bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular vesicles released by host epithelial cells during Pseudomonas aeruginosa infection function as homing beacons for neutrophils
Authors: Ayilam Ramachandran Rajalakshmy , Lemoff Andrew , Robertson Danielle M.
Published: June 2024

Background

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that can cause sight threatening infections in the eye and fatal infections in the cystic fibrosis airway. Extracellular vesicles (EVs) are released by host cells during infection and by the bacteria themselves; however, there are no studies on the composition and functional role of host-derived EVs during PA infection of the eye or lung. Here we investigated the composition and capacity of EVs released by PA infected epithelial cells to modulate innate immune responses in host cells.

Methods

Human telomerase immortalized corneal epithelial cells (hTCEpi) cells and human telomerase immortalized bronchial epithelial cells (HBECs) were treated with a standard invasive test strain of Pseudomonas aeruginosa, PAO1, for 6 h. Host derived EVs were isolated by qEV size exclusion chromatography. EV proteomic profiles during infection were compared using mass spectrometry and functional studies were carried out using hTCEpi cells, HBECs, differentiated neutrophil-like HL-60 cells, and primary human neutrophils isolated from peripheral blood.

Results

EVs released from PA infected corneal epithelial cells increased pro-inflammatory cytokine production in naïve corneal epithelial cells and induced neutrophil chemotaxis independent of cytokine production. The EVs released from PA infected bronchial epithelial cells were also chemotactic although they failed to induce cytokine secretion from naïve HBECs. At the proteomic level, EVs derived from PA infected corneal epithelial cells exhibited lower complexity compared to bronchial epithelial cells, with the latter having reduced protein expression compared to the non-infected control.

Conclusions

This is the first study to comprehensively profile EVs released by corneal and bronchial epithelial cells during Pseudomonas infection. Together, these findings show that EVs released by PA infected corneal and bronchial epithelial cells function as potent mediators of neutrophil migration, contributing to the exuberant neutrophil response that occurs during infection in these tissues.
Mechanisms underlying neutrophils adhesion to triple-negative breast cancer cells via CD11b-ICAM1 in promoting breast cancer progression
Authors: Yang Chenghui , Li Lili , Ye Zhiqiang , Zhang Anqi , Bao Yunjia , Wu Xue , Ren Guohong , Jiang Chao , Wang Ouchen , Wang Zhen
Published: June 2024

Background

Triple-negative breast cancer (TNBC) is recognized as the most aggressive and immunologically infiltrated subtype of breast cancer. A high circulating neutrophil-to-lymphocyte ratio (NLR) is strongly linked to a poor prognosis among patients with breast cancer, emphasizing the critical role of neutrophils. Although the involvement of neutrophils in tumor metastasis is well documented, their interactions with primary tumors and tumor cells are not yet fully understood.

Methods

Clinical data were analyzed to investigate the role of neutrophils in breast cancer. In vivo mouse model and in vitro co-culture system were used for mechanism researches. Blocking experiments were further performed to identify therapeutic agents against TNBC.

Results

TNBC cells secreted GM-CSF to sustain the survival of mature neutrophils and upregulated CD11b expression. Through CD11b, neutrophils specifically binded to ICAM1 on TNBC cells, facilitating adhesion. Transcriptomic sequencing combined with human and murine functional experiments revealed that neutrophils, through direct CD11b-ICAM1 interactions, activated the MAPK signaling pathway in TNBC cells, thereby enhancing tumor cell invasion and migration. Atorvastatin effectively inhibited ICAM1 expression in tumor cells, and tumor cells with ICAM1 knockout or treated with atorvastatin were unresponsive to neutrophil activation. The MAPK pathway and MMP9 expression were significantly inhibited in the tumor tissues of TNBC patients treated with atorvastatin.

Conclusions

Targeting CD11b-ICAM1 with atorvastatin represented a potential clinical approach to reduce the malignant characteristics of TNBC.

Graphical Abstract
Trends and off-label utilization of antipsychotics in children and adolescents from 2016 to 2021 in China: a real-world study
Authors: Zhaojian Wang , Meizhu Jiang , Jun Hong , Shanshan Guo , Jiping Huo , Zhigang Zhao , Ying Gong , Cao Li
Published: June 2024

Background

Global antipsychotic usage, including off-label prescriptions, has increased in recent decades. However, trends in China, particularly for children and adolescents, remain unclear. This study explored these trends from 2016 to 2021 and identified factors associated with off-label prescriptions.

Methods

In this retrospective study, we analyzed on-label and off-label prescriptions based on drug information approved by the China National Medical Products Administration. To identify factors associated with off-label prescriptions, we conducted multivariate logistic regression analysis.

Results

Our study included 48,258 antipsychotic prescriptions, 52.4% (25,295) of which were prescriptions for males. Of these, 61.7% (29,813) were off-label. Over time, the number of antipsychotics and the percentage of off-label prescriptions for children and adolescents overall increased from 2016 to 2021. The use of atypical antipsychotics increased, whereas that of typical antipsychotics decreased. For off-label usage, all of the factors in our study were associated with off-label usage, including age, sex, year, region, department, reimbursement, antipsychotic type, drug expense, number of polypharmacy and diagnoses. Additionally, tiapride (15.8%) and aripiprazole (18.6%) were the most common typical and atypical antipsychotics, respectively. For pediatric diseases, common diagnoses included mood or affective disorders (31.7%) and behavioral and emotional disorders, with onset usually occurring in childhood and adolescence (29.1%). Furthermore, a depressive state was the most common diagnosis for which antipsychotic polypharmacy was used for treatment.

Conclusion

In this retrospective study, off-label antipsychotic prescriptions were common, with trends generally increasing among children and adolescents from 2016 to 2021. However, there is a lack of evidence supporting off-label usage, thus emphasizing the need for studies on the efficacy and safety of these treatments.
Disagreements in risk of bias assessment for randomized controlled trials in hypertension-related Cochrane reviews
Authors: Yao Yi , Shen Jing , Luo Jianzhao , Li Nian , Liao Xiaoyang , Zhang Yonggang
Published: June 2024

Background

The inter-reviewer reliability of the risk of bias (RoB) assessment lacked agreement in previous studies. It is important to analyse these disagreements to improve the repeatability of RoB assessment. The objective of the study was to evaluate the frequency and reasons for disagreements in RoB assessments for randomised controlled trials (RCTs) that were included in multiple Cochrane reviews in the field of hypertension.

Methods

A cross-sectional study was employed. We retrieved any RCTs that had been included in multiple Cochrane reviews in the field of hypertension from ARCHIE. The results of the RoB assessments were extracted, and the distributions of agreements and possible reasons for disagreement were analyzed.

Results

Twenty-six Cochrane reviews were included in this study. A total of 78 RCTs appeared in more than one Cochrane review. The level of agreement ranged from domain to domain. “Blinding of outcome assessment” showed a reasonably high level of agreement (94.9%), while “incomplete outcome data”, “selective outcome reporting” and “other sources of bias” showed moderate levels of agreement (74.6%, 79.2% and 75.6%, respectively). However, the domains of “allocation concealment”, “random sequence generation” and “blinding of participants and personnel” showed low levels of agreement (24.4%, 23.5%, and 47.4%, respectively). In the domains of “allocation concealment” and “blinding of participants and personnel”, the agreement group had higher proportion of publication year ≤ 1996 than the disagreement group (P = 0.008 and P < 0.001, respectively). In the “blinding of participants and personnel”, the impact factor was higher in the agreement group (P < 0.001). By analyzing the support text, we found that the most likely reason for disagreement was extracting different information from the same RCT.

Conclusion

For Cochrane reviews in the field of hypertension using the 2011 version of the RoB tool, there was a large disagreement in the RoB assessment. It is suggested that the results of RoB assessments in systematic reviews that used the 2011 version of the RoB tool need to be interpreted with caution. More accurate information from RCTs needs to be collected when we synthesize clinical evidence.
Studying harms of interventions with an equity lens in randomized trials
Authors: Li Tianjing , Mayo-Wilson Evan , Shaughnessy Daniel , Qureshi Riaz
Published: June 2024

Equity and health equity are fundamental pillars in fostering a just and inclusive society. While equity underscores fairness in resource allocation and opportunity, health equity aims to eradicate avoidable health disparities among social groups. The concept of harms in interventions—undesirable consequences associated with the use of interventions—often varies across populations due to biological and social factors, necessitating a nuanced understanding. An equity lens reveals disparities in harm distribution, urging researchers and policymakers to address these differences in their decision-making processes. Furthermore, interventions, even well-intentioned ones, can inadvertently exacerbate disparities, emphasizing the need for comprehensive harm assessment. Integrating equity considerations in research practices and trial methodologies, through study design or through practices such as inclusive participant recruitment, is pivotal in advancing health equity. By prioritizing interventions that address disparities and ensuring inclusivity in research, we can foster a more equitable healthcare system.
Diabetic microenvironment deteriorates the regenerative capacities of adipose mesenchymal stromal cells
Authors: Ahmed Sara M. , Elkhenany Hoda A. , Ahmed Toka A. , Ghoneim Nehal I. , Elkodous Mohamed Abd , Mohamed Rania Hassan , Magdeldin Sameh , Osama Aya , Anwar Ali Mostafa , Gabr Mahmoud M. , El-Badri Nagwa
Published: June 2024

Background

Type 2 diabetes is an endocrine disorder characterized by compromised insulin sensitivity that eventually leads to overt disease. Adipose stem cells (ASCs) showed promising potency in improving type 2 diabetes and its complications through their immunomodulatory and differentiation capabilities. However, the hyperglycaemia of the diabetic microenvironment may exert a detrimental effect on the functionality of ASCs. Herein, we investigate ASC homeostasis and regenerative potential in the diabetic milieu.

Methods

We conducted data collection and functional enrichment analysis to investigate the differential gene expression profile of MSCs in the diabetic microenvironment. Next, ASCs were cultured in a medium containing diabetic serum (DS) or normal non-diabetic serum (NS) for six days and one-month periods. Proteomic analysis was carried out, and ASCs were then evaluated for apoptosis, changes in the expression of surface markers and DNA repair genes, intracellular oxidative stress, and differentiation capacity. The crosstalk between the ASCs and the diabetic microenvironment was determined by the expression of pro and anti-inflammatory cytokines and cytokine receptors.

Results

The enrichment of MSCs differentially expressed genes in diabetes points to an alteration in oxidative stress regulating pathways in MSCs. Next, proteomic analysis of ASCs in DS revealed differentially expressed proteins that are related to enhanced cellular apoptosis, DNA damage and oxidative stress, altered immunomodulatory and differentiation potential. Our experiments confirmed these data and showed that ASCs cultured in DS suffered apoptosis, intracellular oxidative stress, and defective DNA repair. Under diabetic conditions, ASCs also showed compromised osteogenic, adipogenic, and angiogenic differentiation capacities. Both pro- and anti-inflammatory cytokine expression were significantly altered by culture of ASCs in DS denoting defective immunomodulatory potential. Interestingly, ASCs showed induction of antioxidative stress genes and proteins such as SIRT1, TERF1, Clusterin and PKM2.

Conclusion

We propose that this deterioration in the regenerative function of ASCs is partially mediated by the induced oxidative stress and the diabetic inflammatory milieu. The induction of antioxidative stress factors in ASCs may indicate an adaptation mechanism to the increased oxidative stress in the diabetic microenvironment.
The efficacy of self-monitoring of blood glucose (SMBG) intervention package through a subscription model among type-2 diabetes mellitus in Malaysia: a preliminary trial
Authors: Johari Sa’ida Munira , Razalli Nurul Huda , Chua Kai Jia , Shahar Suzana
Published: June 2024

Background

The aim of this study was to determine the effect of a Self-Monitoring Blood Glucose (SMBG) intervention package through a subscription model in improving HbA1c and health parameters among type-2 diabetes mellitus (T2DM) individuals in Malaysia.

Methods

This is a quasi-experimental study involving a total number of 111 individuals with T2DM (mean age 57.0 ± 11.7 years, 61% men) who were assigned to intervention (n = 51) and control (n = 60) groups. The intervention group participants were the subscribers of SugO365 program which provided a personalized care service based on self-recorded blood glucose values. Subscribers received a Contour®Plus One glucometer which can connect to Health2Sync mobile app to capture all blood glucose readings as well as physical and virtual follow up with dietitians, nutritionists, and pharmacists for 6 months. Outcome measures were body weight, body mass index (BMI), random blood glucose (RBG), glycated haemoglobin (HbA1c) and health-related quality of life (HRQoL, assessed by SF-36 questionnaire). Data were measured at baseline, third and sixth months.

Results

Repeated-measure analysis of covariance showed significant improvement in HbA1c level (ƞp2 = 0.045, p = 0.008) in the intervention (baseline mean 7.7% ± 1.1%; end mean 7.3% ± 1.3%) as compared to control (baseline mean 7.7% ± 0.9%; end mean 8.1% ± 1.6%) group. Similar trend was observed for Role Emotional domain of the quality of life (ƞp2 = 0.047, p = 0.023) in the intervention (baseline mean 62.8 ± 35.1, end mean 86.3 ± 21.3) compared to control (baseline mean group 70.5 ± 33.8; end mean 78.4 ± 27.3) group. Negative association was found in HbA1c changes using Z-score and Physical Function domain (r = − 0.217, p = 0.022).

Conclusion

A 6 months SMBG intervention package through a subscription model improved blood glucose control as measured by HbA1c and health-related quality of life, particularly the Role Emotional domain. Elevated HbA1c levels are correlated with decreased physical function.There is a need to further examine the efficacy of SMBG intervention package using a larger sample and a longer period of intervention and to determine its cost efficacy.
J-shaped relationship between stress hyperglycemia ratio and 90-day and 180-day mortality in patients with a first diagnosis of acute myocardial infarction: analysis of the MIMIC-IV database
Authors: Hu Ben , Chen Xinghua , Wang Yuhui , Wei Xing , Feng Jun , Hou Linlin
Published: June 2024

Aims

The Stress Hyperglycemia Ratio (SHR) potently predicts adverse outcomes in patients with cardiovascular and cerebrovascular diseases. However, the relationship between SHR and short-term mortality risk in patients with a first diagnosis of acute myocardial infarction (AMI) remains contentious. This study sought to understand better the relationship between SHR and short-term mortality risk in patients with a first diagnosis of AMI.

Methods

We conducted a cohort study using data from 1961 patients with a first diagnosis of AMI from the MIMIC-IV (version 2.2) database. Patients were divided into three groups based on SHR tertiles. The Cox proportional hazards model and a two-segmented Cox proportional hazards model were used to elucidate the nonlinear relationship between SHR in patients with a first diagnosis of AMI and mortality.

Results

Of the surveyed population, 175 patients (8.92%) died within 90 days, and 210 patients (10.71%) died within 180 days. After multivariate adjustments, elevated SHR levels were significantly and non-linearly associated with a higher risk of 90-day and 180-day mortality in patients with a first diagnosis of AMI, showing a J-shaped correlation with an inflection point at 0.9. Compared to participants with SHR levels below the inflection point, those with higher SHR levels had a fivefold increased risk of 90-day mortality (hazard ratio [HR] 5.74; 95% confidence interval [CI] 3.19, 10.33) and a fourfold increased risk of 180-day mortality (HR 4.56; 95% CI 2.62, 7.95). In the subgroup analysis, patients with pre-diabetes mellitus (pre-DM) and higher SHR levels had increased 90-day (HR 6.90; 95% CI  1.98, 24.02) and 180-day mortality risks (HR 5.30; 95% CI  1.96, 14.27).

Conclusion

In patients with a first diagnosis of AMI, there is a J-shaped correlation between SHR and 90-day and 180-day mortality, with an adverse prognostic inflection point of SHR at 0.9.
Spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support: a case report
Authors: Ohtaka Kazuto , Ohtake Setsuyuki , Ishii Yu , Kaku Saya , Takeuchi Yuta , Mizota Tomoko , Yamamura Yoshiyuki , Ichinokawa Masaomi , Yoshioka Tatsuya , Tamoto Eiji , Murakawa Katsuhiko , Ono Koichi , Kato Tatsuya
Published: June 2024

Background

Intercostal artery bleeding often occurs in a single vessel; in rare cases, it can occur in numerous vessels, making it more difficult to manage.

Case presentation

A 63-year-old Japanese man was admitted to the emergency department owing to sudden chest and back pain, dizziness, and nausea. Emergency coronary angiography revealed myocardial infarction secondary to right coronary artery occlusion. After intra-aortic balloon pumping, percutaneous coronary intervention was performed in the right coronary artery. At 12 hours following percutaneous coronary intervention, the patient developed new-onset left anterior chest pain and hypotension. Contrast-enhanced computed tomography revealed 15 sites of contrast extravasation within a massive left extrapleural hematoma. Emergency angiography revealed contrast leakage in the left 6th to 11th intercostal arteries; hence, transcatheter arterial embolization was performed. At 2 days after transcatheter arterial embolization, his blood pressure subsequently decreased, and contrast-enhanced computed tomography revealed the re-enlargement of extrapleural hematoma with multiple sites of contrast extravasation. Emergency surgery was performed owing to persistent bleeding. No active arterial hemorrhage was observed intraoperatively. Bleeding was observed in various areas of the chest wall, and an oxidized cellulose membrane was applied following ablation and hemostasis. The postoperative course was uneventful.

Conclusion

We report a case of spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support that was difficult to manage. As bleeding from numerous vessels may occur during antithrombotic therapy, even without trauma, appropriate treatments, such as transcatheter arterial embolization and surgery, should be selected in patients with such cases.
In-vitro evaluation of different antimicrobial combinations with and without colistin against carbapenem-resistant Acinetobacter baumannii clinical isolates
Authors: Müderris Tuba , Dursun Manyaslı Gülden , Sezak Nurbanu , Kaya Selçuk , Demirdal Tuna , Gül Yurtsever Süreyya
Published: June 2024

Background

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are one of the most common causes of nosocomial infections and have high mortality rates due to difficulties in treatment. In this study, the in vitro synergistic interactions of the colistin (CT)–meropenem (MEM) combination and patient clinical outcomes were compared in CRAB-infected patients that receive CT–MEM antimicrobial combination therapy. In addition, in vitro synergistic interactions of MEM–ertapenem (ETP), MEM–fosfomycin (FF) and CT–FF antimicrobial combinations were investigated. Finally, the epsilometer (E) test and checkerboard test results were compared and the compatibility of these two tests was evaluated.

Methods

Twenty-one patients were included in the study. Bacterial identification was performed with MALDI–TOF, and antimicrobial susceptibility was assessed with an automated system. Synergy studies were performed using the E test and checkerboard method.

Results

For the checkerboard method, the synergy rates for CT–MEM, MEM–FF, MEM–ETP and CT–FF were 100%, 52.3%, 23.8% and 28.5%, respectively. In the E test synergy tests, synergistic effects were detected for two isolates each in the CT–MEM and CT–FF combinations. Microbial eradication was achieved in nine (52.9%) of the 17 patients that received CT–MEM combination therapy. The agreement between the E test and the checkerboard test was 6.5%.

Conclusions

A synergistic effect was found with the checkerboard method for the CT–MEM combination in all isolates in our study, and approximately 70% of the patients benefited from treatment with this combination. In addition, more than half of the isolates showed a synergistic effect for the MEM–FF combination. Combinations of CT–MEM and MEM–FF may be options for the treatment of CRAB infections. However, a comprehensive understanding of the potential of the microorganism to develop resistant mutants under applied exposures, as well as factors that directly affect antimicrobial activity, such as pharmacokinetics/pharmacodynamics, is essential for providing treatment advice. We found a low rate of agreement between the E test method and the checkerboard test method in our study, in contrast to the literature. Comprehensive studies that compare clinical results with methods are needed to determine the ideal synergy test and interpretation method.
Association analyses of apolipoprotein E genotypes and cognitive performance in patients with Parkinson’s disease
Authors: Zhu Shi-Guo , Chen Zhu-Ling , Xiao Ke , Wang Zi-Wei , Lu Wen-Bin , Liu Rong-Pei , Huang Shi-Shi , Zhu Jian-Hong , Zhang Xiong , Wang Jian-Yong
Published: June 2024

Background

Cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer’s disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD.

Methods

A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson’s Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson’s Progression Marker Initiative (PPMI).

Results

No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aβ42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance.

Conclusions

APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aβ42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.
Agreement of tonometer for measuring intraocular pressure in Wistar rats: a systematic review
Authors: Nayak Anush , Deveswaran R. , Swati S. , Srividhya L.
Published: June 2024

Glaucoma is the most common cause of irreversible blindness in the world. It is associated with elevated intraocular pressure (IOP). Fluctuations in tonometer readings have implications for glaucoma research, where accurate IOP measurements are vital for evaluating disease progression and treatment efficacy. Researchers should carefully select the appropriate tonometer and consider biases associated with different tonometers. Validation against standard measurements can improve IOP measurement accuracy in rat models. In conclusion, this systematic review will emphasize on the importance of selecting the appropriate tonometer for IOP measurement in rat models, considering potential biases and their implications for glaucoma research. Accurate and consistent IOP measurement in rat models is crucial for understanding glaucoma pathophysiology and developing effective treatments. This systematic review aims to assess agreement among tonometers used for measuring IOP in Wistar rat models primarily focusing on TonoLab, TonoVet, and Tono-pen. The review was conducted using PRISMA guidelines. Two articles were included for qualitative synthesis. The studies compared manometric IOP with TonoLab, rebound tonometer, and Tono-pen XL readings. It was observed that TonoLab consistently underestimated IOP, while Tono-pen XL tended to overestimate IOP compared to manometric measurements. The study’s findings will help researchers in making decisions about tonometer selection, leading to more reliable outcomes in glaucoma research using rat models. Further research, specifically RCT’s (randomized controlled trial) is needed to confirm the results and enhance IOP measurement precision in rat models.
Variation of adverse drug events in different settings in Africa: a systematic review
Authors: Nyame Linda , Hu Yuhua , Xue Hui , Fiagbey Emmanuel D. K. , Li Xi , Tian Yong , Fan Lijun , Du Wei
Published: June 2024

Background

Adverse drug events (ADEs) represent challenges affecting Africa’s healthcare systems owing to the increased healthcare expenditure and negative health outcomes of ADEs.

Objectives

We aimed to systematically review published studies on ADEs and synthesize the existing evidence of ADE prevalence in Africa.

Methods

Studies reporting on ADE occurrence in African settings and published from Jan 1, 2000 to Oct 1, 2023 were identified by searching PubMed, EBSCO, Science Direct, and Web of Science. Studies that either articulately investigated ADEs caused by clinical condition (such as HIV patients) or ADEs caused by exposure to specific drug(s) (such as antibiotics) were considered specific and the remaining were general. Grouped ADE prevalence rates were described using median and interquartile range (IQR). PROSPERO registration (CRD42022374095).

Results

We included 78 observational studies from 15 African countries that investigated the prevalence of ADEs leading to hospital admissions (17 studies), developed during hospitalizations (30 studies), and captured in the outpatient departments (38 studies) or communities (4 studies). Twelve studies included multiple settings. The median prevalence of ADE during hospitalization was 7.8% (IQR: 4.2–21.4%) and 74.2% (IQR: 54.1–90.7%) in general and specific patients, respectively. The ADE-related fatality rate was 0.1% and 1.3% in general and specific patients. The overall median prevalence of ADEs leading to hospital admissions was 6.0% (IQR: 1.5–9.0%); in general, patients and the median prevalence of ADEs in the outpatient and community settings were 22.9% (IQR: 14.6–56.1%) and 32.6% (IQR: 26.0–41.3%), respectively, with a median of 43.5% (IQR: 16.3–59.0%) and 12.4% (IQR: 7.1–28.1%) of ADEs being preventable in general and specific patients, respectively.

Conclusions

The prevalence of ADEs was significant in both hospital and community settings in Africa. A high ADE prevalence was observed in specific patients, emphasizing important areas for improvement, particularly in at-risk patient groups (e.g., pediatrics, HIV, and TB patients) in various settings. Due to limited studies conducted in the community setting, future research in this setting is encouraged.
Latest insights into the epidemiology, characteristics, and therapeutic strategies of chronic hepatitis B patients in indeterminate phase
Authors: Liu Junye , Yu Yan , Zhao Heping , Guo Lei , Yang Wenjuan , Yan Yuzhu , Lv Jing
Published: June 2024

As a hepatotropic virus, hepatitis B virus (HBV) can establish a persistent chronic infection in the liver, termed, chronic hepatitis B (CHB), which causes a series of liver-related complications, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCC with HBV infection has a significantly increased morbidity and mortality, whereas it could be preventable. The current goal of antiviral therapy for HBV infection is to decrease CHB-related morbidity and mortality, and achieve sustained suppression of virus replication, which is known as a functional or immunological cure. The natural history of chronic HBV infection includes four immune phases: the immune-tolerant phase, immune-active phase, inactive phase, and reactivation phase. However, many CHB patients do not fit into any of these defined phases and are regarded as indeterminate. A large proportion of indeterminate patients are only treated with dynamic monitoring rather than recommended antiviral therapy, mainly due to the lack of definite guidelines. However, many of these patients may gradually have significant liver histopathological changes during disease progression. Recent studies have focused on the prevalence, progression, and carcinogenicity of indeterminate CHB, and more attention has been given to the prevention, detection, and treatment for these patients. Herein, we discuss the latest understanding of the epidemiology, clinical characteristics, and therapeutic strategies of indeterminate CHB, to provide avenues for the management of these patients.
The variability of muscle–blubber interface temperature with activity level in a captive Risso’s dolphin (Grampus griseus)
Authors: Sakai Kino , Fukui Daisuke , Shirouzu Hiroshi , Watanabe Yurie , Inamori Daiki , Funasaka Noriko , Aoki Kagari , Sakamoto Kentaro Q.
Published: June 2024

Background

To reduce heat loss underwater, marine mammals cover their bodies with insulation. Cetaceans in particular rely solely on blubber for insulation which has low conductivity. Blubber establishes a great thermal gradient between the warmer body core and cooler body surface, reducing heat transfer to the environment. A temperature gradient within the blubber determines the conductive heat transfer from the body trunk, where conduction and convection are the primary heat transfer mechanisms in cetaceans. Therefore, measuring the temperature at the innermost part of the blubber, i.e., the temperature at the muscle–blubber interface (Tmbi), can enhance our understanding of thermoregulatory mechanisms in cetaceans. In thermoregulation, activity-induced heat produced by increased muscle metabolism is another factor that plays an important role, however, the effects of activity on Tmbi have not been investigated in cetaceans. To assess this relationship in free-swimming cetaceans, we measured Tmbi and activity levels in a captive Risso’s dolphin (Grampus griseus) using an implantable biologging device.

Results

Tmbi and activity data were analyzed for 11 days. The average Tmbi was 35.1 ± 0.6 ºC and the temperature gradient between Tmbi and the water temperature was 13.0 ± 0.7 ºC. Tmbi was higher during the daytime and lower in the early morning. The variation in Tmbi was best explained by both the activity levels and time of day. Tmbi did not simply increase with activity levels; it appeared to remain relatively constant at most activity levels. However, Tmbi appeared to decrease when the animal was inactive and increase when it was intensely active.

Conclusion

Our results provide important insights into how a dolphin regulates its body temperature underwater. Thermal insulation by blubber and heat production by activity were suggested to play important roles in thermoregulation. Whole-body heat dissipation might be used to regulate temperature increases when heat production is excessive due to intense activity. During inactive periods, decreasing temperature gradient may help reduce heat loss from the body.
Analysis of two glass eye (Jatim) beads unearthed from the Northern Wei tomb complex in Dongxin, Datong
Authors: Jia Yanqin , Cui Jianfeng , Cao Chenming
Published: June 2024

This study analyzed two glass eye beads discovered in an ancient tomb complex at Dongxin Furniture Square in Datong, Shanxi Province in China. The tomb complex was dated to the Northern Wei Dynasty (398–494 AD), when Datong was known as Pingcheng. We used scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) as well as a 3D microscope system with ultra-depth of field to conduct non-destructive tests on the beads. We examined the beads’ manufacturing techniques, including matrices, eye patterns, and bead holes. The composition analysis revealed that both beads belonged to the mix of v-Na-Ca and m-Na-Al glass system, which is a key indicator of local production in Java. The bases were colored using Co2+, whereas the white, red, and yellow colors of the eye patterns were achieved using SnO2, Cu2O, or Cu0, and PbSnO3, respectively. These findings indicated that both objects were Jatim beads originating in the Kingdom of Java in Southeast Asia. This study provides valuable insights into ancient trade routes between different regions and offers reliable scientific evidence of the glass trade and technical exchanges in ancient times.
Discovery, characterization and mechanism of a Microbacterium esterase for key d-biotin chiral intermediate synthesis
Authors: Li Xinjia , Yu Haoran , Liu Shengli , Ma Baodi , Wu Xiaomei , Zheng Xuesong , Xu Yi
Published: June 2024

Esterases are crucial biocatalysts in chiral compound synthesis. Herein, a novel esterase EstSIT01 belonging to family V was identified from Microbacterium chocolatum SIT101 through genome mining and phylogenetic analysis. EstSIT01 demonstrated remarkable efficiency in asymmetrically hydrolyzing meso-dimethyl ester [Dimethyl cis-1,3-Dibenzyl-2-imidazolidine-4,5-dicarboxyate], producing over 99% yield and 99% enantiomeric excess (e.e.) for (4S, 5R)-monomethyl ester, a crucial chiral intermediate during the synthesis of d-biotin. Notably, the recombinant E. coli expressing EstSIT01 exhibited over 40-fold higher activity than that of the wild strain. EstSIT01 displays a preference for short-chain p-NP esters. The optimal temperature and pH were 45 °C and 10.0, with Km and kcat values of 0.147 mmol/L and 5.808 s− 1, respectively. Molecular docking and MD simulations suggest that the high stereoselectivity for meso-diester may attribute to the narrow entrance tunnel and unique binding pocket structure. Collectively, EstSIT01 holds great potential for preparing chiral carboxylic acids and esters.
Co-designing discharge communication interventions for mental health visits to the pediatric emergency department: a mixed-methods study
Authors: Ali Amber Z. , Wright Bruce , Curran Janet A. , Fawcett-Arsenault Joelle , Newton Amanda S.
Published: June 2024

Background

Discharge communication is essential to convey information regarding the care provided and follow-up plans after a visit to a hospital emergency department (ED), but it can be lacking for visits for pediatric mental health crises. Our objective was to co-design and conduct usability testing of new discharge communication interventions to improve pediatric mental health discharge communication.

Methods

The study was conducted in two phases using experience-based co-design (EBCD). In phase 1 (Sep 2021 to Jan 2022), five meetings were conducted with a team of six parents and two clinicians to co-design new ED discharge communication interventions for pediatric mental health care. Thematic analysis was used to identify patterns in team discussions and participant feedback related to discharge communication improvement and the Capability, Opportunity, Motivation, Behavior (COM-B) model was used to identify strategies to support the delivery of the new interventions. After meeting five, team members completed the Public and Patient Engagement Evaluation Tool (PPEET) to evaluate the co-design experience. In phase 2 (Apr to Jul 2022), intervention usability and satisfaction were evaluated by a new group of parents, youth aged 16–24 years, ED physicians, and nurses (n = 2 of each). Thematic analysis was used to identify usability issues and a validated 5-point Likert survey was used to evaluate user satisfaction. Evaluation results were used by the co-design team to finalize the interventions and delivery strategies.

Results

Two discharge communication interventions were created: a brochure for families and clinicians to use during the ED visit, and a text-messaging system for families after the visit. There was high satisfaction with engagement in phase 1 (overall mean PPEET score, 4.5/5). In phase 2, user satisfaction was high (mean clinician score, 4.4/5; mean caregiver/youth score, 4.1/5) with both interventions. Usability feedback included in the final intervention versions included instructions on intervention use and ensuring the text-messaging system activates within 12–24 h of discharge.

Conclusions

The interventions produced by this co-design initiative have the potential to address gaps in current discharge practices. Future testing is required to evaluate the impact on patients, caregivers, and health care system use after the ED visit.
Conceptualising the correlates of adolescent suicidal behaviour in Benin: evidence from a national survey
Authors: Sarfo Jacob Owusu , Debrah Timothy Pritchard , Gbordzoe Newton Isaac , Attigah Dean Kormla , Obeng Paul , Torsu Cyril Sewornu
Published: June 2024

Background

Despite efforts to increase awareness about suicide, related behaviours among adolescents in Benin persist as a significant health challenge globally. Nonetheless, there is a dearth of empirical evidence that conceptualises suicidal behaviour and its correlates to provide a better picture for preventive interventions. We analysed a national survey dataset of school-going Benin adolescents, with an analytical sample of 2,536.

Results

The prevalence of suicidal ideation, plan, and attempt were 14.8%, 16.3%, and 15.3%, respectively. The likelihood of ideating suicide increased among adolescents who engaged in marijuana usage, encountered bullying, felt lonely, and experienced anxiety. Additionally, the likelihood of planning suicide was high among individuals who skipped school, used marijuana, encountered bullying, felt lonely, experienced anxiety, and engaged in multiple sexual relationships. Similarly, the likelihood of attempting suicide was increased among adolescents in grades 3-6 who skipped school, used marijuana, encountered bullying, and felt lonely. Nonetheless, being a male was protective against suicidal ideation and suicidal plans, while younger age was protective against suicidal attempts. Also, having parents who respected adolescents’ autonomy and privacy (never inspected their things without their knowledge) had lower odds of suicidal ideation.

Conclusion

Suicide prevention programmes must consider multidimensional protective and risk factors concerning adolescents’ personal, parental, family, and community settings in Benin.
Investor sentiment and sustainable investment: evidence from North African stock markets
Authors: El Oubani Ahmed
Published: June 2024

This paper examines the connectedness between investor sentiment and returns and volatility on environmental, social, and governance (ESG) indices in Morocco and Egypt. Therefore, we construct a new investor sentiment index and use weekly data from January 2018 to December 2023, along with the time, frequency and quantile connectedness methods. The results show that investor sentiment sometimes influences the returns and volatility of the ESG indices, and sometimes it is influenced by them. This connectedness is stronger during distress events, namely, the COVID-19 outbreak and geopolitical tensions (the Russian-Ukrainian and Israeli-Palestinian conflicts). Furthermore, the spillover effect between sentiment and returns on the ESG indices is mainly due to short-term spillovers, except during the COVID-19 period, when long-term spillovers dominate. However, the spillover effect between sentiment and volatility on the ESG indices is mainly due to long-term spillover, especially during the COVID-19 outbreak and the Russia-Ukraine War, implying the persistence of shock transmission due to high uncertainty. The findings also highlight the impact of market conditions on spillovers. These findings can help socially responsible investors successfully diversify their portfolios and adjust their strategy according to investor sentiment; they also have beneficial implications for policymakers in achieving sustainable development goals.
Microbial cell factories in the remediation of e-wastes: an insight
Authors: Khan Sahiba , Alam Farheen Sabina , Borah Debajit
Published: June 2024

Electronic waste, also known as e-waste, is the discarded or by-products of electronic appliances, constituting a major percentage of the total solid waste produced globally. Such e-waste is mostly composed of plastics, various heavy metals, azo dyes, and xenobiotic components, which are mostly non-biodegradable or less degradable in nature. As a result, they increase environmental toxicity, preventing the growth of crops and causing health issues for humans and other animals. On the other hand, recycling e-waste may also lead to the consumption of heavy metals through water or the inhalation of polluted air after combustion, which may cause various health issues such as asthma, nerve, respiratory, kidney, liver disease, and even cancer. Hence, microbial degradation of e-waste has become a new trend in managing such solid wastes. However, their mode of action is somewhat less explored. Microbes degrade various components of e-waste through a number of mechanisms such as bioleaching, biosorption, biotransformation, bioaccumulation, and biomineralization. Some microorganisms release enzymes such as reductases, laccases, esterases, carboxylesterases, catalases, and dioxygenases for the bioconversion of various components of e-waste into their less toxic forms. This review provides insight into the role of microbes in the conversion of various components of e-wastes such as polyaromatic hydrocarbons (PAHs), azo dyes, and heavy metals and their mode of action.
Upcycling of tetra pack waste cellulose into reducing sugars for bioethanol production using Saccharomyces cerevisiae
Authors: Rinki  , Yadav Pooja , Sharma Aditya , Dahiya Pushpak , Kashyap Aakash , Walia Abhishek , Bhatt Arvind Kumar , Bhatia Ravi Kant
Published: June 2024

Bioethanol production from waste materials offers a promising avenue for sustainable energy and waste management. In this study, fermentable sugars derived from tetra pack waste cellulose were bio-transformed into bioethanol using Saccharomyces cerevisiae. Tetra pack waste (180 g) yielded tetra pack cellulosic pulp (TPCP) of 145 g, after removing the different layers representing 80.56 ± 0.32% of the original weight. Cellulase from Bacillus sp. RL-07, with a cellulolytic potential of 6.98 ± 0.36 U/ml, released 32.72 ± 0.12 mg/ml of reducing sugars, achieving 44.60 ± 0.56% saccharification of TPCP under optimized conditions. Subsequent fermentation of the broth (1 L) with tetra pack cellulosic pulp hydrolysate (TPCPH) (50% v/v), containing 5.12 g of reducing sugars, by S. cerevisiae yielded 1.42 g of bioethanol per g of reducing sugars under optimized conditions, with a volume productivity of 0.24 g/l/h and a purity of 96.42% was confirmed by GC/MS analysis.

The results of this study underscore the viability of utilizing tetra pack waste for bioethanol production, offering a sustainable solution for waste management while alleviating energy deficits and reducing environmental pollution. These findings align with objectives aimed at fostering sustainable progress and development.
Ultrasound-assisted transesterification of waste cooking oil to biodiesel utilizing banana peel derived heterogeneous catalyst
Authors: Ashok Chithra , Sankarrajan Eniyaa , Kumar P. Senthil , Janani G , Suresh Ashwin Raj , Muthuvelu Kirupa Sankar , Rangasamy Gayathri
Published: June 2024

Scientists are considering substitute energies as a consequence of the increasing global demand for energy. An eco-friendly and high flash point biofuel, biodiesel, can be obtained from different types of animal fats, vegetable oils, and algal oils through transesterification with methanol with the support of a catalyst. The current study focused on exploring a bio-based heterogeneous catalyst, Nendran banana peel (NBP), for biodiesel production from promising feedstocks like waste cooking oil (WCO) using ultrasound-based transesterification. Catalyst morphological characterization showed a microporous structure and shows the minerals like potassium and calcium present in it which help to catalyze the reaction. The resultant biodiesel yield calculated using 1H NMR showed 72.25% conversion. The outcomes of this study showed that the Nendran banana peel can act as a potent catalyst for the biodiesel manufacturing process.

Graphical Abstract