefits and drawbacks comparing the two surgical procedures.

Result

According to our inclusion and exclusion criteria, six articles were included in the present study. A total of 501 patients were analyzed as part of this study. The results indicated that both the surgical treatments provided excellent functional improvements and tendon integrity. However, no significant differences for the visual analogue scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, constant score, range of motion, postoperative adhesive capsulitis, tendon integrity and patient satisfaction were found between the two cohorts (p > 0.05).

Conclusions

Both transtendon technique and repair after completion of the tear for articular-sided partial rotator cuff tear provide improvements in clinical outcome with a low complication rate and a high rate of healing.