bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPASS: deCOMPressing stomA and two-Stage elective resection vs. emergency reSection in patients with left-sided obstructive colon cancer
Authors: Pecqueux Mathieu , Distler Marius , Radulova-Mauersberger Olga , Neckmann Ulrike , Korn Sandra , Praetorius Christian , Fritzmann Johannes , Klimova Anna , Weitz Jürgen , Kahlert Christoph
Published: October 2023

Background

Colorectal cancer stands as a prevalent cause of cancer-related mortality, necessitating effective treatment strategies. Acute colonic obstruction occurs in approximately 20% of patients and represents a surgical emergency with substantial morbidity and mortality. The optimal approach for managing left-sided colon cancer with acute colonic obstruction remains debatable, with no consensus on whether emergency resection or bridge-to-surgery, involving initial decompressing stoma and subsequent elective resection after recovery, should be employed. Current studies show a decrease in morbidity and short-term mortality for the bridge-to-surgery approach, yet it remains unclear if the long-term oncological outcome is equivalent to emergency resection.

Methods

This prospective, randomized, multicenter trial aims to investigate the management of obstructive left-sided colon cancer in a comprehensive manner. The study will be conducted across 26 university hospitals and 40 academic hospitals in Germany. A total of 468 patients will be enrolled, providing a cohort of 420 evaluable patients, with an equal distribution of 210 patients in each treatment arm. Patients with left-sided colon cancer, defined as cancer between the left splenic flexure and > 12 cm ab ano and obstruction confirmed by X-ray or CT scan, are eligible. Randomization will be performed in a 1:1 ratio, assigning patients either to the oncological emergency resection group or the bridge-to-surgery group, wherein patients will undergo diverting stoma and subsequent elective oncological resection after recovery. The primary endpoint of this trial will be 120-day mortality, allowing for consideration of the time interval between diverting stoma and resection.

Discussion

The findings derived from this trial possess the potential to reshape the current clinical approach of emergency resection for obstructive left-sided colon cancer by favoring the bridge-to-surgery practice, provided that a reduction in morbidity can be achieved without compromising the oncological long-term outcome.

Trial registration

German Clinical Trials Register (DRKS) under the identifier DRKS00031827. Registered on May 15, 2023.

Protocol: 28.04.2023, protocol version 2.0F.
Assessment of anti-malondialdehyde-acetaldehyde antibody frequencies in rheumatoid arthritis with new data from two independent cohorts, meta-analysis, and meta-regression
Authors: Rodriguez-Martinez Lorena , García-Moreno Cristina , Perez-Pampin Eva , Gómara María J. , Sarmiento-Monroy Juan C. , Lopez-Golán Yolanda , Gómez-Puerta José A. , Mera-Varela Antonio , Conde Carmen , Sanmartí Raimon , Haro Isabel , González Antonio
Published: October 2023

Background

Autoantibodies are critical elements in RA pathogenesis and clinical assessment. The anti-malondialdehyde-acetaldehyde (anti-MAA) antibodies are potentially useful because of their claimed high sensitivity for all RA patients, including those lacking RF and anti-CCP antibodies. Therefore, we aimed to replicate these findings.

Methods

We independently attempted replication in Santiago and Barcelona using sera from 517 and 178 RA patients and 272 and 120 healthy controls, respectively. ELISA protocols for anti-MAA antibodies included five antigens (human serum albumin in three formulations, fibrinogen, and a synthetic peptide) and assays for the IgG, IgM, and IgA isotypes. We integrated our results with information found by searching the Web of Science for reports of anti-MAA antibodies in RA. The available patients (4989 in 11 sets) were included in a meta-analysis aimed at heterogeneity between studies. Factors accounting for heterogeneity were assessed with meta-regression.

Results

The sensitivity of anti-MAA antibodies in our RA patients was low, even in seropositive patients, with the percentage of positives below 23% for all ELISA conditions. Our results and bibliographic research showed IgG anti-MAA positive patients ranging from 6 to 92%. The extreme between-studies heterogeneity could be explained (up to 43%) in univariate analysis by sex, African ethnicity, the site of study, or recruitment from the military. The best model, including African ancestry and smoking, explained a high heterogeneity fraction (74%).

Conclusion

Anti-MAA antibody sensitivity is extremely variable between RA patient collections. A substantial fraction of this variability cannot be attributed to ELISA protocols. On the contrary, heterogeneity is determined by complex factors that include African ethnicity, smoking, and sex.
A comparison of misoprostol with and without methylergometrine and oxytocin in outpatient medical abortion: a phase III randomized controlled trial
Authors: Jahromi Athar Rasekh , Rahmanian Vahid , Taghizadeh Hajar , Zareibabaarabi Zahra
Published: October 2023

Objective

The complications associated with miscarriages have surfaced as a major concern in maintaining women’s physical and mental health. The present study evaluated the efficacy of three medication regimes for the complete expulsion of retained intrauterine tissues in patients who underwent a miscarriage.

Methods

In this randomized clinical trial, 90 patients participated with their gestational age below 12 weeks, each having undergone a recent miscarriage. After being screened for underlying diseases and coagulative blood disorders, they were randomly allocated into three groups. For the first group, labeled as the control group, misoprostol was administered alone. In contrast, the combination of misoprostol plus methylergometrine and misoprostol plus oxytocin was prescribed for the second and third groups, respectively. Further, the data obtained were analyzed by descriptive and inferential statistics using Stata software version 14.

Results

The mean age of participants and gestational age were 29.76 ± 5.53 years and 8.23 ± 2.29 weeks, respectively. There was no significant difference between the three treatment groups regarding the amount of bleeding after the abortion(P = 0.627). Regarding pain severity, the group that received Misoprostol plus Methylergometrine had less pain intensity than the other two groups(p = 0.004). The mean rate of RPOC expulsion was in the Misoprostol plus Oxytocin (9.68 ± 10.36) group, Misoprostol plus Methylergometrine (11.73 ± 12.86), and Misoprostol groups (19.07 ± 14.31)(p = 0.013). The success rate in outpatient medical abortion in the misoprostol plus oxytocin and misoprostol plus methylergonovine group was 93.33%, but in patients treated by misoprostol alone was 83.33%.

Conclusion

The effectiveness of the drugs in the two drug groups combined with oxytocin and methylergometrine is higher than the misoprostol group alone. An outpatient approach was deemed more satisfactory against surgical maneuvers and hospitalizations by patients since family support influenced their pain coping mechanism.

Trial registration

The trial was registered in the Iranian registry of clinical trials on 04/10/2019. (https://fa.irct.ir/trial/34519; registration number: IRCT20150407021653N19).
The expression of matrix metalloproteinase 2, 9 and 11 in Ethiopian breast cancer patients
Authors: Belachew Esmael Besufikad , Desta Adey Feleke , Deneke Dinikisira Bekele , Gebremariam Tewodros Yalew , Tefera Dessalegn Abeje , Atire Fikadu Alemu , Alemayehu Dawit Hailu , Seyoum Tamirayehu , Bauer Marcus , Girma Selfu , Sewasew Dareskedar Tsehay , Kantelhardt Eva J. , Tessema Tesfaye Sisay , Howe Rawleigh
Published: October 2023

Introduction

Matrix metalloproteinases (MMPs) play a pathophysiological role in cancer initiation and progression. Numerous studies have examined an association between MMP-2, MMP-9, and MMP-11 expression and clinicopathological characteristics of breast cancer (BC); however, no research has been done on the MMP expression levels in BC cases from Ethiopia.

Materials and methods

A total of 58 formalin-fixed paraffin-embedded breast tissue samples encompassing 16 benign breast tumors and 42 BC were collected. The RNA was extracted and quantitative reverse-transcription PCR was performed. GraphPad Prism version 8.0.0 was used for statistical analysis.

Results

The MMP-11 expression levels were significantly higher in breast cancer cases than in benign breast tumors (P = 0.012). Additionally, BC cases with positive lymph nodes and ER-positive receptors had higher MMP-11, MMP-9, and MMP-2 expression than cases with negative lymph nodes and ER-negative, respectively. The MMP-11 and MMP-9 expressions were higher in grade III and luminal A-like tumors than in grade I-II and other subtypes, respectively.

Conclusion

The MMP-11 expression was higher in BC than in benign breast tumors. Additionally, MMP-11, MMP-9, and MMP-2 were higher in BC with positive lymph nodes and estrogen receptors. Our findings suggest an important impact of MMPs in BC pathophysiology, particularly MMP-11.
Expansions to the MGDrivE suite for simulating the efficacy of novel gene-drive constructs in the control of mosquito-borne diseases
Authors: Bennett Jared B. , Wu Sean L. , Chennuri Pratima R. , Myles Kevin M. , Ndeffo-Mbah Martial L.
Published: October 2023

Objective

The MGDrivE (MGDrivE 1 and MGDrivE 2) modeling framework provides a flexible and expansive environment for testing the efficacy of novel gene-drive constructs for the control of mosquito-borne diseases. However, the existing model framework did not previously support several features necessary to simulate some types of intervention strategies. Namely, current MGDrivE versions do not permit modeling of small molecule inducible systems for controlling gene expression in gene drive designs or the inheritance patterns of self-eliminating gene drive mechanisms.

Results

Here, we demonstrate a new MGDrivE 2 module that permits the simulation of gene drive strategies incorporating small molecule-inducible systems and self-eliminating gene drive mechanisms. Additionally, we also implemented novel sparsity-aware sampling algorithms for improved computational efficiency in MGDrivE 2 and supplied an analysis and plotting function applicable to the outputs of MGDrivE 1 and MGDrivE 2.
Difference in risk of preterm and small-for-gestational-age birth depending on maternal occupations in Japan
Authors: Okui Tasuku
Published: October 2023

Objectives

In this study, an association between the mother’s occupations with preterm and small-for-gestational-age (SGA) births was investigated using national data in Japan, and individual-level birth data from the Report of Vital Statistics: Occupational and Industrial Aspects in the 2015 fiscal year were used. Preterm and SGA birth rates were calculated for each of infant characteristics, and relative risk of each type of maternal occupations (categorized into 12 types) for the outcomes was estimated using a log binomial regression model.

Results

Data of 997,600 singleton births were analyzed. Among maternal occupations, preterm birth rate was highest among carrying, cleaning, packaging, and related workers (5.65%) and lowest among security workers (4.24%). SGA birth rate was highest among manufacturing process workers (5.91%) and lowest among security workers (4.00%). We found significantly elevated risks for preterm birth among manufacturing process workers compared with unemployed mothers, and significantly elevated risks for SGA birth compared with unemployed mothers were observed among sales workers, service workers, and manufacturing process workers. In contrast, security workers had a significantly decreased risk for SGA birth compared with unemployed mothers.
Growth differentiation factor 7 autocrine signaling promotes hepatic progenitor cell expansion in liver fibrosis
Authors: Kong Defu , Mourtzinos Apostolos , Heegsma Janette , Blokzijl Hans , de Meijer Vincent E. , Faber Klaas Nico
Published: October 2023

Background and aim

Liver fibrosis is prevalent among chronic diseases of the liver and represents a major health burden worldwide. Growth differentiation factor 7 (GDF7), a member of the TGFβ protein superfamily, has been recently investigated for its role in repair of injured organs, but its role in chronic liver diseases remains unclear. Here, we examined hepatic GDF7 expression and its association with development and progression of human liver fibrosis. Moreover, we determined the source and target cells of GDF7 in the human liver.

Methods

GDF7 expression was analyzed in fibrotic and healthy human liver tissues by immunohistochemistry and qPCR. Cell-specific accumulation of GDF7 was examined by immunofluorescence through co-staining of cell type-specific markers on formalin-fixed paraffin-embedded human liver tissues. Public single cell RNA sequence databases were analyzed for cell type-specific expression of GDF7. In vitro, human liver organoids and LX-2 hepatic stellate cells (LX-2) were treated with recombinant human GDF7. Human liver organoids were co-cultured with activated LX-2 cells to induce an autocrine signaling circuit of GDF7 in liver organoids.

Results

GDF7 protein levels were elevated in fibrotic liver tissue, mainly detected in hepatocytes and cholangiocytes. In line, GDF7 mRNA was mainly detected in liver parenchymal cells. Expressions of BMPR1A and BMPR2, encoding GDF7 receptors, were readily detected in hepatocytes, cholangiocytes and stellate cells in vivo and in vitro. In vitro, recombinant GDF7 promoted liver organoid growth and enhanced expression of the progenitor cell markers (LGR5, AXIN2), but failed to activate LX-2 cells. Still, activated LX-2 cells induced GDF7 and LGR5 expression in co-cultured human liver organoids.

Conclusions

Collectively, this study reveals a role of GDF7 in liver fibrosis and suggests a potential pro-regenerative function that can be utilized for amelioration of hepatic fibrosis caused by chronic liver disease.
Enteric neurospheres retain the capacity to assemble neural networks with motile and metamorphic gliocytes and ganglia
Authors: Chen Jeng-Chang , Yang Wendy , Tseng Li-Yun , Chang Hsueh-Ling
Published: October 2023

Background

Neurosphere medium (NSM) and self-renewal medium (SRM) were widely used to isolate enteric neural stem cells (ENSCs) in the form of neurospheres. ENSCs or their neurosphere forms were neurogenic and gliogenic, but the compelling evidence for their capacity of assembling enteric neural networks remained lacking, raising the question of their aptitude for rebuilding the enteric nervous system (ENS) in ENSC therapeutics. It prompted us to explore an effective culture protocol or strategy for assembling ENS networks, which might also be employed as an in vitro model to simplify the biological complexity of ENS embedded in gut walls.

Methods

NSM and SRM were examined for their capacity to generate neurospheres in mass culture of dispersed murine fetal enterocytes at serially diluted doses and assemble enteric neural networks in two- and three-dimensional cell culture systems and ex vivo on gut explants. Time-lapse microphotography was employed to capture cell activities of assembled neural networks. Neurosphere transplantation was performed via rectal submucosal injection.

Results

In mass culture of dispersed enterocytes, NSM generated discrete units of neurospheres, whereas SRM promoted neural network assembly with neurospheres akin to enteric ganglia. Both were highly affected by seeding cell doses. SRM had similar ENSC mitosis-driving capacity to NSM, but was superior in driving ENSC differentiation in company with heightened ENSC apoptosis. Enteric neurospheres were motile, capable of merging together. It argued against their clonal entities. When nurtured in SRM, enteric neurospheres proved competent to assemble neural networks on two-dimensional coverslips, in three-dimensional hydrogels and on gut explants. In the course of neural network assembly from enteric neurospheres, neurite extension was preceded by migratory expansion of gliocytes. Assembled neural networks contained motile ganglia and gliocytes that constantly underwent shapeshift. Neurospheres transplanted into rectal submucosa might reconstitute myenteric plexuses of recipients’ rectum.

Conclusion

Enteric neurospheres mass-produced in NSM might assemble neural networks in SRM-immersed two- or three-dimensional environments and on gut explants, and reconstitute myenteric plexuses of the colon after rectal submucosal transplantation. Our results also shed first light on the dynamic entity of ENS and open the experimental avenues to explore cellular activities of ENS and facilitate ENS demystification.
On nonlinear fractional Choquard equation with indefinite potential and general nonlinearity
Authors: Liao Fangfang , Chen Fulai , Geng Shifeng , Liu Dong
Published: October 2023

In this paper, we consider a class of fractional Choquard equations with indefinite potential $$ (-\Delta )^{\alpha}u+V(x)u= \biggl[ \int _{{\mathbb{R}}^{N}} \frac{M(\epsilon y)G(u)}{ \vert x-y \vert ^{\mu}}\,\mathrm{d}y \biggr]M( \epsilon x)g(u), \quad x\in {\mathbb{R}}^{N}, $$

(
−
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)

α

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+
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(
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)
u
=

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∫

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N

M
(
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μ

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]

M
(
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)
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,

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where $\alpha \in (0,1)$
α
∈
(
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)
, $N> 2\alpha $
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>
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α
, $0<\mu <2\alpha $
0
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, ϵ is a positive parameter. Here $(-\Delta )^{\alpha}$

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stands for the fractional Laplacian, V is a linear potential with periodicity condition, and M is a nonlinear reaction potential with a global condition. We establish the existence and concentration of ground state solutions under general nonlinearity by using variational methods.
Resveratrol: a potential medication for the prevention and treatment of varicella zoster virus-induced ischemic stroke
Authors: Wang Xu , Chen Hao , Song Feiyu , Zuo Kuiyang , Chen Xin , Zhang Xu , Liang Lanqian , Ta Qiyi , Zhang Lin , Li Jinhua
Published: October 2023

Background

Infection rate of varicella zoster virus (VZV) is 95% in humans, and VZV infection is strongly associated with ischemic stroke (IS). However, the underlying molecular mechanisms of VZV-induced IS are still unclear, and there are no effective agents to treat and prevent VZV-induced IS.

Objective

By integrating bioinformatics, this study explored the interactions between VZV and IS and potential medication to treat and prevent VZV-induced IS.

Methods

In this study, the VZV and IS datasets from the GEO database were used to specify the common genes. Then, bioinformatics analysis including Gene Ontology, Kyoto Encyclopedia Genes Genomes and Protein–Protein Interaction network analysis was performed. Further, the hub genes, transcription factor (TF) gene interactions, TF-miRNA co-regulatory network and potential drug were obtained. Finally, validation was performed using molecular docking and molecular dynamics simulations.

Results

The potential molecular mechanisms of VZV-induced IS were studied using multiple bioinformatics tools. Ten hub genes were COL1A2, DCN, PDGFRB, ACTA2, etc. TF genes and miRNAs included JUN, FOS, CREB, BRCA1, PPARG, STAT3, miR-29, etc. A series of mechanism may be involved, such as inflammation, oxidative stress, blood–brain barrier disruption, foam cell generation and among others. Finally, we proposed resveratrol as a potential therapeutic medicine for the prevention and treatment of VZV-induced IS. Molecular docking and molecular dynamics results showed that resveratrol and hub genes exhibited strong binding score.

Conclusions

Resveratrol could be an alternative for the prevention and treatment of VZV-IS. More in vivo and in vitro studies are needed in the future to fully explore the molecular mechanisms between VZV and IS and for medication development.
Comparative risk perceptions of switching to JUUL vs. continued smoking and subsequent switching away from cigarettes: a longitudinal observational study
Authors: Selya Arielle , Shiffman Saul
Published: October 2023

Background

Evidence indicates that electronic nicotine delivery systems (ENDS) pose lower risk than cigarettes; however, many smokers harbor misperceptions that ENDS are equally or more harmful, possibly deterring them from switching. This study examines whether comparative risk perceptions of JUUL vs. smoking are associated with subsequent switching, among smokers who recently purchased JUUL.

Methods

N = 16,996 current established smokers who recently purchased a JUUL Starter Kit were followed 6 times over 12 months. Comparative risk perceptions were assessed using both direct and indirect measures (i.e., contrasting JUUL and smoking directly in questions, and deriving from separate absolute scales). Repeated-measures logistic regression examined switching across follow-up (no smoking in past 30 days) as a function of baseline risk perceptions, adjusting for demographics and baseline smoking behavior.

Results

Perceiving JUUL as less harmful than smoking was associated with higher switching rates, using both direct (e.g., adjusted odds ratio [AOR] = 1.48 for “JUUL much less” vs. “more/much more harmful”) and indirect (AOR = 1.07, for each 10-unit increase in fraction; AOR = 1.51 for highest (6-100) vs. lowest (0 to < 1) fraction categories) comparative risk measures (all p < 0.0001). Among the subset smoking 10 + cigarettes per day, associations between risk perceptions and switching were more pronounced (AOR = 2.51 for “JUUL much less” vs. “more/much more harmful”; AOR = 1.81 for 6-100 vs. 0 to < 1 fraction, both p < 0.0001).

Conclusions

Smokers who perceive JUUL as less harmful than cigarettes have higher odds of switching. Future research should examine whether messaging which aligns comparative risk perceptions with current evidence can facilitate switching, especially among heavier smokers.
Mitochondrial transfer in hematological malignancies
Authors: Guo Xiaodong , Can Can , Liu Wancheng , Wei Yihong , Yang Xinyu , Liu Jinting , Jia Hexiao , Jia Wenbo , Wu Hanyang , Ma Daoxin
Published: October 2023

Mitochondria are energy-generated organelles and take an important part in biological metabolism. Mitochondria could be transferred between cells, which serves as a new intercellular communication. Mitochondrial transfer improves mitochondrial defects, restores the biological functions of recipient cells, and maintains the high metabolic requirements of tumor cells as well as drug resistance. In recent years, it has been reported mitochondrial transfer between cells of bone marrow microenvironment and hematological malignant cells play a critical role in the disease progression and resistance during chemotherapy. In this review, we discuss the patterns and mechanisms on mitochondrial transfer and their engagement in different pathophysiological contexts and outline the latest knowledge on intercellular transport of mitochondria in hematological malignancies. Besides, we briefly outline the drug resistance mechanisms caused by mitochondrial transfer in cells during chemotherapy. Our review demonstrates a theoretical basis for mitochondrial transfer as a prospective therapeutic target to increase the treatment efficiency in hematological malignancies and improve the prognosis of patients.
Cryo-EM structures of tau filaments from the brains of mice transgenic for human mutant P301S Tau
Authors: Schweighauser Manuel , Murzin Alexey G. , Macdonald Jennifer , Lavenir Isabelle , Crowther R. Anthony , Scheres Sjors H.W. , Goedert Michel
Published: October 2023

Mice transgenic for human mutant P301S tau are widely used as models for human tauopathies. They develop neurodegeneration and abundant filamentous inclusions made of human mutant four-repeat tau. Here we used electron cryo-microscopy (cryo-EM) to determine the structures of tau filaments from the brains of Tg2541 and PS19 mice. Both lines express human P301S tau (0N4R for Tg2541 and 1N4R for PS19) on mixed genetic backgrounds and downstream of different promoters (murineThy1for Tg2541 and murinePrnpfor PS19). The structures of tau filaments from Tg2541 and PS19 mice differ from each other and those of wild-type tau filaments from human brains. The structures of tau filaments from the brains of humans with mutations P301L, P301S or P301T inMAPTare not known. Filaments from the brains of Tg2541 and PS19 mice share a substructure at the junction of repeats 2 and 3, which comprises residues I297-V312 of tau and includes the P301S mutation. The filament core from the brainstem of Tg2541 mice consists of residues K274-H329 of tau and two disconnected protein densities. Two non-proteinaceous densities are also in evidence. The filament core from the cerebral cortex of line PS19 extends from residues G271-P364 of tau. One strong non-proteinaceous density is also present. Unlike the tau filaments from human brains, the sequences following repeat 4 are missing from the cores of tau filaments from the brains of Tg2541 and PS19 mice.
Generalized anxiety disorder and sleep quality during COVID-19 lockdown in Egypt: a web-based cross-sectional survey
Authors: Elfar Eman , Abdelhai Rehab , Oraby Mohammed , Hosney Mennatallah Said
Published: October 2023

Background

Coronavirus disease (COVID-19) was identified in China in December 2019. During any major epidemic, psychosocial disturbance occurs, which can surpass people’s capacity to handle the condition.

Objective

The study aimed to estimate the prevalence of anxiety disorder and to assess sleep quality among Egyptian adults during COVID-19 lockdown.

Methods

The study was cross-sectional study through an anonymous web-based survey.

Results

Majority of participants were females (80.3%), highly educated (96.8%), and with mean age of 32.9 ± 8.7 years. Nearly two-thirds were healthcare workers (65.5%). The overall prevalence of anxiety (generalized anxiety disorder score more than 9) was 42.5%. Nearly three-fourth (73.5%) of participants reported poor sleep quality (Pittsburgh Sleep Quality Index score more than 5). In the multivariate logistic regression models, being female (adjusted odds ratio = 1.75, 95% confidence interval: 1.13–2.7 for anxiety and adjusted odds ratio = 2.217, 95% confidence interval: 1.461–3.364 for poor sleep quality), younger than 35 years (adjusted odds ratio = 0.537, 95% confidence interval: 0.376–0.767 for anxiety and adjusted odds ratio = 0.578, 95% confidence interval: 0.397–0.841 for poor sleep quality), and focusing more time on COVID-19 news (adjusted odds ratio = 1.937, 95% confidence interval: 1.601–2.343 for anxiety and adjusted odds ratio = 1.494, 95% confidence interval: 1.219–1.83 for poor sleep quality) were significant predictors of anxiety and poor sleep quality.

Conclusion

There was an increase in both anxiety and sleep disorders during COVID-19 pandemic. Young women spending more time on COVID-19 were at higher risk of developing anxiety and poor sleep quality.
Study of transcription factor 7-like 2 (TCF7L2) gene polymorphism in cirrhotic patients with diabetes
Authors: Hassouna Mona Mahmoud , Moustafa Mohammed Sayed , Hamdy Mona , Abdelsameea Eman , Abbasy Mohamed , Naguib Mary
Published: October 2023

Patients with chronic liver disease (CLD) as chronic hepatitis C (CHC) are at high risk of diabetes type 2 (T2D). Genetic factors are suggested to modulate diabetes development in cirrhotic patients. TCF7L2 gene has been reported to be associated with type 2 diabetes, but the association of TCF7L2 with cirrhotic patients with diabetes is unclear. We aimed to study the TCF7L2 gene polymorphisms (rs 290487) in cirrhotic patients with diabetes.

Method The study was assessed on 25 cirrhotic patients with type 2 diabetes who were compared to 25 cirrhotic HCV patients (nondiabetic), 25 diabetic type 2 patients, and 25 age- and gender-matched healthy control groups. After the collection of relevant clinical data and basic laboratory tests, single-nucleotide polymorphism (SNP) in the TCF7L2 gene (rs290487) was performed by a real-time PCR technique.

Results Cirrhotic patients with diabetes presented significantly poorer liver function, higher incidence of cirrhotic complications, and higher glucose levels compared with cirrhotic nondiabetic patients. The TCF7L2 rs290487 TT variant showed significantly increased diabetes risk in cirrhotic patients compared with CC and CT genotypes.

Conclusions TCF7L2 rs290487 polymorphism could be associated with increased diabetic risk in cirrhotic patients.
Role of serum survivin as a predictor of response to biological treatment in rheumatoid arthritis patients
Authors: Salama Sherihan M. , Fawaz Shereen I.
Published: October 2023

Background

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disorder characterised by synovial hypertrophy, proliferation, and pannus formation encroaching on articular structures resulting in uncontrolled spread of joint destruction. Survivin is an anti-apoptotic protein that plays an important role in tissue growth and tumour development. The objective of this research is to study the role of Survivin as a predictor of treatment response to anti-tumor necrosis factor (anti-TNF) in RA patients who had failure of conventional disease modifying anti rheumatic drugs (DMARDs) treatment.

Results

All patients had active RA evaluated with DAS 28 activity score: 73.3% of them had high disease activity, while 22.7% were in moderate activity. Serum survivin level ranged from 725 pg/ml to 2750 pg/ml. Its level was significantly higher in patients than in controls with a p value of < 0.001. After receiving anti-TNF treatment for 3 months, serum survivin level was reassessed, and it ranged from 525 pg/ml to 2100 pg/ml. There was a significant decreased in the biomarker serum level after receiving the treatment when compared to its level before starting treatment.

Conclusion

Our results showed that the assessment of serum survivin may be a useful diagnostic tool for detection of RA patients also it has a valuable predictive value in assessment of responce to biologic treatments given to the patients. This conclusion was reached after detection of high survivin levels in the sera of RA with high disease activity and reduced functional outcomes. Moreover, the biomarker has a good prognostic value in detection of response to biologic treatment indicated by the reduction of serum level after receiving the treatment and improvement of clinical disease activity.
Comparing tuberculosis symptom screening to chest X-ray with artificial intelligence in an active case finding campaign in Northeast Nigeria
Authors: John Stephen , Abdulkarim Suraj , Usman Salisu , Rahman Md. Toufiq , Creswell Jacob
Published: October 2023

Background

Ultra-portable X-ray devices with artificial intelligence (AI) are increasingly used to screen for tuberculosis (TB). Few studies have documented their performance. We aimed to evaluate the performance of chest X-ray (CXR) and symptom screening for active case finding of TB among remote populations using ultra-portable X-ray and AI.

Methods

We organized screening camps in rural northeast Nigeria, and all consenting individuals ≥ 15 years were screened for TB symptoms (cough, fever, night sweats, and weight loss) and received a CXR. We used a MinXray Impact system interpreted by AI (qXR V3), which is a wireless setup and can be run without electricity. We collected sputum samples from individuals with an qXR abnormality score of 0.30 or higher or if they reported any TB symptoms. Samples were tested with Xpert MTB/RIF. We documented the TB screening cascade and evaluated the performance of screening with different combinations of symptoms and CXR interpreted by AI.

Results

We screened 5297 individuals during 66 camps: 2684 (51%) were females, and 2613 (49%) were males. Using ≥ 2 weeks of cough to define presumptive TB, 1056 people (20%) would be identified. If a cough of any duration was used, the number with presumptive TB increased to 1889 (36%) and to 3083 (58%) if any of the four symptoms were used. Overall, 769 (14.5%) had abnormality scores of 0.3 or higher, and 447 (8.4%) had a score of 0.5 or higher. We collected 1021 samples for Xpert testing and detected 85 (8%) individuals with TB. Screening for prolonged cough only identified 40% of people with TB. Any symptom detected 90.6% of people with TB, but specificity was 11.4%. Using an AI abnormality score of 0.50 identified 89.4% of people with TB with a specificity of 62.8%.

Conclusions

Ultra-portable CXR can be used to provide more efficient TB screening in hard-to-reach areas. Symptom screening missed large proportions of people with bacteriologically confirmed TB. Employing AI to read CXR can improve triaging when human readers are unavailable and can save expensive diagnostic testing costs.
FRI011 Exploring The Contribution Of PARP1-mediated Site-specific ADP-Ribosylation Of C/EBPb In Macrophages To Diet-induced Obesity
Authors: Whitaker Amy L , Gupte Rebecca , Nandu Tulip Sunil , Lee Kraus W
Published: October 2023

Disclosure: A.L. Whitaker: None. R. Gupte: None. T.S. Nandu: None.

Inflammation is an important component of the pathological effects of obesity, which are mediated in part by adipose-associated macrophages (TAMs). Signal-regulated post-translational modifications in the TAMs help modulate the transcriptional programs that mediate biological outcomes. ADP-ribosylation is a posttranslational modification that regulates various cellular processes, including macrophage activation. ADP-ribosylation is the covalent attachment of ADP-ribose units on proteins by poly(ADP-ribose) polymerase (PARP) enzymes, mainly PARP1 in the nucleus. We have shown that ADP-ribosylation of key transcription factors (e.g., C/EBPβ and STAT1α) by PARP1 regulates adipogenesis, as well as pro-inflammatory responses in macrophages. Here we aim to investigate the role of PARP1-mediated ADP-ribosylation of C/EBPβ in inflammation and obesity using monocyte-specific mouse models. We have found that knockout (KO) of PARP1 in the monocyte/macrophage lineage (i.e., using a LysM-Cre driver) results in dramatic weight gain in mice with a nearly 2-fold increase in fat body mass in animals fed a high fat diet. Further analysis revealed decreases in adipose-associated macrophages and adipose hypertrophy, as well as increased hepatic lipid accumulation. Our findings exemplify the critical role that PARP1 in macrophages plays in maintaining homeostasis in key metabolic tissues. Moreover, our results indicate that regulation by PARP1 in macrophages contributes to resistance of diet-induced obesity through tissue-collaborative mechanisms. Our ongoing experiments suggest that PARP1 regulates LPS-induced inflammatory gene expression in macrophages. PARP1 controls LPS-mediated gene expression, in part, by ADP-ribosylating two sites (Glu 135 and Glu 139) in the regulatory domain of C/EBPβ; mutation of these sites inhibits PARP1-mediated PARylation of C/EBPβ and LPS-mediated gene expression through C/EBPβ. Additionally, treatment with a PARP inhibitor decreases LPS-mediated gene expression associated with upstream C/EBPβ enhancers. Moreover, treatment with a PARP inhibitor also decreases histone H3 lysine 27 acetylation (H3K27ac) at these C/EBPβ enhancers.

To investigate the physiological impact of loss of C/EBPβ ADP-ribosylation in macrophages, we have generated a knock-in mouse model for inducible monocyte-specific expression of a C/EBPβ ADP-ribosylation site mutant (CebpbE135A/E139A). This is the first physiological model for the study of site-specific ADP-ribosylation in vivo. Using this model, we are investigating the impact of site-specific ADP-ribosylation of C/EBPβ in mice fed a high fat diet. With these studies, we hope to reveal the specific roles of PARP1-mediated ADP-ribosylation in diet-induced obesity.

Presentation: Friday, June 16, 2023
FRI039 Endothelial Dysfunction Is Associated With Adiponectin And Leptin In Adolescents With PCOS
Authors: Gavryutina Irina , Badran Ahmed , Thakkar Amruta , Bargman Renee , Umpaichitra Vatcharapan , Chin Vivian
Published: October 2023

Disclosure: I. Gavryutina: None. A. Badran: None. A. Thakkar: None. R. Bargman: None. V. Umpaichitra: None. V. Chin: None.

Endothelial dysfunction (ED) was found to be prevalent in women with polycystic ovarian syndrome (PCOS) and was associated with increased leptin and decreased adiponectin levels but has not been studied in children. We performed a cross-sectional study of non-smoking adolescents aged 12-19 years old with PCOS by NIH-criteria (n=20) and controls (n=7) to study the differences in ghrelin, endothelin, anti-mullerian hormone (AMH), leptin, adiponectin and reactive-hyperemia index (RHI) a non-invasive single measure of ED using EndoPAT®. Exclusion criteria were: pregnancy, diabetes, thyroid disease, adrenal disorder, hepatic, cardiovascular disease, hypertension, or medications (other than metformin or oral contraceptive pills which were allowed for the PCOS group). Between PCOS and control groups, there was no difference (mean±SD) in age (16.5±1.8 vs 17.1±2.3 years, p=0.31), BMI (35.7 ±9.7 vs 30.9±10.3 kg/m2, p=0.15) and A1C levels (5.45±0.4 vs 5.37±0.15%, p=0.22). Total and free testosterone was higher in PCOS group (60.7±21.8 vs 34.6±12.8 ng/dl, p=0.00063; 8.51 vs 3.76, p=0.0019, respectively). PCOS group had worse (lower) RHI (1.26±0.43 vs 1.72±0.40, p=0.015, normal RHI >1.67). PCOS group had higher leptin (1085.5±116.9 vs 896.4±176 pg/ml, p=0.014) and lower adiponectin (2.02±0.19 vs 2.27±0.13 µg/ml, p=0.001). There were no differences in endothelin-1 (10.9±1.2 vs 34.3±3.1 pg/ml, p=0.11), ghrelin (6060.1±13057.2 vs 5495.7±5474 pg/dl, p=0.44) and AMH levels (11.86±27 vs 3.8±10.1, p=0.14). HOMA-IR or insulin resistance was not significantly different between the PCOS and control groups (2.05 vs 3.48, p=0.26). Leptin is a proinflammatory product of adipose tissue and via its receptor on the endothelium, likely promotes platelet aggregation, thrombosis and stimulation of free radical production contributing to ED. Adiponectin on the other hand, is known to reduce levels of TNFα and suppress its inflammatory effects on endothelial cells. Low adiponectin has previously been found in women with PCOS when corrected for BMI and even insulin resistance. Our adolescents with PCOS had lower RHI, higher leptin and lower adiponectin levels. These findings suggest increased risk of cardiovascular disease in adolescents which has not been previously reported in children before. Further studies are needed to investigate the relationship between ED and differences in leptin and adiponectin in adolescents with PCOS.

Presentation: Friday, June 16, 2023
FRI081 Quality Improvement Initiative To Improve Management Of Obesity In A Primary Care Resident Continuity Clinic
Authors: Fernandez Maria Gabriela , Hillhouse Melodie , Ozimek David , Salvo Marissa
Published: October 2023

Disclosure: M.G. Fernandez: None. M. Hillhouse: None. D. Ozimek: None. M. Salvo: None.

Background: Obesity is a leading health concern in the US and a growing epidemic worldwide. Despite the substantial evidence on weight management interventions, it remains the least commonly addressed medical problem. Physicians also document obesity infrequently in medical records. It has been well established that increasing documentation of obesity improves its management as a chronic disease. Objective: The main aim of our project was to increase the percentage of patients with a body mass index (BMI) ≥30kg/m2 with documented obesity in the electronic medical record (EMR) from 42% to 70%. The second aim was to increase the percentage of patients with a BMI ≥30kg/m2 prescribed weight loss pharmacotherapy from 10% to 40%. The project was performed in an Internal Medicine residency program continuity clinic over six months. Methods: We used three cycles of the Plan-Do- Study-Act methodology; all included education in obesity medicine, distribution of a hard copy list of the patients who met inclusion criteria, and EMR message reminders to address obesity by the following medical appointment. The EMR was used to generate reports to track outcomes. The first report listed all the resident clinic patients with a documented BMI ≥30kg/m2. The following list the number of patients with BMI ≥30kg/m2 and a corresponding diagnosis of obesity in their chart. The last report listed the number of patients with BMI ≥30kg/m2 on weight loss pharmacotherapy. Reports were generated bi-monthly, and percentages were used to determine the efficacy of each cycle. Results: There were 25% of residents’ patients who met project inclusion criteria. Of this, 11% were prescribed pharmacotherapy at baseline. Of those receiving treatment, 98% had type 2 diabetes. After the interventions, the documentation of obesity in the EMR increased from 42% to 60%. As a result, the overall number of patients on weight loss pharmacotherapy increased from 10.53% to 12.68%. Conclusion: The overall goal of the interventions was successful. There was an increase in both EMR documentation of obesity and increased weight loss pharmacotherapy prescribing; however, both were lower than anticipated. It was also found that the resident physicians responded more to printed metrics of their population of patients. In addition, physicians were more susceptible to treating patients when obesity was documented as a chronic disease. However, this project emphasizes that more efforts should be made to engage residents in multidisciplinary training to improve the management of obesity and increase tools to navigate through barriers to obesity treatments.

Presentation: Friday, June 16, 2023
SAT652 The Expression Of The Immunoproteasome Subunit Psmb9 Is Related To Obesity And The Differentiation Of Human Preadipocytes
Authors: Cui Yan , Zhang Xiaoxiao , You Lianghui , Zhong Hong , Cui Xianwei , Ji Chenbo
Published: October 2023

Disclosure: Y. Cui: None. X. Zhang: None. L. You: None. H. Zhong: None. X. Cui: None. C. Ji: None.

Obesity and its associated chronic diseases, such as type 2 diabetes mellitus, hypertension, and coronary artery disease, afflicting adults and children globally. PSMB9, a proteolytic subunit of the immunoproteasome that shapes the repertoire of antigenic peptides, is hypothesized to be associated with obesity. To investigate this association, we examined PSMB9 expression in primary mature adipocytes from obese and normal individuals. LC-MS/MS-PRM was used to quantify PSMB9 content in primary mature adipocytes, revealing a negative correlation between PSMB9 content and obesity while positively correlated with high-density lipoprotein levels. Furthermore, we examined the effect of PSMB9 on human preadipocyte differentiation. During the early stages of differentiation, the expression of PSMB9 was at its highest level, decreasing as preadipocytes matured. Overexpression of PSMB9 significantly inhibited preadipocyte differentiation, resulting in reduced lipid droplets and decreased expression levels of classical differentiation markers such as FABP4, C/EBPα, and PPARγ. These findings suggest that PSMB9 could be a potential therapeutic target for preventing and treating obesity and metabolic disorders. In conclusion, our study provides insights into the role of the immunoproteasome in obesity and highlights the importance of further exploration of this pathway.

Presentation: Saturday, June 17, 2023
SAT156 Two Cases Of Hypoglycemia From Inhalation Of Heroin Adulterated With A Sulfonylurea
Authors: Kim Keun Young , Hwang Jessica , Sam Susan
Published: October 2023

Disclosure: K. Kim: None. J. Hwang: None. S. Sam: None.

Context: Hypoglycemic disorders in non-diabetic patients are rare. In the setting of concomitant illicit opioid abuse, hypoglycemia is highly unusual and an underlying cause should be systematically investigated. Objective: We report two separate cases of non-diabetic women both admitted to our intensive care unit for critical hypoglycemia secondary to inhaled heroin containing sulfonylureas. Case 1—A 51 year old female with a history of heroin addiction (on methadone) was brought to the emergency department with altered mental status. She was found to have refractory hypoglycemia and was transferred to the medical intensive care unit (MICU) for monitoring. She reported poor appetite and food intake in the past week and endorsed consuming one alcoholic beverage the night before. Case 2—A 61 year old female with a history of heroin and cocaine abuse was found by the paramedics at home with a decreased level of responsiveness and blood sugar of <30 mg/dL who also required MICU admission. She endorsed using heroin, cocaine and substantial alcohol 2 days prior to admission at a party. She reported 2 episodes of hypoglycemia in the past requiring hospitalization, with no known cause. Kidney and liver disease were ruled out in both subjects. A thorough history including illicit drug use and critical blood samples at the time of hypoglycemia including drug toxicity screen, sulfonylurea screen were obtained. Labs demonstrated an insulin-mediated hypoglycemia and positive sulfonylurea screen for glipizide in both patients. Results: Because of their non-diabetic status, their compelling history and the results of their comprehensive laboratory work-up, we conclude that these subjects had a common exposure- insufflation of heroin contaminated with an oral hypoglycemic agent shortly before their admissions with critical hypoglycemia and clinical instability. Conclusions: This is the first report of hypoglycemia related to inhalation of heroin adulterated with the sulfonylurea glipizide. Frequently heroin is intentionally mixed with other agents (diphenhydramine) to increase the volume for sale, optimize the drug uptake or to ease the side effects. These cases highlight the importance of obtaining a thorough clinical history including potential illicit drug use, acquiring timely and appropriate laboratory samples for toxicologic analysis, and interpreting the findings to curb a potentially deadly epidemic.

Presentation: Saturday, June 17, 2023
SAT436 Endocrine Disruptor Of Organochlorine Pesticides Levels In Saudi Arabian Produce
Authors: Alokail Majed S , Al-Daghri Nasser M , Alnaami Abdullah M , Sabico Shaun , Hussain Syed D , Amer Osama E , Abd-Alrahman Sherif H
Published: October 2023

Disclosure: M.S. Alokail: None. N.M. Al-Daghri: None. A.M. Alnaami: None. S. Sabico: None. S.D. Hussain: None. O.E. Amer: None. S.H. Abd-Alrahman: None.

Food monitoring (FM) is a system used to evaluate and monitor hazardous contaminants, including pollutants such as organochlorine pesticides (OCPs). Long term exposure to organochlorine pesticides (OCPs) can lead to a variety of endocrine and reproductive disruptors including gonadal changes, changes in reproductive behavior, reduced sperm quality, an increase in organ malformations, testicular failure, fetal defects, thyroid dysfunction, and lactation. The present study aimed to determine and quantify OCPs in different local produce collected from different regions in Saudi Arabia. A total of 179 local produce samples were obtained in four regions in Saudi Arabia: Riyadh (N=55), Qassim (N=61), Eastern province (N=38) and Western region (N=25). Solid phase extraction method (QuEChERS) was used to detect OCP residues in samples and levels were quantified using gas chromatograph-electron capture detector (GC-ECD). The results have shown that a total of 11 OCPs were detected overall (9 OCPs in Qassim, Eastern province and Riyadh; 8 in Western region). Levels of alpha BHC was highest in Riyadh; 6 OCPs were highest in Qassim (Beta-BHC, Delta BCH, Dieldrin, Gamma-BHC, heptachlorepoxide and heptachlor); 4 OCPs were highest in the Eastern province (DDD, DDE, endosulfan and endrin), with endrin and endosulfan having the highest levels among all OCPs assessed. A total of 6 OCPs were found in all regions at varying concentrations (Beta-BHC, DDE, Delta-BCH, Dieldrin, endosulfan and heptachlor. Worthy to note is that heptachlorepoxide was found only in Qassim. In conclusion, the endocrine disruptor pesticides such as OCP residues require further investigation for a possible etiologic role in some hormone related cancers such as breast cancer.

Presentation: Saturday, June 17, 2023