bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Complete response after tislelizumab treatment in a hepatocellular carcinoma patient with abdominal lymph node metastasis
Authors: Deng Haihui , Chen Bin , Peng Deti , He Jian , Zhao Weicheng , Chen Tuantuan , Xie Zonggui , Pang Fuwen 
Published: April 2023

BackgroundAbdominal lymph node (ALN) metastasis is associated with a poor prognosis in patients with hepatocellular carcinoma (HCC) because of the limited number of effective therapeutic options available. Immunotherapy with immune checkpoint inhibitors, such as those targeting programmed death receptor-1 (PD-1), have produced encouraging results in patients with advanced HCC. Here, we report a complete response (CR) in a patient with advanced HCC and ALN metastasis after combination treatment with tislelizumab (a PD-1 inhibitor) and locoregional therapy.Case summaryA 58-year-old man with HCC experienced progressive disease with multiple ALN metastases after undergoing transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), and laparoscopic resection. Because the patient did not wish to receive systemic therapy, including chemotherapy and targeting therapy, we prescribed tislelizumab (as a single immunotherapeutic agent) together with RFA. After four tislelizumab treatment cycles, the patient achieved a CR without tumor recurrence for up to 15 months.ConclusionTislelizumab monotherapy can be effectively used to treat advanced HCC with ALN metastasis. Moreover, the combination of locoregional therapy and tislelizumab is likely to further increase therapeutic efficacy.
SARS-CoV-2 vaccination of convalescents boosts neutralization capacity against Omicron subvariants BA.1, BA.2 and BA.5 and can be predicted by anti-S antibody concentrations in serological assays
Authors: Seidel Alina , Hoffmann Simone , Jahrsdörfer Bernd , Körper Sixten , Ludwig Carolin , Vieweg Christiane , Albers Dan , von Maltitz Pascal , Müller Rebecca , Lotfi Ramin , Wuchter Patrick , Klüter Harald , Kirchhoff Frank , Schmidt Michael , Münch Jan , Schrezenmeier Hubert 
Published: April 2023

BackgroundRecent data on immune evasion of new SARS-CoV-2 variants raise concerns about the efficacy of antibody-based COVID-19 therapies. Therefore, in this study the in-vitro neutralization capacity against SARS-CoV-2 variant B.1 and the Omicron subvariants BA.1, BA.2 and BA.5 of sera from convalescent individuals with and without boost by vaccination was assessed.Methods and findingsThe study included 313 serum samples from 155 individuals with a history of SARS-CoV-2 infection, divided into subgroups without (n=25) and with SARS-CoV-2 vaccination (n=130). We measured anti-SARS-CoV-2 antibody concentrations by serological assays (anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S) and neutralizing titers against B.1, BA.1, BA.2 and BA.5 in a pseudovirus neutralization assay. Sera of the majority of unvaccinated convalescents did not effectively neutralize Omicron sublineages BA.1, BA.2 and BA.5 (51.7%, 24.1% and 51.7%, resp.). In contrast, 99.3% of the sera of superimmunized individuals (vaccinated convalescents) neutralized the Omicron subvariants BA.1 and BA.5 and 99.6% neutralized BA.2. Neutralizing titers against B.1, BA.1, BA.2 and BA.5 were significantly higher in vaccinated compared to unvaccinated convalescents (p&lt;0.0001) with 52.7-, 210.7-, 141.3- and 105.4-fold higher geometric mean of 50% neutralizing titers (NT50) in vaccinated compared to unvaccinated convalescents. 91.4% of the superimmunized individuals showed neutralization of BA.1, 97.2% of BA.2 and 91.5% of BA.5 with a titer ≥ 640. The increase in neutralizing titers was already achieved by one vaccination dose. Neutralizing titers were highest in the first 3 months after the last immunization event. Concentrations of anti-S antibodies in the anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S assays predicted neutralization capacity against B.1 and Omicron subvariants BA.1, BA.2 and BA.5.ConclusionsThese findings confirm substantial immune evasion of the Omicron sublineages, which can be overcome by vaccination of convalescents. This informs strategies for choosing of plasma donors in COVID-19 convalescent plasma programs that shall select specifically vaccinated convalescents with very high titers of anti-S antibodies.
High overlap in patients diagnosed with hypermobile Ehlers-Danlos syndrome or hypermobile spectrum disorders with fibromyalgia and 40 self-reported symptoms and comorbidities
Authors: Fairweather DeLisa , Bruno Katelyn A. , Darakjian Ashley A. , Bruce Barbara K. , Gehin Jessica M. , Kotha Archana , Jain Angita , Peng Zhongwei , Hodge David O. , Rozen Todd D. , Munipalli Bala , Rivera Fernando A. , Malavet Pedro A. , Knight Dacre R. T. 
Published: April 2023

BackgroundJoint pain is a common symptom in patients with hypermobile Ehlers-Danlos Syndrome (hEDS), hypermobility spectrum disorders (HSD) and fibromyalgia. The goal of this study was to determine whether symptoms and comorbidities overlap in patients diagnosed with hEDS/HSD and/or fibromyalgia.MethodsWe retrospectively examined self-reported data from an EDS Clinic intake questionnaire in patients diagnosed with hEDS/HSD, fibromyalgia, or both vs. controls with an emphasis on joint issues.ResultsFrom 733 patients seen at the EDS Clinic, 56.5% (n = 414) were diagnosed with hEDS/HSD and fibromyalgia (Fibro), 23.8% (n = 167) hEDS/HSD, 13.3% (n = 98) fibromyalgia, or 7.4% (n = 54) none of these diagnoses. More patients were diagnosed with HSD (76.6%) than hEDS (23.4%). Patients were primarily White (95%) and female (90%) with a median age in their 30s (controls 36.7 [18.0, 70.0], fibromyalgia 39.7 [18.0, 75.0], hEDS/HSD 35.0 [18.0, 71.0], hEDS/HSD&amp;Fibro 31.0 [18.0, 63.0]). There was high overlap in all 40 symptoms/comorbidities that we examined in patients diagnosed with fibromyalgia only or hEDS/HSD&amp;Fibro, regardless of whether they had hEDS or HSD. Patients that only had hEDS/HSD without fibromyalgia had far fewer symptoms/comorbidities than patients with hEDS/HSD&amp;Fibro. The top self-reported issues in patients that only had fibromyalgia were joint pain, hand pain when writing or typing, brain fog, joint pain keeping from daily activities, allergy/atopy and headache. Five issues that significantly and uniquely characterized patients diagnosed with hEDS/HSD&amp;Fibro were subluxations (dislocations in hEDS patients), joint issues like sprains, the need to stop sports due to injuries, poor wound healing, and migraine.ConclusionThe majority of patients seen at the EDS Clinic had a diagnosis of hEDS/HSD plus fibromyalgia that was associated with more severe disease. Our findings indicate that fibromyalgia should be routinely assessed in patients with hEDS/HSD and vis-a-versa to improve patient care.
The significance of wrist immobilization for endoscopic carpal tunnel release
Authors: Zhang Fei , Jiang Hong , Lu Zhenfeng , Yang Haoyu , Zhang Qian , Mi Jingyi , Rui Yongjun , Zhao Gang 
Published: April 2023

BackgroundOver the years, endoscopic carpal tunnel release (ECTR) has gained significant interest as an alternative to surgery. However, no consensus has been reached on the necessity of postoperative wrist immobilization. This study aims to compare the outcomes of wrist immobilization for a period of 2 weeks to immediate wrist mobilization after ECTR.MethodsA total of 24 patients with idiopathic carpal tunnel syndrome undergoing dual-portal ECTR from May 2020 to Feb 2022 were enrolled and randomly divided into two groups postoperatively. In one group, patients wore a wrist splint for 2 weeks. In another group, wrist mobilization was allowed immediately after surgery. The two-point discrimination test (2PD test); the Semmes–Weinstein monofilament test (SWM test); the occurrence of pillar pain, digital and wrist range of motion (ROM); grip and pinch strength; the visual analog score (VAS), the Boston Carpal Tunnel Questionnaire (BCTQ) score; the Disabilities of the Arm, Shoulder, and Hand (DASH) score; and complications were evaluated at 2 weeks and 1, 2, 3, and 6 months after the surgery.ResultsAll 24 subjects finished this study with no dropouts. During the early follow-up, patients with wrist immobilization demonstrated lower VAS scores, lower occurrence of pillar pain, and higher grip and pinch strength compared with the immediate mobilization group. No significant difference was obtained between these two groups in terms of the 2PD test, the SWM test, digital and wrist ROM, BCTQ, and the DASH score. In total, two patients without splints reported transient scar discomfort. No one complained of neurapraxia, injury of the flexor tendon, median nerve, and major artery. At the final follow-up, no significant difference was found in any parameters between both groups. The local scar discomfort mentioned above disappeared and left no serious sequela.ConclusionWrist immobilization during the early postoperative period demonstrated significant pain alleviation along with stronger grip and pinch strength. However, wrist immobilization yielded no obvious superiority regarding clinical outcomes at the final follow-up.
Tremor suppression following treatment with MRgFUS: skull density ratio consistency and degree of posterior dentatorubrothalamic tract lesioning predicts long-term clinical outcomes in essential tremor
Authors: Kyle Kain , Maller Jerome , Barnett Yael , Jonker Benjamin , Barnett Michael , D’Souza Arkiev , Calamante Fernando , Maamary Joel , Peters James , Wang Chenyu , Tisch Stephen 
Published: April 2023

ObjectivesMagnetic resonance-guided focussed ultrasound (MRgFUS) is an incisionless ablative procedure, widely used for treatment of Parkinsonian and Essential Tremor (ET). Enhanced understanding of the patient- and treatment-specific factors that influence sustained long-term tremor suppression could help clinicians achieve superior outcomes via improved patient screening and treatment strategy.MethodsWe retrospectively analysed data from 31 subjects with ET, treated with MRgFUS at a single centre. Tremor severity was assessed with parts A, B and C of the Clinical Rating Scale for Tremor (CRST) as well as the combined CRST. Tremor in the dominant and non-dominant hand was assessed with Hand Tremor Scores (HTS), derived from the CRST. Pre- and post-treatment imaging data were analysed to determine ablation volume overlap with automated thalamic segmentations, and the dentatorubrothalamic tract (DRTT) and compared with percentage change in CRST and HTS following treatment.ResultsTremor symptoms were significantly reduced following treatment. Combined pre-treatment CRST (mean: 60.7 ± 17.3) and HTS (mean: 19.2 ± 5.7) improved by an average of 45.5 and 62.6%, respectively. Percentage change in CRST was found to be significantly negatively associated with age (β = −0.375, p = 0.015), and SDR standard deviation (SDRSD; β = −0.324, p = 0.006), and positively associated with ablation overlap with the posterior DRTT (β = 0.535, p &lt; 0.001). Percentage HTS improvement in the dominant hand decreased significantly with older age (β = −0.576, p &lt; 0.01).ConclusionOur results suggest that increased lesioning of the posterior region of the DRTT could result in greater improvements in combined CRST and non-dominant hand HTS, and that subjects with lower SDR standard deviation tended to experience greater improvement in combined CRST.
Delayed low cerebellar perfusion status is associated with poor outcomes in top-of-basilar occlusion treated with thrombectomy
Authors: Ryu Jae-Chan , Kwon Boseong , Song Yunsun , Lee Deok Hee , Chang Jun Young , Kang Dong-Wha , Kwon Sun U. , Kim Jong S. , Kim Bum Joon 
Published: April 2023

Background and purposeTop-of-basilar artery occlusion (TOB) is one of the most devastating strokes despite successful mechanical thrombectomy (MT). We aimed to investigate the impact of initial low cerebellum perfusion delay on the outcomes of TOB treated with MT.MethodsWe included patients who underwent MT for TOB. Clinical and peri-procedural variables were obtained. Perfusion delay in the low cerebellum was defined as (1) time-to-maximum (Tmax) &gt;10 s lesions or (2) relative time-to-peak (rTTP) map &gt;9.5 s with a diameter of ≥6 mm in the low cerebellum. The good functional outcome was defined as the achievement of a modified Rankin Scale score of 0–3 at 3 months after stroke.ResultsAmong the 42 included patients, 24 (57.1%) patients showed perfusion delay in the low cerebellum. The admission National Institutes of Health Stroke Scale (NIHSS) score was significantly higher in those with perfusion delay [17 (12–24) vs. 8 (6–15), P = 0.002]. Accordingly, the proportion of good functional outcomes was lower in those with perfusion delay than in those without [5 (20.8%) vs. 13 (72.2%), P = 0.003]. From the multivariable analysis, the admission NIHSS score [odds ratio (OR) = 0.86, 95% confidence intervals (CIs) = 0.75–0.98, P = 0.021] and low cerebellum perfusion delay (OR = 0.18, 95% Cis = 0.04–0.86, P = 0.031) were independently associated with the 3-month functional outcomes.ConclusionWe found that initial perfusion delay proximal to TOB in the low cerebellum might be a predictor for poor functional outcomes in TOB treated with MT.
Combining transcranial direct current stimulation with group cognitive behavioral therapy developed to treat rumination: a clinical pilot study
Authors: Horczak Paula , Wang Chanyu , De Witte Sara , De Smet Stefanie , Remue Jonathan , De Raedt Rudi , Vanderhasselt Marie-Anne , Wu Guo-Rong , Lemmens Gilbert M. D. , Baeken Chris 
Published: April 2023

BackgroundAs part of repetitive negative thinking (RNT), rumination is a maladaptive cognitive response style to stress or negative mood which can increase the risk of depression and may prohibit complete recovery. Cognitive behavioral therapy (CBT) and transcranial direct current stimulation (tDCS) both proved to be effective in decreasing rumination. However, the combined effects of tDCS and CBT interventions on rumination have not yet been explored. The first aim of this pilot study is to investigate whether the combination of tDCS and CBT has an accumulating positive effect on modulating state rumination. The second aim is to assess the feasibility and safety profile of the proposed combined approach.MethodSeventeen adults aged 32–60 years, suffering from RNT, were referred by their primary care professional to participate in an 8-week group intervention for RNT (“Drop It”) comprising 8 sessions of CBT. Before each CBT session, patients underwent one double-blinded prefrontal active (2 mA for 20 min) or sham tDCS (anode over F3, cathode over the right supraorbital region) combined with an internal cognitive attention task focused on individual RNT, i.e., online tDCS priming. During each session, the Brief State Rumination Inventory was used to assess state rumination.ResultsA mixed effects model analysis revealed no significant differences between the stimulation conditions, weekly sessions, or their interaction in terms of state rumination scores.ConclusionOverall, the combination of online tDCS priming followed by group CBT was found to be safe and feasible. On the other hand, no significant additional effects of this combined approach on state rumination were established. Although our pilot study may have been too small to find significant clinical effects, future larger RCT studies on combined tDCS-CBT treatment protocols may reevaluate the selection of internal cognitive attention tasks and more objective neurophysiological measurements, consider the optimal timing of the combination (concurrently or sequentially), or may add additional tDCS sessions when following CBT.
Characteristics of current perception produced by intermediate-frequency contact currents in healthy adults
Authors: Uehara Shintaro , Yuasa Akiko , Ushizawa Kazuki , Kodera Sachiko , Kamimura Yoshitsugu , Hirata Akimasa , Otaka Yohei 
Published: April 2023

IntroductionContact electrical currents in humans stimulate peripheral nerves at frequencies of &lt;100 kHz, producing sensations such as tingling. At frequencies above 100 kHz, heating becomes dominant, resulting in a sensation of warmth. When the current amplitude exceeds the threshold, the sensation results in discomfort or pain. In international guidelines and standards for human protection from electromagnetic fields, the limit for the contact current amplitude has been prescribed. Although the types of sensations produced by contact current at low frequencies, i.e., approximately 50–60 Hz, and the corresponding perception thresholds have been investigated, there is a lack of knowledge about those in the intermediate-frequency band—particularly from 100 kHz to 10 MHz.MethodsIn this study, we investigated the current-perception threshold and types of sensations for 88 healthy adults (range: 20–79 years old) with a fingertip exposed to contact currents at 100 kHz, 300 kHz, 1 MHz, 3 MHz, and 10 MHz.ResultsThe current perception thresholds at frequencies ranging from 300 kHz to 10 MHz were 20–30% higher than those at 100 kHz (p &lt; 0.001). In addition, a statistical analysis revealed that the perception thresholds were correlated with the age or finger circumference: older participants and those with larger finger circumferences exhibited higher thresholds. At frequencies of ≥300 kHz, the contact current mainly produced a warmth sensation, which differed from the tingling/pricking sensation produced by the current at 100 kHz.DiscussionThese results indicate that there exists a transition of the produced sensations and their perception threshold between 100 kHz and 300 kHz. The findings of this study are useful for revising the international guidelines and standards for contact currents at intermediate frequencies.Clinical trial registrationhttps://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000045660, identifier UMIN 000045213.
Decreased RNA polymerase III subunit expression leads to defects in oligodendrocyte development
Authors: Macintosh Julia , Michell-Robinson Mackenzie , Chen Xiaoru , Bernard Geneviève 
Published: April 2023

IntroductionRNA polymerase III (Pol III) is a critical enzymatic complex tasked with the transcription of ubiquitous non-coding RNAs including 5S rRNA and all tRNA genes. Despite the constitutive nature of this enzyme, hypomorphic biallelic pathogenic variants in genes encoding subunits of Pol III lead to tissue-specific features and cause a hypomyelinating leukodystrophy, characterized by a severe and permanent deficit in myelin. The pathophysiological mechanisms in POLR3- related leukodystrophy and specifically, how reduced Pol III function impacts oligodendrocyte development to account for the devastating hypomyelination seen in the disease, remain poorly understood.MethodsIn this study, we characterize how reducing endogenous transcript levels of leukodystrophy-associated Pol III subunits affects oligodendrocyte maturation at the level of their migration, proliferation, differentiation, and myelination.ResultsOur results show that decreasing Pol III expression altered the proliferation rate of oligodendrocyte precursor cells but had no impact on migration. Additionally, reducing Pol III activity impaired the differentiation of these precursor cells into mature oligodendrocytes, evident at both the level of OL-lineage marker expression and on morphological assessment, with Pol III knockdown cells displaying a drastically more immature branching complexity. Myelination was hindered in the Pol III knockdown cells, as determined in both organotypic shiverer slice cultures and co-cultures with nanofibers. Analysis of Pol III transcriptional activity revealed a decrease in the expression of distinct tRNAs, which was significant in the siPolr3a condition.DiscussionIn turn, our findings provide insight into the role of Pol III in oligodendrocyte development and shed light on the pathophysiological mechanisms of hypomyelination in POLR3-related leukodystrophy.
Spectral-domain optical coherence tomography combined with electroretinography in the assessment of conbercept for neovascular age-related macular degeneration: a preliminary study
Authors: Wang Xing , Wang Peng 
Published: April 2023

ObjectiveTo observe the effect of three consecutive intravitreal injections of conbercept in the treatment of neovascular age-related macular degeneration (nAMD), to investigate the correlation between retinal anatomy and retinal function by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG), to evaluate the short-term clinical efficacy of conbercept in the treatment of nAMD, and to explore the value of ERG as a predictor of treatment efficacy.MethodA retrospective investigation was conducted on 36 patients (36 eyes) treated with intravitreal injections of conbercept at 0.5 mg a month for three consecutive courses. Data collected included the best corrected visual acuity (BCVA), central retinal thickness (CRT), retinal pigment epithelium (RPE) elevation volume in 1 mm-diameter (1RV), 3 mm-diameter (3RV), and 6 mm-diameter circles around the fovea (6RV), amplitude density and latency of the P1 wave in the multifocal electroretinography (mf-ERG) R1 ring and amplitude and latency in full-field electroretinography (ff-ERG) at baseline and monthly. The paired t test was used to compare the difference between pre- and posttreatment. Pearson correlation analysis was used to analyze the correlation between macular retinal structure and function. The difference was significant when p &lt; 0.05.ResultsAt 12 weeks, the BCVA, CRT, 1RV, 3RV, 6RV, the P1 wave amplitude density of the mf-ERG R1 ring and the ff-ERG amplitude parameters were all significantly improved (p &lt; 0.001). The BCVA in logMAR was positively correlated with CRT; 1RV, 3RV, and 6RV were negatively correlated with the amplitude density and latency of the mf-ERG R1 ring P1 wave. There were no severe ocular or systemic complications during the follow-up period.ConclusionConbercept is useful for the short-term treatment of nAMD. It can safely improve the visual acuity of affected eyes and restore the structure and function of the retina. ERG could serve as an objective indicator of function for evaluating the efficacy of and determining the need for retreatment during nAMD treatment.