bluuebunny/crossref_metadata_2025 huggingface dataset:
Tryptophan metabolism in digestive system tumors: unraveling the pathways and implications
Authors: Yu Liang , Lu Juan , Du Weibo
Published: March 2024

Tryptophan (Trp) metabolism plays a crucial role in influencing the development of digestive system tumors. Dysregulation of Trp and its metabolites has been identified in various digestive system cancers, including esophageal, gastric, liver, colorectal, and pancreatic cancers. Aberrantly expressed Trp metabolites are associated with diverse clinical features in digestive system tumors. Moreover, the levels of these metabolites can serve as prognostic indicators and predictors of recurrence risk in patients with digestive system tumors. Trp metabolites exert their influence on tumor growth and metastasis through multiple mechanisms, including immune evasion, angiogenesis promotion, and drug resistance enhancement. Suppressing the expression of key enzymes in Trp metabolism can reduce the accumulation of these metabolites, effectively impacting their role in the promotion of tumor progression and metastasis. Strategies targeting Trp metabolism through specific enzyme inhibitors or tailored drugs exhibit considerable promise in enhancing therapeutic outcomes for digestive system tumors. In addition, integrating these approaches with immunotherapy holds the potential to further enhance treatment efficacy.
Discovery of a novel small molecule as CD47/SIRPα and PD-1/PD-L1 dual inhibitor for cancer immunotherapy
Authors: Jin Shengzhe , Wang Hongfei , Li Yang , Yang Jingwen , Li Beibei , Shi Peishang , Zhang Xiangrui , Zhou Xiaowen , Zhou Xiuman , Niu Xiaoshuang , Wu Menghan , Wu Yahong , Zhai Wenjie , Qi Yuanming , Gao Yanfeng , Zhao Wenshan
Published: March 2024

Background

Targeting the tumor microenvironment (TME) has emerged as a promising strategy in cancer treatment, particularly through the utilization of immune checkpoint blockade (ICB) agents such as PD-1/PD-L1 inhibitors. Despite partial success, the presence of tumor-associated macrophages (TAMs) contributes to an immunosuppressive TME that fosters tumor progression, and diminishes the therapeutic efficacy of ICB. Blockade of the CD47/SIRPα pathway has proven to be an effective intervention, that restores macrophage phagocytosis and yields substantial antitumor effects, especially when combined with PD-1/PD-L1 blockade. Therefore, the identification of small molecules capable of simultaneously blocking CD47/SIRPα and PD-1/PD-L1 interactions has remained imperative.

Methods

SMC18, a small molecule with the capacity of targeting both SIRPα and PD-L1 was obtained using MST. The efficiency of SMC18 in interrupting CD47/SIRPα and PD-1/PD-L1 interactions was tested by the blocking assay. The function of SMC18 in enhancing the activity of macrophages and T cells was tested using phagocytosis assay and co-culture assay. The antitumor effects and mechanisms of SMC18 were investigated in the MC38-bearing mouse model.

Results

SMC18, a small molecule that dual-targets both SIRPα and PD-L1 protein, was identified. SMC18 effectively blocked CD47/SIRPα interaction, thereby restoring macrophage phagocytosis, and disrupted PD-1/PD-L1 interactions, thus activating Jurkat cells, as evidenced by increased secretion of IL-2. SMC18 demonstrated substantial inhibition of MC38 tumor growths through promoting the infiltration of CD8+ T and M1-type macrophages into tumor sites, while also priming the function of CD8+ T cells and macrophages. Moreover, SMC18 in combination with radiotherapy (RT) further improved the therapeutic efficacy.

Conclusion

Our findings suggested that the small molecule compound SMC18, which dual-targets the CD47/SIRPα and PD-1/PD-L1 pathways, could be a candidate for promoting macrophage- and T-cell-mediated phagocytosis and immune responses in cancer immunotherapy.
Geniposide alleviates cholesterol-induced endoplasmic reticulum stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway
Authors: Zhong Mingliang , Wu Zhenyu , Chen Zhixi , Wu Longhuo , Zhou Jianguo
Published: March 2024

Background

Cholesterol (CHO) is an essential component of the body. However, high CHO levels in the body can damage bone mass and promote osteoporosis. CHO accumulation can cause osteoblast apoptosis, which has a negative effect on bone formation. The pathogenesis of osteoporosis is a complicate process that includes oxidative stress, endoplasmic reticulum (ER) stress, and inflammation. Geniposide (GEN) is a natural compound with anti-osteoporotic effect. However, the roles of GEN in osteopathogenesis are still unclear. Our previous studies demonstrated that GEN could reduce the accumulation of CHO in osteoblasts and the activation of ER stress in osteoblasts. However, the molecular mechanism of GEN in inhibiting CHO-induced apoptosis in osteoblasts needs to be further investigated.

Methods

MC3T3-E1 cells were treated with osteogenic induction medium (OIM). Ethanol-solubilized cholesterol (100 µM) was used as a stimulator, and 10 µM and 25 µM geniposide was added for treatment. The alterations of protein expression were detected by western blot, and the cell apoptosis was analyzed by a flow cytometer.

Results

CHO promoted osteoblast apoptosis by activating ER stress in osteoblasts, while GEN alleviated the activation of ER stress and reduced osteoblast apoptosis by activating the GLP-1R/ABCA1 pathway. Inhibition of ABCA1 or GLP-1R could eliminate the protective activity of GEN against CHO-induced ER stress and osteoblast apoptosis.

Conclusion

GEN alleviated CHO-induced ER stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway.
Salvianolic acid C attenuates cerebral ischemic injury through inhibiting neuroinflammation via the TLR4-TREM1-NF-κB pathway
Authors: Guo Wenbo , Xu Xiaojing , Xiao Yulin , Zhang Jiatian , Shen Peiqiang , Lu Xiaoyan , Fan Xiaohui
Published: March 2024

Background

Stroke is a leading cause of mortality and disability with ischemic stroke being the most common type of stroke. Salvianolic acid C (SalC), a polyphenolic compound found in Salviae Miltiorrhizae Radix et Rhizoma, has demonstrated therapeutic potential in the recovery phase of ischemic stroke. However, its pharmacological effects and underlying mechanisms during the early stages of ischemic stroke remain unclear. This study aimed to examine the potential mechanism of action of SalC during the early phase of ischemic stroke using network pharmacology strategies and RNA sequencing analysis.

Methods

SalC effects on infarct volume, neurological deficits, and histopathological changes were assessed in a mouse model of transient middle cerebral artery occlusion (tMCAO). By integrating RNA sequencing data with a cerebral vascular disease (CVD)-related gene database, a cerebral ischemic disease (CID) network containing dysregulated genes from the tMCAO model was constructed. Network analysis algorithms were applied to evaluate the key nodes within the CID network. In vivo and in vitro validation of crucial targets within the identified pathways was conducted.

Results

SalC treatment significantly reduced infarct volume, improved neurological deficits, and reversed pathological changes in the tMCAO mouse model. The integration of RNA sequencing data revealed an 80% gene reversion rate induced by SalC within the CID network. Among the reverted genes, 53.1% exhibited reversion rates exceeding 50%, emphasizing the comprehensive rebalancing effect of SalC within the CID network. Neuroinflammatory-related pathways regulated by SalC, including the toll-like-receptor 4 (TLR4)- triggering receptor expressed on myeloid cells 1 (TREM1)-nuclear factor kappa B (NF-κB) pathway, were identified. Further in vivo and in vitro experiments confirmed that TLR4-TREM1-NF-κB pathway was down-regulated by SalC in microglia, which was essential for its anti-inflammatory effect on ischemic stroke.

Conclusions

SalC attenuated cerebral ischemic injury by inhibiting neuroinflammation mediated by microglia, primarily through the TLR4-TREM1-NF-κB pathway. These findings provide valuable insights into the potential therapeutic benefits of SalC in ischemic stroke.
Evaluating the progression to abnormal thyrotropin in euthyroid preconception women: a population-based study
Authors: Gao Rili , Lyu Xinyi , Yang Ying , Fu Jinrong , Zhao Chuanyu , Guan Haixia , Ma Xu
Published: March 2024

Background

Abnormal preconception thyrotropin levels were associated with fecundability and adverse fetomaternal outcomes, however, little is known regarding the natural change of serum thyrotropin in euthyroid preconception women. Thus, we performed a population-based study to evaluate the progression to abnormal thyrotropin in euthyroid preconception women.

Methods

This retrospective cohort study used data from the National Free Prepregnancy Checkups Project (NFPCP) collected between 2010 and 2020. Female Han Chinese participants aged 20–49 years who had two repeated NFPCP participations with a time interval of 1.5–3.0 years, confirmed non-pregnant status within this duration, and normal thyrotropin levels during their first participation were included for the analysis of thyrotropin abnormalities during the second NFPCP examination. Data were analyzed between June 1 and October 1, 2023.

Results

This study included 186,095 euthyroid women of reproductive age (mean ± SD, 26.72 ± 4.70 years) whose preconception thyrotropin levels were between 0.37 and 4.87 mIU/L. The median follow-up time was 2.13 (IQR, 1.85–2.54) years. A total of 8,497 (4.57%) women developed abnormal thyrotropin, including 4,118 (2.21%) subnormal thyrotropin and 4,379 (2.35%) supranormal thyrotropin. Compared with the reference group (thyrotropin 1.01–2.00 mIU/L), the lower baseline thyrotropin group had greater risk of developing subnormal thyrotropin, and the higher baseline thyrotropin group had greater risk of developing supranormal thyrotropin. Moreover, the restricted cubic spline analysis revealed a U-shaped dose–response association of baseline thyrotropin levels or thyrotropin multiples of the median (MOM) levels against risk of subnormal thyrotropin in the follow-up, and a J-shaped dose–response association against risk of supranormal thyrotropin levels in the follow-up. We further found that baseline thyrotropin outside of 1.43–1.93 mIU/L or baseline thyrotropin MOM outside 0.59–1.36 would hava a higher risk of developing of abnormal thyrotropin.

Conclusions

Both low and high baseline thyrotropin were associated with a significantly increased risk of developing abnormal thyrotropin outcomes. The optimal preconception baseline thyrotropin levels may be between 1.43 mIU/L and 1.93 mIU/L or baseline thyrotropin MoM between 0.59 and 1.36 to minimize progression toward abnormal thyrotropin after 1.5–3.0 years. These findings may help with counseling of preconception thyroid function monitoring.
Critical illness-related corticosteroid insufficiency (CIRCI) in paediatric patients: a diagnostic and therapeutic challenge
Authors: Morabito Letteria Anna , Corica Domenico , Pepe Giorgia , Li Pomi Alessandra , Aversa Tommaso , Wasniewska Malgorzata Gabriela
Published: March 2024

Critical illness-related corticosteroid insufficiency or CIRCI is characterized by acute and life-threatening disfunction of hypothalamic–pituitary–adrenal (HPA) axis observed among intensive care unit- staying patients.

It is associated with increased circulating levels of biological markers of inflammation and coagulation, morbidity, length of ICU stay, and mortality.

Several mechanisms are involved in CIRCI pathogenesis: reduced CRH-stimulated ACTH release, peripheral resistance to glucocorticoids, altered cortisol synthesis, impaired cortisol-free fraction and bioavailability.

Diagnostic and therapeutic management of this condition in children is still debated, probably because of the lack of agreement among intensive care specialists and endocrinologists regarding diagnostic criteria and prevalence of CIRCI in paediatric age.

In the present narrative review, we focused on definition of CIRCI in paediatric age and we advise on how to diagnose and treat this poorly understood condition, based on current literature data.
HER2-low and tumor infiltrating lymphocytes in triple-negative breast cancer: Are they connected?
Authors: Baez-Navarro Ximena , van den Ende Nadine S. , Nguyen Anh H. , Sinke Renata , Westenend Pieter , van Brakel Johannes Bastiaan , Stobbe Claudia , Westerga Johan , van Deurzen Carolien H. M.
Published: March 2024

Most patients with triple-negative breast cancer (TNBC) are not candidates for targeted therapy, leaving chemotherapy as the primary treatment option. Recently, immunotherapy has demonstrated promising results in TNBC, due to its immunogenicity. In addition, a novel antibody–drug conjugate, namely, trastuzumab-deruxtecan, has shown effectiveness in TNBC patients with low-HER2 expression (HER2-low). These novel treatment options raise the question about the potential association between the density of stromal tumor-infiltrating lymphocytes (sTILs) and the level of HER2 expression. We aimed to evaluate the association between the level of HER2 expression (HER2-low versus HER2-0) and density of sTILs in TNBC patients, and how they impact the response to neoadjuvant chemotherapy (NAC). This was a retrospective multicenter study including all TNBC patients diagnosed between 2018 and 2022. Central pathology review included sTILs percentages and level of HER2 expression. Tumors were reclassified as either HER2-0 (HER2 IHC 0) or HER2-low (IHC 1 + or 2 + with negative reflex test). Various clinicopathologic characteristics, including sTILs density, and response to NAC were compared between HER2-0 and HER2-low cases. In total, 753 TNBC patients were included in this study, of which 292 patients received NAC. Interobserver agreement between the original pathology report and central review was moderate (77% had the same IHC status after reclassification in either HER2-0 or HER2-low; k = 0.45). HER2-low TNBC represented about one third (36%) of the tumors. No significant difference in sTILs density or complete pathologic response rate was found between HER2-0 and HER2-low cases (p = 0.476 and p = 0.339, respectively). The density of sTILs (≥ 10% sTILs vs. < 10%) was independently associated with achieving a pCR (p = 0.011). In conclusion, no significant association was found between HER2-low status and density of sTILs nor response to NAC. Nonetheless, sTILs could be an independent biomarker for predicting NAC response in TNBC patients.
Cell morphology best predicts tumorigenicity and metastasis in vivo across multiple TNBC cell lines of different metastatic potential
Authors: Conner Sydney J. , Guarin Justinne R. , Le Thanh T. , Fatherree Jackson P. , Kelley Charlotte , Payne Samantha L. , Parker Savannah R. , Bloomer Hanan , Zhang Crystal , Salhany Kenneth , McGinn Rachel A. , Henrich Emily , Yui Anna , Srinivasan Deepti , Borges Hannah , Oudin Madeleine J.
Published: March 2024

Background

Metastasis is the leading cause of death in breast cancer patients. For metastasis to occur, tumor cells must invade locally, intravasate, and colonize distant tissues and organs, all steps that require tumor cell migration. The majority of studies on invasion and metastasis rely on human breast cancer cell lines. While it is known that these cells have different properties and abilities for growth and metastasis, the in vitro morphological, proliferative, migratory, and invasive behavior of these cell lines and their correlation to in vivo behavior is poorly understood. Thus, we sought to classify each cell line as poorly or highly metastatic by characterizing tumor growth and metastasis in a murine model of six commonly used human triple-negative breast cancer xenografts, as well as determine which in vitro assays commonly used to study cell motility best predict in vivo metastasis.

Methods

We evaluated the liver and lung metastasis of human TNBC cell lines MDA-MB-231, MDA-MB-468, BT549, Hs578T, BT20, and SUM159 in immunocompromised mice. We characterized each cell line's cell morphology, proliferation, and motility in 2D and 3D to determine the variation in these parameters between cell lines.

Results

We identified MDA-MB-231, MDA-MB-468, and BT549 cells as highly tumorigenic and metastatic, Hs578T as poorly tumorigenic and metastatic, BT20 as intermediate tumorigenic with poor metastasis to the lungs but highly metastatic to the livers, and SUM159 as intermediate tumorigenic but poorly metastatic to the lungs and livers. We showed that metrics that characterize cell morphology are the most predictive of tumor growth and metastatic potential to the lungs and liver. Further, we found that no single in vitro motility assay in 2D or 3D significantly correlated with metastasis in vivo.

Conclusions

Our results provide an important resource for the TNBC research community, identifying the metastatic potential of 6 commonly used cell lines. Our findings also support the use of cell morphological analysis to investigate the metastatic potential and emphasize the need for multiple in vitro motility metrics using multiple cell lines to represent the heterogeneity of metastasis in vivo.
UCHL1 contributes to insensitivity to endocrine therapy in triple-negative breast cancer by deubiquitinating and stabilizing KLF5
Authors: Li Juan , Liang Yu , Zhou Shijie , Chen Jie , Wu Chihua
Published: March 2024

Background

Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that regulates ERα expression in triple-negative cancer (TNBC). This study aimed to explore the deubiquitination substrates of UCHL1 related to endocrine therapeutic responses and the mechanisms of UCHL1 dysregulation in TNBC.

Methods

Bioinformatics analysis was conducted using online open databases. TNBC representative MDA-MB-468 and SUM149 cells were used for in vitro and in-vivo studies. Co-immunoprecipitation was used to explore the interaction between UCHL1 and KLF5 and UCHL1-mediated KIF5 deubiquitination. CCK-8, colony formation and animal studies were performed to assess endocrine therapy responses. The regulatory effect of TET1/3 on UCHL1 promoter methylation and transcription was performed by Bisulfite sequencing PCR and ChIP-qPCR.

Results

UCHL1 interacts with KLF5 and stabilizes KLF5 by reducing its polyubiquitination and proteasomal degradation. The UCHL1-KLF5 axis collaboratively upregulates EGFR expression while downregulating ESR1 expression at both mRNA and protein levels in TNBC. UCHL1 knockdown slows the proliferation of TNBC cells and sensitizes the tumor cells to Tamoxifen and Fulvestrant. KLF5 overexpression partially reverses these trends. Both TET1 and TET3 can bind to the UCHL1 promoter region, reducing methylation of associated CpG sites and enhancing UCHL1 transcription in TNBC cell lines. Additionally, TET1 and TET3 elevates KLF5 protein level in a UCHL1-dependent manner.

Conclusion

UCHL1 plays a pivotal role in TNBC by deubiquitinating and stabilizing KLF5, contributing to endocrine therapy resistance. TET1 and TET3 promote UCHL1 transcription through promoter demethylation and maintain KLF5 protein level in a UCHL1-dependent manner, implying their potential as therapeutic targets in TNBC.
Prediction of metabolites associated with somatic mutations in cancers by using genome-scale metabolic models and mutation data
Authors: Lee GaRyoung , Lee Sang Mi , Lee Sungyoung , Jeong Chang Wook , Song Hyojin , Lee Sang Yup , Yun Hongseok , Koh Youngil , Kim Hyun Uk
Published: March 2024

Background

Oncometabolites, often generated as a result of a gene mutation, show pro-oncogenic function when abnormally accumulated in cancer cells. Identification of such mutation-associated metabolites will facilitate developing treatment strategies for cancers, but is challenging due to the large number of metabolites in a cell and the presence of multiple genes associated with cancer development.

Results

Here we report the development of a computational workflow that predicts metabolite-gene-pathway sets. Metabolite-gene-pathway sets present metabolites and metabolic pathways significantly associated with specific somatic mutations in cancers. The computational workflow uses both cancer patient-specific genome-scale metabolic models (GEMs) and mutation data to generate metabolite-gene-pathway sets. A GEM is a computational model that predicts reaction fluxes at a genome scale and can be constructed in a cell-specific manner by using omics data. The computational workflow is first validated by comparing the resulting metabolite-gene pairs with multi-omics data (i.e., mutation data, RNA-seq data, and metabolome data) from acute myeloid leukemia and renal cell carcinoma samples collected in this study. The computational workflow is further validated by evaluating the metabolite-gene-pathway sets predicted for 18 cancer types, by using RNA-seq data publicly available, in comparison with the reported studies. Therapeutic potential of the resulting metabolite-gene-pathway sets is also discussed.

Conclusions

Validation of the metabolite-gene-pathway set-predicting computational workflow indicates that a decent number of metabolites and metabolic pathways appear to be significantly associated with specific somatic mutations. The computational workflow and the resulting metabolite-gene-pathway sets will help identify novel oncometabolites and also suggest cancer treatment strategies.
Personalized, interdisciplinary patient pathway for cross-sector care of multimorbid patients (eliPfad trial): study protocol for a randomized controlled trial
Authors: Lindemann Christoph Heinrich , Burst Volker , Völker Linus Alexander , Brähler Sebastian , Simic Dusan , Becker Ingrid , Hellmich Martin , Kurscheid Clarissa , Scholten Nadine , Krauspe Ruben , Leibel Kerstin , Stock Stephanie , Brinkkoetter Paul Thomas
Published: March 2024

Background

Multimorbid and frail elderly patients often carry a high burden of treatment. Hospitalization due to the onset of an acute illness can disrupt the fragile balance, resulting in further readmissions after hospital discharge. Current models of care in Germany do not meet the needs of this patient group. Rather lack of coordination and integration of care combined with a lack of interdisciplinary approaches result in fragmented and inadequate care and increase the burden of treatment even more.

Methods

eliPfad is a randomized controlled trial conducted in 6 hospitals in Germany. Multimorbid elderly patients aged 55 or older are randomly assigned to the intervention or control group. Patients in the intervention group receive the eliPfad intervention additional to standard care. The core components of eliPfad are:

Early assessment of patients’ individual treatment burden and support through a specially trained case manager

Involvement of the patient’s general practitioner (GP) right from the beginning of the hospital stay

Preparation of an individual, cross-sectoral treatment plan through the interdisciplinary hospital team with the involvement of the patient’s GP

Establishment of a cross-sectoral electronic patient record (e-ePA) for documentation and cross-sectoral exchange

Support/Promote patient adherence

Tailored early rehabilitation during the hospital stay, which is continued at home

Close-tele-monitoring of medically meaningful vital parameters through the use of tablets, digital devices, and personal contacts in the home environment

The intervention period begins in the hospital and continues 6 weeks after discharge. Patients in the control group will be treated according to standard clinical care and discharged according to current discharge management. The primary aim is the prevention/reduction of readmissions in the first 6 months after discharge. In addition, the impact on health-related quality of life, the burden of treatment, survival, self-management, medication prescription, health literacy, patient-centered care, cost-effectiveness, and process evaluation will be examined. Nine hundred forty-eight patients will be randomized 1:1 to intervention and control group.

Discussion

If eliPfad leads to fewer readmissions, proves (cost-)effective, and lowers the treatment burden, it should be introduced as a new standard of care in the German healthcare system.

Trial registration

The trial was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) on 08/14/2023 under the ID DRKS00031500.
Association between insulin resistance, metabolic syndrome and its components and lung cancer: a systematic review and meta-analysis
Authors: Liu Jingxuan , Wang Rui , Tan Song , Zhao Xiaohu , Hou Aihua
Published: March 2024

Background

A growing body of evidence points to the association between insulin resistance (IR), metabolic syndrome (MetS) and its components and lung cancer incidence, but remains controversial and unknown.

Methods

A systematic search was conducted through PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI) and Wanfang databases for the corresponding studies. Each study reported the risk estimate and 95% confidence intervals (CI) for lung cancer, and a fixed effects model or random effects model was used for outcome.

Results

We included 31 publications involving 6,589,383 people with 62,246 cases of lung cancer. Diabetes mellitus (DM) (RR = 1.11, 95% CI  1.06–1.16, P = 0.000) and IR (RR = 2.35, 95% CI  1.55–3.58, P = 0.000) showed a positive association with lung cancer risk. BMI (RR = 0.66, 95% CI  0.54–0.81, P = 0.000) and HDL-C (RR = 0.88, 95% CI  0.79–0.97, P = 0.010) were negatively correlated with lung cancer. MetS(RR = 0.99, 95% CI  0.90–1.09, P = 0.801), TC (RR = 0.93, 95% CI  0.81–1.06, P = 0.274), TG (RR = 0.99, 95% CI  0.88–1.12,P = 0.884), LDL-C (RR = 1.01, 95% CI  0.87–1.16, P = 0.928), hypertension (RR = 1.01, 95% CI  0.88–1.15, P = 0.928), FBG (RR = 1.02, 95% CI  0.92–1.13, P = 0.677) and obesity (RR = 1.11, 95% CI  0.92–1.35, P = 0.280) were not associated with lung cancer.

Conclusion

Our study showed that the risk of lung cancer is correlated with DM, IR, BMI, and HDL-C. Timely control of these metabolic disorders may have a positive effect on preventing lung cancer.

Trial registration Our study has been registered in the Prospective Register of Systematic Reviews (PROSPERO), ID: CRD42023390710.
The role of Smarcad1 in retroviral repression in mouse embryonic stem cells
Authors: Bren Igor , Tal Ayellet , Strauss Carmit , Schlesinger Sharon
Published: March 2024

Background

Moloney murine leukemia virus (MLV) replication is suppressed in mouse embryonic stem cells (ESCs) by the Trim28-SETDB1 complex. The chromatin remodeler Smarcad1 interacts with Trim28 and was suggested to allow the deposition of the histone variant H3.3. However, the role of Trim28, H3.3, and Smarcad1 in MLV repression in ESCs still needs to be fully understood.

Results

In this study, we used MLV to explore the role of Smarcad1 in retroviral silencing in ESCs. We show that Smarcad1 is immediately recruited to the MLV provirus. Based on the repression dynamics of a GFP-reporter MLV, our findings suggest that Smarcad1 plays a critical role in the establishment and maintenance of MLV repression, as well as other Trim28-targeted genomic loci. Furthermore, Smarcad1 is important for stabilizing and strengthening Trim28 binding to the provirus over time, and its presence around the provirus is needed for proper deposition of H3.3 on the provirus. Surprisingly, the combined depletion of Smarcad1 and Trim28 results in enhanced MLV derepression, suggesting that these two proteins may also function independently to maintain repressive chromatin states.

Conclusions

Overall, the results of this study provide evidence for the crucial role of Smarcad1 in the silencing of retroviral elements in embryonic stem cells. Further research is needed to fully understand how Smarcad1 and Trim28 cooperate and their implications for gene expression and genomic stability.
Reducing the energy consumption of buildings by implementing insulation scenarios and using renewable energies
Authors: Shahee Arash , Abdoos Mahmood , Aslani Alireza , Zahedi Rahim
Published: March 2024

The reduction of fossil energy sources, the harmful environmental effects caused by high energy consumption, and the increase in the share of energy consumption in the building sector have increased the need to pay attention to building energy consumption. This study offers an intricate examination of a residential locality in Florida, with a particular emphasis on the architectural design of a building, issues related to the local environment and several possibilities for enhancing energy efficiency. It examines the influence of the environment in the area on architectural design and investigates two different possibilities for improving energy efficiency. The first scenario focuses on assessing thermal insulation and shading, while the second scenario envisions utilizing photovoltaic cells to achieve a zero-energy building. The proposed initiatives seek to optimize energy efficiency, save expenses, and foster environmental sustainability in the region. In this research, the total energy consumption of a building with residential use in the climate of the case study was validated by DesignBuilder®simulation software, and the results obtained from the software. Then, using the standard of energy consumption of the building, various strategies for optimizing energy consumption have been simulated. Using energy simulation software, solutions for using external horizontal awnings and installing a thermal insulation sheet on the external wall of the building were investigated, which resulted in a reduction of 200 kWh of energy consumption compared to the normal state. Then, the building’s energy consumption intensity was calculated for each of the proposed solutions, and the building’s energy classification was determined with energy star and LEED standards.
Demographic and Clinical Factors Associated With Health-Related Quality-of-Life Profiles Among Prostate Cancer Survivors
Authors: Potosky Arnold L. , Ahn Jaeil , Xia Yi , Lin Li , Chen Ronald C. , Graves Kristi D. , Pan Wei , Fall-Dickson Jane M. , Keegan Theresa H.M. , Paddock Lisa E. , Wu Xiao-Cheng , Shrestha Anshu , Reeve Bryce B.
Published: March 2024

PURPOSE

Our purpose was to describe the prevalence and predictors of symptom and function clusters related to physical, emotional, and social components of general health-related quality of life (HRQOL) in a population-based sample of prostate cancer (PCa) survivors.

METHODS

Participants (N = 1,162) completed a baseline survey at a median of 9 months after diagnosis to ascertain the co-occurrence of eight symptom and functional domains that are common across all cancers and not treatment-specific. We used latent profile analysis (LPA) to identify subgroup profiles of survivors with low, moderate, or high HRQOL levels. Multinomial logistic regression models were used to identify clinical and sociodemographic factors associated with survivors' membership in the low versus moderate or high HRQOL profile.

RESULTS

The LPA identified 16% of survivors who were categorized in the low HRQOL profile at baseline, indicative of the highest symptom burden and lowest functioning. Factors related to survivors' membership in the low versus higher HRQOL profile groups included less than age 65 years at diagnosis, identifying as non-Hispanic Black race, not working, being a former versus never smoker, systemic therapy, less companionship, more comorbidities, lower health care financial well-being, or less spirituality. Several factors remained associated with remaining in the low versus higher HRQOL profiles on the follow-up survey (n = 699), including younger age, Black race, comorbidity, and lower financial and spiritual well-being.

CONCLUSION

About one of six PCa survivors experienced elevated physical and psychosocial symptoms that were independent of local curative therapy, but with younger age, race, comorbidity, and lower financial and spiritual well-being as stable risk factors for poor HRQOL over time.
The Drosophila neuroblast polarity cycle at a glance
Authors: Penkert Rhiannon R. , LaFoya Bryce , Moholt-Siebert Lucille , Vargas Elizabeth , Welch Sarah E. , Prehoda Kenneth E.
Published: March 2024

Drosophila neural stem cells, or neuroblasts, rapidly proliferate during embryonic and larval development to populate the central nervous system. Neuroblasts divide asymmetrically to create cellular diversity, with each division producing one sibling cell that retains the neuroblast fate and another that differentiates into glia or neurons. This asymmetric outcome is mediated by the transient polarization of numerous factors to the cell cortex during mitosis. The powerful genetics and outstanding imaging tractability of the neuroblast make it an excellent model system for studying the mechanisms of cell polarity. This Cell Science at a Glance article and the accompanying poster explore the phases of the neuroblast polarity cycle and the regulatory circuits that control them. We discuss the key features of the cycle – the targeted recruitment of proteins to specific regions of the plasma membrane and multiple phases of highly dynamic actomyosin-dependent cortical flows that pattern both protein distribution and membrane structure.
Μια νέα ερμηνεία ενός γκράφιτι από υστερορωμαϊκή οικία της αρχαίας Ελεύθερνας
Authors: Δεληγιαννάκης Γεώργιος
Published: March 2024

P. Themelis (Κριτική Εστία 5, [1994-1996], 269; SEG 45, 1266) published a shortgraffito that was engraved on the door lintel connecting the rooms 23 and 26of the so-called House 2 of Sector I of ancient Eleftherna. It reads Νείκην τῷΚυρείῳ. It has been dated to the third or the early fourth century CE and ithas been interpreted as a wish to the God by Christians, possibly related to thereligious persecutions of the Roman State against them ca. 250 CE. The use ofthe terms κύριος and ν(ε)ίκη in Roman and Late Roman acclamations foundin textual sources, in both religious and secular contexts, is here analysed;the author rejects the previous interpretations and argues that this graffito isan acclamatory wish for a victory and/or the well-being of the owner of thehouse. Based on Amm. Marc. 16.8.9, he, moreover, connects it with a contem-porary ritual of the Roman house.
Konfiskaty kosztowności w świątyniach różnych związków religijnych w Mińsku i Białoruskiej Socjalistycznej Republice Radzieckiej w świetle dokumentu z maja 1922 roku. Przyczynek do realizacji bolszewickiej polityki ekonomicznej i wyznaniowej
Authors: Gil Andrzej
Published: March 2024

W artykule autor przedstawia wybrane aspekty bolszewickiej polityki konfiskaty kosztowności przechowywanych w świątyniach związków wyznaniowych na terenie Białoruskiej Socjalistycznej Republiki Radzieckiej w 1922 r. Dopełnieniem treści jest przechowywane w Narodowym Archiwum Republiki Białoruś sprawozdanie Centralnej Białoruskiej Komisji ds. Konfiskaty Kosztowności Cerkiewnych na terytorium Sowieckiej Socjalistycznej Republiki Białorusi z maja 1922 r.
Explicit models of ℓ_1-preduals and the weak* fixed point property in ℓ_1
Authors: Casini Emanuele , Miglierina Enrico , Piasecki Łukasz
Published: March 2024

We provide a concrete isometric description of all the preduals of $\ell_1$
for which the standard basis in $\ell_1$ has a finite number of $w^*$-limit points.
Then, we apply this result to give an example of an $\ell_1$-predual $X$ such
that its dual $X^*$ lacks the weak$^*$ fixed point property for nonexpansive
mappings (briefly, $w^*$-FPP), but $X$ does not contain an isometric copy
of any hyperplane $W_{\alpha}$ of the space $c$ of convergent sequences such
that $W_\alpha$ is a predual of $\ell_1$ and $W_\alpha^*$ lacks the $w^*$-FPP.
This answers a question left open in the 2017 paper of the present authors.
Estimating Demand for Subscription Products: Identification of Willingness to Pay Without Price Variation
Authors: Chou Cheng , Kumar Vineet
Published: March 2024

We obtain consumer willingness to pay for subscription product lacking price variation by leveraging the usage and subscription choice variation.
Bartonella henselae related unilateral anterior uveitis and subsequent multifocal retinitis in a case under certolizumab treatment
Authors: Kayabaşı Mustafa , Kefeli Işıl , Çakar Özdal Pınar , Saatci Ali Osman
Published: March 2024

Introduction: A case of ocular bartonellosis under anti-tumour necrosis factor treatment is described. Case description: A 29-year-old woman with psoriasis who had been on certolizumab treatment was examined with a left visual deterioration following a fever bout, malaise, and placoid erythematous rashes on her neck. As there was acute anterior uveitis in her left eye, it was recommended to stop certolizumab treatment for a possible infectious aetiology. However, her physician elected to continue the certolizumab treatment. Ten days later, the patient noticed further visual decline despite the topical steroid treatment. This time, there were scattered yellow-white small retinitis foci at the left posterior pole. Infectious agents were searched and while Bartonella henselae antibodies were negative for immunoglobulin M, the immunoglobulin G titre was 1/80. Clinical findings were improved with the systemic treatment of oral trimethoprim-sulfamethoxazole (160/800 mg twice daily for six weeks) and azithromycin (500 mg once daily for two weeks). Discussion: Though extremely rare, ocular bartonellosis should be kept in mind in patients on anti-tumour necrosis factor treatment as rapid and accurate diagnosis may end up with an excellent visual outcome and full recovery.
Extrato de espinafre como fonte de nitrito em linguiça frescal: atributos de qualidade e estabilidade durante o armazenamento refrigerado
Authors: Cherobin Ana Karolina , Do Amaral Adrieli Maiandra Piccinin , Moroni Liziane Schittler , Cavalheiro Darlene , Sehn Georgia Ane Raquel
Published: March 2024

Introdução: Os consumidores têm inúmeras preocupações em relação à saúde, dentre as quais o consumo elevado de aditivos químicos, como os conservantes, que ao reagir com substâncias presentes nos alimentos podem produzir compostos cancerígenos. Alguns vegetais, como o espinafre, podem ser fontes naturais desses conservantes, e sua aplicação pode aumentar a saudabilidade dos produtos cárneos. Objetivo: Avaliar os efeitos do extrato de espinafre como fonte de nitrito para conservação de linguiças frescais, armazenadas durante 35 dias sob refrigeração. Material e Método: Quatro formulações foram produzidas: controle positivo, com sal de cura comercial (CP), controle negativo, sem sal de cura (CN), extrato de espinafre (EE) e extrato de espinafre pré-convertido por bactérias nitrato-redutoras (EEPC). As linguiças foram avaliadas através da composição centesimal, cor, teor residual de nitrito, TBARS e avaliação microbiológica. Resultados: O sal de cura (CP) resultou em menores alterações na coloração das linguiças frescais. O TBARS aumentou aproximadamente 2,5 vezes (p<0,05) ao longo dos 35 dias, em todas as formulações, e os menores valores, ao final desse período, foram encontrados nas formulações CP e EEPC. Estas mesmas formulações apresentaram os maiores teores residuais de nitrito e menor contagem de BAL e enterobactérias (35 dias), o que comprova que o EEPC é tão eficiente quanto o sal de cura comercial como conservante em linguiça frescal armazenada sob refrigeração. Conclusão: O uso de EEPC pode ser uma alternativa promissora para a indústria cárnea, possibilitando o desenvolvimento de produtos clean label que atendam à demanda por produtos mais saudáveis.
Leading the Charge
Authors: Milton Tina
Published: March 2024

As the demand for wireless charging devices in consumer electronics surges, CET&D explores the testing, standards and regulatory landscape for this emerging technology.
Law of Nature
Authors: Riedl Andreas
Published: March 2024

In this essential guide Atlas Material Testing Technology introduces us to the key standards and organizations required to make accelerated weathering testing accurate, realistic and reliable.
Standard Practice
Authors: Wai Cheebeng
Published: March 2024

Manufacturers need to ready themselves – and their product lines – for the new edition of the IEC 62368-1 safety standard, says CSA Group.
Immunoglobulin A glomerulonephropathy: A review
Authors: El Labban Mohamad , Surani Salim
Published: March 2024

In this editorial, we comment on the article by Meng et al published in the World Journal of Clinical Cases. We comprehensively review immunoglobulin A nephropathy (IgAN), including epidemiology, clinical presentation, diagnosis, and management. IgAN, also known as Berger's disease, is the most frequent type of primary glomerulonephritis (GN) globally. It is mostly found among the Asian population. The presentation can be variable, from microscopic hematuria to a rapidly progressive GN. Around 50% of patients present with single or recurring episodes of gross hematuria. An upper respiratory infection and tonsillitis often precede these episodes. Around 30% of patients present microscopic hematuria with or without proteinuria, usually detected on routine examination. The diagnosis relies on having a renal biopsy for pathology and immunofluorescence microscopy. We focus on risk stratification and management of IgAN. We provide a review of all the landmark studies to date. According to the 2021 KDIGO (kidney disease: Improving Global Outcomes) guidelines, patients with non-variant form IgAN are first treated conservatively for three to six months. This approach consists of adequate blood pressure control, reduction of proteinuria with renin-angiotensin system blockade, treatment of dyslipidemia, and lifestyle modifications (weight loss, exercise, smoking cessation, and dietary sodium restrictions). Following three to six months of conservative therapy, patients are further classified as high or low risk for disease progression. High-risk patients have proteinuria ≥ 1 g/d or < 1 g/d with significant microscopic hematuria and active inflammation on kidney biopsy. Some experts consider proteinuria ≥ 2 g/d to be very high risk. Patients with high and very high-risk profiles are treated with immunosuppressive therapy. A proteinuria level of < 1 g/d and stable/improved renal function indicates a good treatment response for patients on immunosuppressive therapy.
Effect of comprehensive nursing on the quality of life and swallowing function in individuals diagnosed with ischemic stroke
Authors: Hu Heng-Fen , Sang Yu-Fei , Xiao Yan-Qing
Published: March 2024

BACKGROUND

Ischemic stroke (IS) is a widely recognized disease characterized by high prevalence, mortality, morbidity, disability, and recurrence rates. It ranks prominently in terms of mortality, constituting 60%-80% of stroke cases.

AIM

To explore the impact of comprehensive nursing care on the quality of life and swallowing function in individuals diagnosed with IS.

METHODS

This study comprised 172 patients with IS admitted to our hospital between February 2018 to March 2021. The participants were divided into two groups, namely the control group (n = 80) receiving routine care and the research group (n = 92) receiving comprehensive care. Various assessment scales, including the standard swallowing function assessment scale (SSA), National Institutes of Health Stroke scale (NIHSS), European stroke scale (ESS), self-rating anxiety scale (SAS), self-rating depression scale (SDS), Barthel index (BI), and the motor function assessment scale (MAS), were employed to evaluate the improvement in swallowing function, neurological deficits, clinical outcomes, anxiety, depression, daily living activities, and motor function before and after care. Furthermore, the study compared the occurrence of adverse reactions during the nursing period, life quality before and after the intervention, rehabilitation compliance, and nursing satisfaction between the two groups.

RESULTS

After the nursing intervention, the research group exhibited significantly improved SSA and NIHSS scores compared to the control group (P < 0.05). Moreover, both groups demonstrated significant reductions in SAS and SDS scores (P < 0.05), with the research group showing more obvious advantages (P < 0.05). Compared to the control group, the research group displayed significantly better ESS, BI, and MAS scores (P < 0.05), coupled with a lower incidence of adverse reactions (P < 0.05). Additionally, the research group demonstrated markedly higher levels of life quality, rehabilitation compliance, and nursing satisfaction compared to the control group (P < 0.05).

CONCLUSION

Comprehensive nursing effectively improved swallowing function, quality of life, and patient satisfaction, highlighting its clinical significance.
Appendiceal intussusception complicated by adenocarcinoma of the cecum: A case report
Authors: Long Yu , Xiang Yi-Ning , Huang Fei , Xu Lei , Li Xiao-Yun , Zhen Yun-Huan
Published: March 2024

BACKGROUND

Appendiceal intussusception is a pathological condition in which the appendix is inverted into the cecum, which may cause symptoms that resemble those of other gastrointestinal disorders and may induce intestinal obstruction. The rarity of this case presentation is the co-occurrence of appendiceal intussusception and cecal adenocarcinoma, a combination that to our knowledge has not previously been reported in the medical literature. This case provides new insights into the complexities of diagnosing and managing overlapping pathologies.

CASE SUMMARY

A 25-year-old woman presented with persistent periumbilical pain and bloody stools. An initial biopsy showed cecal cancer; however, subsequent colonoscopy and computed tomography findings raised the suspicion of appendiceal intussusception, which was later confirmed postoperatively. This unique case was characterized by a combination of intussusception and adenocarcinoma of the cecum. The intervention included a laparoscopic right hemicolectomy, which led to the histopathological diagnosis of mucinous adenocarcinoma with appendiceal intussusception. The patient recovered well postoperatively and was advised to initiate adjuvant chemotherapy. This case highlights not only the importance of considering appendiceal intussusception in the differential diagnosis, but also the possibility of appendicitis and the atypical presentation of neoplastic lesions.

CONCLUSIONS

Physicians should consider the possibility of appendiceal intussusception in cases of atypical appendicitis, particularly when associated with neoplastic presentation.
Multilocular thymic cysts can be easily misdiagnosed as malignant tumor on computer tomography: A case report
Authors: Sun Jun , Yang Qing-Ning , Guo Yi , Zeng Ping , Ma Long-Yan , Kong Ling-Wen , Zhao Bo-Ying , Li Chuan-Ming
Published: March 2024

BACKGROUND

Multilocular thymic cyst (MTC) is a rare mediastinal lesion which is considered to occur in the process of acquired inflammation. It is usually characterized by well-defined cystic density and is filled with transparent liquid.

CASE SUMMARY

We report on a 39-year-old male with a cystic-solid mass in the anterior mediastinum. Computer tomography (CT) imaging showed that the mass was irregular with unclear boundaries. After injection of contrast agent, there was a slight enhancement of stripes and nodules. According to CT findings, it was diagnosed as thymic cancer.

CONCLUSION

After surgery, MTC accompanied by bleeding and infection was confirmed by pathological examination. The main lesson of this case was that malignant thymic tumor and MTC of the anterior mediastinum sometimes exhibit similar CT findings. Caution is necessary in clinical work to avoid misdiagnosis.