bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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

BackgroundPrecise 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 methodsBetween 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.ResultsThe 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).ConclusionThe 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

BackgroundThe 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.MethodsA 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.ResultsAmong 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 &lt; 32 kg in men and &lt; 19 kg in women. Low HGS were associated with all-cause mortality [HR (95% CI): 1.77 (1.49–2.11), p &lt; 0.001]. The addition of HGS thresholds improved the predictive ability of an established office-based risk score (C-index change: 0.022, p &lt; 0.001).ConclusionOn 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

BackgroundPsoriatic 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.MethodsA 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.ResultsNinety-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.DiscussionThe 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.
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 objectiveHeavy 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 methodsTwo 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.ResultsBoth 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.ConclusionOur 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

AimWhile 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 methodsThis 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.ResultsThe 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).ConclusionThe 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

IntroductionAneurysms 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.MethodsThe 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.ResultsThe 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).ConclusionDirect 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

IntroductionRecent 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.MethodsForty-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.ResultsZW significantly decreased the immobility time in the FST, indicating an antidepressant effect (p &lt; 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.ConclusionOur 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.
Assessing functional impulsivity using functional near-infrared spectroscopy
Authors: Nakazawa Kenta , Hirabayashi Kazue , Kawai Wakana , Kyutoku Yasushi , Kawabata Duncan Keith , Dan Ippeita 
Published: December 2023

IntroductionIn neuromarketing, a recently developing, inter-disciplinary field combining neuroscience and marketing, neurophysiological responses have been applied to understand consumers' behaviors. While many studies have focused on explicit attitudes, few have targeted implicit aspects. To explore the possibility of measuring implicit desire for a product, we focused on functional impulsivity related to obtaining a product as a reward and devised a product-rewarded traffic light task (PRTLT). The PRTLT requires participants to take risks under time pressure in order for them to maximize rewards in the form of commercial products, with the brand of products being an independent variable. Thus, we explored the feasibility of applying a PRTLT in a neuromarketing context to implicitly differentiate between the perceived value of products and supported our data with neurophysiological evidence obtained using fNIRS to concurrently monitor cortical activation.MethodsThirty healthy students were asked to perform the PRTLT. We compared participants' functional impulsivity toward two different chocolate products that had obviously different values. Along with their behavioral responses, participants' cerebral hemodynamic responses during the PRTLT were measured using fNIRS covering the lateral prefrontal cortices and the neighboring regions. We conducted adaptive general linear model (GLM) analysis for hemodynamic responses. First, we identified the regions involved in the PRTLT. Second, we compared activation patterns between expensive and inexpensive conditions.ResultsBehavioral analysis confirmed that the expensive condition trended toward producing a higher PRTLT score than did the inexpensive condition. fNIRS neuroimaging analysis showed task-derived activation in the bilateral dorsolateral prefrontal cortex (DLPFC) and frontopolar cortex (FPC). Moreover, we found significant differences between expensive and inexpensive conditions in the cortical activations in the FPC and the left-DLPFC.ConclusionThese results imply that the two products evoked different functional impulsivity, and the hemodynamic responses reflect that. Thus, we concluded that it is possible to observe differences in demand for products using a PRTLT that evokes functional impulsivity. The current study presents a new possibility in neuromarketing research of observing differences between consumers' covert attitudes toward commercially available products, possibly providing a neural basis related to hidden needs for some products.
Implementation of morbidity and mortality conference in a community hospital NICU and narrative review
Authors: Chan Christina , Pazandak Christine , Angelis Dimitrios 
Published: December 2023

BackgroundThe process of morbidity and mortality review (MMR) is recognized as an essential component of quality improvement, patient safety, attitudes towards patient safety, and continuing education. Despite the common use of MMR for all disciplines of medical care, recommendations have not been published regarding the implementation of MMR in a community hospital setting in the United States.ObjectivesReview the literature on MMR conferences. Describe the implementation of an MMR conference in a community hospital neonatal intensive care unit (NICU).ConclusionsThe establishment of a case overview method of MMR is feasible for a community hospital NICU. It increases staff and physician group awareness and education over common and complex mortality and morbidity etiologies, improves staff participation with unit management, links case presentation with open discussion and action items, and identifies opportunities for systemic changes to improve patient care.