bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of NOAC vs. VKA in patients treated by PCI: a retrospective study of the FRANCE PCI registry
Authors: Durand Eric , Verrez Thibault , Gillibert Andre , Levesque Thomas , Barbe Thomas , Koning René , Motreff Pascal , Eltchaninoff Hélène , Collet Jean-Philippe , Rangé Gregoire
Published: January 2024

Introduction

Dual antithrombotic therapy (DAT) combining oral anticoagulation (OAC), preferentially Non-vitamin K antagonist OAC (NOAC) and single antiplatelet therapy (SAPT) for a period of 6–12 months is recommended after percutaneous coronary intervention (PCI) in patients with an indication for OAC.

Objective

To compare outcomes between vitamin K antagonist (VKA) and NOAC-treated patients in the nation-wide France PCI registry.

Methods

All consecutive patients from the France PCI registry treated by PCI and discharged with OAC between 2014 and 2020 were included and followed one-year. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) classification ≥3 and major adverse cardiac events (MACE) as the composite of all-cause mortality, myocardial infarction (MI), and ischemic stroke. A propensity-score analysis was used.

Results

Of the 7,277 eligible participants, 2,432 (33.4%) were discharged on VKA and 4,845 (66.6%) on NOAC. After propensity-score adjustment, one-year major bleeding was less frequent in NOAC vs. VKA-treated participants [3.1% vs. 5.2%, −2.1% (−3.6% to −0.6%), p = 0.005 as well as the rate of MACE [9.2% vs. 11.9%, −2.7% (−5.0% to −0.4%), p = 0.02]. One-year mortality was also significantly decreased in NOAC vs. VKA-treated participants [7.4% vs. 9.9%, −2.6% (−4.7% to −0.5%), p = 0.02]. The area under ROC curves of the anticoagulant treatment propensity score was estimated at 0.93, suggesting potential indication bias

Conclusions

NOAC seems to have a better efficacy and safety profile than VKA. However, potential indication bias were found.
Study on failure mechanism and control of surrounding rock of inclined strata crossing roadway in deep coal mine
Authors: Fang Wanwei , Li Mingxin , Huang Peng , Shi Taotao , Chen Yeqiang , Ma Shijin , Ren Guohui
Published: January 2024

China’s coal mines are mainly underground mines, and a large number of roadways have to be excavated underground. It is of great significance for coal mine production to adopt safe and reasonable roadway support methods. In the process of roadway excavation, the rock stratum is inclined and the roadway pass through the layer. Since the surrounding rock conditions of the roadway passing through the layer are more complicated, it is easy to cause deformation of surrounding rock, failure and floor heave, which makes the support work difficult. In order to solve this problem, the mechanical properties of roadway surrounding rock were tested and the failure of roadway surrounding rock was analyzed using the +260 horizontal centralized transportation roadway in Changcheng No.2 mine. The surrounding rock of the roadway was divided into 8 regions, and the stress analysis of the surrounding rock in different regions was carried out. It is found that the left shoulder pit, the right side and the floor of the roadway are prone to damage. The influence of the lateral pressure coefficient, the rock dip angle and the lithology on the failure of the roadway surrounding rock was analyzed by Mohr-Coulomb failure criterion, and the specific failure range of the roadway surrounding rock was obtained. The support optimization design of the roadway was carried out, and the weak area of the surrounding rock was reinforced. The deformation monitoring of roadway surrounding rock after support optimization was carried out. The field monitoring results show that after the optimized support, the displacement of the roof and floor of the roadway section and the two sides are reduced by 43.6% and 40.8% respectively compared with the original scheme, and the deformation of the surrounding rock also shows a trend of gradual stability, and the surrounding rock of the roadway is effectively controlled. The research can provide a new way for the stress and failure analysis of the surrounding rock of the inclined rock roadway.
Comparison of EMG amplitudes recorded by ipsilateral and contralateral electrodes placement during using trans-thyroid cartilage recording method in thyroid surgery
Authors: Chiang Feng-Yu , Shih Yu-Chen , Lien Ching-Feng , Wang Chih-Chun , Wang Chien-Chung , Hwang Tzer-Zen , Huang Yaw-Chang , Wu Che-Wei , Yeh Tai-Hung , Huang Tzu-Yen
Published: January 2024

Objectives

The feasibility and reliability of trans-thyroid cartilage EMG recording method (TCERM) during intraoperative monitoring (IONM) of the recurrent laryngeal nerve (RLN) in thyroid surgery have been established. This study compared two different recording electrode placements on the ipsi-lateral and contra-lateral lamina of the thyroid cartilage (TC).

Methods

Fifty consecutive patients undergoing total thyroidectomy with 100 RLNs at risk were enrolled. Two paired subdermal needle electrodes were inserted into the subperichondrium of the bilateral TC lamina to record electromyography (EMG) signals. The channel leads from the TC electrodes were connected to the patient interface with two different modes. In A-mode, the electrode leads were placed ipsi-laterally, and channel 1 monitored the left RLN and channel 2 monitored the right RLN respectively. In B-mode, the electrode leads were placed contra-laterally, and channels 1 and 2 simultaneously monitored the same side of the RLN. The amplitudes of four EMG signals (V1-R1-R2-V2) recorded by A-mode and B-mode were compared.

Results

All EMG amplitudes of V1-R1-R2-V2 signals recorded with B-mode were all above 500μV and significantly higher than those with A-mode (p<0.001). No false loss of signal, electrode dislodgement, or needle-related complications were noted during IONM. Postoperatively, all patients had symmetrical vocal cord movement. Lower EMG amplitudes were observed in older and male patients. Histopathology and laterality showed no significant differences in EMG amplitude.

Conclusion

During using TCERM in thyroid surgery, the recording electrodes should be placed contra-laterally on the TC lamina. This approach ensures high and stable EMG signals, which are important for high-quality IONM of the RLN.
Exendin-4 affects calcium signalling predominantly during activation and activity of beta cell networks in acute mouse pancreas tissue slices
Authors: Paradiž Leitgeb Eva , Kerčmar Jasmina , Križančić Bombek Lidija , Pohorec Vilijem , Skelin Klemen Maša , Slak Rupnik Marjan , Gosak Marko , Dolenšek Jurij , Stožer Andraž
Published: January 2024

Tight control of beta cell stimulus-secretion coupling is crucial for maintaining homeostasis of energy-rich nutrients. While glucose serves as a primary regulator of this process, incretins augment beta cell function, partly by enhancing cytosolic [Ca2+] dynamics. However, the details of how precisely they affect beta cell recruitment during activation, their active time, and functional connectivity during plateau activity, and how they influence beta cell deactivation remain to be described. Performing functional multicellular Ca2+ imaging in acute mouse pancreas tissue slices enabled us to systematically assess the effects of the GLP-1 receptor agonist exendin-4 (Ex-4) simultaneously in many coupled beta cells with high resolution. In otherwise substimulatory glucose, Ex-4 was able to recruit approximately a quarter of beta cells into an active state. Costimulation with Ex-4 and stimulatory glucose shortened the activation delays and accelerated beta cell activation dynamics. More specifically, active time increased faster, and the time required to reach half-maximal activation was effectively halved in the presence of Ex-4. Moreover, the active time and regularity of [Ca2+]IC oscillations increased, especially during the first part of beta cell response. In contrast, subsequent addition of Ex-4 to already active cells did not significantly enhance beta cell activity. Network analyses further confirmed increased connectivity during activation and activity in the presence of Ex-4, with hub cell roles remaining rather stable in both control experiments and experiments with Ex-4. Interestingly, Ex-4 demonstrated a biphasic effect on deactivation, slightly prolonging beta cell activity at physiological concentrations and shortening deactivation delays at supraphysiological concentrations. In sum, costimulation by Ex-4 and glucose increases [Ca2+]IC during beta cell activation and activity, indicating that the effect of incretins may, to an important extent, be explained by enhanced [Ca2+]IC signals. During deactivation, previous incretin stimulation does not critically prolong cellular activity, which corroborates their low risk of hypoglycemia.
Association between the weight-adjusted waist index and the odds of type 2 diabetes mellitus in United States adults: a cross-sectional study
Authors: Zheng Dongdong , Zhao Suzhen , Luo Dan , Lu Feng , Ruan Zhishen , Dong Xiaokang , Chen Wenjing
Published: January 2024

Objective

To examine the association between the weight-adjusted waist index (WWI) and the odds of type 2 diabetes mellitus(T2DM)among U.S. adults.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) spanning six years (2007–2018) were utilized, encompassing 31001 eligible participants. Weighted multivariate logistic regression models and smoothed fit curves were employed to assess the association between WWI and the odds of T2DM, as well as dose-response relationships in the overall population and the odds of T2DM in various subgroups.

Results

In the fully adjusted continuous model, each one-unit increase in WWI was associated with a 1.14-fold increase in the odds of T2DM within the entire study population (2.14 [1.98,2.31], P < 0.0001). In the fully adjusted categorical model, when using the lowest tertile of WWI (T1) as the reference group, the second tertile (T2) and the third tertile (T3) were associated with a 0.88-fold (1.88 [1.64,2.17], P < 0.0001) and a 2.63-fold (3.63 [3.11,4.23], P < 0.0001) increase in the odds of T2DM. These findings indicated a positive correlation between WWI values and the odds of T2DM, aligning with the results of the smoothed-fitted curves. In the analysis of subgroups, in addition to maintaining consistency with the overall population results, we found interactions between age and hypertension subgroups.

Conclusion

In conclusion, WWI was found to be positively associated with the odds of T2DM in U.S. adults.
Multi-objective particle swarm optimization for optimal scheduling of household microgrids
Authors: Huang Yu , He Gengsheng , Pu Zengxin , Zhang Ying , Luo Qing , Ding Chao
Published: January 2024

Addressing the challenge of household loads and the concentrated power consumption of electric vehicles during periods of low electricity prices is critical to mitigate impacts on the utility grid. In this study, we propose a multi-objective particle swarm algorithm-based optimal scheduling method for household microgrids. A household microgrid optimization model is formulated, taking into account time-sharing tariffs and users’ travel patterns with electric vehicles. The model focuses on optimizing daily household electricity costs and minimizing grid-side energy supply variances. Specifically, the mathematical model incorporates the actual input and output power of each distributed energy source within the microgrid as optimization variables. Furthermore, it integrates an analysis of capacity variations for energy storage batteries and electric vehicle batteries. Through arithmetic simulation within the Pareto optimal solution set, the model identifies the optimal solution that effectively mitigates fluctuations in energy input and output on the utility side. Simulation results confirm the effectiveness of this strategy in reducing daily household electricity costs. The proposed optimization approach not only improves the overall quality of electricity consumption but also demonstrates its economic and practical feasibility, highlighting its potential for broader application and impact.
RET is a sex-biased regulator of intestinal tumorigenesis
Authors: Koester Sean T. , Li Naisi , Dey Neelendu
Published: January 2024

Ret is implicated in colorectal cancer (CRC) as both a proto-oncogene and a tumor suppressor. We asked whether RET signaling regulates tumorigenesis in an Apc-deficient preclinical model of CRC. We observed a sex-biased phenotype: ApcMin/+Ret+/- females had significantly greater tumor burden than ApcMin/+Ret+/- males, a phenomenon not seen in ApcMin/+ mice, which had equal distributions by sex. Dysfunctional RET signaling was associated with gene expression changes in diverse tumor signaling pathways in tumors and normal-appearing colon. Sex-biased gene expression differences mirroring tumor phenotypes were seen in 26 genes, including the Apc tumor suppressor gene. Ret and Tlr4 expression were significantly correlated in tumor samples from female but not male ApcMin/+Ret+/- mice. Antibiotics resulted in reduction of tumor burden, inverting the sex-biased phenotype such that microbiota-depleted ApcMin/+Ret+/- males had significantly more tumors than female littermates. Reconstitution of the microbiome rescued the sex-biased phenotype. Our findings suggest that RET represents a sexually dimorphic microbiome-mediated “switch” for regulation of tumorigenesis.
Impact of disease burden and late loss of B cell aplasia on the risk of relapse after CD19 chimeric antigen receptor T Cell (Tisagenlecleucel) infusion in pediatric and young adult patients with relapse/refractory acute lymphoblastic leukemia: role of B-cell monitoring
Authors: Molinos-Quintana Águeda , Alonso-Saladrigues Anna , Herrero Blanca , Caballero-Velázquez Teresa , Galán-Gómez Víctor , Panesso Melissa , Torrebadell Montserrat , Delgado-Serrano Javier , Pérez de Soto Concepción , Faura Anna , González-Martínez Berta , Castillo-Robleda Ana , Diaz-de-Heredia Cristina , Pérez-Martínez Antonio , Pérez-Hurtado José María , Rives Susana , Pérez-Simón José Antonio
Published: January 2024

Introduction

Loss of B-cell aplasia (BCA) is a well-known marker of functional loss of CD19 CAR-T. Most relapses and loss of BCA occur in the first months after CD19 CAR-T infusion. In addition, high tumor burden (HTB) has shown to have a strong impact on relapse, especially in CD19-negative. However, little is known about the impact of late loss of BCA or the relationship between BCA and pre-infusion tumor burden in patients infused with tisagenlecleucel for relapsed/refractory B-cell acute lymphoblastic leukemia. Therefore, the optimal management of patients with loss of BCA is yet to be defined.

Methods

We conducted a Spanish, multicentre, retrospective study in patients infused with tisagenlecleucel after marketing authorization. A total of 73 consecutively treated patients were evaluated.

Results

Prior to infusion, 39 patients had HTB (≥ 5% bone marrow blasts) whereas 34 had a low tumor burden (LTB) (<5% blasts). Complete remission was achieved in 90.4% of patients, of whom 59% relapsed. HTB was associated with inferior outcomes, with a 12-month EFS of 19.3% compared to 67.2% in patients with LTB (p<0.001) with a median follow-up of 13.5 months (95% CI 12.4 – 16.2). In the HTB subgroup relapses were mainly CD19-negative (72%) whereas in the LTB subgroup they were mainly CD19-positive (71%) (p=0.017). In the LTB group, all CD19-positive relapses were preceded by loss of BCA whereas only 57% (4/7) of HTB patients experienced CD19-positive relapse. We found a positive correlation between loss of BCA and CD19-positive relapse (R-squared: 74) which persisted beyond six months post-infusion. We also explored B-cell recovery over time using two different definitions of loss of BCA and found a few discrepancies. Interestingly, transient immature B-cell recovery followed by BCA was observed in two pediatric patients. In conclusion, HTB has an unfavorable impact on EFS and allo-SCT might be considered in all patients with HTB, regardless of BCA. In patients with LTB, loss of BCA preceded all CD19-positive relapses. CD19-positive relapse was also frequent in patients who lost BCA beyond six months post-infusion. Therefore, these patients are still at significant risk for relapse and close MRD monitoring and/or therapeutic interventions should be considered.
Evaluating NetMHCpan performance on non-European HLA alleles not present in training data
Authors: Atkins Thomas Karl , Solanki Arnav , Vasmatzis George , Cornette James , Riedel Marc
Published: January 2024

Bias in neural network model training datasets has been observed to decrease prediction accuracy for groups underrepresented in training data. Thus, investigating the composition of training datasets used in machine learning models with healthcare applications is vital to ensure equity. Two such machine learning models are NetMHCpan-4.1 and NetMHCIIpan-4.0, used to predict antigen binding scores to major histocompatibility complex class I and II molecules, respectively. As antigen presentation is a critical step in mounting the adaptive immune response, previous work has used these or similar predictions models in a broad array of applications, from explaining asymptomatic viral infection to cancer neoantigen prediction. However, these models have also been shown to be biased toward hydrophobic peptides, suggesting the network could also contain other sources of bias. Here, we report the composition of the networks’ training datasets are heavily biased toward European Caucasian individuals and against Asian and Pacific Islander individuals. We test the ability of NetMHCpan-4.1 and NetMHCpan-4.0 to distinguish true binders from randomly generated peptides on alleles not included in the training datasets. Unexpectedly, we fail to find evidence that the disparities in training data lead to a meaningful difference in prediction quality for alleles not present in the training data. We attempt to explain this result by mapping the HLA sequence space to determine the sequence diversity of the training dataset. Furthermore, we link the residues which have the greatest impact on NetMHCpan predictions to structural features for three alleles (HLA-A*34:01, HLA-C*04:03, HLA-DRB1*12:02).
Intratumoral microbiota: implications for cancer onset, progression, and therapy
Authors: Wu Jinmei , Zhang Pengfei , Mei Wuxuan , Zeng Changchun
Published: January 2024

Significant advancements have been made in comprehending the interactions between the microbiome and cancer. However, prevailing research predominantly directs its focus toward the gut microbiome, affording limited consideration to the interactions of intratumoral microbiota and tumors. Within the tumor microenvironment (TME), the intratumoral microbiome and its associated products wield regulatory influence, directing the modulation of cancer cell properties and impacting immune system functionality. However, to grasp a more profound insight into the intratumoral microbiota in cancer, further research into its underlying mechanisms is necessary. In this review, we delve into the intricate associations between intratumoral microbiota and cancer, with a specific focus on elucidating the significant contribution of intratumoral microbiota to the onset and advancement of cancer. Notably, we provide a detailed exploration of therapeutic advances facilitated by intratumoral microbiota, offering insights into recent developments in this burgeoning field.
Prediction of antigen-responding VHH antibodies by tracking the evolution of antibody along the time course of immunization
Authors: Matsuda Tomonari , Akazawa-Ogawa Yoko , Komaba Lilian-Kaede , Kiyose Norihiko , Miyazaki Nobuo , Mizuguchi Yusaku , Fukuta Tetsuo , Ito Yuji , Hagihara Yoshihisa
Published: January 2024

Antibody maturation is the central function of the adaptive immune response. This process is driven by the repetitive selection of mutations that increase the affinity toward antigens. We hypothesized that a precise observation of this process by high-throughput sequencing along the time course of immunization will enable us to predict the antibodies reacting to the immunized antigen without any additional in vitro screening. An alpaca was immunized with IgG fragments using multiple antigen injections, and the antibody repertoire development was traced via high-throughput sequencing periodically for months. The sequences were processed into clusters, and the antibodies in the 16 most abundant clusters were generated to determine whether the clusters included antigen-binding antibodies. The sequences of most antigen-responsive clusters resembled those of germline cells in the early stages. These sequences were observed to accumulate significant mutations and also showed a continuous sequence turnover throughout the experimental period. The foregoing characteristics gave us >80% successful prediction of clusters composed of antigen-responding VHHs against IgG fragment. Furthermore, when the prediction method was applied to the data from other alpaca immunized with epidermal growth factor receptor, the success rate exceeded 80% as well, confirming the general applicability of the prediction method. Superior to previous studies, we identified the immune-responsive but very rare clusters or sequences from the immunized alpaca without any empirical screening data.
Association between dietary selenium intake and the prevalence of hypertension: results from the National Health and Nutrition Examination Survey 2003–2018
Authors: Wu Yilin , Yu Zongliang
Published: January 2024

Aim

The epidemiological evidence regarding the impact of dietary selenium intake on hypertension continues to be a subject of controversy. Our objective is to examine the correlation between dietary selenium intake and the prevalence of hypertension within a substantial and diverse population in the United States.

Methods

We carried out a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) to assess the association between dietary selenium intake and hypertension prevalence. Weight logistic regression analysis and smooth curve fitting were utilized to explore potential linear relationships. Subgroup analysis was further employed to investigate potential differences in this relationship across populations and assess potential synergies.

Results

The study included 32,928 individuals, and the average dietary selenium intake was 1.12 ± 0.53 μg. The prevalence rate of hypertension was 36.55% overall and decreased with the higher dietary selenium intake quartiles (quartiles 1, 40.25%; quartiles 2, 37.71%; quartiles 3, 36.04%, quartiles 4, 32.23%, p < 0.001). Each quartile increase in dietary selenium intake associated with 11% decreased the likelihood of prevalence of hypertension [OR = 0.89; 95% CI: 0.80–1.00; p = 0.0425]. Subgroup analyses revealed that there was no significant correlation between gender, age, body mass index, smoking status, alcohol consumption, and diabetes mellitus in relation to the association between dietary selenium intake and the prevalence of hypertension.

Conclusion

The prevalence of hypertension in adults was found to be linearly and negatively correlated with dietary selenium intake. In order to improve the prevention and treatment of hypertension, greater emphasis should be placed on selenium consumption.
Paralichthys olivaceus MLKL-mediated necroptosis is activated by RIPK1/3 and involved in anti-microbial immunity
Authors: Hao Kangwei , Xu Hang , Jiang Shuai , Sun Li
Published: January 2024

Necroptosis is a type of proinflammatory programmed necrosis essential for innate immunity. The receptor interacting protein kinases 1/3 (RIPK1/3) and the substrate mixed lineage kinase domain-like protein (MLKL) are core components of the necroptotic axis. The activation and immunological function of necroptosis in fish remain elusive. Herein, we studied the function and activation of RIPK1/3 (PoRIPK1/3) and MLKL (PoMLKL) in teleost Paralichthys olivaceus. Bacterial infection increased the expression of RIPK1/3 and MLKL. The N-terminal four-helix bundle (4HB) domain of PoMLKL exhibited necroptosis-inducing activity, and the C-terminal pseudokinase domain exerted auto-inhibitory effect on the 4HB domain. PoRIPK3 was capable of phosphorylating the T360/S361 residues in the PoMLKL C-terminal domain and initiated necroptosis, and this necroptosis-inducing activity was enhanced by PoRIPK1. PoRIPK1/3 interacted with PoMLKL in a manner that depended on the RIP homotypic interaction motif (RHIM), and deletion of RHIM from PoRIPK1/3 led to the dissociation of PoRIPK1/3 with PoMLKL. Inhibition of PoMLKL-mediated necroptosis increased Edwardsiella tarda infection in fish cells and tissues, and led to significantly enhanced lethality of the host. Taken together, these results revealed the activation mechanism of PoRIPK1/3-PoMLKL signaling pathway and the immunological function of necroptosis in the immune defense of teleost.
Mitogenome-based phylogeny of the gastropod order Neomphalida points to multiple habitat shifts and a Pacific origin
Authors: Zhang Lili , Gu Xinyu , Chen Chong , He Xing , Qi Ying , Sun Jin
Published: January 2024

Neomphalida is an order of gastropod molluscs with highly diverse morphology and a global distribution across various chemosynthesis-based ecosystems from organic falls to hot vents. The phylogenetic relationships of taxa within this order remain contentious, due to the rarity of material leading to a low taxonomic coverage and few genetic markers used. Neomphalida includes three families—Melanodrymiidae, Neomphalidae, and Peltospiridae—and molecular sequences are especially lacking in Melanodrymiidae. Here, we assembled a total of 11 mitogenomes covering these three families and 14 genus-level groups to reconstruct the most complete phylogeny of Neomphalida to date. Our current result recovered the monophyly of three families with maximum support and a likely interfamilial relationship of (Melanodrymiidae + Neomphalidae) + Peltospiridae. These indicate the possibility of habitat shifting from non-chemosynthetic deep sea to hot vent and then to sunken wood, accompanied by elevated mitogenome rearrangements and amino acid substitution rates in Melanodrymiidae. By mapping species distribution on the phylogeny, our findings suggest a Pacific origin of Neomphalida and multiple historical dispersal events of Peltospiridae to the Indian Ocean and at least once to the Atlantic.
Experimental study on deterioration characteristics of foamed concrete under dry-wet cycles in acidic environment
Authors: Wu Yongmei , Chai Shaoqiang , Chen Yong , Zou Songzhe , Chai Lianzeng
Published: January 2024

Foamed concrete, which has excellent performance, has been gradually used to enhance the thermal insulation performance of buildings in recent years. However, there are few studies on the durability of foamed concrete under environmental action. In order to understand the law of damage and deterioration of foamed concrete under dry-wet cycles in acidic environment, the standard sample of foamed concrete was first pre-treated with different times of dry-wet cycles under neutral and two acidic environments, then quality inspection, uniaxial compression test and scanning electron microscope were carried out on the treated foamed concrete by electronic scale, universal testing machine and electron microscope. Accordingly, the deterioration effect and deterioration mechanism of foamed concrete under dry-wet cycles in acidic environment is analyzed. The results show that the quality and uniaxial compressive strength of foamed concrete decrease gradually with the increase of the number of dry-wet cycles in both neutral and two acidic environments; the stronger the acidity of dry-wet cycles, the more the quality of foamed concrete decreases and the more obvious the deterioration effect of uniaxial compressive strength of foamed concrete; the acidic dry-wet cycles will corrode the foamed concrete, resulting in the expansion and consolidation of pores and the appearance of cracks, and the more the number of dry-wet cycles, the more obvious the corrosion effect of the foamed concrete. The research results can provide scientific basis for the analysis of the safety and stability of foamed concrete members under the dry-wet cycle in acidic environment.
A bibliometric and visual analysis of epigenetic research publications for Alzheimer’s disease (2013–2023)
Authors: Zhao YaPing , Ai WenJing , Zheng JingFeng , Hu XianLiang , Zhang LuShun
Published: January 2024

Background

Currently, the prevalence of Alzheimer’s disease (AD) is progressively rising, particularly in developed nations. There is an escalating focus on the onset and progression of AD. A mounting body of research indicates that epigenetics significantly contributes to AD and holds substantial promise as a novel therapeutic target for its treatment.

Objective

The objective of this article is to present the AD areas of research interest, comprehend the contextual framework of the subject research, and investigate the prospective direction for future research development.

Methods

ln Web of Science Core Collection (WOSCC), we searched documents by specific subject terms and their corresponding free words. VOSviewer, CiteSpace and Scimago Graphica were used to perform statistical analysis on measurement metrics such as the number of published papers, national cooperative networks, publishing countries, institutions, authors, co-cited journals, keywords, and visualize networks of related content elements.

Results

We selected 1,530 articles from WOSCC from January 2013 to June 2023 about epigenetics of AD. Based on visual analysis, we could get that China and United States were the countries with the most research in this field. Bennett DA was the most contributed and prestigious scientist. The top 3 cited journals were Journal of Alzheimer’s Disease, Neurobiology of Aging and Molecular Neurobiology. According to the analysis of keywords and the frequency of citations, ncRNAs, transcription factor, genome, histone modification, blood DNA methylation, acetylation, biomarkers were hot research directions in AD today.

Conclusion

According to bibliometric analysis, epigenetic research in AD was a promising research direction, and epigenetics had the potential to be used as AD biomarkers and therapeutic targets.
Characterization of viscerofugal neurons in human colon by retrograde tracing and multi-layer immunohistochemistry
Authors: Chen Bao Nan , Humenick Adam G. , Hibberd Timothy James , Yew Wai Ping , Wattchow David A. , Dinning Phil G. , Costa Marcello , Spencer Nick J. , Brookes Simon J. H.
Published: January 2024

Background and Aims

Viscerofugal neurons (VFNs) have cell bodies in the myenteric plexus and axons that project to sympathetic prevertebral ganglia. In animals they activate sympathetic motility reflexes and may modulate glucose metabolism and feeding. We used rapid retrograde tracing from colonic nerves to identify VFNs in human colon for the first time, using ex vivo preparations with multi-layer immunohistochemistry.

Methods

Colonic nerves were identified in isolated preparations of human colon and set up for axonal tracing with biotinamide. After fixation, labeled VFN cell bodies were subjected to multiplexed immunohistochemistry for 12 established nerve cell body markers.

Results

Biotinamide tracing filled 903 viscerofugal nerve cell bodies (n = 23), most of which (85%) had axons projecting orally before entering colonic nerves. Morphologically, 97% of VFNs were uni-axonal. Of 215 VFNs studied in detail, 89% expressed ChAT, 13% NOS, 13% calbindin, 9% enkephalin, 7% substance P and 0 of 123 VFNs expressed CART. Few VFNs contained calretinin, VIP, 5HT, CGRP, or NPY. VFNs were often surrounded by dense baskets of axonal varicosities, probably reflecting patterns of connectivity; VAChT+ (cholinergic), SP+ and ENK+ varicosities were most abundant around them. Human VFNs were diverse; showing 27 combinations of immunohistochemical markers, 4 morphological types and a wide range of cell body sizes. However, 69% showed chemical coding, axonal projections, soma-dendritic morphology and connectivity similar to enteric excitatory motor neurons.

Conclusion

Viscerofugal neurons are present in human colon and show very diverse combinations of features. High proportions express ChAT, consistent with cholinergic synaptic outputs onto postganglionic sympathetic neurons in prevertebral ganglia.
Efficacy and safety of zuranolone in the treatment of major depressive disorder: a meta-analysis
Authors: Wang Shuyu , Zhang Wenxing , Liu Zhang , Zhang Tian , Wang Yi , Li Weihong
Published: January 2024

Objective

This study aimed to systematically review zuranolone’s efficacy and safety in treating major depressive disorder (MDD).

Methods

We conducted electronic searches in databases like PubMed, Embase, Cochrane, and Web of Science to identify randomized controlled trials using zuranolone for severe depression from study inception to September 15, 2023. Two independent reviewers screened studies, extracted data, and assessed study quality. Our meta-analysis included four studies with 1,454 patients. The findings showed significant improvements with zuranolone across various measures: Hamilton Depression Rating Scale (HAM-D) scores indicated notable alleviation in depressive symptoms (WMD: −2.03; 95% CI: −2.42 to −1.65); the treatment group’s HAM-D score response rate was significantly higher than the control group’s at day 15 (OR: 1.46, 95% CI: 1.11 to 1.92, P = 0.01). The meta-analysis also revealed higher remission rates for the treatment group compared to the control group at day 15 (OR: 1.68, 95% CI: 1.18 to 2.39, P = 0.03). Additionally, HAM-A scores on day 15 and MADRS scores on day 15 showed improvement, and HAM-D scores for 30 mg zuranolone on different treatment days exhibited improvement (WMD, −2.55; 95% CI, −3.24 to −1.58; P = 0.05). However, analyzing HAM-D scores on day 15 for various zuranolone doses revealed no significant differences. Importantly, zuranolone use was associated with an increased incidence of adverse reactions.

Results

Our meta-analysis included four studies with 1454 patients, showing significant improvements with zuranolone across various measures, including HAM-D scores, HAM-A scores, MADRS scores, and specific HAM-D scores for 30 mg zuranolone on different treatment days. However, no significant differences were found in HAM-D scores on day 15 for various doses of zuranolone.

Conclusions

Our findings suggest that zuranolone is a promising, simple, and convenient treatment for patients with major depressive disorder, offering potential guidance for clinical practice.
Production of natural flavor compounds using Bacillus subtilis-fermented soybean meal extract and their biological potential: a comprehensive in vitro study
Authors: Abd-Alrahman Abeer M. , Ramadan Manal M. , Maraay Mohamed F. , Salem Rabab , Saleh Fatma M. , Hashim Mahmood A , Zhernyakova Anastasia , El-Messery Tamer M.
Published: January 2024

This study aims to investigate the production of natural flavor compounds through the utilization of Bacillus subtilis-fermented soybean meal extract and evaluate their biological potential. The experiment involved a comprehensive in vitro investigation to assess the capabilities and effects of the produced flavor compounds. The resulting flavor compounds were subjected to various in vitro tests to assess their properties, including cytotoxicity, antioxidant activity, anticancer potential, antiviral activity, and antimicrobial activity. To enhance the fermentation process, soybean meal extract was fortified with a combination of L-Lysine and L-Threonine. Gas chromatography-mass spectrometry (GC/MS) analysis was conducted on the fermented soybean meal using two strains of Bacillus subtilis, namely NRCH123 and NRCZ144. This analysis revealed the presence of various volatile compounds in all extracts, including Butylated hydroxytoluene. The fermented soybean extract with bacillus subtilis NRCZ144 (B2) fortified with a combination of 2.5% (w/w) L-Lysine and 2.5% w/w L-threonine (SLT2) exhibited a rich profile of flavor compounds, with Eucalyptol being identified as the predominant compound. The antioxidant activity of the SLT2 extract was found to be 72.04% at a concentration of 100 μg/mL, indicating significant antioxidant potential. Furthermore, when tested against the human liver cancer cell line HepG2, the extract demonstrated anticancer activity with an IC50 value of 2.26 μg/mL. The extract exhibited potent cytotoxicity, with an IC50 value of 1.02 μg/mL. Importantly, the SLT2 extract displayed strong antibacterial and antifungal activity, even at very low concentrations. The extract’s antimicrobial properties indicate its potential for inhibiting the growth of bacteria and fungi.
Case report: A kidney metastasis from vulvar squamous cell carcinoma
Authors: He Junwei , Xiao Yuhe , Wang Lu , Wang Zhaohui , Pan Jun , Bai Zunguang
Published: January 2024

Introduction

Distant metastases of vulvar SCC most commonly involve the lung, liver, bone, skin, and lymph nodes. Metastasis from vulvar SCC to the kidneys is extremely rare, with only one case reported in the literature to date.

Case presentation

We report the case of a 53-year-old postmenopausal female patient was diagnosed with vulvar squamous cell carcinoma in an external hospital and following the diagnosis, she had been performed a vulvectomy for squamous cell carcinoma of the vulva, at that time, the patient had not undergone inguinal lymphadenectomy. In July 2019, she was admitted to our hospital due to upper right quadrant pain. An enhanced whole-body CT scan showed a mixed-density tumor of the right kidney with invasion into the right renal portal vein and multiple enlarged retroperitoneal lymph nodes. Positron emission tomography-computed tomography (PET - CT) scan showed a significantly increased radioactivity uptake in the tumor and enlarged lymph nodes, but PET-CT did not show abnormal enlargement of bilateral inguinal lymph nodes and no abnormal increase in radioactivity uptake. PET-CT examination did not show recurrence in terms of local of vulvar. These results led us to be gravely worried about possible renal carcinoma, so it was agreed upon to perform laparoscopic nephrectomy of the right kidney in the same month. Histology of the resected tumor confirmed it to be poorly differentiated squamous cell carcinoma with invasion consistent with metastatic vulvar carcinoma. Based on clinical history, radiological and histological facts, the patient was diagnosed with kidney metastasis from vulvar squamous cell carcinoma. Recovery from surgery went well and the patient was transferred to the oncology department and underwent a chemotherapy regimen consisting of paclitaxel and nedaplatin for further treatment. After 6 courses of chemotherapy. For a year after treatment, the patient had lived progression-free. Unfortunately, she died of tumor progression in July 2022.

Conclusion

Although renal metastasis from vulvar SCC is rare, renal metastasis should be considered for the patient with a history of vulvar cancer, whenever a mass is identified in the kidney. Timely surgical removal of renal metastasis may prolong the survival time.
Clinical considerations of CDK4/6 inhibitors in HER2 positive breast cancer
Authors: Zhang Cui , Zhou Fulin , Zou Jiali , Fang Yanman , Liu Yuncong , Li Libo , Hou Jing , Wang Guanghui , Wang Hua , Lai Xiaolian , Xie Lu , Jiang Jia , Yang Can , Huang Yisidan , Chen Yingji , Zhang Hanqun , Li Yong
Published: January 2024

Deregulation of cell cycles can result in a variety of cancers, including breast cancer (BC). In fact, abnormal regulation of cell cycle pathways is often observed in breast cancer, leading to malignant cell proliferation. CDK4/6 inhibitors (CDK4/6i) can block the G1 cell cycle through the cyclin D-cyclin dependent kinase 4/6-inhibitor of CDK4-retinoblastoma (cyclinD-CDK4/6-INK4-RB) pathway, thus blocking the proliferation of invasive cells, showing great therapeutic potential to inhibit the spread of BC. So far, three FDA-approved drugs have been shown to be effective in the management of advanced hormone receptor positive (HR+) BC: palbociclib, abemaciclib, and ribociclib. The combination strategy of CDK4/6i and endocrine therapy (ET) has become the standard therapeutic regimen and is increasingly applied to advanced BC patients. The present study aims to clarify whether CDK4/6i can also achieve a certain therapeutic effect on Human epidermal growth factor receptor 2 positive (HER2+) BC. Studies of CDK4/6i are not limited to patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced BC, but have also expanded to other types of BC. Several pre-clinical and clinical trials have demonstrated the potential of CDK4/6i in treating HER2+ BC. Therefore, this review summarizes the current knowledge and recent findings on the use of CDK4/6i in this type of BC, and provides ideas for the discovery of new treatment modalities.
Propranolol: a new pharmacologic approach to counter retinopathy of prematurity progression
Authors: Pascarella Francesca , Scaramuzzo Rosa Teresa , Pini Alessandro , Cammalleri Maurizio , Bagnoli Paola , Ciantelli Massimiliano , Filippi Luca
Published: January 2024

Despite the evident progress in neonatal medicine, retinopathy of prematurity (ROP) remains a serious threat to the vision of premature infants, due to a still partial understanding of the mechanisms underlying the development of this disease and the lack of drugs capable of arresting its progression. Although ROP is a multifactorial disease, retinal vascularization is strictly dependent on oxygen concentration. The exposition of the retina of a preterm newborn, still incompletely vascularized, to an atmosphere relatively hyperoxic, as the extrauterine environment, induces the downregulation of proangiogenic factors and therefore the interruption of vascularization (first ischemic phase of ROP). However, over the following weeks, the growing metabolic requirement of this ischemic retina produces a progressive hypoxia that specularly promotes the surge of proangiogenic factors, finally leading to proliferative retinopathy (second proliferative phase of ROP). The demonstration that the noradrenergic system is actively involved in the coupling between hypoxia and the induction of vasculogenesis paved the way for a pharmacologic intervention aimed at counteracting the interaction of noradrenaline with specific receptors and consequently the progression of ROP. A similar trend has been observed in infantile hemangiomas, the most common vascular lesion of childhood induced by pre-existing hypoxia, which shares similar characteristics with ROP. The fact that propranolol, an unselective antagonist of β1/2 adrenoceptors, counteracts the growth of infantile hemangiomas, suggested the idea of testing the efficacy of propranolol in infants with ROP. From preclinical studies, ongoing clinical trials demonstrated that topical administration of propranolol likely represents the optimal approach to reconcile its efficacy and maximum safety. Given the strict relationship between vessels and neurons, recovering retinal vascularization with propranolol may add further efficacy to prevent retinal dysfunction. In conclusion, the strategy of contrasting precociously the progression of the disease appears to be more advantageous than the current wait-and-see therapeutic approach, which instead is mainly focused on avoiding retinal detachment.
Development and validation of a structured questionnaire for assessing risk factors of medication non-adherence among pulmonary tuberculosis patients in Indonesia
Authors: Rianto Leonov , Agustina Ika , Alfian Sofa D. , Iskandarsyah Aulia , Pradipta Ivan Surya , Abdulah Rizky
Published: January 2024

Background:Medication non-adherence is a significant concern in tuberculosis (TB) treatment, requiring a precise understanding of the associated risk factors. However, there is a lack of appropriate means to assess the risk factors among TB patients in Indonesia, leading to the development and validation of a structured questionnaire for this purpose.

Method:This study unfolded in two distinct phases, namely, the first included questionnaire construction through framework development, item generation, item screening, and pretesting (in 50 patients). The second comprised questionnaire validation with 346 participants using confirmatory factor analysis (CFA) and structural equation modeling-partial least squares (SEM-PLS). Additionally, reliability testing was conducted using Cronbach’s alpha and composite reliability statistical techniques.

Results:In the development phase, 168 items were defined, consisting of sociodemographic characteristics (8 items) and risk factors for medication non-adherence (160 items). Expert evaluation reduced the number of items to 60, which decreased to 22 after performing a pilot study. Subsequent SEM-PLS modeling resulted in the identification of 14 valid items, representing five major risk factors, namely, socioeconomics (4 items), healthcare team (4 items), condition (3 items), therapy (2 items), and patient (1 item). Only condition-related factors were found to influence non-adherence, and all constructs showed good reliability based on Cronbach’s alpha (>0.6) and composite reliability (0.7) values.

Conclusion:The final 22 items that emerged from this rigorous process indicated a valid and robust questionnaire for assessing risk factors of medication non-adherence among pulmonary tuberculosis patients in Indonesia. The developed questionnaire was positioned to be a valuable tool for healthcare professionals, policymakers, and scientists in creating patient-centered strategies and interventions to address non-adherence.
Linoleate-pazopanib conjugation as active pharmacological ingredient to abolish hepatocellular carcinoma growth
Authors: Wang Ke , Liao Pei-Yin , Chang Wei-Chun , Yang Cian-Ru , Su Yu-Ting , Wu Ping-Ching , Wu Yang-Chang , Hung Yao-Ching , Akhtar Najim , Lai Hsueh-Chou , Ma Wen-Lung
Published: January 2024

Small molecule compounds targeting multiple kinases involved in neoangiogenesis have shown survival benefits in patients with unresectable hepatocellular carcinoma (HCC). Nonetheless, despite the beneficial effects of multikinase inhibitors (MKIs), a lack of boosting adjuvant limits their objective response rate. Lipid conjugates have been used to improve delivery efficacy or pharmaceutical benefits for decades. However, the feasibility of utilizing lipid-drug conjugates (LDCs) in HCC regimens remains untested. In this study, oral feeding of linoleate-fluorescein isothiocyanate conjugates showed that the compound was well distributed in a spontaneous HCC mouse model. Therefore, a rationale design was developed for chemically synthesizing a linoleate-pazopanib conjugate (LAPC). The LAPC showed a significantly improved cytotoxicity compared to the parental drug pazopanib. Pazopanib’s angiogenic suppressing signals were not observed in LAPC-treated HCC cells, potentially suggesting an altered mechanism of action (MOA). In an efficacy trial comparing placebo, oral pazopanib, and LAPC treatments in the hepatitis B virus transgene-related spontaneous HCC mouse model (HBVtg-HCC), the LAPC treatment demonstrated superior tumor ablating capacity in comparison to both placebo and pazopanib treatments, without any discernible systemic toxicity. The LAPC exposure is associated with an apoptosis marker (Terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) and an enhanced ferroptosis (glutathione peroxidase 4 [GPX4]) potential in HBVtg-HCC tumors. Therefore, the LAPC showed excellent HCC ablative efficacy with altered MOA. The molecular mechanisms of the LAPC and LDCs for HCC therapeutics are of great academic interest. Further comprehensive preclinical trials (e.g., chemical-manufacture-control, toxicity, distribution, and pharmacokinetics/pharmacodynamics) are expected.