bluuebunny/crossref_metadata_2025 huggingface dataset:
ШЛЯХИ ПОДОЛАННЯ ПРОБЛЕМ ПІД ЧАС ДИСТАНЦІЙНОГО НАВЧАННЯ ДІТЕЙ З ОСОБЛИВИМИ ОСВІТНІМИ ПОТРЕБАМИ В УМОВАХ НУШ
Authors: Сухарєва Лариса
Published: July 2024

В Україні в Новій українській школі (НУШ) вже існує значний досвід у галузі освіти людей з особливими освітніми потребами, але все ще залишаються невирішені питання та суперечності, зокрема і у сфері дистанційної освіти. Ці суперечності охоплюють: 1) розбіжності між об’єктивною потребою дітей з особливими потребами в освіті та соціально-педагогічних послугах для їх інтеграції в освітній процес та відсутністю адекватної теоретичної бази, кваліфікованих спеціалістів та потрібних технологій; 2) необхідністю інтеграції молоді з інвалідністю в суспільство та браком розвитку ефективних способів і механізмів їх включення на інституційному рівні; 3) потенціалом освітніх закладів у соціально-педагогічній роботі з молоддю з особливими потребами та реальним станом розв’язання цієї проблеми; 4) необхідністю розвитку особистості молодих людей з проблемами здоров’я, стимуляцією їх компенсаторних можливостей та домінуванням у суспільстві підходів, які сприяють споживацькому ставленню до життя та пасивності, на шкоду активному включенню в суспільне життя; 5) недостатньою реабілітацією та соціальною адаптацією молоді з особливими потребами. Існує важливість формування єдиного освітнього середовища в Новій українській школі, де діти з різним рівнем здоров’я мають змогу взаємодіяти, незважаючи на психофізичні відмінності та різний рівень розвитку. У зв’язку з цим виникає необхідність раннього виявлення та корекції особистісного розвитку та соціально-педагогічної підтримки дітей з особливими потребами, зокрема в освітніх закладах, які повинні стати лідерами у цьому процесі.
Sequencing of cellular therapy and bispecific antibodies for the management of diffuse large B-cell lymphoma
Authors: Melody Megan , Gordon Leo I.
Published: July 2024

Historically, the management of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) following first-line chemoimmunotherapy has been second-line chemotherapy, followed by high-dose chemotherapy and consolidative autologous hematopoietic stem cell transplantation (HSCT), resulting in durable remissions in approximately 40% of patients. In 2017, chimeric antigen receptor (CAR) T-cell therapy changed the landscape of treatment for patients with R/R DLBCL, with complete response rates ranging from 40-58% and long-term disease-free survival of >40% in the highest risk subgroups, including patients who relapsed after autologous HSCT. Since that time further studies have demonstrated improved overall response rates and survival outcomes in patients with primary refractory or early-relapsed (relapse within 1 year) DLBCL treated with CAR T-cell therapy compared with autologous HSCT, advancing CAR T-cell therapy into the second-line setting. However, >50% of patients will relapse in the post-CAR T-cell setting. In the past 2 years, two CD20 x CD3 bispecific antibodies were approved by the Food and Drug Administration for the treatment of R/R DLBCL after two or more lines of systemic therapy. These bispecific antibodies have demonstrated overall response rates exceeding 50% and durable remissions at >2 years of follow-up. Additionally, a notable treatment advantage of bispecific antibodies is their ability to be administered in the community setting, making treatment more accessible for patients. The development and advancement of these novel therapies raise questions regarding the ongoing role of HSCT in the management of R/R DLBCL and the best sequence of cellular and bispecific therapies to optimize patients’ outcomes.
Risk of infections in multiple myeloma. A population-based study on 8672 multiple myeloma patients diagnosed 2008-2021 from the Swedish Myeloma Registry
Authors: Blimark Cecilie Hveding , Carlson Kristina , Day Christopher , Einarsdottir Sigrun , Juliusson Gunnar , Karma Moshtak , Knut-Bojanowska Dorota , Larfors Gunnar , Turesson Ingemar , Villegas-Scivetti Mariana , Sverrisdóttir Ingigerdur
Published: July 2024

In multiple myeloma (MM), advancements in treatments and toxicity management have enhanced survival rates. This, coupled with shifting age demographics in MM, necessitates an updated understanding of infection risks in MM patients compared to the general population. Using Swedish population-based registries, we investigated the incidence of infections in 8,672 Swedish symptomatic MM patients diagnosed 2008-2021 and 34,561 matched controls. Overall, MM patients had a 5-fold risk (hazard ratio (HR) = 5.30; 95%, Confidence Interval = CI 5.14-5.47) of developing any clinically significant infection compared to matched controls. Bacterial infections represented a 5-fold (HR 4.88; CI 4.70-5.07) increased risk, viral and fungal infections 7-fold compared to controls. The 1st year after MM diagnosis the risk of infections compared to controls was 7 –fold (HR 6.95; CI 6.61-7.30) and remained elevated up to 5 years after the myeloma diagnosis. The risk of infection compared to controls remained 5-fold in MM patients with follow-up till 2022. Preceding MM diagnosis, the risk compared to matched controls was significantly increased up to four years before MM diagnosis (HR1.16; CI 1.05-1.28). Among MM patients, 8% had died within 2 months of diagnosis and infection contributed to 32% of all deaths. After 1 year, 20% MM patients had died, and infection-related mortality was 27%. Our data constitute the largest population-based study to date on the risk of infections compared to the normal population in the era of modern MM therapies and confirms that infections still represent a major threat to patients and underscores importance of preventive strategies.
Development of quasi aromatic hybrid rice (Oryza sativa L) through genetic enhancement of local rice genotypes from Bangladesh
Authors: Islam M Z , Mian M A K , Ivy N A , Khalequzzaman M K , Ali M
Published: July 2024

Aromatic rice has tremendous economic and social value, but commercial production in Bangladesh is limited due to lower yields. In this study, the heterosis of hybrid rice was exploited to improve the yield of aromatic rice. A total of 120 aromatic rice germplasm was tested against five cytoplasmic male sterility (CMS) lines (A) with 40 maintainer (B) and 11 restorer (R) lines and the B lines were converted into CMS lines using backcrossing. The identified 11 restorer lines were being maintained, four local R-lines (Sakkorkhora, Chinigura, Kataribhog and BAU dhan2) were used by assessing pollen and spikelet fertility of the F1 generation from crosses of 50 selected R-lines against one CMS line (IR58025A). Quasi-hybrid-1 has a yield potential >5.0 t/ha. Growth duration varied in-between 85-90 days during the transplanted Aman season, and there was heightened zinc content (>22 mg/kg) in the hybrid grains. Identified restorer and maintainer local genotypes provide broad resources for increasing aromatic rice yield and could help meet the demand for aromatic rice in domestic and international markets.
Bangladesh J. Agri. 2024, 49(1): 19-32
Exploring Genetic Variability of Chilli Genotypes in Relation to Yield and Associated Traits
Authors: Alam M A , Obaidullah A J , Naher S , Hasan M M , Fahim A H F , Hoque A H M S
Published: July 2024

Chilli peppers, integral to Capsicum spp., are globally vital crops valued for culinary, economic, and nutritional contributions. Assessing genotypes is essential for improving varieties with traits like higher yield, disease resilience, and enhanced nutritional value. This study was conducted at the Spices Research Centre in Shibganj, Bogura, during the period of 2019-20 to evaluate 20 genotypes of chilli. Employing an alpha lattice design with two replications, the evaluation considered genetic diversity, variation, heritability, clustering, and trait associations as key components. All the traits exhibited remarkable significance ( < 0.01) for the studied genotypes, underscoring the genetic variability inherent to the traits in focus. Heritability varied from 79% to 99% for the traits investigated. Foremost in yield was found in the AVPP 1111 genotype (21.62 t/ha), trailed by the Indch 39 (21.19 t/ha), and A1511050 (20.57 t/ha). The cluster analysis dendrogram visually demonstrated the proximity among different genotypes concerning their similarities, ultimately forming six distinct clusters. While the studied traits displayed higher genotypic co-efficient of variation (GCV), and phenotypic co-efficient of variation (PCV) values, however, GCV values were closely aligned with PCV values across the traits. Notably, a robust positive correlation existed between yield and both single fruit weight and the weight of fruit per plant. The outcomes of this study, i.e., the promising genotypes AVPP 1111, Indch 39, A1511050 etc.; grouping; and significant positive correlations of different traits with grain yield, hold valuable insights for future chili improvement initiatives.
Bangladesh J. Agri. 2024, 49(1): 95-105
Curling Sporcularında Antrenöre Güven, Motivasyon ve Kaygı İlişkisi
Authors: Karababa Burak , Kurudirek Alparslan
Published: July 2024

Bu çalışmanın amacı, curling sporcularında antrenöre güven, motivasyon ve kaygı ilişkisinin incelenmesidir. Çalışmaya, 106 erkek, 113 kadın olmak üzere toplam 219 curling sporcusu katılmıştır. Bu çalışmada verileri toplamak için 4 bölümden oluşan anket formundan yararlanılmıştır. Belirtilen anket formuna ait ilk bölümde kişisel bilgi formu, ikinci bölümde “antrenörlere güven ölçeği” kullanılmıştır. Ölçeğin Cronbach’s alpha değeri ,97 olarak tespit edilmiştir. Anket formunun üçüncü bölümünde “sporda güdülenme ölçeği-II” kullanılmıştır. Ölçeğin Cronbach’s alpha değeri ,79 olarak tespit edilmiştir. Anket formunun dördüncü bölümünde “Sürekli Kaygı Ölçeği”nden yararlanılmıştır. Ölçegin Cronbach’s alpha değeri ,88 olarak tespit edilmiştir. Verilerin homojen dağılıma sahip olmaları nedeniyle parametrik istatistik yöntemlerinden yararlanılmıştır. Katılımcıların antrenöre güven, motivasyon ve kaygı düzeyleri arasındaki yordayıcı etkiyi ortaya koymak için korelasyon ve regresyon analizi yapılmıştır. Çalışmada veriler %95 güven aralığında işlenmiştir. Yapılan korelasyon analizi sonucunda katılımcıların antrenöre güven ve motivasyon düzeyleri arasında istatistiksel olarak anlamlı, pozitif yönlü ve orta düzeyde; antrenöre güven ve kaygı düzeyleri arasında istatistiksel olarak anlamlı, negatif yönlü ve düşük düzeyde korelasyon ilişkisi olduğu saptanmıştır. Buna göre katılımcıların antrenöre güven düzeyleri arttıkça motivasyonları artmaktadır ve katılımcıların antrenöre güven düzeyleri arttıkça kaygı düzeyleri azalmaktadır. Katılımcıların yaş değişkenine göre antrenöre güven, motivasyon ve kaygı ortalamalarının karşılaştırılması sonucunda kaygı alt boyutunda 18 ve altı, 24 ve üzeri yaş grubuna sahip olan katılımcıların 19-23 yaş aralığında olan katılımcılara göre istatistiksel olarak anlamlı düzeyde yüksek ortalamalara sahip oldukları görülmektedir. Bu çalışma doktora tezinden üretilmiştir.
Knowledge of independent events by prospective primary school teachers
Authors: Fernandes José António
Published: July 2024

In this quantitative study, prospective primary school teachers’ knowledge of independent events is investigated based on three objectives: 1) classify two given events as independent or non-independent; 2) state the definition of independent events; and 3) formulate examples of independent events. The study included 37 students attending the 2nd year of the teaching degree in basic education at a university in the north of Portugal, who solved a task about independent events. In terms of results, it should be noted that the students revealed difficulties in all objectives, more pronounced in the formulation of examples of independent events and less in the definition of independent events. Therefore, it can be inferred that many students, despite knowing the definition of independent events, could not apply this knowledge to distinguish independent events from non-independent events and formulate examples of independent events.
MiR-539-3p Alleviates Apoptosis and Extracellular Matrix Degradation in Chondrocytes of Childhood-Onset Osteoarthritis by Targeting RUNX2
Authors: Jin T , Zheng H , Feng X , Wu T , Yang K , Huang Y
Published: July 2024

Recent research has identified that miR-539-3p impedes chondrogenic differentiation, yet its specific role and underlying mechanisms in childhood-onset osteoarthritis (OA) remain unclear. This study found that miR-539-3p levels were considerably lower in cartilage samples derived from childhood-onset OA patients compared to the control group. Enhancing miR-539-3p expression or suppressing RUNX2 expression notably reduced apoptosis, inflammation, and extracellular matrix (ECM) degradation in OA chondrocytes. In contrast, reducing miR-539-3p or increasing RUNX2 had the opposite effects. RUNX2 was confirmed as a direct target of miR-539-3p. Further experiments demonstrated that miR-539-3p targeting RUNX2 effectively lessened apoptosis, inflammation, and ECM degradation in OA chondrocytes, accompanied by changes in key molecular markers like reduced caspase-3 and matrix metallopeptidase 13 (MMP-13) levels, and increased B-cell lymphoma 2 (Bcl-2) and collagen type X alpha 1 chain (COL2A1). This study underscores the pivotal role of miR-539-3p in alleviating inflammation and ECM degradation in childhood-onset OA through targeting RUNX2, offering new insights for potential therapeutic strategies against this disease.
A tízfilléres sátán
Authors: Domokos Áron
Published: July 2024

Egyes adatok szerint a negyvenes évek elejére a pengős regények havonta 200.000, az ötvenfilléresek 150.000, a húszfilléresek 1.200.000, a tízfilléres füzetek pedig 2.000.000 példányban jelentek meg. Ha a két világháború közötti, ill. a negyvenes évekbeli ponyva világát („a ponyva aranykorát”) vizsgáljuk, több szempontból érdemes hozzáállni a munkához. Az intézményi struktúrák szintje mellett (kiadók, stratégiák, sorozatok), az állam kontra piac viszonylatára („kultúrharc”: szabályozások, rendeletek), a nyilvánosság diskurzusrendjeire (viták a ponyváról), a műfajokra (vadnyugati, légiós, feltalálós, ifjúsági, fantasztikus stb.) és befogadóik szempontjaira is tekintettel kell lenni. Tanulmányomban az 1935 és 1942 között, kéthetente megjelenő, tíz fillérért árult, több mint 200 címet közlő Friss Újság Színes Regénytára sorozatát mutatom be úgy, hogy közben a sorozatot kiadó Friss Újság napilapot és a korabeli konkurens ponyvákat is szem előtt tartom. Célom, hogy egy ponyvaelméleti-rendszer alapjait lefektetve kimutassam a háborús légkör hatásait a Friss Újság-ponyvákra.
Healthy Livers, Healthy Lives
Authors: Zurowska Aleksandra
Published: July 2024

NON-COMMUNICABLE diseases (NCD) represent a major global health challenge, with significant mortality and morbidity. Among these, metabolic-associated steatotic liver disease (MASLD) and its more severe form, metabolic-associated steatohepatitis (MASH), have emerged as critical, but often under-recognised, public health threats. At this year’s European Association for the Study of the Liver (EASL) Congress, experts delivered insightful presentations on the topic.
Multidisciplinary management of type 2 inflammation diseases using a screening tool
Authors: Palomares Oscar , Cisneros Carolina , Ortiz de Frutos Francisco Javier , Villacampa José Miguel , Dávila Ignacio
Published: July 2024

Dysregulation of type 2 (T2) immune response leads to an aberrant inflammatory reaction that constitutes the pathophysiological basis of diseases involving various organs. For this reason, several disorders can coexist in a single patient; however, as different specialists often treat these pathologies, T2 dysregulation, particularly when mild, is not always the first diagnostic suspicion. A breakdown in interdisciplinary communication or the lack of adequate tools to detect these entities can delay diagnosis, and this, together with a lack of coordination, can lead to suboptimal care. In this context, a multidisciplinary group of specialists in pneumology, immunology, allergology, dermatology and otorhinolaryngology compiled a list of the cardinal symptoms reported by patients presenting with T2 inflammation-related diseases: asthma, chronic rhinosinusitis, allergic rhinitis, allergic conjunctivitis, IgE-mediated food allergy, atopic dermatitis, eosinophilic oesophagitis, and NSAID-exacerbated respiratory disease (NERD). Using this information, we propose a simple, patient-friendly questionnaire that can be administered at any level of care to initially screen patients for suspected coexisting T2 diseases and referral to the appropriate specialist.
This time with feeling: recommendations for full-bodied reporting of research on dance
Authors: Barnstaple Rebecca Elizabeth , Laurita-Spanglet Jessie , Fanning Jason , Soriano Christina , Hugenschmidt Christina E.
Published: July 2024

Collaborations that employ methods from arts and sciences to address research questions through multimodal study design are becoming more frequent, as it is increasingly apparent that complex challenges require transdisciplinary solutions. These different modalities rely on interdisciplinary exchange while involving unique expertise in associated delivery practices. In human subject driven scientific research specifically, guidelines for arts-based interventions deserve detailed reporting to allow for fidelity, replicability, and uptake of innovation and results. Details such as frequency, duration, delivery method, expected outcomes, historical precedence, and instructor training are crucial, along with nuanced descriptions pertaining to embodied aspects of specific dance or movement style(s) and adaptations made for the population or study design. This Perspective Paper outlines the current state and challenges of reporting on dance interventions and makes recommendations based on our experience as teaching artists who work in research settings alongside researchers who collaborate with dance professionals.
Value of the triglyceride–glucose index and related parameters in heart failure patients
Authors: Fang Yunteng , Shen Jiayi , Lyu Lingchun
Published: July 2024

The triglyceride–glucose (TyG) index, proven to be a crucial insulin resistance biomarker (better than the Homeostasis Model Assessment for Insulin Resistance), is simple and non-invasive. Recently, indisputable evidence has shown that the TyG index is strongly associated with cardiovascular disease [CVD, including atherosclerosis, heart failure (HF), and hypertension] prognosis and mortality. Nevertheless, the value of the TyG index in HF patients treated with sodium–glucose cotransporter 2 inhibitors (SGLT2is) has not been systematically evaluated. Therefore, in this review, we summarized the value of the TyG index and its related parameters as markers of CVD, especially HF. Furthermore, we addressed the use of SGLT2is and GLP-1 receptor antagonists in HF patients. Finally, we summarized the mechanism of the “obesity paradox.”
Satellite-based re-examination of changes in terrestrial near-surface wind speed in the last 30 years
Authors: Zhang Wei , Zhang Lishui , Liu Jikai
Published: July 2024

Wind plays a crucial role in shaping climatic and environmental conditions; however, its spatial and temporal variabilities over land remain poorly understood. This study utilizes combined datasets from multiple satellite platforms to examine the spatial patterns and temporal trends of wind speed over land during the past 30 years (1988–2017). The results demonstrate a significantly increasing trend in global wind speed, with variations on both annual and monthly scales. Spatially, wind speeds are lower in low-latitude regions, particularly in the tropics. High wind speeds primarily occur in mid- to high-latitude regions, with the highest speeds observed in the Arctic. Temporally, wind speed trends are characterized by an increase in low-speed winds and decrease in high-speed winds. Overall, wind speed shows a significant correlation with temperature in the Amazon, northern Europe, and central Asia. Negative wind–temperature correlation is confined to small regions in central North America and northern Africa. The findings of this study help clarify wind trends, providing valuable insights for future research on global climate and environmental change.
Assessing changes in indicators of fish health measured between 1997 and 2019 relative to multiple natural and anthropogenic stressors in Canada’s oil sands region using spatio-temporal modeling
Authors: Arciszewski Tim J. , Ussery Erin. J. , Tetreault Gerald R. , Hicks Keegan A. , McMaster Mark E.
Published: July 2024

Industrial development in Canada’s oil sands region influences the ambient environment. Some of these influences, such as the atmospheric deposition of emitted particles and gases are well-established using chemical indicators, but the effects of this process on bioindicators examined in field studies are less well-supported. This study used an extensive dataset available from 1997 to 2019, spatio-temporal modeling (Integrated Nested Laplace Approximation), and data on industrial and non-industrial covariates, including deposition patterns estimated using HYSPLIT (Hybrid Single Particle Lagrangian Integrated Trajectory) to determine if changes in sentinel fishes collected in streams from Canada’s Oil Sands Region were associated with oil sands industrial activity. While accounting for background variables (e.g., precipitation), estimated deposition of particles emitted from mine fleets (e.g., Aurora North), in situ stacks (e.g., Primrose and Cold Lake), mine stacks (e.g., Kearl), mine dust (e.g., Horizon), road dust (e.g., Muskeg River mine), land disturbance in hydrologically-connected areas, and wildfires were all associated with at least one fish endpoint. While many individual industrial stressors were identified, a specific example in this analysis parallels other work: the potential influence of emissions from both Suncor’s powerhouse and dust emitted from Suncor’s petroleum coke pile may both negatively affect fish health. Comparisons of fitted values from models with the estimated industrial effects and with deposition rates set to zero suggested some negative (and persistent) influences of atmospheric deposition at some locations, such as the gonadosomatic index (GSI) in the lower Muskeg and Steepbank rivers. While there is evidence of some large differences at individual locations the mean GSI and body condition estimates have improved throughout the region since the beginning of these collections in the late 1990s potentially highlighting improved environmental performance at the facilities, widespread enrichment effects, or interactions of stressors. However, mean liver-somatic indices have also slightly increased but remain low. These results, coupled with others suggest the utility of spatio-temporal approaches to detect the influence and effects of oil sands development at both local and regional scales.
CAR-T lymphocyte-based cell therapies; mechanistic substantiation, applications and biosafety enhancement with suicide genes: new opportunities to melt side effects
Authors: Ercilla-Rodríguez Paula , Sánchez-Díez Marta , Alegría-Aravena Nicolás , Quiroz-Troncoso Josefa , Gavira-O'Neill Clara E. , González-Martos Raquel , Ramírez-Castillejo Carmen
Published: July 2024

Immunotherapy has made significant strides in cancer treatment with strategies like checkpoint blockade antibodies and adoptive T cell transfer. Chimeric antigen receptor T cells (CAR-T) have emerged as a promising approach to combine these strategies and overcome their limitations. This review explores CAR-T cells as a living drug for cancer treatment. CAR-T cells are genetically engineered immune cells designed to target and eliminate tumor cells by recognizing specific antigens. The study involves a comprehensive literature review on CAR-T cell technology, covering structure optimization, generations, manufacturing processes, and gene therapy strategies. It examines CAR-T therapy in haematologic cancers and solid tumors, highlighting challenges and proposing a suicide gene-based mechanism to enhance safety. The results show significant advancements in CAR-T technology, particularly in structure optimization and generation. The manufacturing process has improved for broader clinical application. However, a series of inherent challenges and side effects still need to be addressed. In conclusion, CAR-T cells hold great promise for cancer treatment, but ongoing research is crucial to improve efficacy and safety for oncology patients. The proposed suicide gene-based mechanism offers a potential solution to mitigate side effects including cytokine release syndrome (the most common toxic side effect of CAR-T therapy) and the associated neurotoxicity.
Ocular fundus changes and association with systemic conditions in systemic lupus erythematosus
Authors: Meng Lihui , Wang Yinhan , Yang Zhikun , Lin Shiqun , Wang Yuelin , Chen Huan , Zhao Xinyu , Chen Youxin
Published: July 2024

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs and systems. Ocular involvement is estimated to manifest in one-third of individuals with SLE, of which lupus retinopathy and choroidopathy represent the severe subtype accompanied by vision impairment. Advancements in multimodal ophthalmic imaging have allowed ophthalmologists to reveal subclinical microvascular and structural changes in fundus of patients with SLE without ocular manifestations. Both ocular manifestations and subclinical fundus damage have been shown to correlate with SLE disease activity and, in some patients, even precede other systemic injuries as the first presentation of SLE. Moreover, ocular fundus might serve as a window into the state of systemic vasculitis in patients with SLE. Given the similarities of the anatomy, physiological and pathological processes shared among ocular fundus, and other vital organ damage in SLE, such as kidney and brain, it is assumed that ocular fundus involvement has implications in the diagnosis and evaluation of other systemic impairments. Therefore, evaluating the fundus characteristics of patients with SLE not only contributes to the early diagnosis and intervention of potential vision damage, but also holds considerate significance for the evaluation of SLE vasculitis state and prediction of other systemic injuries.
Tetanus-diphtheria vaccine can prime SARS-CoV-2 cross-reactive T cells
Authors: Fernandez Sara Alonso , Pelaez-Prestel Hector F. , Fiyouzi Tara , Gomez-Perosanz Marta , Reiné Jesús , Reche Pedro A.
Published: July 2024

Vaccines containing tetanus-diphtheria antigens have been postulated to induce cross-reactive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which could protect against coronavirus disease (COVID-19). In this work, we investigated the capacity of Tetanus-diphtheria (Td) vaccine to prime existing T cell immunity to SARS-CoV-2. To that end, we first collected known SARS-CoV-2 specific CD8+ T cell epitopes targeted during the course of SARS-CoV-2 infection in humans and identified as potentially cross-reactive with Td vaccine those sharing similarity with tetanus-diphtheria vaccine antigens, as judged by Levenshtein edit distances (≤ 20% edits per epitope sequence). As a result, we selected 25 potentially cross-reactive SARS-CoV-2 specific CD8+ T cell epitopes with high population coverage that were assembled into a synthetic peptide pool (TDX pool). Using peripheral blood mononuclear cells, we first determined by intracellular IFNγ staining assays existing CD8+ T cell recall responses to the TDX pool and to other peptide pools, including overlapping peptide pools covering SARS-CoV-2 Spike protein and Nucleocapsid phosphoprotein (NP). In the studied subjects, CD8+ T cell recall responses to Spike and TDX peptide pools were dominant and comparable, while recall responses to NP peptide pool were less frequent and weaker. Subsequently, we studied responses to the same peptides using antigen-inexperienced naive T cells primed/stimulated in vitro with Td vaccine. Priming stimulations were carried out by co-culturing naive T cells with autologous irradiated peripheral mononuclear cells in the presence of Td vaccine, IL-2, IL-7 and IL-15. Interestingly, naive CD8+ T cells stimulated/primed with Td vaccine responded strongly and specifically to the TDX pool, not to other SARS-CoV-2 peptide pools. Finally, we show that Td-immunization of C57BL/6J mice elicited T cells cross-reactive with the TDX pool. Collectively, our findings support that tetanus-diphtheria vaccines can prime SARS-CoV-2 cross-reactive T cells and likely contribute to shape the T cell responses to the virus.
A future directions of renal cell carcinoma treatment: combination of immune checkpoint inhibition and carbon ion radiotherapy
Authors: Zheng Zhouhang , Yang Tianci , Li Yixuan , Qu Pei , Shao Zhiang , Wang Yuan , Chang Wei , Umar Shahzad Muhammad , Wang Jufang , Ding Nan , Wang Wei
Published: July 2024

Renal cell carcinoma (RCC) is considered radio- and chemo-resistant. Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical efficacy in advanced RCC. However, the overall response rate of RCC to monotherapy remains limited. Given its immunomodulatory effects, a combination of radiotherapy (RT) with immunotherapy is increasingly used for cancer treatment. Heavy ion radiotherapy, specifically the carbon ion radiotherapy (CIRT), represents an innovative approach to cancer treatment, offering superior physical and biological effectiveness compared to conventional photon radiotherapy and exhibiting obvious advantages in cancer treatment. The combination of CIRT and immunotherapy showed robust effectiveness in preclinical studies of various tumors, thus holds promise for overcoming radiation resistance of RCC and enhancing therapeutic outcomes. Here, we provide a comprehensive review on the biophysical effects of CIRT, the efficacy of combination treatment and the underlying mechanisms involved in, as well as its therapeutic potential specifically within RCC.
Approaches of wearable and implantable biosensor towards of developing in precision medicine
Authors: Ghazizadeh Elham , Naseri Zahra , Deigner Hans-Peter , Rahimi Hossein , Altintas Zeynep
Published: July 2024

In the relentless pursuit of precision medicine, the intersection of cutting-edge technology and healthcare has given rise to a transformative era. At the forefront of this revolution stands the burgeoning field of wearable and implantable biosensors, promising a paradigm shift in how we monitor, analyze, and tailor medical interventions. As these miniature marvels seamlessly integrate with the human body, they weave a tapestry of real-time health data, offering unprecedented insights into individual physiological landscapes. This log embarks on a journey into the realm of wearable and implantable biosensors, where the convergence of biology and technology heralds a new dawn in personalized healthcare. Here, we explore the intricate web of innovations, challenges, and the immense potential these bioelectronics sentinels hold in sculpting the future of precision medicine.
GABAA receptors and neuroligin 2 synergize to promote synaptic adhesion and inhibitory synaptogenesis
Authors: Sui Yusheng , Mortensen Martin , Yuan Banghao , Nicholson Martin W. , Smart Trevor G. , Jovanovic Jasmina N.
Published: July 2024

GABAA receptors (γ-aminobutyric acid-gated receptors type A; GABAARs), the major structural and functional postsynaptic components of inhibitory synapses in the mammalian brain, belong to a family of GABA-gated Cl−/HCO3− ion channels. They are assembled as heteropentamers from a family of subunits including: α (1–6), β(1–3), γ(1–3), δ, ε, π, θ and ρ(1–3). GABAARs together with the postsynaptic adhesion protein Neuroligin 2 (NL2) and many other pre- and post-synaptic proteins guide the initiation and functional maturation of inhibitory GABAergic synapses. This study examined how GABAARs and NL2 interact with each other to initiate the formation of synapses. Two functionally distinct GABAAR subtypes, the synaptic type α2β2γ2-GABAARs versus extrasynaptic type α4β3δ-GABAARs were expressed in HEK293 cells alone or together with NL2 and co-cultured with striatal GABAergic medium spiny neurons to enable innervation of HEK293 cells by GABAergic axons. When expressed alone, only the synaptic α2β2γ2-GABAARs induced innervation of HEK293 cells. However, when GABAARs were co-expressed with NL2, the effect on synapse formation exceeded the individual effects of these proteins indicating a synergistic interaction, with α2β2γ2-GABAAR/NL2 showing a significantly greater synaptogenic activity than α4β3δ-GABAAR/NL2 or NL2 alone. To investigate the molecular basis of this interaction, different combinations of GABAAR subunits and NL2 were co-expressed, and the degree of innervation and synaptic activity assessed, revealing a key role of the γ2 subunit. In biochemical assays, the interaction between NL2 and α2β2γ2-GABAAR was established and mapped to the large intracellular domain of the γ2 subunit.
Stress and the gut-brain axis: an inflammatory perspective
Authors: Morys Julia , Małecki Andrzej , Nowacka-Chmielewska Marta
Published: July 2024

The gut-brain axis (GBA) plays a dominant role in maintaining homeostasis as well as contributes to mental health maintenance. The pathways that underpin the axis expand from macroscopic interactions with the nervous system, to the molecular signals that include microbial metabolites, tight junction protein expression, or cytokines released during inflammation. The dysfunctional GBA has been repeatedly linked to the occurrence of anxiety- and depressive-like behaviors development. The importance of the inflammatory aspects of the altered GBA has recently been highlighted in the literature. Here we summarize current reports on GBA signaling which involves the immune response within the intestinal and blood-brain barrier (BBB). We also emphasize the effect of stress response on altering barriers' permeability, and the therapeutic potential of microbiota restoration by probiotic administration or microbiota transplantation, based on the latest animal studies. Most research performed on various stress models showed an association between anxiety- and depressive-like behaviors, dysbiosis of gut microbiota, and disruption of intestinal permeability with simultaneous changes in BBB integrity. It could be postulated that under stress conditions impaired communication across BBB may therefore represent a significant mechanism allowing the gut microbiota to affect brain functions.
Calcium-dependent activator protein for secretion 2 is involved in dopamine release in mouse midbrain neurons
Authors: Iguchi Hirotoshi , Katsuzawa Takumi , Saruta Chihiro , Sadakata Tetsushi , Kobayashi Shota , Sato Yumi , Sato Akira , Sano Yoshitake , Maezawa So , Shinoda Yo , Furuichi Teiichi
Published: July 2024

The Ca2+-dependent activator protein for secretion (CAPS/CADPS) family protein facilitates catecholamine release through the dense-core vesicle exocytosis in model neuroendocrine cell lines. However, it remains unclear if it induces dopamine release in the central neurons. This study aimed to examine the expression and function of CADPS2, one of the two CADPS paralogs, in dopamine neurons of the mouse midbrain. This study shows that CADPS2 was expressed in tyrosine hydroxylase and the vesicular monoamine transporter 2 (VMAT2)-positive dopaminergic neurons of the midbrain samples and primary mesencephalic cell cultures. Subcellular fractions rich in dopamine were collected using immunoaffinity for CADPS2 from midbrain protein extracts. Cell imaging using fluorescent false neurotransmitter FFN511 as a substrate for VMAT2 showed decreased activity-dependent dopamine release in Cadps2-deficient cultures, compared to that in wild-type cultures. These results suggest that CADPS2 is involved in dopamine release from the central neurons, indicating its involvement in the central dopamine pathway.
WP15 ConCorD state-of-the-art report (container corrosion under disposal conditions)
Authors: Muñoz Andrés G. , Abdelouas Abdesselam , Alonso Ursula , Fernández Ana María , Bernier-Latmani Rizlan , Cherkouk Andrea , Gaggiano Roberto , Hesketh James , Smart Nick , Padovani Cristiano , Mijnendonckx Kristel , Montoya Vanessa , Idiart Andrés , Pont Arnau , Riba Olga , Finck Nicolas , Singh Ashutosh R. , King Fraser , Diomidis Nikitas
Published: July 2024

A sealed container for the geological disposal of spent nuclear fuel and vitrified high-level waste is the only component of a deep geological repository that provides complete containment of radionuclides. As such, attention is focused on its lifetime. The lifetime of the container is influenced by material degradation processes during disposal and is typically of the order of several millennia and, for some container materials, up to one million years. Designing, manufacturing, and predicting the performance of containers over such long periods requires an in-depth understanding of their material properties, fabrication processes, and degradation mechanisms. Scientific and technological progress can improve both the performance of containers and the robustness of lifetime predictions. Optimization of these aspects is of primary importance for many national radioactive waste disposal programs. In this article, the state of the art of complex coupled degradation processes, as well as the optimization potential of novel container materials, is presented. Furthermore, the existing tools allowing the prediction of long-term barrier integrity are discussed.
A fine-tuned vision transformer based enhanced multi-class brain tumor classification using MRI scan imagery
Authors: Reddy C. Kishor Kumar , Reddy Pulakurthi Anaghaa , Janapati Himaja , Assiri Basem , Shuaib Mohammed , Alam Shadab , Sheneamer Abdullah
Published: July 2024

Brain tumors occur due to the expansion of abnormal cell tissues and can be malignant (cancerous) or benign (not cancerous). Numerous factors such as the position, size, and progression rate are considered while detecting and diagnosing brain tumors. Detecting brain tumors in their initial phases is vital for diagnosis where MRI (magnetic resonance imaging) scans play an important role. Over the years, deep learning models have been extensively used for medical image processing. The current study primarily investigates the novel Fine-Tuned Vision Transformer models (FTVTs)—FTVT-b16, FTVT-b32, FTVT-l16, FTVT-l32—for brain tumor classification, while also comparing them with other established deep learning models such as ResNet50, MobileNet-V2, and EfficientNet - B0. A dataset with 7,023 images (MRI scans) categorized into four different classes, namely, glioma, meningioma, pituitary, and no tumor are used for classification. Further, the study presents a comparative analysis of these models including their accuracies and other evaluation metrics including recall, precision, and F1-score across each class. The deep learning models ResNet-50, EfficientNet-B0, and MobileNet-V2 obtained an accuracy of 96.5%, 95.1%, and 94.9%, respectively. Among all the FTVT models, FTVT-l16 model achieved a remarkable accuracy of 98.70% whereas other FTVT models FTVT-b16, FTVT-b32, and FTVT-132 achieved an accuracy of 98.09%, 96.87%, 98.62%, respectively, hence proving the efficacy and robustness of FTVT’s in medical image processing.
The role of immune checkpoint inhibitors in the first-line treatment for patients with advanced biliary tract cancer: a systematic review and meta-analysis of randomized trials
Authors: Vitale Elsa , Rizzo Alessandro , Maistrello Lorenza , Nardulli Patrizia , Talienti Tiziana , Quaresmini Davide , De Summa Simona , Massafra Raffaella , Silvestris Nicola , Brunetti Oronzo
Published: July 2024

Background

We performed a systematic review and meta-analysis to further explore the impact of the addition of immunotherapy to gemcitabine–cisplatin as first-line treatment for advanced biliary tract cancer (BTC) patients.

Methods

Literature research was performed, and hazard ratio values and 95% confidence intervals were calculated. Heterogeneity among studies was assessed using the tau-squared estimator (τ2). The total Cochrane Q test (Q) was also assessed. The overall survival rate, objective response rate, and progression-free survival in the selected studies were assessed.

Results

A total of 1,754 participants were included. Heterogeneity among the studies selected was found to be non-significant (p = 0.78; tau2 = 0, I2 = 0%). The model estimation results and the forest plot suggested that the test for the overall effect was significant (Z = −3.51; p< 0.01).

Conclusion

The results of the current meta-analysis further confirm the role of immune checkpoint inhibitors plus gemcitabine–cisplatin as the new standard first-line treatment for advanced BTC patients.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier CRD42023488095.
Uptake of evidence-based practice and its predictors among nurses in Ethiopia: a systematic review and meta-analysis
Authors: Wudu Muluken Amare , Tarekegn Setegn Mihret , Wondifraw Endalk Birrie , Birhanu Tarikua Afework , Hailu Molla Kassa , Bekalu Yemane Eshetu , Yosef Selamyhun Tadesse , Belete Melaku Ashagrie
Published: July 2024

Background: While evidence-based practice has demonstrated its capacity to enhance healthcare quality and bolster clinical outcomes, the translation of research into clinical practice encounters persistent challenges. In Ethiopia, there remains a dearth of comprehensive and nationally representative data concerning the extent of Evidence-based practice adoption among nurses. Thus, this systematic review and meta-analysis endeavors to assess the overall prevalence of Evidence-based practice implementation and delve into its determinants among Ethiopian nurses.

Methods: A systematic review and meta-analysis were conducted following the PRISMA guidelines. In order to identify pertinent studies, a search was conducted across PubMed, Scopus, Google Scholar, and EMBASE databases. A weighted inverse variance random-effects model was employed to estimate the pooled prevalence. Cochrane’s Q-test and I2 statistics were calculated to assess heterogeneity among studies. Funnel plots and Egger’s test were utilized to evaluate publication bias. Pooled implementation rates and meta-regression analysis were carried out using STATA 17.

Results: Of the total 1,590 retrieved articles, twelve studies including 4,933 nurses were included in the final analysis. The pooled prevalence of Evidence-based practice uptake among nurses in Ethiopia is 53% (95% CI: 46%–60%). Having knowledge about Evidence-based practice (AOR = 2.29; 95% CI: 1.90, 2.69; I2 = 70.95%), holding a favorable attitude towards Evidence-based practice (AOR = 2.56; 95% CI: 1.63, 3.49; I2 = 88.39%), occupying a head nurse position (AOR = 3.15; 95% CI: 1.85, 4.46; I2 = 87.42%), possessing effective communication skills (AOR = 4.99; 95% CI: 1.47, 8.51; I2 = 99.86%), and having access to Evidence-based practice guidelines (AOR = 1.90; 95% CI: 1.55, 2.24; I2 = 57.24%) were identified as predictors of the uptake of Evidence-based practice.

Conclusion: Only half of Ethiopia’s nurses exhibit a strong embrace of Evidence-Based Practice within clinical settings, underscoring the urgent necessity for coordinated endeavors to cultivate this essential practice. Possessing knowledge, effective communication skills, access to updated guidelines, maintaining a positive attitude towards Evidence-Based Practice, and holding a position as head nurse emerged as predictors of successful implementation of Evidence-Based Practice. Hence, policymakers must prioritize capacity-building initiatives, disseminate the latest EBP guidelines widely, and strengthen mentorship roles for head nurses.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/#searchadvanced, identifier CRD42023488943
Sargassum pallidum reduces inflammation to exert antidepressant effect by regulating intestinal microbiome and ERK1/2/P38 signaling pathway
Authors: Su Dan , Li Qianmin , Lai Xin , Song Yonggui , Li Huizhen , Ai Zhifu , Zhang Qi , Shao Wenxiang , Yang Ming , Zhu Genhua
Published: July 2024

Immune inflammation is one of the main factors in the pathogenesis of depression. It is an effective and active way to find more safe and effective anti-inflammatory depressant drugs from plant drugs. The purpose of this study is to explore the potential of marine plant Sargassum pallidum (Turn).C.Ag. (Haihaozi, HHZ) in the prevention and treatment of depression and to explain the related mechanism. Phytochemical analysis showed that alkaloids, terpenes, and organic acids are the main constituents. In vitro and in vivo activity studies showed the anti-neuroinflammatory and antidepressant effect of Sargassum pallidum, furthermore, confirmed that 7-Hydroxycoumarin, Scoparone, and Kaurenoic Acid are important plant metabolites in Sargasum pallidum for anti-neuroinflammation. Mechanism exploration showed that inhibition of ERK1/2/p38 inflammatory signaling pathway contributing to the antidepressant effect of Sargassum pallidum in reducing intestinal inflammatory levels. This study confirmed the value of Sargassum pallidum and its rich plant metabolites in anti-inflammatory depression, providing a new choice for the follow-up research and development of antidepressant drugs.
A standardized Boswellia serrata extract shows improvements in knee osteoarthritis within five days-a double-blind, randomized, three-arm, parallel-group, multi-center, placebo-controlled trial
Authors: Majeed Anju , Majeed Shaheen , Satish G. , Manjunatha R. , Rabbani Shaikh Nawazish , Patil Neelanagowda V. P. , Mundkur Lakshmi
Published: July 2024

Background

Boswellin® Super is a standardized extract of Boswellia serrata Roxb gum resin, standardized to contain 30% 3-acetyl-11-keto-β-boswellic acid along with other β-boswellic acids (BSE). A randomized, double-blind, placebo-controlled clinical trial was conducted at two doses of BSE to understand its safety and efficacy in supporting joint health and improving mobility and symptoms of osteoarthritis (OA) of the knee.

Methods

Based on the inclusion/exclusion criteria, 105 newly diagnosed participants with degenerative hypertrophy OA were recruited and randomized into Placebo, BSE-150 mg or BSE-300 mg (n = 35 in each group) to receive either 150 mg or 300 mg BSE or a placebo tablet twice a day for 90 days. All the participants were evaluated for pain and physical function using the standard tools including the Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne Functional Index (LFI), EuroQol- 5 Dimension (EQ-5D) quality of life, 6-min walk test at day 0, days 5, 30, 60 and 90 of treatment. Additionally, the circulating levels of inflammatory biomarkers, tumor necrosis factor-α (TNFα), high-sensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were evaluated. Safety was evaluated by blood biochemical, hematological analysis, urinary analyses and by monitoring adverse events throughout the study.

Results

Ninety-eight subjects completed the study. Improvements in pain scores were observed as early as 5 days after the start of the supplement in the BSE-150 and BSE-300 groups. By 90 days, the VAS pain score reduced by 45.3% and 61.9%, WOMAC- total score improved by 68.5% and 73.6% in the BSE-150 and BSE-300 groups respectively. WOMAC pain (70.2%, 73.9%, WOMAC stiffness (65.6%,68.9%), WOMAC function (68.8%,74.2%), LFI severity (50%,53.3%), decreased and EQ5D (56.9%, 62.9%) and distance walked in 6 minutes (21.2%, 21.9%) improved in the BSE-150 and BSE-300 groups in 90 days. Further, the levels of TNFα, hs-CRP, and IL-6 were found to decrease in the serum in BSE-supplemented participants. No significant adverse events were recorded during the study.

Conclusion

The study confirms that Boswellin® Super can be used as a safe and effective supplement to support joint health and mobility in the management of osteoarthritis.

Clinical Trial Registration:

https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NzU2Nzc=&Enc=&userName=CTRI, identifier CTRI/2022/11/047397