bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGASUHAN ANAK USIA DINI DI ERA TEHNOLOGI DIGITAL
Authors: Diananda Amita
Published: February 2024

Digital technology, such as gadgets (hardware) and their applications (software), has been able to change the world order in interacting and communicating. In the process of parenting early childhood, the use of gadgets is nothing unfamiliar. However, the use of gadgets, without control, in parenting, can make children experience a change in mental and attitude where gadgets begin to dwindle the attachment of children's relationships to parents and switches it into the attachment to gadgets. The use of digital technology for early childhood at home and school has increased in intensity, especially during the Covid-19 outbreak. The teaching and learning process in schools has changed from face-to-face meetings (offline) to long distance meetings (online). The purpose of this study is to anticipate early childhood from being addicted to gadgets, and parental control is needed then, mainly in controlling the duration of the use of the gadget devices and the selection of the content in the form of pictures/videos that the children watch. The task of parents is to be a controller in the transfer process of knowledge, values, and guidance. Thus the mental and psychological health and moral of children are well maintained. The results of this literature research show that "children with a high duration of smartphone use without parental supervision have lower pro-social behavior than other children who use devices under parental supervision". Also, â€œthe higher the intensity of smartphone use, the lower the interaction of children with their parents. On the other hand, the lower the intensity of smartphone use, the higher the interaction between children and their parents.â€Keywords: Parenting, early childhood, and the era of digital.
Peningkatan Kemampuan Bahasa Anak Menggunakan Metode Bernyanyi Pada Anak 5-6 Tahun
Authors: Fitria Selvi
Published: February 2024

The purpose of this study is to facilitate children to improve language skills in students of group B KB Cempaka Putri by using singing methods. Because singing method is one way to stimulate the development of language in life. Singing can improve children's vocabulary so that they can develop aspects of their language development. This research is classroom action research. The research is divided into two cycles, with each cycle consisting of design, execution of actions, observations, and reflections. The subjects of the study were students of group B KB. Cempaka Putri, numbering 6 people. The data source comes from teachers and students. Data collection techniques are observation, interview, and documentation. Validity of data using source triangulation techniques, triangulation methods and time triangulation. Data analysis using qualitative data analysis techniques and quantitative data analysis. The results showed that the use of singing methods can improve children's language skills from pre-cycle to cycle I and from cycle I to cycle II that is carried out well and effectively, this can be seen from the change in aspects of language skills in listening, understanding language, and expressing language better than ever. The conclusion of this study is that the application of singing methods can improve the language skills of students of group B KB Cempaka Putri.
Peran Guru sebagai Komunikator dalam Menanamkan Nilai Karakter Komunikatif (Analisis Film Aisyah: Biarkan Kami Bersaudara Karya Herwin Novianto)
Authors: Farhan Muhammad Nabil
Published: February 2024

This study intended to analyse, describe and comprehend the application of the teacherâ€™s role as a communicator in building the importance of pleasant, conversational character education in Aisyahâ€™s film: Let Us Be Brothers by Hewin Novianto. This study employed a qualitative method of library research type. The data collection applied content analysis techniques. The studyâ€™s findings indicated there was a message and relevance of the teacherâ€™s role as a communicator and the value of communicative character education in Aisyahâ€™s film: Let Us Be Brothers, by Herwin Novianto, namely: 1) The teachersâ€™s role as communicators (able to channel their knowledge for the good of society, create harmony, solve problems for the benefit and sincerely help students who are having difficulties). 2) The value of pleasant communicative education (being patient, adaptive, inquiring about studentsâ€™ conditions further, socialising with students, and visiting their houses) Â
PENGARUH BUDAYA RELIGIUS TERHADAP AHKLAK SISWA
Authors: Fitri Ana , Candra Bach Yunof
Published: February 2024

This research is a descriptive quantitative research, in this research the researcher uses two variables, namely religious culture (X) and student morals (Y). This research was conducted by distributing questionnaires to students of MTs esa nusa islamic school housing binong kec.curug kab.Tangerang, Adapu subjects in this study were all students at MTs Esa Nusa Islamic School Binong totaling 74 students. The validity of the data uses the triangulation method, the analysis uses descriptive statistical analysis SPSS persi 34. The results show that there is a significant influence between the influence of religious culture on the morals of students at MTs esa nusa Islamic school binong, which is in accordance with the coefficient of determination test (R2) the influence of religious culture on student morals by 14.7% while the rest is influenced by other variables.
Computational identification of antibody-binding epitopes from mimotope datasets
Authors: Li Rang , Wilderotter Sabrina , Stoddard Madison , Van Egeren Debra , Chakravarty Arijit , Joseph-McCarthy Diane
Published: February 2024

Introduction: A fundamental challenge in computational vaccinology is that most B-cell epitopes are conformational and therefore hard to predict from sequence alone. Another significant challenge is that a great deal of the amino acid sequence of a viral surface protein might not in fact be antigenic. Thus, identifying the regions of a protein that are most promising for vaccine design based on the degree of surface exposure may not lead to a clinically relevant immune response.

Methods: Linear peptides selected by phage display experiments that have high affinity to the monoclonal antibody of interest (“mimotopes”) usually have similar physicochemical properties to the antigen epitope corresponding to that antibody. The sequences of these linear peptides can be used to find possible epitopes on the surface of the antigen structure or a homology model of the antigen in the absence of an antigen-antibody complex structure.

Results and Discussion: Herein we describe two novel methods for mapping mimotopes to epitopes. The first is a novel algorithm named MimoTree that allows for gaps in the mimotopes and epitopes on the antigen. More specifically, a mimotope may have a gap that does not match to the epitope to allow it to adopt a conformation relevant for binding to an antibody, and residues may similarly be discontinuous in conformational epitopes. MimoTree is a fully automated epitope detection algorithm suitable for the identification of conformational as well as linear epitopes. The second is an ensemble approach, which combines the prediction results from MimoTree and two existing methods.
Three-dimensional gait analysis of orthopaedic common foot and ankle joint diseases
Authors: Wang Yifan , Qi Yansong , Ma Bingxian , Wu Haihe , Wang Yongxiang , Wei Baogang , Wei Xinghua , Xu Yongsheng
Published: February 2024

Walking is an indispensable mode of transportation for human survival. Gait is a characteristic of walking. In the clinic, patients with different diseases exhibit different gait characteristics. Gait analysis describes the specific situation of human gait abnormalities by observing and studying the kinematics and dynamics of limbs and joints during human walking and depicting the corresponding geometric curves and values. In foot and ankle diseases, gait analysis can evaluate the degree and nature of gait abnormalities in patients and provide an important basis for the diagnosis of patients’ diseases, the correction of abnormal gait and related treatment methods. This article reviews the relevant literature, expounds on the clinical consensus on gait, and summarizes the gait characteristics of patients with common ankle and foot diseases. Starting from the gait characteristics of individuals with different diseases, we hope to provide support and reference for the diagnosis, treatment and rehabilitation of clinically related diseases.
Automatic segmentation of skeletal muscles from MR images using modified U-Net and a novel data augmentation approach
Authors: Lin Zhicheng , Henson William H. , Dowling Lisa , Walsh Jennifer , Dall’Ara Enrico , Guo Lingzhong
Published: February 2024

Rapid and accurate muscle segmentation is essential for the diagnosis and monitoring of many musculoskeletal diseases. As gold standard, manual annotation suffers from intensive labor and high inter-operator reproducibility errors. In this study, deep learning (DL) based automatic muscle segmentation from MR scans is investigated for post-menopausal women, who normally experience a decline in muscle volume. The performance of four Deep Learning (DL) models was evaluated: U-Net and UNet++ and two modified U-Net networks, which combined feature fusion and attention mechanisms (Feature-Fusion-UNet, FFU, and Attention-Feature-Fusion-UNet, AFFU). The models were tested for automatic segmentation of 16-lower limb muscles from MRI scans of two cohorts of post-menopausal women (11 subjects in PMW-1, 8 subjects in PMW-2; from two different studies so considered independent datasets) and 10 obese post-menopausal women (PMW-OB). Furthermore, a novel data augmentation approach is proposed to enlarge the training dataset. The results were assessed and compared by using the Dice similarity coefficient (DSC), relative volume error (RVE), and Hausdorff distance (HD). The best performance among all four DL models was achieved by AFFU (PMW-1: DSC 0.828 ± 0.079, 1-RVE 0.859 ± 0.122, HD 29.9 mm ± 26.5 mm; PMW-2: DSC 0.833 ± 0.065, 1-RVE 0.873 ± 0.105, HD 25.9 mm ± 27.9 mm; PMW-OB: DSC 0.862 ± 0.048, 1-RVE 0.919 ± 0.076, HD 34.8 mm ± 46.8 mm). Furthermore, the augmentation of data significantly improved the DSC scores of U-Net and AFFU for all 16 tested muscles (between 0.23% and 2.17% (DSC), 1.6%–1.93% (1-RVE), and 9.6%–19.8% (HD) improvement). These findings highlight the feasibility of utilizing DL models for automatic segmentation of muscles in post-menopausal women and indicate that the proposed augmentation method can enhance the performance of models trained on small datasets.
Oral streptococci: modulators of health and disease
Authors: Bloch Susanne , Hager-Mair Fiona F. , Andrukhov Oleh , Schäffer Christina
Published: February 2024

Streptococci are primary colonizers of the oral cavity where they are ubiquitously present and an integral part of the commensal oral biofilm microflora. The role oral streptococci play in the interaction with the host is ambivalent. On the one hand, they function as gatekeepers of homeostasis and are a prerequisite for the maintenance of oral health - they shape the oral microbiota, modulate the immune system to enable bacterial survival, and antagonize pathogenic species. On the other hand, also recognized pathogens, such as oral Streptococcus mutans and Streptococcus sobrinus, which trigger the onset of dental caries belong to the genus Streptococcus. In the context of periodontitis, oral streptococci as excellent initial biofilm formers have an accessory function, enabling late biofilm colonizers to inhabit gingival pockets and cause disease. The pathogenic potential of oral streptococci fully unfolds when their dissemination into the bloodstream occurs; streptococcal infection can cause extra-oral diseases, such as infective endocarditis and hemorrhagic stroke. In this review, the taxonomic diversity of oral streptococci, their role and prevalence in the oral cavity and their contribution to oral health and disease will be discussed, focusing on the virulence factors these species employ for interactions at the host interface.
Systemic-to-pulmonary collateral flow associations with antegrade pulmonary flow in single ventricle patients: insights from cardiac magnetic resonance imaging
Authors: Yanovskiy Anna , Martelius Laura , Nyman Nicolina , Vepsäläinen Teemu , Mattila Ilkka , Rahkonen Otto , Ojala Tiina
Published: February 2024

Purpose

In the palliated single ventricle anomalies, a considerable amount of the aortic flow may be absorbed by the systemic-pulmonary collateral flow (SPCF), which can be noninvasively assessed by cardiac magnetic resonance (CMR). The aims of this study were to (1) identify factors associated with SCPF in pediatric single ventricle patients, and (2) establish a cutoff values indicating an association between SCPF and a reduction in antegrade pulmonary flow.

Methods

A retrospective single-tertiary-center cohort study included 158 consecutive CMR studies of patients with a single ventricle. In the uni- and multivariable analysis, SPCF was presented as a percentage of the total pulmonary venous flow (SPCF%PV). The minimal clinically important difference in QP/QS ratios was estimated as ≥0.50, and an optimal cutoff value was defined using the receiver operating characteristic (ROC) curve.

Results

SPCF%PV was significantly smaller in the post-total cavopulmonary connection (TCPC) group than in the pre-TCPC patients (p < 0.001). The patient's higher age and a higher antegrade pulmonary flow were associated with a lower SPCF%PV. A negative weak association was observed between the SPCF%PV and systemic saturation (r = −0.39, p < 0.001). SPCF%PV did not associate with ventricular volumes nor ejection fraction. The SPCF%PV was significantly smaller in patients that were palliated primarily with a pulmonary artery banding compared to those palliated with a BT-shunt (p = 0.002) or RV-PA- shunt (p = 0.044). In the ROC analysis, for pre-TCPC patient's, a cutoff of SPCF%PV 42% yielded a sensitivity of 100% and specificity of 80% for significantly reduced antegrade pulmonary flow (AUC 0.97). In the post-TCPC group, the optimal SPCF%PV cutoff was 34% (sensitivity 100%, specificity 98%, AUC 0.99).

Conclusion

SPCF results in a considerable left-to-right shunt, which subsequently diminishes spontaneously after TCPC. Our findings indicated that for pre-TCPC patients, an SPCF%PV threshold of 42% (sensitivity 100%, specificity 80%), and for the post-TCPC group, a threshold of 34% (sensitivity 100%, specificity 98%) were effective in identifying reduced antegrade pulmonary flow.
Association between high-density lipoprotein cholesterol and type 2 diabetes mellitus: dual evidence from NHANES database and Mendelian randomization analysis
Authors: Yan Zhaoqi , Xu Yifeng , Li Keke , Liu Liangji
Published: February 2024

Background

Low levels of high-density lipoprotein cholesterol (HDL-C) are commonly seen in patients with type 2 diabetes mellitus (T2DM). However, it is unclear whether there is an independent or causal link between HDL-C levels and T2DM. This study aims to address this gap by using the The National Health and Nutrition Examination Survey (NHANES) database and Mendelian randomization (MR) analysis.

Materials and methods

Data from the NHANES survey (2007-2018) with 9,420 participants were analyzed using specialized software. Logistic regression models and restricted cubic splines (RCS) were used to assess the relationship between HDL-C and T2DM incidence, while considering covariates. Genetic variants associated with HDL-C and T2DM were obtained from genome-wide association studies (GWAS), and Mendelian randomization (MR) was used to evaluate the causal relationship between HDL-C and T2DM. Various tests were conducted to assess pleiotropy and outliers.

Results

In the NHANES study, all groups, except the lowest quartile (Q1: 0.28-1.09 mmol/L], showed a significant association between HDL-C levels and reduced T2DM risk (all P < 0.001). After adjusting for covariates, the Q2 [odds ratio (OR) = 0.67, 95% confidence interval (CI): (0.57, 0.79)], Q3 [OR = 0.51, 95% CI: (0.40, 0.65)], and Q4 [OR = 0.29, 95% CI: (0.23, 0.36)] groups exhibited average reductions in T2DM risk of 23%, 49%, and 71%, respectively. In the sensitivity analysis incorporating other lipid levels, the Q4 group still demonstrates a 57% reduction in the risk of T2DM. The impact of HDL-C levels on T2DM varied with age (P for interaction = 0.006). RCS analysis showed a nonlinear decreasing trend in T2DM risk with increasing HDL-C levels (P = 0.003). In the MR analysis, HDL-C levels were also associated with reduced T2DM risk (OR = 0.69, 95% CI = 0.52-0.82; P = 1.41 × 10-13), and there was no evidence of pleiotropy or outliers.

Conclusion

This study provides evidence supporting a causal relationship between higher HDL-C levels and reduced T2DM risk. Further research is needed to explore interventions targeting HDL-C levels for reducing T2DM risk.
Unveiling the pathogenesis and therapeutic approaches for diabetic nephropathy: insights from panvascular diseases
Authors: Zhang Xiaoqian , Zhang Jiale , Ren Yan , Sun Ranran , Zhai Xu
Published: February 2024

Diabetic nephropathy (DN) represents a significant microvascular complication in diabetes, entailing intricate molecular pathways and mechanisms associated with cardiorenal vascular diseases. Prolonged hyperglycemia induces renal endothelial dysfunction and damage via metabolic abnormalities, inflammation, and oxidative stress, thereby compromising hemodynamics. Concurrently, fibrotic and sclerotic alterations exacerbate glomerular and tubular injuries. At a macro level, reciprocal communication between the renal microvasculature and systemic circulation establishes a pernicious cycle propelling disease progression. The current management approach emphasizes rigorous control of glycemic levels and blood pressure, with renin-angiotensin system blockade conferring renoprotection. Novel antidiabetic agents exhibit renoprotective effects, potentially mediated through endothelial modulation. Nonetheless, emerging therapies present novel avenues for enhancing patient outcomes and alleviating the disease burden. A precision-based approach, coupled with a comprehensive strategy addressing global vascular risk, will be pivotal in mitigating the cardiorenal burden associated with diabetes.
Exploring genetic variation and phylogenetic patterns of Tropilaelaps mercedesae (Mesostigmata: Laelapidae) populations in Asia
Authors: Mohamadzade Namin Saeed , Joharchi Omid , Aryal Sunil , Thapa Ratna , Kwon Sun-Ho , Kakhramanov Boymakhmat A. , Jung Chuleui
Published: February 2024

Introduction

The mites belonging to the genus Tropilaelaps are ectoparasites of honey bees, primarily infesting the larval and pupal stages. Originating from subtropical regions, these mites can cause brood malformation, bee mortality, and subsequent decline or absconding of colonies.

Material and methods

During field surveys conducted in Nepal, South Korea, and Uzbekistan to investigate honey bee pests, several populations of T. mercedesae were collected. This is the first record of T. mercedesae from Uzbekistan. The morphological characteristics of the collected populations were analyzed, and their phylogenetic relationship with other Asian populations was examined.

Results and discussion

The molecular analysis of cytochrome oxidase I gene revealed high similarity between Uzbekistan and Pakistan populations, signaling the potential invasion of subtropical honey bee parasites into the Central Asian beekeeping sectors. Phylogenetic analysis indicated the presence of four distinct lineages within the mainland-Indonesian populations of T. mercedesae. Notably, an evolutionary divergence was observed between the haplotypes from Sri Lanka and the Philippines compared to the remaining mainland Asian and Indonesian haplotypes, suggesting the possible existence of subspecies or separate species in these isolated locations. To gain a deeper understanding of this phenomenon, it is essential to continue monitoring the spread of this significant honey bee pest and conduct comprehensive morphological and molecular analyses of samples collected from these specific localities.
Spatio-temporal evolution and driving factors of regulating ecosystem service value: a case study of Poyang Lake Area, China
Authors: Liu Yaobin , Huang Nan , Liu Chenghao , Li Shuoshuo , Giannetti Biagio Fernando
Published: February 2024

Clarifying the driving mechanisms of spatial and temporal changes in the regulating ecosystem service value (RESV) is an important part of realizing the goal of sustainable development. Existing studies have focused on specific factors, ignoring the complex interactions between factors and their regional differences. In this regard, the spatial and temporal changes of RESV and its driving mechanisms in the different zones (core area, fringe area, and peripheral area) were explored in the Poyang Lake Area, China. The results showed that RESV spatially showed the distribution characteristics of fringe area > core area > peripheral area, while the lakes influenced the provision of regulating ecosystem services, showing that RESV per unit area was higher in the core area, and gradually declined with the increase of distance from the lakes, presenting the decreasing trend of fringe area > peripheral area. From 2000 to 2020, the study area lost 70.5988 billion CNY for RESV, in which the core area was the most affected. Further analysis of the driving mechanism of RESV in different areas found that there are regional differences in the paths of the driving factors: Population density mainly affects the core area, precipitation mainly affects the fringe area, and GDP per land mainly affects the peripheral area.
Potential causal associations of PM2.5 and osteoporosis: a two-sample mendelian randomization study
Authors: Zhang Yi , Yu Jinsheng , Pei Hang , Zhao Xinzheng , Wang Chao , Wang Guanyin , Shen Zan , Hua Jiang , He Bangjian
Published: February 2024

Background: Observational studies suggest a potential association between atmospheric particulate matter 2.5 (PM2.5) and osteoporosis, but a causal association is unclear due to the presence of confounding factors.

Methods: We utilized bone mineral density indices at four specific sites to represent osteoporosis: femoral neck (FN-BMD), lumbar spine (LS-BMD), forearm (FA-BMD), and heel (HE-BMD). The PM2.5 data was obtained from the UK Biobank database, while the datasets for FN-BMD, LS-BMD, and FA-BMD were obtained from the GEFOS database, and the dataset for HE-BMD was obtained from the EBI database. A two-sample Mendelian randomization analysis was conducted using mainly the inverse variance weighted method, horizontal pleiotropy and heterogeneity were also assessed.

Results: The results indicated that PM2.5 was not correlated with a decrease in FN-BMD (β: −0.305, 95%CI: −0.762, 0.153), LS-BMD (β: 0.134, 95%CI: −0.396, 0.666), FA-BMD (β: -0.056, 95%CI: −1.172,1.060), and HE-BMD (β: −0.084, 95%CI: −0.261,0.093). Additionally, acceptable levels of horizontal pleiotropy and heterogeneity were observed.

Conclusion: In contrast to most observational studies, our research did not discover a potential causal relationship between PM2.5 and the development of osteoporosis.
A case of IgG4-related ophthalmic disease after SARS-CoV-2 vaccination: case report and literature review
Authors: Zhang Peixuan , Wu Qian , Xu Xiao , Chen Minliang
Published: February 2024

Coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is affecting the world with a surge in cases. A variety of autoimmune diseases occur after SARS-CoV-2 infection or vaccination, of which IgG4-related disease (IgG4-RD) is an important type. IgG4-RD can involve multiple organs of the body. The ocular manifestation of IgG4-RD is called IgG4-related ophthalmic disease (IgG4-ROD). We herein report a patient diagnosed with IgG4-ROD. The patient developed ptosis and vision loss after SARS-CoV-2 vaccination, and the symptoms worsened after SARS-CoV-2 infection. After excluding other diseases like myasthenia gravis and Eaton-Lambert syndrome that may cause ptosis, the diagnosis of IgG4-ROD was confirmed by pathological examination. We discussed the predisposing factors, diagnosis and treatment of this patient to provide a more empirical and theoretical basis for clinical diagnosis and treatment. We conducted a literature review of previously reported cases of IgG4-RD following SARS-CoV-2 infection or vaccination. We retrieved a total of 9 cases, of which 5 developed symptoms after vaccination and 4 after infection. Demographic and clinical characteristics were summarized. In conclusion, our case represents the first case of proven IgG4-ROD after COVID-19 vaccination. We believe that IgG4-ROD and SARS-CoV-2 infection or vaccination are closely related, and the immune system disorder caused by SARS-CoV-2 infection or vaccination may be a key factor in the pathogenesis of IgG4-RD. But for now, there is no direct evidence that there is a causal relationship between SARS-CoV-2 infection or vaccination and IgG4-ROD, which still needs more research and exploration to confirm.
Using protein geometry to optimize cytotoxicity and the cytokine window of a ROR1 specific T cell engager
Authors: Zhou Xueyuan , Geyer Felix Klaus , Happel Dominic , Takimoto Jeffrey , Kolmar Harald , Rabinovich Brian
Published: February 2024

T cell engaging bispecific antibodies have shown clinical proof of concept for hematologic malignancies. Still, cytokine release syndrome, neurotoxicity, and on-target-off-tumor toxicity, especially in the solid tumor setting, represent major obstacles. Second generation TCEs have been described that decouple cytotoxicity from cytokine release by reducing the apparent binding affinity for CD3 and/or the TAA but the results of such engineering have generally led only to reduced maximum induction of cytokine release and often at the expense of maximum cytotoxicity. Using ROR1 as our model TAA and highly modular camelid nanobodies, we describe the engineering of a next generation decoupled TCE that incorporates a “cytokine window” defined as a dose range in which maximal killing is reached but cytokine release may be modulated from very low for safety to nearly that induced by first generation TCEs. This latter attribute supports pro-inflammatory anti-tumor activity including bystander killing and can potentially be used by clinicians to safely titrate patient dose to that which mediates maximum efficacy that is postulated as greater than that possible using standard second generation approaches. We used a combined method of optimizing TCE mediated synaptic distance and apparent affinity tuning of the TAA binding arms to generate a relatively long but persistent synapse that supports a wide cytokine window, potent killing and a reduced propensity towards immune exhaustion. Importantly, this next generation TCE induced significant tumor growth inhibition in vivo but unlike a first-generation non-decoupled benchmark TCE that induced lethal CRS, no signs of adverse events were observed.
Revolutionizing cancer treatment: the power of bi- and tri-specific T-cell engagers in oncolytic virotherapy
Authors: Zarezadeh Mehrabadi Ali , Tat Mahdi , Ghorbani Alvanegh Akbar , Roozbahani Fatemeh , Esmaeili Gouvarchin Ghaleh Hadi
Published: February 2024

Bi- or tri-specific T cell engagers (BiTE or TriTE) are recombinant bispecific proteins designed to stimulate T-cell immunity directly, bypassing antigen presentation by antigen-presenting cells (APCs). However, these molecules suffer from limitations such as short biological half-life and poor residence time in the tumor microenvironment (TME). Fortunately, these challenges can be overcome when combined with OVs. Various strategies have been developed, such as encoding secretory BiTEs within OV vectors, resulting in improved targeting and activation of T cells, secretion of key cytokines, and bystander killing of tumor cells. Additionally, oncolytic viruses armed with BiTEs have shown promising outcomes in enhancing major histocompatibility complex I antigen (MHC-I) presentation, T-cell proliferation, activation, and cytotoxicity against tumor cells. These combined approaches address tumor heterogeneity, drug delivery, and T-cell infiltration, offering a comprehensive and effective solution. This review article aims to provide a comprehensive overview of Bi- or TriTEs and OVs as promising therapeutic approaches in the field of cancer treatment. We summarize the cutting-edge advancements in oncolytic virotherapy immune-related genetic engineering, focusing on the innovative combination of BiTE or TriTE with OVs.
Corrosion fatigue performance of modified 17-4PH in simulated geothermal environment
Authors: Li Zhipeng , Sun Ming , Zhang Hongguang , Xu Weiwei , Wu Lianlian
Published: February 2024

Corrosion fatigue behavior of a new candidate material for geothermal turbine blade, modified 17-4PH, was investigated in detail. The environmental acceleration of crack growth rate was discussed in terms of∆K. Fracture surface and side surface were observed by SEM. The crack path on side surface was also analyzed by EBSD. Then, the corrosion mechanism was discussed. Striation width on the fracture surface was compared to the crack growth per cycle. Since pitting occurred during the corrosion fatigue test, anodic polarization test was exercised to measure the pitting potential, and the cause for the pitting was also discussed. The hardness was also characterized by micro-hardness test and auger electron mapping.
Trends in cognitive function before and after myocardial infarction: findings from the China Health and Retirement Longitudinal Study
Authors: Shang Jing , Dong Jianye , Zhu Sijia , Chen Qingmei , Hua Jianian
Published: February 2024

Objectives

Incident stroke was associated with cognitive dysfunction after stroke and even before stroke. However, cognitive trends prior to myocardial infarction (MI) and the timeline of cognitive decline in a few years following incident MI remain unclear, especially among the Chinese population. We aimed to evaluate whether MI was associated with cognitive change both before and after MI in China.

Methods

This cohort study included 11,287 participants without baseline heart problems or stroke from the China Health and Retirement Longitudinal Study. The exposure was self-reported MI. The outcomes were scores of cognitive functions in five domains, which reflected abilities of episodic memory, visuospatial abilities, orientation, attention and calculation, and global cognition as a summary measure. A Linear mixed model was constructed to explore cognitive function before and after incident MI among the MI participants and the cognitive trends of participants free of MI.

Results

During the 7-year follow-up, 421 individuals [3.7% of 11,287, mean (SD) age, 60.0 (9.0) years; 59.1% female] experienced MI events. The cognitive scores of participants of both the MI group and the control group without MI declined gradually as time went by. The annual decline rate of the MI group before incident MI was similar to that of the control group during the whole follow-up period. Incident MI was not associated with acute cognitive decline in all five cognitive domains. Moreover, MI did not accelerate the cognitive decline rate after MI compared with the pre-MI cognitive trends. The decline rate of cognitive function after MI was similar to the rate before MI.

Conclusions

Different from stroke, participants who had an MI did not show steeper cognitive decline before MI. MI was not associated with acute cognitive decline and accelerated decline in several years after MI. Future studies are needed to learn the mechanisms behind the different patterns of cognitive decline between MI and stroke.
New organizational principles and 3D cytoarchitectonic maps of the dorsolateral prefrontal cortex in the human brain
Authors: Bruno Ariane , Lothmann Kimberley , Bludau Sebastian , Mohlberg Hartmut , Amunts Katrin
Published: February 2024

Areas of the dorsolateral prefrontal cortex (DLPFC) are part of the frontoparietal control, default mode, salience, and ventral attention networks. The DLPFC is involved in executive functions, like working memory, value encoding, attention, decision-making, and behavioral control. This functional heterogeneity is not reflected in existing neuroanatomical maps. For example, previous cytoarchitectonic studies have divided the DLPFC into two or four areas. Macroanatomical parcellations of this region rely on gyri and sulci, which are not congruent with cytoarchitectonic parcellations. Therefore, this study aimed to provide a microstructural analysis of the human DLPFC and 3D maps of cytoarchitectonic areas to help address the observed functional variability in studies of the DLPFC. We analyzed ten human post-mortem brains in serial cell-body stained brain sections and mapped areal boundaries using a statistical image analysis approach. Five new areas (i.e., SFG2, SFG3, SFG4, MFG4, and MFG5) were identified on the superior and middle frontal gyrus, i.e., regions corresponding to parts of Brodmann areas 9 and 46. Gray level index profiles were used to determine interregional cytoarchitectural differences. The five new areas were reconstructed in 3D, and probability maps were generated in commonly used reference spaces, considering the variability of areas in stereotaxic space. Hierarchical cluster analysis revealed a high degree of similarity within the identified DLPFC areas while neighboring areas (frontal pole, Broca's region, area 8, and motoric areas) were separable. Comparisons with functional imaging studies revealed specific functional profiles of the DLPFC areas. Our results indicate that the new areas do not follow a simple organizational gradient assumption in the DLPFC. Instead, they are more similar to those of the ventrolateral prefrontal cortex (Broca's areas 44, 45) and frontopolar areas (Fp1, Fp2) than to the more posterior areas. Within the DLPFC, the cytoarchitectonic similarities between areas do not seem to follow a simple anterior-to-posterior gradient either, but cluster along other principles. The new maps are part of the publicly available Julich Brain Atlas and provide a microstructural reference for existing and future imaging studies. Thus, our study represents a further step toward deciphering the structural-functional organization of the human prefrontal cortex.
The efficacy of furmonertinib in untreated advanced NSCLC patients with sensitive EGFR mutations in a real-world setting: a single institutional experience
Authors: Yan Ningning , Guo Sanxing , Huang Siyuan , Zhang Huixian , Li Xingya
Published: February 2024

Background

Furmonertinib is the standard treatment option in the first-line setting for advanced non-small cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) mutations in China. However, there are limited real-world data available.

Methods

We conducted a retrospective study at a single center, analyzing a cohort of 73 NSCLC patients who tested positive for EGFR mutations and were treated with furmonertinib as their initial therapy between August 2022 and December 2023. The primary endpoint was progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), overall survival (OS), and safety profile.

Results

The median observation period was 9 months (95% confidence interval [CI], 8.0–20.0). The median PFS was 19.5 months (95% CI, 14.6–24.4). OS data were not yet mature. Univariate analysis showed no significant correlation between PFS and factors such as Eastern Cooperative Oncology Group performance status (ECOG PS) score, presence of brain or liver metastases, sex, age, EGFR mutation status, or number of metastatic sites. However, multivariate analysis indicated a potential trend toward extended PFS in patients younger than 65 years (p = 0.053, 95% CI, 0.10–1.02), although the p-value was only marginally significant. The most common adverse events were diarrhea (24%), anemia (36%), and liver injury (32%); however, only four cases experienced severe adverse events.

Conclusion

In a real-world setting, furmonertinib appears to be a favorable treatment option for EGFR-mutated patients. The manageable nature of adverse events further supports its use in clinical practice.
Pain, comorbidities, and clinical decision-making: conceptualization, development, and pilot testing of the Pain in Aging, Educational Assessment of Need instrument
Authors: Siaton Bernadette C. , Hogans Beth B. , Frey-Law Laura A. , Brown Lana M. , Herndon Christopher M. , Buenaver Luis F.
Published: February 2024

Introduction

Pain is highly prevalent in older adults and often contextualized by multiple clinical conditions (pain comorbidities). Pain comorbidities increase with age and this makes clinical decisions more complex. To address gaps in clinical training and geriatric pain management, we established the Pain in Aging—Educational Assessment of Need (PAEAN) project to appraise the impacts of medical and mental health conditions on clinical decision-making regarding older adults with pain. We here report development and pilot testing of the PAEAN survey instrument to assess clinician perspectives.

Methods

Mixed-methods approaches were used. Scoping review methodology was applied to appraise both research literature and selected Medicare-based data. A geographically and professionally diverse interprofessional advisory panel of experts in pain research, medical education, and geriatrics was formed to advise development of the list of pain comorbidities potentially impacting healthcare professional clinical decision-making. A survey instrument was developed, and pilot tested by diverse licensed healthcare practitioners from 2 institutions. Respondents were asked to rate agreement regarding clinical decision-making impact using a 5-point Likert scale. Items were scored for percent agreement.

Results

Scoping reviews indicated that pain conditions and comorbidities are prevalent in older adults but not universally recognized. We found no research literature directly guiding pain educators in designing pain education modules that mirror older adult clinical complexity. The interprofessional advisory panel identified 26 common clinical conditions for inclusion in the pilot PAEAN instrument. Conditions fell into three main categories: “major medical”, i.e., cardio-vascular-pulmonary; metabolic; and neuropsychiatric/age-related. The instrument was pilot tested by surveying clinically active healthcare providers, e.g., physicians, nurse practitioners, who all responded completely. Median survey completion time was less than 3 min.

Conclusion

This study, developing and pilot testing our “Pain in Aging—Educational Assessment of Need” (PAEAN) instrument, suggests that 1) many clinical conditions impact pain clinical decision-making, and 2) surveying healthcare practitioners about the impact of pain comorbidities on clinical decision-making for older adults is highly feasible. Given the challenges intrinsic to safe and effective clinical care of older adults with pain, and attendant risks, together with the paucity of existing relevant work, much more education and research are needed.
Effects of whole-body electromyostimulation with different impulse intensity on blood pressure changes in hyper- and normotensive overweight people. A pilot study
Authors: Kemmler Wolfgang , Kohl Matthias , von Stengel Simon , Willert Sebastian , Kast Stephanie , Uder Michael
Published: February 2024

Hypertension is a frequent condition in untrained middle-aged to older adults, who form the core group of whole-body electromyostimulation (WB-EMS) applicants. So far, the acute effects of varying impulse intensities on blood pressure responses have not been evaluated in normo- and hypertensive people. Thirteen hypertensive and twelve normotensive overweight WB-EMS novices, 40–70 years old, conducted the same WB-EMS protocol (20 min, bipolar, 85 Hz, 350 µs, 4 s impulse-4 s rest; combined with easy movements) with increasing impulse intensity (low, moderate, advanced) per session. Mean arterial blood pressure (MAP) as determined by automatic sphygmomanometry rose significantly (p < .001) from rest, 5 min pre-WB-EMS to immediately pre-WB-EMS assessment. Of importance, a 20-min WB-EMS application does not increase MAP further. In detail, maximum individual MAP does not exceed 128 mmHg (177 mmHg systolic or 110 mmHg diastolic) in any case. Two-min post-WB-EMS, MAP was significantly lower (p = .016) compared to immediately pre-WB-EMS. In contrast, heart rate increased significantly from immediately pre to immediately post-exercise (p < .001), though individual peak values did not exceed 140 beats/min−1 and heart rate decreased rapidly (p < .001) post-exercise. No significant differences in MAP and HR kinetics were observed for impulse intensity categories or hypertensive status. In summary, largely independently of impulse intensity and status, the acute effect of WB-EMS on MAP in novice applicants seem to be largely negligible. Although definite evidence might not have been provided by the present study, we conclude that hypertension, at least under treatment, should not be considered as a barrier for WB-EMS application in moderately old or older cohorts.
Are You Curious About Curiosity?
Authors: Oosterwijk Suzanne , Noordewier Marret K. , Gruber Matthias J.
Published: February 2024

Kids (and adults) are often curious. Maybe you are curious about dinosaurs, giant squids, or rollercoaster rides. But have you ever been curious about why you are curious about some things but not about other things? In the last 10 years, scientists have asked similar questions about curiosity. In this article, we will share some of the answers. We explain how scientists across the world study curiosity. We also explain that people become curious to seek out specific information or to explore new things. Based on research on curiosity and the brain, scientists think that curiosity is a signal that it is valuable (or rewarding) to learn something or figure something out. Curiosity can even make you remember information better. After reading this article, we hope that your curiosity is satisfied!
Transnational innovation systems for bioeconomy: insights from cassava value chains in East Africa
Authors: Lutta Alphayo I. , Bößner Stefan , Johnson Francis X. , Virgin Ivar , Trujillo Monica , Osano Philip
Published: February 2024

In this study, we analyze the purpose, challenges, and opportunities of transnational innovation systems using cassava as the case study crop in the East Africa region. Cassava scientifically referred to as Manihot esculenta Crantz, is an important food security crop for the poor and vulnerable and a potential building block for advancing the bioeconomy in Africa and the global South. Semi-structured interviews with researchers, government official, and small and medium enterprise representatives from the region were done to determine their level of collaborations with other partners across the region and the opportunities and challenges for transnational innovation systems along the cassava value chain. The selection of interviewees followed a purposive sampling technique according to their knowledge on transnational innovation in the cassava value chain. This was corroborated by a focused literature review on innovation systems concepts gathered from scholarly literature. The findings show that transnational collaborations and innovations in the East African region offer opportunities for expansion of biomass production, bioprocessing, and value addition to the rich bioresources available. Collaboration across borders and transnational innovation systems were found to play an important role for advancing and/or upscaling cassava breeding, growing, value-adding products and novel processing methods and contributing to a growing East African bioeconomy. Other than the regional policy challenges, organizational and cultural barriers were more prominent in venturing, participation, and involvement of parties and users in transnational innovations. These findings draw attention to the often unnoticed, but vital, role that institutional and policy frameworks play in initiating as well as supporting transnational innovation systems that address issues of current and future global concern. Therefore, appropriate policy environment and partnerships that offer opportunities for synergy and complementarity are vital for building effective transnational innovation systems that enhance the sustainability of production, value addition and end-uses of biobased cassava products.
Triangular osteosynthesis and lumbopelvic fixation as a valid surgical treatment in posterior pelvic ring lesions: a systematic review
Authors: Rovere Giuseppe , De Mauro Domenico , Smakaj Amarildo , Sassara Giulia , De Vitis Rocco , Farsetti Pasquale , Camarda Lawrence , Maccauro Giulio , Liuzza Francesco
Published: February 2024

Objective

Unstable fractures of the sacrum often occur in patients with pelvic fractures and represent a real challenge for the orthopedic surgeon. Triangular osteosynthesis (TOS) and lumbopelvic fixation (LP) may represent a valid management option for the treatment of this condition. We present a systematic literature review about lumbopelvic fixation and triangular fixation as treatment option for unstable sacral fractures, to assess clinical and radiological outcomes after surgery and to evaluate appropriate indications and impact on the natural history of sacral fractures.

Methods

The review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 50 articles out of 108 titles, were considered eligible for the full-text analysis. Finally, 16 studies that met inclusion criteria were included in this review.

Results

Overall, 212 patients (87 males, 58 females) with sacral fractures treated with TOS triangular fixation or LP lumbopelvic fixation were collected. The mean age was 37.6 years. Mean follow-up reported in all studies was 24.14 months.

Conclusion

The results presented by the different authors, highlight the effectiveness of TOS triangular fixation and LP lumbopelvic fixation for the treatment of unstable sacral fractures associated with other pelvic fractures, in terms of function, stability, cost-effectiveness, and quality of life postoperatively.
Development of a Self-Regulating Solar Shading Actuator Based on the Thermal Shape Memory Effect
Authors: Stelzmann Mario , Zakner Felix , Navarro de Sosa Iñaki , Nemati Amir , Kahnt Alexander , Maaß Burkhard , Drossel Welf-Guntram
Published: February 2024

In the field of adaptive building technologies, this research introduces the development of a self-regulating solar shading actuator that utilizes the thermal shape memory effect. The study focuses on addressing the actuator’s performance under diverse environmental conditions. Thermal simulations were carried out during the development of the individual components of the actuator and for the prediction of specific switching temperatures. The investigation includes an analysis of the sunshade’s response to varying environmental conditions, emphasizing its effectiveness on clear summer days and identifying challenges during overcast periods. The critical coordination between the solar collector and the shape memory alloy (SMA) wire is examined, shedding light on the impact of SMA temperature dynamics on the actuation performance. Through the integration of simulation data and real-world measurements, the study validates the thermal model for the solar collector, establishing the robustness of the system’s operation. This research work contributes significantly to the development of intelligent actuators and outlines the importance of validation of SMA-based applications under real conditions.