bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pentad: A reproducible cytoarchitectonic protocol and its application to parcellation of the human hippocampus
Authors: Williams Emily M. , Rosenblum Emma W. , Pihlstrom Nicole , Llamas-Rodríguez Josué , Champion Samantha , Frosch Matthew P. , Augustinack Jean C. 
Published: February 2023

IntroductionThe hippocampus is integral for learning and memory and is targeted by multiple diseases. Neuroimaging approaches frequently use hippocampal subfield volumes as a standard measure of neurodegeneration, thus making them an essential biomarker to study. Collectively, histologic parcellation studies contain various disagreements, discrepancies, and omissions. The present study aimed to advance the hippocampal subfield segmentation field by establishing the first histology based parcellation protocol, applied to n = 22 human hippocampal samples.MethodsThe protocol focuses on five cellular traits observed in the pyramidal layer of the human hippocampus. We coin this approach the pentad protocol. The traits were: chromophilia, neuron size, packing density, clustering, and collinearity. Subfields included were CA1, CA2, CA3, CA4, prosubiculum, subiculum, presubiculum, parasubiculum, as well as the medial (uncal) subfields Subu, CA1u, CA2u, CA3u, and CA4u. We also establish nine distinct anterior-posterior levels of the hippocampus in the coronal plane to document rostrocaudal differences.ResultsApplying the pentad protocol, we parcellated 13 subfields at nine levels in 22 samples. We found that CA1 had the smallest neurons, CA2 showed high neuronal clustering, and CA3 displayed the most collinear neurons of the CA fields. The border between presubiculum and subiculum was staircase shaped, and parasubiculum had larger neurons than presubiculum. We also demonstrate cytoarchitectural evidence that CA4 and prosubiculum exist as individual subfields.DiscussionThis protocol is comprehensive, regimented and supplies a high number of samples, hippocampal subfields, and anterior-posterior coronal levels. The pentad protocol utilizes the gold standard approach for the human hippocampus subfield parcellation.
Bilateral ankle deformities affects gait kinematics in chronic stroke patients
Authors: Kim Hogene , Cho Ji-Eun , Seo Kyeong-Jun , Lee Jooyoung 
Published: February 2023

ObjectivesStroke patients suffer from ankle joint deformities due to spastic ankle muscles. This study evaluated the viability of using 3D scanned surface images of the feet of stroke victims to visually assess the deformities of a hemiparetic foot and investigated the influences of deformed ankle joints on gait kinematics.MethodsA total of 30 subjects with stroke-induced hemiparesis and 11 age-matched healthy controls completed the clinical assessments. We analyzed their feet's morphometric characteristics using a 3D scanner, identified convenient anthropometric measurements, and conducted gait trials on even and uneven terrains. The 3D foot morphometric characteristics were evaluated using the geometric morphometrics method (GMM).ResultsResults showed that there were significant differences in bilateral foot shapes between the chronic stroke patients and healthy controls and between the paretic and non-paretic sides in the chronic stroke patients. In stroke patients, those with the smaller medial malleoli's vertical tilt angles showed significantly different ankle ranges of motion of dorsi-/plantar flexion during gaits on uneven terrains (p = 0.009). In addition, those with the greater medial malleoli's vertical tilt angles showed significantly different ankle ranges of motion of inversion/eversion during gaits on even and uneven terrains (p &lt; 0.05).ConclusionUsing 3D scanning technology, bilateral morphometric changes in the feet of chronic stroke patients were shown by GMM and the simple anthropometric measurements identified its shape deformities in the feet. Their possible effects on gait kinematics while walking on uneven terrains were investigated. Current methodology can be potentially useful in applying conventional productions of clinically manufactured, patient-fitted ankle-foot-orthosis in orthotics and prosthetics, and in detecting various unidentified pathological deformities in the feet.
Pathogenic free-living amoebic encephalitis from 48 cases in China: A systematic review
Authors: Chen Xiang-Ting , Zhang Qian , Wen Si-Yuan , Chen Fei-Fei , Zhou Chang-Qing 
Published: February 2023

BackgroundFree-living amoebae (FLA) including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris can become pathogenic and cause severe cerebral infections, named primary amoebic meningoencephalitis (PAM), granulomatous amoebic encephalitis (GAE), and balamuthia amoebic encephalitis (BAE), respectively. FLA encephalitis has been reported across China, but the clinical data descriptions and analytical results of these different reports vary widely. Currently, no consensus treatment has been established. We conduct a systematic review to evaluate the exposure location, clinical symptoms, diagnosis, treatment, and prognosis of three FLA encephalitis and aim to reveal the differences between three FLA encephalitis in China.MethodsWe used MEDLINE (PubMed interface), EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang database, and China Biology Medicine disc (CBMdisc) databases for literatures published and manually retrieve the hospital records of our hospital. The search time was up to August 30, 2022, with no language restrictions.ResultsAfter excluding possible duplicate cases, a total of 48 patients of three FLA encephalitis were collected. One from the medical records of our hospital and 47 patients from 31 different studies. There were 11 patients of PAM, 10 patients of GAE, and 27 patients of BAE. The onset of PAM is mostly acute or subacute, and the clinical symptoms are acute and fulminant hemorrhagic meningoencephalitis. Most patients with GAE and BAE have an insidious onset and a chronic course. A total of 21 BAE patients (77.8%) had skin lesions before onset of symptoms. Additionally, 37 cases (77.1%) were diagnosed with FLA encephalitis before death. And there were 4 of PAM, 2 of GAE, and 10 of BAE diagnosed using next generation sequencing. No single agent can be proposed as the ideal therapy by itself. Only 6 cases were successfully treated.ConclusionsThis review provides an overview of the available data and studies of FLA encephalitis in China and identify some potential differences. FLA encephalitis is a rare but pathogenic infection, and physicians should early identify this encephalitis to improve survival.
Management of carotid cavernous fistulas: A single center experience
Authors: Alatzides Georgios Luca , Opitz Marcel , Li Yan , Goericke Sophia , Oppong Marvin Darkwah , Frank Benedikt , Eckstein Anja Katrin , Köhrmann Martin , Wrede Karsten , Forsting Michael , Wanke Isabel , Deuschl Cornelius 
Published: February 2023

PurposeMultimodal endovascular therapy (EVT) of carotid cavernous fistula (CCF) with different approaches and a variety of available embolization material enable high occlusion rates with good clinical and functional outcome but until now there is still little evidence available. This retrospective single-center study aims to evaluate EVT of CCF with different neuroendovascular techniques regarding occlusion rates, complications and outcomes.Materials and methodsFrom 2001 to 2021 59 patients with CCF were treated at our tertiary university hospital. Patient records and all imaging data including angiograms were reviewed for demographic and epidemiological data, symptoms, fistula type, number of EVTs, complications of EVT, type of embolic materials, occlusion rates and recurrences.ResultsEtiology of the CCF were spontaneous (41/59, 69.5%) post-traumatic (13/59, 22%) and ruptured cavernous aneurysms (5/59, 8.5%). Endovascular therapy was completed in one session in 74.6% (44/59). Transvenous access was most frequent (55.9% 33/59) followed by transarterial catheterization in 33.9% (20/59) and a combination of both (6/59, 10.2%). Exclusively coils were used in 45.8% (27/59), a combination of ethylene vinyl alcohol (EVOH) copolymer (Onyx) and coils in 42.4% (25/59). Complete obliteration was achieved in 96.6% of patients (57/59) with an intraprocedural-related complication rate of 5.1% (3/59) and no mortality.ConclusionEndovascular therapy of CCF has been shown to be safe and effective with high cure rates and low rates of intraprocedural complications and morbidity even in complex scenarios.
Late neurological consequences of SARS-CoV-2 infection: New challenges for the neurologist
Authors: Korchut Agnieszka , Rejdak Konrad 
Published: February 2023

ObjectiveIn this study, a systematic review of the literature was performed to study the frequency of neurological symptoms and diseases in adult patients with COVID-19 that may be late consequences of SARS-CoV-2 infection.MethodsRelevant studies were identified through electronic explorations of Scopus, PubMed, and Google Scholar. We followed PRISMA guidelines. Data were collected from studies where the diagnosis of COVID-19 was confirmed and its late neurological consequences occurred at least 4 weeks after initial SARS-CoV-2 infection. Review articles were excluded from the study. Neurological manifestations were stratified based on frequency (above 5, 10, and 20%), where the number of studies and sample size were significant.ResultsA total of 497 articles were identified for eligible content. This article provides relevant information from 45 studies involving 9,746 patients. Fatigue, cognitive problems, and smell and taste dysfunctions were the most frequently reported long-term neurological symptoms in patients with COVID-19. Other common neurological issues were paresthesia, headache, and dizziness.ConclusionOn a global scale of patients affected with COVID-19, prolonged neurological problems have become increasingly recognized and concerning. Our review might be an additional source of knowledge about potential long-term neurological impacts.
The efficacy and safety of acupuncture therapy for sciatica: A systematic review and meta-analysis of randomized controlled trails
Authors: Zhang Zhihui , Hu Tingting , Huang Peiyan , Yang Mengning , Huang Zheng , Xia Yawen , Zhang Xinchang , Zhang Xiaolin , Ni Guangxia 
Published: February 2023

Background and objectiveSciatica is a common type of neuropathic pain disease which poses a huge financial burden to the patient. For patients with sciatica, acupuncture has been recommended as an effective method for pain relief, while there is currently a lack of sufficient evidence to support its efficacy and safety. In this review, we aimed to critically assess the published clinical evidence on the efficacy and safety of acupuncture therapy for treating sciatica.MethodsAn extensive literature search strategy was established in seven databases from their inception to 31 March 2022. Two independent reviewers performed the literature search, identification, and screening. Data extraction was performed on studies that meet the inclusion criteria, and a further quality assessment was performed according to the Cochrane Handbook and Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) recommendations. Summary Risk ratio (RR) and standardized mean differences (SMDs) with 95% confidence interval (CI) were calculated using the fixed-effects or the random-effects model. Heterogeneity in effect size across studies was explored using the subgroup analysis and the sensitivity analysis. The quality of evidence was estimated following the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.ResultsA total of 30 randomized controlled trials (RCTs) involving 2,662 participants were included in the meta-analysis. The results of the integration of clinical outcomes showed that the clinical efficacy of acupuncture was superior to that of medicine treatment (MT) in improving the total effective rate (relative risk (RR) = 1.25, 95% confidence interval (CI) [1.21, 1.30]; moderate certainty of evidence), reducing the Visual Analog Scale (VAS) pain score (standardized mean difference (SMD) = −1.72, 95% CI [-2.61, −0.84]; very low certainty of evidence), increasing pain threshold (SMD = 2.07, 95% CI [1.38, 2.75]; very low certainty of evidence), and decreasing recurrence rate (RR = 0.27, 95% CI [0.13, 0.56]; low certainty of evidence). In addition, a few adverse events (RR = 0.38, 95% CI [0.19, 0.72]; moderate certainty of evidence) were reported during the intervention, which indicated that acupuncture was a safe treatment option.ConclusionsAcupuncture therapy is an effective and safe treatment for patients with sciatica, and it can be considered a suitable replacement for medicine treatment (MT). However, given the high heterogeneity and a low methodological quality of previous studies, future RCTs should be well-designed according to the rigorous methodology.Systematic review registrationInternational Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) (https://inplasy.com/register/), identifier [INPLASY202240060].
Electrical nerve stimulation for sensory-neural pathway reconstruction in upper-limb amputees
Authors: Wang Yingying , Liu Hongyu , Zeng Peiying , Ji Lingchao , Zhou Yaqi , Zhou Liufang , Tao Yuan 
Published: February 2023

IntroductionThe loss of the neural sensory function pathways between the stump limbs and the brain greatly impacts the rehabilitation of limb function and the daily lives of amputees. Non-invasive physical stressors, such as mechanical pressure and transcutaneous electrical nerve stimulation (TENS), could be potential solutions for recovering somatic sensations in amputees. Previous studies have shown that stimulating the residual or regenerated nerves in the stumps of some amputees can produce phantom hand sensations. However, the results are inconclusive due to unstable physiological responses caused by inaccurate stimulus parameters and positions.MethodsIn this study, we developed an optimal TENS strategy by mapping the distribution of the nerves in the stump skin that elicitsphantom sensations known as a “phantom hand map.” We evaluated the effectiveness and stability of the confirmed stimulus configuration in a long-term experiment using single- and multi-stimulus paradigms. Additionally, we evaluated the evoked sensations by recording electroencephalograms (EEG) and analyzing brain activities.ResultsThe results demonstrated that various types of intuitive sensations for amputees could be stably induced by adjusting TENS frequencies, particularly at 5 and 50 Hz. At these frequencies, 100% stability of sensory types was achieved when the stimuli were applied to two specific locations on the stump skin. Furthermore, at these locations, the stability of sensory positions was 100% across different days. Moreover, the evoked sensations were objectively supported by specific patterns of event-related potentials in brain responses.DiscussionThis study provides an effective method for developing and evaluating physical stressor stimulus strategies, which could play an important role in the somatosensory rehabilitation of amputees and other patients suffering from somatomotor sensory dysfunction. The paradigm developed in this study can provide effective guidelines for stimulus parameters in physical and electrical nerve stimulation treatments for a variety of symptoms related to neurological disorders.
Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study
Authors: Wodschow Helena Zander , Davidovski Filip Søskov , Christensen Jacob , Lassen Mats Christian Højbjerg , Skaarup Kristoffer Grundtvig , Nygaard Hanne , Møller Niels , Rungby Jørgen , Biering-Sørensen Tor , Rossing Peter , Jensen Nicole Jacqueline , Laursen Jens Christian 
Published: February 2023

BackgroundCOVID-19 is associated with subclinical myocardial injury. Exogenous ketone esters acutely improve left myocardial function in healthy participants and patients with heart failure, but the effects have not been investigated in participants previously hospitalized for COVID-19.MethodsThis is a randomized placebo-controlled double-blind crossover study comparing a single oral ketone ester dose of 395 mg/kg with placebo. Fasting participants were randomized to either placebo in the morning and oral ketone ester in the afternoon or vice versa. Echocardiography was performed immediately after intake of the corresponding treatment. Primary outcome was left ventricular ejection fraction (LVEF). Secondary outcomes were absolute global longitudinal strain (GLS), cardiac output and blood oxygen saturation. Linear mixed effects models were used to assess differences.ResultsWe included 12 participants previously hospitalized for COVID-19 with a mean (±SD) age of 60 ± 10 years. The mean time from hospitalization was 18 ± 5 months. Oral ketone esters did not increase LVEF between placebo and oral ketone ester [mean difference: −0.7% (95% CI −4.0 to 2.6%), p = 0.66], but increased GLS [1.9% (95% CI: 0.1 to 3.6%), p = 0.04] and cardiac output [1.2 L/min (95% CI: −0.1 to 2.4 L/min), p = 0.07], although non-significant. The differences in GLS remained significant after adjustment for change in heart rate (p = 0.01). There was no difference in blood oxygen saturation. Oral ketone esters increased blood ketones over time (peak level 3.1 ± 4.9 mmol/L, p &lt; 0.01). Ketone esters increased blood insulin, c-peptide, and creatinine, and decreased glucose and FFA (all p ≤ 0.01) but did not affect glucagon, pro-BNP, or troponin I levels (all p &gt; 0.05).ConclusionIn patients previously hospitalized with COVID-19, a single oral dose of ketone ester had no effect on LVEF, cardiac output or blood oxygen saturation, but increased GLS acutely.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04377035.
Resveratrol analog, triacetylresveratrol, a potential immunomodulator of lung adenocarcinoma immunotherapy combination therapies
Authors: He Jian , Qiu Nianxiang , Zhou Xianchao , Meng Mei , Liu Zixue , Li Jingquan , Du Shiyu , Sun Zhiqiang , Wang Hui 
Published: February 2023

IntroductionResveratrol, an activator for longevity regulatory genes-sirtuin family (SIRTs) and Sirtuin 2 (SIRT2) is an important factor of SIRTs which demonstrated biological function in cancers, but the underlying mechanism is unrevealed.MethodsWe investigated the mRNA and protein levels of SIRT2 in a variety of cancers and the potential role for clinical prognosis, as well as analysed the association between the gene and immune infiltration in various cancers. And an analysis of two types of lung cancer was conducted to construct a systematic prognostic landscape. Finally, putative binding site of the triacetylresveratrol bound to SIRT2 was built from homology modeling.Results and discussionWe concluded that higher mRNA and protein levels of SIRT2 affected prognosis in various types of cancers, especially in LUAD cohorts. In addition, SIRT2 is linked with a better overall survival (OS) in LUAD patients. Further research suggested a possible explanation for this phenotype might be that SIRT2 mRNA levels are positively correlated with infiltrating status of multiple immunocytes in LU-AD but not LUSC, i.e. SIRT2 expression may contribute to the recruitment of CD8+T cell, CD4+ T cell, T cell CD4+ memory resting, Tregs, T cell NK and positively correlated to the expression of PD-1, also excluding neutrophil, T cell CD8+ naïve and B cell plasma cells in LUAD. We found that triacetyl-resveratrol demonstrated the most potent agonist efficiency to SIRT2 and the EC 50 as low as 142.79 nM. As a result, SIRT2 appears to be a promising novel biomarker for prognosis prediction in patients with LUAD and triacetylresveratrol might be a potential immunomodulator of LUAD to anti-PD-1 based immunotherapy combination therapies.
Combinatory analysis of immune cell subsets and tumor-specific genetic variants predict clinical response to PD-1 blockade in patients with non-small cell lung cancer
Authors: Dutta Nikita , Rohlin Anna , Eklund Ella A. , Magnusson Maria K. , Nilsson Frida , Akyürek Levent M. , Torstensson Per , Sayin Volkan I. , Lundgren Anna , Hallqvist Andreas , Raghavan Sukanya 
Published: February 2023

ObjectivesImmunotherapy by blocking programmed death protein-1 (PD-1) or programmed death protein-ligand1 (PD-L1) with antibodies (PD-1 blockade) has revolutionized treatment options for patients with non-small cell lung cancer (NSCLC). However, the benefit of immunotherapy is limited to a subset of patients. This study aimed to investigate the value of combining immune and genetic variables analyzed within 3–4 weeks after the start of PD-1 blockade therapy to predict long-term clinical response.Materials and methodologyBlood collected from patients with NSCLC were analyzed for changes in the frequency and concentration of immune cells using a clinical flow cytometry assay. Next-generation sequencing (NGS) was performed on DNA extracted from archival tumor biopsies of the same patients. Patients were categorized as clinical responders or non-responders based on the 9 months’ assessment after the start of therapy.ResultsWe report a significant increase in the post-treatment frequency of activated effector memory CD4+ and CD8+ T-cells compared with pre-treatment levels in the blood. Baseline frequencies of B cells but not NK cells, T cells, or regulatory T cells were associated with the clinical response to PD-1 blockade. NGS of tumor tissues identified pathogenic or likely pathogenic mutations in tumor protein P53, Kirsten rat sarcoma virus, Kelch-like ECH-associated protein 1, neurogenic locus notch homolog protein 1, and serine/threonine kinase 11, primarily in the responder group. Finally, multivariate analysis of combined immune and genetic factors but neither alone, could discriminate between responders and non-responders.ConclusionCombined analyses of select immune cell subsets and genetic mutations could predict early clinical responses to immunotherapy in patients with NSCLC and after validation, can guide clinical precision medicine efforts.
A novel signature constructed by super-enhancer-related genes for the prediction of prognosis in hepatocellular carcinoma and associated with immune infiltration
Authors: Wei Xueyan , Zhou Zihan , Long Meiying , Lin Qiuling , Qiu Moqin , Chen Peiqin , Huang Qiongguang , Qiu Jialin , Jiang Yanji , Wen Qiuping , Liu Yingchun , Li Runwei , Nong Cunli , Guo Qian , Yu Hongping , Zhou Xianguo 
Published: February 2023

BackgroundSuper-enhancer (SE) refers to a regulatory element with super transcriptional activity, which can enrich transcription factors and drive gene expression. SE-related genes play an important role in the pathogenesis of malignant tumors, including hepatocellular carcinoma (HCC).MethodsThe SE-related genes were obtained from the human super-enhancer database (SEdb). Data from the transcriptome analysis and related clinical information with HCC were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. The upregulated SE-related genes from TCGA-LIHC were identified by the DESeq2R package. Multivariate Cox regression analysis was used to construct a four-gene prognostic signature. According to the median risk score, HCC patients were divided into high-risk and low-risk group patients.ResultsThe Kaplan-Meier (KM) curve showed that a significantly worse prognosis was found for the high-risk group (P&lt;0.001). In the TCGA-LIHC dataset, the area under the curve (AUC) values were 0.737, 0.662, and 0.667 for the model predicting overall survival (OS) over 1-, 3-, and 5- years, respectively, indicating the good prediction ability of our prediction model. This model’s prognostic value was further validated in the LIRI-JP dataset and HCC samples (n=65). Furthermore, we found that higher infiltration level of M0 macrophages and upregulated of CTLA4 and PD1 in the high-risk group, implying that immunotherapy could be effective for those patients.ConclusionThese results provide further evidence that the unique SE-related gene model could accurately predict the prognosis of HCC.