bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel method for PET connectomics guided by fibre‐tracking MRI: Application to Alzheimer's disease
Authors: Sun Zhuopin , Naismith Sharon L. , Meikle Steven , Calamante Fernando ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: March 2024

This study introduces a novel brain connectome matrix, track‐weighted PET connectivity (twPC) matrix, which combines positron emission tomography (PET) and diffusion magnetic resonance imaging data to compute a PET‐weighted connectome at the individual subject level. The new method is applied to characterise connectivity changes in the Alzheimer's disease (AD) continuum. The proposed twPC samples PET tracer uptake guided by the underlying white matter fibre‐tracking streamline point‐to‐point connectivity calculated from diffusion MRI (dMRI). Using tau‐PET, dMRI and T1‐weighted MRI from the Alzheimer's Disease Neuroimaging Initiative database, structural connectivity (SC) and twPC matrices were computed and analysed using the network‐based statistic (NBS) technique to examine topological alterations in early mild cognitive impairment (MCI), late MCI and AD participants. Correlation analysis was also performed to explore the coupling between SC and twPC. The NBS analysis revealed progressive topological alterations in both SC and twPC as cognitive decline progressed along the continuum. Compared to healthy controls, networks with decreased SC were identified in late MCI and AD, and networks with increased twPC were identified in early MCI, late MCI and AD. The altered network topologies were mostly different between twPC and SC, although with several common edges largely involving the bilateral hippocampus, fusiform gyrus and entorhinal cortex. Negative correlations were observed between twPC and SC across all subject groups, although displaying an overall reduction in the strength of anti‐correlation with disease progression. twPC provides a new means for analysing subject‐specific PET and MRI‐derived information within a hybrid connectome using established network analysis methods, providing valuable insights into the relationship between structural connections and molecular distributions.

Practitioner Points

New method is proposed to compute patient‐specific PET connectome guided by MRI fibre‐tracking.

Track‐weighted PET connectivity (twPC) matrix allows to leverage PET and structural connectivity information.

twPC was applied to dementia, to characterise the PET nework abnormalities in Alzheimer's disease and mild cognitive impairment.
The impact of HIV/AIDS on marriage in the early years of the epidemic
Authors: Shahid Hasan
Published: March 2024

The advent of the HIV/AIDS crisis transformed the desirability of committed heterosexual relationships. This paper employs a difference‐in‐differences approach to investigate the impact of the HIV/AIDS crisis on marriage rates. By using HIV/AIDS death rates as a proxy for HIV incidence, the study exploits county‐level variations in HIV/AIDS mortality and finds that counties with higher HIV/AIDS death rates experienced larger gains in marriage rates in the early years of the epidemic. Estimates suggest that the virus increased marriage rates by approximately 0.9% in the early years of the virus (1981–1988).
Evaluation of the safety and effectiveness of robot‐assisted neck dissections
Authors: Snyder Vusala , Smith Brandon , Kim Seungwon , Spector Matthew E. , Duvvuri Umamaheswar
Published: March 2024

Background

Robot‐assisted neck dissection (RAND) for the management of the regional lymphatic basin offers the potential for improved cosmesis and reduced lymphedema. While RAND has been previously described, functional outcome and oncologic control rates need further elucidation.

Methods

A retrospective, matched cohort study of neck dissections completed at UPMC from 2017 to 2021 was conducted. RAND was identified and matched to open neck dissections (open) in a 1:2 ratio. Matching characteristics included primary cancer site, pre‐operative clinical N‐stage, age at time of surgery, HPV status, and previous chemoradiation treatment (salvage vs. nonsalvage procedure). Additional information was collected on patient demographics, surgery characteristics, and outcomes. Comparisons were made using t‐test, chi‐square test, Fisher's exact test, and Kaplan–Meier Wilcoxon (KMW) test with p < 0.05 indicating significance.

Results

Overall, RAND and open groups had similar distributions of age, gender, BMI, primary site of cancer, HPV status, clinical N‐stage, clinical T‐stage, known neck disease prior to procedure, prior chemoradiation therapy, and level(s) of neck dissection. Surgically, RAND procedures yielded less drainage on average (124 mL in RAND vs. 220 mL in open approaches; p = 0.01). There was no difference in the rates of complications, estimated blood loss, or number of lymph nodes obtained. There were also no differences in the rates of adjuvant therapy. Long term, there were no differences in the rates of local, locoregional, and distant recurrence of primary disease between RAND and open procedures. There were also no differences in postprocedure disease‐free survival time (KMW p‐value = 0.32; HR [of RAND compared with open] = 0.62). Similarly, there were no statistical differences in the overall survival of RAND patients when compared with the open group (75 vs. 58.9 months; HR = 0.11, p = 0.87).

Conclusion

This study is the first to report the long‐term effectiveness of robot‐assisted surgery compared with the traditional, open approach. In addition to well‐known cosmetic benefits, robot‐assisted surgery may also offer patients a reduction in uncomfortable drains and improved effects from lymphedema. Overall, this study provides initial data that the RAND may be considered as an alternative approach to open surgery.
Intelligent method to predict intensive care unit admission after drainage operation in patients with deep neck space abscess: A multicenter retrospective study
Authors: Lei Han , Lin Yu , Chen Weixiong , Liu Tianrun , Ye Jin , Cai Qian , Ye Fei , He Long , Xie Xingqiang , Xiong Guoping , Gao Wenxiang , Lei Wenbin
Published: March 2024

Backgrounds

A deep neck space abscess (DNSA) is a critical condition resulting from infection of deep neck fascia and soft issue, leading to high morbidity and mortality. Therefore, intensive care can be very significant for patients with DNSA. This study aimed to develop models to predict the need for postoperative intensive care in patients with DNSA.

Methods

We retrospectively analyzed the records of 332 patients with DNSA who received drainage operation between 2015 and 2020. Multivariate logistic regression analysis and the eXtrem Gradient Boosting (XGBoost) algorithm were used to develop predictive models.

Results

We developed two predictive models, the nomogram and the XGBoost model. The area under the curve (AUC) of the nomogram was 0.911 and of the XGBoost model was 0.935.

Conclusion

We developed two predictive models for guiding clinical decision making for postoperative ICU admission for DNSA patients, which may help improve prognosis and optimize intensive care resource allocation.
Multi‐omics analysis reveals epigenetically regulated processes and patient classification in lung adenocarcinoma
Authors: Brativnyk Anastasia , Ankill Jørgen , Helland Åslaug , Fleischer Thomas
Published: March 2024

Aberrant DNA methylation is a hallmark of many cancer types. Despite our knowledge of epigenetic and transcriptomic alterations in lung adenocarcinoma (LUAD), we lack robust multi‐modal molecular classifications for patient stratification. This is partly because the impact of epigenetic alterations on lung cancer development and progression is still not fully understood. To that end, we identified disease‐associated processes under epigenetic regulation in LUAD. We performed a genome‐wide expression‐methylation Quantitative Trait Loci (emQTL) analysis by integrating DNA methylation and gene expression data from 453 patients in the TCGA cohort. Using a community detection algorithm, we identified distinct communities of CpG‐gene associations with diverse biological processes. Interestingly, we identified a community linked to hormone response and lipid metabolism; the identified CpGs in this community were enriched in enhancer regions and binding regions of transcription factors such as FOXA1/2, GRHL2, HNF1B, AR, and ESR1. Furthermore, the CpGs were connected to their associated genes through chromatin interaction loops. These findings suggest that the expression of genes involved in hormone response and lipid metabolism in LUAD is epigenetically regulated through DNA methylation and enhancer‐promoter interactions. By applying consensus clustering on the integrated expression‐methylation pattern of the emQTL‐genes and CpGs linked to hormone response and lipid metabolism, we further identified subclasses of patients with distinct prognoses. This novel patient stratification was validated in an independent patient cohort of 135 patients and showed increased prognostic significance compared to previously defined molecular subtypes.
Brain tumor image segmentation algorithm based on multimodal feature fusion of Bayesian weight distribution
Authors: Li Ju , Wang Yanhui , Wang Guoliang
Published: March 2024

This 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

Phosphodiesterase‐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

Estrogen 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

Normoxic 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

An 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

A 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

Purpose

To 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.

Methods

This 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.

Results

The 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).

Conclusion

These 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

Purpose

While 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.

Methods

In 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.

Results

There 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%.

Conclusion

Pleural 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

Introduction

Recent 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.

Objective

Review 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.

Methodology

This 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.

Results

Thirty‐five eligible articles were collected, analyzed, and grouped according to the levels of alterations.

Conclusion

The 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

Purpose

Refixation 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.

Methods

Sixty 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.

Results

Two‐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.

Conclusion

The 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 Evidence

Level 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

Acute 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

ETV6::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

Acquired 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

This 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.
Prolonged viral shedding in an immunocompromised Korean patient infected with hMPXV, sub‐lineage B.1.3, with acquired drug resistant mutations during tecovirimat treatment
Authors: Lee Minji , Choi Chi‐Hwan , Kim Jin‐Won , Sim Gyuri , Lee Sang Eun , Shin Hwachul , Lee Jeong hyun , Choi Myung‐Min , Yi Hwajung , Chung Yoon‐Seok
Published: March 2024

Following the worldwide surge in mpox (monkeypox) in 2022, cases have persisted in Asia, including South Korea, and sexual contact is presumed as the predominant mode of transmission, with a discernible surge in prevalence among immunocompromised patients. Drugs such as tecovirimat can result in drug‐resistant mutations, presenting obstacles to treatment. This study aimed to ascertain the presence of tecovirimat‐related resistant mutations through genomic analysis of the monkeypox virus isolated from a reported case involving prolonged viral shedding in South Korea. Here, tecovirimat‐resistant mutations, previously identified in the B.1 clade, were observed in the B.1.3 clade, predominant in South Korea. These mutations exhibited diverse patterns across different samples from the same patient and reflected the varied distribution of viral subpopulations in different anatomical regions. The A290V and A288P mutant strains we isolated hold promise for elucidating these mechanisms, enabling a comprehensive analysis of viral pathogenesis, replication strategies, and host interactions. Our findings imply that acquired drug‐resistant mutations, may present a challenge to individual patient treatment. Moreover, they have the potential to give rise to transmitted drug‐resistant mutations, thereby imposing a burden on the public health system. Consequently, the meticulous genomic surveillance among immunocompromised patients, conducted in this research, assumes paramount importance.
Age‐dependent changes in collagen crosslinks reduce the mechanical toughness of human meniscus
Authors: Nesbitt Derek Q. , Pu Xinzhu , Turner Matthew W. , Zavala Anamaria G. , Bond Laura , Oxford Julia T. , Lujan Trevor J.
Published: March 2024

The mechanical resilience of the knee meniscus is provided by a group of structural proteins in the extracellular matrix. Aging can alter the quantity and molecular structure of these proteins making the meniscus more susceptible to debilitating tears. In this study, we determined the effect of aging on the quantity of structural proteins and collagen crosslinks in human lateral meniscus, and examined whether the quantity of these molecules was predictive of tensile toughness (area under the stress‐strain curve). Two age groups were tested: a young group under 40 and an older group over 65 years old. Using mass spectrometry, we quantified the abundance of proteins and collagen crosslinks in meniscal tissue that was adjacent to the dumbbell‐shaped specimens used to measure uniaxial tensile toughness parallel or perpendicular to the circumferential fiber orientation. We found that the enzymatic collagen crosslink deoxypyridinoline had a significant positive correlation with toughness, and reductions in the quantity of this crosslink with aging were associated with a loss of toughness in the ground substance and fibers. The non‐enzymatic collagen crosslink carboxymethyl‐lysine increased in quantity with aging, and these increases corresponded to reductions in ground substance toughness. For the collagenous (Types I, II, IV, VI, VIII) and non‐collagenous structural proteins (elastin, decorin, biglycan, prolargin) analyzed in this study, only the quantity of collagen VIII was predictive of toughness. This study provides valuable insights on the structure‐function relationships of the human meniscus, and how aging causes structural adaptations that weaken the tissue's mechanical integrity.
One‐bite‐sized 3D printed finger foods, oriented to malnutrition, sarcopenia and frailty prevention in the older people
Authors: Kurapkienė Aušrinė , Vinauskienė Rimantė , Jasutienė Ina , Damulevičienė Gytė , Knašienė Jurgita , Lesauskaitė Vita , Sulmont‐Rossé Claire , Eisinaitė Viktorija , Leskauskaitė Daiva
Published: March 2024

BACKGROUND

In this study, innovative chocolate, citrus and mixture flavoured tofu‐based nutritionally customised, dysphagia‐oriented, comfortably consumed, appetising, one‐bite‐sized finger foods, oriented to malnutrition, sarcopenia and frailty prevention in older people were created by using 3D printing technology. Developed products were characterised by evaluating chemical composition and physical properties and performing sensory evaluation among geriatric clinic residents (≥60 years).

RESULTS

The dietary composition of the developed foods was: 19–21 g (100 g)−1 protein, 6–8 g (100 g)−1 fibre, 8–9 g (100 g)−1 fat, 11 mg (100 g)−1 iron, 14 mg (100 g)−1 zinc, 70 μg (100 g)−1 selenium. Foods were also enriched with branched‐chain amino acids, such as leucine, isoleucine and valine. All formulated foods were classified as level 6 by International Dysphagia Diet Standardisation Initiative classification. Chocolate‐flavoured food was much harder (4914 g) with lower adhesiveness value (−33.6 g s), compared to the citrus‐ or mixture‐flavoured foods. Older people evaluated all finger foods as very easy handled by hand, soft, easy to swallow, having a moderate flavour intensity and a weak afterfeel. Despite the fact that the chocolate food was evaluated as having the highest hardness and gumminess values by the instrumental method, this difference was not noticeable to the evaluators. However 7% of the participants said that 3D printed foods were sticky to dentures.

CONCLUSION

The results suggest that it is possible to create nutrient‐dense comfortably consumed 3D printed foods, oriented to malnutrition, sarcopenia and frailty prevention in older people. © 2024 Society of Chemical Industry.
Natural landscape performance: Environmental restorativeness and its influence on tourist behavior
Authors: Chen Xiaohua , Lee Gyehee , Joo Dongoh
Published: March 2024

This study uses environmental psychology theory to explore creative natural landscape performance (NLP), a form of tourism performing arts that combines natural beauty and cultural resources. Tourists who had experienced an NLP during the previous 2 years were surveyed, and 408 valid responses were collected through this online survey. The findings indicate that the natural setting of NLPs possesses the key characteristics of restorative environments. Further, the five dimensions of a restorative environment positively affect favorable emotions (i.e., happy, excited, relaxed) in the order of compatibility, being away, fascination, scope, and coherence of the performance. Positive emotions have a positive and substantial influence on the quality of the experience and its perceived flow. Additionally, quality of experience and perceived flow has direct and positive impacts on loyalty. Therefore, this study suggests utilizing and improving natural environments' restorative qualities to enhance NLPs for tourists and foster destination loyalty based on this.
Superiority of kinematic alignment over mechanical alignment in total knee arthroplasty during medium‐ to long‐term follow‐up: A meta‐analysis and trial sequential analysis
Authors: Wang Guiguan , Chen Long , Luo Fenqi , Luo Jun , Xu Jie
Published: March 2024

Purpose

To compare and determine the reliability and conclusiveness of the medium‐ and long‐term efficacy in terms of patient‐reported outcome measures and the risk of revisions or reoperations (RRRs) of kinematic alignment (KA) and mechanical alignment (MA) in total knee arthroplasty.

Methods

A comprehensive search was conducted in Medline, EMBASE, Web of Science and Cochrane Database Library to identify relevant literature. Only randomised clinical trials (RCTs) published before July 2023 were included. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), Forgotten Joint Score (FJS) and RRR were compared. Additionally, OKS and RRR were subjected to a trial sequential analysis.

Results

Seven RCTs involving 572 knees were identified. The pooled analysis of the included studies demonstrated that KA showed better medium‐term WOMAC and OKS (mean difference [MD] = −6.3, 95% confidence interval [CI]: −9.52 to −2.99, p < 0.05 and MD = 1.1, 95% CI: 0.05–2.15, p < 0.05), respectively), but no significant differences were observed in the long‐term follow‐up (MD = 2.1, 95% CI: −3.21 to 7.31, not significant [n.s.] and MD = 0.01, 95% CI: −2.43 to 2.46, n.s., respectively). FJS (standardised MD = −0.03, 95% CI: −0.25 to 0.19, n.s.) and RRR (risk ratio = 1.0, 95% CI: 0.57 to 1.74, n.s.) showed no significant intergroup differences (n.s.). The evidence quality ranged from moderate to high, and the trial sequential analysis indicated the need for additional high‐quality RCTs to draw more conclusive results.

Conclusions

KA showed better medium‐term WOMAC and OKS, while KA and MA had similar FJS without increasing the RRR in medium‐ and long‐term follow‐up. Further research is needed for more conclusive results.

Level of Evidence

Level II (meta‐analyses).
From technical to understandable: Artificial Intelligence Large Language Models improve the readability of knee radiology reports
Authors: Butler James J. , Puleo James , Harrington Michael C. , Dahmen Jari , Rosenbaum Andrew J. , Kerkhoffs Gino M. M. J. , Kennedy John G.
Published: March 2024

Purpose

The purpose of this study was to evaluate the effectiveness of an Artificial Intelligence‐Large Language Model (AI‐LLM) at improving the readability of knee radiology reports.

Methods

Reports of 100 knee X‐rays, 100 knee computed tomography (CT) scans and 100 knee magnetic resonance imaging (MRI) scans were retrieved. The following prompt command was inserted into the AI‐LLM: ‘Explain this radiology report to a patient in layman's terms in the second person:[Report Text]’. The Flesch–Kincaid reading level (FKRL) score, Flesch reading ease (FRE) score and report length were calculated for the original radiology report and the AI‐LLM generated report. Any ‘hallucination’ or inaccurate text produced by the AI‐LLM‐generated report was documented.

Results

Statistically significant improvements in mean FKRL scores in the AI‐LLM generated X‐ray report (12.7 ± 1.0–7.2 ± 0.6), CT report (13.4 ± 1.0–7.5 ± 0.5) and MRI report (13.5 ± 0.9–7.5 ± 0.6) were observed. Statistically significant improvements in mean FRE scores in the AI‐LLM generated X‐ray report (39.5 ± 7.5–76.8 ± 5.1), CT report (27.3 ± 5.9–73.1 ± 5.6) and MRI report (26.8 ± 6.4–73.4 ± 5.0) were observed. Superior FKRL scores and FRE scores were observed in the AI‐LLM‐generated X‐ray report compared to the AI‐LLM‐generated CT report and MRI report, p < 0.001. The hallucination rates in the AI‐LLM generated X‐ray report, CT report and MRI report were 2%, 5% and 5%, respectively.

Conclusions

This study highlights the promising use of AI‐LLMs as an innovative, patient‐centred strategy to improve the readability of knee radiology reports. The clinical relevance of this study is that an AI‐LLM‐generated knee radiology report may enhance patients' understanding of their imaging reports, potentially reducing the responder burden placed on the ordering physicians. However, due to the ‘hallucinations’ produced by the AI‐LLM‐generated report, the ordering physician must always engage in a collaborative discussion with the patient regarding both reports and the corresponding images.

Level of Evidence

Level IV.
A Bibliometric Analysis of Chickpea Agronomic Practices in the World During 45 Years of Scientific Research
Authors: Calia Claudio , Pulvento Cataldo , Sellami Mohamed Houssemeddine , Tedone Luigi , Ruta Claudia , De Mastro Giuseppe
Published: March 2024

Chickpea (Cicer arietinum L.) cultivation practices underwent significant transformation in recent decades due to advancements in scientific knowledge and the need for sustainable, productive farming systems. In this study, a bibliometric analysis of scientific publications from 1977 to 2023 on chickpea agronomic practices was conducted, revealing critical insights. India, as the world's leading chickpea producer, plays a pivotal role, not only in production but also as a significant contributor to scholarly research and international collaborations. The choice of journals for publication is found to influence research impact.

Analysis of research trends using co‐occurrence networks of keywords reveals evolving focuses, with a recent shift towards qualitative aspects, such as protein content and nutritional quality, as well as sustainable agricultural practices. The study also emphasizes the necessity for further research on chickpea quality characteristics, strategies to mitigate antinutritional factors, yield optimization, and the impact of climate change on chickpea cultivation. Ultimately, chickpea cultivation research holds great promise in contributing to global food security and environmental sustainability. This bibliometric analysis provides a comprehensive overview of chickpea cultivation research and offers valuable insights for researchers, policymakers, and stakeholders as they navigate the future of sustainable agriculture and the quest for protein‐rich food production while minimizing the environmental footprint.
Drug Efficacy Comparison of pH‐Sensitive and Non‐pH‐Sensitive Taxol Delivery Nanoparticles in Cancer Therapy
Authors: Wang Jianquan , Ruan Xinyan , Guan Hangmin , Fu Hailuo , Ai Shichao , Wang Yiqing
Published: March 2024

Taxol is one of the most widely used chemotherapeutic agents but is restricted by its poor solubility and severe side effects in clinical practice. To overcome these limitations, pH‐sensitive nanoparticles, Acetalated Dextran6k‐PEG5k‐PLA2k‐Taxol (ADPP‐PTX), non‐pH‐sensitive nanoparticles, and Propionic Anhydride modified Dextran6k‐PEG5k‐PLA2k‐Taxol (PDPP‐PTX) are developed for the delivery of Taxol. Compared with PDPP‐PTX, ADPP‐PTX shows higher sensitivity to acid response and greater anti‐proliferative effect on cancer cells. In the in vivo study, ADPP‐PTX treatment effectively suppresses the growth of tumors, while only half the dose of Taxol is used, which significantly reduces systemic toxicity compared with Taxol and PDPP‐PTX.
Enhancing the Potential of Poly(hydroxybutyrate)/Poly(lactic acid) Films with Olive Oil and Zinc Oxide for Active Food Packaging
Authors: Ahuja Simran , Mittal Mahak , Aggarwal Neeraj K. , Arora Sanjiv
Published: March 2024

To tackle the persistent global issue of nonbiodegradable petro‐plastics, this study undertakes the challenge of developing environmentally sustainable and active packaging alternatives. The approach involves preparing composite films by blending poly(hydroxybutyrate) (PHB) and poly(lactic acid) (PLA) while integrating olive oil and zinc oxide to augment their effectiveness. The films are fabricated by mixing different concentrations of ZnO (0.5% to 2.5%) and 10% olive oil into PHB/PLA (70/30) matrix using solvent‐casting. A comprehensive analysis is conducted to assess the properties of prepared films, including Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, X‐ray diffraction, mechanical testing, water vapor permeability, and UV‐blocking properties. Among the tested samples, film containing 1.5% ZnO (referred to as PPOZ1.5) displays highest tensile strength (30.8 MPa) along with improved water vapor permeability. Consequently, PPOZ1.5 film is selected for further investigations which include DPPH (diphenyl‐picrylhydrazyl) radical scavenging activity, and antimicrobial activity. PPOZ1.5 film exhibits exceptional antioxidant activity (>65%) and significant antimicrobial efficacy against Escherichia coli, Staphylococcus aureus, and Aspergillus niger. Moreover, when utilized to package bread samples, PPOZ1.5 film effectively inhibits microbial growth, ensuring food safety for an extended storage period of more than 12 days, ultimately contributing to the preservation and safety of packaged bakery products.