bluuebunny/crossref_metadata_2025 huggingface dataset:
ВИЗНАЧЕННЯ ОСОБЛИВОСТЕЙ КОМУНІКАТИВНОЇ ДІЯЛЬНОСТІ В ДІТЕЙ РАННЬОГО ВІКУ З ІНТЕЛЕКТУАЛЬНИМИ ПОРУШЕННЯМИ
Authors: ТУБИЧКО Юлія
Published: March 2024

У статті розкрито проблему визначення особливостей комунікативної діяльності в дітей раннього віку з інтелектуальними порушеннями. Мета статті – визначити особливості, критерії і рівні сформованості комунікативної діяльності в дітей раннього віку з інтелектуальними порушеннями. Методологія дослідження заснована на концепції вікового розвитку дитини; провідної ролі дорослого у розвитку комунікації дитини раннього віку, відповідності змісту комунікації рівню розвитку комунікативної потреби дитини; в ході дослідження використано загальнонаукові методи аналізу і синтезу, систематизації та теоретичного узагальнення досліджень психологів і корекційних педагогів; спостереження; бесіди; вивчення історій розвитку дітей; анкетування; ігрові та практичні методи; кількісний та якісний аналіз результатів дослідження. Наукова новизна дослідження полягає в розробці та апробації методики вивчення процесу комунікативної діяльності дітей раннього віку з порушеннями інтелектуального розвитку; визначені критеріїв ефективності та особливостей процесу комунікативної діяльності дітей даної категорії. Висновки. Результати дослідження довели, що в дітей з інтелектуальними порушеннями не сформована потреба у комунікативній діяльності (відсутність інтересу до нового дорослого чи однолітка, відсутність інтересу до спільних предметно-ігрових дій і, як наслідок, несформованість комунікативних умінь). Для цих дітей процес комунікації з дорослими і однолітками не стає психологічним новоутворенням – формою вираження потреби у спілкуванні, як це спостерігається у дітей з нормо-типовим розвитком. Вище зазначене свідчить про те, що для формування комунікативної діяльності у дітей раннього віку з порушеннями інтелектуального розвитку необхідне створення спеціальних умов, розробка змісту та методів корекційно-педагогічної роботи.
ОЦІНЮВАННЯ ЕКОЛОГІЧНОГО ЕФЕКТУ РЕАЛІЗАЦІЇ СХЕМ КОМПЕНСАЦІЇ ВТРАТ ЕКОСИСТЕМ
Authors: Кобзар Олена
Published: March 2024

Метою статті є визначення підходів та критеріїв оцінювання екологічного ефекту застосування схем компенсації втрат екосистем з особливою природоохоронною цінністю при реалізації проектів економічного розвитку. Запропоновано оцінювання змін екосистем в результаті застосування схем компенсації при реалізації проектів економічного розвитку проводити з позицій підходу оцінювання екосистемних активів – за протяжністю та станом екосистем. При оцінюванні мають бути враховані зміни у двох групах екосистем: у екосистемах, з особливою природоохоронною цінністю, які були знищені при реалізації проекту економічного розвитку; у екосистемах на ділянках компенсації. Визначено, що результатом застосування схем компенсації є збереження екосистем з особливою природоохоронною цінністю за рахунок змін тих екосистем, що існують на ділянці компенсації. При цьому загальна площа екосистем зменшується на величину, рівну площі знищеної екосистеми з особливою природоохоронною цінністю в межах території реалізації проекту економічного розвитку.
НАПРЯМИ ВИКОРИСТАННЯ ЦИФРОВОГО ОДЯГУ В СУЧАСНІЙ ФЕШН-ІНДУСТРІЇ
Authors: Процик Богдан Олександрович , Пашкевич Калина Лівіанівна , Герасименко Олена Дмитрівна , Люклян Надія Романівна
Published: March 2024

У статті розглянуто особливості використання цифрового одягу, на прикладі провідних компаній у цій галузі, таких як The Fabricant, DRESSX, Carling, Auroboros, FINCH та ін. Кожна з наведених компаній вирізняється інноваційним підходом та внеском у сферу дизайну одягу. The Fabricant виступає піонером у сфері цифрової моди, спеціалізуючись на фотореалістичному 3D-дизайні та анімації. DRESSX, як перший онлайн магазин цифрового одягу, відкриває нові можливості для електронної комерції та персоналізації віртуальних гардеробів. Бренд Carling цифровою колекцією Neo-EX підсилює ідею індивідуалізації через персоналізацію цифрового одягу. Auroboros, в свою чергу, досліджує екологічні аспекти цифрового одягу та впроваджує у свої технології відновлювальні матеріали. Українські компанії FINCH і FFFACE додають свою унікальність у фешн-індустрію, використовуючи технології віртуальної реальності. У статті розглянуто та визначено ключові етапи створення цифрового одягу, починаючи від розробки концепції та завершуючи приміркою віртуальних моделей, що дозволяє виявити не лише технічні та дизайнерські завдання, але й визначити найбільш оптимальні та ефективні методи на кожному етапі творчого процесу. Результати дослідження надають практичну цінність, оскільки вони слугують основою для вдосконалення сучасних технологій у галузі дизайну одягу. Крім того, результати дослідження визначають перспективи використання цифрового одягу в індустрії моди, вказуючи на потенційні напрями розвитку та інновації. Сучасні технології відкривають нові можливості для дизайнерів та виробників, дозволяючи їм експериментувати з формами, кольорами та текстурами в цифровому просторі. Однак, для успішного впровадження цифрового одягу в індустрію моди, важливо продовжувати досліджувати та вдосконалювати технології, враховуючи не лише естетичні аспекти, але й економічну та екологічну стійкість.
Community-wide masting improves predator satiation in North American oaks
Authors: Szymkowiak Jakub , Bogdziewicz Michał , Marino Shealyn , Steele Michael
Published: March 2024

Mast seeding, a phenomenon observed in numerous perennial plant species, is highly variable reproduction across years, synchronized among individuals within a population. One major fitness advantage of masting lies in the reduction of seed predation rates, achieved through alternating phases of seed scarcity and abundance that starve and subsequently satiate seed consumers. Proximately, the variability in seed production frequently correlates with weather conditions. Convergent responses among species to weather fluctuations often lead to synchronized masting events across species, which may help with predator satiation, but this hypothesis has been rarely tested. In this study, we address this gap by using 23 years of seed production and pre-dispersal seed predation monitoring in three North American oak species (\emph{Quercus rubra}, \emph{Quercus alba}, \emph{Quercus montana}). We found that spring and summer weather patterns correlated with masting events in all three species, resulting in intraspecific synchrony levels ranging from 0.21 to 0.38, depending on the species pair. Intraspecific masting synchrony facilitated efficient insect starvation in \emph{Q. rubra} and \emph{Q. alba}, while community-wide mast years were necessary for satiation in \emph{Q. montana}. Our findings present a rare empirical test supporting the hypothesis that intraspecific masting synchrony enhances reproductive efficiency by minimizing seed losses to generalist seed predators.
PALYNOFACIES STUDIES OF THE LATE CRETACEOUS (TURONIAN-MAASTRICHTIAN) STRATA FROM JAURO JATAU, GONGOLA SUB-BASIN, NORTHERN BENUE TROUGH, NIGERIA
Authors: Aliyu Abdulkarim Haruna , Maigari Abubakar , Umar Bappah , Nabage Nuru , Shirputda John , Saidu Fatima , Mohammed Mohammed
Published: March 2024

Geographically located within Gombe, Bauchi, and Yobe states, the Gongola Sub-basin has drawn attention from several academics looking to increase Nigeria's oil reserves relative to the inland frontier basins. This paper's goal is to determine the thermal maturity of strata from drill samples of the Fika shales in Nigeria's Northern Benue Trough, Gongola Sub-basin. To predict the well section's maturity and kerogen type, this study uses optical and organic facies studies. Twenty-seven samples of ditch cuttings were prepared using the universally accepted acid palynological procedure. The dispersed mounted slides revealed a variety of pollen, spores, and palynomacerals upon microscopic inspection. The well section under study exhibits a range of thermal maturation from mature to late mature, indicating the possibility of producing oil and gas. This corresponds to a range of thermal alteration values of 4 – 6 and equivalent vitrinite reflectance (%Ro) values of 0.6% – 1.35%. The total recovered Sedimentary Organic Matter (SOM) in this study was classified into Palynomorphs, Amorphous Organic Matter (AOM) and Phytoclasts and plotted on a ternary graph. The Percentage frequencies of AOM, Phytoclast and Palynomorphs were compared with the zones of the Tyson Ternary diagram. Most of the distribution frequencies lie within zones II, IX, VI and Iva suggesting Kerogen types III (gas-prone) and II (oil-prone).
Prevalence, risks and outcomes of frailty in People Experiencing Homelessness: a protocol for secondary analysis of Health Needs Audit data
Authors: Dawes Jo , Walters Kate , Frost Rachael , Bagkeris Emmanouil , Burton Alexandra , Hertzberg Debra , Hayward Andrew
Published: March 2024

Frailty describes a health state related to ageing where people become less resilient to health challenges and more likely to have adverse outcomes if they become unwell. People experiencing homelessness (PEH) are known to have poor health, with research suggesting that many become frail at a younger age than the general population. Previous research using small-scale primary data collection suggests that the prevalence of frailty in homeless populations varies widely (16–55%), with variations in sample sizes and settings partially accounting for differences in current estimates. The prevalence, risks, and outcomes of frailty in PEH are poorly understood. We propose to carry out a secondary analysis of existing health survey data collected from 2,792 PEH. This will involve creating a Frailty Index (FI) to identify frail people within the dataset. Regression analyses will be used to identify associations between potential risk factors and outcomes of frailty in this population. This protocol will: 1) Outline the creation of a FI to assess the frailty prevalence within a dataset of health information collected from a cohort of PEH and 2) Describe proposed methods of regression analysis for identification of associations between frailty and risks factors/outcomes of frailty in the cohort of PEH within the dataset. The processes described in this paper can inform future development of FIs in other datasets. It is expected that the FI created will be an appropriate and robust method for identifying frailty in a cohort of PEH and results of the secondary data analysis will provide a more robust estimate of the associations between frailty and risk factors/outcomes.
PENGEMBANGAN BAHAN AJAR MENULIS BERITA BERDASARKAN PENDEKATAN PROSES GENRE
Authors: Wismanto Agus
Published: March 2024

This study aims to (1) describe the needs of textbooks in learning to write news writing which are used as development teaching materials, (2) design textbooks that are in accordance with the analysis of student needs, (3) develop text books for writing news writing based on a genre process approach for students at the Indonesian Language and Literature Education Study Program, Faculty of Language and Letters, University of PGRI Semarang, (4) to find out the potential influence of developing news writing text books based on the genre process approach to learning outcomes. This research is research and development. The subjects in this study were 26 students of the Indonesian Language and Literature Education Study Program, Faculty of Language and Art, University of PGRI Semarang. The results of the study indicate that the news writing text book as a result of this development has a potential influence in improving students' abilities and understanding of news writing materials in university.
SURVEI PEMBELAJARAN MENULIS TEKS BERITA SEBAGAI REFLEKSI LITERASI MEMBACA SISWA
Authors: Pramesti Utami Dewi , Sastromiharjo Andoyo , Anshori Dadang S. , Mulyati Yeti
Published: March 2024

This article describes the comparison of news-writing learning during offline learning and online learning with the aim of getting a portrait of news-writing learning in both types of learning. Research conducted is descriptive quantitative. The research sample was Junior High School teachers in all regions of Indonesia who were randomly selected. The questionnaire is an instrument in this studywhich is distributed via google form. The research steps were as follows: (1) determining the topic; (2) exploring theoretical studies; (3) formulating instruments; (4) validating the instrument; (5) disseminating instruments; (6) collecting and calculating the results of the questionnaire that has been obtained; (7) discussing and concluding the research results. The results of research on both types of learning show several similarities and differences. The findings that contain the similarities between offline and online learning are: (1) more than 50% of the teachers did not use certain learning models for news writing materials; (2) that audiovisual media is the most widely used (50-51.8%); (3) news text is the final product of learning more than 50%; and (4) performance assessment used 50-56.1%. The resulting differences are: (1) offline learning does not use applications, while applications that are widely used online are the WA Group (48.6%); (2) the most prominent learning methods and techniques used when offline were discussion (48.2%), while online was direct observation (35.7%).
RESPON SISWA TERHADAP PEMBELAJARAN BERKELOMPOK PADA PEMBELAJARAN JARAK JAUH ONLINE
Authors: Ramadhan Syahrul , Atmazaki Atmazaki , Indriyani Vivi , Sukma Elfia
Published: March 2024

The COVID-19 pandemic has resulted in learning having turned into online distance learning. The learning is dominated by independent learning, even though the ability to socialize and work in teams is needed at this time. Collaborating is one of the skills needed in the 21st century. Students' opinions differ, because the rapid development of education or internet access does not guarantee the quality of education and student satisfaction. Based on this explanation, the purpose of this study was to determine student responses regarding group learning in online distance learning. This research is a descriptive research using survey method. The instrument used is a questionnaire sheet. The number of respondents who filled out the questionnaire was 484 students. Questionnaire data were analyzed by describing the findings obtained which were described through descriptive statistics. The results showed that students gave a positive response to implementing group learning during online distance learning, for the following reasons: the task was carried out more easily; can get help when experiencing difficulties; can discuss by expressing opinions; can share ideas with group members, etc. However, there are also some weaknesses in this learning, such as the role of group members; domination that works unevenly; talk a lot, etc.
PERSEPSI SISWA TERHADAP MODEL PEMBELAJARAN BERBASIS OTAK (MPBO) DALAM PEMBELAJARAN MEMBACA PEMAHAMAN
Authors: Kohar Dadun
Published: March 2024

This study aims to determine students’ perception of the Brain-Based Learning Model (MPBO) in learning of comprehension reading. This study uses a descriptive method with a qualitative approach. The data collection technique used is a questionnaire in the form of a Likert scale. The data for each variable is processed by the following steps: grouping the data, tabulating the data, presenting the data in tabular form, calculating scores, presenting the data in the form of pictures, and drawing conclusions both for each variable and as a whole. This study concludes that students consider MPBO is good when used in learning of comprehension reading. This can be seen from the perception score given by students, which is 424. If it is presented, the score becomes 84.50%. This means that students' perceptions are slightly agree.
Social Inclusivity in Teaching: In Pursuit of Students’ Advanced Capabilities
Authors: Skourdoumbis Andrew
Published: March 2024

The study explores social inclusivity in primary schools in Indonesia, focusing on three main elements: acceptance of student diversity, empowerment of student agency, and establishment of democracy in the classroom. This research uses qualitative methods with case study methods. The data collection process obtained from curriculum documents, lesson plans, interviews, and observations are used to describe existing practices and opportunities for increasing social inclusivity. The collected data were analyzed in depth to illustrate existing practices and opportunities for increasing social inclusivity in primary school education settings in Indonesia. The research identifies three important aspects of social inclusivity: accepting diversity, empowering agency and student voices, and upholding democracy. Although the curriculum recognizes diversity and some teaching practices involve student voices, there is still room to promote more intact democratic practices in the classroom. The implication of this study is to emphasize the need for an equitable and participatory learning environment in the context of primary education. The findings emphasize the importance of acknowledging cultural diversity, encouraging student engagement, and strengthening democratic principles in the context of primary education in Indonesia.
Characterization of moisture migration and diffusion in two types of tobacco biomass during the dehydration process by the TG-NMR analysis
Authors: Zhu Wenkui , Zhou Bo , Duan Kun , Huang Duoduo , Han Lifeng , Zhang Rongya , Wen Wu , Wang Bing , Li Bin
Published: March 2024

The tobacco waste generated from the tobacco agriculture and industry, including the discarded stem and leaf, often needs dehydration pretreatment before thermal conversion utilization. In order to study the water activity and migration of tobacco waste during the pretreatment process, TG-NMR (Thermogravimetric Nuclear Magnetic Resonance) was used to obtain the drying curves and LF-NMR (Low Field Nuclear Magnetic Resonance) T2 inversion spectrum at each stage of tobacco drying. Meanwhile, the variation pattern of pore distribution during the dehydration process of two types of tobacco waste has been obtained. Combined with the pore distribution changes, a possible spatial migration mode of water was proposed. The change of adsorption energy of water during tobacco drying was calculated, and verified the above hypothesis. This study results provide reference for the optimization of dehydration pretreatment process for different tobacco waste in order to reduce energy consumption during recycling of tobacco biomass.
Genotyping of ticks: first molecular report of Hyalomma asiaticum and molecular detection of tick-borne bacteria in ticks and blood from Khyber Pakhtunkhwa, Pakistan
Authors: Obaid Muhammad Kashif , Shehla Shehla , Guan Guiquan , Rashid Muhammad , Shams Sumaira
Published: March 2024

Multiple ticks (Acari: Ixodoidea) carrying Rickettsiales bacteria have significant importance for both human and animal health. Thus, the purpose of this work was to genetically analyze tick species and their associated Rickettsiales bacteria in animal hosts. In order to achieve these objectives, various animals (including camels, cattle, goats, sheep, dogs, and mice) were inspected in four districts (Mardan, Peshawar, Kohat, and Karak) of Khyber Pakhtunkhwa to collect ticks, while blood samples were collected from all the symptomatic and asymptomatic cattle in all four districts. A total of 234 ticks were obtained from 86 out of 143 (60.14%) host animals, which were morphologically identified as Rhipicephalus turanicus, Rhipicephalus microplus, Haemaphysalis cornupunctata, and Hyalomma asiaticum. Among these, their representative ticks (126/234, 53.85%) were processed for molecular confirmation using cytochrome c oxidase (cox1) gene. Obtained cox1 sequences of four different tick species showed 99.72%–100% maximum identity with their corresponding species reported from Pakistan, China, India, and Kazakhstan and clustered phylogenetically. This study presented the first genetic report of Hy. asiaticum ticks in Pakistan. Moreover, genetically confirmed tick species were molecularly analyzed by PCR for detection of Rickettsiales DNA using partial fragments of 16S rDNA, 190-kDa outer membrane protein A (ompA), and 120-kDa outer membrane protein B (ompB) genes. In addition, blood samples were analyzed to identify Rickettsiales bacteria using the aforementioned genes. Rickettsiales bacteria were found in 24/126 (19.05%) ticks and 4/16 (25.00%) in symptomatic cattle’s blood. The obtained ompA and ompB sequences from Hy. asiaticum ticks showed 99.73%–99.87% with Candidatus Rickettsia shennongii and unidentified Rickettsia sp., whereas the obtained 16S rDNA sequences from cattle’s blood and ticks (Hae. cornupunctata) showed 99.67% highest identity with Anaplasma phagocytophilum. The 16S rDNA sequence of Rickettsiales DNA from Rh. turanicus ticks showed 100% identity with Ehrlichia canis and unidentified Ehrlichia sp. Obtained sequences of Rickettsiales bacteria were grouped along with their respective species in phylogenetic trees, which were previously reported in Greece, Cuba, Iraq, Turkey, Pakistan, South Korea, and China (mainland and Taiwan). This extensive study explores the wide range of damaging ticks and their corresponding tick-borne bacteria in the area, suggesting a possible danger to both livestock and human communities.
Adfluvial migration and passage of Steelhead before and after dam removal at a major Great Lakes tributary
Authors: Bunt Christopher M. , Jacobson Bailey
Published: March 2024

Despite the importance of Great Lakes fisheries and the increasing popularity of dam removal as a method to restore river connectivity and increase fish passage, the adfluvial migration of Steelhead (Oncorhynchus mykiss) has been drastically understudied and only relatively few published studies have examined the impacts of dam removal on fish movement and timing. To help fill these knowledge gaps, spawning migrations of Great Lakes adfluvial Steelhead tagged in spring and fall were monitored for two years before and three years after removal of a dam that partially blocked upstream movement for 100 years. Removal of the dam not only reduced downstream delay and increased passage at the site of the dam removal itself, but increased travel speeds and increased passage at remaining upstream dams for both spring and fall run fish, underscoring the cumulative impact of successive dam passage on fish migration. Fall fish were most impacted by the dam removal and were able to pass not only the dam footprint, but, for the first time, were also able to pass both remaining upstream dams, allowing them to overwinter at locations closer to known spawning areas. For these fish, delay at the footprint was reduced from the order of 100+ days to < 1 hour and the number of days passage occurred compared to the number of days fish were present and blocked increased from 2% to 82%. The benefits of dam removal should ultimately equate to increases in fish production, as more critical habitat becomes reconnected and more fish are able to pass dams and arrive at spawning beds. The observation that fish are likely able to remain in better condition and retain more energy for continued migration and reproduction warrants further study.
Integrative analysis identifies cancer cell-intrinsic RARRES1 as a predictor of prognosis and immune response in triple-negative breast cancer
Authors: Yu Zhengheng , Liu Hongjin , Ye Jingming , Liu Yinhua , Xin Ling , Liu Qian , Cheng Yuanjia , Yin Lu , Xu Ling
Published: March 2024

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and limited treatment options. Although immune checkpoint inhibitors (ICIs) have been proven to improve outcomes in TNBC patients, the potential mechanisms and markers that determine the therapeutic response to ICIs remains uncertain. Revealing the relationship and interaction between cancer cells and tumor microenvironment (TME) could be helpful in predicting treatment efficacy and developing novel therapeutic agents. By analyzing single-cell RNA sequencing dataset, we comprehensively profiled cell types and subpopulations as well as identified their signatures in the TME of TNBC. We also proposed a method for quantitatively assessment of the TME immune profile and provided a framework for identifying cancer cell-intrinsic features associated with TME through integrated analysis. Using integrative analyses, RARRES1 was identified as a TME-associated gene, whose expression was positively correlated with prognosis and response to ICIs in TNBC. In conclusion, this study characterized the heterogeneity of cellular components in TME of TNBC patients, and brought new insights into the relationship between cancer cells and TME. In addition, RARRES1 was identified as a potential predictor of prognosis and response to ICIs in TNBC.
mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020
Authors: Allen James D. , Ross Ted M.
Published: March 2024

Background

The implementation of mRNA vaccines against COVID-19 has successfully validated the safety and efficacy of the platform, while at the same time revealing the potential for their applications against other infectious diseases. Traditional seasonal influenza vaccines often induce strain specific antibody responses that offer limited protection against antigenically drifted viruses, leading to reduced vaccine efficacy. Modern advances in viral surveillance and sequencing have led to the development of in-silico methodologies for generating computationally optimized broadly reactive antigens (COBRAs) to improve seasonal influenza vaccines.

Methods

In this study, immunologically naïve mice were intramuscularly vaccinated with mRNA encoding H1 and H3 COBRA hemagglutinins (HA) or wild-type (WT) influenza HAs encapsulated in lipid nanoparticles (LNPs).

Results

Mice vaccinated with H1 and H3 COBRA HA-encoding mRNA vaccines generated robust neutralizing serum antibody responses against more antigenically distinct contemporary and future drifted H1N1 and H3N2 influenza strains than those vaccinated with WT H1 and H3 HA-encoding mRNA vaccines. The H1 and H3 COBRA HA-encoding mRNA vaccines also prevented influenza illness, including severe disease in the mouse model against H1N1 and H3N2 viruses.

Conclusions

This study highlights the potential benefits of combining universal influenza antigen design technology with modern vaccine delivery platforms and exhibits how these vaccines can be advantageous over traditional WT vaccine antigens at eliciting superior protective antibody responses against a broader number of influenza virus isolates.
An analysis of neutrophil-to-lymphocyte ratios and monocyte-to-lymphocyte ratios with six-month prognosis after cerebral contusions
Authors: Zhang Dangui , Zhuang Dongzhou , Li Tian , Liu Xueer , Zhang Zelin , Zhu Lihong , Tian Fei , Chen Xiaoxuan , Li Kangsheng , Chen Weiqiang , Sheng Jiangtao
Published: March 2024

Background and purpose

Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) have been identified as potential prognostic markers in various conditions, including cancer, cardiovascular disease, and stroke. This study aims to investigate the dynamic changes of NLR and MLR following cerebral contusion and their associations with six-month outcomes.

Methods

Retrospective data were collected from January 2016 to April 2020, including patients diagnosed with cerebral contusion and discharged from two teaching-oriented tertiary hospitals in Southern China. Patient demographics, clinical manifestations, laboratory test results (neutrophil, monocyte, and lymphocyte counts) obtained at admission, 24 hours, and one week after cerebral contusion, as well as outcomes, were analyzed. An unfavorable outcome was defined as a Glasgow Outcome Score (GOS) of 0-3 at six months. Logistic regression analysis was performed to identify independent predictors of prognosis, while receiver characteristic curve analysis was used to determine the optimal cutoff values for NLR and MLR.

Results

A total of 552 patients (mean age 47.40, SD 17.09) were included, with 73.19% being male. Higher NLR at one-week post-cerebral contusion (adjusted OR = 4.19, 95%CI, 1.16 - 15.16, P = 0.029) and higher MLR at admission and at 24 h (5.80, 1.40 - 24.02, P = 0.015; 9.06, 1.45 - 56.54, P = 0.018, respectively) were significantly associated with a 6-month unfavorable prognosis after adjustment for other risk factors by multiple logistic regression. The NLR at admission and 24 hours, as well as the MLR at one week, were not significant predictors for a 6-month unfavorable prognosis. Based on receiver operating characteristic curve analysis, the optimal thresholds of NLR at 1 week and MLR at admission after cerebral contusion that best discriminated a unfavorable outcome at 6-month were 6.39 (81.60% sensitivity and 70.73% specificity) and 0.76 (55.47% sensitivity and 78.26% specificity), respectively.

Conclusion

NLR measured one week after cerebral contusion and MLR measured at admission may serve as predictive markers for a 6-month unfavorable prognosis. These ratios hold potential as parameters for risk stratification in patients with cerebral contusion, complementing established biomarkers in diagnosis and treatment. However, further prospective studies with larger cohorts are needed to validate these findings.
Long-term analysis of humoral responses and spike-specific T cell memory to Omicron variants after different COVID-19 vaccine regimens
Authors: Ho Chia-Lo , Yen Li-Chen , Huang Hong-Wei , Lu Chun-Chi , Hung Yi-Jen , Liao Ching-Len , Hung Chin-Mao , Chiu Kuo-Chou
Published: March 2024

Background

The emergence of SARS-CoV-2 variants has raised concerns about the sustainability of vaccine-induced immunity. Little is known about the long-term humoral responses and spike-specific T cell memory to Omicron variants, with specific attention to BA.4/5, BQ.1.1, and XBB.1.

Methods

We assessed immune responses in 50 uninfected individuals who received varying three-dose vaccination combinations (2X AstraZeneca + 1X Moderna, 1X AstraZeneca + 2X Moderna, and 3X Moderna) against wild-type (WT) and Omicron variants at eight months post-vaccination. The serum antibody titers were analyzed by enzyme-linked immunosorbent assays (ELISA), and neutralizing activities were examined by pseudovirus and infectious SARS-CoV-2 neutralization assays. T cell reactivities and their memory phenotypes were determined by flow cytometry.

Results

We found that RBD-specific antibody titers, neutralizing activities, and CD4+ T cell reactivities were reduced against Omicron variants compared to WT. In contrast, CD8+ T cell responses, central memory, effector memory, and CD45RA+ effector memory T cells remained unaffected upon stimulation with the Omicron peptide pool. Notably, CD4+ effector memory T cells even exhibited a higher proportion of reactivity against Omicron variants. Furthermore, participants who received three doses of the Moderna showed a more robust response regarding neutralization and CD8+ T cell reactions than other three-dose vaccination groups.

Conclusion

Reduction of humoral and CD4+ T cell responses against Omicron variants in vaccinees suggested that vaccine effectiveness after eight months may not have sufficient protection against the new emerging variants, which provides valuable information for future vaccination strategies such as receiving BA.4/5 or XBB.1-based bivalent vaccines.
Enhanced T cell receptor specificity through framework engineering
Authors: Rosenberg Aaron M. , Ayres Cory M. , Medina-Cucurella Angélica V. , Whitehead Timothy A. , Baker Brian M.
Published: March 2024

Development of T cell receptors (TCRs) as immunotherapeutics is hindered by inherent TCR cross-reactivity. Engineering more specific TCRs has proven challenging, as unlike antibodies, improving TCR affinity does not usually improve specificity. Although various protein design approaches have been explored to surmount this, mutations in TCR binding interfaces risk broadening specificity or introducing new reactivities. Here we explored if TCR specificity could alternatively be tuned through framework mutations distant from the interface. Studying the 868 TCR specific for the HIV SL9 epitope presented by HLA-A2, we used deep mutational scanning to identify a framework mutation above the mobile CDR3β loop. This glycine to proline mutation had no discernable impact on binding affinity or functional avidity towards the SL9 epitope but weakened recognition of SL9 escape variants and led to fewer responses in a SL9-derived positional scanning library. In contrast, an interfacial mutation near the tip of CDR3α that also did not impact affinity or functional avidity towards SL9 weakened specificity. Simulations indicated that the specificity-enhancing mutation functions by reducing the range of loop motions, limiting the ability of the TCR to adjust to different ligands. Although our results are likely to be TCR dependent, using framework engineering to control TCR loop motions may be a viable strategy for improving the specificity of TCR-based immunotherapies.
Redefining the battle against colorectal cancer: a comprehensive review of emerging immunotherapies and their clinical efficacy
Authors: Shebbo Salima , Binothman Najat , Darwaish Manar , Niaz Hanan A. , Abdulal Rwaa H. , Borjac Jamilah , Hashem Anwar M. , Mahmoud Ahmad Bakur
Published: March 2024

Colorectal cancer (CRC) is the third most common cancer globally and presents a significant challenge owing to its high mortality rate and the limitations of traditional treatment options such as surgery, radiotherapy, and chemotherapy. While these treatments are foundational, they are often poorly effective owing to tumor resistance. Immunotherapy is a groundbreaking alternative that has recently emerged and offers new hope for success by exploiting the body’s own immune system. This article aims to provide an extensive review of clinical trials evaluating the efficacy of various immunotherapies, including CRC vaccines, chimeric antigen receptor T-cell therapies, and immune checkpoint inhibitors. We also discuss combining CRC vaccines with monoclonal antibodies, delve into preclinical studies of novel cancer vaccines, and assess the impact of these treatment methods on patient outcomes. This review seeks to provide a deeper understanding of the current state of CRC treatment by evaluating innovative treatments and their potential to redefine the prognosis of patients with CRC.
Super resolution-based methodology for self-supervised segmentation of microscopy images
Authors: Bommanapally Vidya , Abeyrathna Dilanga , Chundi Parvathi , Subramaniam Mahadevan
Published: March 2024

Data-driven Artificial Intelligence (AI)/Machine learning (ML) image analysis approaches have gained a lot of momentum in analyzing microscopy images in bioengineering, biotechnology, and medicine. The success of these approaches crucially relies on the availability of high-quality microscopy images, which is often a challenge due to the diverse experimental conditions and modes under which these images are obtained. In this study, we propose the use of recent ML-based image super-resolution (SR) techniques for improving the image quality of microscopy images, incorporating them into multiple ML-based image analysis tasks, and describing a comprehensive study, investigating the impact of SR techniques on the segmentation of microscopy images. The impacts of four Generative Adversarial Network (GAN)- and transformer-based SR techniques on microscopy image quality are measured using three well-established quality metrics. These SR techniques are incorporated into multiple deep network pipelines using supervised, contrastive, and non-contrastive self-supervised methods to semantically segment microscopy images from multiple datasets. Our results show that the image quality of microscopy images has a direct influence on the ML model performance and that both supervised and self-supervised network pipelines using SR images perform better by 2%–6% in comparison to baselines, not using SR. Based on our experiments, we also establish that the image quality improvement threshold range [20–64] for the complemented Perception-based Image Quality Evaluator(PIQE) metric can be used as a pre-condition by domain experts to incorporate SR techniques to significantly improve segmentation performance. A plug-and-play software platform developed to integrate SR techniques with various deep networks using supervised and self-supervised learning methods is also presented.
A single point mutation in the Listeria monocytogenes ribosomal gene rpsU enables SigB activation independently of the stressosome and the anti-sigma factor antagonist RsbV
Authors: Ma Xuchuan , Tempelaars Marcel H. , Zwietering Marcel H. , Boeren Sjef , O’Byrne Conor P. , den Besten Heidy M. W. , Abee Tjakko
Published: March 2024

Microbial population heterogeneity leads to different stress responses and growth behavior of individual cells in a population. Previously, a point mutation in the rpsU gene (rpsUG50C) encoding ribosomal protein S21 was identified in a Listeria monocytogenes LO28 variant, which leads to increased multi-stress resistance and a reduced maximum specific growth rate. However, the underlying mechanisms of these phenotypic changes remain unknown. In L. monocytogenes, the alternative sigma factor SigB regulates the general stress response, with its activation controlled by a series of Rsb proteins, including RsbR1 and anti-sigma factor RsbW and its antagonist RsbV. We combined a phenotype and proteomics approach to investigate the acid and heat stress resistance, growth rate, and SigB activation of L. monocytogenes EGDe wild type and the ΔsigB, ΔrsbV, and ΔrsbR1 mutant strains. While the introduction of rpsUG50C in the ΔsigB mutant did not induce a SigB-mediated increase in robustness, the presence of rpsUG50C in the ΔrsbV and the ΔrsbR1 mutants led to SigB activation and concomitant increased robustness, indicating an alternative signaling pathway for the SigB activation in rpsUG50C mutants. Interestingly, all these rpsUG50C mutants exhibited reduced maximum specific growth rates, independent of SigB activation, possibly attributed to compromised ribosomal functioning. In summary, the increased stress resistance in the L. monocytogenes EGDe rpsUG50C mutant results from SigB activation through an unknown mechanism distinct from the classical stressosome and RsbV/RsbW partner switching model. Moreover, the reduced maximum specific growth rate of the EGDe rpsUG50C mutant is likely unrelated to SigB activation and potentially linked to impaired ribosomal function.
Bickerstaff encephalitis in childhood: a review of 74 cases in the literature from 1951 to today
Authors: Giaccari Luca Gregorio , Mastria Donatella , Barbieri Rosella , De Maglio Rossella , Madaro Francesca , Paiano Gianfranco , Pace Maria Caterina , Sansone Pasquale , Pulito Giuseppe , Mascia Luciana
Published: March 2024

Bickerstaff brainstem encephalitis (BBE) is a rare autoimmune disease characterized by the subacute onset of bilateral external ophthalmoplegia, ataxia, and decreased level of consciousness. BBE is part of a group of rare autoimmune diseases in children that can affect the nervous system at any level. The onset of neurological deficits is often sudden and nonspecific. The diagnosis is based on clinical findings and abnormal findings on cerebrospinal fluid (CSF), electroencephalography (EEG), electromyography (EMG), and magnetic resonance imaging (MRI). BBE is associated with the presence of the antiganglioside antibody, anti-GQ1b and anti-GM1. Intravenous immunoglobulin (IVIg) and plasma exchange are often used as treatments for these patients. We conducted a review on clinical presentation, diagnosis, treatment and outcome of reported cases of BBE. 74 cases are reported in the literature from the first cases described in 1951 to today. The prevalence is unknown while the incidence is higher in males. In 50% of cases, BBE occurs following respiratory or gastrointestinal tract infections. The most frequent initial symptoms were consciousness disturbance, headache, vomiting, diplopia, gait disturbance, dysarthria and fever. During illness course, almost all the patients developed consciousness disturbance, external ophthalmoplegia, and ataxia. Lumbar puncture showed pleocytosis or cytoalbuminological dissociation. Abnormal EEG and MRI studies revealed abnormalities in most cases. Anti-GQ1b antibodies were detected in more than half of the patients; anti-GM1 antibodies were detected in almost 40% of patients. Treatment guidelines are missing. In our analysis, steroids and IVIg were administered alone or in combination; as last option, plasmapheresis was used. BBE has a good prognosis and recovery in childhood is faster than in adulthood; 70% of patients reported no sequelae in our analysis. Future studies need to investigate pathogenesis and possible triggers, and therapeutic possibilities.
The Prescription trends and dosing appropriateness analysis of novel oral anticoagulants in ischemic stroke patients: a retrospective study of 9 cities in China
Authors: Wu Mingfen , Jiang Hailun , Yu Kefu , Zhao Zhigang , Zhu Bin
Published: March 2024

Background: Novel oral anticoagulants (NOACs) have been recommended by guidelines as the first-line drugs for preventing cardiogenic stroke. We aimed to provide an overview of the prescription trends and dosing appropriateness of NOACs in China.

Methods: We conducted a retrospective analysis of NOAC prescriptions using the Hospital Prescription Analysis Cooperation Project data from 2016 to 2022. Various patient features, such as gender, age, city, year, source, department visited, original diagnosis, dosing, cost, and insurance type, were collected and analyzed to examine the trends and dosing appropriateness of NOAC usage in ischemic stroke patients.

Results: 62,014 NOAC prescriptions were analyzed, including 16,602 for dabigatran, 45,253 for rivaroxaban, and 159 for apixaban. 85.14% of the patients were aged 65 or above, and tertiary hospitals accounted for 95.97% of NOAC prescriptions. NOAC prescriptions rose from 1828 in 2016 to 13,998 in 2021 but dropped to 13,166 in 2022. The percentage of annual prescriptions for NOACs among stroke patients has increased from 0.05% in 2016 to 0.37% in 2022. Total drug cost increased from ¥704541.18 in 2016 to ¥4128648.44 in 2021, then decreased to ¥1680109.14 in 2022. Prescriptions were divided into 48,321 appropriate and 11,262 inappropriate dosing groups, showing significant differences in medications, age, year, city type, hospital level, source, insurance type, and department visited (all p < 0.001). The median drug cost for inappropriate dosing was higher than for appropriate dosing (¥55.20 VS ¥83.80). The top comorbidities in ischemic stroke patients were atrial fibrillation (35.30%), hypertension (32.75%), and coronary heart disease (16.48%).

Conclusion: The application of NOACs in the Chinese population is increasing. Our findings highlight the frequent deviation from labeled dosing of NOACs in clinical practice. Continued efforts are necessary to promote the appropriate use of NOACs according to the standard dosage in the drug insert.
Forcing a square into a circle: why South Africa’s draft revised material transfer agreement is not fit for purpose
Authors: Esselaar Paul , Swales Lee , Bellengère Devarasi , Mhlongo Banele , Thaldar Donrich
Published: March 2024

The South African National Health Research Ethics Council (NHREC) recently released a final draft revision of the standard material transfer agreement (MTA) that was promulgated into law in 2018. This new draft MTA raises pertinent questions about the NHREC’s mandate, the way in which the draft MTA deals with data and with human biological material, and its avoidance of the concept of ownership. After South Africa’s data protection legislation, the Protection of Personal Information Act (POPIA), became operational in mid 2021, the legal landscape changed and it is doubtful that the NHREC has a residual mandate to govern personal information in health research. Furthermore, data is dealt with in a superficial, throw-away fashion in the draft MTA. The position with human biological material is not substantially better, as the draft MTA fails to recognise that human biological material can contain pathogens, which has important legal and ethical ramifications that are not sufficiently addressed. A central problem with the draft MTA is its use of the term ‘steward’, and avoidance of the legal concept of ‘ownership’. This is not only misaligned with the South African legal framework, but also fails to consider the ethical case for recognising ownership. Finally, a call to embrace decolonial thinking in health research underscores the importance of recognising ownership in order to foster the growth of the local bio-economy. Key recommendations to reshape the draft MTA include: Making use of the eventual revised MTA optional, and allowing it to evolve with input from scientific and legal communities; regulating the transfer of associated data in a separate data transfer agreement that can be incorporated by reference in the MTA; enhancing guidance on liability and risk management in respect of human biological material that contains pathogens; and, finally, adopting a decolonial approach in health research governance, which requires recognising the ownership rights of South African research institutions.
Antiretroviral drugs from multiple classes induce loss of excitatory synapses between hippocampal neurons in culture
Authors: McMullan Hannah M. , Gansemer Benjamin M. , Thayer Stanley A.
Published: March 2024

Introduction: Antiretroviral (ARV) drugs have improved prognoses for people living with HIV. However, HIV-associated neurocognitive disorders (HAND) persist despite undetectable viral loads. Some ARVs have been linked to neuropsychiatric effects that may contribute to HAND. Synapse loss correlates with cognitive decline in HAND and synaptic deficits may contribute to the neuropsychiatric effects of ARV drugs.

Methods: Using an automated high content assay, rat hippocampal neurons in culture expressing PSD95-eGFP to label glutamatergic synapses and mCherry to fill neuronal structures were imaged before and after treatment with 25 clinically used ARVs.

Results and Discussion: At a concentration of 10 μM the protease inhibitors nelfinavir and saquinavir, the non-nucleoside reverse transcriptase inhibitors etravirine and the 8-OH metabolite of efavirenz, the integrase inhibitor bictegravir, and the capsid inhibitor lenacapavir produced synaptic toxicity. Only lenacapavir produced synapse loss at the nanomolar concentrations estimated free in the plasma, although all 4 ARV drugs induced synapse loss at Cmax. Evaluation of combination therapies did not reveal synergistic synaptic toxicity. Synapse loss developed fully by 24 h and persisted for at least 3 days. Bictegravir-induced synapse loss required activation of voltage-gated Ca2+ channels and bictegravir, etravirine, and lenacapavir produced synapse loss by an excitotoxic mechanism. These results indicate that select ARV drugs might contribute to neuropsychiatric effects in combination with drugs that bind serum proteins or in disease states in which synaptic function is altered. The high content imaging assay used here provides an efficient means to evaluate new drugs and drug combinations for potential CNS toxicity.