bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Metabolic Syndrome and Risk of Esophageal Cancer: a Nationwide Population-Based Study
Authors: Lee Ji Eun , Han Kyungdo , Yoo Juhwan , Yeo Yohwan , Cho In Young , Cho Belong , Park Jin-Ho , Shin Dong Wook , Cho Jong Ho , Park Yong-Moon 
Published: September 2022

Abstract

Background:
Metabolic syndrome (MetS) is believed to increase the risk of esophageal cancer. However, most studies have been conducted in Western countries, focusing on esophageal adenocarcinoma (EAC). We aimed to investigate the association between MetS and risk of esophageal cancer in nationally representative large dataset in Korea, where esophageal squamous cell carcinoma (ESCC) is predominant.

Methods:
We analyzed the health examinations and claims data from the Korean National Health Insurance Service (NHIS). A total of 6,795,738 subjects who received an NHIS provided health examination in 2009 (index year) were included. Cox proportional hazards models were used to estimate multivariable adjusted HRs (aHR) and 95% confidence intervals (CI) for the association of MetS and its components (elevated waist circumference, blood pressure, triglycerides, fasting blood glucose, reduced high-density lipoprotein cholesterol) with the risk of esophageal cancer.

Results:
During a mean (± SD) follow-up of 8.2 (± 1.1) years, 6,414 cases of esophageal cancer occurred. MetS was associated with an increased risk of esophageal cancer (aHR, 1.11; 95% CI, 1.05–1.18). Among the components of MetS, elevated waist circumference (aHR, 1.24; 95% CI, 1.16–1.33), high blood pressure (aHR, 1.29; 95% CI, 1.22–1.37), and fasting blood glucose (aHR, 1.16; 95% CI, 1.11–1.22) were associated with increased risk of esophageal cancer.

Conclusions:
MetS was associated with an increased risk of esophageal cancer.

Impact:
Our findings suggest that individuals with MetS may be at increased risk for esophageal cancer, specifically ESCC. Further studies are needed to establish the relationship between MetS and esophageal cancer.
Serologic Profiling Using an Epstein-Barr Virus Mammalian Expression Library Identifies EBNA1 IgA as a Prediagnostic Marker for Nasopharyngeal Carcinoma
Authors: Paudel Sarita , Warner Benjamin E. , Wang Renwei , Adams-Haduch Jennifer , Reznik Alex S. , Dou Jason , Huang Yufei , Gao Yu-Tang , Koh Woon-Puay , Bäckerholm Alan , Yuan Jian-Min , Shair Kathy H.Y. 
Published: September 2022

AbstractPurpose:The favorable prognosis of stage I and II nasopharyngeal carcinoma (NPC) has motivated a search for biomarkers for the early detection and risk assessment of Epstein-Barr virus (EBV)–associated NPC. Although EBV seropositivity is ubiquitous among adults, a spike in antibodies against select EBV proteins is a harbinger of NPC. A serologic survey would likely reveal which EBV antibodies could discriminate those at risk of developing NPC.Experimental Design:Lysates from a new EBV mammalian expression library were used in a denaturing multiplex immunoblot assay to survey antibodies against EBV in sera collected from healthy individuals who later developed NPC (incident cases) in a prospective cohort from Singapore and validated in an independent cohort from Shanghai, P.R. China.Results:We show that IgA against EBV nuclear antigen 1 (EBNA1) discriminated incident NPC cases from matched controls with 100% sensitivity and 100% specificity up to 4 years before diagnosis in both Singapore and Shanghai cohorts. Incident NPC cases had a greater IgG repertoire against lytic-classified EBV proteins, and the assortment of IgA against EBV proteins detected by the immunoblot assay increased closer to diagnosis.Conclusions:Although NPC tumors consistently harbor latent EBV, the observed heightened systemic and mucosal immunity against lytic-classified antigens years prior to clinical diagnosis is consistent with enhanced lytic transcription. We conclude that an expanding EBV mucosal reservoir (which can be latent and/or lytic) is a risk factor for NPC. This presents an opportunity to identify those at risk of developing NPC using IgA against EBNA1 as a biomarker.
Obesity Is Associated with Altered Tumor Metabolism in Metastatic Melanoma
Authors: Hahn Andrew W. , Menk Ashley V. , Rivadeneira Dayana B. , Augustin Ryan C. , Xu Mingchu , Li Jun , Wu Xiaogang , Mishra Aditya K. , Gide Tuba N. , Quek Camelia , Zang Yan , Spencer Christine N. , Menzies Alexander M. , Daniel Carrie R. , Hudgens Courtney W. , Nowicki Theodore , Haydu Lauren E. , Khan M.A. Wadud , Gopalakrishnan Vancheswaran , Burton Elizabeth M. , Malke Jared , Simon Julie M. , Bernatchez Chantale , Putluri Nagireddy , Woodman Scott E. , Vashisht Gopal Y.N. , Guerrieri Renato , Fischer Grant M. , Wang Jian , Wani Khalida M. , Thompson John F. , Lee Jeffrey E. , Hwu Patrick , Ajami Nadim , Gershenwald Jeffrey E. , Long Georgina V. , Scolyer Richard A. , Tetzlaff Michael T. , Lazar Alexander J. , Schadendorf Dirk , Wargo Jennifer A. , Kirkwood John M. , DeBerardinis Ralph J. , Liang Han , Futreal Andrew , Zhang Jianhua , Wilmott James S. , Peng Weiyi , Davies Michael A. , Delgoffe Greg M. , Najjar Yana G. , McQuade Jennifer L. 
Published: September 2022

Abstract

Purpose:
Overweight/obese (OW/OB) patients with metastatic melanoma unexpectedly have improved outcomes with immune checkpoint inhibitors (ICI) and BRAF-targeted therapies. The mechanism(s) underlying this association remain unclear, thus we assessed the integrated molecular, metabolic, and immune profile of tumors, as well as gut microbiome features, for associations with patient body mass index (BMI).

Experimental Design:
Associations between BMI [normal (NL &lt; 25) or OW/OB (BMI ≥ 25)] and tumor or microbiome characteristics were examined in specimens from 782 patients with metastatic melanoma across 7 cohorts. DNA associations were evaluated in The Cancer Genome Atlas cohort. RNA sequencing from 4 cohorts (n = 357) was batch corrected and gene set enrichment analysis (GSEA) by BMI category was performed. Metabolic profiling was conducted in a subset of patients (x = 36) by LC/MS, and in flow-sorted melanoma tumor cells (x = 37) and patient-derived melanoma cell lines (x = 17) using the Seahorse XF assay. Gut microbiome features were examined in an independent cohort (n = 371).

Results:
DNA mutations and copy number variations were not associated with BMI. GSEA demonstrated that tumors from OW/OB patients were metabolically quiescent, with downregulation of oxidative phosphorylation and multiple other metabolic pathways. Direct metabolite analysis and functional metabolic profiling confirmed decreased central carbon metabolism in OW/OB metastatic melanoma tumors and patient-derived cell lines. The overall structure, diversity, and taxonomy of the fecal microbiome did not differ by BMI.

Conclusions:
These findings suggest that the host metabolic phenotype influences melanoma metabolism and provide insight into the improved outcomes observed in OW/OB patients with metastatic melanoma treated with ICIs and targeted therapies.
See related commentary by Smalley, p. 5
Faecalibacterium prausnitzii
Attenuates CKD via Butyrate-Renal GPR43 Axis
Authors: Li Hong-Bao , Xu Meng-Lu , Xu Xu-Dong , Tang Yu-Yan , Jiang Hong-Li , Li Lu , Xia Wen-Jie , Cui Nan , Bai Juan , Dai Zhi-Ming , Han Bei , Li Ying , Peng Bo , Dong Yuan-Yuan , Aryal Sachin , Manandhar Ishan , Eladawi Mahmoud Ali , Shukla Rammohan , Kang Yu-Ming , Joe Bina , Yang Tao 
Published: September 2022

Background:

Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of
Faecalibacterium prausnitzii
in CKD are reported. However, the mechanisms about if and how
F prausnitzii
can be used as a probiotic to treat CKD remains unknown.

Methods:
We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes.

Results:

We observed significant depletion of
Faecalibacterium
in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of
F prausnitzii
to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by
F prausnitzii
-derived butyrate were through the GPR (G protein-coupled receptor)-43.

Conclusions:

Using a mouse CKD model, we uncovered a novel beneficial role of
F prausnitzii
in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of
F prausnitzii
for ameliorating CKD.
MST1 Suppresses Disturbed Flow Induced Atherosclerosis
Authors: Quan Meixi , Lv Huizhen , Liu Zening , Li Kan , Zhang Chenghu , Shi Lei , Yang XinYu , Lei Ping , Zhu Yi , Ai Ding 
Published: September 2022

Background:
Atherosclerosis occurs mainly at arterial branching points exposed to disturbed blood flow. How MST1 (mammalian sterile 20-like kinase 1), the primary kinase in the mechanosensitive Hippo pathway modulates disturbed flow induced endothelial cells (ECs) activation and atherosclerosis remains unclear.

Methods:

To assess the role of MST1 in vivo, mice with EC-specific
Mst1
deficiency on

ApoE
−/−

background (

Mst1
iECKO
ApoE
−/−

) were used in an atherosclerosis model generated by carotid artery ligation. Mass spectrometry, immunoprecipitation, proximity ligation assay, and dye uptake assay were used to identify the functional substrate of MST1. Human umbilical vein endothelial cells and human aortic endothelial cells were subjected to oscillatory shear stress that mimic disturbed flow in experiments conducted in vitro.

Results:

We found that the phosphorylation of endothelial MST1 was significantly inhibited in oscillatory shear stress-exposed regions of human and mouse arteries and ECs. Ectopic lenti-mediated overexpression of wild-type MST1, but not a kinase-deficient mutant of MST1, reversed disturbed flow-caused EC activation and atherosclerosis in EC-specific
Mst1
deficiency on

ApoE
−/−

background (

Mst1
iECKO
ApoE
−/−

). Inhibition of MST1 by oscillatory shear stress led to reduced phosphorylation of Cx43 (connexin 43) at Ser255, the Cx43 hemichannel open, EC activation, and atherosclerosis, which were blocked by TAT-GAP19, a Cx43 hemichannel inhibitory peptide. Mass spectrometry studies identified that Filamin B fueled the translocation of Cx43 to lipid rafts for further hemichannel open. Finally, lenti-mediated overexpression of the Cx43
S255
mutant into glutamate to mimic phosphorylation blunted disturbed flow-induced EC activation, thereby inhibiting the atherogenesis in both

ApoE
−/−

and
Mst1

iECKO

ApoE
−/−

mice.

Conclusions:
Our study reveals that inhibition of the MST1-Cx43 axis is an essential driver of oscillatory shear stress-induced endothelial dysfunction and atherosclerosis, which provides a new therapeutic target for the treatment of atherosclerosis.
Opening Questions in Visual Working Memory
Authors: Nobre Anna C. 
Published: September 2022

Abstract
In this reflective piece on visual working memory, I depart from the laboriously honed skills of writing a review. Instead of integrating approaches, synthesizing evidence, and building a cohesive perspective, I scratch my head and share niggles and puzzlements. I expose where my scholarship and understanding are stumped by findings and standard views in the literature.
Giant Cell Arteritis: Focusing on Current Aspects From the Clinic to Diagnosis and Treatment
Authors: Vaiopoulos Aristeidis , Kanakis Meletios , Vaiopoulos George , Samanidis George , Kaklamanis Phedon 
Published: September 2022

Giant cell arteritis (GCA) is a granulomatous arteritis involving large arteries, particularly the aorta and its major proximal branches, including the carotid and temporal arteries. GCA involves individuals over 50 years old. The etiopathogenesis of GCA may involve a genetic background triggered by unknown environmental factors (eg infections), the activation of dendritic cells as well as inflammatory and vascular remodeling. However, its pathogenetic mechanism still remains unclear, although progress has been made in recent years. In the past, inflammatory markers and arterial biopsy were considered as gold standard for the diagnosis of GCA. However, emerging imaging methods have been made more sensitive and specific for the diagnosis of GCA. Treatment includes biological and other modalities including interleukin-6 (IL-6) inhibitors.
Systematic review of exercise therapy in the management of post-thrombotic syndrome
Authors: Jasionowska Sara , Turner Benedict R H , Machin Matthew , Onida Sarah , Gwozdz Adam M , Shalhoub Joseph , Davies Alun H 
Published: September 2022

Objectives Exercise improves haemodynamic parameters in patients with chronic venous disease. There is a paucity of evidence on its effect in post-thrombotic syndrome (PTS). The aim of this systematic review is to assess the impact of exercise in PTS. Methods Adhering to PRISMA guidelines and following PROSPERO registration (CRD42021220924), MEDLINE, Cochrane Library, EMBASE database, and trial registries were searched on 19th May 2022. Results One article met the inclusion criteria and a narrative synthesis was carried out. The included randomised controlled trial reported a between-group mean difference of 4.6 points ( p = .027) in the VEINES-QOL score and −2.0 points ( p = .14) in the Villalta score, in favour of exercise therapy. The statistical significance threshold was not reached. Conclusion Data on exercise in PTS remains sparse but exercise appears to be a safe intervention. In the context of this literature, a potential future trial and outcome reporting measures are suggested.
The effect of AUT00206, a Kv3 potassium channel modulator, on dopamine synthesis capacity and the reliability of [18F]-FDOPA imaging in schizophrenia
Authors: Angelescu Ilinca , Kaar Stephen J , Marques Tiago Reis , Borgan Faith , Veronesse Mattia , Sharman Alice , Sajjala Anil , Deakin Bill , Hutchison John , Large Charles , Howes Oliver D 
Published: September 2022

Background: Current treatments for schizophrenia act directly on dopamine (DA) receptors but are ineffective for many patients, highlighting the need to develop new treatment approaches. Striatal DA dysfunction, indexed using [18F]-FDOPA imaging, is linked to the pathoetiology of schizophrenia. We evaluated the effect of a novel drug, AUT00206, a Kv3.1/3.2 potassium channel modulator, on dopaminergic function in schizophrenia and its relationship with symptom change. Additionally, we investigated the test–retest reliability of [18F]-FDOPA PET in schizophrenia to determine its potential as a biomarker for drug discovery. Methods: Twenty patients with schizophrenia received symptom measures and [18F]-FDOPA PET scans, before and after being randomised to AUT00206 or placebo groups for up to 28 days treatment. Results: AUT00206 had no significant effect on DA synthesis capacity. However, there was a correlation between reduction in striatal dopamine synthesis capacity (indexed as Kicer) and reduction in symptoms, in the AUT00206 group ( r = 0.58, p = 0.03). This was not observed in the placebo group ( r = −0.15, p = 0.75), although the placebo group may have been underpowered to detect an effect. The intraclass correlation coefficients of [18F]-FDOPA indices in the placebo group ranged from 0.83 to 0.93 across striatal regions. Conclusions: The relationship between reduction in DA synthesis capacity and improvement in symptoms in the AUT00206 group provides evidence for a pharmacodynamic effect of the Kv3 channel modulator. The lack of a significant overall reduction in DA synthesis capacity in the AUT00206 group could be due to variability and the low number of subjects in this study. These findings support further investigation of Kv3 channel modulators for schizophrenia treatment. [18F]-FDOPA PET imaging showed very good test–retest reliability in patients with schizophrenia.
The Effect of the Art Therapy Interventions on Depression Symptoms Among Older Adults: A Meta-analysis of Controlled Clinical Trials
Authors: Jenabi Ensiyeh , Bashirian Saeid , Ayubi Erfan , Rafiee Masoud , Bashirian Mozhdeh 
Published: September 2022

Background To our knowledge, no systematic reviews and meta-analyses have yet been published that examine the effect of art therapy (AT) interventions on depression symptoms among older adults, and this study aimed to systematically review and meta-analysis of clinical trials, summarize eligible relevant studies and provide a true effect measure for the association between AT and depression symptoms in older adults. Methods The databases of PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials were searched until 15 February 2022. The methodological quality of the included studies was evaluated by the Delphi checklist. The heterogeneity across studies was conducted by chi-squared test and measured its quantity by the I2 statistic. We performed this meta-analysis to obtain a summary measure of the mean difference in depression scores between AT and control groups using a random-effects model. All statistical analyses were carried out at a significance level of .05 using Stata software, version 14. Results Until 15 February 2022, 222 studies through databases and 199 studies through review of references were included in the present meta-analysis. In total, the analysis covered 8 studies. The difference in mean depression score between the intervention and control groups showed significant reductions in the AT group (MD −.78; 95% CI: −1.17, −.38; I 2 = 67.9%). Conclusion Our findings suggest that AT can be considered an effective intervention for reducing depression symptoms among older adults and art therapists/psychotherapists can use this method to reduce the symptoms of depression among older adults.
The SLICC-FI Predicts Damage Accrual in SLE Patients. Data From the Almenara Lupus Cohort
Authors: Elera-Fitzcarrald Claudia , Gamboa-Cárdenas Rocío V , Reatégui-Sokolova Cristina , Pimentel-Quiroz Victor , Rodriguez-Bellido Zoila , Pastor-Asurza César A , Perich-Campos Risto , Alarcón Graciela S , Ugarte-Gil Manuel F 
Published: September 2022

Objective To evaluate the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI) as a predictor of damage accrual in a primarily Mestizo SLE patient cohort. Methods Patients from a single-center prevalent cohort were included. Damage accrual was defined as the increase in the SLICC/American College of Rheumatology (ACR) damage index (SDI) scores between the baseline and the last visits. The SLICC-FI was measured at baseline. Univariable and multivariable Cox regression models were performed to determine the association between the baseline SLICC-FI (per 0.05 increase) and the increase in the SDI, adjusted for possible confounders. Alternative analyses using negative binomial regression models including the difference between the last and the first SDI as outcome were performed. Results Of the 265 patients included, 248 (93.6%) were female with mean (SD) age of 35.1 (13.6) years at diagnosis. At baseline, mean (SD) SLE disease duration was 7.3 (6.5) years, SDI was 1.0 (1.2) and the SLICC-FI was 0.22 (0.05). After a mean (SD) of 5.2 (2.2) years of follow-up, the SDI increased in 126 (47.5%) patients, and the final mean (SD) SDI score was 1.7 (1.7). Higher SLICC-FI scores at baseline predicted greater damage accrual in the univariable analysis [Hazard Ratio (HR) =1.38, (CI95% 1.16–1.65); p < 0.001] and in the multivariable model, after adjustment for possible confounders [HR = 1.30 (CI95% 1.02–1.66); p = 0.033]. Conclusion SLICC-FI predicts the occurrence of damage accrual in a prevalent SLE Latin-American cohort with short or long disease duration, supporting the relevance of this index in the evaluation of SLE patients.
Impact of the COVID-19 pandemic on colorectal cancer screening in New York City
Authors: Lee Briton , Young Sigrid , Williams Renee , Liang Peter S 
Published: September 2022

Background The COVID-19 pandemic significantly impacted the delivery of cancer screening. The resulting decrease in outpatient visits and cancellations of non-urgent procedures have negatively affected colorectal cancer (CRC) screening. We aimed to determine the effect of the pandemic on CRC screening at a safety-net hospital and a private health system based in New York City. Methods We identified individuals eligible for CRC screening aged 50 to 75 years presenting for outpatient care at a safety-net public hospital and private health system in April through September of 2019 and 2020. The primary outcome was the proportion of screening-eligible patients seen in primary care who underwent CRC screening. Results The safety-net hospital had 516 (6.1% of screening-eligible individuals) and 269 (4.3%) screening tests completed in 2019 and 2020, respectively (p < 0.01). Fecal immunochemical tests (FIT) accounted for 69.6% of screening in 2019 and 88.1% in 2020. Colonoscopy accounted for 20.3% of screening in 2019 and 11.9% in 2020. The private health system had 39 (0.7%) and 21 (0.6%) screening tests completed in 2019 and 2020, respectively (p = 0.48). FIT accounted for 61.9% of screening in 2019 and 57.1% in 2020. Colonoscopy accounted for 38.1% of screening in 2019 and 42.9% in 2020. Conclusion Absolute numbers of screening tests decreased for both institutions during the COVID-19 pandemic. We observed a decrease in screening uptake and increase in proportional FIT use in the safety-net hospital but no change in the private health system.
The anatomic – magnetic resonance imaging study of distal triceps brachii tendon
Authors: Kholinne Erica , Kwak Jae-Man , Heo Yijin , Hwang Seung-Jun 
Published: September 2022

Purpose The study aimed to describe the distal triceps brachii insertion on the olecranon and to correlate the findings with those seen in normal MR (Magnetic Resonance) anatomy of the triceps brachii insertion. Materials and methods 14 un-paired fresh frozen elbows were included according to the institution guidelines and dissected. Histologic examination was performed to the distal triceps brachii insertion. The dimension of the distal triceps brachii tendon insertion was measured and defined based on its layer. The measurement of distal triceps brachii insertion was performed with image processing program (Image J, National Institute of Health, Bethesda, Maryland). T1-weighted elbow MR images (3.0 T) of a 102 patients were acquired and analyzed according to its sagittal plane. Results All specimens shows that distal triceps brachii tendon is with three distinct insertional areas in the olecranon which are: (1) capsular, (2) deep muscular, (3) superficial tendinous insertion with the areas of 80.7 mm2, 56.4 mm2, and 175.2 mm2, respectively. The superficial tendinous insertion was observed with a thickened portion, the “central cord” with 0.5 occupation ratio. MR analysis showed that 30% (31/102) of the distal biceps brachii insertion was with a cleft between the bipartite insertion of the superficial tendinous and the deep muscular insertion on olecranon which designated as the “lacuna” which was also found in 35% (5/14) of the specimens. Conclusions The distal triceps brachii has three distinct insertion on the olecranon. The superficial tendinous layer was separated with the deep muscular layer by a cleft in one third of the cases. Knowledge of this anatomy will help surgeon to understand the partial triceps injury and to avoid iatrogenic injury to the distal triceps tendon during surgery.