bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-omic Analysis of Human B-cell Activation Reveals a Key Lysosomal BCAT1 Role in mTOR Hyperactivation by B-cell receptor and TLR9
Authors: Guo Rui , Lim Matthew , Shah Hardik , Paulo Joao , Zhang Yuchen , Yang Haopeng , Wang Liang Wei , Strebinger Daniel , Smith Nicolas , Li Meng , Leong Merrin , Lutchenkov Michael , Liang Jin-Hua , Li Zhixuan , Wang Yin , Puri Rishi , Melnick Ari , Green Michael , Asara John , Papathanassiu Adonia , Gygi Steven , Mootha Vamsi , Gewurz Benjamin
Published: May 2024

B-lymphocytes play major adaptive immune roles, producing antibody and driving T-cell responses. However, how immunometabolism networks support B-cell activation and differentiation in response to distinct receptor stimuli remains incompletely understood. To gain insights, we systematically investigated acute primary human B-cell transcriptional, translational and metabolomic responses to B-cell receptor (BCR), Toll-like receptor 9 (TLR9), CD40-ligand (CD40L), interleukin-4 (IL4) or combinations thereof. T-independent BCR/TLR9 co-stimulation, which drives malignant and autoimmune B-cell states, jointly induced PD-L1 plasma membrane expression, supported by NAD metabolism and oxidative phosphorylation. BCR/TLR9 also highly induced the transaminase BCAT1, which localized to lysosomal membranes to support branched chain amino acid synthesis and mTORC1 hyperactivation. BCAT1 inhibition blunted BCR/TLR9, but not CD40L/IL4-triggered B-cell proliferation, IL10 expression and BCR/TLR pathway-driven lymphoma xenograft outgrowth. These results provide a valuable resource, reveal receptor-mediated immunometabolism remodeling to support key B-cell phenotypes including PD-L1 checkpoint signaling, and identify BCAT1 as a novel B-cell therapeutic target.
Behavioural patterns of Octopus tetricus (Mollusca: Cephalopoda) and their responses to fisheries trap and bait combinations
Authors: Vrandich Adam Anthony , Kelaher Brendan P , Hall Karina
Published: May 2024

Octopus fisheries are expanding globally. However, given their complex behavioural repertoires, cognitive capacities and individual personalities among octopuses, careful consideration of their interactions with and capture by fishing gears is required to inform efficient, sustainable, and ethical fisheries development. Here, the behaviour of Octopus tetricus was assessed in response to different bait and trap combinations in an outdoor mesocosm experiment. Eight wild octopuses were collected, maintained in individual tanks with flow-through seawater and aeration, and monitored with a 24-h video surveillance system. Six different trap types and four different baits were presented to each octopus in various combinations during four sequential trials. Fine-mesh crab traps were the most successful in capturing octopus, accounting for 23 of the total 30 captures across all trials. Whereas solid trigger traps produced the greatest number of other interactions (e.g., octopus sitting on trap or in the entrance), averaging 43 interactions per trial, but were rarely triggered. Bait type did not influence octopus capture, trap interaction frequency, or octopus activity. Octopus were generally inactive, dedicating only 9.5% of their total time to active behaviours. Octopus activity varied with time of day, with peak activity during morning daylight (0800–1200) and the lowest activity during the dark hours of the very early morning (0000–0400). Additionally, capture numbers, trap interactions, and activity varied among individuals, with bolder personalities in some octopus. This natural variation among individual octopuses may lead to fishery-induced selection associated with the elevated capture frequency of bold or more active individuals.
Perceptions of sedentary behaviour in people with severe asthma: A qualitative study
Authors: Guerrero Paola D Urroz , Gibson Peter G , Lewthwaite Hayley , Majellano Eleanor , Hiles Sarah A , McDonald Vanessa M
Published: May 2024

People with severe asthma often lead sedentary lifestyles, which adversely affects overall health and asthma-specific outcomes. To inform future sedentary behaviour- interventions, this study aimed to explore perceptions of sedentary behaviour among people with severe asthma. Adults (≥ 18 years) with severe asthma (n = 21) participated in face-to-face interviews. Participants were asked open-ended questions about factors influencing their sitting behaviour. A thematic analysis was conducted on phrases and sentences relevant to sedentary behaviour. Participants were predominantly females (62%), with controlled asthma (median [Q1, Q3]: ACQ6 0.5 [0.2,1.8]) and receiving monoclonal antibody therapy (71%). Participants were inactive (19.1 [11.3, 44.5] minutes of MVPA per day) and sedentary (10.8 [9.7, 11.4] hours of sedentary behaviour per day). The analysis generated four main themes: (1) Sedentary behaviour often stems from habits and routines, (2) Asthma and associated health issues contribute to sedentary behaviour, (3) Participants' responsibilities influence their activity levels, and; (4) Participants’ conscious balance between being physically active and sedentary. The results of this qualitative study offers insights into the perspectives of people with severe asthma regarding sedentary behaviour, highlighting the identification of strategies that can be implemented to optimise sedentary behaviour in this population.
Huajieling virus: A newly discovered member of the Caliciviridae family from mosquito, China
Authors: zhu wenbing , Chen Jiahao , Lu Ke , Sun Hengyi , Niu Guoyu
Published: May 2024

Mosquito associated virus have always been a significant threat to global health. Metagenomics offers a straightforward and quantitative means to acquire the information of novel virus and has greatly enriched the content of mosquito associated virus databases. During an entomological surveillance for arthropod-borne viruses in China, we identified a previously unrecognized virus from mosquitoes, temporarily named Huajieling virus. In this study, a total of 3,960 mosquitoes were collected and then divided into 91 pools, according to location and species. QRT-PCR and nested PCR were performed to confirm the presence of Huajieling virus. Its genomic features and phylogenetic relationships were further analyzed. Our results showed that Huajieling virus was detected in 7 of the 91 mosquito pools and that the minimum infection rate (MIR) was 0.18% (7/3,960). One complete genome sequence and 2 viral partial sequences were obtained from the Huajieling virus-positive pools. Pairwise distances analysis indicated that these amplified sequences shared high nucleotide identity. Phylogenetic analysis demonstrated that Huajieling virus is most closely related to Wufeng shrew picorna like virus 43, which belonging to Caliciviridae. Further analyses indicated that Huajieling virus is a new member of unclassified Caliciviridae.
Assessment of the Efficacy and Safety of Baricitinib Treatment in COVID-19 Patients: a real-world study
Authors: Cheng Mengyu , Zhang Junyan , Xue Zhifeng , Li Jian , Pang Zhigang , Wang Ruiying , Wang Lei , Li Ping , Kurts Christian , Wei Jia , Mei Qi , Wei Shuang , Liu Xiansheng
Published: May 2024

Backgroud
This retrospective cohort study assessed the real-world effectiveness and safety of Baricitinib (BAR) in hospitalized adult patients with severe or critical COVID-19 infection.
Methods
Utilizing real-world data. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to address imbalances in baseline characteristics. The Cox regression model was employed to assess the hazard ratio of treatment efficacy, utilizing both unmatched and matched datasets. The primary outcome focused on all-cause mortality among hospitalized patients.
Results
Among initially screened 2,731 adults with COVID-19 infection, 2,454 were included in this analysis (2,312 non-BAR, 142 BAR). In total, there were 39 deaths, with 36 occurring in the non-BAR group and 3 in the BAR group. Multivariable Cox regression analysis demonstrated that BAR was associated with a lower risk of all-cause mortality (hazard ratio [HR] = 0.24, 95% confidence interval [CI] 0.07–0.83, p < 0.024). Analysis based on the PSM datasets consistently showed that BAR reduced the risk of all-cause mortality in 1:1 (HR = 0.10, 95% CI 0.01–0.86), 1:2 (HR = 0.11, 95% CI 0.01–0.88, p = 0.038), and 1:3 (HR = 0.08, 95% CI 0.01–0.66) matched databases. Analysis based on the IPTW dataset also indicated that BAR reduced the risk of all-cause mortality (HR = 0.06, 95% CI 0.01–0.41, p = 0.004). The incidence of Venous Thrombosis Events (VTE) was higher in the BAR group compared to the non-BAR group (11.27% vs. 6.14%, p = 0.016).
Conclusions
BAR demonstrated effectiveness in reducing all-cause mortality in hospitalized COVID-19 patients, with an acceptable safety profile.
The indication of palliative whole-brain radiotherapy for patients with brain metastases: A simple prognostic scoring system in the era of stereotactic radiosurgery
Authors: Hirose Toshiaki , Deguchi Shoichi , Yasui Kazuaki , Inoue Minoru , Onoe Tsuyoshi , Ogawa Hirofumi , Asakura Hirofumi , Mitsuya Koichi , Harada Hideyuki , Murayama Shigeyuki , Hayashi Nakamasa , Nishimura Tetsuo , Saito Ryuta
Published: May 2024

Background: Stereotactic irradiation has become the mainstay treatment for brain metastases (BM), and whole-brain radiotherapy (WBRT) is often used for symptom palliation. However, the survival time of patients with BM undergoing palliative WBRT (pWBRT) is limited, making it difficult to select patients who should receive treatment.
Methods:We collected patient data from 2016 to 2022 at the Shizuoka Cancer Center and retrospectively analyzed the factors related to survival time. Overall survival (OS) was defined as the survival time after WBRT.
Results:A total of 322 patients (median age, 66 years) who underwent pWBRT were included. The primary cancers were lung, breast, gastrointestinal tract, and other cancers in 210 (65%), 46 (14%), 38 (12%), and 28 (9%) patients, respectively. Median OS of all patients was 4.0 months. In the multivariate analysis, male sex (hazard ratio [HR]:1.4), Karnofsky Performance Status (KPS) ≤60 (HR:1.7), presence of extracranial metastasis (ECM) (HR:1.6), neutrophil-lymphocyte ratio (NLR) ≥5 (HR:1.6), and albumin <3.5 g/dl (HR:1.4) were significantly associated with shorter OS (all P<0.05). To predict the OS, we created a prognostic scoring system (PSS). We gave one point to each independent prognostic factor. Patients with scores of 0–2 showed a significantly better survival than those with scores of 3–5 (median OS, 7.4 vs. 2.1 months, P<0.01).
Conclusions:Male sex, KPS ≤60, presence of ECM, NLR ≥5, and albumin <3.5 g/dl were poor prognostic factors for patients with BM undergoing pWBRT. By PSS combining these factors, it may be possible to select patients who should undergo pWBRT.
Distribution Patterns of Ceracris kiangsu (Orthoptera ： Arcypteridae) Under Global Climate Change Scenarios - A Case Study of China and Southeast Asian Countries
Authors: Li ChuRui , Yue CaiRong , Duan YunFang , Liu Yu , Yang Song , Wang ZeMing , Chen Peng
Published: May 2024

Ceracris kiangsu (Orthoptera: Arcypteridae), is greatly affected by climatic factors and exhibits strong adaptability, posing a serious threat to the ecological environment. Therefore, predicting its potential suitable habitat distribution provides a proactive theoretical basis for pest control. This study using the Biomod2 package of R simulated and predicted the current and future potential distribution, area changes, changes in the center points of suitable habitats, and niche shifts of C. kiangsu under two different greenhouse gas emission scenarios, SSP1-26 and SSP5-85. The results show that: (1) Currently, the high suitability areas for C. kiangsu are mainly distributed in Yunnan, Jiangxi, Hunan provinces in southern China and phongsaly province in northern Laos. In the future, the center of the suitable habitat distribution pattern of C. kiangsu will remain unchanged, primarily expanding outward from medium and high suitability areas. Additionally, significant suitable habitats for C. kiangsu were discovered in Southeast Asian countries without previous pest records. (2) Compared to the present, the overall suitable habitat area for C. kiangsu is expected to expand, particularly under the SSP5-85 climate change scenario. (3) In the SSP1-26 and SSP5-85 climate scenarios, the geometric center of the suitable habitat generally shows a trend of gradually shifting northeast. (4) Under different climate scenarios, the suitable habitat of C. kiangsu has highly overlapping, indicating that the suitable habitat of C. kiangsu in the invaded areas is broader than in its native regions. In conclusion, the research findings represent a breakthrough in identifying the potential distribution areas of C. kiangsu, which is of great practical significance for the monitoring and control of C. kiangsu pest infestation in China and Southeast Asian countries.
Exploring the Deep Learning of Artificial Intelligence in Nursing: A Concept Analysis with Walker and Avant’s Approach
Authors: Wangpitipanit Supichaya , Lininger Jiraporn , Anderson Nick
Published: May 2024

Background: In recent years, increased attention has been given to the use ofartificial intelligence (AI) or artificial intelligence (AI) deep learning(DL) in healthcare to address nursing challenges. However, the adoption of new technologies in nursing needs to be improved, and AI in nursing is still in its early stages. However, the current literature needs more clarity, which affects clinical practice, research, and theory development. This study aimed to clarify the meaning of deep learning and identify the defining attributes of artificial intelligence within nursing.
Methods: We conducted a concept analysis of the deep learning of AI in nursing care using Walker and Avant's 8-step approach. Our search strategy employed Boolean techniques across databases, including BMC, CINAHL, ClinicalKey for Nursing, Embase, Google Scholar, Ovid, Scopus, SpringerLink, ProQuest, PubMed, and Web of Science. By focusing on relevant keywords in titles and abstracts from articles published between 2018 and 2024, we initially found 574 sources.
Results: Thirty-six articles that met the inclusion criteria were analyzed in this study. The attributes of evidence included four themes: focus and immersion, coding and understanding, arranging layers and algorithms, and implementing within the process of use cases to modify recommendations. Antecedents, unclear systems and communication, insufficient data management knowledge and support, and compound challenges can lead to suffering and risky caregiving tasks. The application of DL deep learning techniques enables nurses to simulate scenarios, predict outcomes, and plan care with greater precision. Embracing deep learning equipment allows nurses to makebetter decisions and empower them with enhanced knowledge, while ensuring adequate support and resources is essential for caregiver and patient well-being, and access to necessary equipment is vital for high-quality home healthcare.
Conclusion: This study provides a clearer understanding of the use of deep learning in nursing and its implications for nursing practice. Future research should focus on exploring the impact of deep learning on healthcare operations management through quantitative and qualitative studies. Additionally, the development of a framework to guide the integration of deep learning into nursing practice is recommended to facilitate its adoption and implementation.
The relationship between physical activity and general self-efficacy: a three-way interaction model
Authors: Liu Chong , Ding Zifan , Sun Zongchen , Chen Hanwen , Lu Tianci , Yan Jun
Published: May 2024

General self-efficacy is crucial for university students who are about to enter the workplace and society. However, the association between physical activity, a widely recognized and convenient way to promote various psychological qualities, and general self-efficacy or other aspects of self-efficacy is often overlooked. Through psychological measurements of 480 university students, this study found that social comparison orientation and perceived social support jointly moderate the impact of physical activity on general self-efficacy among university students. Specifically, under conditions of high social comparison orientation and high levels of perceived social support, physical activity has a significant predictive effect on individuals' general self-efficacy. These findings suggest that universities and social institutions should pay attention to the importance of physical activity for university students' general self-efficacy. By encouraging their participation in physical activity and providing appropriate social support, they can help them establish positive self-evaluation and confidence to better cope with future challenges and difficulties.
Treatment of corneal dermoid with fibrin glue boned multi-layer lenticules derived from SMILE surgery
Authors: Li Zhen , Cheng Zhongxia , Jia Ziyu , Tang Yuyan
Published: May 2024

Purpose
Dermoid resection combined with lamellar keratoplasty was one of the most common surgical techniques for corneal dermoid. The aim of this preliminary study was to investigate the safety and feasibility of FG boned SMILE-derived multi-layer lenticules as corneal grafts to treat corneal dermoid.
Methods
5 patients with corneal dermoid were involved in this study. All patients were treated with dermoid resection combined with FG boned multi-layer corneal lenticules transplantation. Ocular appearance, corneal grafts’ growth, location, epithelialization, transparency, and limbal pannus were assessed using slit lamp microscopy and anterior-segmental optical coherence tomography. The change of best-corrected visual acuity (BCVA) and astigmatism were examined preoperatively and postoperatively.
Results
Total of 5 patients were satisfied with the postoperative ocular appearance. All FG boned multi-layer lenticules grafts were successfully adhered to the corneal beds, without any dislocation or Interlayer separation. The lenticule grafts grew well and kept transparent during the follow-up time. Corneal epithelialization was observed in one week after transplantation, with smooth corneal epithelial coverage on the corneal surface, meanwhile, the grafts gradually merged with the recipient corneal stroma after 1mo post-operation. BCVA had been statistically improved from 0.36 ± 0.21 to 0.76 ± 0.17 in decimal at 3mo post-operation (Z=-2.060, P = 0.039). Postoperative corneal astigmatism also had been statistically decreased from 2.65 ± 0.42 D to 1.25 ± 0.18 D at 3mo postoperative (Z=-2.023, P = 0.043).
Conclusion
FG boned multi-layer lenticules would be the novel and feasible substitute for lamellar keratoplasty in the treatment of corneal dermoid. FG could not be only used as binder adhering multi-layer lenticules, closing the interlayer space of multi-layer lenticules, preventing the formation of interlayer fluid, but also increasing the thickness and toughness of lenticules, and therefore which is more facilitate to intraoperative suture.
Impact of co-morbid common mental disorder symptoms in people with epilepsy in Ethiopia on quality of life and functional disability: cohort study
Authors: Tsigebrhan Ruth , Medhin Girmay , Belina Merga , Newton Charles , Hanlon Charlotte
Published: May 2024

Background
There is very limited prospective evidence on the impact of co-morbid mental health conditions in people with epilepsy living in low and middle-income countries. The objective of this study was to investigate the impact of common mental disorder (CMD; depression/anxiety) symptoms and risky substance use in people with epilepsy in Ethiopia on quality of life and functioning over six months.
Methods
A prospective cohort study of people with epilepsy was carried out in four districts of south-central Ethiopia. Comorbid CMD symptoms, risky substance uses (exposures) and the primary outcome, quality of life (QoL) was measured at baseline and 6 months follow-up. Secondary outcomes functional disability and seizure frequency were measured at follow-up. Multivariable linear regression was employed to evaluate whether comorbid CMD symptoms predicted a change in QoL and functional disability. Structural equation modelling (SEM) was employed to examine direct and indirect pathways linking co-morbid CMD symptoms with QoL or functional disability.
Results
In the multivariable regression model, neither CMD symptoms (β coef= -0.37, 95%CI -1.30, + 0.55) nor moderate to high risk of alcohol use (β= -0.70, 95% CI -9.20, + 7.81) were significantly associated with a change in QoL, and there was no effect modification by treatment engagement. In SEM, QoL at 6 months was significantly predicted by seizure frequency. The summative effect of CMD on QoL was significant (B= -0.27, 95%CI -0.48, -0.056), although direct and indirect associations were non-significant. Change in functional disability was not significantly associated with baseline CMD symptoms (β coef.= -0.03, 95% CI-0.48,+0.54) or with moderate to high risk of alcohol use (β coef.= -1.31, 95% CI -5.89, 3.26). However, in the SEM model, functional disability at 6 months was predicted by both baseline CMD symptoms (B = 0.24, 95% CI 0.06, 0.41) and seizure frequency (B = 0.67, 95% CI 0.46, 0.87).
Conclusions
In this rural Ethiopian setting, co-morbid CMD symptoms and seizure frequency in PWE independently predicted functional disability in people with epilepsy. The association between CMD symptoms and QoL was less conclusive. Integrated management of mental health and neurological conditions is needed to better address the psychosocial needs and improved functioning of people with epilepsy.
Evolutionary Dynamics in the Genome of Ocular Chlamydia trachomatis Strains from Northern Tanzania, pre- and post- Mass Drug Administration
Authors: Ghasemian Ehsan , Ramadhani Athumani , Harte Anna , Mafuru Elias , Derrick Tamsyn , Mtuy Tara , Massae Patrick , Malissa Aiweda , Breuer Judith , Pickering Harry , Bailey Robin L. , Mabey David , Burton Matthew J. , Holland Martin J.
Published: May 2024

Trachoma, caused by Chlamydia trachomatis (Ct), remains a leading cause of preventable infection induced blindness worldwide. We conducted a four-year longitudinal study in three trachoma-endemic villages in Northern Tanzania, tracking infection dynamics and factors influencing trachomatous scarring progression and persistence pre- and post-Mass Drug Administration (MDA) interventions.
We analysed 118 whole genomes of Ct originating from ocular swabs of children. Sample collection was conducted at three-month intervals over four years, encompassing 15 timepoints. We studied Ct phylogeny, patterns of single nucleotide polymorphism (SNP) accumulation in individual isolates and single nucleotide variation (SNV) in the population, with association of clinical signs of trachoma and scarring progression.
Seventy-one (60.2%) samples were classified as serovar A (SvA) and 47 (39.8%) as serovar B (SvB) genomes. Initially, SvB dominated among pre-MDA samples (36/40, 90%), but SvA gradually became dominant after the first round of MDA (67/78, 85.9%) (P<0.0001). Two distinct subsets of SvA were found: subset_1 (29 sequences) pre-MDA, aligning with Tanzanian reference strain A/2497; subset_2 (42 sequences) post-MDA, showing a mutation rate roughly twice as high as subset_1, a 6 kbp genome reduction in the PZ, and forming a distinct cluster. Similarly, 13 SvB sequences exhibited diverse PZ genome reduction (~4 and ~10 kbp), yet all grouped with Tanzanian reference strain B/TZ1A828/OT.
Importantly, we observed a shift in the types of Ct serovars after the first round of MDA, with the emergence of a unique SvA subset with distinct genetic characteristics compared to those circulating before MDA. The observed decrease in the size of the Ct genome suggests a process where the Tanzanian ocular Ct strains may be streamlining, highlighting ongoing evolution. Further research is needed to understand the factors driving these changes and their impact on Ct biology and response to azithromycin.
Is it feasible to selectively perform axillary lymph node surgery for patients with biopsy diagnosed Ductal Carcinoma in Situ? A study based on developed and validation of nomogram
Authors: Peng Yuan , Wu Jinbo , Guo Hanyin , Xie Fei , Yang Houpu , Wang Siyuan , Wang Chaobin , Yang Yang , Du Wei , Lliu Miao , Wang Shu
Published: May 2024

Purpose
It is still unclear which patients diagnosed with DCIS through biopsy can benefit from lymph node surgery. We aimed to developed and validated a nomogram to predict the risk of upstaging to invasion, and explore the factors related to lymph node metastasis in biopsy diagnosis of DCIS patients.
Methods
A retrospective study was conducted on 526 cases diagnosed with DCIS before surgery in the period of January 2016 to December 2022. Nomograms for predicting the probability of invasion disease were constructed according to multivariate logistic regression analysis. This nomogram was validated using a second data set of 133 patients between January to December 2023. Univariate and multivariate analysis were used to evaluate the risk factors for lymph node metastasis.
Results
Underestimating invasive carcinoma occurred in 42.0% of patients, of whom 37 had positive lymph node. Core needle biopsy, mass on mammography, moderate nuclear grade of DCIS and increased Ki-67 expression were associated with upstaging. Nomogram developed depending on these factors showed acceptable performance on predicting upstaging (AUC 0.724). This nomogram was validated in a second dataset with an AUC of 0.641. calcification on mammography, mass on MRI performance and large radiological size were independent risk factors of lymph node metastasis.
Conclusion
Underestimating invasive carcinoma with DCIS detected prior to surgery is common, but with a low probability of lymph node metastasis. This nomogram and factors associated with positive lymph node may provide help in selecting suitable patients for axillary lymph node excision.
Therapeutic protein targets for cardiometabolic diseases: Mendelian randomization integrating plasma proteomes with genome-wide association data
Authors: Zhou Ruixin , Qiao Jun , Cai Liuyang , Pauklin Siim , Feng Yuliang
Published: May 2024

Cardiovascular disease (CVD) is the leading cause of death worldwide, and its risk is inseparable from metabolic abnormalities. Through summary-data-based Mendelian randomization and colocalization analysis, we investigated the causal relationships between plasma proteins, 6 cardiovascular diseases, and 19 metabolic phenotypes. We identified 49 proteins genetically associated with CVDs, validated across two platforms, with 35 associated with one or more metabolic phenotypes and six having support of colocalization. These six candidate proteins were classified into three categories based on the utilization of drugs that are currently approved or in clinical trial phases, with PCSK9 already successful in drug development for CVDs and hypercholesterolemia. DUSP13B, LRIG1, APOH, INHBC, and GUSB also showed high drug potential. Further phenome-wide Mendelian randomization analysis indicated no potential side effects from targeting PCSK9 and APOH. This study revealed causal proteins for the onset of cardiovascular diseases and metabolic abnormalities, which contributed to understanding the molecular mechanisms underlying disease pathogenesis and the development of related drugs.
Limited Immunogenicity of an HLA-A*03:01-restricted Epitope of Erv-k-env in Non-hiv-1 Settings: Implications for Adoptive Cell Therapy in Cancer
Authors: Grundy Erin E. , Shaw Lauren C. , Wang Loretta , Powell Daniel J. , Ostrowski Mario , Jones R. Brad , Cruz C. Russell Y. , Gordish-Dressman Heather , Bollard Catherine M. , Chiappinelli Katherine B.
Published: May 2024

Repetitive elements (REs) are often expressed at higher levels in tumor cells than normal cells, implicating these genomic regions as an untapped pool of tumor-associated antigens. In ovarian cancer (OC), protein from the RE ERV-K is frequently expressed by tumor cells. Here we determined whether the targeting of a previously identified immunogenic epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity in non-HIV-1 settings. We found that transducing healthy donor T cells with an ERV-K-Env-specific T cell receptor construct resulted in antigen specificity only when co-cultured with HLA-A*03:01 B lymphoblastoid cells. Furthermore, these transduced T cells were not specific for HLA-A*03:01 + OC cells nor for the cognate peptide in HLA-matched systems from multiple healthy donors. These data suggest that the ERV-K-Env epitope recognized by this T cell receptor is of low immunogenicity and has limited potential as a T cell target for OC.
Manganese primed immunochemotherapy in platinum-resistant/refractory ovarian cancer: a randomized, single-blind, placebo-controlled, phase 2 trial
Authors: Han Weidong , Mei Qian , Zhang Yan , Liu Jiejie , Chen Meixia , Gong Yandong , Liu Yang , Wang Tiance , Ye Mingxia , Jiang Zhengfan , Ming Qianyi , Lv Zijian , Fan Runjia , Yang Qingming , Du Yuan , Meng Yuanguang
Published: May 2024

Platinum-resistant or refractory ovarian cancer (PROC) remains without immunotherapy approval and dismal prognosis, emphasizing the urgent need for novel therapies. This phase 2, single-blind, placebo-controlled, randomized trial evaluated the safety and efficacy of manganese chloride or placebo plus sintilimab, nab-paclitaxel and cisplatin in these patients. 84 patients were randomized to the Mn2+ (n=55) or placebo (n=29) arm. The primary endpoint of objective response rate (ORR) was met at 61.8% in the Mn2+ and 13.8% in placebo group. The secondary endpoints of median PFS (9.8 vs. 3.9 months), OS (21.4 vs. 7.9 months) and DOR (14.9 vs. 1.8 months) were significantly prolonged in the Mn2+ group. No significant differences in AEs and quality of life were document during the treatment period. The serum cytokines and scRNA-seq evidenced the cGAS-STING agonist function of Mn2+. Our study supported Mn2+-priming immunochemotherapy as a promising treatment regimen for PROC patients. ClinicalTrials.gov identifier: NCT03989336.
Deciphering Fracture Risk: A Comprehensive Analysis of Blood Metabolites via Mendelian Randomization.
Authors: Ren Chuan , Yao Meng-xuan , Zhang Yi-Fan , Zhu Yan-bin , Wang Juan , Lv Hong-zhi , Zhang Yu-Qin , Shi Tai-Long , Wang Hai-cheng , Ding Kai , Shui Wei , Chen Wei
Published: May 2024

Purpose: The study aims to explore the complex relationship between plasma metabolites and fracture risk, addressing the gap in comprehensive analysis of 1,400 plasma metabolites and their potential causal association with fracture risk.
Methods: The study employed bidirectional Mendelian Randomization (MR) analysis using data from European ancestry GWASs. It examined the potential causal relationships of 1,400 unique blood metabolites with fracture risk, using various statistical tols and sensitivity analyses in R language.
Results: The study identified 89 metabolites significantly associated with fracture risk, with 36 showing protective effects and 53 as risk factors. The study identified 89 metabolites significantly associated with fracture risk. Of these, 36 showed a protective effect (OR < 1) and 53 were identified as risk factors (OR > 1). Three metabolites demonstrated consistent associations across various methods: (1) 2R3R-dihydroxybutyrate showed a positive effect on fracture risk with an OR of 1.005 (p = 0.0002, 95% CI: 1.002 to 1.008) using the IVW method. Other methods, including MR-Egger and weighted median, did not show significant results. (2) 1-stearoyl-2-arachidonoyl-gpc (18:0/20:4) had a consistent positive association with fracture risk across different methods, with an OR of 1.003 (p = 0.0003, 95% CI: 1.001 to 1.005) using IVW. Similar results were obtained with MR-Egger and weighted median methods. (3) Adenosine 5'-diphosphate (ADP) to glycerol 3-phosphate ratio showed a positive association with an OR of 1.006 (p= 0.00003, 95% CI: 1.003 to 1.009) using IVW. However, the MR-Egger and other methods did not show statistical significance.
Conclusions:The study provided new insights into the biochemical mechanisms of fractures, highlighting the significant role of specific metabolites in fracture risk. It suggests potential targets for future fractures prevention and treatment strategies.
Atmospheric preconditions investigation of wet-cold compound events in Greece between 1980 and 2004
Authors: Markantonis Iason , Vlachogiannis Diamando , Sfetsos Athanasios , Kioutsioukis Ioannis
Published: May 2024

This study investigates the origins and the atmospheric circulation patterns that led to the occurrence of Wet-Cold compound events (WCCEs) recorded by the Hellenic National Meteorological Service (HNMS) between 1980 and 2004. The study employed two methods to provide insights into the issue. The first method involved identifying clusters from backward trajectories (BTs) at three heights above the arrival point (500, 1500 and 5500 metres). The second method aimed at detecting weather patterns (WPs) that result from the clustering of atmospheric pressure at sea level (SLP) and the geopotential height (GH500) at 500hPa from ERA5. To detect clusters for both methods, k-means clustering is applied. The analysis of backward trajectories produced seven clusters of BTs at each height level. Most of these clusters originated from the Northwest or North, with medium, short, and long-distance clusters being observed at 500m, 1500m and 5500m height levels, respectively. Despite analysing the temporal data, no clear connection was established between the clusters and months. From the cluster of GH500 and SLP variables for 94 different dates, we derived three main WPs. All WPs showed high GH500 values in Western Europe and lower GH500 values in Eastern Europe. Although SLP values differed significantly among the clusters, they helped to identify distinct weather patterns. Finally, we identified that on 7 out of the total of 94 different dates with WCCEs, large amounts of moisture are transported to Greece through the atmosphere over long distances by atmospheric rivers (ARs).
Lipopolysaccharide Enhances Microglia Antiviral Control of Betacoronavirus Infection through TLR4-Dependent Induction of IFNβ with Concomitant Modulation of dsRNA Sensors MDA5 and TLR3
Authors: Davis Elijah H , Glass Adam M , LaBier Brett A , Tang Alexis A , Pabon Valeria Bornacelli , Mayes Armoni A , Navas-Martin Sonia
Published: May 2024

Microglia play a pivotal role in brain homeostasis and are essential to protective immunity within the central nervous system by coordinating the innate immune response to neuroinvasive pathogens. Bacterial endotoxin (lipopolysaccharide, LPS) is the most used pro-inflammatory stimulus for microglia, both in vitroand in vivo. However, the impact of LPS in microglia response to viral infection, including coronaviruses remains ill-defined. Murine coronaviruses productively infect microglia and are well established models of RNA virus-induced encephalitis and demyelination. In the present study, we investigated the effects of TLR4 stimulation with a TLR4-specific agonist [smooth (s)-form LPS (E. coli 0111:B4)] on murine coronavirus MHV-JHM and -A59 infection of microglia in vitro. Mechanistically, our data revealed that LPS stimulation of microglia restrict coronavirus replication through TLR4-dependent induction of interferon (IFN-b) with concomitant modulation of dsRNA sensors melanoma differentiation-associated gene 5 (MDA5) and toll-like receptor 3 (TLR3). Moreover, in the absence of coronavirus infection, LPS induces TLR4-dependent upregulation of MDA5 expression and activation of TLR3, as measured by phosphorylation of its residue Y759, a hallmark of TLR3 signaling initiation. Supporting LPS-induced TLR3 activation, we demonstrated that TLR3 selectively contributes to TLR4-dependent, LPS-induced neuroinflammation even in the absence of virus infection. Overall, the present study provides novel mechanistic insights regarding microglia responses to coronavirus infection and highlights a previously unrecognized crosstalk between bacterial TLR4 and dsRNA sensors in microglia with implications beyond viral infection.
Fly-by-Feel: Wing Strain-based Flight Control of Flapping-Wing Drones through Reinforcement Learning
Authors: Kang Daeshik , Han Seungyong , Koh Je-sung , Kim Taewi , Hong Insic , Im Sunghoon , Rho Seungeun , Kim Minho , Roh Yeonwook , Kim Changhwan , Park Jieun , Lim Daseul , Lee Doohoe , Lee Seunggon , Lee Jingoo , Back Inryeol , Lee Joonho , Seo Sungchul , Kim Uikyum , Cho Junggwang , Hong Myung Rae , Kang Sanghun , Choi Young-Man
Published: May 2024

Although drone technology has progressed significantly, replicating the dynamic control and wind-sensing abilities of biological flights is still beyond our reach. Biological studies have revealed that insect wings are equipped with mechanoreceptors known as campaniform sensilla, which detect complex aerodynamic loads critical for flight agility. By leveraging robotic experiments designed to mimic these biological systems, we confirmed that wing strain provides crucial information about the drone's attitude, as well as the direction and velocity of the wind. We introduce a novel wing strain-based flight controller, termed 'fly-by-feel'. This methodology employs the aerodynamic forces exerted on a flapping drone's wings to deduce vital flight data, such as attitude and airflow without accelerometers and gyroscopic sensors. Our empirical approach spanned five key experiments: initially validating the wing strain sensor system for state information provision, followed by a single degree of freedom (1 DOF) control in changing winds, a two degrees of freedom (2 DOF) control for gravitational attitude adjustment, a test for position control in windy conditions, and finally, demonstrating precise flight path manipulation in a windless condition using only wing strain sensors. We have successfully demonstrated control of a flapping drone in a various environment using only wing strain sensors, with the aid of reinforcement learning-driven flight controller. The fly-by-feel system holds the potential to revolutionize autonomous drone operations, providing enhanced adaptability to environmental shifts. This will be beneficial across varied applications, from gust resistance to wind-assisted flight, paving the way toward the next generation of resilient and autonomous flying robots.
Performance Comparison Index for Image Super-Resolution Models
Authors: Koçmarlı Gökhan , Esmer Gökhan Bora
Published: May 2024

Image super-resolution is a critical aspect of image enhancement, facilitating the reconstruction of high-quality images from low-resolution inputs. Traditional quality assessment metrics like SSIM, MSE, and PSNR have limitations in effectively evaluating super-resolution models due to their focus on pixel values and statistical properties, overlooking overall visual quality. This article introduces a technique for comparing super-resolution models using a pattern-based approach. The proposed method evaluates image quality by analyzing the harmonics, providing a performance comparison index that surpasses traditional metrics. By focusing on the frequency domain and magnitudes of Fourier components, this technique effectively captures image features and patterns, enabling a more comprehensive assessment of super-resolution model performance.
A roadmap to human hippocampal neurogenesis in adulthood, aging and AD.
Authors: Lazarov Orly , Disouky Ahmed , Sanborn Mark , Mostafa Mostafa , Sabitha K. , Schantz Aimee , Kim Namhee , Pawlowski Szymon , Honer William , Bennett David , Zhou Yi , Keene C. , Maienschein-Cline Mark , Rehman Jalees
Published: May 2024

In the rodent, hippocampal neurogenesis plays critical roles in learning and memory 1,2, is tightly regulated by inhibitory neurons 3-7 and contributes to memory dysfunction in Alzheimer’s disease (AD) mouse models 8-10. In contrast, the mechanisms regulating neurogenesis in the adult human hippocampus, the dynamic shifts in the transcriptomic and epigenomic profiles in aging and AD and putative niche interactions within the cellular environment, remain largely unknown. Using single nuclei multi-omics of postmortem human hippocampi we map the molecular mechanisms of hippocampal neurogenesis across aging, cognitive decline, and AD neuropathology. Transcriptomic and epigenetic profiling of neural stem cells (NSCs), neuroblasts and immature neurons suggests that the earliest shift in the characteristics of neurogenesis takes place in NSCs in aging. Cognitive impairment was associated with changes in neuroblast profile. In AD, there was a widespread cessation of the transcription machinery in immature neurons, with robust downregulation of genes regulating ribosomal and mitochondrial function. Further, there was substantial loss of parvalbumin+ inhibitory neurons in the hippocampus in aging. The number of the rest of inhibitory neurons were reduced as a function of age and diagnosis. Notably, a similar system-level effect was observed between immature and inhibitory neurons in the transition from aging to AD, manifested by common molecular pathways that were ultimately lost in AD. The numbers of neuroblasts, immature and GABAergic neurons inversely correlated with extent of neuropathology. Using CellChat and NeuronChat, we inferred the ligands and receptors by which neurogenic cells communicate with their cellular environment. Loss of synaptic adhesion molecules and neurotransmitters, either sent or received by neurogenic cells, was observed in AD. Together, this study delineates the molecular mechanisms and dynamics of human neurogenesis, functional association with inhibitory neurons and a mechanism of hippocampal hyperexcitability in AD.
Beyond the Diagnosis: Insight Into Posterior Reversible Encephalopathy Syndrome: A Case Series
Authors: Biswas Himel Kumar , Ishaque Khadija Tanbil , Biswas Rama
Published: May 2024

An acute neurological condition known as posterior reversible encephalopathy syndrome (PRES) manifests as nonspecific symptoms such as headache, seizure, disorientation and visual abnormalities. PRES has been known for the last few decades, with characteristic radiologic findings, but the natural history of PRES has not yet been fully established. Although PRES is thought to be reversible, this may not always be true because there is a significant risk of neurological impairment and mortality. Here, we discuss three patients with different ages of PRES and a common association with hypertension. We observed different outcomes in these patients who were treated with antihypertensive, anticonvulsant, or supportive care agents.
Individual Work Performance Questionnaire: Translation and validation in Greek
Authors: Galanis Petros , Katsiroumpa Aglaia , Derizioti Konstantina , Moisoglou Ioannis , Papanikolaou Vasiliki
Published: May 2024

Background: Scholars should measure work performance with valid tools for improving understanding of employees’ attitudes.
Aim: To translate and validate the “Individual Work Performance Questionnaire” (IWPQ) in Greek.
Methods: Study population included 233 nurses in Greece. We collected our data in December 2023. We employed the forward-backward method to translate and adapt the IWPQ in Greek language. We conducted confirmatory factor analysis to examine the construct validity of the IWPQ. We examined the reliability of the IWPQ by calculating Cronbach’s alpha.
Results: The IWPQ showed very good psychometric properties. Our confirmatory factor analysis confirmed the three-factor structure of the IWPQ. All indices indicated an acceptable three-factor model. Cronbach’s coefficient alpha for task performance scale, contextual performance scale, and counterproductive work behavior scale was 0.743, 0.872, and 0.769, respectively.
Conclusions: The Greek version of the “Individual Work Performance Questionnaire” is a reliable and valid tool to measure employees’ work performance.
DS-BEV:An Efficient Multi-Modal Fusion in Object Detection with Unified Bird's-Eye View Representation
Authors: Hu Minghui
Published: May 2024

Multi-sensor fusion is essential for an accurate and reliable autonomous driving system. Recently, BEVFusion has been proposed to integrate LiDAR and image features in a unified Bird's Eye View (BEV) representation. However, there is an issue with the loss of local image information during the extraction of global image information on the backbone network. In order to fully integrate local features with global features, this paper proposes a network called DS-BEV based on feature selection and refinement. It includes a Feature Selection Fusion module (FSM) and a Feature Refinement module (FRM). In the FSM, the features of different modal are first extracted by using specific networks and projected into a unified BEV representation space. Through channel and spatial learning, important information is selected from the initial features and fused to generate preliminary fusion features. Then,the image features extracted by a CNN network and the preliminary fusion features output by the FSM are sent to the FRM together. By combining the local features generated by CNN network, the fusion features are refined. We evaluate our model on the nuScenes dataset. Experiments show that our DS-BEV achieves 69.5% mAP and 72.3% NDS in detection accuracy.
A comparative study of diabetic foot treatment
Authors: Alsaleh Joud , Aziz Nooran Abdul , Hammoud Taghrid
Published: May 2024

Background: The diabetic foot ulcers consider a serious complication that related to diabetes, ulcers required medical and nursing care, that started with determine the degree of ulcer and applying Dressing which is from responsibility of nurses. There are many kinds of dressing for grade 1&2 diabetic foot ulcers such as dry and honey dressings.
Aim of the study: Assessment the effect of applying the dry and honey dressings on the healing of grade (1&2) diabetic foot ulcers.
Material and Methods: The study conducted A special center for diabetic foot in Damascus city. A convenient sample of 200 adult diabetic patients whose meet the sample selection criteria were chosen. The sample divided randomly to two equal groups, either the first group who subjected to dry dressing technique, or to the second group who subjected to honey dressing technique. Dressing changed for six weeks.
Results: At the end of the study: (55%) of patients had complete ulcer healing, (35%) had partial healing and (20%) had no ulcer wound healing in the dry dressing group. Whereas (85%) of patients had complete ulcer healing and (15%) had partial healing. Conclusions: Honey dressing had statistical significant effects on the healing of grade (1&2) diabetic foot ulcers.
Associations Between Vitamin D Receptor Gene Polymorphisms and Carpal Tunnel Syndrome
Authors: Yıldız Bilal , Algül Fatma Ebru , Yeşilada Elif
Published: May 2024

Background
Vitamin D deficiency is associated with Carpal tunnel syndrome (CTS), and Vitamin D supplementation may improve symptoms and electrophysiological findings in CTS patients. The biological effects of vitamin D may be modified by various genetic factors, including single nucleotide polymorphisms in the vitamin D receptor (VDR) gene. With this study, we aimed to investigate the relationship between CTS and Taq I and Fok I polymorphisms of the VDR gene.
Materials and Methods
100 CTS patients and 100 healthy controls were included in this study. The severity of CTS was determined by electromyography and the patients were divided into 3 groups: mild, moderate and severe CTS. The Fok I and Taq I genotypes of the participants were determined from the peripheral blood samples taken from all participants. Genotypes and allele frequencies were compared between patient and control groups.
Results
VDR Fok I genotype distribution and allele frequency showed a significant relationship with the risk of developing CTS and its severity. Taq I, on the other hand, was not associated with the risk of developing CTS or its severity.
Conclusion
VDR Fok I polymorphism increases the risk of developing CTS and the risk of severe CTS in the Turkish population. Further studies on this subject are needed to further understand the relationship between CTS and VDR polymorphisms and explain its mechanism.