bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancements in 3D MRI Brain Tumor Segmentation: A Comprehensive Exploration of Fully Convolutional Networks
Authors: Dutta Rituraj , Sarma Jayana , Deb Nabamita , Ghosh Rajdeep
Published: February 2024

This work presents a comprehensive study on brain tumor segmentation, utilizing the MICCAI Brain Tumor Segmentation(BraTS) 2016 and 2017 datasets as primary sources for analysis and assessment. The BraTS dataset provides annotated multimodal 3D brain Magnetic Resonance Imaging( MRI), enabling the detection of three tumor classes – Edema (ED), Enhancing Tumor (ET), and Necrotic and Non-Enhancing Tumor (NET/NCR). The study involves the utilization of five distinct 3D Deep Convolutional Networks for analysis and evaluation. Binary Cross Entropy and Dice Loss are investigated as loss functions and three different in-layer normalization techniques are explored using Unet3D to gain a deeper understanding of their impact on performance. Quantitative results reveal that DenseVoxelNet performs poorly due to limited and complex data, while UNet3D consistently outperforms other models. The qualitative analysis demonstrates Unet3D’s superiority over other models, particularly DenseVoxelNet. The findings underscore the significance of skip connections in enhancing the analysis of medical images, revealing a notable 29% increase across multiple evaluation metrics. The classwise evaluation reveals that within the context of NET/NCR segmentation, UNet3D displays a marginal underperformance of 0.7% in terms of Dice Score Coefficient (DSC) and 0.4% in terms of Intersection over Union (IoU). However, UNet3D demonstrates superiority in ED and ET segmentation, exhibiting improvements of 0.4% and 0.9% for DSC and 0.5% and 0.7% for IoU respectively.
Direct Air Capture and Utilization: Life Cycle Assessment and CO2 Reduction Potential Estimation
Authors: Keeley Alexander Ryota , Chapman Andrew , Yoo Sunbin , Kurita Kenichi , Kumagai Junya , Rinawati Dyah Ika , Fan Tianhui , Managi Shunsuke
Published: February 2024

Reducing the concentration of carbon dioxide (CO2) in the atmosphere to combat climate change is a global challenge. Direct air capture (DAC) is a new set of technologies that directly removes CO2 from the air; therefore, DAC can address emissions from any source. This paper begins by reviewing the literature on negative emission technologies to summarize the most recent technological developments. We then conduct a life cycle assessment on one of the most recently developed technologies, the direct air capture and utilization (DAC-U) system. DAC-U systems, like photovoltaic systems, can be installed in various locations, including homes, offices, and mega-plants, resulting in a highly scalable, on-site system that can be deployed in various ways. Based on the life cycle assessment results, this article presents the CO2 capture and reduction potential of the DAC-U system, with a focus on installations in households, and examines the willingness to adopt the system in Japan. Our results show that the DAC-U system functions as a negative emission technology and demonstrate the large CO2 capture and reduction potential of the DAC-U system through household-level installations.
Accuracy of Abott Freestyle Libre versus Dexcom G6 in a patient with pre-diabetes: a case report and review of literature
Authors: Kutoh Eiji
Published: February 2024

Abbott FreeStyle Libre and Dexcom G6 represent widely employed continuous glucose monitoring (CGM) systems globally. However, their precision remains unexplored concerning postprandial glucose levels in individuals with pre-diabetes following the consumption of diverse dietary regimens. A 58-year-old Japanese man diagnosed with pre-diabetes (postprandial hyperglycemia) underwent simultaneous monitoring using Abbott FreeStyle Libre and Dexcom G6 following the consumption of diverse diets. In the pre-meal state, both systems exhibited comparable and reliable values (around 80–100 mg/dl). However, around 60 minutes following meals containing specific amounts of carbohydrates (approximately above 50 g), FreeStyle Libre demonstrated a more pronounced acceleration in the increase and peak glucose values compared to G6. These discrepancies were further validated through self-monitoring of blood glucose (SMBG) measurements, confirming the less accurate performance of FreeStyle Libre under these conditions. To this end, it appears that fermented products (beans, yogurt, cheese) could suppress postprandial glucose spikes. The study results suggest that, when compared to G6, FreeStyle Libre yielded elevated glucose values and exhibited reduced accuracy in measuring postprandial glucose levels following the ingestion of a specific amount of carbohydrates in a patient with pre-diabetes.
Gait Compensation Strategies to Expected and Unexpected Yielding Terrain
Authors: Petrarca Maurizio , Favetta Martina , Carniel Sacha , Gazzellini Simone , Bella Gessica Della , Castelli Enrico , Berthoz Alain , Summa Susanna
Published: February 2024

Preventing falls is closely tied to the ability to compensate for perturbations during walking. Some of the most significant perturbations arise from irregular terrain, which can lead to expected or unexpected disturbances. In pathological conditions, these compensation abilities are often greatly compromised, while in children, they are still developing. Research is scarce in this area. To address this gap, we developed a custom Stewart platform for studying perturbations during walking. We recruited ten healthy young adults. Participants walked along a path where the upper plate of a Stewart Platform, controlled in force, was positioned. The platform would move vertically downward when participants stepped on it. The perturbations were normalized based on leg length, while random sequence repetition to induce expected or unexpected conditions was defined. We conducted a comprehensive 3D gait analysis of three strides using an optoelectronic system, before, on, and after the platform. Statistical analysis was performed using one-dimensional Statistical Parametric Mapping to compare perturbed conditions (expected or unexpected) to normal walking. The main findings revealed alterations in spatiotemporal parameters, increased clearance, and increased dorsiflexion of the ankle, with minor effects on knee and hip flexion, pelvis, and trunk anteversion. Furthermore, during unexpected perturbations, participants raised their hands. In summary, our observations indicated an overlap between Anticipatory and Predictive strategies, with signs of anticipation looking at foot clearance and signs of prediction looking at hand elevation. This detailed description forms the foundation for investigating available resources in pathological conditions and their maturation across the lifespan.
Myositis and Interstitial Lung Disease as a Presentation of Primary Sjogren’s Syndrome, A Case Report
Authors: Aly Mohammed H , Mahmoud Ahmed A , Hassan Abdulrahman M , Mohammed Abdelgaffar , shehri Abdulrahman A Al
Published: February 2024

Primary Sjogren's syndrome (SS), defined as an autoimmune disorder, is the most prevalent autoimmune disorder, succeeding rheumatoid arthritis, but persists undiagnosed in more than half of cases. The distinctive attribute of histopathological characteristics of SS is peri-epithelial lymphocytic infiltration of the impacted organs. Antibodies to SSA (Ro) and SSB (La) are characteristically correlated with SS. Pulmonary involvement in primary SS has been reported in multiple cases of Sjogren syndrome, with a range that includes various forms, starting from small airway diseases to interstitial lung diseases (ILD). We are reporting a primary SS case presenting with myositis and ILD.
Seasonal Diet Partition among Top Predators of a Small Island, Iriomotejima Island in the Ryukyu Archipelago, Japan
Authors: Tobe Alisa , Sato Yukuto , Wachi Nakatada , Nakanishi Nozomi , Izawa Masako
Published: February 2024

Small islands lack predators because species at higher trophic levels often cannot survive. However, two top predators—the Iriomote cat Prionailurus bengalensis iriomotensis, and the Crested Serpent Eagle Spilornis cheela perplexus—live on small Iriomotejima Island in the Ryukyu Archipelago. To understand how these predators coexist on the island with limited resources, we focused on their seasonal diets which are considered crucial for survival in such an island ecosystem. To compare the diets of them, we used DNA metabarcoding analysis of their fecal samples. In the summer, we identified 16 prey items from Iriomote cat fecal samples, and 15 from Crested Serpent Eagle fecal samples. In the winter, we identified 37 and 14 prey items, respectively. Using a non-metric multidimensional scaling and a permutational multivariate analysis of variance, our study reveals significant differences in the diet composition at the order level between the predators during both seasons. Furthermore, although some prey items at the species-to-order level overlapped between them, the frequency of occurrence of most prey items differed in both seasons. These results suggest that this difference in diets was one of the reasons why the Iriomote cat and the Crested Serpent Eagle coexisted on such a small island.
Effect of Progesterone Treatment on Synchronising Oestrus during Non-Breeding Season in South African Merino Ewes
Authors: Zulu Nhlakanipho , Ramukhithi Fhulufhelo Vincent , Lehloenya Khoboso Christine
Published: February 2024

The aim of the study was to compare the effect of short and long-term progesterone treatment and their combination with or without equine chorionic gonadotropin (eCG) on oestrous response and hormonal profiles during non-breeding season. Seventy-six (76) Merino ewes aged between 2–5 years were allocated into two groups, 36 for short-term and 40 for long-term progesterone treatments. In the short and long-term progesterone treatment groups, controlled internal drug release devices (CIDR) were inserted for 11 and 14 days, respectively. At withdrawal of CIDR, half of each group were injected intramuscularly with 300 IU of eCG. Blood samples were collected to measure the level of progesterone and oestradiol. Ewes treated with both short or long-term progesterone combined with or without eCG resulted in the same oestrus response, onset of oestrus and duration of oestrus. The levels of progesterone hormone were the same at CIDR insertion, and removal and 48 hours post CIDR removal. However, oestradiol hormone was significantly higher at CIDR removal and 48 hours post CIDR removal than at insertion in all treated groups. Therefore, it can be concluded that oestrous synchronisation protocols of both short and long-term progesterone combined with or without eCG during non-breeding season can be used to synchronise oestrus during non-breeding season.
Molecular epidemiology of carbapenem-resistant Escherichia coli in a tertiary hospital located in the Dabie Mountains region, China
Authors: Wang Lu , Gong Wanxian , Zhang Jie , Zhang Runan , Jing Ying , Xu Yuanhong
Published: February 2024

Objective: The objective of this study was to conduct a molecular epidemiological study of carbapenem-resistant Escherichia coli (CREco) within a tertiary hospital situated in the Dabie Mountains region of China, while also elucidating the underlying mechanisms of antimicrobial resistance.
Patients and methods: Between 2018 and 2022, a total of 33 CREco isolates were isolated from 33 patients in a tertiary hospital situated in the Dabie Mountains region of China. Subsequently, the next-generation sequencing of CREco isolates was performed, and the clinical retrospective analysis and the comprehensive bioinformatic analysis were presented. Phenotypic identification of carbapenemase and AmpC-type β-lactamase were also conducted.
Results: Two kinds of carbapenemase genes blaNDM (n = 30) and blaKPC-2 (n = 2) were identified in 33 CREco isolates. Of blaNDM-positive isolates, 24 belonged to blaNDM-5, and the remaining were blaNDM-13 (n = 4), blaNDM-1 (n = 1), and blaNDM-6 (n = 1). The predominant STs of these isolates were ST410 (13.3%, 4/30), ST692 (10.0%, 3/30), and ST156 (10.0%, 3/30). Except for carbapenemase genes, the most prevalent resistance genes were sulfonamide (97%, 32/33), and aminoglycoside (94%, 31/33) genes. By the disserted annotation of the core genetic envirionment of blaNDM and blaKPC, we identified that blaNDM and blaKPC were harbored by Tn125 and Tn6296, respectively. Although the core genetic environment of them were conserved, but the different truncations were underwent in the upstream/downstream of the prototype of Tn125 and Tn6296.
Conclusion: The blaNDM-5 was the principal carbapenem resistance mechanism of CREco isolates in the Dabie Mountains region in China. Besides, two rare NDM variants blaNDM-6 and blaNDM-13 were detected herein, and the dissemination risk of these two genes was needed to be attention and the further surveillance was needed in China.
A spatial examination of alcohol availability and the level of disadvantage of schools in Ireland
Authors: Doyle Anne , Foley Ronan , Houghton Frank
Published: February 2024

Background
The availability of alcohol is a major factor in underage drinking and according to the alcohol harm paradox, those living in more deprived communities are more susceptible to the negative consequences of alcohol use, despite drinking the same or less than those from more affluent areas. Alcohol availability within the vicinity of the home or school normalises alcohol for schoolchildren. This study examined the number of premises licensed to sell alcohol within 300 meters of all schools in Ireland and differences in this number between disadvantaged and non-disadvantaged schools.
Methods
Using publicly available data from the Department of Education and Revenue, the addresses of all schools and all premises with at least one liquor licence were geocoded and analysed using the Geographic Information System software, QGIS. Schools were identified by their disadvantaged classification and the number of liquor licences within 300 meters of each school type was examined.
Results
There was a mean of two licenced premises within 300 meters of all schools in Ireland, but when disadvantaged schools were compared to non-disadvantaged schools, there was a significantly higher number of licenced premises around disadvantaged schools.
Primary schools are further classified according to their level of disadvantage and the results indicated that those schools classified as the most disadvantaged had a significantly greater number of liquor licences within 300 meters. There was no significant difference in density of licenced premises when comparing disadvantaged secondary schools with non-disadvantaged secondary schools.
Conclusion
Ireland is considering increasing alcohol availability through the Sale of Alcohol Bill, 2022. However, this analysis indicates already problematic numbers of licenced premises within close proximity of schools in Ireland. It is essential that the harms associated with alcohol availability are considered, especially for those living and attending school in disadvantaged communities, where higher numbers of licenced premises were identified
Diversity and ecological niche model of malaria vector and non-vector mosquito species in Covè, Ouinhi, and Zangnanado, Southern Benin
Authors: Adoha Constantin J. , Sovi Arthur , Padonou Germain G. , Yovogan Boulais , Akinro Bruno , Accrombessi Manfred , Dangbénon Edouard , Sidick Aboubakar , Ossè Razaki , Tokponon Filémon T. , Odjo Esdras M. , Koukpo Come Z. , Fassinou Arsène , Missihoun Antoine A. , Sominanhouin André , Messenger Louisa A. , Agboho Prudenciène A. , Akpodji Serge , Ngufor Corine , Cook Jackie , Agbangla Clément , Protopopoff Natacha , Kulkarni Manisha A. , Akogbéto Martin C.
Published: February 2024

The present study aimed to assess mosquito species diversity, distribution, and ecological preferences in the Covè, Ouinhi, and Zangnanado communes, Southern Benin. Such information is critical to understand mosquito bio-ecology and to focus control efforts in high-risk areas for vector-borne diseases. Mosquito collections occurred quarterly in 60 clusters between June 2020 and April 2021, using human landing catches. In addition to the seasonal mosquito abundance, Shannon's diversity, Simpson, and Pielou's equitability indices were also evaluated to assess mosquito diversity. Ecological niche models were developed with MaxEnt using environmental variables to assess species distribution. Overall, mosquito density was higher in the wet season than in the dry season in all communes. A significantly higher Shannon's diversity index was also observed in the wet season than in the dry seasons in all communes (p<0.05). Habitat suitability of An. gambiae s.s., An. coluzzii, C. quinquefasciatus and M. africana was highly influenced by slope, isothermality, site aspect, elevation, and precipitation seasonality in both wet and dry seasons. Overall, depending on the season, the ecological preferences of the four main mosquito species were variable across study communes. This emphasizes the impact of environmental conditions on mosquito species distribution. Moreover, mosquito populations were found to be more diverse in the wet season compared to the dry season.
Concept-Drifts Adaptation For Machine Learning EEG Epilepsy Seizure Prediction
Authors: Pontes Edson David , Pinto Mauro , Lopes Fábio , Teixeira César
Published: February 2024

The administration of antiepileptic drugs or surgical interventions fails to control seizures in about 30% of patients. Seizure prediction is a viable strategy for enhancing their quality of life because it can be used in intervention or warning systems. These systems may disarm seizures or, at the very least, lessen their adverse effects. Identifying the preictal interval, which marks the change from regular brain activity to a seizure, is critical to this research field. Even though several predictive studies applied various Electroencephalogram based methodologies, only some have been used in medical devices, and none have been clinically applicable. Recent studies have shown that tracking and handling data changes with time, known as concept drifts is highly relevant in seizure prediction; therefore, it is essential to develop methods able to automatically detect and address changes in context without human intervention. In this work, we aimed to evaluate the impact of automatic concept drift adapting methods in seizure prediction. We tested approaches to predict seizures while adapting to concept drifts during the model’s learning process; for that, we proposed and compared to the Control three patient-specific seizure prediction approaches with a 10-minute seizure prediction horizon: a seizure prediction algorithm incorporating a window adjustment method by optimising performance with Support Vector Machines1 (Backwards-Landmark Window), a seizure prediction algorithm incorporating a data-batch (seizures)selection method using a logistic regression2 (Seizure-batch Regression), and a seizure prediction algorithm with a dynamicintegration of classifiers3 (Dynamic Weighted Ensemble). The proposed methodologies included a retraining process after eachseizure and combined a set of univariate linear features with classifiers based on Support Vector Machines. The Firing Power wasused as a post-processing technique to generate alarms before seizures. Considering a group of 37 patients with Temporal LobeEpilepsy from the EPILEPSIAE database, the best-performing approach (Backwards-Landmark Window) aimed to select datafrom the concept closest to the preictal period of the last training seizure; this led to results of 0.75 ± 0.33 for sensitivity and 1.03 ± 1.00 for false positive rate per hour. Even though the best-performing approach statistically validated 89% of the patients with the surrogate predictor, it is necessary to determine the maximum false positive rate appropriate for each intervention system.
Phase II Study of Ramucirumab and Docetaxel for Previously Platinum-treated Patients with Non-Small Cell Lung Cancer and Malignant Pleural Effusion (PLEURAM study)
Authors: Takemoto Shinnosuke , Fukuda Minoru , Ogata Ryosuke , Senju Hiroaki , Sugasaki Nanae , Nakatomi Katsumi , Tomono Hiromi , Suyama Takayuki , Sasaki Eisuke , Matsuo Midori , Akagi Kazumasa , Hayashi Fumiko , Dotsu Yosuke , Ono Sawana , Honda Noritaka , Taniguchi Hirokazu , Gyotoku Hiroshi , Ikeda Takaya , Nagashima Seiji , Soda Hiroshi , Kinoshita Akitoshi , Mukae Hiroshi
Published: February 2024

Introduction: The prognosis of patients with lung cancer and malignant pleural effusion (MPE) caused by carcinomatous pleurisy is poor. Chemical pleurodesis is typically performed clinically but often has a high failure rate. Further, the risk of exacerbating the Eastern Cooperative Oncology Group Performance Status associated with pleurodesis and delaying the introduction of systemic drug therapy is a major concern. Therefore, both systemic and MPE-specific treatments are necessary. Ramucirumab, an antibody targeting vascular endothelial growth factor receptor 2, is expected to be effective in treating MPE. However, there are no data supporting this hypothesis. Therefore, a single-arm phase II study was performed to examine the efficacy and safety of ramucirumab + docetaxel in MPE.
Materials and methods: The primary objective was to evaluate the MPE control proportion at 8 weeks after treatment initiation with ramucirumab in combination with DTX in patients previously subjected to platinum treatment for non-small cell lung cancer (NSCLC) and MPE. The secondary objectives of the study were to determine the toxicity profile, objective response rate (ORR), progression-free survival (PFS), 1-year survival rates, overall survival (OS), and toxicity profile.
Results: Between September 2019 and March 2022, 15 patients were enrolled. The pleural effusion control proportion at 8 weeks was 100% (90% confidence interval [CI]: 95%CI: 784.0–100%), and the primary endpoint of the currentstudy was met. The ORR was 6.7% (90%CI: 84.0–100%, 95%CI: 76.8–100%), the median PFS was 6.3 months (95%CI: 1.9–6.9 months), and the median OS was 10.4 months (95%CI: 3.2–16.5 months). No Grade 5 or unexpected adverse events were observed.
Conclusion: Ramucirumab+ docetaxel is a promising and safe treatment option for previously platinum-treated patients with NSCLC and MPE and shows a high proportion of pleural effusion control.
Gravity-Informed Deep Learning Framework for Predicting Ship Traffic Flow and Invasion Risk of Non-Indigenous Species via Ballast Water Discharge
Authors: Spadon Gabriel , Song Ruixin , Pelot Ronald , Matwin Stan , Soares Amilcar
Published: February 2024

Aquatic invasive species are a significant threat to biodiversity and ecosystems worldwide. Due to the fast growth of global trade and transportation networks, non-native species have been introduced and spread unintentionally in new environments. These invasive species can damage ecosystems by disrupting the balance, out-competing native species, and causing significant economic losses to agriculture, forestry, and fisheries. Therefore, there is a pressing need for risk assessment and management techniques to mitigate the impact of these invasions. This study aims to develop a new physics-inspired model to forecast maritime shipping traffic and thus inform risk assessment of invasive species spread through global transportation networks. Inspired by the gravity model for international trades, our model considers various factors that influence the likelihood and impact of vessel activities, such as shipping flux density, distance between ports, trade flow, and centrality measures of transportation hubs. Additionally, by analyzing the risk network of invasive species, we provide a comprehensive framework for assessing the invasion threat level given a pair of origin and destination. Accordingly, in this paper, we introduce transformers to gravity models to rebuild the short- and long-term dependencies that make the risk analysis feasible. Thus, we introduce a physics-inspired framework that achieves an 89% segmentation accuracy for existing and non-existing trajectories and an 84.8% accuracy for the number of vessels flowing between key port areas, representing more than 10% improvement over the traditional deep-gravity model. Along these lines, this research contributes to a better understanding of invasive species risk assessment. It allows policymakers, conservationists, and stakeholders to prioritize management actions by identifying high-risk invasion pathways. Besides, our model is versatile and can include new data sources, making it suitable for assessing species invasion risks in a changing global landscape.
Metastable Helium Atom Creation Dynamics in High-Voltage Pulsed Discharge with Transverse Magnetic Field Effects
Authors: Rabadanov K. M. , Ashurbekov N. A. , Iminov K.O. , Shahsinov G. Sh. , Zakaryaeva М. Z. , Murtazaeva A.A.
Published: February 2024

In this work, we investigate the effect of an external transverse weak magnetic field on the creation of metastable helium atoms and excited helium molecules in a high-voltage pulsed discharge in helium at medium pressure. A two-dimensional fluid model is used to describe a high-voltage pulsed discharge in helium in the external transverse weak magnetic field. The dynamics of discharge development in the high-voltage pulsed discharge in helium at a pressure of 30 Torr in the presence and absence of the magnetic field is studied. The effect of the external magnetic field on the behavior of the density of charged particles, metastable helium atoms, and excited helium molecules in the high-voltage pulsed helium discharge has been investigated. It is shown that in the discharge region, the density of metastable atoms decreases when a transverse magnetic field is applied, which is a consequence of an increase in the frequency of stepwise ionization.
Impact of Oxidative Stress on Myocardial Performance in Diabetic Patients: A Focus on Subclinical Left Ventricular Dysfunction Running title: Oxidative Stress in Diabetic Cardiac Dysfunction
Authors: Oksen Dogac , Aslan Muzaffer
Published: February 2024

Introduction & Objective: Oxidative stress is known to affect left ventricular functions negatively. There is a strong bidirectional connection between diabetes mellitus (DM) and oxidative stress. In parallel, left ventricular dysfunction is observed more frequently, even in DM patients without other risk factors. In this context, the objective of this study is to comparatively investigate the potential relationship between oxidative stress and subclinical left ventricular dysfunction (SCLVD) assessed by myocardial performance index (MPI) in patients with and without DM.
Materials & Methods: The sample of this observational cross-sectional single-center study consisted of 151 patients who were evaluated biochemically for oxidative stress and SCLVD by tissue Doppler echocardiography. The sample was divided into two groups: DM and non-DM. Patients’ total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) values were calculated. The correlation, if any, between OSI and MPI was examined in both groups. The effects of oxidative stress and DM on MPI were analyzed.
Results: There were 81 (58% male) and 70 (68.6% male) patients in the DM (mean age: 46.17 ± 10.33 years) and non-DM (mean age: 45.72 ± 9.04 years) groups, respectively. There was no significant difference between the groups in gender. Mean TOS and OSI values of the DM group were statistically significantly higher than those of the non-DM group (5.72 ± 0.55 vs. 5.31 ± 0.50, p= <0.001; and 4.92 ± 1.93 vs. 1.79 ± 0.39, p = <0.001; respectively). On the other hand, the mean TAS value of the DM group was significantly higher than that of the non-DM group (1.21 ± 0.40 vs. 3.23 ±0.51, p= <0.001). There was a significant correlation between OSI and MPI mitral in the DM group (R -0.554 p= <0.001) but not in the non-DM group (R - 0.069, p= 0.249).
Conclusions: Both oxidative stress and myocardial dysfunction were found to be more common in patients with DM. The study's findings indicated the negative effect of oxidative stress on myocardial functions. Accordingly, increased oxidative stress caused more significant deterioration in MPI in patients with DM compared to patients without DM.
Genetically determined sex hormones and functional outcome after ischemic stroke: A Mendelian randomization study
Authors: Gao Tianxiang , Zhang Hongjian , Liu Hanchen , Ge Manyue , Mo Shaojun , Zhang Lei , Yang Pengfei
Published: February 2024

Background and purpose
Sex hormones may affect functional outcome after ischemic stroke (IS). However, the effects reported in previous studies were inconsistent, and randomized data were absent. We performed a two-sample Mendelian randomization analysis to explore the causal effects of genetically determined sex hormones on the 3-month functional outcome after IS.
Methods
Using genome-wide association studies, we obtained sex-specific genetic instruments for evaluating serum estradiol and bioavailable testosterone levels. The sex-specific functional outcome after IS were estimated via inverse-variance weighted Mendelian randomization analysis. Mendelian randomization-Egger regression, weighted median leave-one-SNP-out analysis, Mendelian randomization-Pleiotropy Residual Sum, and Outlier methods were used for sensitivity analyses. To validate our primary results, we also performed independent repeated and bidirectional Mendelian randomization analyses.
Results
Genetic predisposition to high levels of bioavailable testosterone was associated with excellent functional outcome in males (OR = 0.41, 95% CI: 0.21–0.79, P = 0.008), but worse outcome in females (OR = 2.49, 95% CI: 1.24–4.99, P = 0.009). Females with genetically predicted higher estradiol levels tend to have excellent and favorable functional outcome (excellent functional outcome, OR = 0.53; 95% CI: 0.41–0.85, P = 0.005); (favorable functional outcome, OR = 0.69; 95% CI: 0.48–0.98, P = 0.036). There was limited evidence that genetically predicted estradiol levels affect functional outcome in men (P > 0.05).
Conclusions
Our findings suggested that bioavailable testosterone and estradiol were promising neuroprotectants that could respectively improve the functional outcome of IS in males and females.
Psychological Distress among family caregivers of persons with Alzheimer's Disease and Related Dementias in Uganda
Authors: Onoria Joy Louise Gumikiriza - , Nakigudde Janet , Giordani Bruno , Mayega Roy William , Sajatovic Martha , Mukasa Mark Kaddu , Buwembo Dennis , Lwere Kamada , Nakasujja Noeline
Published: February 2024

Background:Alzheimer's disease and related dementia (ADRD) present growing global health challenges, especially in aging populations such as Uganda. In Uganda, familial caregiving, predominantly undertaken by female relatives, is the primary form of support for patients with ADRD. Cultural stigma around dementia and limited access to support services amplify caregivers' challenges. This study examined psychological distress, depression, and quality of life (QoL) among family caregivers of patients with ADRD in Wakiso District, Uganda.
Methods: This cross-sectional study involved 90 caregivers from three sub-counties in Wakiso selected through purposive sampling to capture diverse experiences. Data were collected using the Kessler Psychological Distress Scale, Caregiver Dementia Quality of Life Measurement Scale, and Center for Epidemiologic Studies Depression Scale, with an 80% response rate achieved through local collaboration. Statistical analyses focused on psychological distress, QoL, and depression.
Results: The study included 82.2% females and 17.8% males, with a median age of 52 years for females and 35 years, respectively. Females were more likely to be single or widowed, whereas males were more likely to be married. The study revealed a high prevalence of psychological distress and depression among caregivers (64.4%) regardless of sex. The analysis indicated that having children was a significant predictor of better QoL (OR 3.04, 95% CI 1.79-5.66, p=0.034) and lower risk of depression (OR 0.10, 95% CI 0.01-0.86, p=0.036). No other sociodemographic factor was significantly associated with health outcomes across the models.
Conclusion: Our findings revealed a heavy burden of psychological distress and depression among Ugandan caregivers of patients with ADRD, highlighting the need for structured support systems, including mental health services and gender-responsive interventions, in low-resource settings.
In Vivo Modulatory Effect of Malachite Green on Cytochrome P450 and Antioxidant Enzyme Activities in Rainbow Trout Liver
Authors: Bozcaarmutlu-Büken Azra , Yıldırım Volkan , Sapmaz Canan , Günbür Ahmet , Türker Hakan
Published: February 2024

Malachite green is a mutagenic and carcinogenic chemical used in textile and paper industry as a dye and fish farms against ectoparasites as well as bacteria and fungal infections. Aquatic organisms are under the risk of malachite green exposure. In this study, our aim was to determine the effect of two different doses of malachite green on cytochrome P450 system and antioxidant system in rainbow trout (Oncorhynchus mykiss). For this purpose, 24 fish were randomly divided into three groups namely control, 0.1 mg/L malachite green treatment group and 0.5 mg/L malachite green treatment group. Highly elevated 7-ethoxyresorufin-O-deethylase activities (EROD) were measured in fish treated with 0.5 mg/L malachite green. 7-pentoxyresorufin O-depentylase (PROD) activities increased with increasing doses of malachite green. Catalase (CAT) and glutathione reductase (GR) activities of 0.1 mg/L malachite green administration group were higher than that of the control group. Erythromycin N-demethylase (ERND) activities were higher in treatment groups than that of the control group. However, these differences in ERND activities were not statistically significant. Glutathione S-transferase (GST) activities were not affected from the malachite green treatment in both of the treatment groups. In this study, it is clear that malachite green has modulatory effect on EROD, PROD, CAT and GR activities in rainbow trout.
PVP-AuNP impedes glycation mediated Hen Egg White Lysozyme aggregation under physiological condition
Authors: Johnson Jennifer , Tyagi Tushar , Maity Prasenjit , Kumar Satish
Published: February 2024

Protein glycation a non-enzymatic protein modification, alters the structure of biomolecule leading to several neurodegenerative and other disorders. As onset of disorders due to protein glycation is primarily driven by the development of advanced glycation end products (AGEs), therapeutic intervention against related disorders by inhibiting AGEs production is imperative. Nanoparticles have recently gained more prominence as therapeutic agents in biological field such as medicine, drug discovery and diagnosis. In present study, we extensively investigated the effect of chemically synthesized polyvinylpyrrolidone conjugated gold nanoparticles (PVP-AuNP) on D-ribose induced glycation of hen egg white lysozyme (HEWL) under physiological conditions. Our finding shows that AGEs formation was inhibited by PVP-AuNP over the period of 20 days. Interaction of gold nanoparticles prevented glycation induced misfolding and aggregation of lysozyme by stabilizing its native structure, which was evident with static light scattering, ThT, Congo red and ANS fluorescence coupled with CD spectroscopy. Further, by estimating carbonyl content and thiol group, our study suggests that PVP-AuNP possesses antioxidant property thus prevent the HEWL against glycation driven oxidative damage. Present study therefore elucidates that PVP-AuNP a significant antiglycation agent can be used against wide range of disorders induced by AGEs.
Exploring the Impact of Simulated Microgravity on Cellular DNA: A Comparative Analysis of Cancer and Normal Cell Lines
Authors: Altaie Saifaldeen , Alrawi Amera , Xuexin Duan , Alnada Qater
Published: February 2024

The examination of the impact of microgravity on biological systems has gained considerable attention owing to its potential implications for health and disease. Simulated microgravity serves as a valuable methodology for elucidating the intricate cellular responses to altered gravitational conditions. This study investigates the effects of simulated microgravity on cellular DNA, employing four distinct cell lines—breast, brain, and esophageal cancer cells, in conjunction with normal cells for comparative analysis. The experiment utilized the comet assay test to quantitatively assess DNA damage. The results revealed a discernible disparity in the response to simulated microgravity, notably with cancer cells exhibiting a significant increase in DNA damage compared to the relatively minimal effects observed in both control and normal cells. Furthermore, within the cancer cell lines, significant variations in the extent of DNA damage were evident, implying a cell type-dependent response to simulated microgravity. These findings illuminate the potential differential susceptibility of cancerous and normal cells to microgravity-induced DNA damage. Consequently, this research substantially contributes to our comprehension of microgravity-induced cellular responses and unveils promising avenues for targeted interventions in cancer therapy.
Early generation of a precursor CD8 T cell that can adapt to acute or chronic viral infection
Authors: Ahmed Rafi , McManus Daniel , Valanparambil Rajesh , Medina Christopher , Hu Yinghong , Scharer Chris , Sobierajska Ewelina , Chang Daniel , Wieland Andreas , Lee Judong , Nasti Tahseen , Hashimoto Masao , Ross James , Prokhnevska Nataliya , Cardenas Maria , Gill Amanda , Clark Elisa , Abadie Kathleen , Kueh Hao Yuan , Kaye Jonathan , Au-Yeung Byron , Kissick Haydn
Published: February 2024

Virus specific PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells are essential for maintaining T cell responses during chronic infection and are also critical for PD-1 directed immunotherapy. In this study we have used the mouse model of chronic LCMV infection to examine when these virus specific stem-like CD8+ T cells are generated during the course of chronic infection and what is the role of antigen in maintaining the stem-like program. We found that these stem-like CD8+ T cells are generated early (day 5) during chronic infection and that antigen is essential for maintaining their stem-like program. This early generation of stem-like CD8+ T cells suggested that the fate commitment to this cell population was agnostic to the eventual outcome of infection and the immune system prepares a priori for a potential chronic infection. Indeed, we found that an identical virus specific stem-cell like CD8+ T cell population was also generated during acute LCMV infection but these cells were lost once the virus was cleared. To determine the fate of these early PD-1+TCF-1+TOX+ stem-like CD8+ T cells that are generated during both acute and chronic LCMV infection we set up two reciprocal adoptive transfer experiments. In the first experiment we transferred day 5 stem-like CD8+ T cells from chronically infected into acutely infected mice and examined their differentiation after viral clearance. We found that these early stem-like CD8+ T cells downregulated canonical markers of the chronic stem-like CD8+ T cells and expressed markers (CD127 and CD62L) associated with central memory CD8+ T cells. In the second experiment, we transferred day 5 stem-like cells from acutely infected mice into chronically infected mice and found that these CD8+ T cells could function like resource cells after transfer into a chronic environment by generating effector CD8+ T cells in both lymphoid and non-lymphoid tissues while also maintaining the number of stem-like CD8+ T cells. These findings provide insight into the generation and maintenance of virus specific stem-like CD8+ T cells that play a critical role in chronic viral infection. In particular, our study highlights the early generation of stem-like CD8+ T cells and their ability to adapt to either an acute or chronic infection. These findings are of broad significance since these novel stem-like CD8+ T cells play an important role in not only viral infections but also in cancer and autoimmunity.
BZDRs promote breast cancer progression through GABRA3-ECM signaling
Authors: Yang Wei-Chung , Lin Yen-Yi , Ding Jeak Ling , Zhang Bo-Xiang , Nguyen Phung-Anh , Hung Chin-Sheng , Hsieh Tsung-Han , Chang Shu-Chun
Published: February 2024

BZDRs (benzodiazepines and related Z-drugs), are widely used for clinical treatment of insomnia and anxiety disorders. BZDRs act on GABA type A receptors to inhibit neurotransmitters. Previously, we have demonstrated that clinical use of Diazepam (benzodiazepines) and Zolpidem (Z-drugs) are associated with the risk of breast cancer (BRCA) as the treatment time increased. Here, we further investigated the effects and underlying mechanisms of action of BZDRs, Diazepam and Zolpidem, in breast cancer progression. We showed that these BZDRs significantly stimulated BRCA cell migration and invasion, and that long-term usage of BZDRs increased the mortality rate of BRCA patients (p = 0.034). Retrospective studies on patient samples indicate that among 16 GABA receptors examined, GABRA3 (a pro-tumorigenic player) was significantly upregulated during BRCA advancement. BZDRs stimulated GABRA3, which downregulated anti-tumorigenic ECM (extracellular matrix) molecules (S100B, COL6A6 and VIT) and upregulated pro-tumorigenic FBN3 in BRCA cells. Notably, GABRA3-knockdown dramatically suppressed BRCA cell invasion induced by BZDRs, which seemed to work via manipulation of the ECM molecules. Altogether, our data support GABRA3-associated ECM signaling, through the axes of GABRA3-S100B, GABRA3-COL6A6, GABRA3-VIT and GABRA3-FBN3, which might individually or collaboratively play pivotal roles in exacerbating BZDR-mediated breast cancer progression.
Chiari malformation in a restricted-resource setting and treatment challenges: Case report and literature review
Authors: Hakimi Turyalai , Qasem Khalid Mohammad , Hakimi Zamaryalai , Jawed Mohammad Anwar
Published: February 2024

Background
Chiari malformations encompass many abnormalities in the skull, primarily impacting the cerebellum and typically involving the back part of the skull. It is defined by the downward displacement of one or both cerebellar tonsils via the foramen magnum. The clinical manifestations are a result of impaired function in the brainstem and lower cranial nerves. Decompressive surgery, with or without duraplasty, is the preferred therapeutic option. However, it can be particularly difficult in low-resource settings due to a lack of technical facilities.
Case presentation
A 40-day-old infant was brought to our pediatric surgery unit with a large cystic mass located in her occipital area. The patient was administered a suitable antibiotic regimen in response to the respiratory illness and prepped for definitive treatment. She underwent tension-free decompressive repair with the preservation of both cerebellar tonsils without duraplasty for the purpose of preventing post-operative complications, mostly hydrocephalus. The surgical procedure and postoperative period were without any notable incidents.
Conclusion
Chiari malformation is a complex neurosurgical condition with varying levels of surgical outcome, depending on the extent of the problem. A specialized pediatric neurosurgical center and a controlled follow-up system are the essential components of better surgical results and enhancing the quality of life.
Effects of a Modified Heat Treatment on the Quasi-Static and Dynamic Behavior of Additively Manufactured Lattice Structures
Authors: Rowe Russell , Almeida Nara , Prather Andy , Beck Sadie , Palazotto Anthony N , Davami Keivan
Published: February 2024

The flexibility of additive manufacturing techniques that produce parts from powders layer-by-layer directly from a digital model, enabled the fabrication of complex lightweight lattice structures with precisely engineered mechanical properties. Herein, an investigation of the quasi-static and dynamic behavior of additively manufactured (AM) triply periodic minimal surface (TPMS) lattice structures before and after a novel post-process heat treatment step is conducted. The specimens were fabricated out of Inconel 718, a nickel-chromium-based superalloy, using a selective laser melting technique with three different topologies, namely, Gyroid, Primitive, and I-WP. The quasi-static tests were conducted at a strain rate of 0.002 s− 1 and dynamic experiments were conducted using a split Hopkinson pressure bar at three different strain rates, 600 s− 1, 800 s− 1, and 1000 s− 1. It was shown that while the strain rate does not significantly affect the mechanical responses of the lattice structures, the heat treatment step dramatically changes their behavior. Results demonstrated that after the heat treatment, the yield strength of the I-WP specimens increased by 65.2% under a quasi-static load. Also, flow stress after yielding in the dynamic tests was shown to increase around 9.6% for I-WP specimens and up to 12.8% for Gyroid specimens. The specific energy absorption values were 10.5, 19.1, and 10.7 for I-WP, Gyroid, and Primitive, respectively, before the heat treatment, and changed to 19.6, 19.8, and 15.4 after the heat treatment. The results confirm that by precisely designing the architecture of a lattice structure and implementing a modified heat treatment process, it is possible to optimize the weight, strength, and energy absorption capability of this type of metamaterial.
Mental health impacts of multidrug-resistant tuberculosis in patients and household contacts: A mixed-method study
Authors: M Yogesh , Parmar Dipesh V , Patel Nirmalkumar Shaileshbhai
Published: February 2024

Background: Multidrug-resistant tuberculosis (MDR-TB) patients experience disproportionately worse mental health with implications for adherence, outcomes, and families. Comprehensive assessments of comorbid depression/anxiety and related factors remain limited. Objective: To assess the prevalence, predictors, and qualitative experiences of depression and anxiety in MDR-TB patients and Household contacts.
Methods: A sequential explanatory mixed methods study was conducted in Gujarat, India with 403 smear-positive MDR-TB patients and 403 contacts. The quantitative phase administered structured questionnaires on sociodemographic factors, clinical history, depression/anxiety symptoms, and psychosocial stressors. Logistic regression models were used. The qualitative phase included in-depth interviews with 30 purposively sampled patients for thematic content analysis. Results were integrated to contextualize quantitative findings.
Results: High rates of depression (37.5%, n=151) and anxiety (45.2%, n=182) were documented among MDR-TB patients, significantly greater than household contacts (20.1%, n=81 and 25.1%, n=101 respectively. Older age, female gender, divorced/widowed status, financial constraints, substance abuse, disease severity, medication side effects, and perceived stigma emerged as significant risk factors. Themes highlighted depression, stigma, caretaking demands, and suggestions for patient support services.
Conclusion: MDR-TB patients experience a substantially higher dual disease burden of depression/anxiety elevating the risk for adverse outcomes and transmission. Improving psychosocial support is vital to patient-centric care pathways for vulnerable groups. Mixed methods provide comprehensive evidence to inform integrated physical-mental health services.