bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of ethosuximide loaded alginate/polyethylene oxide scaffolds for epilepsy research using 3D-printing method
Authors: Karabulut Hatice , Dutta Abir , Moukbil Yunis , Cisen Akyol Aysim , Ulag Songul , Aydin Banu , Gulhan Rezzan , Us Zeynep , Kalaskar Deepak M. , Gunduz Oguzhan
Published: December 2023

Epilepsy is a medical condition that causes seizures and impairs the mental and physical activities of patients. Unfortunately, over one-third of patients do not receive adequate relief from oral Antiepileptic Drugs (AEDs) and continue to experience seizures. In addition to that, long term usage of Antiepileptic Drugs can cause a range of side effects. To overcome this problem, the precision of 3D printing technology is combined with the controlled release capabilities of biodegradable polymers, allowing for tailored and localized AED delivery to specific seizure sites. As a result of this novel technique, therapeutic outcomes can be enhanced, side effects of AEDs are minimized, and patient-specific dosage forms can be created. This study focused on the use of ethosuximide, an antiepileptic drug, at different concentrations (10, 13, and 15 mg) loaded into 3D-printed sodium alginate and polyethylene oxide scaffolds. The scaffolds contained varying concentrations (0.25%, 0.50%, and 0.75% w/v) and had varying pores created by 3D patterning sizes from 159.86 ± 19.9 µm to 240.29 ± 10.7 µm to optimize the releasing system for an intracranial administration. The addition of PEO changed the Tg and Tm temperatures from 65°C to 69°C and from 262°C to 267°C, respectively. Cytotoxicity assays using the human neuroblastoma cell line (SH-SY5Y) showed that cell metabolic activity reached 130% after 168 h, allowing the cells to develop into mature neural cells. In vitro testing demonstrated sustained ethosuximide release lasting 2 hours despite crosslinking with 3% CaCl2. The workpaves the way for the use of ethosuximide -loaded scaffolds for treating epilepsy.
Integration of RNA-seq and ATAC-seq analyzes the effect of low dose neutron-γ radiation on gene expression of lymphocytes from oilfield logging workers
Authors: Li Weiguo , Gao Gang , Pan Yan , Wang Ziqiang , Ruan Jianlei , Fan Li , Shen Yingjie , Wang Haiqing , Li Mian , Zhang Pinhua , Fang Lianying , Fu Jinghong , Liu Jianxiang
Published: December 2023

Objective: Although radiation workers are exposed to much lower doses of neutron-γ rays than those suffered in nuclear explosions and accidents, it does not mean that their health is not affected by radiation. Lower doses of radiation do not always cause morphological aberrations in chromosomes, so more sophisticated tests must be sought to specific alterations in the exposed cells. Our goal was to characterize the specific gene expression in lymphocytes from logging workers who were continuously exposed to low doses of neutron-γ radiation. We hypothesized that the combination of cell type-specific transcriptomes and open chromatin profiles would identify lymphocyte-specific gene alterations induced by long-term radiation with low-dose neutron-γ-rays and discover new regulatory pathways and transcriptional regulatory elements.

Methods: Lymphocytes were extracted from workers who have been occupationally exposed to neutron-γ and workers unexposed to radiation in the same company. mRNA-seq and ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) were performed, followed integrative analysis to identify specific gene regulatory regions induced by neutron-γ radiation. A qPCR assay was then performed to verify the downregulation of RNA coding for ribosomal proteins and flow cytometry was used to detect ribosomal protein expression and cell cycle alterations.

Results: We identified transcripts that were specifically induced by neutron-γ radiation and discovered differential open chromatin regions that correlated with these gene activation patterns. Notably, we observed a downward trend in the expression of both differentially expressed genes and open chromatin peaks. Our most significant finding was that the differential peak upregulated in ATAC-seq, while the differential gene was downregulated in the ribosome pathway. We confirmed that neutron-γ radiation leads to transcriptional inhibition by analyzing the most enriched promoters, examining RPS18 and RPS27A expression by qPCR, and analyzing protein-protein interactions of the differential genes. Ribosomal protein expression and cell cycle were also affected by neutron-γ as detected by flow cytometry.

Conclusion: We have comprehensively analyzed the genetic landscape of human lymphocytes based on chromatin accessibility and transcript levels, enabling the identification of novel neutron-γ induced signature genes not previously known. By comparing fine-mapping of open chromatin and RNA reads, we have determined that neutron-γ specifically leads to downregulation of genes in the ribosome pathway, with pseudogenes potentially playing a crucial role.
Improving lexical retrieval with LingoTalk: an app-based, self-administered treatment for clients with aphasia
Authors: Heide Judith , Netzebandt Jonka , Ahrens Stine , Brüsch Julia , Saalfrank Teresa , Schmitz-Antonischki Dorit
Published: December 2023

Introduction

LingoTalk is a German speech-language app designed to enhance lexical retrieval in individuals with aphasia. It incorporates automatic speech recognition (ASR) to provide therapist-independent feedback. The execution and effectiveness of a self-administered intervention with LingoTalk was explored in a case series study.

Methods

Three individuals with chronic aphasia participated in a highly individualized, supervised self-administered intervention lasting 3 weeks. The LingoTalk app closely monitored the frequency, intensity and progress of the intervention. Treatment efficacy was assessed using a multiple baseline design, examining both item-specific treatment effects and generalization to untreated items, an untreated task, and spontaneous speech.

Results

All participants successfully completed the intervention with LingoTalk, although one participant was not able to use the ASR feature. None of the participants fully adhered to the treatment protocol. All participants demonstrated significant and sustained improvement in the naming of practiced items, although there was limited evidence of generalization. Additionally, there was a slight reduction in word-finding difficulties during spontaneous speech.

Discussion

This small-scale study indicates that self-administered intervention with LingoTalk can improve oral naming of treated items. Thus, it has the potential to complement face-to-face speech-language therapy, such as within in a “flipped speech room” approach. The choice of feedback mode is discussed. Transparent progress monitoring of the intervention appears to positively influence patients' motivation.
Enhancing predictive accuracy of the cardiac risk score in open abdominal aortic surgery: the role of left ventricular wall motion abnormalities
Authors: Djokic Ivana , Milicic Biljana , Matic Predrag , Ilijevski Nenad , Milojevic Milan , Jovic Miomir
Published: December 2023

Background

Open abdominal aortic surgery carries many potential complications, with cardiac adverse events being the most significant concern. The Vascular Study Group Cardiac Risk Index (VSG-CRI) is a commonly used tool for predicting severe cardiac complications and guiding clinical decision-making. However, despite the potential prognostic significance of left ventricular wall motion abnormalities (LVWMAs) and reduced LV ejection fraction (LVEF) for adverse outcomes, the VSG-CRI model has not accounted for them. Hence, the main objective of this study was to analyze the added value of LV wall motion on the discriminatory power of the modified VSG-CRI in predicting major postoperative cardiac complications.

Methods

A prospective study was conducted involving 271 patients who underwent elective abdominal aortic surgery between 2019 and 2021. VSG-CRI scores were calculated, and preoperative transthoracic echocardiography was conducted for all patients. Subsequently, a modified version of the VSG-CRI, accounting for reduced LVEF and LVWMAs, was developed and incorporated into the dataset. The postoperative incidence of the composite endpoint of major adverse cardiac events (MACEs), including myocardial infarction, clinically relevant arrhythmias treated with medicaments or by cardioversion, or congestive heart failure, was assessed at discharge from the index hospitalization, with adjudicators blinded to events. The predictive accuracy of both the original and modified VSG-CRI was assessed using C-Statistics.

Results

In total, 61 patients (22.5%) experienced MACEs. Among these patients, a significantly higher proportion had preoperative LVWMAs compared to those without (62.3% vs. 32.9%, p < 0.001). Multivariable regression analysis revealed the VSG-CRI [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.21–1.77; p < 0.001] and LVWMA (OR 2.76; 95% CI 1.46–5.23; p = 0.002) as independent predictors of MACEs. Additionally, the modified VSG-CRI model demonstrated superior predictability compared to the baseline VSG-CRI model, suggesting an improved predictive performance for anticipating MACEs following abdominal aortic surgery [area under the curve (AUC) 0.74; 95% CI 0.68–0.81 vs. AUC 0.70; 95% CI 0.63–0.77; respectively].

Conclusion

The findings of this study suggest that incorporating preoperative echocardiography can enhance the predictive accuracy of the VSG-CRI for predicting MACEs after open abdominal aortic surgery. Before its implementation in clinical settings, external validation is necessary to confirm the generalizability of this newly developed predictive model across different populations.
University consortium to address public health priorities and research capacity building in the Caribbean
Authors: Li Allison , Lindo John F. , Beckles Hilary , Mohler James L. , Reid Marvin , Boyne Michael , DeHovitz Jack , Diaz Patricia I. , Brown Paul , Anzinger Joshua , Carrington Christine , Anderson Kathryn B. , Landay Alan , Cummings Michael , Chernyak Elizabeth , Prescott Gina , Cha Raymond , Thangamani Saravanan , Barthelemy Ernest , Dubovsky Steven , Ennis Ative , Evans-Gilbert Tracy , Morse Gene D.
Published: December 2023

The State University of New York (SUNY) – University of the West Indies (UWI) Health Research Consortium (HRC) was implemented in 2015 by the SUNY Global Health Institute (GHI) and the SUNY-UWI Center for Leadership and Sustainable Development. The goal was to advance public health in the Caribbean through collaborative research and education among faculty and students at SUNY and UWI. The Consortium is now a dynamic matrix addressing health priorities that were initially agreed upon with the Jamaica Ministry of Health and Wellness. The HRC has built a foundational matrix that is planning for cutting edge laboratory instrumentation, biomedical informatics system, seamless electronic medical records network, national laboratory data management system, and novel biotechnology (e.g., robotic surgery cluster). The SUNY-UWI partnership fills existing gaps through collaborative programs with the SUNY GHI that facilitate UWI faculty interactions with SUNY faculty and core resources and incubators that encourage collaborations while UWI infrastructure expands. The Health Research Consortium utilizes existing academic models at UWI and SUNY to promote collaboration, capacity building, and program implementation. Consortium teams develop sound business development models that foster sustained economic growth and form the pipeline for workforce development and career opportunities. The Caribbean diaspora and UWI alumni are engaged in working together on this effort. In addition, mentoring in K-12 and beyond is needed to create a vision for the next generations.
Brain and serum metabolomic studies reveal therapeutic effects of san hua decoction in rats with ischemic stroke
Authors: Liu Ruisi , Cao Shengxuan , Cai Yufeng , Zhou Mingmei , Gou Xiaojun , Huang Ying
Published: December 2023

San Hua Decoction (SHD) is a traditional four-herbal formula that has long been used to treat stroke. Our study used a traditional pharmacodynamic approach combined with systematic and untargeted metabolomics analyses to further investigate the therapeutic effects and potential mechanisms of SHD on ischemic stroke (IS). Male Sprague-Dawley rats were randomly divided into control, sham-operated, middle cerebral artery occlusion reperfusion (MCAO/R) model and SHD groups. The SHD group was provided with SHD (7.2 g/kg, i.g.) and the other three groups were provided with equal amounts of purified water once a day in the morning for 10 consecutive days. Our results showed that cerebral infarct volumes were reduced in the SHD group compared with the model group. Besides, SHD enhanced the activity of SOD and decreased MDA level in MCAO/R rats. Meanwhile, SHD could ameliorate pathological abnormalities by reducing neuronal damage, improving the structure of damaged neurons and reducing inflammatory cell infiltration. Metabolomic analysis of brain and serum samples with GC-MS techniques revealed 55 differential metabolites between the sham and model groups. Among them, the levels of 12 metabolites were restored after treatment with SHD. Metabolic pathway analysis showed that SHD improved the levels of 12 metabolites related to amino acid metabolism and carbohydrate metabolism, 9 of which were significantly associated with disease. SHD attenuated brain inflammation after ischemia-reperfusion. The mechanisms underlying the therapeutic effects of SHD in MCAO/R rats are related to amino acid and carbohydrate metabolism.
Adaptive design of tipping bucket flow meters for continuous runoff measurement
Authors: Schwamback Dimaghi , Persson Magnus , Berndtsson Ronny , Anache Jamil A. A. , Wendland Edson Cezar
Published: December 2023

Introduction: Runoff measurement and monitoring is a laborious, time-consuming, and costly task. Additionally, common runoff monitoring usually primarily provide water level, requiring information on the stage-discharge relation. Automatic equipment such as flow meter tipping bucket (TB) is a potential option to simplify and provide continuous runoff monitoring in small catchments. However, a proper description of how to size and adapt the design under different flow conditions is still lacking.

Methodology: In this paper we present a novel standardized framework for the design of TB that can be used for low-cost and real-time runoff monitoring under many different conditions. The framework consists of an estimation of the runoff peak rate using the rational equation and a volumetric capacity estimate of the cavity based on runoff rate, operation speed, and inclination angle of TB when at resting position. The proposed framework was implemented in a case study where four TBs were designed for continuous runoff monitoring from experimental plots (100 m2) with different land use (sugarcane, soybean, and bare soil).

Results: During field tests (five months), the designed TBs had a recovery rate of actual runoff ranging from 61% to 81% and were able to capture features poorly studied (starting/ending time and peak flow) that have potential importance in hydrological models.

Discussion: The proposed framework is flexible and can be used for different environmental conditions to provide continuous runoff data records.
Carrier frequency and incidence of alpha-mannosidosis: population database-based study—focus on the East Asian and Korean population
Authors: Park Jong Eun , Lee Taeheon , Ha Kyeongsu , Cho Eun Hye , Ki Chang-Seok
Published: December 2023

Background: Alpha-mannosidosis caused by mutations in the MAN2B1 gene is a rare genetic disorder characterized by physical abnormalities and intellectual disabilities. The objective of this study was to analyze the carrier frequency and estimated incidence of alpha-mannosidosis in East Asian populations, as limited data exists on its incidence in this group.

Methods: In this study, a total of 125,748 exomes from the gnomAD database was analyzed. Additionally, 5,305 data from the KOVA and 1,722 data from the KRGDB, both representing Korean populations, were included.

Results: The global carrier frequency of alpha-mannosidosis in gnomAD was 0.23%; the highest carrier frequency was observed in the Finnish at 0.49%, and East Asians had the second highest carrier frequency at 0.30%. Globally, the approximate incidence of alpha-mannosidosis was calculated at 1 in 784,535, l in 166,801 Europeans (Finnish), and l in 431,689 East Asians. By integrating the data from the 8,936 Koreans in gnomAD Korean, KOVA and KRGDB, the carrier frequency of alpha-mannosidosis in the Korean population was 0.04% and estimated incidence was 1 in 19,963,024.

Conclusion: This study is the first to investigate the carrier frequencies of alpha-mannosidosis in East Asians and Koreans, including specific subpopulations, utilizing gnomAD and the Korean genomic database. The variant spectrum of MAN2B1 genes in East Asians showed significant differences compared to other ethnic groups. Our data provide valuable reference information for future investigations into alpha-mannosidosis, aiding in understanding the genetic diversity and specific variants associated with the condition in East Asian populations.
Disparate viral pandemics from COVID19 to monkeypox and beyond: a simple, effective and universal therapeutic approach hiding in plain sight
Authors: Johnson Howard M. , Ahmed Chulbul M.
Published: December 2023

The field of antiviral therapeutics is fixated on COVID19 and rightly so as the fatalities at the height of the pandemic in the United States were almost 1,000,000 in a twelve month period spanning parts of 2020/2021. A coronavirus called SARS–CoV2 is the causative virus. Development of a vaccine through molecular biology approaches with mRNA as the inducer of virus spike protein has played a major role in driving down mortality and morbidity. Antivirals have been of marginal value in established infections at the level of hospitalization. Thus, the current focus is on early symptomatic infection of about the first five days. The Pfizer drug paxlovid which is composed of nirmatrelvir, a peptidomimetic protease inhibitor of SARS–CoV2 Mpro enzyme, and ritonavir to retard degradation of nirmatrelvir, is the current FDA recommended treatment of early COVID19. There is no evidence of broad antiviral activity of paxlovid against other diverse viruses such as the influenza virus, poxviruses, as well as a host of respiratory viruses. Although type I interferons (IFNs) are effective against SARS–CoV2 in cell cultures and in early COVID19 infections, they have not been broadly recommended as therapeutics for COVID19. We have developed stable peptidomimetics of both types I and II IFNs based on our noncanonical model of IFN signaling involving the C-terminus of the IFNs. We have also identified two members of intracellular checkpoint inhibitors called suppressors of cytokine signaling (SOCS), SOCS1 and SOCS3 (SOCS1/3), and shown that they are virus induced intrinsic virulence proteins with activity against IFN signaling enzymes JAK2 and TYK2. We developed a peptidomimetic antagonist, based on JAK2 activation loop, against SOCS1/3 and showed that it synergizes with the IFN mimetics for potent broad spectrum antiviral activity without the toxicity of intact IFN molecules. IFN mimetics and the SOCS1/3 antagonist should have an advantage over currently used antivirals in terms of safety and potency against a broad spectrum of viruses.
Challenges in drug discovery and description targeting Leishmania spp.: enzymes, structural proteins, and transporters
Authors: Mendoza-León Alexis , Serrano G. María Luisa , Ponte-Sucre Alicia
Published: December 2023

Leishmaniasis is a complex tropical disease caused by the protozoan parasite Leishmania spp. Classical chemotherapy includes pentavalent antimonial; however, pentamidine, amphotericin B, and miltefosine have been used. Chemo-resistance remains a risk for successful treatment; thus, target identification and development of selective drugs remain a priority in controlling this disease. Evidence indicates that 6-phosphogluconate dehydrogenase (6PGDH), β-tubulin protein, and ATP-dependent transporters (ABCs-T) are potential targets to be addressed. The pentose phosphate pathway key enzyme 6PGDH is essential for protecting kinetoplastid parasites from oxidative stress and differs from the mammalian host enzyme (<35% AA sequence identity). An optimized 3D model has been used to select high -affinity compounds toward the enzyme through virtual screening and subsequent evaluation in vivo. In kinetoplasts, tubulins are highly conserved proteins essential for microtubule formation. However, compared to other eukaryotic cells, there is a differential susceptibility of kinetoplastid proteins to antimicrotubular agents, e.g., colchicine resistance. A comparison of experimental models between bovine and Leishmania β-tubulin protein allowed us to identify structural modification products of various amino acid substitutions, which hinder the access of colchicine to the binding pocket of the Leishmania protein. Similar changes are found in the β-tubulin sequence of other kinetoplastids such as Trypanosoma cruzi, T. brucei, and T. evansi. The evaluation of the β-tubulin protein as a therapeutic target and the compounds that selectively interact with it was carried out using in silico approaches. The activities of ABC-Transporters are related to the main causes of drug resistance, and the collected evidence suggests that for the ABC-Transporter blocker glibenclamide, there is a: (1) differential susceptibility of Leishmania spp. vs. macrophages; (2) greater susceptibility of axenic amastigotes vs. promastigotes; and (3) glibenclamide-glucantime synergistic drug interaction in macrophage-infected cells. Herein, we discuss the potential value of designing ABC-Transporter blockers for combination therapy in the treatment of leishmaniasis. The examples mentioned above highlight the importance of the search for new therapeutic targets and pharmacophores for the design of alternative treatments for the disease.
China's marine environmental public interest litigation: current situation, challenges, and improvement approach –analysis based on 339 cases
Authors: Yang Lei
Published: December 2023

Marine pollution and ecological damage seriously undermine economic and social development and human life and health and threaten the sustainable development of human society. With the rapid development of industrialization and urbanization and the intense exploitation of marine space and marine natural resources, China’s marine ecology is facing serious problems such as pollution of marine waters, the decline of marine plant and animal resources, and the impairment of the ecological function of coastal zones. China’s marine environmental public interest litigation (MEPIL) has achieved remarkable results in protecting marine natural resources, safeguarding the marine ecosystem, and preventing marine pollution and ecological damage. The paper closely combines the judicial practice of Chinese MEPIL, exploring 339 legal cases brought by administrative organs, public prosecutors, and non-governmental organizations (NGOs) presented on the China Judgment Online from 2018 to 2023. It can be concluded that three modes of MEPIL, namely civil, administrative, and civil public interest litigation incidental to criminal proceedings, have been constructed. Attempts have been made to confirm the standing of the litigation, improve the pre-litigation procedure, and clarify the types of compensation. However, significant obstacles exist in China’s MEPIL. Theoretical clarifications and practical distinctions with other types of proceedings should be made. The current standing should be improved regarding procuratorial organs, administrative authorities, and social organizations. Court jurisdiction systems need to be enhanced. Inconsistencies in the legal provisions on whether MEPIL cases must be under the exclusive jurisdiction of the maritime courts have impeded the efficiency of the handling of cases. The corresponding solutions to the aforementioned obstacles are also analyzed. Clarifying the MEPIL’s nature and improving the relevant laws, and regulations, are essential measures. In addition, providing the explicit interpretation of the legal provisions, expanding the standing, and improving the jurisdictional and other legal system should be explored.
Deep learning-based clinical-radiomics nomogram for preoperative prediction of lymph node metastasis in patients with rectal cancer: a two-center study
Authors: Ma Shiyu , Lu Haidi , Jing Guodong , Li Zhihui , Zhang Qianwen , Ma Xiaolu , Chen Fangying , Shao Chengwei , Lu Yong , Wang Hao , Shen Fu
Published: December 2023

Background

Precise preoperative evaluation of lymph node metastasis (LNM) is crucial for ensuring effective treatment for rectal cancer (RC). This research aims to develop a clinical-radiomics nomogram based on deep learning techniques, preoperative magnetic resonance imaging (MRI) and clinical characteristics, enabling the accurate prediction of LNM in RC.

Materials and methods

Between January 2017 and May 2023, a total of 519 rectal cancer cases confirmed by pathological examination were retrospectively recruited from two tertiary hospitals. A total of 253 consecutive individuals were selected from Center I to create an automated MRI segmentation technique utilizing deep learning algorithms. The performance of the model was evaluated using the dice similarity coefficient (DSC), the 95th percentile Hausdorff distance (HD95), and the average surface distance (ASD). Subsequently, two external validation cohorts were established: one comprising 178 patients from center I (EVC1) and another consisting of 88 patients from center II (EVC2). The automatic segmentation provided radiomics features, which were then used to create a Radscore. A predictive nomogram integrating the Radscore and clinical parameters was constructed using multivariate logistic regression. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were employed to evaluate the discrimination capabilities of the Radscore, nomogram, and subjective evaluation model, respectively.

Results

The mean DSC, HD95 and ASD were 0.857 ± 0.041, 2.186 ± 0.956, and 0.562 ± 0.194 mm, respectively. The nomogram, which incorporates MR T-stage, CEA, CA19-9, and Radscore, exhibited a higher area under the ROC curve (AUC) compared to the Radscore and subjective evaluation in the training set (0.921 vs. 0.903 vs. 0.662). Similarly, in both external validation sets, the nomogram demonstrated a higher AUC than the Radscore and subjective evaluation (0.908 vs. 0.735 vs. 0.640, and 0.884 vs. 0.802 vs. 0.734).

Conclusion

The application of the deep learning method enables efficient automatic segmentation. The clinical-radiomics nomogram, utilizing preoperative MRI and automatic segmentation, proves to be an accurate method for assessing LNM in RC. This approach has the potential to enhance clinical decision-making and improve patient care.

Research registration unique identifying number (UIN)

Research registry, identifier 9158, https://www.researchregistry.com/browse-the-registry#home/registrationdetails/648e813efffa4e0028022796/.
Establishing thresholds of handgrip strength based on mortality using machine learning in a prospective cohort of Chinese population
Authors: Zhou Haofeng , Chen Zepeng , Liu Yuting , Liao Yingxue , Guo Lan , Xu Mingyu , Bai Bingqing , Liu Fengyao , Ma Huan , Yao Xiaoxuan , Geng Qingshan
Published: December 2023

Background

The relative prognostic importance of handgrip strength (HGS) in comparison with other risk factors for mortality remains to be further clarified, and thresholds used for best identify high-risk individuals in health screening are not yet established. Using machine learning and nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), the study aimed to investigate the prognostic importance of HGS and establish sex-specific thresholds for health screening.

Methods

A total of 6,762 participants from CHARLS were enrolled. A random forest model was built using 30 variables with all-cause mortality as outcome. SHapley Additive exPlanation values were applied to explain the model. Cox proportional hazard models and Harrell’s C index change were used to validate the clinical importance of the thresholds.

Results

Among the participants, 3,102 (45.9%) were men, and 622 (9.1%) case of death were documented follow-up period of 6.78 years. The random forest model identified HGS as the fifth important prognostic variable, with thresholds for identifying high-risk individuals were < 32 kg in men and < 19 kg in women. Low HGS were associated with all-cause mortality [HR (95% CI): 1.77 (1.49–2.11), p < 0.001]. The addition of HGS thresholds improved the predictive ability of an established office-based risk score (C-index change: 0.022, p < 0.001).

Conclusion

On the basis of our thresholds, low HGS predicted all-cause mortality better than other risk factors and improved prediction of a traditional office-based risk score. These results reinforced the clinical utility of measurement of HGS in health screening.
Management of psoriatic arthritis: a consensus opinion by expert rheumatologists
Authors: D’Angelo Salvatore , Atzeni Fabiola , Benucci Maurizio , Bianchi Gerolamo , Cantini Fabrizio , Caporali Roberto Felice , Carlino Giorgio , Caso Francesco , Cauli Alberto , Ciccia Francesco , D’Agostino Maria Antonietta , Dagna Lorenzo , Dejaco Christian , Epis Oscar Massimiliano , Ferrucci Maria Grazia , Franceschini Franco , Fusaro Enrico , Gabini Marco , Gerli Roberto , Giacomelli Roberto , Govoni Marcello , Gremese Elisa , Guggino Giuliana , Iagnocco Annamaria , Iannone Florenzo , Laganà Bruno , Lubrano Ennio , Montecucco Carlomaurizio , Peluso Rosario , Ramonda Roberta , Rossini Maurizio , Salvarani Carlo , Sebastiani Gian Domenico , Sebastiani Marco , Selmi Carlo , Tirri Enrico , Marchesoni Antonio
Published: December 2023

Background

Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease involving several articular and extra-articular structures. Despite the important progresses recently made in all of the aspects of this disease, its management is still burdened by unresolved issues. The aim of this exercise was to provide a set of statements that may be helpful for the management of PsA.

Methods

A group of 38 Italian rheumatologists with recognized expertise in PsA selected and addressed the following four topics: “early PsA,” “axial-PsA,” “extra-articular manifestations and comorbidities,” “therapeutic goals.” Relevant articles from the literature (2016–2022) were selected by the experts based on a PubMed search. A number of statements for each topic were elaborated.

Results

Ninety-four articles were selected and evaluated, 68 out of the 1,114 yielded by the literature search and 26 added by the Authors. Each of the four topic was subdivided in themes as follows: transition from psoriasis to PsA, imaging vs. CASPAR criteria in early diagnosis, early treatment for “early PsA”; axial-PsA vs. axialspondyloarthritis, diagnosis, clinical evaluation, treatment, standard radiography vs. magnetic resonance imaging for “axial PsA”; influence of inflammatory bowel disease on the therapeutic choice, cardiovascular comorbidity, bone damage, risk of infection for “comorbidities and extra-articular manifestations”; target and tools, treat-to-target strategy, role of imaging for “therapeutic goals.” The final document consisted of 49 statements.

Discussion

The final product of this exercise is a set of statements concerning the main issues of PsA management offering an expert opinion for some unmet needs of this complex disease.
Unveiling the mechanisms of neuropathic pain suppression: perineural resiniferatoxin targets Trpv1 and beyond
Authors: Shehab Safa , Javed Hayate , Johnson Aishwarya Mary , Tariq Saeed , Kumar Challagandla Anil , Emerald Bright Starling
Published: December 2023

Neuropathic pain arises from damage or disorders affecting the somatosensory system. In rats, L5 nerve injury induces thermal and mechanical hypersensitivity/hyperalgesia. Recently, we demonstrated that applying resiniferatoxin (RTX) directly on uninjured L3 and L4 nerves alleviated thermal and mechanical hypersensitivity resulting from L5 nerve injury. Herein, using immunohistochemistry, Western blot, and qRT-PCR techniques, we reveal that perineural application of RTX (0.002%) on the L4 nerve substantially downregulated the expression of its receptor (Trpv1) and three different voltage-gated ion channels (Nav1.9, Kv4.3, and Cav2.2). These channels are found primarily in small-sized neurons and show significant colocalization with Trpv1 in the dorsal root ganglion (DRG). However, RTX treatment did not affect the expression of Kv1.1, Piezo2 (found in large-sized neurons without colocalization with Trpv1), and Kir4.1 (localized in satellite cells) in the ipsilateral DRGs. Furthermore, RTX application on L3 and L4 nerves reduced the activation of c-fos in the spinal neurons induced by heat stimulation. Subsequently, we investigated whether applying RTX to the L3 and L4 nerves 3 weeks before the L5 nerve injury could prevent the onset of neuropathic pain. Both 0.002 and 0.004% concentrations of RTX produced significant analgesic effects, while complete prevention of thermal and mechanical hypersensitivity required a concentration of 0.008%. Importantly, this preventive effect on neuropathic manifestations was not associated with nerve degeneration, as microscopic examination revealed no morphological changes. Overall, this study underscores the mechanisms and the significance of perineural RTX treatment applied to adjacent uninjured nerves in entirely preventing nerve injury-induced neuropathic pain in humans and animals.
Altered expression of inflammation-associated molecules in striatum: an implication for sensitivity to heavy ion radiations
Authors: Chen Zixuan , Li Yumeng , Rasheed Madiha , Wang Hao , Lei Runhong , Zhao Tuo , Deng Yulin , Ma Hong
Published: December 2023

Background and objective

Heavy ion radiation is one of the major hazards astronauts face during space expeditions, adversely affecting the central nervous system. Radiation causes severe damage to sensitive brain regions, especially the striatum, resulting in cognitive impairment and other physiological issues in astronauts. However, the intensity of brain damage and associated underlying molecular pathological mechanisms mediated by heavy ion radiation are still unknown. The present study is aimed to identify the damaging effect of heavy ion radiation on the striatum and associated underlying pathological mechanisms.

Materials and methods

Two parallel cohorts of rats were exposed to radiation in multiple doses and times. Cohort I was exposed to 15 Gy of 12C6+ ions radiation, whereas cohort II was exposed to 3.4 Gy and 8 Gy with 56Fe26+ ions irradiation. Physiological and behavioural tests were performed, followed by 18F-FDG-PET scans, transcriptomics analysis of the striatum, and in-vitro studies to verify the interconnection between immune cells and neurons.

Results

Both cohorts revealed more persistent striatum dysfunction than other brain regions under heavy ion radiation at multiple doses and time, exposed by physiological, behavioural, and 18F-FDG-PET scans. Transcriptomic analysis revealed that striatum dysfunction is linked with an abnormal immune system. In vitro studies demonstrated that radiation mediated diversified effects on different immune cells and sustained monocyte viability but inhibited its differentiation and migration, leading to chronic neuroinflammation in the striatum and might affect other associated brain regions.

Conclusion

Our findings suggest that striatum dysfunction under heavy ion radiation activates abnormal immune systems, leading to chronic neuroinflammation and neuronal injury.
Association of high-estimated glomerular filtration rate with the severity of ischemic stroke during non-vitamin K antagonist oral anticoagulants therapy: a nationwide cohort study
Authors: Kang Min Kyoung , Lee Dongwhane , Oh Mi Sun , Lee Ji-Sung , Jeong Han-Yeong , Shin Jung Hwan , Yoon Byung-Woo , Park Jong-Moo
Published: December 2023

Aim

While the relationship between impaired kidney function and non-vitamin K antagonist oral anticoagulants (NOACs) is well established, there is limited research exploring the association between an elevated estimated glomerular filtration rate (eGFR) and the efficacy of NOACs, especially concerning the outcomes of acute ischemic stroke (AIS). This study aimed to examine the association between higher-than-normal eGFR and the severity of AIS during the use of NOACs using a nationwide multicenter stroke registry in Korea.

Material and methods

This study utilized data from the Korean Stroke Registry (KSR) database, examining information from 2,379 patients with AIS, who had atrial fibrillation (AF) and a history of utilizing NOACs prior to hospitalization due to incident stroke occurring between 2016 and 2021. Patients with a history involving two or more types of anticoagulants or one or more forms of antiplatelet agents were excluded. Baseline characteristics, medical history, medication usage, CHADS2-VASc score, and the anticoagulation and risk factors in atrial fibrillation (ATRIA) score were evaluated. Renal function was assessed using eGFR levels and calculated with the Cockcroft–Gault equation. The severity of stroke was measured by the National Institutes of Health Stroke Scale as an outcome. For sensitivity analysis, further evaluation was performed using eGFR levels according to the modification of diet in renal disease (MDRD) study equation.

Results

The mean age of subjects was 76.1 ± 8.9 years. The moderate-to-severe stroke severity group exhibited an elevation in creatinine levels. The eGFR of 60 to 89 mL/min/1.73 m2 group was associated with a decreased risk of moderate-to-severe stroke severity [hazard ratio (HR)] (0.77, 95% confidence interval (CI) [0.61, 0.98], p = 0.031) compared to the eGFR≥90 mL/min/1.73 m2 group. An increment of 10 units in eGFR was marginally associated with an increased risk of moderate-to-severe stroke severity (HR: 1.03, 95% CI [1.00, 1.07], p = 0.054).

Conclusion

The study revealed that individuals with eGFR ≥ 90 mL/min/1.73 m2 had an association linked to an increased risk of moderate-to-severe stroke severity. Our study suggests that patients taking NOACs with higher-than-normal eGFR levels may have an increased severity of AIS.
Resection of ruptured aneurysm associated with bilateral anomalous posterior inferior cerebellar anastomotic arteries: case report and review of literature
Authors: Han Qingdong , Wang Zongqi , Liu Tong , Huang Yabo
Published: December 2023

Introduction

Aneurysms on the posterior inferior cerebellar artery (PICA) may not be the major part of intracranial aneurysm. Especially, an aneurysm located on the bilateral posterior inferior cerebellar anastomotic artery has abnormal anatomical characteristics in the vessel wall and then causes stroke including subarachnoid hemorrhage. This case report explores the direct resection of a ruptured aneurysm associated with the bilateral anomalous anastomotic artery of PICA.

Methods

The case report discusses a 53-year-old woman who suffered from sudden severe headache and vomiting for more than 3 h admitted to our hospital. Emergency computed tomography (CT) revealed subarachnoid hemorrhage (SAH) in the third and fourth ventricles. Preoperative 3 Dimensions-digital subtraction angiography (3-D DSA) indicated a ruptured aneurysm located on the bilateral posterior inferior cerebellar anastomotic artery. Postoperative pathological findings indicated the characteristics of parent artery PICA and control aneurysm. The authors performed an overview of PICA aneurysms with anomalous variation in the Pubmed, Web of Science, and Medline databases. The search was until 1 August 2023. Related terms “posterior inferior cerebellar artery” And “aneurysm” AND “anatomical variants” were used to search the review. The reasons for anomalous variation anastomosis between bilateral PICAs were analyzed.

Results

The aneurysm was resected successfully. Post-operative 3-D DSA revealed the disappearance of the aneurysm. The vessel wall of anastomotic PICA showed neovascularized hyperplasia, abnormal arrangement of smooth muscle, CD31+ endothelial cells, and SMA+ smooth muscle cells. In contrast, when it came to aneurysm, the wall at the location of the fracture thinned, which could be used to explain that the local nodular protrusion was formed and CD31+ endothelial cells existed. No neurological deficits were found at her 1-year follow-up visit (mRS score of 0).

Conclusion

Direct resection of ruptured aneurysm associated with bilateral anomalous posterior inferior cerebellar anastomotic arteries was an effective treatment and careful consideration of the anatomical characteristics concerning the interesting aneurysm and the variant PICA was critical for sate treatment. Also, the literature on the lesion was reviewed.
Anxiolytic and antidepressant like effects of Zamzam water in STZ-induced diabetic rats, targeting oxidative stress, neuroinflammation, BDNF/ERK/CREP pathway with modulation of hypothalamo-pituitary–adrenal axis
Authors: Taha Medhat , Mahmoud Mohamed Ezzat , Al-Kushi Abdullah G. , Sarhan Anas , Abdelbagi Omer , Baokbah Tourki A. S. , Babateen Omar , El-Shenbaby Ibrahim , Qusty Naeem F. , Elazab Sara T.
Published: December 2023

Introduction

Recent studies have reported a strong relationship between diabetes and anxiety- and depression-like behaviors; however, there is a lack of information on the underlying pathophysiology. Alkaline Zamzam water (ZW), which is rich in several trace elements, has neuroprotective properties. This study aimed to investigate the anxiolytic and antidepressant effects of ZW against diabetes-induced behavioral changes and shed light on the possible underlying mechanisms.

Methods

Forty-eight rats were divided into four experimental groups (n = 12): group I (control group), group II (Zamzam water group), group III (diabetic group), and group IV (diabetic + Zamzam water group). Diabetes was induced by an intraperitoneal injection of 60 mg/kg streptozotocin (STZ). At the end of the experiment, the forced swimming test (FST) was used to assess depression-like effects. The elevated plus maze test (EPMT) and open field test (OFT) were performed to evaluate anxiety-like behavior. Blood levels of the hypothalamic–pituitary–adrenal (HPA) axis were measured, and prefrontal cortex and hippocampal tissue samples were removed for histological, immunohistochemical, ELISA, and Q-PCR analyses.

Results

ZW significantly decreased the immobility time in the FST, indicating an antidepressant effect (p < 0.001). Additionally, ZW significantly improved the OFT and open field entry (OFE) percentages in the EPMT, increasing center crossing and decreasing grooming and fecal boli in the OFT. This indicated an anxiolytic-like effect in diabetic rats with histological improvement. Interestingly, ZW significantly increased prefrontal cortical and hippocampal levels of antioxidant enzymes and the Nrf2/HO-1 pathway. It also modulated the HPA axis by increasing cortisol and corticotropin-releasing hormone (CRH) levels, with a decrease in ACTH and an increase in monoamine neurotransmitters. Furthermore, diabetic rats that received ZW showed a decrease in the inflammatory markers TNF-α and GFAP by immunohistochemistry and in the mRNA levels of NFκB, IL-1β, and IL6. In addition, ZW downregulated the expression of the BDNF/ERK2/CREP pathway.

Conclusion

Our results suggested a neuroprotective effect of ZW against diabetes-induced anxiety- and depression-like behaviors and explored the underlying mechanisms. These findings suggest a promising therapeutic strategy for patients with diabetes who experience anxiety and depression.
Developmental synapse pathology triggered by maternal exposure to the herbicide glufosinate ammonium
Authors: Izumi Hironori , Demura Maina , Imai Ayako , Ogawa Ryohei , Fukuchi Mamoru , Okubo Taisaku , Tabata Toshihide , Mori Hisashi , Yoshida Tomoyuki
Published: December 2023

Environmental and genetic factors influence synapse formation. Numerous animal experiments have revealed that pesticides, including herbicides, can disturb normal intracellular signals, gene expression, and individual animal behaviors. However, the mechanism underlying the adverse outcomes of pesticide exposure remains elusive. Herein, we investigated the effect of maternal exposure to the herbicide glufosinate ammonium (GLA) on offspring neuronal synapse formation in vitro. Cultured cerebral cortical neurons prepared from mouse embryos with maternal GLA exposure demonstrated impaired synapse formation induced by synaptic organizer neuroligin 1 (NLGN1)–coated beads. Conversely, the direct administration of GLA to the neuronal cultures exhibited negligible effect on the NLGN1-induced synapse formation. The comparison of the transcriptomes of cultured neurons from embryos treated with maternal GLA or vehicle and a subsequent bioinformatics analysis of differentially expressed genes (DEGs) identified “nervous system development,” including “synapse,” as the top-ranking process for downregulated DEGs in the GLA group. In addition, we detected lower densities of parvalbumin (Pvalb)-positive neurons at the postnatal developmental stage in the medial prefrontal cortex (mPFC) of offspring born to GLA–exposed dams. These results suggest that maternal GLA exposure induces synapse pathology, with alterations in the expression of genes that regulate synaptic development via an indirect pathway distinct from the effect of direct GLA action on neurons.