bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll-like receptor 2 activation in monocytes contributes to systemic inflammation and alcohol-associated liver disease in humans
Authors: Maccioni Luca , Kasavuli Joyce , Leclercq Sophie , Pirlot Boris , Laloux Géraldine , Horsmans Yves , Leclercq Isabelle , Schnabl Bernd , Stärkel Peter 
Published: April 2023

Background and Rationale:
In the context of gut leakiness and translocation of microbial products in alcohol-associated liver disease (ALD), it is possible that systemic and liver inflammation involve the activation of circulating monocyte through gut-derived factors. We explored the association between monocytes, microbial translocation, systemic inflammation, and ALD.

Methods:
Patients with alcohol use disorder following a rehabilitation program were compared with healthy controls. We determined the circulating number and proportion of monocyte subsets by FACS. The activation of signaling pathways by gut-derived microbes was analyzed by quantitative PCR in isolated monocytes. Cytokines secretion by monocytes and phagocytosis were assessed in vitro. Serum microbial translocation markers and cytokines were measured by ELISA and multiplex assay, respectively. ALD severity and liver inflammatory responses were analyzed in liver biopsies by various methods.

Results:
In patients with alcohol use disorder, the number of blood monocytes increased compared with controls. Monocytes from patients with alcohol use disorder upregulated IL-1β and IL-8 together with toll-like receptor 2 and downstream AP-1, while fungal sensor CARD9 was downregulated. IL-1β and IL-8 were actively secreted upon stimulation in vitro with the toll-like receptor 2 ligand peptidoglycan. Exposure with Escherichia coli confirmed preserved bacterial phagocytic activity. In contrast, Candida albicans stimulation leads to downregulation of IL-1β and TNFα compared with controls. Systemic cytokines and monocyte changes correlated with microbial translocation. Hepatic IL-1β and IL-8 increased with ALD severity together with liver macrophage activation and upregulation of chemokines involved in monocyte attraction.

Conclusions:
Our results point to the contribution of activated monocytes to systemic inflammation and ALD. Monocytes likely infiltrate the liver, transform into monocyte-derived macrophages and release IL-1β and IL-8 in response to peptidoglycan and toll-like receptor 2 activation.
Low vitamin A levels are associated with liver-related mortality: a nationally representative cohort study
Authors: Song Jiunn , Jiang Z. Gordon 
Published: April 2023

Introduction:
Vitamin A, a fat-soluble vitamin that includes retinol and carotenoids, is implicated in liver fibrosis, whereas its deficiency has been associated with various liver diseases and higher overall mortality. This study aims to determine the relationship between levels of vitamin A species and liver fibrosis, as well as liver-related mortality in the population of the US.

Methods:
A total of 12,299 participants from the National Health and Nutrition Examination Survey III (NHANES III) were analyzed to provide nationally representative estimates of the relationship between the levels of vitamin A species and liver fibrosis measured by Fibrosis-4 (FIB-4) index and liver-related mortality.

Results:
A low blood level of retinol, but not other retinoid derivatives, was associated with significant liver fibrosis after adjustment for demographics, anthropometric measurements, medical history, retinol, and carotene intakes. Compared with vitamin D and E, retinol deficiency demonstrated much stronger associations with a high FIB-4 score. Individuals with known risks of chronic liver disease (CLD) and the lowest pentile of retinol levels had ORs of 3.12 (95% CI, 1.64–5.91) for possible fibrosis and 19.7 (95% CI, 5.71–67.7) for likely fibrosis, and an HR of 7.76 (95% CI, 1.19–50.5) for liver-related mortality compared with those in the highest retinol-level pentile. These relationships were more pronounced among individuals with known risks of chronic liver disease than without.

Conclusions:
A low circulating retinol level is associated with liver fibrosis and liver-related mortality in chronic liver disease. This relationship is potentially driven by a mechanistic link rather than the malabsorption of fat-soluble vitamins and may be leveraged for disease prognostication and have therapeutic implications.
Patient survey augments detection of harmful alcohol relapse after liver transplant for alcohol-associated cirrhosis
Authors: Rice Brooke A. , Mehta Neil , Grab Joshua , Dodge Jennifer L. , Sherman Courtney B. 
Published: April 2023

Background:
Predicting the risk of alcohol relapse after a liver transplant for alcohol-associated liver disease is critical to guide candidate selection and optimize alcohol use disorder management. We aimed to use patient survey to augment the detection of alcohol relapse and its risk factors and to understand patient perceptions of the importance of alcohol abstinence.

Methods:
In this retrospective cohort study, we used a telephone survey and chart review to assess the incidence of post-transplant harmful alcohol relapse, risk factors, and long-term outcomes for patients transplanted for alcohol-associated cirrhosis at our center from 2002 to 2016.

Results:
Over the median follow-up of 5.9 years, 20.4% relapsed, with 9.3% harmful relapse after median of 4.0 years. The survey response rate was 44.0% (n=110). Of survey responders, 44.3% did not recall discussing alcohol in post-transplant clinics, and 17.6% of relapses were identified by the survey alone. In univariate analysis, shorter pretransplant sobriety (OR: 0.96 per month, p=0.02) and history of pretransplant relapse (OR: 2.99, p=0.02) were associated with post-transplant harmful relapse. After adjusting for these factors, High-risk Alcoholism Relapse score ≥4 predicted harmful relapse (OR: 3.43, p=0.049). A total of 27.3% of patients with both pretransplant relapse and High-risk Alcoholism Relapse score ≥4 relapsed to harmful use compared with 5.2% of those with 1 or neither risk factor (p < 0.001). Harmful relapse was associated with increased graft loss (30.4% vs. 17.4%) and inferior 10-year post–liver transplant survival (61.5% vs. 80.7%).

Conclusions:
Incorporating patient survey data allowed the detection of relapses otherwise unreported to clinicians, highlighting the need for novel strategies to detect relapse. Utilizing this augmented data, we identified pretransplant sobriety length, pretransplant relapse, and High-risk Alcoholism Relapse score ≥4 as risk factors that should be evaluated pretransplant to guide candidate selection and peritransplant alcohol use disorder management.
Single-cell transcriptome analysis revealed the immune profile of PD-1 blockade in gallbladder carcinoma liver metastasis
Authors: Xie Lin , Ning Zhouyu , Hua Yongqiang , Wang Peng , Meng Zhiqiang 
Published: April 2023

Background:
Gallbladder carcinoma is the most common cancer of the biliary tract, and the immune checkpoint blockade showed promising efficacy in the treatment of advanced gallbladder carcinoma. However, the underlying mechanisms remain unknown.

Methods:
Single-cell RNA sequencing was used to reveal immune cell dynamics in an anti-PD-1 responder with gallbladder carcinoma liver metastases. Gene set variation analysis, pseudotime analysis, single-cell regulatory network inference and clustering analysis, and CellChat analysis were used to identify the functions of each cell cluster. Immunohistochemistry and multicolored immunohistochemistry analysis were applied to confirm the intratumoral cell types, and the prognostic value of CXCL13+CD8+T cells in patients with gallbladder carcinoma liver metastases with immunotherapy was evaluated. Four biliary tract carcinoma and 3 immunotherapy bulk RNA-seq datasets were analyzed to investigate the prognostic value of CXCL13+CD8+T cells and SPP1+TAMs.

Result:
A total of 19,648 high-quality single-cell transcriptome data were obtained from liver metastasis before and after aPD-1 therapy. We discovered improved cytotoxic activity in CD8+T cells and enhanced proinflammatory phenotypes in myeloid cells. The identified SPP1+TAMs were related to poor prognosis. The increased effector/memory T cells represented characteristics similar to exhausted T cells in transitory status after aPD-1therapy, which may play a crucial role in the antitumor immune response. We further revealed that CXCL13+T cells in a high subtype of biliary tract carcinoma were characterized as a ‘hot tumor’ profile with high immune scores, correlated to the immunostimulatory context with favorable survival, and can predict effective responses to immunotherapy.

Conclusions:
Our study provided an overview of immune cell dynamics in gallbladder carcinoma liver metastases after aPD-1 treatment and highlighted the importance of CXCL13+T cells in biliary tract carcinoma and effective responses to immunotherapy, which would advance the understanding and treatment of the disease.
SULT2B1-CS-DOCK2 axis regulates effector T-cell exhaustion in HCC microenvironment
Authors: Wang Shuai , Wang Rui , Xu Nan , Wei Xuyong , Yang Yijie , Lian Zhengxing , Cen Beini , Shen Chenchen , Li Wangyao , Wang Jianguo , Zhang Zhensheng , Tang Linsong , Wei Qiang , Lu Di , Xu Xiao 
Published: April 2023

Background and Aims:
HCC is a malignant disease. Compared with tyrosine kinase inhibitors (the classical therapy), immune checkpoint inhibitors are more effective in the treatment of HCC, despite their limited efficacy. Among these restricted factors, exhaustion of tumor-infiltrated lymphocytes, especially CD8+ T cells, is a core event. We aimed to determine the key factors contributing to CD8+ T-cell infiltration in HCC and investigate the underlying mechanisms.

Approach and Results:
Using machine learning and multiplex immunohistochemistry analysis, we showed that dedicator of cytokinesis protein 2 (DOCK2) was a potential indicator of infiltrated CD8+ T cells in HCC. Using RNA sequencing, flow cytometry analysis, and mouse HCC models, we demonstrated that DOCK2 inactivation accounted for infiltrated CD8+ T-cell exhaustion in tumors. Using quasi-targeted metabolomics, mass spectrum, and mass cytometry by time of flight analysis, we found that cholesterol sulfate synthesized by sulfotransferase 2B1 in tumor cells suppressed DOCK2 enzymatic activity of T cells. Through virtual screening, molecular docking simulation, and experiments validation, we demonstrated that tolazamide reversed DOCK2 inactivation-mediated CD8+ T-cell exhaustion and enhanced anti–programmed death-ligand 1 antibody+apatinib immunotherapeutic effects on HCC.

Conclusions:
This study indicates that DOCK2 controls CD8+ T-cell infiltration in HCC, and cholesterol sulfate synthesized by sulfotransferase 2B1 in tumor cells promotes effector T-cell exhaustion. The findings suggest that the usage of conventional drugs affects immunotherapy efficacy in HCC patients.
SGLT2i reduces risk of developing HCC in patients with co-existing type 2 diabetes and hepatitis B infection: A territory-wide cohort study in Hong Kong
Authors: Lee Chi-Ho , Mak Lung-Yi , Tang Eric Ho-Man , Lui David Tak-Wai , Mak Jimmy Ho-Cheung , Li Lanlan , Wu Tingting , Chan Wing Lok , Yuen Man-Fung , Lam Karen Siu-Ling , Wong Carlos King Ho 
Published: April 2023

Background and Aims:
Type 2 diabetes (T2D) and chronic hepatitis B infection (CHB) are risk factors of HCC. Sodium glucose co-transporter 2 inhibitors (SGLT2i) inhibit HCC oncogenesis in preclinical studies. However, clinical studies are lacking. This study aimed to evaluate the impact of SGLT2i use on incident HCC using a territory-wide cohort of exclusively patients with co-existing T2D and CHB.

Approach and Results:
Patients with co-existing T2D and CHB between 2015 and 2020 were identified from the representative electronic database of the Hong Kong Hospital Authority. Patients with and without SGLT2i use were 1:1 matched by propensity score for their demographics, biochemistry results, liver-related characteristics, and background medications. Cox proportional hazards regression model was used to assess the association between SGLT2i use and incident HCC. A total of 2,000 patients with co-existing T2D and CHB (1,000 in each SGLT2i and non-SGLT2i group; 79.7% on anti-HBV therapy at baseline) were included after propensity-score matching. Over a follow-up of 3,704 person-years, the incidence rates of HCC were 1.39 and 2.52 cases per 100 person-year in SGLT2i and non-SGLT2i groups, respectively. SGLT2i use was associated with a significantly lower risk of incident HCC (HR 0.54, 95%CI: 0.33-0.88, p=0.013). The association remained similar regardless of sex, age, glycemic control, diabetes duration, presence of cirrhosis and hepatic steatosis, timing of anti-HBV therapy, and background antidiabetic agents including dipeptidyl peptidase-4 inhibitors, insulin, or glitazones (all p interaction>0.05).

Conclusions:
Among patients with co-existing T2D and CHB, SGLT2i use was associated with a lower risk of incident HCC.
No effect of social interaction on experimental pain sensitivity: a randomized experimental study
Authors: Nim Casper Glissmann , Ravn Sophie Lykkegaard , Andersen Tonny E. , Engelsholm Emma , Hestbech Fie , Hvidkær Inge S. , Traidl Amanda N. , O'Neill Søren 
Published: April 2023

AbstractQuantitative sensory testing (QST) is a commonly applied paradigm to investigate pain, which is a subjective experience influenced by a myriad of social and contextual factors. Therefore, it is important to consider the potential sensitivity of QST to the test setting and the social interaction that naturally is a part of it. This may particularly be the case in clinical settings where patients have something at stake. Therefore, we investigated differences in pain responses using QST in different test setups with varying degrees of human interaction. In a parallel three-armed randomized experimental study, we included 92 participants with low back pain and 87 healthy volunteers allocated to 1 of the 3 QST setups: 1 setup with manual tests performed by a human tester, 1 setup with automated tests performed by a robot and orally guided by a human tester, and 1 setup with automated tests performed solely by a robot without social interaction with a human tester. All 3 setups consisted of the same pain tests in the same order, including pressure pain threshold and cold pressor tests. We found no statistically significant differences between setups on the primary outcome of conditioned pain modulation nor any secondary QST outcomes. While this study is not without limitations, the results indicate that QST procedures are robust enough not to be influenced by social interaction to an appreciable degree.
Risk of Two Sport-Related Concussions in the Same Year: Is the Second Concussion Worse?
Authors: Williams Kristen , Zeoli Tyler , Allen Jackson H. , Jo Jacob , Yengo-Kahn Aaron M. , Terry Douglas P. , Zuckerman Scott L. 
Published: April 2023

Objectives:(
1) Evaluate the frequency of same-year, repeat concussions; (2) assess predictors of sustaining a repeat concussion; and (3) compare outcomes of athletes with repeat concussions with athletes with single concussion.

Design:
A retrospective, case–control study.

Setting:
Regional sports concussion center.

Patients:
Adolescents sustaining a sport-related concussions (SRC) from November 2017 to October 2020.

Independent Variables:
Participants were dichotomized into 2 groups: (1) athletes with a single concussion; and (2) athletes with repeat concussions.

Main Outcome Measures:
Between group and within group analyses were completed to look for differences in demographics, personal and family history, concussion history, and recovery metrics between the 2 groups.

Results:
Of 834 athletes with an SRC, 56 (6.7%) sustained a repeat concussion and 778 (93.3%) had a single concussion. Between group: Personal history of migraines (19.6% vs 9.5%, χ2 = 5.795, P = 0.02), family history of migraines (37.5% vs 24.5%, χ2 = 4.621, P = 0.03), and family history of psychiatric disorders (25% vs 13.1%, χ2 = 6.224, P = 0.01) were significant predictors of sustaining a repeat concussion. Within group: Among those with a repeat concussion, initial symptom severity was greater (Z = −2.422; P = 0.02) during the repeat concussion and amnesia was more common (χ2 = 4.775, P = 0.03) after the initial concussion.

Conclusions:
In a single-center study of 834 athletes, 6.7% suffered a same-year, repeat concussion. Risk factors included personal/family migraine history and family psychiatric history. For athletes with repeat concussions, initial symptom score was higher after the second concussion, yet amnesia was more common after the initial concussion.
Dietary supplementation with resistant starch contributes to intestinal health
Authors: Wen Jia-jia , Li Ming-zhi , Nie Shao-Ping 
Published: April 2023

Purpose of review
Resistant starch has received much attention recently as a healthy carbohydrate component of the diet. Resistant starch is not digested in the small intestine and can thus affect the gut microbiota of the host because of its fermentability. This review summarizes the interactions along the resistant starch–gut microbiota–host axis to help understand the health effects of resistant starch.

Recent findings
Recent studies indicate that resistant starch can be a helpful dietary component for special disease states like diabetes, metabolic syndrome, chronic kidney disease, constipation, and colitis. Its health effects are associated with modulation of the gut microbiota, and with gut microbes converting resistant starch into active and bioavailable metabolites that promote intestinal health.

Summary
The results from human clinical trials and studies in animal models indicate that supplementation of the diet with resistant starch in different metabolic diseases help remodel gut microbiota, especially increasing short-chain fatty acid (SCFA)-producing bacteria, and produce bioactive metabolites like SCFA, bile acids, and amino acids responsible for a variety of health effects. The gut microbiota and microbial metabolites probably mediate the effects of resistant starch on intestinal health.
A systematic review and meta-analysis of retrograde type A aortic dissection after thoracic endovascular aortic repair in patients with type B aortic dissection
Authors: Ali-Hasan-Al-Saegh Sadeq , Halloum Nancy , Scali Salvatore , Kriege Marc , Abualia Mohannad , Stamenovic Davor , Bashar Izzat Mohammad , Bohan Patrick , Kloeckner Roman , Oezkur Mehmet , Dorweiler Bernhard , Treede Hendrik , El Beyrouti Hazem 
Published: April 2023

Background:
Retrograde type A dissection (RTAD) is a devastating complication of thoracic endovascular repair (TEVAR) with low incidence but high mortality. The objective of this study is to report the incidence, mortality, potential risk factors, clinical manifestation and diagnostic modalities, and medical and surgical treatments.

Methods:
A systematic review and single-arm and two-arm meta-analyses evaluated all published reports of RTAD post-TEVAR through January 2021. All study types were included, except study protocols and animal studies, without time restrictions. Outcomes of interest were procedural data (implanted stent-grafts type, and proximal stent-graft oversizing), the incidence of RTAD, associated mortality rate, clinical manifestations, diagnostic workouts and therapeutic management.

Results:
RTAD occurred in 285 out of 10,600 patients: an estimated RTAD incidence of 2.3% (95% CI: 1.9–2.8); incidence of early RTAD was approximately 1.8 times higher than late. Wilcoxon signed-rank testing showed that the proportion of RTAD patients with acute type B aortic dissection (TBAD) was significantly higher than those with chronic TBAD (P = .008). Pooled meta-analysis showed that the incidence of RTAD with proximal bare stent TEVAR was 2.1-fold higher than with non-bare stents: risk ratio was 1.55 (95% CI: 0.87–2.75; P = .13). Single arm meta-analysis estimated a mortality rate of 42.2% (95% CI: 32.5–51.8), with an I
2 heterogeneity of 70.11% (P < .001).

Conclusion:
RTAD is rare after TEVAR but with high mortality, especially in the first month post-TEVAR with acute TBAD patients at greater risk as well as those treated with proximal bare stent endografts.
Comparison the efficacy of amiodarone and lidocaine for cardiac arrest: A network meta-analysis
Authors: Wang Qi , Lin Zhen , Chen Hairong , Pan Biyun 
Published: April 2023

Background:
There is no evidence that antiarrhythmic drugs can improve long-term survival or survival with favorable neurological outcomes in cardiac arrest patients. We did this network meta-analysis to comprehensively compare the efficacy of various antiarrhythmic drugs for cardiac arrest patients.

Methods:
We searched studies from inception until Nov 11, 2022 through PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, and Wanfang database. All studies comparing different antiarrhythmic drugs for cardiac arrest were included in this meta-analysis. Outcomes were survival to hospital discharge in cardiac arrest, survival to hospital admission/24 h and favorable neurological outcome. This network meta-analysis was performed by R software.

Results:
Finally, a total of 9 studies (10,980 patients) were finally included in this network meta-analysis. Amiodarone (odd ratio [OR] 2.28, 95% credibility interval [CrI] 1.61–3.27) and lidocaine (OR 1.53, 95% CrI 1.05–2.25) was superior than placebo in terms of the survival to hospital admission/24 h with statistically significant. Amiodarone (OR 2.19, 95% CrI 1.54–3.14) and lidocaine (OR 1.58, 95% CrI 1.09–2.32) was superior than placebo in terms of the survival to hospital discharge with statistically significant. Amiodarone (OR 2.43, 95% CrI 1.61–3.68) and lidocaine (OR 1.62, 95% CrI 1.04–2.53) was superior than placebo in terms of the favorable neurological outcome with statistically significant. The surface under the cumulative ranking (SUCRA) shows that amiodarone ranked first (SUCRA, 99.6%), lidocaine ranked second (SUCRA, 49.6%), placebo ranked the last (SUCRA, 0.86%). Inverted funnel plot is essentially symmetrical, it is possible that this study has a small sample effect or a small publication bias.

Conclusions:
Amiodarone had the best effect on both survival to hospital admission, discharge and more favorable neurological outcome. Thus, amiodarone should be listed as first line drug for cardiac arrest. However, the quality of available evidence limits the formation of powerful conclusions regarding the comparative efficacy or safety of amiodarone or lidocaine used to treat cardiac arrest. Higher-quality randomized controlled trials are required for further research in future.
Pseudophakic pupillary block after reverse sulcus intraocular lens implantation: A case report
Authors: Funarunart Panrapee , Treesit Isaraporn 
Published: April 2023

Introduction:
Reverse sulcus intraocular lens (IOL) implantation can cause serious ophthalmic complications. Even routine ocular examinations can provoke significant consequences. Herein, we present a case of recurrent pupillary capture and pseudophakic pupillary block related to reverse sulcus IOL implantation.

Case report:
A 44-year-old man developed a pseudophakic pupillary block after pupil dilation aimed at relieving pupillary capture in an undetected reverse position of the sulcus IOL. The pupillary block was successfully treated with 2% pilocarpine and laser peripheral iridotomywas performed to prevent recurrence. The patient experienced recurrent pupillary capture with decreased vision in the affected eye. IOL exchange was the definite treatment resulting in improved vision and proper positioning of the IOL.

Conclusions and importance:
When the reverse position of sulcus IOL is detected postoperatively, prophylactic laser peripheral iridotomy should be considered to prevent pupillary block particularly when pupillary capture is present. Pharmacologic pupillary dilation should be performed cautiously. Recurrent pupillary capture is possible and IOL repositioning should be considered to prevent further complications.