bluuebunny/crossref_metadata_2025 huggingface dataset:
Students’ perceived research skills development and satisfaction after completion of a mandatory research project: results from five cohorts of the Sydney medical program
Authors: Kaur Rajneesh , Hakim Jonathan , Jeremy Richmond , Coorey Genevieve , Kalman Eszter , Jenkin Rebekah , Bowen David G , Hart Joanne
Published: July 2023

Background

Research activities undertaken during University studies contribute to preparation of medical students for practice of evidence-based medicine. This study aimed to understand medical students’ experiences, perceived research skills development and satisfaction associated with completion of mandatory research projects.

Methods

An online survey was sent to five cohorts of students (n = 1375) from years 2017–2021 at the completion of their research projects. Univariate analysis was conducted to understand students’ perception of research skills development, followed by linear regression modeling to explore factors influencing satisfaction with their research project. Manifest content analysis employing a framework approach was used to analyse qualitative data from responses to open ended questions.

Results

Response rate was 42%, with 513 (89%) returned surveys being complete and included in analysis. Whilst 37% of students felt they had requisite research skills before undertaking the research project, 84% reported they had these skills after completing the project (χ2 = 8.99, P = 0.02). Mean satisfaction score of the students was 5.0/10 (+/- 2.5, median = 6 (IQR = 3.0–7.0) with 59% of students reporting satisfaction scores higher than the average. Higher satisfaction scores were reported by those who perceived that: research methods and teaching was useful in preparing them for conducting research; the research project helped them acquire new skills; the project resulted in peer-reviewed publication; and, who felt supported by their supervisors. Responses to open ended questions offered important insights into student experience and emphasised the importance of supportive supervisors and the need for a dedicated research block in the busy medical program.

Conclusions

The majority of students reported positive outcomes from the mandatory research project. Student satisfaction can be improved by ensuring supportive research environments and high-quality supervision, and inclusion of dedicated research time in the medical curriculum.
Measuring behavioral and social drivers of COVID-19 vaccination in health workers in Eastern and Southern Africa
Authors: Bon Helena Ballester , Brouwers Symen A. , Mote Jenna , de Almeida Sofia , Markle Laurie , Sommariva Silvia , Fol Natalie
Published: July 2023

Background

In 2021, twenty out of twenty-one countries in the Eastern and Southern Africa (ESA) region introduced COVID-19 vaccines. With variable willingness to uptake vaccines across countries, the aim of the present study was to better understand factors that impact behavioral and social drivers of vaccination (BeSD). Using the theory-based “increasing vaccination model”, the drivers Thinking & Feeling, Social Processes, Motivation, and Practical Issues were adapted to the COVID-19 context and utilized in a cross-country assessment.

Methods

Data was collected on 27.240 health workers in Kenya, Malawi, Mozambique, South Africa and South Sudan. This was done by administering a survey of seven target questions via the UNICEF Internet of Good Things (IoGT) online platform between February and August 2021.

Results

Findings showed a gap between perceived importance and trust in vaccines: Most health workers thought Covid-19 vaccination was very important for their health, while less than 30% trusted it very much. The pro-vaccination social and work norm was not well established since almost 66% of all respondents would take the vaccine if recommended to them, but only 49% thought most adults would, and only 48% thought their co-workers would. Access was highlighted as a crucial barrier, with less than a quarter reporting that accessing vaccination services for themselves would be very easy. Women exhibited slightly lower scores than men across the board. When testing the associations between drivers in Kenya and South Africa, it appears that when target interventions are developed for specific age groups, social norms become the main drivers of intention to get vaccinated.

Conclusions

The present study revealed various key relations with demographic variables that would help immunization programmes and implementing partners to develop targeted interventions. First, there is a serious gap between perceived importance of COVID-19 vaccines and how much trust people in them. Second, problems with access are still rather serious and solving this would strongly benefit those who demand a vaccine, Third, the role of social norms is the most important predictor of willingness when considering age differences.
Assessing the performance of European-derived cardiometabolic polygenic risk scores in South-Asians and their interplay with family history
Authors: Hassanin Emadeldin , Maj Carlo , Klinkhammer Hannah , Krawitz Peter , May Patrick , Bobbili Dheeraj Reddy
Published: July 2023

Background & aims

We aimed to assess the performance of European-derived polygenic risk scores (PRSs) for common metabolic diseases such as coronary artery disease (CAD), obesity, and type 2 diabetes (T2D) in the South Asian (SAS) individuals in the UK Biobank. Additionally, we studied the interaction between PRS and family history (FH) in the same population.

Methods

To calculate the PRS, we used a previously published model derived from the EUR population and applied it to the individuals of SAS ancestry from the UKB study. Each PRS was adjusted according to an individual’s genotype location in the principal components (PC) space to derive an ancestry adjusted PRS (aPRS). We calculated the percentiles based on aPRS and stratified individuals into three aPRS categories: low, intermediate, and high. Considering the intermediate-aPRS percentile as a reference, we compared the low and high aPRS categories and generated the odds ratio (OR) estimates. Further, we measured the combined role of aPRS and first-degree family history (FH) in the SAS population.

Results

The risk of developing severe obesity for SAS individuals was almost twofold higher for individuals with high aPRS than for those with intermediate aPRS, with an OR of 1.95 (95% CI = 1.71–2.23, P < 0.01). At the same time, the risk of severe obesity was lower in the low-aPRS group (OR = 0.60, CI = 0.53–0.67, P < 0.01). Results in the same direction were found in the EUR data, where the low-PRS group had an OR of 0.53 (95% CI = 0.51–0.56, P < 0.01) and the high-PRS group had an OR of 2.06 (95% CI = 2.00-2.12, P < 0.01). We observed similar results for CAD and T2D. Further, we show that SAS individuals with a familial history of CAD and T2D with high-aPRS are associated with a higher risk of these diseases, implying a greater genetic predisposition.

Conclusion

Our findings suggest that CAD, obesity, and T2D GWAS summary statistics generated predominantly from the EUR population can be potentially used to derive aPRS in SAS individuals for risk stratification. With future GWAS recruiting more SAS participants and tailoring the PRSs towards SAS ancestry, the predictive power of PRS is likely to improve further.
Impact of type 2 diabetes on life expectancy and role of kidney disease among inpatients with heart failure in Switzerland: an ambispective cohort study
Authors: Salvador Dante , Bano Arjola , Wehrli Faina , Gonzalez-Jaramillo Valentina , Laimer Markus , Hunziker Lukas , Muka Taulant
Published: July 2023

Background

Type 2 diabetes (T2D) is expected to worsen the prognosis of inpatients with heart failure (HF) but the evidence from observational studies is inconsistent. We aimed to compare mortality outcomes and life expectancy among inpatients with HF with or without T2D and explored whether chronic kidney disease (CKD) influenced these associations.

Methods

We collected hospital and civil registry records of consecutive inpatients from a tertiary hospital in Switzerland with a diagnosis of HF from the year 2015 to 2019. We evaluated the association of T2D with mortality risk using Cox regression and adjusted for confounders.

Results

Our final cohort consisted of 10,532 patients with HF of whom 27% had T2D. The median age (interquartile range [IQR]) was 75 [68 to 82] and 78 [68 to 86] for the diabetes and non-diabetes groups, respectively. Over a median follow-up [IQR] of 4.5 years [3.3 to 5.6], 5,347 (51%) of patients died. T2D patients had higher risk of all-cause mortality (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.14 to 1.29). Compared to control (i.e. no T2D nor CKD), average life expectancy (95% CI) among T2D patients, CKD, or both was shorter by 5.4 months (95% CI 1.1 to 9.7), 9.0 months (95% CI 8.4 to 9.6), or 14.8 months (95% CI 12.4 to 17.2), respectively. No difference by sex or ejection fraction category was observed.

Conclusions

T2D is associated with a significantly higher risk of all-cause mortality and shorter life expectancy compared to those without among middle-aged and elderly inpatients with HF; presence of CKD may further increase these risks.
The emerging role of MicroRNA-182 in tumorigenesis; a promising therapeutic target
Authors: Sameti Pouriya , Tohidast Maryam , Amini Mohammad , Bahojb Mahdavi Seyedeh Zahra , Najafi Souzan , Mokhtarzadeh Ahad
Published: July 2023

A wide range of studies have indicated that microRNAs (miRNAs), a type of small single-stranded regulatory RNAs, are dysregulated in a different variety of human cancers. Therefore, they are expected to play important roles in tumorigenesis by functioning as oncogenic (oncomiRs) or tumor-suppressive miRNAs. Subsequently, their potential as diagnostic and therapeutic targets for malignancies has attracted attention in recent years. In particular, studies have revealed the aberrant expression of miR-182 through tumorigenesis and its important roles in various aspects of malignancies, including proliferation, metastasis, and chemoresistance. Accumulating reports have illustrated that miR-182, as a dual-role regulator, directly or indirectly regulates the expression of a wide range of genes and modulates the activity of various signaling pathways involved in tumor progression, such as JAK / STAT3, Wnt / β-catenin, TGF-β, and P13K / AKT. Therefore, considering the high therapeutic and diagnostic potential of miR-182, this review aims to point out the effects of miR-182 dysregulation on the signaling pathways involved in tumorigenesis.
Apoptotic bodies: bioactive treasure left behind by the dying cells with robust diagnostic and therapeutic application potentials
Authors: Yu Lina , Zhu Guanxiong , Zhang Zeyu , Yu Yang , Zeng Liting , Xu Zidan , Weng Jinlong , Xia Junyi , Li Jiang , Pathak Janak L.
Published: July 2023

Apoptosis, a form of programmed cell death, is essential for growth and tissue homeostasis. Apoptotic bodies (ApoBDs) are a form of extracellular vesicles (EVs) released by dying cells in the last stage of apoptosis and were previously regarded as debris of dead cells. Recent studies unraveled that ApoBDs are not cell debris but the bioactive treasure left behind by the dying cells with an important role in intercellular communications related to human health and various diseases. Defective clearance of ApoBDs and infected-cells-derived ApoBDs are possible etiology of some diseases. Therefore, it is necessary to explore the function and mechanism of the action of ApoBDs in different physiological and pathological conditions. Recent advances in ApoBDs have elucidated the immunomodulatory, virus removal, vascular protection, tissue regenerative, and disease diagnostic potential of ApoBDs. Moreover, ApoBDs can be used as drug carriers enhancing drug stability, cellular uptake, and targeted therapy efficacy. These reports from the literature indicate that ApoBDs hold promising potential for diagnosis, prognosis, and treatment of various diseases, including cancer, systemic inflammatory diseases, cardiovascular diseases, and tissue regeneration. This review summarizes the recent advances in ApoBDs-related research and discusses the role of ApoBDs in health and diseases as well as the challenges and prospects of ApoBDs-based diagnostic and therapeutic applications.

Graphical Abstract
Development and validation of a clinic machine-learning nomogram for the prediction of risk stratifications of prostate cancer based on functional subsets of peripheral lymphocyte
Authors: Yang Chunguang , Liu Zhenghao , Fang Yin , Cao Xinyu , Xu Guoping , Wang Zhihua , Hu Zhiquan , Wang Shaogang , Wu Xinglong
Published: July 2023

Background

Non-invasive risk stratification contributes to the precise treatment of prostate cancer (PCa). In previous studies, lymphocyte subsets were used to differentiate between low-/intermediate-risk and high-risk PCa, with limited clinical value and poor interpretability. Based on functional subsets of peripheral lymphocyte with the largest sample size to date, this study aims to construct an easy-to-use and robust nomogram to guide the tripartite risk stratifications for PCa.

Methods

We retrospectively collected data from 2039 PCa and benign prostate disease (BPD) patients with 42 clinical characteristics on functional subsets of peripheral lymphocyte. After quality control and feature selection, clinical data with the optimal feature subset were utilized for the 10-fold cross-validation of five Machine Learning (ML) models for the task of predicting low-, intermediate- and high-risk stratification of PCa. Then, a novel clinic-ML nomogram was constructed using probabilistic predictions of the trained ML models via the combination of a multivariable Ordinal Logistic Regression analysis and the proposed feature mapping algorithm.

Results

197 PCa patients, including 56 BPD, were enrolled in the study. An optimal subset with nine clinical features was selected. Compared with the best ML model and the clinic nomogram, the clinic-ML nomogram achieved the superior performance with a sensitivity of 0.713 (95% CI 0.573–0.853), specificity of 0.869 (95% CI 0.764–0.974), F1 of 0.699 (95% CI 0.557–0.841), and AUC of 0.864 (95% CI 0.794–0.935). The calibration curve and Decision Curve Analysis (DCA) indicated the predictive capacity and net benefits of the clinic-ML nomogram were improved.

Conclusion

Combining the interpretability and simplicity of a nomogram with the efficacy and robustness of ML models, the proposed clinic-ML nomogram can serve as an insight tool for preoperative assessment of PCa risk stratifications, and could provide essential information for the individual diagnosis and treatment in PCa patients.
Disease-modifying effects of a glial-targeted inducible nitric oxide synthase inhibitor (1400W) in mixed-sex cohorts of a rat soman (GD) model of epilepsy
Authors: Vasanthi Suraj S. , Rao Nikhil S. , Samidurai Manikandan , Massey Nyzil , Meyer Christina , Gage Meghan , Kharate Mihir , Almanza Aida , Wachter Logan , Mafuta Candide , Trevino Lily , Carlo Adriana M. , Bryant Elijah , Corson Brooke E. , Wohlgemuth Morgan , Ostrander Morgan , Showman Lucas , Wang Chong , Thippeswamy Thimmasettappa
Published: July 2023

Background

Acute exposure to seizurogenic organophosphate (OP) nerve agents (OPNA) such as diisopropylfluorophosphate (DFP) or soman (GD), at high concentrations, induce immediate status epilepticus (SE), reactive gliosis, neurodegeneration, and epileptogenesis as a consequence. Medical countermeasures (MCMs—atropine, oximes, benzodiazepines), if administered in < 20 min of OPNA exposure, can control acute symptoms and mortality. However, MCMs alone are inadequate to prevent OPNA-induced brain injury and behavioral dysfunction in survivors. We have previously shown that OPNA exposure-induced SE increases the production of inducible nitric oxide synthase (iNOS) in glial cells in both short- and long- terms. Treating with a water soluble and highly selective iNOS inhibitor, 1400W, for 3 days significantly reduced OPNA-induced brain changes in those animals that had mild–moderate SE in the rat DFP model. However, such mitigating effects and the mechanisms of 1400W are unknown in a highly volatile nerve agent GD exposure.

Methods

Mixed-sex cohort of adult Sprague Dawley rats were exposed to GD (132 μg/kg, s.c.) and immediately treated with atropine (2 mg/kg, i.m) and HI-6 (125 mg/kg, i.m.). Severity of seizures were quantified for an hour and treated with midazolam (3 mg/kg, i.m.). An hour post-midazolam, 1400W (20 mg/kg, i.m.) or vehicle was administered daily for 2 weeks. After behavioral testing and EEG acquisition, animals were euthanized at 3.5 months post-GD. Brains were processed for neuroinflammatory and neurodegeneration markers. Serum and CSF were used for nitrooxidative and proinflammatory cytokines assays.

Results

We demonstrate a significant long-term (3.5 months post-soman) disease-modifying effect of 1400W in animals that had severe SE for > 20 min of continuous convulsive seizures. 1400W significantly reduced GD-induced motor and cognitive dysfunction; nitrooxidative stress (nitrite, ROS; increased GSH: GSSG); proinflammatory cytokines in the serum and some in the cerebrospinal fluid (CSF); epileptiform spikes and spontaneously recurring seizures (SRS) in males; reactive gliosis (GFAP + C3 and IBA1 + CD68-positive glia) as a measure of neuroinflammation, and neurodegeneration (especially parvalbumin-positive neurons) in some brain regions.

Conclusion

These findings demonstrate the long-term disease-modifying effects of a glial-targeted iNOS inhibitor, 1400W, in a rat GD model by modulating reactive gliosis, neurodegeneration (parvalbumin-positive neurons), and neuronal hyperexcitability.
On the relevance of (the New) Phenomenology to an ethics of health promotions: toward a prudent balance of understanding and explanation
Authors: Röhrich Christina , Kohls Nikola B. , Krüger Eckard , Giordano James
Published: July 2023

The field of health promotions faces considerable ethical and programmatic challenge – and we believe opportunity – in addressing the relative normativity of the concept(s) of health and its professional handling. To date, distinctions of objective and subjective indicants of “health” have fostered normative tension(s) within the utilitarian ethics of health promotions, which we opine to be anathema to the ultimate goal(s) of attaining and sustaining healthy individuals and societies. Objective and subjective metrics and values should be reconciled, as reciprocal and complementary on both idiosyncratic and systemic levels. In this light, we propose that a philosophical and ethical approach, based primarily upon Schmitz’s New Phenomenology and its specific understanding of subjectivity could afford epistemological bases for non-normative engagement of health promotion within a structural–functional framework of ethics. We dialectically address its potential benefit, limitations and value for health promotion and health care ethics and present an approach which points towards a more substantial encouragement of diversity through the legitimation of subjectivity.
Sub-axillary cosmetic incision versus single-incision thoracoscopic surgery for primary spontaneous pneumothorax
Authors: Zheng Yuan-Liang , Huang Ri-Sheng
Published: July 2023

Background

In recent years, single-incision thoracoscopic surgery (SITS) has been increasingly applied as an optimal treatment option for primary spontaneous pneumothorax (PSP). However, most SITS techniques are used in the fourth to sixth intercostal space between the anterior axillary and mid axillary lines. To find out more concealed incisions, this study performed PSP surgery via the sub-axillary cosmetic incision (SACI) technique.

Methods

A total of 128 PSP patients were subjected to video-assisted thoracoscopic surgery (VATS) between January 2017 and January 2019 at our institution. These patients were evaluated and assigned into SACI (n = 21) and SITS (n = 57) groups. Propensity score matching (PSM) was performed based on patients’ backgrounds, and the enrolled cohort was divided into 21 pairs. The incision satisfaction was assessed at 2 weeks and 6 months post-surgery.

Results

The 21 pairs with matching baseline characteristics in the two groups did not exhibit significant differences in their backgrounds and surgical results. However, compared with the SITS group, the operation time was longer in the SACI group (p = 0.013). There were no post-operative complications in both groups. At 2 weeks and 6 months, incision satisfaction scores in the SACI group were significantly lower than those in the SITS group (p = 0.022 and p = 0.039, respectively). There were no recurrences of ipsilateral pneumothorax in both groups.

Conclusions

SACI is a safe and feasible surgical method for PSP treatment. In addition, incision concealment can be used for patients with incision needs.
Bacteraemia caused by Lactobacillus casei in a patient after cardiac surgery. A case report
Authors: Guzek Aneta , Filipowski Paweł , Rybicki Zbigniew , Grabski Piotr , Gryszko Leszek , Sopolińska Emilia , Tomaszewski Dariusz
Published: July 2023

Background

Bacteria of the Lactobacillus family are a part of the physiological flora of the oral cavity, gastrointestinal tract, and urinary tract. We have used them in the food industry as probiotics and supplements. In some settings, rod-shaped lactic acid bacteria may become pathogenic. It may occur in immunocompromised or heart disease patients after cardiac surgery, patients with disturbed intestinal wall permeability, or those treated with broad-spectrum antibiotics.

Case presentation

We present rare bacteraemia induced by the probiotic bacterium Lactobacillus casei in a 63-year-old patient after the attempted removal of ICD electrodes, complicated by acute regurgitation of the tricuspid valve. The patient underwent urgent cardiac surgery, the electrode elements were removed, and the tricuspid valve was replaced with a biological prosthesis. After surgery, the patient required intensive, multidisciplinary treatment with mechanical ventilation, continuous renal replacement therapy, broad-spectrum empirical antibiotic therapy, parenteral nutrition, and blood product transfusion because of multiple organ failure. On the 14th day of hospitalisation, the clinical symptoms of septic shock were observed. The microbiological investigation was performed, and Lactobacillus casei was cultured from a dialysis catheter sample. Dedicated antimicrobials were administered, and the patient was discharged home in good overall condition.

Conclusions

The present case shows that the promoted use of probiotics must be cautiously administered to patients in severe conditions, especially when accompanied by reduced immune system efficiency symptoms.
ACSS2-dependent histone acetylation improves cognition in mouse model of Alzheimer’s disease
Authors: Lin Yingbin , Lin Anlan , Cai Lili , Huang Weibin , Yan Shanzhi , Wei Yuanxiang , Ruan Xinglin , Fang Wenting , Dai Xiaoman , Cheng Jinbo , Zhang Jie , Chen Wanjin , Ye Qinyong , Chen Xiaochun , Zhang Jing
Published: July 2023

Background

Nuclear acetyl-CoA pools govern histone acetylation that controls synaptic plasticity and contributes to cognitive deterioration in patients with Alzheimer’s disease (AD). Nuclear acetyl-CoA pools are generated partially from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). However, the underlying mechanism of histone acetylation dysregulation in AD remains poorly understood.

Methods

We detected ACSS2 expression and histone acetylation levels in the brains of AD patients and 5 × FAD mice. When we altered ACSS2 expression by injecting adeno-associated virus into the dorsal hippocampus of 5 × FAD mice and replenished ACSS2 substrate (acetate), we observed changes in cognitive function by Morris water maze. We next performed RNA-seq, ChIP-qPCR, and electrophysiology to study molecular mechanism underlying ACSS2-mediated spatial learning and memory in 5 × FAD mice.

Results

We reported that ACSS2 expression and histone acetylation (H3K9, H4K12) were reduced in the hippocampus and prefrontal cortex of 5 × FAD mice. Reduced ACSS2 levels were also observed in the temporal cortex of AD patients. 5 × FAD mice exhibited a low enrichment of acetylated histones on the promoters of NMDARs and AMPARs, together with impaired basal and activity-dependent synaptic plasticity, all of which were rescued by ACSS2 upregulation. Moreover, acetate replenishment enhanced ac-H3K9 and ac-H4K12 in 5 × FAD mice, leading to an increase of NMDARs and AMPARs and a restoration of synaptic plasticity and cognitive function in an ACSS2-dependent manner.

Conclusion

ACSS2 is a key molecular switch of cognitive impairment and that targeting ACSS2 or acetate administration may serve as a novel therapeutic strategy for the treatment of intermediate or advanced AD.

Graphical Abstract

Nuclear acetyl-CoA pools are generated partly from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). Model depicts that ACSS2 expression is downregulated in the brains of 5×FAD model mice and AD patients. Of note, ACSS2 downregulation mediates a reduction in ionotropic glutamate receptor expression through histone acetylation, which exacerbates synaptic plasticity impairment in AD. These deficits can be rescued by ACSS2 upregulation or acetate supplementation (GTA, an FDA-approved food additive), which may serve as a promising therapeutic strategy for AD treatment.
Suicidal behaviours and their correlates in school-going Lebanese adolescents: findings from a national survey
Authors: Dadras Omid , Wang Chia-Wen
Published: July 2023

Background

Adolescent suicide is regarded as a serious phenomenon that affects the well-being of the youth. This study aims to investigate the prevalence of suicidal behaviours and their association with physical/psychological harm and substance use in a nationally representative sample of adolescents in Grades 7–12 in Lebanon.

Methods

Data from the latest Global School-Based Student Health Survey conducted in 2017 were used in this study. The prevalence and correlates of suicidal ideation and suicide attempts among those who had considered committing suicide, at least once, were explored.

Results

An estimated 13.45% of Lebanese adolescents, particularly females in Grades 7–12 had considered suicide at least once in the past 12 months. More importantly, almost half of them had attempted it at least once in the past 12 months. Those who frequently felt lonely or worried (previous year), were involved in physical fights or assaults (previous year), had been verbally or physically bullied (previous month), had missed more school days, experienced food insecurity, and had a history of substance abuse (marijuana, amphetamine, alcohol, and tobacco products) were more likely to exhibit suicidal behaviours. Parental support and older age at drug initiation appeared to be protective factors.

Discussion

The findings characterise the correlates of suicidal behaviours among school-going Lebanese adolescents and determine the attributes of the risk group susceptible to engaging in suicide attempts. Future interventions and policies should consider these attributes when monitoring target groups, particularly those with the alarming behaviours identified in this study. In addition, awareness campaigns that engage all stakeholders, particularly parents, should be prioritised by the authorities.
Early hyperbaric oxygen therapy is associated with favorable outcome in patients with iatrogenic cerebral arterial gas embolism: systematic review and individual patient data meta-analysis of observational studies
Authors: Fakkert Raoul A. , Karlas Noa , Schober Patrick , Weber Nina C. , Preckel Benedikt , van Hulst Robert A. , Weenink Robert P.
Published: July 2023

Background

Iatrogenic cerebral arterial gas embolism (CAGE) caused by invasive medical procedures may be treated with hyperbaric oxygen therapy (HBOT). Previous studies suggested that initiation of HBOT within 6–8 h is associated with higher probability of favorable outcome, when compared to time-to-HBOT beyond 8 h. We performed a group level and individual patient level meta-analysis of observational studies, to evaluate the relationship between time-to-HBOT and outcome after iatrogenic CAGE.

Methods

We systematically searched for studies reporting on time-to-HBOT and outcome in patients with iatrogenic CAGE. On group level, we meta-analyzed the differences between median time-to-HBOT in patients with favorable versus unfavorable outcome. On individual patient level, we analyzed the relationship between time-to-HBOT and probability of favorable outcome in a generalized linear mixed effects model.

Results

Group level meta-analysis (ten studies, 263 patients) shows that patients with favorable outcome were treated with HBOT 2.4 h (95% CI 0.6–9.7) earlier than patients with unfavorable outcome. The generalized linear mixed effects model (eight studies, 126 patients) shows a significant relationship between time-to-HBOT and probability of favorable outcome (p = 0.013) that remains significant after correcting for severity of manifestations (p = 0.041). Probability of favorable outcome decreases from approximately 65% when HBOT is started immediately, to 30% when HBOT is delayed for 15 h.

Conclusions

Increased time-to-HBOT is associated with decreased probability of favorable outcome in iatrogenic CAGE. This suggests that early initiation of HBOT in iatrogenic CAGE is of vital importance.
Randomised controlled trials of behavioural nudges delivered through text messages to increase influenza and COVID-19 vaccines among pregnant women (the EPIC study): study protocol
Authors: Andraweera Prabha H. , Wang Bing , Danchin Margie , Blyth Christopher , Vlaev Ivo , Ong Jason , Dodd Jodie , Couper Jennifer , Sullivan Thomas R. , Karnon Jonathan , Spurrier Nicola , Cusack Michael , Mordaunt Dylan , Simatos Dimi , Dekker Gus , Carlson Samantha , Tuckerman Jane , Wood Nicholas , Whop Lisa , Marshall Helen S.
Published: July 2023

Background

Influenza and COVID-19 infections during pregnancy may have serious adverse consequences for women as well as their infants. However, uptake of influenza and COVID-19 vaccines during pregnancy remains suboptimal. This study aims to assess the effectiveness of a multi-component nudge intervention to improve influenza and COVID-19 vaccine uptake among pregnant women.

Methods

Pregnant women who receive antenatal care at five tertiary hospitals in South Australia, Western Australia and Victoria will be recruited to two separate randomised controlled trials (RCTs). Women will be eligible for the COVID-19 RCT is they have received two or less doses of a COVID-19 vaccine. Women will be eligible for the influenza RCT if they have not received the 2023 seasonal influenza vaccine. Vaccination status at all stages of the trial will be confirmed by the Australian Immunisation Register (AIR). Participants will be randomised (1:1) to standard care or intervention group (n = 1038 for each RCT). The nudge intervention in each RCT will comprise three SMS text message reminders with links to short educational videos from obstetricians, pregnant women and midwives and vaccine safety information. The primary outcome is at least one dose of a COVID-19 or influenza vaccine during pregnancy, as applicable. Logistic regression will compare the proportion vaccinated between groups. The effect of treatment will be described using odds ratio with a 95% CI.

Discussion

Behavioural nudges that facilitate individual choices within a complex context have been successfully used in other disciplines to stir preferred behaviour towards better health choices. If our text-based nudges prove to be successful in improving influenza and COVID-19 vaccine uptake among pregnant women, they can easily be implemented at a national level.

Trial registration

ClinicalTrials.gov Identifier NCT05613751. Registered on November 14, 2022.
Osteopoikilosis: a case report
Authors: Mohsenpour Behzad , Ahmadi Amjad
Published: July 2023

Background

Osteopoikilosis, also referred to as disseminated condensing osteopathy, spotted bone disease, or osteopecilia, is a rare bone disorder. The case presented here showcases multiple disc lesions in the spine, extensive multifocal skin lesions, and positive test results for dermatomyositis and multifocal enthesopathy, accompanied by neurological symptoms. This manifestation represents a novel variant of the disease.

Case presentation

Our patient is a 46-year-old mosque Kurdish servant presenting with complaints of pain in the right leg, lower back, right hand, and neck. Additionally, the patient has been experiencing redness in the right buttock and ipsilateral thigh, as well as gradually expanding and stiffening skin lesions on the left shin for the past 3 weeks. Painful neck movements and a positive Lasegue test were also observed in the right leg. The patient reports pain in the right buttock accompanied by a substantial erythematous area with induration measuring 8 × 15 cm, as well as an erythematous and maculopapular lesion measuring 6 × 18 cm on the left shin.

Conclusions

Our patient is a 46-year-old man presenting with complaints of skin lesions and pain in the lower back, pelvis, neck, and limbs. The X-ray reveals shoulder, pelvis, knee, and ankle involvement, while spinal involvement is observed in the neck and lumbar region. Furthermore, the bone scan indicates extensive enthesopathy in various regions, a unique manifestation not previously reported in similar cases.
Age-related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species-specific changes
Authors: Shavlakadze Tea , Xiong Kun , Mishra Shawn , McEwen Corissa , Gadi Abhilash , Wakai Matthew , Salmon Hunter , Stec Michael J. , Negron Nicole , Ni Min , Wei Yi , Atwal Gurinder S. , Bai Yu , Glass David J.
Published: July 2023

Background

As a result of aging, skeletal muscle undergoes atrophy and a decrease in function. This age-related skeletal muscle weakness is known as “sarcopenia”. Sarcopenia is part of the frailty observed in humans. In order to discover treatments for sarcopenia, it is necessary to determine appropriate preclinical models and the genes and signaling pathways that change with age in these models.

Methods and results

To understand the changes in gene expression that occur as a result of aging in skeletal muscles, we generated a multi-time-point gene expression signature throughout the lifespan of mice and rats, as these are the most commonly used species in preclinical research and intervention testing. Gastrocnemius, tibialis anterior, soleus, and diaphragm muscles from male and female C57Bl/6J mice and male Sprague Dawley rats were analyzed at ages 6, 12, 18, 21, 24, and 27 months, plus an additional 9-month group was used for rats. More age-related genes were identified in rat skeletal muscles compared with mice; this was consistent with the finding that rat muscles undergo more robust age-related decline in mass. In both species, pathways associated with innate immunity and inflammation linearly increased with age. Pathways linked with extracellular matrix remodeling were also universally downregulated. Interestingly, late downregulated pathways were exclusively found in the rat limb muscles and these were linked to metabolism and mitochondrial respiration; this was not seen in the mouse.

Conclusions

This extensive, side-by-side transcriptomic profiling shows that the skeletal muscle in rats is impacted more by aging compared with mice, and the pattern of decline in the rat may be more representative of the human. The observed changes point to potential therapeutic interventions to avoid age-related decline in skeletal muscle function.
Bioconversion of vitamin D3 into calcitriol by Actinomyces hyovaginalis isolate CCASU- A11-2
Authors: Abbas Ahmad M. , Elkhatib Walid F. , Aboulwafa Mohammad M. , Hassouna Nadia A. , Aboshanab Khaled M.
Published: July 2023

Vitamin D3 is a fat-soluble prohormone that is activated inside the liver to produce 25-hydroxyvitamin D3 (calcidiol), and in the kidney to produce the fully active 1α, 25-dihydroxy vitamin D3 (calcitriol). A previous work piloted in our laboratory, resulted in a successful recovery of a local soil-promising Actinomyces hyovaginalis isolate CCASU-A11-2 capable of converting vitamin D3 into calcitriol. Despite the rising amount of research on vitamin D3 bioconversion into calcitriol, further deliberate studies on this topic can significantly contribute to the improvement of such a bioconversion process. Therefore, this work aimed to improve the bioconversion process, using the study isolate, in a 14 L laboratory fermenter (4 L fermentation medium composed of fructose (15 g/L), defatted soybean (15 g/L), NaCl (5 g/L), CaCO3 2 g/L); K2HPO4, (1 g/L) NaF (0.5 g/L) and initial of pH 7.8) where different experiments were undertaken to investigate the effect of different culture conditions on the bioconversion process. Using the 14 L laboratory fermenter, the calcitriol production was increased by about 2.5-fold (32.8 µg/100 mL) to that obtained in the shake flask (12.4 µg/100 mL). The optimal bioconversion conditions were inoculum size of 2% v/v, agitation rate of 200 rpm, aeration rate of 1 vvm, initial pH of 7.8 (uncontrolled); addition of vitamin D3 (substrate) 48 h after the start of the main culture. In conclusion, the bioconversion of vitamin D3 into calcitriol in a laboratory fermenter showed a 2.5-fold increase as compared to the shake flask level where, the important factors influencing the bioconversion process were the aeration rate, inoculum size, the timing of substrate addition, and the fixed pH of the fermentation medium. So, those factors should be critically considered for the scaling-up of the biotransformation process.
Aerosol therapy in adult critically ill patients: a consensus statement regarding aerosol administration strategies during various modes of respiratory support
Authors: Li Jie , Liu Kai , Lyu Shan , Jing Guoqiang , Dai Bing , Dhand Rajiv , Lin Hui-Ling , Pelosi Paolo , Berlinski Ariel , Rello Jordi , Torres Antoni , Luyt Charles-Edouard , Michotte Jean-Bernard , Lu Qin , Reychler Gregory , Vecellio Laurent , de Andrade Armèle Dornelas , Rouby Jean-Jacques , Fink James B. , Ehrmann Stephan
Published: July 2023

Background

Clinical practice of aerosol delivery in conjunction with respiratory support devices for critically ill adult patients remains a topic of controversy due to the complexity of the clinical scenarios and limited clinical evidence.

Objectives

To reach a consensus for guiding the clinical practice of aerosol delivery in patients receiving respiratory support (invasive and noninvasive) and identifying areas for future research.

Methods

A modified Delphi method was adopted to achieve a consensus on technical aspects of aerosol delivery for adult critically ill patients receiving various forms of respiratory support, including mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula. A thorough search and review of the literature were conducted, and 17 international participants with considerable research involvement and publications on aerosol therapy, comprised a multi-professional panel that evaluated the evidence, reviewed, revised, and voted on recommendations to establish this consensus.

Results

We present a comprehensive document with 20 statements, reviewing the evidence, efficacy, and safety of delivering inhaled agents to adults needing respiratory support, and providing guidance for healthcare workers. Most recommendations were based on in-vitro or experimental studies (low-level evidence), emphasizing the need for randomized clinical trials. The panel reached a consensus after 3 rounds anonymous questionnaires and 2 online meetings.

Conclusions

We offer a multinational expert consensus that provides guidance on the optimal aerosol delivery techniques for patients receiving respiratory support in various real-world clinical scenarios.
Impact of seed amplification assay and surface-enhanced Raman spectroscopy combined approach on the clinical diagnosis of Alzheimer’s disease
Authors: D’Andrea Cristiano , Cazzaniga Federico Angelo , Bistaffa Edoardo , Barucci Andrea , de Angelis Marella , Banchelli Martina , Farnesi Edoardo , Polykretis Panagis , Marzi Chiara , Indaco Antonio , Tiraboschi Pietro , Giaccone Giorgio , Matteini Paolo , Moda Fabio
Published: July 2023

Background

The current diagnosis of Alzheimer’s disease (AD) is based on a series of analyses which involve clinical, instrumental and laboratory findings. However, signs, symptoms and biomarker alterations observed in AD might overlap with other dementias, resulting in misdiagnosis.

Methods

Here we describe a new diagnostic approach for AD which takes advantage of the boosted sensitivity in biomolecular detection, as allowed by seed amplification assay (SAA), combined with the unique specificity in biomolecular recognition, as provided by surface-enhanced Raman spectroscopy (SERS).

Results

The SAA-SERS approach supported by machine learning data analysis allowed efficient identification of pathological Aβ oligomers in the cerebrospinal fluid of patients with a clinical diagnosis of AD or mild cognitive impairment due to AD.

Conclusions

Such analytical approach can be used to recognize disease features, thus allowing early stratification and selection of patients, which is fundamental in clinical treatments and pharmacological trials.
Evaluating the potential of (epi)genotype-by-low pass nanopore sequencing in dairy cattle: a study on direct genomic value and methylation analysis
Authors: González-Recio Oscar , López-Catalina Adrián , Peiró-Pastor Ramón , Nieto-Valle Alicia , Castro Monica , Fernández Almudena
Published: July 2023

Background

Genotype-by-sequencing has been proposed as an alternative to SNP genotyping arrays in genomic selection to obtain a high density of markers along the genome. It requires a low sequencing depth to be cost effective, which may increase the error at the genotype assigment. Third generation nanopore sequencing technology offers low cost sequencing and the possibility to detect genome methylation, which provides added value to genotype-by-sequencing. The aim of this study was to evaluate the performance of genotype-by-low pass nanopore sequencing for estimating the direct genomic value in dairy cattle, and the possibility to obtain methylation marks simultaneously.

Results

Latest nanopore chemistry (LSK14 and Q20) achieved a modal base calling accuracy of 99.55%, whereas previous kit (LSK109) achieved slightly lower accuracy (99.1%). The direct genomic value accuracy from genotype-by-low pass sequencing ranged between 0.79 and 0.99, depending on the trait (milk, fat or protein yield), with a sequencing depth as low as 2 × and using the latest chemistry (LSK114). Lower sequencing depth led to biased estimates, yet with high rank correlations. The LSK109 and Q20 achieved lower accuracies (0.57–0.93). More than one million high reliable methylated sites were obtained, even at low sequencing depth, located mainly in distal intergenic (87%) and promoter (5%) regions.

Conclusions

This study showed that the latest nanopore technology in useful in a LowPass sequencing framework to estimate direct genomic values with high reliability. It may provide advantages in populations with no available SNP chip, or when a large density of markers with a wide range of allele frequencies is needed. In addition, low pass sequencing provided nucleotide methylation status of > 1 million nucleotides at ≥ 10 × , which is an added value for epigenetic studies.
Determinants and consequences of employer-provided training program resilience post-Covid-19
Authors: Caves Katherine M. , McDonald Patrick
Published: July 2023

Economic shocks provide both risks and opportunities for workplace training programs—the risk of program cancellation or interruption to skills development, and the opportunity to be at the vanguard of economic recovery. This paper analyzes the impact of Covid-19 and the resulting economic shock on training programs in the US using a survey amongst employers participating in training support networks, run from April-June 2021. We anticipate that programs expressly motivated by returns to investment and those that are higher quality and leading to stronger credentials will be most likely to survive the shock and have minimal disruption to skills acquisition. Results suggest that expressed motivations to train are generally not linked to training disruption or skills loss, while there is some evidence of paid programs and those offering better credentials being more likely to survive. Internships and programs that are more demographically diverse show a greater likelihood of disruption and skills loss.
Mathematical modeling of modified atmosphere package/LDPE film combination and its application to design breathing cylinders for extending the shelf life of green asparagus
Authors: Lu Wen-Chien , Cheng Yu-Tsung , Lai Chien-Jung , Chiang Been-Huang , Huang Ping-Hsiu , Li Po-Hsien
Published: July 2023

Background

The O2 levels in food packaging systems play an essential role in the deterioration of food quality and shelf life. Modified atmosphere packaging (MAP) supports the storage of fresh and processed foods by inhibiting chemical and physical changes while reducing the deterioration caused by microorganisms.

Materials and methods

This study established and validated the equations for the relationship between MAP formulation reagents, asparagus respiration, permeability of packaging film, and rates of O2 and CO2 mass transfer in which different interactions occur and affect each other.

Results

The resulting atmosphere of packaging was determined to be the key to achieving the MAP benefits. The active MAP formulations developed in this study were combined with very-low-density polyethylene films to store green asparagus spears. During storage, the combined films effectively maintained the firmness of green asparagus spears, fiber, and vitamin C content, and outperformed the passive MAP and control groups. The above results confirm all the equations in the passive and active MAP systems established in this study.

Conclusions

Hence, maintaining the asparagus quality with an active MAP treatment will reduce economic loss and possibly provide new insights into applying active MAP retail packages to preserve fruits and vegetables in post-harvest shelf life.

Graphical Abstract