bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Primary Hypothyroidism Associated With Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma
Authors: Gubbi Sriram , Al-Jundi Mohammad , Del Rivero Jaydira , Jha Abhishek , Knue Marianne , Zou Joy , Turkbey Baris , Carrasquillo Jorge Amilcar , Lin Emily , Pacak Karel , Klubo-Gwiezdzinska Joanna , Lin Frank I-Kai 
Published: January 2021

BackgroundLutetium 177 (177Lu) - DOTATATE is a form of peptide receptor radionuclide therapy (PRRT) utilized in the treatment of neuroendocrine tumors. Data on 177Lu-DOTATATE-induced thyroid dysfunction is limited.Case DescriptionA 29-year-old male with SDHB positive metastatic paraganglioma enrolled under the 177Lu-DOTATATE trial (NCT03206060) underwent thyroid function test (TFT) evaluation comprised of thyroid stimulating hormone (TSH) and free thyroxine (FT4) immunoassay measurements per protocol prior to 177Lu-DOTATATE therapy. The TSH was suppressed [&lt;0.01 µIU/ml (0.27–4.2 µIU/ml)], and FT4 was normal [1.3 ng/dl (0.9–1.7 ng/dl)]. The TSH receptor antibody and thyroid stimulating immunoglobulin index were undetectable [&lt;1 IU/L (≤1.75 IU/L), and &lt;1 (≤1.3) respectively], while the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies were elevated [605 IU/ml (0.0–34.9 IU/ml), and 178 IU/ml (0.0-40.0 IU/ml) respectively]. Mass spectrometry on a stored (-80°C) plasma sample obtained one-month pre-PRRT revealed elevated total triiodothyronine (TT3) [235 ng/dl (65–193 ng/dl)] and FT4 [3.9 ng/dl (1.2–2.9 ng/dl)] levels. The patient was diagnosed with Hashimoto’s thyrotoxicosis. However, the patient was asymptomatic. One month after the first dose of 200mCi 177Lu-DOTATATE, the patient noted fatigue and a 2.6 Kg weight gain. The TSH (73.04 µIU/ml), anti-TPO antibodies (&gt;1,000 IU/ml), and anti-Tg antibodies (668 IU/ml) had substantially increased, with reductions in FT4 (0.3 ng/dl) and TT3 [54 ng/dl (87–169 ng/dl)]. Diagnostic gallium 68 - DOTATATE positron emission tomography-computed tomography performed prior to 177Lu-DOTATATE treatment revealed diffuse thyroid uptake. Post-therapy single-photon emission computed tomography also revealed diffuse uptake of 177Lu-DOTATATE in the thyroid gland. Levothyroxine therapy was initiated, and the patient’s symptoms resolved.SummaryWe report, for the first time, a patient with asymptomatic primary hyperthyroidism who rapidly developed symptomatic primary hypothyroidism 1 month after 177Lu-DOTATATE therapy, accompanied by marked changes in TFTs and thyroid auto-antibody titers, with functional imaging evidence of diffuse uptake of 177Lu-DOTATATE in the thyroid gland.ConclusionsThyroid dysfunction can be associated with PRRT. Thyroid uptake patterns on pre-treatment diagnostic somatostatin analog scans might predict individual susceptibility to PRRT-associated TFT disruption. Therefore, periodic evaluation of TFTs should be considered in patients receiving PRRT.
A Novel Framework to Predict Breast Cancer Prognosis Using Immune-Associated LncRNAs
Authors: Huang Zhijian , Xiao Chen , Zhang Fushou , Zhou Zhifeng , Yu Liang , Ye Changsheng , Huang Weiwei , Li Nani 
Published: January 2021

Background: Breast cancer (BC) is one of the most frequently diagnosed malignancies among females. As a huge heterogeneity of malignant tumor, it is important to seek reliable molecular biomarkers to carry out the stratification for patients with BC. We surveyed immune- associated lncRNAs that may be used as potential therapeutic targets in BC.Methods: LncRNA expression data and clinical information of BC patients were downloaded from the TCGA database for a comprehensive analysis of candidate genes. A model consisting of immune-related lncRNAs enriched in BC cancerous tissues was established using the univariate Cox regression analysis and the iterative Lasso Cox regression analysis. The prognostic performance of this model was validated in two independent cohorts (GSE21653 and BC-KR), and compared with known prognostic biomarkers. A nomogram that integrated the immune-related lncRNA signature and clinicopathological factors was constructed to accurately assess the prognostic value of this signature. The correlation between the signature and immune cell infiltration in BC was also analyzed.Results: The Kaplan-Meier analysis showed that the OS of Patients in the low-risk group had significantly better survival than those in the high-risk group, Clinical subgroup analysis showed that the predictive ability was independent of clinicopathological factors. Univariate/multivariate Cox regression analysis showed immune lncRNA signature is an important prognostic factor and an independent prognostic marker. In addition, GSEA and GSVA analysis as well as comprehensive analysis of immune cells showed that the signature was significantly correlated with the infiltration of immune cells.Conclusion: We successfully constructed an immune-associated lncRNA signature that can accurately predict BC prognosis.
Activation of the Nlrp3 Inflammasome Contributes to Shiga Toxin-Induced Hemolytic Uremic Syndrome in a Mouse Model
Authors: Song Liqiong , Xiao Yuchun , Li Xianping , Huang Yuanming , Meng Guangxun , Ren Zhihong 
Published: January 2021

ObjectiveTo explore the role of the Nlrp3 inflammasome activation in the development of hemolytic uremic syndrome (HUS) induced by Stx2 and evaluate the efficacy of small molecule Nlrp3 inhibitors in preventing the HUS.MethodsPeritoneal macrophages (PMs) isolated from wild-type (WT) C57BL/6J mice and gene knockout mice (Nlrc4-/-,Aim2-/-, andNlrp3-/-) were treated with Stx2in vitroand their IL-1β releases were measured. WT mice andNlrp3-/-mice were also treated with Stx2in vivoby injection, and the biochemical indices (serum IL-1β, creatinine [CRE] and blood urea nitrogen [BUN]), renal injury, and animal survival were compared. To evaluate the effect of the Nlrp3 inhibitors in preventing HUS, WT mice were pretreated with different Nlrp3 inhibitors (MCC950, CY-09, Oridonin) before Stx2 treatment, and their biochemical indices and survival were compared with the WT mice without inhibitor pretreatment.ResultsWhen PMs were stimulated by Stx2in vitro, IL-1β release inNlrp3-/-PMs was significantly lower compared to the other PMs. TheNlrp3-/-mice treated by Stx2in vivo, showed lower levels of the biochemical indices, alleviated renal injuries, and increased survival rate. When the WT mice were pretreated with the Nlrp3 inhibitors, both the biochemical indices and survival were significantly improved compared to those without inhibitor pretreatment, with Oridonin being most potent.ConclusionNlrp3 inflammasome activation plays a vital role in the HUS development when mice are challenged by Stx2, and Oridonin is effective in preventing HUS.
Bone and Joint Infection Involving Corynebacterium spp.: From Clinical Features to Pathophysiological Pathways
Authors: Chauvelot Pierre , Ferry Tristan , Tafani Virginie , Diot Alan , Tasse Jason , Conrad Anne , Chidiac Christian , Braun Evelyne , Lustig Sébastien , Laurent Frédéric , Valour Florent 
Published: January 2021

Introduction: Corynebacteria represent often-neglected etiological agents of post-traumatic and/or post-operative bone and joint infection (BJI). We describe here clinical characteristics and bacteriological determinants of this condition.Methods: A retrospective cohort study described characteristics, outcome and determinants of treatment failure of all patients with proven Corynebacterium spp. BJI (i.e., ≥2 culture-positive gold-standard samples). Available strains were further characterized regarding their antibiotic susceptibilies, abilities to form early (BioFilm Ring Test®) and mature (crystal violet staining method) biofilms and to invade osteoblasts (gentamicin protection assay).Results: The 51 included BJI were mostly chronic (88.2%), orthopedic device-related (74.5%) and polymicrobial (78.4%). After a follow-up of 60.7 weeks (IQR, 30.1–115.1), 20 (39.2%) treatment failures were observed, including 4 Corynebacterium-documented relapses, mostly associated with non-optimal surgical management (OR 7.291; p = 0.039). Internalization rate within MG63 human osteoblasts was higher for strains isolated from delayed (&gt;3 months) BJI (p &lt; 0.001). Infection of murine osteoblasts deleted for the β1-integrin resulted in a drastic reduction in the internalization rate. No difference was observed regarding biofilm formation.Conclusions: Surgical management plays a crucial role in outcome of BJI involving corynebacteria, as often chronic and device-associated infections. Sanctuarisation within osteoblasts, implicating the β1 cellular integrin, may represent a pivotal virulence factor associated with BJI chronicity.
Transcranial Photobiomodulation to Improve Cognition in Gulf War Illness
Authors: Martin Paula I. , Chao Linda , Krengel Maxine H. , Ho Michael D. , Yee Megan , Lew Robert , Knight Jeffrey , Hamblin Michael R. , Naeser Margaret A. 
Published: January 2021

Introduction: Approximately 25–30% of veterans deployed to Kuwait, 1990-91, report persistent multi-symptom Gulf War Illness (GWI) likely from neurotoxicant exposures. Photobiomodulation (PBM) in red/near-infrared (NIR) wavelengths is a safe, non-invasive modality shown to help repair hypoxic/stressed cells. Red/NIR wavelengths are absorbed by cytochrome C oxidase in mitochondria, releasing nitric oxide (increasing local vasodilation), and increasing adenosine tri-phosphate production. We investigated whether PBM applied transcranially could improve cognition, and health symptoms in GWI.Materials and Methods: Forty-eight (40 M) participants completed this blinded, randomized, sham-controlled trial using Sham or Real, red/NIR light-emitting diodes (LED) applied transcranially. Fifteen, half-hour transcranial LED (tLED) treatments were twice a week (7.5 weeks, in-office). Goggles worn by participant and assistant maintained blinding for visible red. Pre-/Post- testing was at Entry, 1 week and 1 month post- 15th treatment. Primary outcome measures were neuropsychological (NP) tests; secondary outcomes, Psychosocial Questionnaires, including PTSD.Results: Primary Analyses (all participants), showed improvement for Real vs. Sham, for Digit Span Forwards (p &lt; 0.01); and a trend for Trails 4, Number/Letter Sequencing (p &lt; 0.10). For secondary outcomes, Real group reported more improvement on the SF-36V Plus, Physical Component Score (p &lt; 0.08). Secondary Analyses included only subjects scoring below norm (50%ile) at Entry, on specific NP test/s. Real and Sham improved at 1 week after 15th treatment; however, at 1 month, only those receiving Real improved further: Digit Span Total, Forwards and Backwards; Trails 4, Number/Letter Sequencing; California Verbal Learning Test-II, long delay free recall; Continuous Performance Test-II, False Alarm Rate; and Color-Word Interference, Stroop, Trial 3, Inhibition; Sham group worsened, toward Entry values. Only those with more post-traumatic stress disorder (PTSD) symptomatology at Entry, receiving Real, continued to have additional PTSD reduction at 1 month; Sham regressed.Conclusion: This study was underpowered (n = 48), with large heterogeneity at Entry. This likely contributed to significance or trend to significance, for only two of the NP tests (Digit Span Forwards; Trails 4, Number/Letter Sequencing) and only one general health measure, the SF-36V Plus, Physical Component Score. More subjects receiving Real, self-reported increased concentration, relaxation and sleep. Controlled studies with newer, transcranial LED home treatment devices are warranted; this is expected to increase enrollment.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT01782378.
Age-Related Clinical Presentation of MOG-IgG Seropositivity in Israel
Authors: Brill Livnat , Ganelin-Cohen Esther , Dabby Ron , Rabinowicz Shira , Zohar-Dayan Efrat , Rein Netaniel , Aloni Eyal , Karmon Yuval , Vaknin-Dembinsky Adi 
Published: January 2021

Introduction:Myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) have been recognized over the past 10 years as distinct inflammatory, demyelinating diseases of the central nervous system (CNS). Antibodies against MOG are found mostly in patients with optic neuritis (ON), acute disseminated encephalomyelitis (ADEM), and aquaporin-4 antibody (AQP4-abs)-seronegative neuromyelitis optica spectrum disorders (NMOSD). However, data on the disease course and disability outcomes of these patients are scarce.Aim:To describe clinical and paraclinical features associated with MOG antibodies (abs) in a cohort of patients in Israel, and to assess baseline prognostic features of MOG-ab-associated diseases after a first acute demyelinating event.Methods:MOG-abs were identified in serum using a cell-based assay, and clinical data were collected from the patients' medical records.Results:Of 683 patients with demyelinating diseases tested for MOG-abs, 53 were positive (7.7%), with ON the most common presenting phenotype (68%). The age range of MOG-abs seropositive patients was 1–66 years, with increased prevalence in children (19% compared to 6.7% in adults) (p&lt; 0.01). The highest prevalence of seropositivity was observed in children aged younger than 10 years (25.5%), followed by those aged 31–40 years (16.6%).Conclusions:MOGAD are distinct autoimmune diseases that occurs at all stages of life with a significantly higher prevalence in children; the main clinical presenting phenotype in the entire cohort is ON and young children most often presented with ON or ADEM. Our data highlight the need for repeated evaluation of MOG-abs in patients with acquired CNS demyelinating disorders, especially in children under 10 and adults between 31 and 40 years of age.
Imaging Patterns of Recurrent Infarction in the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) Study
Authors: Sangha Rajbeer S. , Prabhakaran Shyam , Feldmann Edward , Honda Tristan , Nizam Azhar , Cotsonis George A. , Campo-Bustillo Iszet , Romano Jose G. , Liebeskind David S. 
Published: January 2021

Introduction: While much is known about recurrent clinical events in patients with intracranial atherosclerotic disease (ICAD), there is limited data on characteristics of recurrent infarcts.Methods: The NIH-funded MyRIAD prospective, observational study was designed to identify mechanisms of ischemia and predictors of recurrence in ICAD. Recurrent infarction was assessed on MRI at 6–8 weeks. We reviewed the DWI/ADC and FLAIR sequences in patients with recurrent stroke and characterized the number of infarcts, infarct location, size, and patterns based on whether they were borderzone (BZ), perforator (SC/P), cortical or territorial (C/T), and mixed. Temporal characteristics were delineated by ADC/FLAIR correlation.Results: Of the 89 patients with 6–8 weeks MRI, 22 (24.7%) had recurrent infarcts in the territory of the symptomatic artery. Recurrent infarcts were evident on DWI in 63.6% and single infarcts in 54.5%. The median recurrent infarct volume was 2.0 cm3 compared to median index infarct volumes of 2.5 cm3. A mixed infarct pattern was most common (40.9%), followed by borderzone (22.7%), cortical or territorial (27.3%), while only 9.1% were in a perforator artery distribution. Amongst those with a mixed pattern, 8/9 had a borderzone distribution infarct as part of their mixed infarct pattern.Conclusion: These findings provide novel data on the characteristics of early recurrent infarcts in patients with symptomatic ICAD.
Dynamics in Endolymphatic Hydrops & Symptoms in Meniere's Disease After Endolymphatic Duct Blockage, Preliminary Results
Authors: He Jun , Peng Anquan , Hu Junjiao , Zhang Zhiwen , Chen Yichao , Wang Qin , Liu Wei , Chao Huang , Deng Kai , Jiang Wenqi 
Published: January 2021

Objective: The purpose of the present study was to evaluate the dynamics of endolymphatic hydrops (EH) and symptoms in a group of patients who underwent endolymphatic duct blockage (EDB) for treatment of intractable Meniere's Disease (MD), and to explore a metric for verifying the effectiveness of EDB procedure.Methods: A total of 22 patients with intractable MD patients who underwent EDB participated in the present study. EH was visualized using locally enhanced inner ear magnetic resonance imaging (MRI) prior to and following surgery. The vestibular hydrops ratio (VHR) in the second MRI examination was compared with the pre-surgery recordings.Results: Following EDB, 6 patients exhibited complete or partial reversal of EH, complete control of vertigo spells and reported improvement in hearing; 13 patients showed no changes in EH or hearing, but 5 of these patients exhibited complete control of vertigo attacks, and the other 8 patients exhibited improved control of vertigo attacks. The final 3 patients showed an increase in EH, but symptomatic worsening in 2 patients, and symptomatic improvement in 1 patient. There was a significant difference in the average VHR prior to and following EDB. Postoperative VHR was positively correlated with the frequency of vertigo spells in the latest 6 months of follow-up and improvement of postoperative average hearing threshold.Conclusion: The decreased EH accompanying the reduction in vertigo attacks and hearing preservation may provide a metric for verifying the effectiveness of EDB treatment in patients with MD.
The Burden of Malnutrition and Fatal COVID-19: A Global Burden of Disease Analysis
Authors: Mertens Elly , Peñalvo José L. 
Published: January 2021

Background: Although reasonable to assume, it is not yet clear whether malnourished countries are at higher risk for severe or fatal coronavirus disease 2019 (COVID-19). This study aims to identify the countries where prevalent malnutrition may be a driving factor for fatal disease after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Methods: Using estimates from the Global Burden of Disease 2019, country-level burden of malnutrition was quantified using four indicators: death rates for child growth failure (underweight, stunting, and/or wasting) and years lived with disability (YLD) attributed to iron and vitamin A deficiencies and high body mass index (BMI). Global mortality descriptors of the ongoing COVID-19 pandemic were extracted from the European Centre for Disease Prevention and Control, and case fatality ratios (CFRs) were calculated introducing a lag time of 10 weeks after the first death of a confirmed case. Bivariate analyses for 172 countries were carried out for malnutrition indicators and fatal COVID-19. Correlations between burden indicators were characterized by Spearman's rank correlation coefficients (ρ) and visually by scatterplots. Restricted cubic splines and underlying negative binomial regressions adjusted for countries' age-structure, prevalent chronic comorbidities related to COVID-19, population density, and income group were used to explore non-linear relationships.Results: Stratified by the World Bank income group, a moderate positive association between YLD rates for iron deficiency and CFRs for COVID-19 was observed for low-income countries (ρ = 0.60, p = 0.027), whereas no clear indications for the association with child growth failure, vitamin A deficiency, or high BMI were found (ρ &lt; 0.30). Countries ranking high on at least three malnutrition indicators and presenting also an elevated CFR for COVID-19 are sub-Saharan African countries, namely, Angola, Burkina Faso, Chad, Liberia, Mali, Niger, Sudan, and Tanzania, as well as Yemen and Guyana.Conclusions: Population-level malnutrition appears to be related to increased rates of fatal COVID-19 in areas with an elevated burden of undernutrition, such as countries in the Sahel strip. COVID-19 response plans in malnourished countries, vulnerable to fatal COVID-19, should incorporate food security, nutrition, and social protection as a priority component in order to reduce COVID-19 fatality.
Long-Term Outcomes and Prognostic Analysis of Computed Tomography-Guided Radioactive 125I Seed Implantation for Locally Recurrent Rectal Cancer After External Beam Radiotherapy or Surgery
Authors: Wang Hao , Wang Lu , Jiang Yuliang , Ji Zhe , Guo Fuxin , Jiang Ping , Li Xuemin , Chen Yi , Sun Haitao , Fan Jinghong , Du Gang , Wang Junjie 
Published: January 2021

BackgroundManagement of locally recurrent rectal cancer (LRRC) after surgery or external beam radiotherapy (EBRT) remains a clinical challenge, given the limited treatment options and unsatisfactory outcomes. This study aimed to assess long-term outcomes of computed tomography (CT)-guided radioactive 125I seed implantation in patients with LRRC and associated prognostic factors.MethodsA total of 101 patients with LRRC treated with CT-guided 125I seed implantation from October 2003 to April 2019 were retrospectively studied. Treatment procedures involved preoperative planning design, 125I seed implantation, and postoperative dose evaluation. We evaluated the therapeutic efficacy, adverse effects, local control (LC) time, and overall survival (OS) time.ResultsAll the patients had previously undergone surgery or EBRT. The median age of patients was 59 (range, 31–81) years old. The median follow-up time was 20.5 (range, 0.89–125.8) months. The median LC and OS time were 10 (95% confidence interval (CI): 8.5–11.5) and 20.8 (95% CI: 18.7–22.9) months, respectively. The 1-, 2-, and 5-year LC rates were 44.2%, 20.7%, and 18.4%, respectively. The 1-, 2-, and 5-year OS rates were 73%, 31.4%, and 5%, respectively. Univariate analysis of LC suggested that when short-time tumor response achieved partial response (PR) or complete response (CR), or D90&gt;129 Gy, or GTV ≤ 50 cm3, the LC significantly prolonged (P=0.044, 0.041, and &lt;0.001, respectively). The multivariate analysis of LC indicated that the short-time tumor response was an independent factor influencing LC time (P&lt;0.001). Besides, 8.9% (9/101) of the patients had adverse effects (≥grade 3): radiation-induced skin reaction (4/101), radiation-induced urinary reaction (1/101), fistula (2/101), and intestinal obstruction (2/101). The cumulative irradiation dose and the activity of a single seed were significantly correlated with adverse effects ≥grade 3 (P=0.047 and 0.035, respectively).ConclusionCT-guided 125I seed implantation is a safe and effective salvage treatment for LRRC patients who previously underwent EBRT or surgery. D90 and GTV significantly influenced prognosis of such patients.