bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic MCPIP1 protein levels are reduced in NAFLD patients and are predominantly expressed in cholangiocytes and liver endothelium
Authors: Pydyn Natalia , Kadluczka Justyna , Major Piotr , Hutsch Tomasz , Belamri Kinga , Malczak Piotr , Radkowiak Dorota , Budzynski Andrzej , Miekus Katarzyna , Jura Jolanta , Kotlinowski Jerzy 
Published: February 2023

Background and Aims:
NAFLD is characterized by the excessive accumulation of fat in hepatocytes. NAFLD can range from simple steatosis to the aggressive form called NASH, which is characterized by both fatty liver and liver inflammation. Without proper treatment, NAFLD may further progress to life-threatening complications, such as fibrosis, cirrhosis, or liver failure. Monocyte chemoattractant protein-induced protein 1 (MCPIP1, alias Regnase 1) is a negative regulator of inflammation, acting through the cleavage of transcripts coding for proinflammatory cytokines and the inhibition of NF-κB activity.

Methods:
In this study, we investigated MCPIP1 expression in the liver and peripheral blood mononuclear cells (PBMCs) collected from a cohort of 36 control and NAFLD patients hospitalized due to bariatric surgery or primary inguinal hernia laparoscopic repair. Based on liver histology data (hematoxylin and eosin and Oil Red-O staining), 12 patients were classified into the NAFL group, 19 into the NASH group, and 5 into the control (non-NAFLD) group. Biochemical characterization of patient plasma was followed by expression analysis of genes regulating inflammation and lipid metabolism. The MCPIP1 protein level was reduced in the livers of NAFL and NASH patients in comparison to non-NAFLD control individuals. In addition, in all groups of patients, immunohistochemical staining showed that the expression of MCPIP1 was higher in the portal fields and bile ducts in comparison to the liver parenchyma and central vein. The liver MCPIP1 protein level negatively correlated with hepatic steatosis but not with patient body mass index or any other analyte. The MCPIP1 level in PBMCs did not differ between NAFLD patients and control patients. Similarly, in patients’ PBMCs there were no differences in the expression of genes regulating β-oxidation (ACOX1, CPT1A, and ACC1) and inflammation (TNF, IL1B, IL6, IL8, IL10, and CCL2), or transcription factors controlling metabolism (FAS, LCN2, CEBPB, SREBP1, PPARA, and PPARG).

Conclusion:
We have demonstrated that MCPIP1 protein levels are reduced in NAFLD patients, but further research is needed to investigate the specific role of MCPIP1 in NAFL initiation and the transition to NASH.
Rates of employment after liver transplant: A nationwide cohort study
Authors: Henson Jacqueline B. , Cabezas Melanie , McElroy Lisa M. , Muir Andrew J. 
Published: February 2023

Background:
Employment outcomes after liver transplant (LT) over the past decade have not been described.

Methods:
LT recipients ages 18–65 from 2010-2018 were identified in Organ Procurement and Transplantation Network data. Employment within two years post-transplant was assessed.

Results:
Of 35,340 LT recipients, 34.2% were employed post-LT, including 70.4% who were working pre-transplant, compared to only 18.2% not working preLT. Younger age, male sex, educational attainment, and functional status were associated with returning to employment.

Conclusion:
Returning to employment is an important goal for many LT candidates and recipients, and these findings can be used to guide their expectations.
Copper deficiency is an independent risk factor for mortality in patients with advanced liver disease
Authors: Yu Lei , Yousuf Sarim , Yousuf Shahrukh , Yeh Jeffrey , Biggins Scott W. , Morishima Chihiro , Shyu Irene , O’Shea-Stone Galen , Eilers Brian , Waldum Annie , Copié Valérie , Burkhead Jason 
Published: February 2023

Background and Aim:
Copper is an essential trace metal serving as a cofactor in innate immunity, metabolism, and iron transport. We hypothesize that copper deficiency may influence survival in patients with cirrhosis through these pathways.

Methods:
We performed a retrospective cohort study involving 183 consecutive patients with cirrhosis or portal hypertension. Copper from blood and liver tissues was measured using inductively coupled plasma mass spectrometry. Polar metabolites were measured using nuclear magnetic resonance spectroscopy. Copper deficiency was defined by serum or plasma copper below 80 µg/dL for women or 70 µg/dL for men.

Results:
The prevalence of copper deficiency was 17% (N=31). Copper deficiency was associated with younger age, race, zinc and selenium deficiency, and higher infection rates (42% vs. 20%, p=0.01). Serum copper correlated positively with albumin, ceruloplasmin, hepatic copper, and negatively with IL-1β. Levels of polar metabolites involved in amino acids catabolism, mitochondrial transport of fatty acids, and gut microbial metabolism differed significantly according to copper deficiency status. During a median follow-up of 396 days, mortality was 22.6% in patients with copper deficiency compared with 10.5% in patients without. Liver transplantation rates were similar (32% vs. 30%). Cause-specific competing risk analysis showed that copper deficiency was associated with a significantly higher risk of death before transplantation after adjusting for age, sex, MELD-Na, and Karnofsky score (HR: 3.40, 95% CI, 1.18–9.82, p=0.023).

Conclusions:
In advanced cirrhosis, copper deficiency is relatively common and is associated with an increased infection risk, a distinctive metabolic profile, and an increased risk of death before transplantation.
Tyrosine kinase receptor B attenuates liver fibrosis by inhibiting TGF-β/SMAD signaling
Authors: Song Yu , Wei Jiayi , Li Rong , Fu Ruifeng , Han Pei , Wang Heming , Zhang Guangcong , Li Shuyu , Chen Sinuo , Liu Zhiyong , Zhao Yicheng , Zhu Changfeng , Zhu Jimin , Zhang Shuncai , Pei Hao , Cheng Jiefei , Wu Jian , Dong Ling , Song Guangqi , Shen Xizhong , Yao Qunyan 
Published: February 2023

Background and Aims:
Liver fibrosis is a leading indicator for increased mortality and long-term comorbidity in NASH. Activation of HSCs and excessive extracellular matrix production are the hallmarks of liver fibrogenesis. Tyrosine kinase receptor (TrkB) is a multifunctional receptor that participates in neurodegenerative disorders. However, paucity of literature is available about TrkB function in liver fibrosis. Herein, the regulatory network and therapeutic potential of TrkB were explored in the progression of hepatic fibrosis.

Methods and Results:
The protein level of TrkB was decreased in mouse models of CDAHFD feeding or carbon tetrachloride-induced hepatic fibrosis. TrkB suppressed TGF-β-stimulated proliferation and activation of HSCs in 3-dimensional liver spheroids and significantly repressed TGF-β/SMAD signaling pathway either in HSCs or in hepatocytes. The cytokine, TGF-β, boosted Nedd4 family interacting protein-1 (Ndfip1) expression, promoting the ubiquitination and degradation of TrkB through E3 ligase Nedd4-2. Moreover, carbon tetrachloride intoxication-induced hepatic fibrosis in mouse models was reduced by adeno-associated virus vector serotype 6 (AAV6)–mediated TrkB overexpression in HSCs. In addition, in murine models of CDAHFD feeding and Gubra-Amylin NASH (GAN), fibrogenesis was reduced by adeno-associated virus vector serotype 8 (AAV8)–mediated TrkB overexpression in hepatocytes.

Conclusion:
TGF-β stimulated TrkB degradation through E3 ligase Nedd4-2 in HSCs. TrkB overexpression inhibited the activation of TGF-β/SMAD signaling and alleviated the hepatic fibrosis both in vitro and in vivo. These findings demonstrate that TrkB could be a significant suppressor of hepatic fibrosis and confer a potential therapeutic target in hepatic fibrosis.
Operational nuclear research reactors in the Asia-Pacific with potential for medical radionuclide production
Authors: Tan Hun Yee , Wong Yin How , Kasbollah Azahari , Md Shah Mohammad Nazri , Perkins Alan Christopher , Yeong Chai Hong 
Published: February 2023

Personalised cancer treatment is of growing importance and can be achieved via targeted radionuclide therapy. Radionuclides with theranostic properties are proving to be clinically effective and are widely used because diagnostic imaging and therapy can be accomplished using a single formulation that avoids additional procedures and unnecessary radiation burden to the patient. For diagnostic imaging, single photon emission computed tomography (SPECT) or positron emission tomography (PET) is used to obtain functional information noninvasively by detecting the gamma (γ) rays emitted from the radionuclide. For therapeutics, high linear energy transfer (LET) radiations such as alpha (α), beta (β-) or Auger electrons are used to kill cancerous cells in close proximity, whereas sparing the normal tissues surrounding the malignant tumour cells.
One of the most important factors that lead to the sustainable development of nuclear medicine is the availability of functional radiopharmaceuticals. Nuclear research reactors play a vital role in the production of medical radionuclides for incorporation into clinical radiopharmaceuticals. The disruption of medical radionuclide supplies in recent years has highlighted the importance of ongoing research reactor operation. This article reviews the current status of operational nuclear research reactors in the Asia-Pacific region that have the potential for medical radionuclide production. It also discusses the different types of nuclear research reactors, their operating power, and the effects of thermal neutron flux in producing desirable radionuclides with high specific activity for clinical applications.
Wnt/β-catenin modulating drugs regulate somatostatin receptor expression and internalization of radiolabelled octreotide in neuroendocrine tumor cells
Authors: Weich Alexander , Rogoll Dorothea , Peschka Melissa , Weich Wolfgang , Pongracz Judit , Brand Markus , Fröhlich Matthias , Serfling Sebastian E. , Rowe Steven P. , Kosmala Aleksander , Reiter Florian P. , Meining Alexander , Werner Rudolf A. , Scheurlen Michael 
Published: February 2023

Background
Differentiated neuroendocrine tumors (NETs) express somatostatin receptors (SSTRs), targets for therapy with either unlabeled or radioactively labeled somatostatin analogs (SSA). Associated with worse prognosis, dedifferentiated NET loose SSTR expression, which may be linked to deregulation of Wnt/β-catenin signaling on an intracellular level. The aim of the present study was to investigate the effect of Wnt/β-catenin signaling pathway alterations on SSTR expression and its function in NET.

Methods
The NET cell lines BON-1 and QGP-1 were incubated with the Wnt-inhibitors 5-aza-2′-deoxycytidine (5-aza-CdR), Quercetin, or Niclosamide, or the Wnt activator lithium chloride (LiCl). Expression of SSTR1, SSTR2, and SSTR5 was determined by quantitative RT-PCR (qRT-PCR), immunocytomicroscopy and western blot. Changes in the Wnt pathway were analyzed by qRT-PCR of selected target genes and the TaqMan Array Human WNT Pathway. Receptor-associated function was determined by measuring the cellular uptake of [125I-Tyr3] octreotide.

Results
The mRNAs of SSTRs 1–5 were expressed in both cell lines. Wnt inhibitors caused downregulation of Wnt target genes, while 5-aza-CdR had the highest inhibitory effect. LiCl lead to an upregulation of Wnt genes, which was more marked in QGP-1 cells. SSTR expression increased in both cell lines upon Wnt inhibition. All three Wnt inhibitors lead to a marked increase in the specific uptake of [125I-Tyr3]octreotide, with 5-aza-CdR showing the greatest effect (increase by more than 50% in BON-1 cells), while a decreased uptake of [125I-Tyr3]octreotide was seen upon activation of Wnt signaling by LiCl.

Conclusions
We demonstrate here that Wnt signaling orchestrates SSTR expression and function in a preclinical NET model. Wnt inhibition increases [125I-Tyr3]octreotide uptake offering an opportunity to enhance the efficacy of SSTR-targeted theranostic approaches.
DECREASE IN THE PLATELET-TO-LYMPHOCYTE RATIO IN DAYS AFTER ADMISSION FOR SEPSIS CORRELATES WITH IN-HOSPITAL MORTALITY
Authors: Zheng Rui , Shi Yi-Yi , Pan Jing-Ye , Qian Song-Zan 
Published: February 2023

ABSTRACT

Background: A previous study has linked an increase in platelet-to-lymphocyte ratio (PLR) to a poor prognosis; however, the relationship between early change in PLR and outcomes in sepsis patients is unclear. Methods: The Medical Information Mart for Intensive Care IV database was for this retrospective cohort analysis on patients meeting the Sepsis-3 criteria. All the patients meet the Sepsis-3 criteria. The platelet-to-lymphocyte ratio (PLR) was calculated by dividing the platelet count by the lymphocyte count. We collected all PLR measurements that were available within 3 days of admission for analysis of longitudinal changes over time. Multivariable logistic regression analysis was used to determine the relationship between the baseline PLR and in-hospital mortality. After correcting for possible confounders, the generalized additive mixed model was used to examine the trends in PLR over time among survivors and nonsurvivors. Results: Finally, 3,303 patients were enrolled, and both low and high PLR levels were significantly associated with higher in-hospital mortality in the multiple logistic regression analysis (tertile 1: odds ratio, 1.240; 95% confidence interval, 0.981–1.568 and tertile 3: odds ratio, 1.410; 95% confidence interval, 1.120–1.776, respectively). The generalized additive mixed model results revealed that the PLR of the nonsurvival group declined faster than that of the survival group within 3 days after intensive care unit admission. After controlling for confounders, the difference between the two groups steadily decreased and increased by an average of 37.38 daily. Conclusions: There was a U-shaped relationship between the baseline PLR and in-hospital mortality of sepsis patients, and there was a significant difference between the nonsurvival and survival groups in the change in PLR over time. The early decrease in PLR was related to an increase in in-hospital mortality.
EARLY INITIATION OF RENAL REPLACEMENT THERAPY IN INTENSIVE CARE UNIT PATIENTS WITH BOTH ACUTE RESPIRATORY DISTRESS SYNDROME AND SEPSIS WITH OR WITHOUT RENAL FAILURE: A RETROSPECTIVE COHORT STUDY BASED ON PROPENSITY SCORE MATCHING
Authors: Li Ziping , Zhang Haoyue , Xie Keliang , Zhang Ying , Zhang Zhen , Zheng Weiqiang , Yang Tianqi , Zhang Linlin , Yu Yonghao 
Published: February 2023

ABSTRACT

Background: It is unknown whether early renal replacement therapy (RRT) initiation strategy in intensive care unit (ICU) patients with both acute respiratory distress syndrome (ARDS) and sepsis with or without renal failure is clinically beneficial. Patients and methods: A total of 818 patients with both ARDS and sepsis admitted to the ICU of Tianjin Medical University General Hospital were included in the analysis. Early RRT was defined as initiating the RRT strategy within 24 h of admission. The relationship between early RRT and clinical outcomes, including primary (30-day mortality) and secondary (90-day mortality, serum creatinine, Pao
2/Fio
2, duration of invasive mechanical ventilation, cumulative fluid output, and cumulative fluid balance) outcomes, was compared using propensity score matching (PSM). Results: A total of 277 patients (33.9% of the total population) underwent an early RRT initiation strategy before PSM. After PSM, a cohort of 147 patients with early RRT and 147 patients without early RRT with matched baseline characteristics (including serum creatinine at admission) were constructed. Early RRT was not significantly associated with 30- (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.85; P = 0.258) or 90-day mortality (HR, 1.30; 95% CI, 0.91–1.87, P = 0.150). At each time point within 72 h after admission, there was no significant difference in serum creatinine, Pao
2/Fio
2 and duration of mechanical ventilation between the early and the no early RRT groups. Early RRT significantly increased total output at all time points within 72 h of admission and reached a statistically significant negative fluid balance at 48 h. Conclusions: Early RRT initiation strategies had no statistically significant survival benefit in ICU patients with both ARDS and sepsis, with or without renal failure, nor did they significantly improve serum creatinine and oxygenation or shorten the duration of mechanical ventilation. The use and timing of RRT in such patients should be thoroughly investigated.
Bariatric Surgery and Suicide Risk in Patients With Obesity
Authors: Hung Anna , Maciejewski Matthew L. , Berkowitz Theodore S.Z. , Arterburn David E. , Mitchell James E. , Bradley Katharine A. , Kimbrel Nathan A. , Smith Valerie A. 
Published: February 2023

Objective:
In a large multisite cohort of Veterans who underwent Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy, we compared the 5-year suicidal ideation and attempt rates with matched nonsurgical controls.

Background:
Bariatric surgery has significant health benefits but has also been associated with adverse mental health outcomes.

Methods:
Five-year rates of suicidal ideation and suicide attempts of Veterans who underwent Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy from the fiscal year 2000–2016 to matched nonsurgical controls using sequential stratification using cumulative incidence functions (ideation cohort: n=38,199; attempt cohort: n=38,661 after excluding patients with past-year outcome events). Adjusted differences in suicidal ideation and suicide attempts were estimated using a Cox regression with a robust sandwich variance estimator.

Results:
In the matched cohorts for suicidal ideation analyses, the mean age was 53.47 years and the majority were males (78.7%) and White (77.7%). Over 40% were treated for depression (41.8%), had a nonrecent depression diagnosis (40.9%), and 4.1% had past suicidal ideation or suicide attempts >1 year before index. Characteristics of the suicide attempt cohort were similar. Regression results found that risk of suicidal ideation was significantly higher for surgical patients (adjusted hazard ratio=1.21, 95% CI: 1.03–1.41), as was risk of suicide attempt (adjusted hazard ratio=1.62, 95% CI: 1.22–2.15).

Conclusions:
Bariatric surgery appears to be associated with a greater risk of suicidal ideation and attempts than nonsurgical treatment of patients with severe obesity, suggesting that patients need careful monitoring for suicidal ideation and additional psychological support after bariatric surgery.
Understanding Disparities in Receipt of Complex Gastrointestinal Cancer Surgery at a Small Geographic Scale
Authors: Dong Weichuan , Kucmanic Matthew , Winter Jordan , Pronovost Peter , Rose Johnie , Kim Uriel , Koroukian Siran M. , Hoehn Richard 
Published: February 2023

Objective:
To define neighborhood-level disparities in the receipt of complex cancer surgery.

Background:
Little is known about the geographic variation of receipt of surgery among patients with complex gastrointestinal (GI) cancers, especially at a small geographic scale.

Methods:
This study included individuals diagnosed with 5 invasive, nonmetastatic, complex GI cancers (esophagus, stomach, pancreas, bile ducts, liver) from the Ohio Cancer Incidence Surveillance System during 2009 and 2018. To preserve patient privacy, we combined US census tracts into the smallest geographic areas that included a minimum number of surgery cases (n=11) using the Max-p-regions method and called these new areas “MaxTracts.” Age-adjusted surgery rates were calculated for MaxTracts, and the Hot Spot analysis identified clusters of high and low surgery rates. US Census and CDC PLACES were used to compare neighborhood characteristics between the high- and low-surgery clusters.

Results:
This study included 33,091 individuals with complex GI cancers located in 1006 MaxTracts throughout Ohio. The proportion in each MaxTract receiving surgery ranged from 20.7% to 92.3% with a median (interquartile range) of 48.9% (42.4–56.3). Low-surgery clusters were mostly in urban cores and the Appalachian region, whereas high-surgery clusters were mostly in suburbs. Low-surgery clusters differed from high-surgery clusters in several ways, including higher rates of poverty (23% vs. 12%), fewer married households (40% vs. 50%), and more tobacco use (25% vs. 19%; all P<0.01).

Conclusions:
This improved understanding of neighborhood-level variation in receipt of potentially curative surgery will guide future outreach and community-based interventions to reduce treatment disparities. Similar methods can be used to target other treatment phases and other cancers.
Racial/Ethnic Disparities in Youth Mental Health Traits and Diagnoses within a Community-based Sample
Authors: Dissanayake Andrew , Dupuis Annie , Burton Christie , Soreni Noam , Peters Paul , Gajaria Amy , Arnold Paul D. , Crosbie Jennifer , Schachar Russell 
Published: February 2023

ABSTRACTBackgroundRacial/ethnic disparities in the prevalence of mental health diagnoses have been reported but have not accounted for the prevalence of the traits that underlies these disorders. Examining rates of diagnoses in relation to traits may yield a clearer understanding of how racial/ethnic youth differ in their access to assessment and care. We sought to examine differences in self/parent-reported rates of diagnoses for obsessive-compulsive disorder (OCD), attention-deficit/ hyperactivity disorder (ADHD), and anxiety disorders after adjusting for differences in trait levels between youth from three racial/ethnic groups: White, South Asian, and East Asian.MethodsWe collected parent or self-reported ratings of OCD, ADHD and anxiety traits and diagnoses for youth (6-17 years) from a general population sample (Spit for Science). We examined racial/ethnic differences in trait levels and the odds of reporting a diagnosis using mixed-effects linear models and logistic regression models.ResultsEast Asian (N = 1301) and South Asian (N = 730) youth reported significantly higher levels of OCD and anxiety traits than White youth (N = 6896). Given the same trait level, East Asian and South Asian youth had significantly lower odds of reporting a diagnosis for OCD (Odds Ratio (OR)East Asian= 0.08 [0.02, 0.41] ; ORSouth Asian= 0.05 [0.00, 0.81]), ADHD (OREast Asian= 0.27 [0.16, 0.45]; ORSouth Asian= 0.09 [0.03, 0.30]), and Anxiety (OREast Asian= 0.21 [0.11, 0.39]; ORSouth Asian= 0.12 [0.05, 0.32]) than White youth.ConclusionsThese results suggest a discrepancy between traits-levels of OCD and anxiety and rates of diagnoses for East Asian and South Asian youth. This discrepancy may be due to increased barriers for ethnically diverse youth to access mental health care. Efforts to understand racial/ethnic barriers to care are needed.Key PointsDespite having lower prevalence of diagnoses, East and South Asian youth reported significantly higher anxiety and OCD trait levels than White youthGiven the same trait level, East Asian youth were at 92% lower odds of having received an OCD diagnosis, 73% lower odds of having received an ADHD diagnosis, and 79% lower odds of having received an Anxiety diagnosis than White youthGiven the same trait level, South Asian youth were at 95% lower odds of having received an OCD diagnosis, 91% lower odds of having received an ADHD diagnosis, and 88% lower odds of having received an anxiety diagnosisFuture research is needed to understand barriers to mental health care and assessment that may underly the discrepancy between mental health traits and diagnoses for ethnic/racially diverse youth.