bluuebunny/crossref_metadata_2025 huggingface dataset:
The generalized STAR modeling with minimum spanning tree approach of spatial weight matrix
Authors: Mukhaiyar Utriweni , Mahdiyasa Adilan Widyawan , Sari Kurnia Novita , Noviana Nur Tashya
Published: August 2024

The weight matrix is one of the most important things in Generalized Space–Time Autoregressive (GSTAR) modeling. Commonly, the weight matrix is built based on the assumption or subjectivity of the researchers. This study proposes a new approach to composing the weight matrix using the minimum spanning tree (MST) approach. This approach reduces the level of subjectivity in constructing the weight matrix since it is based on the observations. The spatial dependency among locations is evaluated through the centrality measures of MST. It is obtained that this approach could give a similar weight matrix to the commonly used, even better in some ways, especially in modeling the data with higher variability. For the study case in traffic problems, the number of vehicles entering the Purbaleunyi toll was modeled by GSTAR with several weight matrix perspectives. According to Space–Time ACF-PACF plots, GSTAR(1;1), GSTAR(1,2), and GSTAR(2;1,1) models are the candidates for appropriate models. Based on the root mean square errors and mean absolute percentage errors, it is concluded that the GSTAR(2,1,1) with MST approach is the best model to forecast the number of vehicles entering the Purbaleunyi toll. This best model is followed by GSTAR(1,1) with an MST approach of spatial weight matrix.
Application of DNA aptamers to block enterotoxigenic Escherichia coli toxicity in a Galleria mellonella larval model
Authors: Barros Maria Margarida , Castro Joana , Araújo Daniela , Oliveira Ricardo , Campos Ana Maria , Silva Sónia , Outor-Monteiro Divanildo , Almeida Carina
Published: August 2024

Enterotoxigenic Escherichia coli (ETEC) is the major bacterial cause of diarrheal diseases in pigs, particularly at young ages, resulting in significant costs to swine farming. The pathogenicity of ETEC is largely dependent on the presence of fimbriae and the ability to produce toxins. Fimbriae are responsible for their initial adhesion to the intestinal epithelial cells, leading to the onset of infection. In particular, the F4 type (K88) fimbriae are often attributed to neonatal infections and have also been associated with post-weaning diarrheal infections. This disease is traditionally prevented or treated with antibiotics, but their use is being severely restricted due to the emergence of resistant bacteria and their impact on human health. Emerging approaches such as aptamers that target the F4-type fimbriae and block the initial ETEC adhesion are a promising alternative. The aim of this study is to assess the effectiveness of two aptamers, Apt31 and Apt37, in controlling ETEC infection in the G. mellonella in vivo model. Initially, the dissociation constant (KD) of each aptamer against ETEC was established using real-time quantitative PCR methodology. Subsequently, different concentrations of the aptamers were injected into Galleria mellonella to study their toxicity. Afterwards, the anti-ETEC potential of Apt31 and Apt37 was assessed in the larvae model. The determined KD was 81.79 nM (95% CI: 31.21–199.4 nM) and 50.71 nM (95% CI: 26.52–96.15 nM) for the Apt31 and Apt37, respectively, showing no statistical difference. No toxicity was observed in G. mellonella following injection with both aptamers at any concentration. However, the administration of Apt31 together with ETEC-F4+ in G. mellonella resulted in a significant improvement of approximately 30% in both larvae survival and health index compared to ETEC-F4+ alone. These findings suggest that aptamers have promising inhibitory effect against ETEC infections and pave the way for additional in vivo studies.
Covalent organic-inorganic polyoxometalate hybrids in catalysis
Authors: Iftikhar Tuba , Rosnes Mali H.
Published: August 2024

Polyoxometalates (POMs) are a class of compounds known for the vast range of tunable structures and properties available, leading to applications in areas such as catalysis, energy, and advanced medicine. The ability to covalently functionalize POMs with organic components has been investigated extensively to tune the physical and chemical properties of the resulting hybrid materials. These hybrids, where the organic entity is covalently attached to the POM-core (Class II hybrid POMs) result in a vast library of promising customizable catalytic systems, displaying tunable properties with a high level of synergy between the polyanion and the organic component. A number of Class II hybrids have been investigated for a wide range of catalytic applications, and here, we give a brief overview of Class II hybrids of the p-block elements and their applications in catalysis.
Development and validation of next-generation sequencing panel for personalized Helicobacter pylori eradication treatment targeting multiple species
Authors: Min Byung-Joo , Seo Myung-Eui , Bae Jung Ho , Kim Ji Won , Kim Ju Han
Published: August 2024

Introduction

The decreasing Helicobacter pylori eradication rate is primarily attributed to antibiotic resistance, and further exacerbated by uniform drug administration disregarding a host’s metabolic capability. Consequently, applying personalized treatment based on antibiotic resistance-associated variants and the host’s metabolic phenotype can potentially increase the eradication rate.

Method

A custom next-generation sequencing panel for personalized H. pylori eradication treatment (NGS-PHET) was designed which targeted the regions for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin-resistance in H. pylori and human proton-pump inhibitor (PPI) metabolism. The libraries were constructed following customized methods and sequenced simultaneously. The customized framework criteria, grounded in previously reported antibiotic resistance associated variants and the host’s PPI metabolism, was applied to the NGS-PHET results and suggested a personalized treatment for each subject, which was validated through each subject’s actual eradication outcome.

Results

Both previously reported and novel variants were identified from H. pylori sequencing results. Concurrently, five CYP2C19 homozygous extensive metabolizers and three CYP3A4 intermediate metabolizers were identified. Among the total of 12 subjects, clarithromycin triple therapy was suggested for five subjects, bismuth quadruple therapy was suggested for six subjects, and rifabutin triple therapy was suggested for one subject by following the customized framework criteria. The treatment suggestion for nine of the 12 subjects was consistent with the treatment that each subject achieved eradication with.

Discussion

Applying the methodology using the NGS-PHET and customized framework helps to perform eradication treatment quickly and effectively in most patients with antibiotic-resistant H. pylori strains, and is also useful in research to find novel antibiotic-resistance candidates.
Early prediction of the bactericidal and bacteriostatic effect of imipenem and doxycycline using tabletop scanning electron microscopy
Authors: Zmerli Omar , Hodzic Alma , Bellali Sara , Azar Eid , Bou Khalil Jacques
Published: August 2024

Introduction

Our work aims at establishing a proof-of-concept for a method that allows the early prediction of the bactericidal and bacteriostatic effects of antibiotics on bacteria using scanning electron microscopy (SEM) as compared to traditional culture-based methods.

Methods

We tested these effects using Imipenem (bactericidal) and Doxycycline (bacteriostatic) with several strains of sensitive and resistant Escherichia coli. We developed a SEM-based predictive score based on three main criteria: Bacterial Density, Morphology/Ultrastructure, and Viability. We determined the results for each of these criteria using SEM micrographs taken with the TM4000Plus II-Tabletop-SEM (Hitachi, Japan) following an optimized, rapid, and automated acquisition and analysis protocol. We compared our method with the traditional culture colony counting gold standard method and classic definitions of the two effects.

Results

Our method revealed total agreement with the CFU method and classic definition by visualizing the effect of the antibiotic at 60 minutes and 120 minutes using SEM.

Discussion

This early prediction allows a rapid and early identification of the bactericidal and bacteriostatic effects as compared to culture that would take a minimum of 18 hours. This has several future applications in the development of SEM-automated assays coupled to machine learning models that identify the antibiotic effect and facilitate determination of bacterial susceptibility.
Imaging biobanks: operational limits, medical-legal and ethical reflections
Authors: Capasso Emanuele , Casella Claudia , Marisei Mariagrazia , Tortora Mario , Briganti Francesco , Di Lorenzo Pierpaolo
Published: August 2024

The extraordinary growth of health technologies has determined an increasing interest in biobanks that represent a unique wealth for research, experimentation, and validation of new therapies. “Human” biobanks are repositories of various types of human biological samples. Through years the paradigm has shifted from spontaneous collections of biological material all over the world to institutional, organized, and well-structured forms. Imaging biobanks represent a novel field and are defined by European Society of Radiology as: “organized databases of medical images, and associated imaging biomarkers shared among multiple researchers, linked to other biorepositories”. Modern radiology and nuclear medicine can provide multiple imaging biomarkers, that express the phenotype related to certain diseases, especially in oncology. Imaging biobanks, not a mere catalogue of bioimages associated to clinical data, involve advanced computer technologies to implement the emergent field of radiomics and radiogenomics. Since Europe hosts most of the biobanks, juridical and ethical framework, with a specific referral to Italy, is analyzed. Linking imaging biobanks to traditional ones appears to be a crucial step that needs to be driven by medical imaging community under clear juridical and ethical guidelines.
Triangulation of family perspectives on father-adolescent talk about sex and relationships
Authors: Grossman Jennifer M. , DiMarco Audrey J. , Richer Amanda M.
Published: August 2024

Introduction

Father-adolescent talk about sex can protect adolescents from sexual risk behaviors. However, few studies explore how family members view fathers' talk with adolescents about sex and relationships. An understanding of how fathers, mothers, and adolescents view fathers' roles in talk with adolescents about sex and relationships can help to guide fathers' talk with adolescents and inform programs to provide targeted support for father-adolescent communication about sex and relationships.

Methods

This study investigates family perceptions of father-adolescent communication about sex and relationships by triangulating data from fathers, mothers, and adolescents using content analysis to conduct between-family analysis and within-family approaches with 15 families (n = 45 individuals) with high school-aged adolescents from across the U.S.

Results

Analyses showed agreement on the importance of fathers' roles in family talk about sex. The findings showed shared recognition of the importance of fathers' roles in family talk about sex. Between-group analyses showed that fathers, mothers, and adolescents view fathers' roles as emotional supports and open communicators with their adolescents about sex and relationships and as educators and advisors for their adolescent children. Within-family analysis showed that families often agreed that there were gender differences in how fathers talked with their sons and daughters, but family members expressed different views on how adolescents' gender impacts father-adolescent communication about sexual topics.

Discussion

These findings may encourage fathers who are uncertain about the value of their roles in talking with their adolescent children about sex and relationships. They also highlight the importance of examining how fathers' messages to their adolescents about sex and relationships may continue to follow patterns of gender stereotypes. This is the first study to qualitatively triangulate perspectives of fathers, mothers, and adolescents on father-adolescent communication about sex and relationships. Since fathers are often less involved than mothers in parent-adolescent communication about sex and relationships, an understanding of how mothers and adolescents see fathers' roles and messages can help provide a pathway for fathers' engagement which works within a family system.
Effect of vocabulary learning strategies on students’ vocabulary knowledge achievement and motivation: the case of grade 11 high school students
Authors: Ayana Haimanot , Mereba Temesgen , Alemu Adege
Published: August 2024

Introduction

Vocabulary knowledge achievement is crucial for effective language learning. However, there is a gap in vocabulary knowledge achievement, particularly at the Seto High School in Ethiopia. This study addresses this gap by focusing on Grade 11 students and investigating the effect of vocabulary learning strategies on students’ vocabulary knowledge achievement and motivation.

Methods

A quasi-experimental design was employed, involving two natural classes of Grade 11 students, with 30 students in the experimental group and 30 in the control group, selected through convenience sampling. A mixed-method research design was also used to gather comprehensive data. The data collected included pretest and posttest assessments of vocabulary knowledge achievement, a vocabulary learning strategies (VLS) questionnaire, and semi structured interviews. The analysis of the data utilized statistical methods such as means, standard deviations, independent t - tests, and correlations to evaluate the effects of vocabulary learning strategies on students’ vocabulary knowledge achievement and motivation.

Results

High reliability was observed for both the VLS questionnaire and the tests. Pretest results revealed no significant (p > 0.05) difference in vocabulary knowledge achievement between the experimental and control groups. Posttest results demonstrated a statistically significant (p < 0.05) improvement in vocabulary achievement in the experimental group compared to the control group. Correlation analysis revealed a positive and significant (p < 0.05) association between VLS use and vocabulary knowledge achievement. Survey results and qualitative data showed that students predominantly relied on dictionary-based vocabulary, saying the new word aloud, using the vocabulary section in textbook, and continuing to study words over time vocabulary learning strategies before training, with a noticeable shift toward increased use of guessing, keyword, and semantic mapping strategies after training. These findings underscore the effectiveness of VLS training in enhancing vocabulary knowledge among Grade 11 students. Finally, some recommendations are proposed.

Conclusion

The study concluded that training in vocabulary learning strategies had a significant impact on students’ vocabulary knowledge achievement.
Effect of paternal age on clinical outcomes of in vitro fertilization-embryo transfer cycles
Authors: Gao Xinyan , Li Xiao , Wang Fanfan , Cai Wen , Sun Shihu , Lu Shaoming
Published: August 2024

Purpose

This study aimed to investigate the impact of paternal age > 40 years on clinical pregnancy and perinatal outcomes among patients undergoing in vitro fertilization treatment.

Methods

We selected 75 male patients (aged > 40 years) based on predefined inclusion and exclusion criteria. Propensity score matching was performed in a 1:3 ratio, resulting in a control group (aged ≤ 40 years) of 225 individuals. Various statistical tests, including the Mann-Whitney U test, Chi-square test, Fisher’s exact test, and binary logistic regression, were used to analyze the association between paternal age and clinical outcomes.

Results

We found no statistically significant differences in semen routine parameters, clinical pregnancy outcomes, and perinatal outcomes between paternal aged > 40 and ≤ 40 years. However, in the subgroup analysis, the live birth rate significantly decreased in those aged ≥ 45 compared to those aged 41–42 and 43–44 years (31.25% vs. 69.23% and 65%, respectively; all p < 0.05). Additionally, the clinical pregnancy rate was significantly lower among those aged ≥ 45 than among those aged 41–42 (43.75% vs. 74.36%; p=0.035).

Conclusion

Paternal age ≥ 45 years was associated with lower live birth and clinical pregnancy rates.
Longitudinal study on metabolic abnormalities and diabetes risk in normal-weight japanese adults
Authors: Huang Cheng , Gao Zhichao , Zhang Yuhang , Li Guofeng
Published: August 2024

Background

Diabetes is a significant global health concern, with a growing prevalence in Japan. Individuals with normal body mass index who are metabolically unhealthy exhibit an elevated risk of diabetes onset. Investigating the relationship between Metabolically Unhealthy Normal-weight (MUNW) status and the risk of diabetes in non-diabetic individual is vital for implementing early preventive strategies.

Methods

Using data from the NAGALA cohort, This study categorized 8,194 Japanese adults based on the score of metabolic syndrome (MetS) components they possessed. Cox proportional hazards regression models and multivariate logistic regression were used to assess the relationship between MUNW and the risk of developing diabetes, with analyses stratified by age and sex.

Results

During an average follow-up of 7.19 years, 123 participants (1.5%) were diagnosed with diabetes. Among the participants, 766 (9.35%) were classified as MUNW, and 157 (1.92%) as having MetS. Compared to those with no MetS components, individuals with 1, 2, and ≥3 MetS components had progressively higher adjusted hazard ratios (HRs) for developing diabetes, at 4.56, 8.79, and 25.16, respectively. Further stratified analysis revealed that men aged ≤40 years had the highest risk of developing diabetes. For men, the adjusted HRs for having 1, 2, and ≥3 MetS components were 5.61, 7.80, and 28.59, respectively, and for participants aged ≤40 years, the HRs were 12.31, 25.57, and 129.82, respectively.

Conclusion

The prevalence of MUNW in non-diabetic individuals in Japan is 9.35%. The score of MetS components was positively correlated with the risk of diabetes. Early intervention and lifestyle modifications are crucial, especially for MUNW individuals and notably young Japanese men aged ≤40 years, for the prevention and management of diabetes.
Energy cost forecasting and financial strategy optimization in smart grids via ensemble algorithm
Authors: Yang Juanjuan
Published: August 2024

Introduction

In the context of energy resource scarcity and environmental pressures, accurately forecasting energy consumption and optimizing financial strategies in smart grids are crucial. The high dimensionality and dynamic nature of the data present significant challenges, hindering accurate prediction and strategy optimization.

Methods

This paper proposes a fusion algorithm for smart grid enterprise decision-making and economic benefit analysis, aiming to enhance decision-making accuracy and predictive capability. The method combines deep reinforcement learning (DRL), long short-term memory (LSTM) networks, and the Transformer algorithm. LSTM is utilized to process and analyze time series data, capturing historical patterns of energy prices and usage. Subsequently, DRL and the Transformer algorithm are employed to further analyze the data, enabling the formulation and optimization of energy purchasing and usage strategies.

Results

Experimental results demonstrate that the proposed approach outperforms traditional methods in improving energy cost prediction accuracy and optimizing financial strategies. Notably, on the EIA Dataset, the proposed algorithm achieves a reduction of over 48.5% in FLOP, a decrease in inference time by over 49.8%, and an improvement of 38.6% in MAPE.

Discussion

This research provides a new perspective and tool for energy management in smart grids. It offers valuable insights for handling other high-dimensional and dynamically changing data processing and decision optimization problems. The significant improvements in prediction accuracy and strategy optimization highlight the potential for widespread application in the energy sector and beyond.
Assessment of the physicochemical properties of the sediment from the Gangetic floodplain wetlands of West Bengal, India, with GIS and a statistical approach
Authors: Das Basanta Kumar , Saha Ajoy , Das Archan Kanti , Chandra Purna , Mondal Kausik , Kayal Tania , Chakraborty Sangeeta , Bhattacharya Shreya , Sahoo Bigan Kumar , Jana Chayna
Published: August 2024

Introduction

Bottom sediments play a pivotal role in wetland productivity, and here, eight Gangetic floodplain wetlands of India were studied to assess the sediment physicochemical characteristics and textural analysis.

Methods

Sediment samples that were collected from each wetland in monsoon and non-monsoon seasons were analysed. ANOVA, Principal component analysis and multiple correlation analysis were used for statistical analysis.

Results and Discussion

Throughout the study period, pH (6.90–8.04), EC (0.20–1.64 dS/m), CaCO3 (1.75%–14.50%), available nitrogen (10.22–22.23 mg/100 g sediment), total nitrogen (80.4–333.8 mg/100 g sediment), available phosphorus (0.20–5.61 mg/100 g sediment), and total phosphorus (19.63–173.33 mg/100 g sediment) were recorded. The sediment quality parameters differ significantly (p > 0.05) among the wetlands. Seasonal variation was only observed on total nitrogen and total phosphorus contents. Sediments were dominated by sand. Sediment nutrient (C, N, and P) stoichiometry of wetlands depicted a comparatively little higher C/P (5.96–66.32) ratio and lower C/N (3.34–22.76) and N/P (1.12–9.25) ratios, which revealed that the physicochemical characteristics of the sediments are influenced by anthropogenic sources. Principal component analysis showed the influence of both natural and anthropogenic causes on wetland ecosystems. The geographic information system (GIS) interpolation approach was used in combination with laboratory analysis methods to give a complete spatial resolution of the sediment quality of each wetland. The study suggests that these wetlands’ sediment quality is favorable for fish culture but requires proper management practices to achieve sustainable production. As it is the first time where monitoring physicochemical properties of sediments of these wetlands are presented, this study can be used as a baseline data for comparison in future environmental assessments of the wetlands.
Macrophage-mediated mechanisms of lung injury in the sensitization reaction to Echinococcus granulosus
Authors: Li Yu-qian , Wang Chun-sheng , Zhou Jing-ru , Wang Jia-ling , Tailaiti Subi , Lin Jia-ying , Bayina Batesurong , Cao Li-wei , Ye Jian-rong
Published: August 2024

Objective

In this study, the impact of inhibiting the PI3K/AKT/NF-κB pathway on lung oxidative damage induced by Echinococcus granulosus cyst fluid was investigated.

Methods

Twenty-four mice were randomly assigned to four groups. Three months after inoculation with hydatid cyst segments, mice in group A were treated with intraperitoneal and intratracheal saline injections; mice in group B were administered a caudal vein injection of a PI3K inhibitor, followed by cyst fluid sensitization; mice in group C received an AKT inhibitor via caudal vein, followed by cyst fluid sensitization; and mice in group D were subjected to cyst fluid sensitization without any inhibitor treatment. Cellular changes in lung tissues across all groups were evaluated, including pathological section analysis. Analysis of pulmonary tissue and serum from these mice included the assessment of PI3K/AKT/NF-κB pathway proteins, inflammatory factors, and related mRNA levels.

Results

Mice in groups B and C exhibited a higher proportion of M2-type macrophages and significantly lower levels of PI3K/AKT/NF-κB pathway proteins, inflammatory factors (interleukin-6 [IL-6]/tumor necrosis factor-α [TNF-α]), and oxidative markers in lung tissues compared to mice in group D (P < 0.05).

Conclusion

Our results in this study indicate that activation of the PI3K/AKT/NF-κB pathway contributed to an increase in the M1 macrophage phenotype, leading to enhanced secretion of peroxidases and inflammatory factors. This mechanism plays a crucial role in the oxidative and inflammatory lung damage associated with allergic reactions to E. granulosus cyst fluid.
Exploring the molecular mechanisms of macrophages in islet transplantation using single-cell analysis
Authors: Pu Zuhui , Chen Shujuan , Lu Ying , Wu Zijing , Cai Zhiming , Mou Lisha
Published: August 2024

Background

Islet transplantation is a promising treatment for type 1 diabetes that aims to restore insulin production and improve glucose control, but long-term graft survival remains a challenge due to immune rejection.

Methods

ScRNA-seq data from syngeneic and allogeneic islet transplantation grafts were obtained from GSE198865. Seurat was used for filtering and clustering, and UMAP was used for dimension reduction. Differentially expressed genes were analyzed between syngeneic and allogeneic islet transplantation grafts. Gene set variation analysis (GSVA) was performed on the HALLMARK gene sets from MSigDB. Monocle 2 was used to reconstruct differentiation trajectories, and cytokine signature enrichment analysis was used to compare cytokine responses between syngeneic and allogeneic grafts.

Results

Three distinct macrophage clusters (Mø-C1, Mø-C2, and Mø-C3) were identified, revealing complex interactions and regulatory mechanisms within macrophage populations. The significant activation of macrophages in allogeneic transplants was marked by the upregulation of allograft rejection-related genes and pathways involved in inflammatory and interferon responses. GSVA revealed eight pathways significantly upregulated in the Mø-C2 cluster. Trajectory analysis revealed that Mø-C3 serves as a common progenitor, branching into Mø-C1 and Mø-C2. Cytokine signature enrichment analysis revealed significant differences in cytokine responses, highlighting the distinct immunological environments created by syngeneic and allogeneic grafts.

Conclusion

This study significantly advances the understanding of macrophage roles within the context of islet transplantation by revealing the interactions between immune pathways and cellular fate processes. The findings highlight potential therapeutic targets for enhancing graft survival and function, emphasizing the importance of understanding the immunological aspects of transplant acceptance and longevity.
Case report: The histopathological analyses of two myelin oligodendrocyte glycoprotein antibody-associated diseases with a distinctive linear radiating gadolinium enhancement on MRI
Authors: Shimizu Mikito , Beck Goichi , Murayama Shigeo , Hoshi Taku , Sumikura Hiroyuki , Higashida Kyoko , Fukasaka Isao , Shimada Yuki , Nagashima Nozomi , Fujioka Tomohiro , Hatayama Naoki , Okuno Tatsusada , Mochizuki Hideki , Sakaguchi Manabu
Published: August 2024

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has highly heterogeneous clinical presentations, in which encephalitis is an important phenotype. Moreover, MOGAD has been reported to exhibit diverse imaging findings. However, there have been no previous reports of cases with perivascular radial gadolinium enhancement in periventricular regions, commonly reported in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. In this paper, we present two cases of MOGAD with this MRI feature, both of which underwent brain biopsy for the lesions. Brain biopsies revealed perivenous demyelination and inflammation consistent with acute disseminated encephalomyelitis (ADEM), with pronounced axonal damage in Case 1 and minimal axonal involvement in Case 2. Case 1 exhibited more severe cerebral atrophy than Case 2, correlating with the extent of axonal damage. Through these cases, we highlight the heterogeneity of radiological manifestations of MOGAD, expanding the spectrum beyond previously defined MRI patterns. Furthermore, histopathological analysis revealed distinct axonal involvement as a potential prognostic marker of brain atrophy. These observations emphasize the importance of considering MOGAD in the differential diagnosis, even in cases with atypical imaging findings, and highlight the significance of brain biopsy in guiding both diagnosis and prognosis.
Metabolic tumor volume and the survival of patients with Non-Hodgkin lymphoma treated with chimeric antigen receptor T cell therapy: a meta-analysis
Authors: Liu Lin , Jin Feng , Fan Hua
Published: August 2024

Background

Chimeric antigen receptor T cell (CAR-T) is a promising treatment for aggressive Non-Hodgkin lymphoma (NHL). The aim of the meta-analysis was to determine the association between metabolic tumor volumes (MTV) derived on positron emission tomography before CAR-T infusion and the survival of patients with NHL.

Methods

Relevant observational studies pertaining to the purpose of the meta-analysis were obtained through a search of PubMed, Web of Science, and Embase from inception of the databases to April 1, 2024. The data was combined using a random-effects model that accounted for the potential influence of between-study heterogeneity.

Results

Fifteen observational studies were included. Pooled results showed that compared to those with a lower MTV, the NHL patients with a higher MTV before CAR-T infusion were associated with a poor progression-free survival (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.48 to 2.02, p < 0.001; I2 = 20%) and overall survival (HR: 2.11, 95% CI: 1.54 to 2.89, p < 0.001; I2 = 58%). Subgroup analysis showed that the association between MTV and survival of NHL patients after CAR-T was not significantly impacted by study design, methods for determination of MTV cutoff, or analytic models (univariate or multivariate, p for each subgroup all < 0.05). Subgroup analysis suggested a stronger association between MTV and poor survival outcomes in patients with median of lines of previous treatment of 2 or 3 as compared to those of 4 (p for subgroup difference < 0.05). Further meta-regression analyses suggested that the association between MTV and survival was not significantly affected by sample size, age, proportion of men, cutoff value of MTV, follow-up duration, or study quality scores (p all > 0.05).

Conclusion

A high MTV at baseline is associated with a poor survival of NHL patients after CAR-T.

Systematic Review Registration

https://inplasy.com/, identifier INPLASY (INPLASY202450069).
CAR-T cell therapy in relapsed or refractory multiple myeloma and access in Turkey
Authors: Hakan Goker , Engin Kelkitli , Elifcan Karakulak Aladag , Haluk Demiroglu , Mehmet Turgut , Suman Kambhampati , Maxwell Krem
Published: August 2024

The past decade has seen the development of immunotherapy for the treatment of multiple myeloma (MM), beginning with monoclonal antibodies (mAbs) in the relapsed and refractory setting and culminating in the market approval of chimeric antigen receptor T cells (CAR-T) and bispecific antibodies (BsAbs). The medical community is evaluating the efficacy and safety of these targeted immunotherapies, most of which currently target B-cell maturation antigen (BCMA) on the surface of plasma cells. Two anti-BCMA CAR-T products are available for treating relapsed or refractory MM: idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). Ide-cel and cilta-cel demonstrate the ability to induce deep responses in heavily pretreated diseases, including patients with triple-class-refractory and penta-refractory diseases. However, there are key similarities and differences regarding these agents, unknowns regarding their comparative efficacy and toxicity, and mechanisms underlying resistance to these new immunotherapies. This review discusses CAR-T cell therapy in relapsed refractory MM, with a focus on efficacy, toxicities, and the evolving trajectories of these therapies in the USA, as well as access in Turkey.
Preemptive multimodal analgesia for gynecologic oncology patients undergoing laparotomy: a randomized controlled trial
Authors: Geng Zhiyu , Wang Bojie , Zhang Yan , Yan Xin , Hu Jun , Cui Ran , Song Linlin
Published: August 2024

Purpose

Gynecologic oncology laparotomy leads to severe postoperative pain. We aimed to evaluate the effects of preemptive multimodal analgesic regimen on postoperative opioid consumption for patients undergoing gynecologic oncology laparotomy.

Methods

In this prospective, randomized clinical trial, 80 female patients scheduled for gynecologic oncology laparotomy were randomized to receive preemptive multimodal analgesia consisted of transversus abdominis plane (TAP) block, cyclooxygenase−2 inhibitors, acetaminophen and intravenous morphine patient-controlled analgesia (PCA) (Study group) or conventional analgesia with cyclooxygenase−2 inhibitors and morphine PCA (Control group). The primary outcome was morphine consumption in the first 24 h after surgery. Secondary outcomes were pain scores, nausea, vomiting, time to ambulation and flatus, length of hospital stay, satisfaction score, the 40-item Quality of Recovery score (QoR-40) and the Short-Form Health Survey (SF-36) scale.

Results

Morphine consumption in the first 24 h was 6 (3–9.8) mg in the Study group and 7 (3.5–12.5) mg in the Control group (p = 0.222). The Study group showed lower morphine consumption up to 6 h, lower pain scores up to 48 h, and earlier time to ambulation and flatus. The global QoR-40 score at 48 h [182 (173–195) vs. 173.5 (154–185.5), p = 0.024], subdimension scores of physical dependence at 24 h, physical comfort and pain at 48 h were significantly improved in the Study group.

Conclusion

Preemptive multimodal analgesia was not superior to conventional analgesia in reducing 24 h morphine consumption; however, it showed a significantly improved pain control and early quality of recovery thus can be recommended for gynecologic oncology patients undergoing laparotomy.
Comparison of the efficacy of pulsed radiofrequency in treating acute herpetic neuralgia and postherpetic neuralgia in the thoracic segment
Authors: Wang Huan , Zhang Dandan , Wang Shiyu , Wang Hui , Nie Huiyong
Published: August 2024

Objectives

This study aimed to compare the efficacy of pulsed radiofrequency (PRF) to dorsal root ganglia (DRG) in treating acute herpetic neuralgia (AHN) and postherpetic neuralgia (PHN) in the thoracic segment.

Methods

A total of 243 patients with thoracic herpes zoster-related pain (AHN or PHN) from January 2020 to September 2022 were retrospectively analyzed. They were divided into two groups based on the timing of PRF after herpes zoster onset: an acute herpetic neuralgia group (within 90 days) and a postherpetic neuralgia group (more than 90 days). All patients were treated with PRF at the thoracic DRG. The Visual Analog Scale (VAS), the Athens Insomnia Scale (AIS), the Generalized Anxiety Disorder-7 items (GAD-7), and the Patient Health Questionnaire-9 items (PHQ-9) scores were assessed before and at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery, and the results were then compared between the two groups.

Results

Postoperative scores of VAS, AIS, GAD-7, and PHQ-9 in both groups were significantly lower than preoperative scores (P < 0.001). From 1 month to 12 months after surgery, the AHN group showed significantly lower VAS, AIS, GAD-7, and PHQ-9 scores compared to the PHN group (P < 0.001). In the AHN group, there was a gradual improvement in these scores from 1 week to 12 months post-surgery. Conversely, the PHN group's scores began to worsen slowly from 1 week to 12 months post-surgery. Over time, the difference in scores between the two groups also increased gradually.

Conclusion

PRF to the DRG is an effective treatment for patients with AHN or PHN who do not respond well to conventional treatments. For AHN patients, PRF to the DRG significantly enhances early pain control, improves sleep and psychological status, and may even prevent the development of PHN.
Evaluation of a biopsychosocial education resource for mild traumatic brain injury: a mixed method exploratory study
Authors: Faulkner Josh W. , Callagher Elise , Snell Deborah , Nielsen Kristopher , Cairncross Molly , Theadom Alice
Published: August 2024

Introduction

Education is strongly advocated as a key component of treatment for mild traumatic brain injury (mTBI) in clinical guidelines. However, there is mixed evidence on the benefit of education. This study aimed to evaluate a new education resource for mTBI. CLARITY is a freely available animated video based on a biopsychosocial conceptualization of mTBI, explaining the complex psychological, environmental and biological mechanisms behind symptoms and recovery.1

Methods

24 adults with a history of mTBI participated in this mixed method study to examine prior experience of mTBI education and to evaluate CLARITY. Following viewing of the education video participants’ were invited to engage in a semi-structured interview and to share their perceptions of it via an online anonymous questionnaire.

Results

Thematic analysis of semi-structured interviews revealed one overarching theme: education is the foundation of recovery. Participants emphasised the critical role of coherent education in facilitating understanding, engagement in rehabilitation, and positive expectations during recovery. However, the first subtheme was that existing foundations are weak. Participants’ previous education was often limited in scope, inconsistent, and delivered in inaccessible ways. The second subtheme was that new foundations are stronger. Participants responded positively to CLARITY, highlighting its explanatory biopsychosocial approach, focus on mental health factors and accessible delivery methods as key strengths. Questionnaire responses revealed favourable endorsement of CLARITY’s utility, comprehensibility and accessibility.

Discussion

Recommendations for minor refinements to CLARITY were provided and made, as well as for its use in health care services.
Exploring causal correlations between plasma proteins and peripheral neuropathy: a Mendelian randomization
Authors: Song Man , Chen Fang , Li Xiaocong , Chen Lu
Published: August 2024

Background

Peripheral neuropathy (PN) is a common neurological disorder, and circulating plasma proteins with causal genetic evidence are a major source of therapeutic targets. This study identifies several potential plasma proteins that are causally related to PN risk, providing new insights into protein-mediated pathogenesis of PN and potential targets for novel therapies.

Methods

To identify potential therapeutic targets for PN, we employed two-sample Mendelian randomization (MR) to identify plasma proteins associated with six common PN. First, we screened for proteins related to PN using genome-wide association studies (GWAS), obtaining genetic data on plasma proteomes from 35,559 Icelanders. Summary data for six common PN, including Carpal Tunnel Syndrome (CTS), Trigeminal Neuralgia (TN), Alcoholic Neuropathy (AIP), Drug-induced Neuropathy (DIP), Diabetic Neuropathy (DP), and Guillain-Barré syndrome (GBS), were obtained from the FinnGen database. Two-sample MR and colocalization analyses were then conducted to further identify protein-PN pairs with presumed causal relationships. Enrichment analysis of positive proteins revealed potential biological processes and pathways. Based on drug-gene interaction analysis, we ultimately identified causal proteins associated with PN that could serve as potential drug targets for treating PN.

Results

Through MR analysis, we identified eight proteins (UBC12, SEM4C, IL23R, Prothrombin, CBS, Microglobulin, MATN4, COLEC12) with causal relationships to PN. We found that UBC12 is a protective factor for DP and CTS, while the remaining proteins are risk factors. Further colocalization analysis showed a posterior probability of hypothesis 4 (PPH4) less than 0.75, indicating no positive colocalization results were found. From the pathway enrichment analysis, we discovered that the proteins were mainly concentrated in pathways related to defense response to bacterium, receptor signaling pathway via STAT, cell killing, negative regulation of cytokine production, and leukocyte mediated immunity. Finally, in Drug-Gene Interaction database (DGIdb), we identified three protein-coding genes (IL23R, F2, CBS) as potential drug targets for PN.

Conclusion

Mendelian randomization studies confirm the causal relationship between genetically predicted PN-related risk and genetically predicted plasma protein abundance. Plasma proteins, as biomarkers associated with PN, can provide potential drug targets for etiological intervention research in PN.
Bilaterally positive head-impulse tests can differentiate AICA infarction from labyrinthitis
Authors: Kim Sung-Hwan , Kim Hanseob , Lee Sun-Uk , Park Euyhyun , Cho Bang-Hoon , Cho Kyung-Hee , Kim Gerard J. , Yu Sungwook , Kim Ji-Soo
Published: August 2024

Introduction

Video head-impulse tests (video-HITs) often fail to detect anterior inferior cerebellar artery (AICA) infarction due to peripheral and central vestibular system involvement. Anecdotal studies suggest that video-HITs may reveal bilateral impairment in AICA infarction. However, the diagnostic utility of video-HITs has not been established, particularly when compared to labyrinthitis, which accounts for the majority of acute audiovestibular syndrome (AAVS) cases.

Methods

We reviewed the medical records of consecutive patients presenting with new-onset acute hearing loss and spontaneous vertigo (i.e., AAVS) between March 2018 and July 2023 at a tertiary hospital in South Korea. Video-HIT patterns were categorized as follows: (1) ipsilaterally positive, (2) contralaterally positive, (3) bilaterally normal, and (4) bilaterally positive.

Results

Twenty-eight patients with AICA infarction (mean age±standard deviation = 67±15 years; 14 men) and 51 with labyrinthitis (63±17 years, 26 men) were included in the analyses. Among the 28 patients with AICA infarction, 15 presented with AAVS in isolation, without other co-morbid neurologic deficits (15/28, 54%). The vestibulo-ocular reflex (VOR) gains of ipsilesional horizontal canals (HCs) ranged from 0.21 to 1.22 (median = 0.81, interquartile range [IQR] = 0.50–0.89). However, those for contralateral HC gain ranged from 0.57 to 1.19 (median = 0.89 [IQR = 0.73–0.97]). Collectively, HITs were bilaterally positive in 13 patients (including 12 patients with bilaterally positive HITs for the horizontal canal), normal in eight, ipsilesionally positive in six, and contralesionally positive in one patient with AICA infarction. The VOR gains were typically decreased ipsilaterally in 28 (28/51, 55%), normal in 17 (17/51, 33%), and decreased bilaterally in six patients with labyrinthitis (6/51, 12%). Logistic regression analysis revealed that bilaterally positive HITs (p = 0.004) and multiple vascular risk factors (p = 0.043) were more frequently associated with AICA infarction than labyrinthitis.

Discussion

Among patients presenting with AAVS, bilaterally positive HITs can be indicative of AICA infarction in patients with multiple vascular risk factors.
Early hippocampal high-amplitude rhythmic spikes predict post-traumatic epilepsy in mice
Authors: Shannon Tyler , Levine Noah , Dirickson Rina , Shen Yuyan , Cotter Christopher , Rajjoub Noora , Fitzgerald Julie , Pardo-Manuel de Villena Fernando , Kokiko-Cochran Olga , Gu Bin
Published: August 2024

Oscillations, a highly conserved brain function across mammalian species, play a pivotal role in both brain physiology and pathology. Traumatic brain injury (TBI) frequently results in subacute and chronic alterations in brain oscillations, which are often associated with complications like post-traumatic epilepsy (PTE) in patients and animal models. We recently conducted longitudinal recordings of local field potential from the contralateral hippocampus of 12 strains of recombinant inbred Collaborative Cross (CC) mice and classical laboratory inbred C57BL/6 J mice after lateral fluid percussion injury. In this study, we profiled the acute (<12 h post-injury) and subacute (12–48 h post-injury) hippocampal oscillatory responses to TBI and evaluated their predictive value for PTE. We found dynamic high-amplitude rhythmic spikes with elevated power density and reduced signal complexity that prevailed exclusively during the acute phase in CC031 mice, which later developed PTE. This characteristic early brain oscillatory alteration was absent in CC031 sham controls, as well as in other CC strains and reference C57BL/6 J mice that did not develop PTE after TBI. Our findings offer quantitative measures linking early hippocampal brain oscillation to PTE at a population level in mice. These insights enhance understanding of circuit mechanisms and suggest potential targets for neuromodulatory intervention.
Association between obesity and sleep disorder in the elderly: evidence from NHANES 2005–2018
Authors: Wang Weifei , Chen Zhong , Zhang Wenyuan , Yuan Rui , Sun Yaqi , Yao Qi , Lu Jian , Zheng Jungang
Published: August 2024

Background

The available data exhibit inconsistent findings regarding the association between obesity and sleep problems among older adults. The objective of this study was to assess the potential association between obesity and sleep disorders in the older population.

Methods

The data utilised in this cross-sectional investigation was obtained from the National Health and Nutritional Examination Survey (NHANES) conducted between 2005 and 2018. The study employed a multivariate logistic regression model and conducted subgroup analysis to evaluate the association between obesity and sleep disturbance.

Results

The investigation consisted of 2,570 older people who provided complete information, out of which 324 individuals satisfied the criteria for sleep disturbance. The findings from the multivariable adjusted logistic regression model indicate that individuals in the overweight and normal weight groups exhibited decreased odds of experiencing sleep disorder, as evidenced by the adjusted odds ratios (AOR) of 0.46 (95% confidence interval [CI] = 0.34–0.61) and 0.33 (95% CI = 0.22–0.47), respectively. These results were statistically significant (p < 0.001) when compared to individuals in the obese group. The investigation of age and gender subgroups demonstrated similar associations between various BMI categories and sleep disorders in the older population.

Conclusion

In summary, there exists a correlation between obesity and sleep disorders in the senior population. A significant association was observed between BMI and the likelihood of experiencing sleep disorders, indicating a dose–response relationship. Individuals with a higher BMI demonstrated a heightened likelihood of experiencing sleep disorders compared to those with a lower BMI.