bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain tumor image segmentation algorithm based on multimodal feature fusion of Bayesian weight distribution
Authors: Li Ju , Wang Yanhui , Wang Guoliang 
Published: March 2024

AbstractThis study proposes an improved U‐Net model to address the issues of large semantic differences in skip connections and insufficient utilization of cross‐channel information in magnetic resonance imaging (MRI) images leading to inaccurate segmentation of brain tumor regions in the field of brain tumor segmentation. Firstly, by adding a deep residual module to alter the receptive field, the network's ability to learn tumor information is enhanced. Secondly, a dual attention mechanism was established using Bayesian weighting technology, achieving multi‐channel and multi‐scale feature fusion, and improving the model's learning and extraction of brain tumor boundary information. Finally, the tumor features extracted from different patterns are concatenated through skip connections, effectively integrating feature information from different levels and scales, and reducing semantic differences. We evaluated the performance of the proposed model on the BraTS2018 and BraTS2019 brain tumor image segmentation datasets. The experimental results showed that for the BraTS2018 dataset, the model improved the average dice score by 12.8%, the average sensitivity by 10.4%, and the average Hausdorff Distance by 5.75 compared to traditional U‐Net. On the BraTS2019 dataset, three indicators improved by 12.6%, 11.2%, and 7.46, respectively. The experimental results show that the proposed improved U‐Net model can improve the segmentation performance of brain tumor MRI images without increasing computational time.
PDE5 inhibitors against cancer via mediating immune cells in tumor microenvironment: AI‐based approach for future drug repurposing exploration
Authors: Zhang Zhenzhan , Huang Donghua , Feng Junjie , Li Wangji , Wang Zhe , Lu Mengting , Luo Yangyang , Yang Weihao , Xu Zhou , Xie Qingfeng , Ding Wenfu , Tan Xin , He Wenjun , Li Guoxin , Liu Hao , Lei Shangtong 
Published: March 2024

AbstractPhosphodiesterase‐5 (PDE5) inhibitors are used clinically for the treatment of erectile dysfunction, pulmonary arterial hypertension, and other urological diseases. Emerging evidences have suggested the therapeutic capacity of PDE5 inhibitors as the repurposed drugs in oncology. However, the essential immune function of PDE5 inhibitors against cancer in tumor microenvironment (TME) remains unclear. This review aimed to summarize the recent advances regarding the repurposing of PDE5 inhibitors as anti‐cancer agents for cancer management to enhance the anti‐tumor immune response by mediating various immune cells, which included the myeloid‐derived suppressor cells, macrophages, T cells, fibroblasts, and natural killer cells in TME. Moreover, artificial intelligence (AI), as a new approach, is composed of traditional machine learning and deep learning methods and could be potentially used to identify the targets of immune cells in TME and predict the efficacy for repurposed drug toward malignancies. In summary, these endeavors provide novel insights into the comprehensive strategies for PDE5 inhibitors mediating immune cells against cancer and AI‐based approach for future drug repurposing exploration.
A nontoxic strontium nanoparticle that holds the potential to act upon osteocompetent cells: An in vitro and in vivo characterization
Authors: Hayann Larwsk , da Rocha Vitor Freire , Cândido Marina Ferreira , Vicente Raphael Martini , Andrilli Luiz H. S. , Fukada Sandra Y. , Brassesco María Sol , Ciancaglini Pietro , Engel Edgard Eduard , Ramos Ana Paula 
Published: March 2024

AbstractEstrogen deficiency, long‐term immobilization, and/or aging are commonly related to bone mass loss, thus increasing the risk of fractures. One option for bone replacement in injuries caused by either traumas or pathologies is the use of orthopedic cement based on polymethylmethacrylate (PMMA). Nevertheless, its reduced bioactivity may induce long‐term detachment from the host tissue, resulting in the failure of the implant. In view of this problem, we developed an alternative PMMA‐based porous cement (pPMMA) that favors cell invasion and improves osteointegration with better biocompatibility. The cement composition was changed by adding bioactive strontium‐nanoparticles that mimic the structure of bone apatite. The nanoparticles were characterized regarding their physical–chemical properties, and their effects on osteoblasts and osteoclast cultures were assessed. Initial in vivo tests were also performed using 16 New Zealand rabbits as animal models, in which the pPMMA‐cement containing the strontium nanoparticles were implanted. We showed that the apatite nanoparticles in which 90% of Ca2+ ions were substituted by Sr2+ (NanoSr 90%) upregulated TNAP activity and increased matrix mineralization. Moreover, at the molecular level, NanoSr 90% upregulated the mRNA expression levels of, Sp7, and OCN. Runx2 was increased at both mRNA and protein levels. In parallel, in vivo tests revealed that pPMMA‐cement containing NanoSr 90%, upregulated two markers of bone maturation, OCN and BMP2, as well as the formation of apatite minerals after implantation in the femur of rabbits. The overall data support that strontium nanoparticles hold the potential to up‐regulate mineralization in osteoblasts when associated with synthetic biomaterials.
Novel furan chalcone modulates PHD‐2 induction to impart antineoplastic effect in mammary gland carcinoma
Authors: Rastogi Shubham , Ansari Mohd Nazam , Saeedan Abdulaziz S. , Singh Sunil Kumar , Mukerjee Alok , Kaithwas Gaurav 
Published: March 2024

AbstractNormoxic inactivation of prolyl hydroxylase‐2 (PHD‐2) in tumour microenvironment paves the way for cancer cells to thrive under the influence of HIF‐1α and NF‐κB. Henceforth, the present study is aimed to identify small molecule activators of PHD‐2. A virtual screening was conducted on a library consisting of 265,242 chemical compounds, with the objective of identifying molecules that exhibit structural similarities to the furan chalcone scaffold. Further, PHD‐2 activation potential of screened compound was determined using in vitro 2‐oxoglutarate assay. The cytotoxic activity and apoptotic potential of screened compound was determined using various staining techniques, including 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide, 4′,6‐diamidino‐2‐phenylindole (DAPI), 1,1′,3,3′‐tetraethylbenzimi‐dazolylcarbocyanine iodide (JC‐1), and acridine orange/ethidium bromide (AO/EB), against MCF‐7 cells. 7,12‐Dimethylbenz[a]anthracene (DMBA) model of mammary gland cancer was used to study the in vivo antineoplastic efficacy of screened compound. [(E)‐1‐(4‐fluorophenyl)‐3‐(furan‐2‐yl) prop‐2‐en‐1‐one] (BBAP‐7) was screened and validated as a PHD‐2 activator by an in vitro 2‐oxo‐glutarate assay. The IC50 of BBAP‐7 on MCF‐7 cells is 18.84 µM. AO/EB and DAPI staining showed nuclear fragmentation, blebbing and condensation in MCF‐7 cells following BBAP‐7 treatment. The red‐to‐green intensity ratio of JC‐1 stained MCF‐7 cells decreased after BBAP‐7 treatment, indicating mitochondrial‐mediated apoptosis. DMBA caused mammary gland dysplasia, duct hyperplasia and ductal carcinoma in situ. Carmine staining, histopathology, and scanning electron microscopy demonstrated that BBAP‐7, alone or with tirapazamine, restored mammary gland surface morphology and structural integrity. Additionally, BBAP‐7 therapy significantly reduced oxidative stress and glycolysis. The findings reveal that BBAP‐7 activates PHD‐2, making it a promising anticancer drug.
Use of caps in the auxiliary basis set formulation of the fragment molecular orbital method
Authors: Fedorov Dmitri G. 
Published: March 2024

AbstractAn auxiliary polarization formulation of the fragment molecular orbital (FMO) method is developed, combining a basis set correction computed for capped isolated fragments with a polarization obtained from uncapped fragments. For a set of organic and inorganic test systems, it is shown that the total energy and atomic charges are accurately reproduced with respect to full unfragmented calculations. It is demonstrated that the method is accurate for computing electronic excited states. The developed approach is applied to rank the isomers of chignolin from experimental NMR data (PDB: 1UAO) according to their relative energy. Contributions of polarization and basis set effects to pair interactions between fragments are elucidated.
Pediatric Extrapolation Approach for U.S. Food and Drug Administration Approval of Brexpiprazole in Patients Aged 13 to 17 Years with Schizophrenia
Authors: Zhang Huixia , Liu Jie , Sharma Vishnu , Zhuang Luning , Horn Pamela , Uppoor Ramana , Mehta Mehul , Zhu Hao 
Published: March 2024

AbstractA pharmacokinetic (PK) bridging approach was successfully employed to support the dosing regimen and approval of brexpiprazole in pediatric patients aged 13‐17 years with schizophrenia. Brexpiprazole was approved in 2015 for the treatment of schizophrenia and the adjunctive treatment of major depressive disorder in adults based on efficacy and safety data from clinical trials. On January 13, 2020, the US Food and Drug Administration issued a general advice letter to sponsors highlighting the acceptance of efficacy extrapolation of certain atypical antipsychotics from adult patients to pediatric patients considering the similarity in disease and exposure–response relationships. Brexpiprazole is the first atypical antipsychotic approved in pediatrics using this approach. The PK data available from pediatric patients aged 13‐17 years have shown high variability due to the limited number of PK evaluable subjects, which limits a robust estimation of differences between adult and pediatric patients. The PK model‐based approach was thus utilized to evaluate the appropriateness of the dosing regimen by comparing PK exposures in pediatric patients aged 13‐17 years with exposures achieved in adults at the approved doses. In addition to exposure matching, safety data from a long‐term open‐label clinical study in pediatric patients informed the safety profile in pediatric patients. This report illustrates the potential of leveraging previously collected efficacy, safety, and PK data in adult patients to make a regulatory decision in pediatric patients for the indication of schizophrenia.
Determination of differences in ultrasound parameters for patellar tendons in males with unilateral patellar tendinopathy—An ancillary analysis of data from two randomized controlled trials
Authors: Hjortshoej M. H. , Agergaard A. , Larsen F. K. , Thomsen L. J. P. , Svensson R. B. , Couppé C. , Magnusson S. P. 
Published: March 2024

AbstractPurposeTo investigate power Doppler (PD) activity and tendon structure (between the injured and contralateral limb) in patients with unilateral patellar tendinopathy (PT) using ultrasonography (US). Secondly, the aim was to determine the intra‐rater reliability of the PD activity and tendon structure.MethodsThis study analyzed US baseline data from 57 male participants with symptomatic unilateral PT who had been enrolled in one of two randomized clinical trials. Data were analyzed to examine if systematic differences existed between injured and contralateral limbs using Fiji ImageJ.ResultsThe PD activity of the symptomatic tendon was larger 25.6 (Q1 = 14.9; Q3 = 41.6) mm2 than the asymptomatic 0 (Q1 = 0.0; Q3 = 0.0) mm2 (p < 0.001). There was a significantly greater tendon thickness at the proximal (2.5 mm 95% CI [2.0; 3.0]), mid (0.8 mm 95% CI [0.5; 1.1]), and distal (0.2 mm 95% CI [0.1; 0.4]) part of the tendon for the symptomatic compared to the asymptomatic tendon. Intra‐rater reliability for PD activity and tendon structure ranged from moderate‐to‐excellent (0.74; 0.99).ConclusionThese results provide mean estimates for tendon thickness of symptomatic and asymptomatic tendons, that can be used for clinicians to reliably estimate pathological tendon thickness.
Breast ultrasound: An opportunity to detect unsuspected pleural and pulmonary abnormalities
Authors: Corvino Antonio , Basile Luigi , Boccatonda Andrea , Varelli Carlo , Tafuri Domenico , Cocco Giulio , Catalano Orlando 
Published: March 2024

AbstractPurposeWhile scanning women for breast US, is possible to observe changes in the appearance of the pleural line or in the most superficial portion of the lung. The objective of this single‐center, prospective study was to determine the prevalence of a variety of pleural and pulmonary US findings during routine breast US.MethodsIn this study, there were 200 women undergoing standard breast US examination. The presence of pleural and pulmonary abnormalities in these cases was recorded. Two off‐site reviewers confirmed the presence of pleura and lung changes.ResultsThere was no abnormal finding in 168 out of 200 cases (84%) while there were one or more abnormal findings in 32 cases (16%). Pleural effusion was observed in 0.5% of cases, thickening of the pleural line 5% of cases, irregularity of the pleural line in 6% of cases, increased number of vertical artifacts in 9% of cases, subpleural nodulations in 2% of cases, and lung consolidation in 0.5%.ConclusionPleural and lung changes are not uncommon during breast US. Operators performing breast US examinations should be aware of the possibility to identify unsuspected pleuro‐pulmonary abnormalities.
Volumetric alterations in the basal ganglia in autism Spectrum disorder: A systematic review
Authors: de Medeiros Marcos Gabriel Victor Teodoro , Feitosa Deymisson Damitene Martins , Paiva Karina Maia , Oliveira Rodrigo Freire , da Rocha Gabriel Sousa , de Medeiros Guerra Luís Marcos , de Araújo Dayane Pessoa , Goes Hosana Mirelle , Costa Silva , de Oliveira Lucidio Clebeson , Guzen Fausto Pierdoná , de Souza Júnior José Edvan , de Moura Freire Marco Aurélio , de Aquino Antonio Carlos Queiroz , de Gois Morais Paulo Leonardo Araújo , de Paiva Cavalcanti José Rodolfo Lopes 
Published: March 2024

AbstractIntroductionRecent research indicates that some brain structures show alterations in conditions such as Autism Spectrum Disorder (ASD). Among them, are the basal ganglia that are involved in motor, cognitive and behavioral neural circuits.ObjectiveReview the literature that describes possible volumetric alterations in the basal ganglia of individuals with ASD and the impacts that these changes have on the severity of the condition.MethodologyThis systematic review was registered in the design and reported according to the PRISMA Items and registered in PROSPERO (CRD42023394787). The study analyzed data from published clinical, case‐contemplate, and cohort trials. The following databases were consulted: PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials, using the Medical Subject Titles (MeSH) “Autism Spectrum Disorder” and “Basal Ganglia”. The last search was carried out on February 28, 2023.ResultsThirty‐five eligible articles were collected, analyzed, and grouped according to the levels of alterations.ConclusionThe present study showed important volumetric alterations in the basal ganglia in ASD. However, the examined studies have methodological weaknesses that do not allow generalization and correlation with ASD manifestations.
Refixation of the anterior cruciate ligament: A biomechanical analysis of suture techniques in a porcine model
Authors: Lutter Christoph , Hiller Natalie , Sass Jan‐Oliver , Hembus Jessica , Jones Gareth , Vogel Danny , Groß Justus , Bader Rainer , Tischer Thomas 
Published: March 2024

AbstractPurposeRefixation of acute anterior cruciate ligament (ACL) tears represents an increasingly popular treatment option. Systematic evaluations of various suture technique parameters are still pending. We therefore aimed to evaluate the mechanical pull‐out outcomes of various suture methods for optimization of ACL refixation.MethodsSixty fresh knees from mature domestic pigs were dissected and the femoral attachment of the ACL was peeled off. The 60 knees were divided in 10 groups and sutured as follows: (A) one suture (1, 2, 4 and 6 passes), (B) two sutures (2, 4 and 6 passes each; sutures knotted together as a loop) and (C) two sutures (2, 4 and 6 passes each, sutures knotted separately). The pull‐out test was conducted using a validated electrodynamic testing machine. First occurrence of failure, maximum pull‐out load and stiffness were measured. Suture failure was defined as pull‐out of the ACL.ResultsTwo‐point fixation, using two sutures, with at least two passes, showed the most favourable biomechanical stability. The maximum pull‐out load was significantly higher with two sutures (529.5 N) used compared to one (310.4 N), p < 0.001. No significant differences were found for maximum pull‐out loads between two‐point fixation versus one‐point fixation but stiffness was significantly higher with two‐point fixation (107.4 N/mm vs. 79.4 N/mm, p < 0.001). More passes resulted in higher maximum pull‐out loads.ConclusionThe results suggest using two independent sutures, refixed separately and at least two suture passes, is appropriate for ACL refixation. More suture passes provide additional strength but are technically challenging to achieve during surgery.Level of EvidenceLevel IV.
Endothelial cell‐derived extracellular vesicles expressing surface VCAM1 promote sepsis‐related acute lung injury by targeting and reprogramming monocytes
Authors: Wang Lu , Tang Ying , Tang Jiajian , Liu Xu , Zi Shuangfeng , Li Songli , Chen Hanbing , Liu Airan , Huang Wei , Xie Jianfeng , Liu Ling , Chao Jie , Qiu Haibo 
Published: March 2024

AbstractAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common life‐threatening syndrome with no effective pharmacotherapy. Sepsis‐related ARDS is the main type of ARDS and is more fatal than other types. Extracellular vesicles (EVs) are considered novel mediators in the development of inflammatory diseases. Our previous research suggested that endothelial cell‐derived EVs (EC‐EVs) play a crucial role in ALI/ARDS development, but the mechanism remains largely unknown. Here, we demonstrated that the number of circulating EC‐EVs was increased in sepsis, exacerbating lung injury by targeting monocytes and reprogramming them towards proinflammatory macrophages. Bioinformatics analysis and further mechanistic studies revealed that vascular cell adhesion molecule 1 (VCAM1), overexpressed on EC‐EVs during sepsis, activated the NF‐κB pathway by interacting with integrin subunit alpha 4 (ITGA4) on the monocyte surface, rather than the tissue resident macrophage surface, thereby regulating monocyte differentiation. This effect could be attenuated by decreasing VCAM1 levels in EC‐EVs or blocking ITGA4 on monocytes. Furthermore, the number of VCAM1+ EC‐EVs was significantly increased in patients with sepsis‐related ARDS. These findings not only shed light on a previously unidentified mechanism underling sepsis‐related ALI/ARDS, but also provide potential novel targets and strategies for its precise treatment.
Gene expression prognostic of early relapse risk in low‐risk B‐cell acute lymphoblastic leukaemia in children
Authors: Gong Xiaowen , Hu Tianyuan , Shen Qiujin , Zhang Luyang , Zhang Wei , Liu Xueou , Zong Suyu , Li Xiaoyun , Wang Tiantian , Yan Wen , Hu Yu , Chen Xiaoli , Zheng Jiarui , Zhang Aoli , Wang Junxia , Feng Yahui , Li Chengwen , Ma Jiao , Gao Xin , Song Zhen , Zhang Yingchi , Gale Robert Peter , Zhu Xiaofan , Chen Junren 
Published: March 2024

AbstractETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low‐risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low‐risk ETV6::RUNX1‐positive B‐cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome‐wide transcriptome and single‐nucleotide variants. We found high TIMD4 expression (> 85th‐percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low‐risk ETV6::RUNX1‐positive B‐cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low‐risk ETV6::RUNX1‐negative B‐cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low‐risk B‐cell ALL in children might be associated with high risk for early relapse.
Emicizumab for acquired hemophilia A: Report of two cases and dosing strategies
Authors: Ahmed Faiza , Kasianchyk Mariia , Moreno Alejandro , Chang Simone , Maharaj Satish 
Published: March 2024

AbstractAcquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by autoantibodies against FVIII. Severe AHA is life‐threatening. Currently, licensed hemostatic agents for the treatment of severe AHA have short half‐lives and require intravenous administration, leading to a need for hospitalization, higher costs, and negative effects on quality of life. We present two cases of severe AHA with high inhibitor titers where emicizumab was safely and effectively used with intensive immunosuppression. These reports suggest in vivo efficacy even in high inhibitor environments. The optimal dosing regimen (accelerated vs. standard loading, maintenance frequency) is unknown and we discuss the current approaches.
Impact of climate change training intervention in savings groups
Authors: Nabami Armande Mahabi , Petre Anaëlle , Mersland Roy 
Published: March 2024

AbstractThis paper investigates the impact of integrating climate change interventions in informal community‐based institutions called savings groups. By integrating climate‐related activities into these groups, the aim is to simultaneously strengthen the group's financial activities as well as improve knowledge and investment capacity in climate adaptation. We find that the introduction of the training increases meeting attendance rate and average loan sizes, suggesting that members can access larger sums for investment to implement the knowledge acquired during the training. We provide evidence that there are opportunities for economies of scope and for a larger positive impact on the livelihoods of the populations at the bottom of the pyramid by combining financial services offered in the savings groups and climate‐related interventions.