bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nociceptive Flexion Reflex Threshold in Chronic Pain Patients
Authors: Amiri Mohammadreza , Esmaili Hamid , Hamad Abdul Hamid , Alavinia Mohammad , Masani Kei , Kumbhare Dinesh 
Published: October 2020

Background
The nociceptive flexion reflex is a physiological, polysynaptic reflex triggered by a nociceptive stimulus activating a withdrawal response. In chronic musculoskeletal-related pain conditions, a decreased nociceptive flexion reflex threshold has been suggested as a possible recognition evidence for central sensitization that may cause alteration of central nervous system processing.

Objective
The aim of the study was to systematically review reported comparisons of the nociceptive flexion reflex threshold in chronic pain patients and healthy individuals.

Methods
Electronic databases covering studies published between January 1990 and December 2019 were systematically searched. After application of exclusion criteria, 20 studies including 28 trials were included in this review. For meta-analysis, we used a random-effects model and funnel plot for publication bias. This research was registered at PROSPERO (CRD42019140354).

Results
Compared with healthy controls, standardized mean differences in nociceptive flexion reflex threshold were significantly lower in the total sample of chronic pain patients. Subgroup analysis indicated a homogenous decreased nociceptive flexion reflex threshold in studies reporting fibromyalgia, chronic pain, and joint pain while heterogeneity existed in other included pain conditions.

Conclusions
A lower nociceptive flexion reflex threshold in patients experiencing chronic pain conditions may imply hyperexcitability in central nervous system processing. As a preliminary study, the findings would act as a basis for developing a methodology assisting current clinical practices
New Insights Into Systemic Lupus Erythematosus Therapies
Authors: Wang Danielle H. , Wallace Daniel J. 
Published: October 2020

Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that may affect every organ. The multiple pathogenic mechanisms and heterogeneous phenotypes of SLE present unique challenges in the management of this complex disease. This article discusses new SLE therapies from the last 10 years. We will address new information in the realms of lifestyle interventions, antimalarials, nonsteroidal anti-inflammatory drugs, glucocorticoids, immunosuppressive disease modifying antirheumatic drugs, biological therapies, and other modalities as they pertain to SLE.
Tonsillar Metastasis From Colon Cancer Detected on 18F-FDG PET/CT Imaging
Authors: Baghdadi Yaser M. , Valdivia Ana Y. 
Published: October 2020

Abstract
A 54-year-old woman with smoking history who was diagnosed with invasive adenocarcinoma of the rectosigmoid colon with subsequent surgical resection and chemotherapy was presented. The patient developed local recurrence and pulmonary metastases that required further chemotherapy and surgical resection. During follow-up, the patient had 18F-FDG PET/CT scan showing asymmetric hypermetabolic tonsils with activity greater on the right compared with the left. The patient underwent bilateral tonsillectomy, and pathology revealed moderately to poorly differentiated adenocarcinoma in the right tonsil, consistent with metastasis from known colonic primary.
18F-FDG PET/CT in the Diagnosis and Follow-up of Balint Syndrome
Authors: Dondi Francesco , Albano Domenico , Paghera Barbara , Bertagna Francesco , Giubbini Raffaele 
Published: October 2020

Abstract
Balint syndrome is a rare neurological disorder characterized by simultanagnosia, optic ataxia, and ocular apraxia, and its etiology can be very heterogeneous. Diagnosis is based on neuropsychological evaluation, but brain radiological and nuclear medicine imaging also plays an important role. Because few case reports have been published in literature, in this work, we present 2 patients affected by Balint syndrome in which 18F-FDG PET/CT helped in the diagnosis and follow-up.
Integrated Plasma and Tissue Proteomics Reveals Attractin Release by Intraluminal Thrombus of Abdominal Aortic Aneurysms and Improves Aneurysm Growth Prediction in Humans
Authors: Lee Regent , Cassimjee Ismail , Huang Honglei , Lapolla Pierfrancesco , Ngetich Elisha , Chandrashekar Anirudh , Charles Philip , Kessler Benedikt , Fischer Roman , Handa Ashok 
Published: October 2020

Objective:
Discovery of novel biomarkers for AAA growth prediction.

Background:
Novel biomarker of AAA growth is a recognized priority in research. Our prior work implicated intraluminal thrombus (ILT) in AAAs to be a potential source of systemic mediators during AAA progression. Here we applied a mass spectrometry proteomics pipeline to discover novel biomarkers for AAA growth prediction.

Methods:
Patients were prospectively recruited. Plasma samples were collected at baseline (n = 62). AAA growth was recorded at 12 months. In Experiment 1, plasma samples from the fastest and slowest growth patients (n = 10 each) were compared. In Experiment 2, plasma samples were collected before and at 10–12 weeks after surgery (n = 29). In Experiment 3, paired ILT and omental biopsies were collected intra-operatively during open surgical repair (n = 3). In Experiment 4, tissue secretome was obtained from ex-vivo culture of these paired tissue samples. Samples were subjected to a liquid chromatography tandem mass spectrometry workflow to discover novel biomarkers.

Results:
We discovered 3 proteins that are: (i) present in ILT; (ii) released by ILT; (iii) reduced in circulation after AAA surgery; (iv) differs between fast and slow growth AAAs. One of these is Attractin. Plasma Attractin correlates significantly with future AAA growth (Spearman r = 0.35, P < 0.005). Using Attractin and AAA diameter as input variables, the area under receiver operating characteristics for predicting no growth and fast growth or AAA at 12 months is 85% and 76%, respectively.

Conclusion:
We show that ILT of AAAs releases mediators during the natural history of AAA growth. These are novel biomarkers for AAA growth prediction in humans.
Multicenter Randomized Phase 2 Trial Comparing Chemoradiotherapy and Docetaxel Plus 5-Fluorouracil and Cisplatin Chemotherapy as Initial Induction Therapy for Subsequent Conversion Surgery in Patients With Clinical T4b Esophageal Cancer
Authors: Sugimura Keijiro , Miyata Hiroshi , Tanaka Koji , Makino Tomoki , Takeno Atsushi , Shiraishi Osamu , Motoori Masaaki , Yamasaki Makoto , Kimura Yutaka , Hirao Motohiro , Fujitani Kazumasa , Yasuda Takushi , Mori Masaki , Eguchi Hidetoshi , Yano Masahiko , Doki Yuichiro 
Published: October 2020

Objective:
We conducted a multicenter randomized prospective phase 2 trial of chemoradiotherapy (CRT) versus chemotherapy (CT) as initial induction therapy for conversion surgery (CS) in clinical T4b esophageal cancer. We compared treatment effects and adverse events (AEs).

Summary Background Data:
Although induction followed by CS is potentially curative for T4b esophageal cancer, the optimal initial induction treatment is unclear.

Methods:
Ninety-nine patients with T4b esophageal cancer were randomly allocated to chemoradiotherapy (Group A, n = 49) or CT (Group B, n = 50) as initial induction treatment. CRT consisted of radiation (50.4 Gy) with cisplatin and 5-fluorouracil. CT consisted of 2 cycles of docetaxel plus cisplatin and 5-fluorouracil (DCF). CRT or CT was followed by CS if resectable. If unresectable, the patient received the other treatment as secondary treatment. CS was performed if resectable after secondary treatment. The primary end point was 2-year overall survival.

Results:
In Group A, CS was performed in 34 (69%) and 7 patients (14%) after initial and secondary treatment. In Group B, CS was performed in 25 (50%) and 17 patients (34%) after initial and secondary treatment. The R0 resection rate after initial and secondary treatment was similar (78% vs 76%, P = 1.000). AEs including leukopenia, neutropenia, febrile neutropenia, and diarrhea were significantly more frequent in Group B. Group A had better histological complete response of the primary tumor (40% vs 17%, P = 0.028) and histological nodal status (P = 0.038).

Conclusion:
Upfront CRT was superior to upfront CT in terms of pathological effects and AEs. The Japan Registry of Clinical Trials (s051180164).
Clinical Outcomes After Liver Transplantation in Patients With Portopulmonary Hypertension
Authors: Cartin-Ceba Rodrigo , Burger Charles , Swanson Karen , Vargas Hugo , Aqel Bashar , Keaveny Andrew P. , Heimbach Julie , Taner Timucin , Nyberg Scott , Rosen Charles , Cajigas Hector , DuBrock Hilary , Krowka Michael J. 
Published: October 2020

Background.
Portopulmonary hypertension (POPH) is the presence of pulmonary arterial (PA) hypertension in patients with portal hypertension and is associated with significant morbidity and mortality. In a cohort of POPH patients, we describe the clinical outcomes of POPH patients who underwent liver transplantation (LT).

Methods.
Retrospectively collected data from a prospectively assembled cohort of all consecutive POPH adults evaluated in 3 transplant centers from 1996 to 2019.

Results.
From a cohort of 228 POPH patients, 50 patients underwent LT. Significant hemodynamic improvement after PA-targeted therapy was observed, with 58% receiving only monotherapy pretransplant. After LT, 21 (42%) patients were able to discontinue and remained off PA-targeted therapy. The 1-, 3-, and 5-y unadjusted survival rates after LT were 72%, 63%, and 60%, respectively. An elevated pulmonary vascular resistance (PVR) before LT was associated with worse survival rate (HR, 1.91; 95% CI, 1.07-3.74, P = 0.04). No survival difference was observed in those granted MELD exception or transplants performed before or after the year 2010.

Conclusions.
Significant number of POPH patients discontinued PA-targeted therapy after LT. Higher PVR before LT was associated with worse survival, as was monotherapy use. Despite effective PA-targeted therapies, POPH survival outcomes after LT in our cohort were modest and may reflect the need for more aggressive therapy.
Coronin-1 is necessary for enteric pathogen-induced transcytosis across human ileal enteroid monolayers expressing M cells
Authors: Staab Janet F. , Doucet Michele , Latanich Rachel , Lee Sun , Estes Mary K. , Kaper James B. , Zachos Nicholas C. 
Published: October 2020

ABSTRACTIn the intestine, luminal sampling by microfold (M) cells is crucial for inducing protective mucosal immune responses but can also serve as an entry pathway for pathogens, including bacteria and viruses. Enteric pathogens can influence intestinal M cell function; however, the molecular mechanisms involved in the regulation of uptake and transcytosis of gut cargo by human M cells remain to be determined. Understanding the mechanisms responsible for regulating human M cell function requires a relevant human model. In this study, human ileal enteroids established from healthy donors were grown as confluent monolayers on permeable supports and differentiated to express mature M cells. Enteric pathogens including enteropathogenicE. coli(EPEC), adherent invasive E. coli (AIEC), and human rotavirus were apically exposed to M cell enteroid monolayers. M cell-mediated uptake and transcytosis was compared in enteroids infected by pathogenic or commensal bacteria (HS strain). EPEC and AIEC, but not HS, stimulated M cell uptake and transcytosis. We discovered that this pathogenspecific effect was dependent on expression of coronin 1a, a cytoskeletal remodeling protein. Using stable coronin 1a knockdown (KD) enteroids, we observed that EPEC-stimulated transcytosis of fluorescent beads was lost and associated with a significant decrease in the number of glycoprotein-2 positive (Gp-2+ve) M cells. The results of these studies demonstrate that coronin 1a is required for uptake and transcytosis of luminal cargo across human M cells and that coronin 1a is necessary for differentiation of mature M cells that actively transcytose luminal gut antigens in response to pathogenic, but not commensal, microbes.
Polybrominated diphenyl ether serum concentrations and depressive symptomatology in pregnant African American women
Authors: Mutic A. , Barr D. , Hertzberg V. , Dunlop A. , Brennan P. , McCauley L. 
Published: October 2020

ABSTRACTBackgroundPolybrominated diphenyl ethers (PBDEs) are lipophilic, persistent endocrine disrupting chemicals often used as flame retardants in products that were widely produced in the United States until 2004. The potential for environmental toxicants such as PBDEs to disrupt normal neuroendocrine pathways resulting in depression and other neurological symptoms has been largely understudied. This study examined whether PBDE exposure in pregnant women was associated with antenatal depressive symptomatology.MethodsThis study is part of a larger longitudinal pregnancy and birth cohort study. Data were collected from 193 African American pregnant women at 8-14 weeks gestation. Serum PBDEs were analyzed using gas chromatography-tandem mass spectrometry. The Edinburgh Depression Scale (EDS) was used to identify depressive symptoms experienced in the last seven days prior to biosampling. The dichotomous depression variable was used to explore varying high-risk EDS cutoffs and illustrated with receiver operating characteristic curves. Logistic regression models were constructed to investigate associations with antenatal depression and a weighted quantile sum (WQS) index was calculated to account for the mixture of PBDE congeners.ResultsOf the total sample, 52 women (26.9%) were categorized as having a high risk of depression. PBDE congeners −47, −99, and −100 were detected in 50% or more of the samples tested. BDE-47 was positively associated with depressive symptoms (β =2.36, p=0.05). The risk of being mild to moderately depressed increased by a factor of 4.52 for BDE-47 (CI 1.50, 13.60) and 1.58 for BDE-99 (CI 1.08, 2.29). The WQS index, a weighted estimate of the body burden of the congener mixture was positively associated with a higher risk of mild to moderate depression using an EDS cutoff ≥10 (OR=2.93; CI 1.18, 7.82).ConclusionBDE-47 and −99 exposures are significantly associated with depressive symptomatology in a pregnant cohort. These exposures will likely continue for years due to slow chemical degradation. Interventions should focus on PBDE mitigation to reduce toxic neuroendocrine effects on vulnerable pregnant women.
Role of the common PRSS1-PRSS2 haplotype in alcoholic and non-alcoholic chronic pancreatitis: meta- and re-analyses
Authors: Herzig Anthony F. , Génin Emmanuelle , Cooper David N. , Masson Emmanuelle , Férec Claude , Chen Jian-Min 
Published: October 2020

AbstractThe association between a common PRSS1-PRSS2 haplotype and alcoholic chronic pancreatitis (ACP), which was revealed by the first genome-wide association study of chronic pancreatitis (CP), has been consistently replicated. However, the association with non-ACP (NACP) has been controversial. Herein, we sought to clarify this basic issue by means of an allele-based meta-analysis of currently available studies. We then used studies informative for genotype distribution to explore the biological mechanisms underlying the association data and to test for gene-environment interaction between the risk haplotype and alcohol consumption by means of a re-analysis. A literature search was conducted to identify eligible studies. Meta-analysis was performed using the Review Manager software. The association between the risk genotypes and NACP or ACP was tested for the best-fitting genetic model. Gene-environment interaction was estimated by both case-only and multinomial approaches. Five and eight studies were employed for the meta-analysis of ACP and NACP findings, respectively. The risk allele was significantly associated with both ACP (pooled OR 1.67, 95% CI 1.56–1.78; P<0.00001) and NACP (pooled OR 1.28, 95% CI 1.17–1.40; P<0.00001). Consistent with a dosage effect of the risk allele on PRSS1/PRSS2 mRNA expression in human pancreatic tissue, both ACP and NACP association data were best explained by an additive genetic model. Finally, the risk haplotype was found to interact synergistically with ACP.
SARS-CoV-2 S protein ACE2 interaction reveals novel allosteric targets
Authors: Raghuvamsi Palur , Tulsian Nikhil , Samsudin Firdaus , Qian Xinlei , Purushotorman Kiren , Yue Gu , Kozma Mary , Lescar Julien , Bond Peter , MacAry Paul , Anand Ganesh 
Published: October 2020

AbstractThe Spike (S) protein is the main handle for SARS-CoV-2 to enter host cells through surface ACE2 receptors. How ACE2 binding activates proteolysis of S protein is unknown. Here, we have mapped the S:ACE2 interface and uncovered long-range allosteric propagation of ACE2 binding to sites critical for viral host entry. Unexpectedly, ACE2 binding enhances dynamics at a distal S1/S2 cleavage site and flanking protease docking site ~27 Å away while dampening dynamics of the stalk hinge (central helix and heptad repeat) regions ~ 130 Å away. This highlights that the stalk and proteolysis sites of the S protein are dynamic hotspots in the pre-fusion state. Our findings provide a mechanistic basis for S:ACE2 complex formation, critical for proteolytic processing and viral-host membrane fusion and highlight protease docking sites flanking the S1/S2 cleavage site, fusion peptide and heptad repeat 1 (HR1) as allosterically exposed cryptic hotspots for potential therapeutic development.One Sentence SummarySARS-CoV-2 spike protein binding to receptor ACE2 allosterically enhances furin proteolysis at distal S1/S2 cleavage sites
Robotic Multi-Probe-Single-Actuator Inchworm Neural Microdrive
Authors: Smith R. D. , Kolb I. , Tanaka S. , Lee A. K. , Harris T. D. , Barbic M. 
Published: October 2020

AbstractElectrophysiology is one of the major experimental techniques used in neuroscience. The favorable spatial and temporal resolution as well as the increasingly larger site counts of brain recording electrodes contribute to the popularity and importance of electrophysiology in neuroscience. Such electrodes are typically mechanically placed in the brain to perform acute or chronic freely moving animal measurements. The micro positioners currently used for such tasks employ a single translator per independent probe being placed into the targeted brain region, leading to significant size and weight restrictions. To overcome this limitation, we have developed a miniature robotic multi-probe neural microdrive that utilizes novel phase-change-material-filled resistive heater micro-grippers. The microscopic dimensions, gentle gripping action, independent electronic actuation control, and high packing density of the grippers allow for micrometer-precision independent positioning of multiple arbitrarily shaped parallel neural electrodes with only a single piezo actuator in an inchworm motor configuration. This multi-probe-single-actuator design allows for significant size and weight reduction, as well as remote control and potential automation of the microdrive. We demonstrate accurate placement of multiple independent recording electrodes into the CA1 region of the rat hippocampusin vivoin acute and chronic settings. Thus, our robotic neural microdrive technology is applicable towards basic neuroscience and clinical studies, as well as other multi-probe or multi-sensor micro-positioning applications.One Sentence SummaryMiniature robotic multi-probe single-actuator microdrive utilizing phase change material based micro-grippers.
A betacoronavirus multiplex microsphere immunoassay detects early SARS-CoV-2 seroconversion and controls for pre-existing seasonal human coronavirus antibody cross-reactivity
Authors: Laing Eric D. , Sterling Spencer L. , Richard Stephanie A. , Phogat Shreshta , Samuels Emily C. , Epsi Nusrat J. , Yan Lianying , Moreno Nicole , Coles Christian , Mehalko Jennifer , Drew Matthew , English Caroline , Chung Kevin K. , Clifton G. Travis , Munster Vincent J. , de Wit Emmie , Tribble David , Agan Brian K. , Esposito Dominic , Lanteri Charlotte , Mitre Edward , Burgess Timothy H. , Broder Christopher C. 
Published: October 2020

ABSTRACTWith growing concern of persistent or multiple waves of SARS-CoV-2 in the United States, sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 surveillance. Here, we describe the development and application of a multiplex microsphere-based immunoassay (MMIA) for COVD-19 antibody studies, utilizing serum samples from non-human primate SARS-CoV-2 infection models, an archived human sera bank and subjects enrolled at five U.S. military hospitals. The MMIA incorporates prefusion stabilized spike glycoprotein trimers of SARS-CoV-2, SARS-CoV-1, MERS-CoV, and the seasonal human coronaviruses HCoV-HKU1 and HCoV-OC43, into a multiplexing system that enables simultaneous measurement of off-target pre-existing cross-reactive antibodies. We report the sensitivity and specificity performances for this assay strategy at 98% sensitivity and 100% specificity for subject samples collected as early as 10 days after the onset of symptoms. In archival sera collected prior to 2019 and serum samples from subjects PCR negative for SARS-CoV-2, we detected seroprevalence of 72% and 98% for HCoV-HKU1 and HCoV-0C43, respectively. Requiring only 1.25 µL of sera, this approach permitted the simultaneous identification of SARS-CoV-2 seroconversion and polyclonal SARS-CoV-2 IgG antibody responses to SARS-CoV-1 and MERS-CoV, further demonstrating the presence of conserved epitopes in the spike glycoprotein of zoonotic betacoronaviruses. Application of this serology assay in observational studies with serum samples collected from subjects before and after SARS-CoV-2 infection will permit an investigation of the influences of HCoV-induced antibodies on COVID-19 clinical outcomes.
shinyCurves, a shiny web application to analyse multisource qPCR amplification data: a COVID 19 case study
Authors: Olaechea-Lázaro S. , García-Santisteban I. , Pineda JR. , Badiola I. , Alonso S. , Bilbao JR. , Fernandez-Jimenez N. 
Published: October 2020

AbstractSummaryQuantitative, reverse transcription polymerase chain reaction (qRT-PCR) has been the gold-standard tool for viral detection during the SARS-CoV-2 pandemic. However, the desperate rush for a quick diagnosis led the use of very different types of machines and proprietary software, leading to an unbearable complexity of data analysis with a limited parameter setup. Here, we present shinyCurves, a shiny web application created to analyse multisource qPCR amplification data from independent multi-plate format. Furthermore, our automated system allows the classification of the results as well as the plot of both amplification and melting curves. Altogether, our web application is an automated qPCR analysis resource available to the research community.AvailabilityThe shinyCurves web application to analyze multisource qPCR amplification data is publicly available under CC license (CC BY-NC-SA 4.0) at https://biosol.shinyapps.io/shinycurves/ and https://github.com/biosol/shinyCurves.