bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome-level genome provides insights into environmental adaptability and innate immunity in the common dolphin (Delphinus delphis)
Authors: Ding Kui , Xu Qinzeng , Zhao Liyuan , Li Yixuan , Li Zhong , Shi Wenge , Zeng Qianhui , Wang Xianyan , Zhang Xuelei
Published: April 2024

The common dolphin (Delphinus delphis) is widely distributed worldwide and well adapted to various habitats. Animal genomes store clues about their pasts, and can reveal the genes underlying their evolutionary success. Here, we report the first high-quality chromosome-level genome of D. delphis. The assembled genome size was 2.56 Gb with a contig N50 of 63.85 Mb. Phylogenetically, D. delphis was close to Tursiops truncatus and T. aduncus. The genome of D. delphis exhibited 428 expanded and 1,885 contracted gene families, and 120 genes were identified as positively selected. The expansion of the HSP70 gene family suggested that D. delphis has a powerful system for buffering stress, which might be associated with its broad adaptability, longevity, and detoxification capacity. The expanded IFN-α and IFN-ω gene families, as well as the positively selected genes encoding tripartite motif-containing protein 25, peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, and p38 MAP kinase, were all involved in pathways for antiviral, anti-inflammatory, and antineoplastic mechanisms. The genome data also revealed dramatic fluctuations in the effective population size during the Pleistocene. Overall, the high-quality genome assembly and annotation represent significant molecular resources for ecological and evolutionary studies of Delphinus and help support their sustainable treatment and conservation.
Occurrence, antimicrobial susceptibility, and resistance genes of Staphylococcus aureus in milk and milk products in the Arsi highlands of Ethiopia
Authors: Deddefo Abiot , Mamo Gezahegne , Asfaw Minda , Edao Adem , Hiko Adem , Fufa Dereje , Jafer Mohammed , Sombo Melaku , Amenu Kebede
Published: April 2024

Background

In Ethiopia, milk production and handling practices often lack proper hygiene measures, leading to the potential contamination of milk and milk products with Staphylococcus aureus (S. aureus), including methicillin-resistant strains, posing significant public health concerns. This study aimed to investigate the occurrence, antimicrobial susceptibility profiles and presence of resistance genes in S. aureus strains isolated from milk and milk products.

Methods

A cross-sectional study was conducted in the Arsi highlands, Oromia, Ethiopia from March 2022 to February 2023. A total of 503 milk and milk product samples were collected, comprising 259 raw milk, 219 cottage cheese, and 25 traditional yogurt samples. S. aureus isolation and coagulase-positive staphylococci enumeration were performed using Baird-Parker agar supplemented with tellurite and egg yolk. S. aureus was further characterized based on colony morphology, Gram stain, mannitol fermentation, catalase test, and coagulase test. Phenotypic antimicrobial resistance was assessed using the Kirby–Bauer disc diffusion method, while the polymerase chain reaction (PCR) was employed for confirming the presence of S. aureus and detecting antimicrobial resistance genes.

Results

S. aureus was detected in 24.9% of the milk and milk products, with the highest occurrence in raw milk (40.9%), followed by yogurt (20%), and cottage cheese (6.4%). The geometric mean for coagulase-positive staphylococci counts in raw milk, yogurt, and cottage cheese was 4.6, 3.8, and 3.2 log10 CFU/mL, respectively. Antimicrobial resistance analysis revealed high levels of resistance to ampicillin (89.7%) and penicillin G (87.2%), with 71.8% of the isolates demonstrating multidrug resistance. Of the 16 S. aureus isolates analyzed using PCR, all were found to carry the nuc gene, with the mecA and blaZ genes detected in 50% of these isolates each.

Conclusion

This study revealed the widespread distribution of S. aureus in milk and milk products in the Arsi highlands of Ethiopia. The isolates displayed high resistance to ampicillin and penicillin, with a concerning level of multidrug resistance. The detection of the mecA and blaZ genes in selected isolates is of particular concern, highlighting a potential public health hazard and posing a challenge to effective antimicrobial treatment. These findings highlight the urgent need to enhance hygiene standards in milk and milk product handling and promote the rational use of antimicrobial drugs. Provision of adequate training for all individuals involved in the dairy sector can help minimize contamination. These measures are crucial in addressing the threats posed by S. aureus, including methicillin-resistant strains, and ensuring the safety of milk and its products for consumers.
Clinical presentation and management of methanol poisoning outbreaks in Riyadh, Saudi Arabia: a retrospective analysis
Authors: Alhusain Faisal , Alshalhoub Mohammed , Homaid Moath Bin , Esba Laila Carolina Abu , Alghafees Mohammad , Al Deeb Mohammad
Published: April 2024

Background

Acute methanol intoxication, whether unintentional or deliberate, necessitates prompt intervention to prevent severe morbidity and mortality. Homemade alcoholic beverages are a frequent source of such poisoning. This retrospective analysis examined two outbreaks of methanol intoxication in Saudi Arabia. It investigated the clinical presentation, implemented management strategies, and any lasting complications (sequelae) associated with these cases. The aim was to assess the potential impact of different treatment modalities and the timeliness of their initiation on patient outcomes.

Methods

This was a retrospective case series of methanol poisoning cases which presented to the adult emergency department (ED) at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. There were two separate outbreaks in the city, the first one was from September 1 to September 10, 2020 and the second one was from May 14 to May 20, 2021. Electronic charts were reviewed, and data were extracted to previously prepared data extraction sheets.

Result

From the 22 patients who arrived in the ED alive, the most common complaints were nausea or vomiting followed by altered level of consciousness. About 9% from the patient were hypotensive, 36% were tachycardic, 41% were tachypneic and 4% were having SpO2 < 94%. Brain CT was abnormal in 6 patients. Vision impairment was the most common sequalae of methanol poisoning (7 out of 12 patients who were assessed by ophthalmologist, 58%). When the patients were divided based on severity (mild, moderate, severe), nausea or vomiting and loss of consciousness were the most common complaints among the moderate group while loss of consciousness predominated in the severe group. Two patients presented with low blood pressure and were in the sever group. The severe group had a mean Glasgow Coma Scale (GCS) of 8. Most of the patients in the severity groups underwent the same management apart from those who died or deposited. Eight patients in the severe group had to be intubated.

Conclusion

This study demonstrates the multifaceted clinical presentation of methanol poisoning, culminating in a 17.4% mortality rate. Notably, our findings emphasize the critical role of prompt diagnosis and swift initiation of combined fomepizole therapy and hemodialysis in mitigating mortality and minimizing the potential for chronic visual sequelae associated with methanol poisoning.
Calcitonin gene-related peptide: a possible biomarker in migraine patients with patent foramen ovale
Authors: Li Chaojie , Yu Yu , Li Ningning , Yin Ya-Na , Zhang Lianjun , Xie Kehang , Huang Donghui
Published: April 2024

Background

Serum CGRP has been found to increase during migraine attack. However, whether CGRP can identify MA with PFO subtypes in MA remains unknown. This study aimed to investigate the differential expression of calcitonin gene-related peptide (CGRP) between migraine (MA) patients with and without patent foramen ovale (PFO), and to evaluate the predictive value of CGRP for MA with PFO.

Methods

A total of 153 patients with MA, 51 patients with PFO and 102 patients without. Venous blood was drawn and HIT-6 score was calculated during the onset of MA, and blood routine, inflammatory indexes and serum CGRP were detected. The differences in serum markers and HIT-6 scores were compared between the two groups, and the risk factors of MA with PFO were determined by univariate and multivariate logistics regression. Furthermore, the correlation between CGRP level with right-to-left shunt (RLS) grades and headache impact test-6 (HIT-6) score in MA patients with PFO were assessed. Independent risk factors were screened out by multivariate Logistic regression analysis. We used the receiver operating characteristic (ROC) curve to analyze the diagnostic value of these risk factors in MA complicated with PFO.

Results

The serum CGRP level and HIT-6 scores in the MA with PFO group were significantly higher than those in the MA group (P < 0.001). Multivariate regression analysis showed that CGRP was an independent risk factor for MA with PFO (OR = 1.698, 95% CI = 1.325–2.179, P < 0.001). CGRP values ​​increased with the increase of RLS grade(Spearmen rho = 0.703, P < 0.001). Furthermore, a positive correlation between CGRP and HIT-6 scores was found (Spearmen rho = 0.227; P = 0.016). ROC curve showed that the optimal cut-off value for diagnosing MA with PFO was 79 pg/mL, the area under the curve (AUC) for predicting MA with PFO was 0.845, with 72.55% sensitivity and 78.43% specificity.

Conclusions

MA patients with PFO have higher serum CGRP level. elevated CGRP concentration was associated with higher RLS grade and increased HIT-6 score. Higher serum CGRP level has certain clinical value in predicting PFO in MA patients.

Trial registration

This study was approved by the Ethics Committee of Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine (Ethics batch number: 20,201,215,005).
Five-factor model personality traits, exclusive breastfeeding, and self-efficacy: a mediational analysis
Authors: Yadollahi Parvin , Padashian Fatemeh , Doostfatemeh Marziyeh
Published: April 2024

Background

Despite the World Health Organization’s (WHO) emphasis on exclusive breastfeeding, the documents show a declining trend worldwide. Studies assert that the mother’s personality traits appear to have an impact on this issue. This study aimed to investigate the potential influence of personality traits on exclusive breastfeeding, which might be channeled by self-efficacy as a mediator variable.

Methods

Data were analyzed from the cross-sectional study. The exclusive breastfeeding scale, the breastfeeding self-efficacy questionnaire, and the Five-Factor Model questionnaire (as follows: neuroticism, extraversion, openness experience, agreeableness, and conscientiousness) were completed by120 Iranian volunteer mothers with an infant aged 6–12 months referred to health centers in Shiraz (a major city in southern Iran) between May to December 2019. The structural equation modeling (SEM) approach was used to obtain the direct and indirect effects of personality traits and self-efficacy on exclusive breastfeeding.

Results

The study showed the significant direct effect of some personality traits (agreeableness, extraversion, and consciousness) and self-efficacy on exclusive breastfeeding. The indirect effect of extraversion on exclusive breastfeeding through self-efficacy was also obtained from the result of SEM analysis. The model fit the data satisfactorily, according to the fit indices criteria extracted from the mediational analysis.

Conclusions

Self-efficacy appears to be a significant predictor of exclusive breastfeeding. Therefore, exclusive breastfeeding could be enhanced by safe education in pregnancy, reinforcing the self-efficacy of pregnant women and considering their personality traits.
The effect of maternal voice and non-nutritional sucking on repeated procedural pain of heel prick in neonates: a quasi-experimental study
Authors: Chen Yushuang , Zhou Leshan , Tan Yanjuan
Published: April 2024

Background

Neonates in the neonatal intensive care unit undergo frequent painful procedures. It is essential to reduce pain using safe and feasible methods.

Purpose

To evaluate the effects of non-nutritional sucking, mother’s voice, or non-nutritional sucking combined with mother’s voice on repeated procedural pain in hospitalized neonates.

Methods

A quasi-experimental study was conducted in which 141 neonates were selected in a hospital in Changsha, China. Newborns were divided into four groups: non-nutritional sucking (NNS) (n = 35), maternal voice (MV) (n = 35), NNS + MV (n = 34), and control (n = 37) groups. The Preterm Infant Pain Profile-Revised Scale (PIPP-R) was used to assess pain.

Results

During the heel prick, the heart rate value and blood oxygen saturation were significantly different between the groups (P < 0.05). Both non-nutritional sucking and maternal voice significantly reduced PIPP-R pain scores of hospitalized newborns (P < 0.05). The pain-relief effect was more robust in the combined group than in other groups.

Conclusions

This study showed that both non-nutritional sucking and the mother’s voice alleviated repeated procedural pain in neonates. Therefore, these interventions can be used as alternatives to reduce repeated procedural pain.
Depressive disorder and elevated risk of bell’s palsy: a nationwide propensity score-weighting study
Authors: Fann Li-Yun , Wen Yuan-Liang , Huang Yu-Chieh , Cheng Chih-Chien , Huang Ying-Che , Fang Chih-Chia , Chen Wan-Ting , Yu Pei-Yeh , Pan Hsiang-Yi , Kao Li-Ting
Published: April 2024

Background

Prior studies have reported a potential relationship between depressive disorder (DD), immune function, and inflammatory response. Some studies have also confirmed the correlation between immune and inflammatory responses and Bell’s palsy. Considering that the pathophysiology of these two diseases has several similarities, this study investigates if DD raises the risk of developing Bell’s palsy.

Methods

This nationwide propensity score-weighting cohort study utilized Taiwan National Health Insurance data. 44,198 patients with DD were identified as the DD cohort and 1,433,650 adult subjects without DD were identified as the comparison cohort. The inverse probability of treatment weighting (IPTW) strategy was used to balance the differences of covariates between two groups. The 5-year incidence of Bell’s palsy was evaluated using the Cox proportional-hazard model, presenting results in terms of hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

The average age of DD patients was 48.3 ± 17.3 years, and 61.86% were female. After propensity score-weighting strategy, no significant demographic differences emerged between the DD and comparison cohort. The Cox proportional hazards model revealed a statistically significant adjusted IPTW-HR of 1.315 (95% CI: 1.168–1.481) for Bell’s palsy in DD patients compared to comparison subjects. Further independent factors for Bell’s palsy in this model were age (IPTW-HR: 1.012, 95% CI: 1.010–1.013, p < 0.0001), sex (IPTW-HR: 0.909, 95% CI: 0.869–0.952, p < 0.0001), hypertension (IPTW-HR: 1.268, 95% CI: 1.186–1.355, p < 0.0001), hyperlipidemia (IPTW-HR: 1.084, 95% CI: 1.001–1.173, p = 0.047), and diabetes (IPTW-HR: 1.513, 95% CI: 1.398–1.637, p < 0.0001)

Conclusion

This Study confirmed that individuals with DD face an elevated risk of developing Bell’s palsy. These findings hold significant implications for both clinicians and researchers, shedding light on the potential interplay between mental health and the risk of certain physical health outcomes.
Subnational estimates of life expectancy at birth in India: evidence from NFHS and SRS data
Authors: Yadav Pawan Kumar , Yadav Suryakant
Published: April 2024

Background

Mortality estimates at the subnational level are of urgent need in India for the formulation of policies and programmes at the district level. This is the first-ever study which used survey data for the estimation of life expectancy at birth ($$ {\text{e}}_{0}$$) for the 640 districts from NFHS-4 (2015-16) and 707 districts from NFHS-5 (2019-21) for the total, male and female population in India.

Methods

This study calculated annual age-specific mortality rates from NFHS-4 and NFHS-5 for India and all 36 states for the total, male and female population. This paper constructed the abridged life tables and estimated life expectancy at birth $$({e_0})$$ and further estimated the model parameters for all 36 states. This study linked state-specific parameters to the respective districts for the estimation of life expectancy at birth $$({e_0})$$for 640 districts from NFHS-4 and 707 districts from NFHS-5 for the total, male and female population in India.

Results

Findings at the state level showed that there were similarities between the estimated and calculated $${e_0}$$ in most of the states. The results of this article observed that the highest $${e_0}$$ varies in the ranges of 70 to 90 years among the districts of the southern region. $${e_0}$$ falls below 70 years among most of the central and eastern region districts. In the northern region districts $${e_0}$$ lies in the range of 70 years to 75 years. The estimates of life expectancy at birth $$({e_0})$$ shows the noticeable variations at the state and district levels for the person, male, and female populations from the NFHS (2015-16) and NFHS (2019-21). In the absence of age-specific mortality data at the district level in India, this study used the indirect estimation method of relating state-specific model parameters with the IMR of their respective districts and estimated $${e_0}$$ across the 640 districts from NFHS-4 (2015-16) and 707 districts from NFHS-5 (2019-21). The findings of this study have similarities with the state-level estimations of $${e_0}$$ from both data sources of SRS and NFHS and found the highest $${e_0}$$ in the southern region and the lowest $${e_0}$$ in the eastern and central region districts.

Conclusions

In the lack of $${e_0}$$ estimates at the district level in India, this study could be beneficial in providing timely life expectancy estimates from the survey data. The findings clearly shows variations in the district level $${e_0}$$. The districts from the southern region show the highest $${e_0}$$ and districts from the central and eastern region has lower $${e_0}$$. Females have higher $${e_0}$$ as compared to the male population in most of the districts in India.
Association between the circulating very long-chain saturated fatty acid and cognitive function in older adults: findings from the NHANES
Authors: Shen Yanxin , Wei Chunxiao , Taishi Yezi , Zhang Guimei , Su Zhan , Zhao Panpan , Wang Yongchun , Li Mingxi , Ji Yingshi , Sun Li
Published: April 2024

Background

Age-related cognitive decline has a significant impact on the health and longevity of older adults. Circulating very long-chain saturated fatty acids (VLSFAs) may actively contribute to the improvement of cognitive function. The objective of this study was to investigate the associations between arachidic acid (20:0), docosanoic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0) with cognitive function in older adults.

Methods

This study used a dataset derived from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). A total of 806 adults (≥ 60 years) were included who underwent comprehensive cognitive testing and plasma fatty acid measurements. Multivariable linear regression, restricted cubic spline (RCS), and interaction analyses were used to assess associations between VLSFAs and cognitive function. Partial Spearman’ s correlation analysis was used to examine the correlations between VLSFAs and palmitic acid (16:0), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, systemic inflammatory markers, and dietary nutrients.

Results

Multivariable linear regression analysis, adjusting for sociodemographic, clinical conditions, and lifestyle factors, showed that 22:0 and 24:0 levels were positively associated with better global cognitive function (β = 0.37, 95% confidence interval [CI] = 0.01, 0.73; β = 0.73, 95% CI = 0.29, 1.2, respectively) as well as better CEARD-DR Z-score (β = 0.82, 95% CI = 0.36, 1.3 and β = 1.2, 95% CI = 0.63, 1.8, respectively). RCS analysis showed linear associations between higher 22:0 and 24:0 levels and better cognitive performance in both global cognitive function and CERAD-DR tests.

Conclusions

The study suggests that higher levels of 22:0 and 24:0 are associated with better global cognitive function in older adults. 22:0 and 24:0 may be important biomarkers for recognizing cognitive impairment, and supplementation with specific VLSFAs (22:0 and 24:0) may be an important intervention to improve cognitive function. Further studies are needed to elucidate the underlying biological mechanisms between VLSFAs and cognitive function.
The association between frailty and survival in patients with pleural disease: a retrospective cohort study
Authors: Barton Eleanor , Verduri A. , Carter B. , Hughes J. , Hewitt J. , Maskell N. A.
Published: April 2024

Background

There are currently no data on the relationship between frailty and mortality in pleural disease. Understanding the relationship between frailty and outcomes is increasingly important for clinicians to guide decisions regarding investigation and management. This study aims to explore the relationship between all-cause mortality and frailty status in patients with pleural disease.

Methods

In this retrospective analysis of a prospectively collected observational cohort study, outpatients presenting to the pleural service at a tertiary centre in Bristol, UK with a radiologically confirmed, undiagnosed pleural effusion underwent comprehensive assessment and were assigned a final diagnosis at 12 months. The modified frailty index (mFI) was calculated and participants classified as frail (mFI ≥ 0.4) or not frail (mFI ≤ 0.2).

Results

676 participants were included from 3rd March 2008 to 29th December 2020. The median time to mortality was 490 days (IQR 161–1595). A positive association was found between 12-month mortality and frailty (aHR = 1.72, 95% CI 1.02–2.76, p = 0.025) and age ≥ 80 (aHR = 1.80, 95% CI 1.24–2.62, p = 0.002). Subgroup analyses found a stronger association between 12-month mortality and frailty in benign disease (aHR = 4.36, 95% CI 2.17–8.77, p < 0.0001) than in all pleural disease. Malignancy irrespective of frailty status was associated with an increase in all-cause mortality (aHR = 10.40, 95% CI 6.01–18.01, p < 0.0001).

Conclusion

This is the first study evaluating the relationship between frailty and outcomes in pleural disease. Our data demonstrates a strong association between frailty and 12-month mortality in this cohort. A malignant diagnosis is an independent predictor of 12-month mortality, irrespective of frailty status. Frailty was also strongly associated with 12-month mortality in patients with a benign underlying cause for their pleural disease. This has clinical relevance for pleural physicians; evaluating patients’ frailty status and its impact on mortality can guide clinicians in assessing suitability for invasive investigation and management.

Trial registration

This study is registered with the Health Research Authority (REC reference 08/H0102/11) and the NIHR Portfolio (Study ID 8960).
Etiology of bacterial pneumonia and multi-drug resistance pattern among pneumonia suspected patients in Ethiopia: a systematic review and meta-analysis
Authors: Tilahun Mihret , Belete Melaku Ashagrie , Gedefie Alemu , Debash Habtu , Alemayehu Ermiyas , Gebretsadik Daniel , Ebrahim Hussein , Mohammed Ousman
Published: April 2024

Background

Bacterial pneumonia can affect all age groups, but people with weakened immune systems, young children, and the elderly are at a higher risk. Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa are the most common causative agents of pneumonia, and they have developed high MDR in recent decades in Ethiopia. This systematic review and meta-analysis aimed to determine the pooled prevalence of bacterial pneumonia and multidrug resistance in Ethiopia.

Methods

The articles were searched extensively in the electronic databases and grey literature using entry terms or phrases. Studies meeting the eligibility criteria were extracted in MS Excel and exported for statistical analysis into STATA version 14 software. The pooled prevalence of bacterial pneumonia and multidrug resistance were calculated using a random-effects model. Heterogeneity was assessed by using the I2 value. Publication bias was assessed using a funnel plot and Egger’s test. A sensitivity analysis was done to assess the impact of a single study on the pooled effect size.

Result

Of the 651 studies identified, 87 were eligible for qualitative analysis, of which 11 were included in the meta-analysis consisting of 1154 isolates. The individual studies reported prevalence of bacterial pneumonia ranging from 6.19 to 46.3%. In this systematic review and metanalysis, the pooled prevalence of bacterial pneumonia in Ethiopia was 37.17% (95% CI 25.72–46.62), with substantial heterogeneity (I2 = 98.4%, p < 0.001) across the studies. The pooled prevalence of multidrug resistance in bacteria isolated from patients with pneumonia in Ethiopia was 67.73% (95% CI: 57.05–78.40). The most commonly isolated bacteria was Klebsiella pneumoniae, with pooled prevalence of 21.97% (95% CI 16.11–27.83), followed by Streptococcus pneumoniae, with pooled prevalence of 17.02% (95% CI 9.19–24.86), respectively.

Conclusion

The pooled prevalence of bacterial isolates from bacterial pneumonia and their multidrug resistance were high among Ethiopian population. The initial empirical treatment of these patients remains challenging because of the strikingly high prevalence of antimicrobial resistance.
Light environment affects the efficiency of surgical suture training
Authors: Gu Yuan , Xie Lihua , Huang Xianzhe , Liu Chan , Ouyang Zhengxiao , Yuan Liqin , Li Wenzhao
Published: April 2024

Background

Suture knotting is the basis of surgical skills. In the process of surgical skills learning, the surrounding environment, especially the light, will affect the efficiency of learning. This study investigated the effect of optical environment on the learning of stitching and knotting skills.

Methods

A total of 44 medical students were randomly divided into four groups and participated in the study of suture knotting in four different optical environments. During the process, we assess objective pressure level by testing salivary amylase activity Likert scale and objective structured clinical examination (OSCE) was used to estimate the subjective psychological state and overall skill mastery in surgical suturing respectively.

Results

Under high illumination conditions (700 lx), the salivary amylase activity of the high color temperature group (6000 K) was significantly higher than that of the low color temperature group (4000 K) (p < 0.0001). Similarly, under low illumination (300 lx), the salivary amylase activity of the high color temperature group was also significantly higher than that of the low color temperature group (p < 0.05). The student under high illumination conditions (700 lx) and the low color temperature (6000 K) have an autonomy score between 37–45, which is significantly higher compared to the other three groups (p < 0.0001). Group 2 has an average OSCE score of 95.09, which were significantly higher than those of the other three groups (p < 0.05).

Conclusion

High illumination combined with low color temperature is considered as the optimal training conditions, promoting trainees' optimism, reducing stress levels, and enhancing learning efficiency. These results highlight the pivotal role of light environment in improving the quality and efficiency of surgical skills training.
Grace Under Pressure: a mixed methods impact assessment of a verbatim theatre intervention to improve healthcare workplace culture
Authors: Hooker Claire , Karageorge Aspasia , Scott Karen M. , Lim Renee , Nash Louise
Published: April 2024

Background

Healthcare workplace mistreatment has been documented globally. Poor workplace behaviour, ranging from incivility to bullying and harassment, is common in healthcare, and contributes significantly to adverse events in healthcare, poor mental health among healthcare workers, and to attrition in the healthcare workforce, particularly in junior years. Poor workplace behaviour is often normalised, and is difficult to address. Verbatim theatre, a form of research informed theatre in which plays are created from informants’ exact words only, is particularly suited to facilitating workplace culture change by raising awareness about issues that are difficult to discuss. The objective of this study was to assess the impact of the verbatim theatre play ‘Grace Under Pressure’ on workplace culture in NSW hospitals.

Methods

The intervention was conducted in 13 hospitals from 8 Local Health Districts (LHDs) in NSW, Australia, in October and November 2019, with aggregated impact across all sites measured by a bespoke survey (‘Pam McLean Centre (PMC) survey’) at the conclusion of the intervention. This study was conducted in 3 Local Health Districts (one urban, one regional, one remote), with data collection conducted in November–December 2019 and December 2020. The study design was a mixed methods assessment of the play’s impact using (1) validated baseline measures of psychosocial risk, analysed descriptively, (2) overall findings from the PMC survey above, analysed descriptively, (3) interviews conducted within a month of the intervention, analysed thematically and (4) interviews conducted one year later, analysed thematically.

Results

Half (51.5%) of the respondents (n = 149) to the baseline survey had scores indicating high risk of job strain and depressive symptoms. Of 478 respondents to the PMC survey (response rate 57%), 93% found the play important, 92% recommended others see the play, 89% considered that it stimulated thinking about workplace behaviour, and 85% that it made discussing these issues easier. Thematic analysis of interviews within one month (n = 21) showed that the play raised awareness about poor workplace behaviour and motivated behaviour change. Interviews conducted one year later (n = 6) attributed improved workplace culture to the intervention due to improved awareness, discussion and capacity to respond to challenging issues.

Conclusions

Verbatim theatre is effective in raising awareness about difficult workplace behaviour in ways that motivate behaviour change, and hence can be effective in catalysing real improvements in healthcare workplace culture. Creative approaches are recommended for addressing similarly complex challenges in healthcare workforce retention.
GATA3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in breast cancer
Authors: Wang Xuejie , Bai Feng , Liu Xiong , Peng Bin , Xu Xingzhi , Zhang Hongquan , Fu Li , Zhu Wei-Guo , Wang Bin , Pei Xin-Hai
Published: April 2024

Background

Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis.

Results

Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor.

Conclusions

These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.
Engineering Streptomyces sp. CPCC 204095 for the targeted high-level production of isatropolone A by elucidating its pathway-specific regulatory mechanism
Authors: Zhang Cong , Xu Qianqian , Fu Jie , Wu Linzhuan , Li Yihong , Lu Yuan , Shi Yuanyuan , Sun Hongmin , Li Xingxing , Wang Lifei , Hong Bin
Published: April 2024

Background

Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs.

Results

Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield—980.8 mg/L of isatropolone A—achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date.

Conclusion

In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.
Considering inequities in national dementia strategies: breadth, depth, and scope
Authors: Godard-Sebillotte Claire , Navani Sanjna , Hacker Georgia , Vedel Isabelle
Published: April 2024

Background

Considering that dementia is an international public health priority, several countries have developed national dementia strategies outlining initiatives to address challenges posed by the disease. These strategies aim to improve the care, support, and resources available to meet the needs of persons living with dementia and their care partners and communities. Despite the known impact of social determinants of health on dementia risk, care, and outcomes, it is unclear whether dementia strategies adequately address related inequities. This study aimed to describe whether and how national dementia strategies considered inequities associated with social determinants of health.

Methods

We conducted an environmental scan of the national dementia strategies of countries that are part of the Organisation for Economic Cooperation and Development (OECD). Included strategies had to be accessible in English or French. Sub-national or provincial plans were excluded. We synthesised information on strategies’ considerations of inequity through a thematic analysis.

Results

Of the 15 dementia strategies that met inclusion criteria, 13 mentioned at least one inequity (M = 2.4, median = 2, range:0–7) related to Race/Ethnicity; Religion; Age; Disability; Sexual Orientation/Gender Identity; Social Class; or Rurality. Age and disability were mentioned most frequently, and religion most infrequently. Eleven strategies included general inequity-focused objectives, while only 5 had specific inequity-focused objectives in the form of tangible percentage changes, deadlines, or allocated budgets for achieving equity-related goals outlined in their strategies.

Conclusions

Understanding if and how countries consider inequities in their dementia strategies enables the development of future strategies that adequately target inequities of concern. While most of the strategies mentioned inequities, few included tangible objectives to reduce them. Countries must not only consider inequities at a surface-level; rather, they must put forth actionable objectives that intend to lessen the impact of inequities in the care of all persons living with dementia.
Blood lipids mediate the effects of gut microbiome on endometriosis: a mendelian randomization study
Authors: Su Chang , Wan Su , Ding Jin , Ni Guantai , Ding Huafeng
Published: April 2024

Background

There is evidence for an association between the gut microbiome and endometriosis. However, their causal relationship and the mediating role of lipid metabolism remain unclear.

Methods

Using genome-wide association study (GWAS) data, we conducted a bidirectional Mendelian randomization (MR) analysis to investigate the causal relationships between gut microbiome and endometriosis. The inverse variance weighted (IVW) method was used as the primary model, with other MR models used for comparison. Sensitivity analysis based on different statistical assumptions was used to evaluate whether the results were robust. A two-step MR analysis was further conducted to explore the mediating effects of lipids, by integrating univariable MR and the multivariate MR method based on the Bayesian model averaging method (MR-BMA).

Results

We identified four possible intestinal bacteria genera associated with the risk of endometriosis through the IVW method, including Eubacterium ruminantium group (odds ratio [OR] = 0.881, 95% CI: 0.795–0.976, P = 0.015), Anaerotruncus (OR = 1.252, 95% CI: 1.028–1.525, P = 0.025), Olsenella (OR = 1.110, 95% CI: 1.007–1.223, P = 0.036), and Oscillospira (OR = 1.215, 95% CI: 1.014–1.456, P = 0.035). The further two-step MR analysis identified that the effect of Olsenella on endometriosis was mediated by triglycerides (proportion mediated: 3.3%; 95% CI = 1.5−5.1%).

Conclusion

This MR study found evidence for specific gut microbiomes associated with the risk of endometriosis, which might partially be mediated by triglycerides.
Associations of U.S. state-level COVID-19 policies intensity with cannabis sharing behaviors in 2020
Authors: Assaf Ryan D. , Hamad Rita , Javanbakht Marjan , Arah Onyebuchi A. , Shoptaw Steven J. , Cooper Ziva D. , Gorbach Pamina M.
Published: April 2024

Background

Cannabis use before the COVID-19 pandemic for many involved sharing prepared cannabis for inhalation, practices that were less prevalent during the pandemic. State-level COVID-19 containment policies may have influenced this decrease. This study examined the extent to which the intensity of state-level COVID-19 policies were associated with individual-level cannabis sharing. Findings have the potential to guide harm reduction policies for future respiratory pandemics and seasonal respiratory virus waves.

Methods

This study used cross-sectional individual-level data from the COVID-19 Cannabis Study, an anonymous U.S.-based web survey on cannabis use disseminated during the early phase of the pandemic (Full sample N = 1,883). We combined individual-level data with state-level policy data from Kaiser Family Foundation’s State COVID-19 Data and Policy Actions for three time-points from June to August 2020 that overlapped with the survey period. Cannabis sharing was dichotomized as any versus no sharing. We adapted a previously published coding framework to score the intensity of COVID-19 policies implemented in each U.S. state and averaged the policy score across the time period. We then used Poisson regression models to quantify the associations of the average state-level COVID-19 policy score with cannabis sharing during the pandemic.

Results

Participants (n = 925) reporting using inhalation as a mode for cannabis use were included in this analysis. Most respondents were male (64.1%), non-Hispanic White (54.3%), with a mean age of 33.7 years (SD 8.8). A large proportion (74.9%) reported sharing cannabis during the pandemic. Those who shared cannabis more commonly lived in states with a lower average policy score (16.7, IQR 12.3–21.5) compared to those who did not share (18.6, IQR 15.3–25.3). In adjusted models, the prevalence ratio of any cannabis sharing per every 5-unit increase in the average COVID-19 policy score was 0.97 (95% CI 0.93, 1.01).

Conclusions

Fewer individuals shared cannabis in states with more intense COVID-19 containment policies compared to those in states with less intense policies. Individuals who use cannabis may be willing to make changes to their behavior and may further benefit from specific and directed public health messaging to avoid sharing during respiratory infection outbreaks.
Health state utility estimates for value assessments of novel treatments in Huntington’s disease: a systematic literature review
Authors: Sawant Ruta , Paret Kyle , Petrillo Jennifer , Koenig Aaron , Wolowacz Sorrel , Ronquest Naoko , Rickards Hugh
Published: April 2024

Background

Huntington’s disease (HD) is a progressive neurodegenerative disease with a devastating impact on patients and their families. Quantifying how treatments affect patient outcomes is critical for informing reimbursement decisions. Many countries mandate a formal value assessment in which the treatment benefit is measured as quality-adjusted life-years, calculated with the use of utility estimates that reflect respondents’ preferences for health states.

Objective

To summarize published health state utility data in HD and identify gaps and uncertainties in the data available that could be used to inform value assessments.

Methods

We conducted a systematic literature review of studies that used preference-based instruments (e.g., EQ-5D and SF-6D) to estimate utility values for people with HD. The studies were published between January 2012 and December 2022.

Results

Of 383 articles screened, 16 articles reported utility values estimated in 11 distinct studies. The utility measure most frequently reported was EQ-5D (9/11 studies). Two studies reported SF-6D data; one used time trade-off methods to value health state descriptions (vignettes). Although utility scores generally worsened to a lower value with increased HD severity, the estimates varied considerably across studies. The EQ-5D index range was 0.89 − 0.72 for mild/prodromal HD and 0.71 − 0.37 for severe/late-stage disease.

Conclusions

This study uncovered high variability in published utility estimates, indicating substantial uncertainty in existing data. Further research is needed to better understand preferences and valuation across all stages and domains of HD symptoms and the degree to which generic utility measures capture the impact of cognitive changes on quality of life.
Enhancing prediction accuracy of coronary artery disease through machine learning-driven genomic variant selection
Authors: Alireza Z. , Maleeha M. , Kaikkonen M. , Fortino V.
Published: April 2024

Machine learning (ML) methods are increasingly becoming crucial in genome-wide association studies for identifying key genetic variants or SNPs that statistical methods might overlook. Statistical methods predominantly identify SNPs with notable effect sizes by conducting association tests on individual genetic variants, one at a time, to determine their relationship with the target phenotype. These genetic variants are then used to create polygenic risk scores (PRSs), estimating an individual's genetic risk for complex diseases like cancer or cardiovascular disorders. Unlike traditional methods, ML algorithms can identify groups of low-risk genetic variants that improve prediction accuracy when combined in a mathematical model. However, the application of ML strategies requires addressing the feature selection challenge to prevent overfitting. Moreover, ensuring the ML model depends on a concise set of genomic variants enhances its clinical applicability, where testing is feasible for only a limited number of SNPs. In this study, we introduce a robust pipeline that applies ML algorithms in combination with feature selection (ML-FS algorithms), aimed at identifying the most significant genomic variants associated with the coronary artery disease (CAD) phenotype. The proposed computational approach was tested on individuals from the UK Biobank, differentiating between CAD and non-CAD individuals within this extensive cohort, and benchmarked against standard PRS-based methodologies like LDpred2 and Lassosum. Our strategy incorporates cross-validation to ensure a more robust evaluation of genomic variant-based prediction models. This method is commonly applied in machine learning strategies but has often been neglected in previous studies assessing the predictive performance of polygenic risk scores. Our results demonstrate that the ML-FS algorithm can identify panels with as few as 50 genetic markers that can achieve approximately 80% accuracy when used in combination with known risk factors. The modest increase in accuracy over PRS performances is noteworthy, especially considering that PRS models incorporate a substantially larger number of genetic variants. This extensive variant selection can pose practical challenges in clinical settings. Additionally, the proposed approach revealed novel CAD-genetic variant associations.