bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia
Authors: Cozzi-Lepri Alessandro , Borghi Vanni , Rotundo Salvatore , Mariani Bianca , Ferrari Anna , Del Borgo Cosmo , Bai Francesca , Colletti Pietro , Miraglia Piermauro , Torti Carlo , Cattelan Anna Maria , Cenderello Giovanni , Berruti Marco , Tascini Carlo , Parruti Giustino , Coladonato Simona , Gori Andrea , Marchetti Giulia , Lichtner Miriam , Coppola Luigi , Sorace Chiara , D'Abramo Alessandra , Mazzotta Valentina , Guaraldi Giovanni , Franceschini Erica , Meschiari Marianna , Sarmati Loredana , Antinori Andrea , Nicastri Emanuele , Mussini Cristina
Published: March 2024

Introduction

Casirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm.

Methods

This is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and β-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality.

Results

A total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data.

Conclusion

The mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions.
Case Report: Dostarlimab for treatment of aggressive cutaneous squamous cell carcinoma
Authors: Gandarillas Sophia , Tang Horace , Dasgeb Bahar
Published: March 2024

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy with the aggressive cSCC subtype being especially worrisome due to its higher metastatic and mortality rate. An 80-year-old immunocompetent Caucasian man presented with a locally advanced and recurrent cSCC for which he underwent six Mohs surgeries, radiation therapy, and standard immunotherapy treatments. Throughout treatment, the patient’s cancer continued to progress across different regions of the face. Biopsy and analysis were performed and showed that the cSCCs had a high mutational burden and oncogenes known to be present in tumors with aggressive nature. After the algorithmically applied standard of care failed to cure or control the progressing disease, the genetic analysis favored dostarlimab as a suitable option. With only three doses of 500 mg dostarlimab q3 weeks, the patient showed a fast response with macroscopic resolution of clinically discernible disease of, the previously noted, locally advanced cSCC on his right forehead, as well as other primary keratinocyte carcinomas on his left contralateral face, nose, left leg, and neck. This remarkable case can present an option for complex patients with locally advanced and recurrent cSCC who failed the current standard of care. Moreover, it warrants a proper clinical trial to assess efficacy and potential indication of dostarlimab in such patients. Of note is the presence of a KMT2D mutation and its well-identified correlation with mismatch repair deficiency (dMMR) and poor prognosis, which can play an informative role in clinical decision making and precision therapeutic choice at the point of care.
Is the cost of the new home dialysis techniques still advantageous compared to in-center hemodialysis? An Italian single center analysis and comparison with experiences from western countries
Authors: Iadarola Gian Maria , Giorda Elisa , Borca Marco , Morero Daniela , Sciascia Savino , Roccatello Dario
Published: March 2024

Introduction

Potential advantages of home dialysis remained a questionable issue. Three main factors have to be considered: the progressive reduction in the cost of consumables for in-Center hemodialysis (IC-HD), the widespread use of incremental Peritoneal Dialysis (PD), and the renewed interest in home hemodialysis (H-HD) in the pandemic era. Registries data on prevalence of dialysis modalities generally report widespread underemployment of home dialysis despite PD and H-HD could potentially provide clinical benefits, improve quality of life, and contrast the diffusion of new infection among immunocompromised patients.

Methods

We examined the economic impact of home dialysis by comparing the direct and indirect costs of PD (53 patients), H-HD (21 patients) and IC-HD (180 patients) in a single hospital of North-west Italy. In order to achieve comparable weekly costs, the average weekly frequency of dialysis sessions based on the dialysis modality was calculated, the cost of individual sessions per patient per week normalized, and the monthly and yearly costs were derived.

Results

As expected, PD resulted the least expensive procedure (€ 23,314.79 per patient per year), but, notably, H-HD has a lower average cost than IC-HD (€ 35,535.00 vs. € 40,798.98). A cost analysis of the different dialysis procedures confirms the lower cost of PD, especially continuous ambulatory PD, compared to any extracorporeal technique.

Discussion

Among the hemodialysis techniques, home bicarbonate HD showed the lowest costs, while the weekly cost of Frequent Home Hemodialysis was found to be comparable to In-Center Bicarbonate Hemodialysis.
Context is key: glucocorticoid receptor and corticosteroid therapeutics in outcomes after traumatic brain injury
Authors: Taylor Morgan A. , Kokiko-Cochran Olga N.
Published: March 2024

Traumatic brain injury (TBI) is a global health burden, and survivors suffer functional and psychiatric consequences that can persist long after injury. TBI induces a physiological stress response by activating the hypothalamic-pituitary-adrenal (HPA) axis, but the effects of injury on the stress response become more complex in the long term. Clinical and experimental evidence suggests long lasting dysfunction of the stress response after TBI. Additionally, pre- and post-injury stress both have negative impacts on outcome following TBI. This bidirectional relationship between stress and injury impedes recovery and exacerbates TBI-induced psychiatric and cognitive dysfunction. Previous clinical and experimental studies have explored the use of synthetic glucocorticoids as a therapeutic for stress-related TBI outcomes, but these have yielded mixed results. Furthermore, long-term steroid treatment is associated with multiple negative side effects. There is a pressing need for alternative approaches that improve stress functionality after TBI. Glucocorticoid receptor (GR) has been identified as a fundamental link between stress and immune responses, and preclinical evidence suggests GR plays an important role in microglia-mediated outcomes after TBI and other neuroinflammatory conditions. In this review, we will summarize GR-mediated stress dysfunction after TBI, highlighting the role of microglia. We will discuss recent studies which target microglial GR in the context of stress and injury, and we suggest that cell-specific GR interventions may be a promising strategy for long-term TBI pathophysiology.
Epilepsy-related functional brain network alterations are already present at an early age in the GAERS rat model of genetic absence epilepsy
Authors: Wachsmuth Lydia , Hebbelmann Leo , Prade Jutta , Kohnert Laura C. , Lambers Henriette , Lüttjohann Annika , Budde Thomas , Hess Andreas , Faber Cornelius
Published: March 2024

Introduction

Genetic Absence Epilepsy Rats from Strasbourg (GAERS) represent a model of genetic generalized epilepsy. The present longitudinal study in GAERS and age-matched non-epileptic controls (NEC) aimed to characterize the epileptic brain network using two functional measures, resting state-functional magnetic resonance imaging (rs-fMRI) and manganese-enhanced MRI (MEMRI) combined with morphometry, and to investigate potential brain network alterations, following long-term seizure activity.

Methods

Repeated rs-fMRI measurements at 9.4 T between 3 and 8 months of age were combined with MEMRI at the final time point of the study. We used graph theory analysis to infer community structure and global and local network parameters from rs-fMRI data and compared them to brain region-wise manganese accumulation patterns and deformation-based morphometry (DBM).

Results

Functional connectivity (FC) was generally higher in GAERS when compared to NEC. Global network parameters and community structure were similar in NEC and GAERS, suggesting efficiently functioning networks in both strains. No progressive FC changes were observed in epileptic animals. Network-based statistics (NBS) revealed stronger FC within the cortical community, including regions of association and sensorimotor cortex, and with basal ganglia and limbic regions in GAERS, irrespective of age. Higher manganese accumulation in GAERS than in NEC was observed at 8 months of age, consistent with higher overall rs-FC, particularly in sensorimotor cortex and association cortex regions. Functional measures showed less similarity in subcortical regions. Whole brain volumes of 8 months-old GAERS were higher when compared to age-matched NEC, and DBM revealed increased volumes of several association and sensorimotor cortex regions and of the thalamus.

Discussion

rs-fMRI, MEMRI, and volumetric data collectively suggest the significance of cortical networks in GAERS, which correlates with an increased fronto-central connectivity in childhood absence epilepsy (CAE). Our findings also verify involvement of basal ganglia and limbic regions. Epilepsy-related network alterations are already present in juvenile animals. Consequently, this early condition seems to play a greater role in dynamic brain function than chronic absence seizures.
Causal relationship between telomere length and risk of intracranial aneurysm: a bidirectional Mendelian randomization study
Authors: Xu Bangjie , Ren Jiangbin , Zhu Siqi , Ding Yu , Zhou Wei , Guo Qing , Fang Yan , Zheng Jing
Published: March 2024

Background

Telomere length is closely linked to the aging phenotype, where cellular aging results in the production of a cascade of cell factors and the senescence-associated secretory phenotype (SASP), leading to an inflammatory response. The presence of inflammation plays a crucial role in the formation of intracranial aneurysms. Nevertheless, the relationship between telomere length and intracranial aneurysms remains unclear. This study aims to explore the causal connection between telomere length and intracranial aneurysms through the utilization of Mendelian randomization (MR) analysis.

Methods

Data on telomere length were obtained from the genome-wide association studies conducted on the UK Biobank, comprising a total of 472,174 participants. Data on intracranial aneurysms were obtained from the summary dataset of the Global Genome-wide Association Study (GWAS) conducted by the International Stroke Genetics Consortium. The dataset consisted of 7,495 cases and 71,934 controls, all of European descent. Initially, the linkage disequilibrium score was used to investigate the connection between telomere length and intracranial aneurysms. Subsequently, a bidirectional MR was conducted using two-sample analysis to assess whether there is a causal connection between telomere length and intracranial aneurysm risk. The results were analyzed utilizing five MR methods, with the inverse variance weighted method serving as the main methodology. In addition, we did various analyses to evaluate the presence of heterogeneity, pleiotropy, and sensitivity in the study results. A reverse MR analysis was conducted to investigate potential reverse causal links.

Results

In the forward MR analysis, it was observed that both the inverse variance-weighted and weighted median analyses implied a potential causal relationship between longer telomere length and a decreased incidence of intracranial aneurysms (IVW: OR = 0.66, 95% CI: 0.47–0.92, p = 1.49 × 10−2). There was no heterogeneity or horizontal pleiotropy. The findings were verified to be robust through the utilization of leave-one-out analysis. The use of reverse MR analysis did not establish a potential causal link between the occurrence of intracranial aneurysms and telomere length.

Conclusion

There may exist a potential correlation between longer telomere length and a decreased likelihood of intracranial aneurysms within the European population. The present study offers novel insights into the correlation between telomere length and intracranial aneurysms. Additional research is required to clarify the underlying mechanisms and validate our discoveries in diverse populations.
A dynamic study of VEGF-A siDOX-EVs trafficking through the in-vitro insert co-culture blood-brain barrier model by digital holographic microscopy
Authors: Shamshiripour Parisa , Rahnama Mehrana , Nikoobakht Mehdi , Hajiahmadi Fahimeh , Moradi Ali-reza , Ahmadvand Davoud
Published: March 2024

Introduction

Modeling the blood-brain barrier has long been a challenge for pharmacological studies. Up to the present, numerous attempts have been devoted to recapitulating the endothelial barrier in vitro to assess drug delivery vehicles’ efficiency for brain disorders. In the current work, we presented a new approach for analyzing the morphometric parameters of the cells of an insert co-culture blood-brain barrier model using rat brain astrocytes, rat brain microvascular endothelial cells, and rat brain pericytes. This analytical approach could aid in getting further information on drug trafficking through the blood-brain barrier and its impact on the brain indirectly.

Methods

In the current work, we cultured rat brain astrocytes, rat brain microvascular endothelial cells, and rat brain pericytes and then used an insert well to culture the cells in contact with each other to model the blood-brain barrier. Then, the morphometric parameters of the porous membrane of the insert well, as well as each cell type were imaged by digital holographic microscopy before and after cell seeding. At last, we performed folate conjugation on the surface of the EVs we have previously tested for glioma therapy in our previous work called VEGF-A siDOX-EVs and checked how the trafficking of EVs improves after folate conjugation as a clathrin-mediated delivery setup. the trafficking and passage of EVs were assessed by flow cytometry and morphometric analysis of the digital holographic microscopy holograms.

Results

Our results indicated that EVs successfully entered through the proposed endothelial barrier assessed by flow cytometry analysis and furthermore, folate conjugation significantly improved EV passage through the blood-brain barrier. Moreover, our results indicated that the VEGF-A siDOX-EVs insert cytotoxic impact on the cells of the bottom of the culture plate.

Conclusion

folate-conjugation on the surface of EVs improves their trafficking through the blood-brain barrier and by using digital holographic microscopy analysis, we could directly assess the morphometric changes of the blood-brain barrier cells for pharmacological purposes as an easy, label-free, and real-time analysis.
Primary pure large cell neuroendocrine carcinoma of the urinary bladder: a case report and literature review
Authors: Sun Zhenpeng , Liang Xin , Zhang Changcun , Song Shizhang , Gao Jiangang
Published: March 2024

Background

The large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is a rare malignancy. With its high aggressiveness and poor prognosis, the disease is often accompanied by metastasis or recurrence. The lack of specific clinical manifestations and imaging features causes considerable challenges for clinical diagnosis and treatment.

Case presentation

We report a case of LCNEC of the urinary bladder. The patient was a 79-year-old male admitted to our hospital with recurrent episodes of asymptomatic gross hematuria. Based on the computed tomography (CT) scan findings, our patient presented with a bladder mass displaying invasion into the serosal layer, suggestive of muscle involvement and indicative of malignancy. The patient received a radical cystectomy, and the postoperative pathology confirmed primary, pure LCNEC of the urinary bladder. We gave him 16 cycles of toripalimab immunotherapy. As of follow-up, the patient was alive, and periodic CT reexamination showed no evidence of recurrence.

Conclusions

We reviewed domestic and foreign literature and found no explicit treatment protocols exist for the disease. Surgical resection combined with chemotherapy were the most common treatments. Herein, we reported the first case of primary, pure LCNEC of the urinary bladder treated by radical cystectomy combined with pure immunotherapy, achieving sustained remission, which provides a new idea for the immunotherapy and integrative treatment of the disease.
The application of artificial intelligence for Rapid On-Site Evaluation during flexible bronchoscopy
Authors: Yan Shuang , Li Yongfei , Pan Lei , Jiang Hua , Gong Li , Jin Faguang
Published: March 2024

Background

Rapid On-Site Evaluation (ROSE) during flexible bronchoscopy (FB) can improve the adequacy of biopsy specimens and diagnostic yield of lung cancer. However, the lack of cytopathologists has restricted the wide use of ROSE.

Objective

To develop a ROSE artificial intelligence (AI) system using deep learning techniques to differentiate malignant from benign lesions based on ROSE cytological images, and evaluate the clinical performance of the ROSE AI system.

Method

6357 ROSE cytological images from 721 patients who underwent transbronchial biopsy were collected from January to July 2023 at the Tangdu Hospital, Air Force Medical University. A ROSE AI system, composed of a deep convolutional neural network (DCNN), was developed to identify whether there were malignant cells in the ROSE cytological images. Internal testing, external testing, and human-machine competition were used to evaluate the performance of the system.

Results

The ROSE AI system identified images containing lung malignant cells with the accuracy of 92.97% and 90.26% on the internal testing dataset and external testing dataset respectively, and its performance was comparable to that of the experienced cytopathologist. The ROSE AI system also showed promising performance in diagnosing lung cancer based on ROSE cytological images, with accuracy of 89.61% and 87.59%, and sensitivity of 90.57% and 94.90% on the internal testing dataset and external testing dataset respectively. More specifically, the agreement between the ROSE AI system and the experienced cytopathologist in diagnosing common types of lung cancer, including squamous cell carcinoma, adenocarcinoma, and small cell lung cancer, demonstrated almost perfect consistency in both the internal testing dataset (κ = 0.930) and the external testing dataset (κ = 0.932).

Conclusions

The ROSE AI system demonstrated feasibility and robustness in identifying specimen adequacy, showing potential enhancement in the diagnostic yield of FB. Nevertheless, additional enhancements, incorporating a more diverse range of training data and leveraging advanced AI models with increased capabilities, along with rigorous validation through extensive multi-center randomized control assays, are crucial to guarantee the seamless and effective integration of this technology into clinical practice.
Research progress on the PEGylation of therapeutic proteins and peptides (TPPs)
Authors: Li Chunxiao , Li Ting , Tian Xinya , An Wei , Wang Zhenlong , Han Bing , Tao Hui , Wang Jinquan , Wang Xiumin
Published: March 2024

With the rapid advancement of genetic and protein engineering, proteins and peptides have emerged as promising drug molecules for therapeutic applications. Consequently, there has been a growing interest in the field of chemical modification technology to address challenges associated with their clinical use, including rapid clearance from circulation, immunogenicity, physical and chemical instabilities (such as aggregation, adsorption, deamination, clipping, oxidation, etc.), and enzymatic degradation. Polyethylene glycol (PEG) modification offers an effective solution to these issues due to its favorable properties. This review presents recent progress in the development and application of PEGylated therapeutic proteins and peptides (TPPs). For this purpose, firstly, the physical and chemical properties as well as classification of PEG and its derivatives are described. Subsequently, a detailed summary is provided on the main sites of PEGylated TPPs and the factors that influence their PEGylation. Furthermore, notable instances of PEG-modified TPPs (including antimicrobial peptides (AMPs), interferon, asparaginase and antibodies) are highlighted. Finally, we propose the chemical modification of TPPs with PEG, followed by an analysis of the current development status and future prospects of PEGylated TPPs. This work provides a comprehensive literature review in this promising field while facilitating researchers in utilizing PEG polymers to modify TPPs for disease treatment.
Understanding the complexities of space anaemia in extended space missions: revelations from microgravitational odyssey
Authors: Lansiaux Edouard , Jain Nityanand , Yatin Chodnekar Swarali , Siddiq Abdelmomen , Ibrahim Muiz , Yèche Mathieu , Kantane Inara
Published: March 2024

Space travel exposes astronauts to several environmental challenges, including microgravity and radiation exposure. To overcome these stressors, the body undergoes various adaptations such as cardiovascular deconditioning, fluid shifts, metabolic changes, and alterations in the state of the bone marrow. Another area of concern is the potential impact of these adaptations on erythrocyte and haemoglobin concentrations, which can lead to what is commonly referred to as space anaemia or microgravity-induced anaemia. It is known that anaemia may result in impaired physical and cognitive performance, making early detection and management crucial for the health and wellbeing of astronauts during extended space missions. However, the effects and mechanisms of space anaemia are not fully understood, and research is underway to determine the extent to which it poses a challenge to astronauts. Further research is needed to clarify the long-term effects of microgravity on the circulatory system and to investigate possible solutions to address spaceflight-induced anaemia. This article reviews the potential link between spaceflight and anaemia, based on existing evidence from simulated studies (e.g., microgravity and radiation studies) and findings from spaceflight studies (e.g., International Space Station and space shuttle missions).
Osteocyte-mediated mechanical response controls osteoblast differentiation and function
Authors: Buck Heather VerValin , Stains Joseph Paul
Published: March 2024

Low bone mass is a pervasive global health concern, with implications for osteoporosis, frailty, disability, and mortality. Lifestyle factors, including sedentary habits, metabolic dysfunction, and an aging population, contribute to the escalating prevalence of osteopenia and osteoporosis. The application of mechanical load to bone through physical activity and exercise prevents bone loss, while sufficient mechanical load stimulates new bone mass acquisition. Osteocytes, cells embedded within the bone, receive mechanical signals and translate these mechanical cues into biological signals, termed mechano-transduction. Mechano-transduction signals regulate other bone resident cells, such as osteoblasts and osteoclasts, to orchestrate changes in bone mass. This review explores the mechanisms through which osteocyte-mediated response to mechanical loading regulates osteoblast differentiation and bone formation. An overview of bone cell biology and the impact of mechanical load will be provided, with emphasis on the mechanical cues, mechano-transduction pathways, and factors that direct progenitor cells toward the osteoblast lineage. While there are a wide range of clinically available treatments for osteoporosis, the majority act through manipulation of the osteoclast and may have significant disadvantages. Despite the central role of osteoblasts to the deposition of new bone, few therapies directly target osteoblasts for the preservation of bone mass. Improved understanding of the mechanisms leading to osteoblastogenesis may reveal novel targets for translational investigation.
Beyond Discrimination: Generative AI Applications and Ethical Challenges in Forensic Psychiatry
Authors: Tortora Leda
Published: March 2024

The advent and growing popularity of generative artificial intelligence (GenAI) holds the potential to revolutionise AI applications in forensic psychiatry and criminal justice, which traditionally relied on discriminative AI algorithms. Generative AI models mark a significant shift from the previously prevailing paradigm through their ability to generate seemingly new realistic data and analyse and integrate a vast amount of unstructured content from different data formats. This potential extends beyond reshaping conventional practices, like risk assessment, diagnostic support, and treatment and rehabilitation plans, to creating new opportunities in previously underexplored areas, such as training and education. This paper examines the transformative impact of generative artificial intelligence on AI applications in forensic psychiatry and criminal justice. First, it introduces generative AI and its prevalent models. Following this, it reviews the current applications of discriminative AI in forensic psychiatry. Subsequently, it presents a thorough exploration of the potential of generative AI to transform established practices and introduce novel applications through multimodal generative models, data generation and data augmentation. Finally, it provides a comprehensive overview of ethical and legal issues associated with deploying generative AI models, focusing on their impact on individuals as well as their broader societal implications. In conclusion, this paper aims to contribute to the ongoing discourse concerning the dynamic challenges of generative AI applications in forensic contexts, highlighting potential opportunities, risks, and challenges. It advocates for interdisciplinary collaboration and emphasises the necessity for thorough, responsible evaluations of generative AI models before widespread adoption into domains where decisions with substantial life-altering consequences are routinely made.
Sleep quality and associated factors among university students in Africa: a systematic review and meta-analysis study
Authors: Nakie Girum , Takelle Girmaw Medfu , Rtbey Gidey , Andualem Fantahun , Tinsae Techilo , Kassa Mulat Awoke , Tadesse Gebresilassie , Fentahun Setegn , Wassie Yilkal Abebaw , Segon Tesfaye , Kibralew Getasew , Melkam Mamaru
Published: March 2024

Background

Poor sleep quality significantly impacts academic performance in university students. However, inconsistent and inconclusive results were found in a study on sleep among university students in several African nations. Therefore, this study aimed to estimate the pooled prevalence and associated factors of poor sleep quality among university students in Africa.

Methods

The databases PubMed, Scopus, Cochrane Library, Science Direct, African Journal Online, and Google Scholar were searched to identify articles. A total of 35 primary articles from 11 African countries were assessed and included in this systematic review and meta-analysis. Data were extracted by using a Microsoft Excel spreadsheet and exported to STATA version 14 for analysis. The I2 test was used to assess the statistical heterogeneity. A random effect meta-analysis model was employed with 95% confidence intervals. Funnel plots analysis and Egger regression tests were used to check the presence of publication bias. A subgroup analysis and a sensitivity analysis were done.

Results

A total of 16,275 study participants from 35 studies were included in this meta-analysis and systematic review. The overall pooled prevalence of poor sleep quality among university students in Africa was 63.31% (95% CI: 56.91-65.71) I2 = 97.2. The subgroup analysis shows that the combined prevalence of poor sleep quality in East, North, West, and South Africa were 61.31 (95% CI: 56.91-65.71), 62.23 (95% CI: 54.07-70.39), 54.43 (95% CI: 47.39-61.48), and 69.59 (95% CI: 50.39-88.80) respectively. Being stressed (AOR= 2.39; 95% CI: 1.63 to 3.51), second academic year (AOR= 3.10; 95% CI: 2.30 to 4.19), use of the electronic device at bedtime (AOR= 3.97 95% CI: 2.38 to 6.61)) and having a comorbid chronic illness (AOR = 2.71; 95% CI: 1.08, 6.82) were factors significantly associated with poor sleep quality.

Conclusion

This study shows that there is a high prevalence of poor sleep quality among university students in Africa. Being stressed, in the second year, using electronic devices at bedtime, and having chronic illness were factors associated with poor sleep quality. Therefore, addressing contributing factors and implementing routine screenings are essential to reduce the burden of poor sleep quality.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023493140.
A 3D tailored monolithic glass chip for stimulating and recording zebrafish neuronal activity with a commercial light sheet microscope
Authors: Schrödter Dominika , Mozafari Mohadeseh , Fichtner Janine , von Trotha Jakob William , Köster Reinhard Wolfgang , Dietzel Andreas
Published: March 2024

Microfluidic technology is unrivaled in its ability to apply soluble chemical stimuli with high spatiotemporal precision. Analogous, light–sheet microscopy is unmatched in its ability of low phototoxic but fast volumetric in vivo imaging with single cell resolution. Due to their optical translucency during the larval stages, zebrafish (Danio rerio) are an ideal model to combine both techniques; yet, thus far this required light–sheet microscopes, which were in most cases custom–built and adapted to the available softlithographic chip technology. Our aim was to use a commercial light–sheet microscope to illuminate a microfluidic chip from two opposite lateral directions and to record images with the detection objective placed orthogonally above the chip. Deep tissue penetration can be achieved by superimposing beams from opposite directions to form a single light sheet. But a microfluidic chip that allows a) targeted stimulus application in a closed microenvironment, b) interference–free incoupling of excitation light from two directions and c) outcoupling of fluorescence in the perpendicular direction through an optically perfect cover glass was not known until now. Here, we present a monolithic glass chip with the required plane-parallel sidewalls and cover slide closure at the top, constructed by advanced femtosecond laser ablation, thermal bonding and surface smoothing processes. In addition, the 3D shape of a fish fixator unit was tailored to match the body shape of a zebrafish larva to ensure stable positioning during whole–brain recording. With hydrodynamic focusing a targeted partial exposure of the larva’s head to chemical stimuli and fast position switching (in less than 10 s) was possible. With the capabilities of this unique monolithic glass chip and its up–scalable wafer–level fabrication process, the new NeuroExaminer is prone to become an excellent addition to neurobiology laboratories already equipped with high–quality commercial light sheet microscopes.
Optimizing androgen receptor prioritization using high-throughput assay-based activity models
Authors: Bever Ronnie Joe , Edwards Stephen W. , Antonijevic Todor , Nelms Mark D. , Ring Caroline , Harris Danni , Lynn Scott G. , Williams David , Chappell Grace , Boyles Rebecca , Borghoff Susan , Markey Kristan J.
Published: March 2024

Introduction: Computational models using data from high-throughput screening assays have promise for prioritizing and screening chemicals for testing under the U.S. Environmental Protection Agency’s Endocrine Disruptor Screening Program (EDSP). The purpose of this work was to demonstrate a data processing method for the determination of optimal minimal assay batteries from a larger comprehensive model, to provide a uniform method of evaluating the performance of future minimal assay batteries compared with the androgen receptor (AR) pathway model, and to incorporate chemical cluster analysis into this evaluation. Although several of the assays in the AR pathway model are no longer available through the original vendor, this approach could be used for future evaluations of minimal assay models for prioritization and screening.

Methods: We compared two previously published models and found that an expanded 14-assay model had higher sensitivity for antagonists, whereas the original 11-assay model had slightly higher sensitivity for agonists. We then investigated subsets of assays in the original AR pathway model to optimize overall testing strategies that minimize cost while maintaining sensitivity across a broad chemical space.

Results and Discussion: Evaluation of the critical assays across subset models derived from the 14-assay model identified three critical assays for predicting antagonism and two critical assays for predicting agonism. A minimum of nine assays is required for predicting agonism and antagonism with high sensitivity (95%). However, testing workflows guided by chemical structure–based clusters can reduce the average number of assays needed per chemical by basing the assays selected for testing on the likelihood of a chemical being an AR agonist, according to its structure. Our results show that a multi-stage testing workflow can provide 95% sensitivity while requiring only 48% of the resources required for running all assays from the original full models. The resources can be reduced further by incorporating in silico activity predictions.

Conclusion: This work illustrates a data-driven approach that incorporates chemical clustering and simultaneous consideration of antagonism and agonism mechanisms to more efficiently screen chemicals. This case study provides a proof of concept for prioritization and screening strategies that can be utilized in future analyses to minimize the overall number of assays needed for predicting AR activity, which will maximize the number of chemicals that can be tested and allow data-driven prioritization of chemicals for further screening under the EDSP.
Effect of diets supplemented with coated plant essential oil on the growth performance, immunity, antioxidant activity, and fecal microbiota of weaned piglets
Authors: Niu Yu , Chen Yiying , Liu Jinsong , Liu Yulan , Xiao Shiping , Yang Caimei , Yang Ting , Huan Weiwei
Published: March 2024

Introduction

This trial was conducted to compare the effect of diets supplemented with plant essential oil (PEO) and coated plant essential oil (CEO) on growth performance, immunity, antioxidant activity, and fecal microbiota of weaned piglets.

Methods

A total of 360 21-day-old weaned piglets were randomly allocated into three groups, namely, CON, PEO, and CEO (basal diets supplemented with 0, 500 mg/kg PEO, and 500 mg/kg CEO, respectively) for a 4-week feeding trial.

Results and discussion

The results showed that dietary supplementation with CEO improved the average final weight and average daily gain, decreased the diarrhea rate, increased antioxidant enzyme activities, enhanced immunoglobulin concentrations, and decreased concentrations of pro-inflammatory cytokines in the serum of weaned piglets (p < 0.05). In addition, CEO addition increased the fecal concentrations of propionic acid and isovaleric acid of piglets (p < 0.05). Spearman correlation analysis showed that fecal microorganisms at the genus level were closely correlated with the volatile fatty acid concentrations. The present study indicated that PEO and CEO could improve growth performance, enhance immunity, and increase antioxidant capacity by modulating the microbial flora in weaned piglets. Moreover, CEO addition seemed to offer more positive results than of PEO addition.
Comparison of Milk Kefirs Obtained from Cow’s, Ewe’s and Goat’s Milk: Antioxidant Role of Microbial-Derived Exopolysaccharides
Authors: M’hir Sana , Ayed Lamia , De Pasquale Ilaria , Fanizza Elisabetta , Tlais Ali Zein Alabiden , Comparelli Roberto , Verni Michela , Latronico Rosanna , Gobbetti Marco , Di Cagno Raffaella , Filannino Pasquale
Published: March 2024

Different types of milk are used in the production of milk kefir, but little information is available on the release of potentially antioxidant exopolysaccharides (EPS). The aim of this study was to investigate whether the microbial dynamics and EPS release are dependent on the milk substrate. In our study, the inoculated microbial consortium was driven differently by each type of milk (cow, ewe, and goat). This was evident in the sugar consumption, organic acid production, free amino release, and EPS production. The amount and the composition of the secreted EPS varied depending on the milk type, with implications for the structure and functional properties of the EPS. The low EPS yield in ewe’s milk was associated with a higher lactic acid production and thus with the use of carbon sources oriented towards energy production. Depending on the milk used as substrate, the EPS showed different monosaccharide and FT-IR profiles, microstructures, and surface morphologies. These differences affected the antiradical properties and reducing power of the EPS. In particular, EPS extracted from cow’s milk had a higher antioxidant activity than other milk types, and the antioxidant activity was concentration dependent.
A Comparison of the Antioxidant Potential and Metabolite Analysis of Marine Fungi Associated with the Red Algae Pterocladiella capillacea from Northern Taiwan
Authors: Kannan Jiji , Pang Ka-Lai , Ho Ying-Ning , Hsu Pang-Hung , Chen Li-Li
Published: March 2024

This study represents a primary investigation centered on screening six marine fungi, Emericellopsis maritima, Engyodontium album, Hypomontagnella monticulosa, Hortaea werneckii, Trichoderma harzianum, and Aspergillus sp.7, associated with the red algae Pterocladiella capillacea, which was collected from Chao-Jin Park in Keelung, Taiwan, as potential immunostimulants for shrimp aquaculture. Recognizing the imperative for novel strategies to combat pathogen resistance arising from the use of antibiotics and vaccines in aquaculture, this study aimed to evaluate the metabolomic profile, antioxidant capabilities, and antibacterial properties of marine fungi. The antibacterial activity of the fungal extract was evaluated against five major aquaculture pathogens: Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Enterobacter aeruginosa, and Vibrio parahaemolyticus. The viability and cytotoxicity of marine fungal extracts were preliminarily evaluated using brine shrimps before assessing cytotoxicity, growth performance, immune efficacy, and disease resistance in white shrimp. The present study demonstrated that total phytochemical analysis correlated with antioxidant activity. Emericellopsis maritima and Trichoderma harzianum exhibited the strongest DPPH antioxidant scavenging activities of half-maximal inhibitory concentration (IC50) 16.5 ± 1.2 and 12.2 ± 2.6, which are comparable to ascorbic acid. LC-HDMSE analysis of the marine fungal extracts identified more than 8000 metabolites mainly classified under the superclass level of organic oxygen compounds, Organoheterocyclic compounds, Phenylpropanoids and polyketides, alkaloid and derivatives, benzenoids, lignans and neolignans, lipid and lipid-like molecules, nucleotides and nucleosides, organic nitrogen compounds, and organic acids and derivatives. Overall, our study significantly contributes to the advancement of sustainable practices by exploring alternative antimicrobial solutions and harnessing the bioactive potential inherent in marine endophytic fungi. In conclusion, our study advances our comprehension of fungal communities and their applications and holds promise for the development of effective and environmentally friendly approaches for enhancing shrimp health and productivity.
Simvastatin-Mediated Nrf2 Activation Induces Fetal Hemoglobin and Antioxidant Enzyme Expression to Ameliorate the Phenotype of Sickle Cell Disease
Authors: Xi Caixia , Palani Chithra , Takezaki Mayuko , Shi Huidong , Horuzsko Anatolij , Pace Betty S. , Zhu Xingguo
Published: March 2024

Sickle cell disease (SCD) is a pathophysiological condition of chronic hemolysis, oxidative stress, and elevated inflammation. The transcription factor Nrf2 is a master regulator of oxidative stress. Here, we report that the FDA-approved oral agent simvastatin, an inhibitor of hydroxymethyl-glutaryl coenzyme A reductase, significantly activates the expression of Nrf2 and antioxidant enzymes. Simvastatin also induces fetal hemoglobin expression in SCD patient primary erythroid progenitors and a transgenic mouse model. Simvastatin alleviates SCD symptoms by decreasing hemoglobin S sickling, oxidative stress, and inflammatory stress in erythroblasts. Particularly, simvastatin increases cellular levels of cystine, the precursor for the biosynthesis of the antioxidant reduced glutathione, and decreases the iron content in SCD mouse spleen and liver tissues. Mechanistic studies suggest that simvastatin suppresses the expression of the critical histone methyltransferase enhancer of zeste homolog 2 to reduce both global and gene-specific histone H3 lysine 27 trimethylation. These chromatin structural changes promote the assembly of transcription complexes to fetal γ-globin and antioxidant gene regulatory regions in an antioxidant response element-dependent manner. In summary, our findings suggest that simvastatin activates fetal hemoglobin and antioxidant protein expression, modulates iron and cystine/reduced glutathione levels to improve the phenotype of SCD, and represents a therapeutic strategy for further development.
The Tale of Staphylococcus aureus Isolated from Mastitis Infections: The Effect of Antimicrobials and Bacterial Relatedness
Authors: Perdomo Angela , Salazar Maria , Janardhanan Rasmi , Calle Alexandra
Published: March 2024

Staphylococcus aureus is a common causative agent of mastitis in dairy cattle, posing a substantial threat to animal health and resulting in significant economic losses. Preventive measures are usually in place to control the spread of the organism between animals and around the dairy environment; however, mastitis outbreaks can still be recurrent. During this investigation, a total of 30 S. aureus isolates were obtained from six deceased cows, all diagnosed with chronic mastitis during an outbreak in West Texas. The aim of this study was to evaluate the response of the S. aureus isolates causing severe mastitis infections to iodine treatments and their antibiotic susceptibility, planktonic growth, and biofilm formation. Udder skin was inoculated with S. aureus and subjected to various iodine concentrations of 0.25%, 0.38%, 0.50%, 0.75%, and 1.00%, with exposure times of 15 s, 10 s, and 60 s. The same concentrations were tested on S. aureus’s biofilm formation. The results of the antimicrobial susceptibility test indicate that the exposure time did not influence the treatment. Lower iodine concentrations were compared with 1.00%, as the standard treatment used by the dairy for teat disinfection, and statistical difference (p < 0.001) was evident in the 0.00% iodine treatment compared to the other iodine concentrations. Moreover, a significant difference (p < 0.001) emerged when comparing the 0.25% and 0.38% iodine concentrations with 1.00%. No difference (p > 0.161) was detected between 0.50%, 0.75%, and 1.00%. These results suggest that, under the conditions investigated, iodine can be lowered to around 50% of the currently used dose without negatively impacting microbial control. On the other hand, S. aureus strains were susceptible to the tested antibiotics, demonstrating that antimicrobial resistance does not always play a role in the persistent mastitis infections caused by S. aureus. Further microbial phenotypic typing conducted on S. aureus strains indicated a possible common source of the infections, demonstrating the potential of there being resident S. aureus strains at this dairy farm.
Enhancing Diagnostic Images to Improve the Performance of the Segment Anything Model in Medical Image Segmentation
Authors: Kong Luoyi , Huang Mohan , Zhang Lingfeng , Chan Lawrence Wing Chi
Published: March 2024

Medical imaging serves as a crucial tool in current cancer diagnosis. However, the quality of medical images is often compromised to minimize the potential risks associated with patient image acquisition. Computer-aided diagnosis systems have made significant advancements in recent years. These systems utilize computer algorithms to identify abnormal features in medical images, assisting radiologists in improving diagnostic accuracy and achieving consistency in image and disease interpretation. Importantly, the quality of medical images, as the target data, determines the achievable level of performance by artificial intelligence algorithms. However, the pixel value range of medical images differs from that of the digital images typically processed via artificial intelligence algorithms, and blindly incorporating such data for training can result in suboptimal algorithm performance. In this study, we propose a medical image-enhancement scheme that integrates generic digital image processing and medical image processing modules. This scheme aims to enhance medical image data by endowing them with high-contrast and smooth characteristics. We conducted experimental testing to demonstrate the effectiveness of this scheme in improving the performance of a medical image segmentation algorithm.