bluuebunny/crossref_metadata_2025 huggingface dataset:
The IRE1α Endonuclease Plays a Dual Role in Regulating the XBP1/miRNA-34a Axis and PD-1 Expression within Natural Killer Cells in Hodgkin Lymphoma
Authors: Bednarska Karolina , Thillaiyampalam Gayathri , Mujaj Sally , Nourse Jamie , Gunawardana Jay , Sabdia Muhammed B. , Law Soi C. , Pilaar Anna , Cui Qingyan , de Long Lilia M. , Vari Frank , Gandhi Maher K. , Cristino Alexandre S.
Published: April 2024

Introduction: Hodgkin lymphoma (HL) is deficient in major histocompatibility complex class I, rendering it susceptible to antitumoral immunity by natural killer (NK) cells. Despite the functional impairment of PD-1+ NK cells in HL, the underlying mechanisms of NK cell dysfunction remain unclear. Methods: This study involved 14 HL patients and SNK10/KHYG-1 cell lines to assess NK cell activation against cancer cells. Activation was measured through transcript (PCR) and protein expression (flow cytometry). Regulatory mechanisms associated with IRE1α activation were validated through knockdown and luciferase reporter assays. Results: Our findings reveal a novel role for IRE1α-endonuclease in fine-tuning NK cell effector functions by orchestrating the XBP1s/microRNA-34a-5p/PD-1 axis. When NK cells encounter cancer cells, IRE1α endonuclease activates the decay of microRNA-34a-5p, resulting in increased expression of XBP1s and PD-1. IRE1α-endonuclease activation enhances NK cell functions while promoting PD-1 expression. In turn, PD-1 is directly regulated by microRNA-34a-5p, which binds to the 3′UTR of PD-1 transcript to repress PD-1 protein on the NK cell surface. Importantly, IRE1α-pathway activation is impaired in NK cells from HL patients. Conclusion: The IRE1α endonuclease emerges as a key player, simultaneously regulating the XBP1s/microRNA-34a-5p/PD-1 axis in NK cells, a process disrupted in HL. Targeting the IRE1α-pathway holds promise as a therapeutic strategy to optimize NK cell functions in Hodgkin lymphoma treatments.
A marca ecológica: comunicação promocional e gestão
Authors:   Universidade de São Paulo. Escola de Comunicações e Artes, Sato Silvio Koiti , Perez Clotilde ,   Universidade de São Paulo. Escola de Comunicações e Artes
Published: April 2024

As marcas ocupam um lugar de destaque no cotidiano atual, em momentos e situações as mais variadas, em múltiplas facetas que acompanham, invadem e se imiscuem na vida das pessoas, queiram elas ou não. Países, lugares, pessoas, alimentos in natura, serviços, espetáculos, entretenimento - tudo é envolto numa lógica marcária. Diante desse cenário, a obra "A marca ecológica: comunicação promocional e gestão" se propõe a apresentar um estudo sobre as marcas na atualidade, a partir de uma retomada histórica na evolução das teorias e discussões que permeiam o Branding, o Marketing e o consumo, mostrando um processo claramente entrelaçado, e com importância crescente das marcas nas interações, tensões e colaborações entre polos com papéis anteriormente distintos e opostos. Destaca-se que o presente texto reflete os estudos de mais de três décadas sobre marcas, integrando as visões do marketing, da publicidade, da comunicação, da gestão estratégica e da semiótica, constantes em diversos projetos de pesquisa junto ao GESC3 - Grupo de Estudos Semióticos em Comunicação, Cultura e Consumo, da ECA USP e da Casa Semio, sustentando a rentabilidade recíproca da articulação da pesquisa de mercado e da pesquisa acadêmica.
Atherosclerotic Plaque Epigenetic Age Acceleration Predicts a Poor Prognosis and Is Associated With Endothelial-to-Mesenchymal Transition in Humans
Authors: Diez Benavente Ernest , Hartman Robin J.G. , Sakkers Tim R. , Wesseling Marian , Sloots Yannicke , Slenders Lotte , Boltjes Arjan , Mol Barend M. , de Borst Gert J. , de Kleijn Dominique P.V. , Prange Koen H.M. , de Winther Menno P.J. , Kuiper Johan , Civelek Mete , van der Laan Sander W. , Horvath Steve , Onland-Moret N. Charlotte , Mokry Michal , Pasterkamp Gerard , den Ruijter Hester M.
Published: April 2024

BACKGROUND:

Epigenetic age estimators (clocks) are predictive of human mortality risk. However, it is not yet known whether the epigenetic age of atherosclerotic plaques is predictive for the risk of cardiovascular events.

METHODS:

Whole-genome DNA methylation of human carotid atherosclerotic plaques (n=485) and of blood (n=93) from the Athero-Express endarterectomy cohort was used to calculate epigenetic age acceleration (EAA). EAA was linked to clinical characteristics, plaque histology, and future cardiovascular events (n=136). We studied whole-genome DNA methylation and bulk and single-cell transcriptomics to uncover molecular mechanisms of plaque EAA. We experimentally confirmed our in silico findings using in vitro experiments in primary human coronary endothelial cells.

RESULTS:

Male and female patients with severe atherosclerosis had a median chronological age of 69 years. The median epigenetic age was 65 years in females (median EAA, −2.2 [interquartile range, −4.3 to 2.2] years) and 68 years in males (median EAA, −0.3 [interquartile range, −2.9 to 3.8] years). Patients with diabetes and a high body mass index had higher plaque EAA. Increased EAA of plaque predicted future events in a 3-year follow-up in a Cox regression model (univariate hazard ratio, 1.7;
P
=0.0034) and adjusted multivariate model (hazard ratio, 1.56;
P
=0.02). Plaque EAA predicted outcome independent of blood EAA (hazard ratio, 1.3;
P
=0.018) and of plaque hemorrhage (hazard ratio, 1.7;
P
=0.02). Single-cell RNA sequencing in plaque samples from 46 patients in the same cohort revealed smooth muscle and endothelial cells as important cell types in plaque EAA. Endothelial-to-mesenchymal transition was associated with EAA, which was experimentally confirmed by
TGFβ
-triggered endothelial-to-mesenchymal transition inducing rapid epigenetic aging in coronary endothelial cells.

CONCLUSIONS:

Plaque EAA is a strong and independent marker of poor outcome in patients with severe atherosclerosis. Plaque EAA was linked to mesenchymal endothelial and smooth muscle cells. Endothelial-to-mesenchymal transition was associated with EAA, which was experimentally validated. Epigenetic aging mechanisms may provide new targets for treatments that reduce atherosclerosis complications.
Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association
Authors: Cheng Richard K. , Kittleson Michelle M. , Beavers Craig J. , Birnie David H. , Blankstein Ron , Bravo Paco E. , Gilotra Nisha A. , Judson Marc A. , Patton Kristen K. , Rose-Bovino Leonie ,   on behalf of the American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology, and Council on Cardiovascular and Stroke Nursing
Published: April 2024

Cardiac sarcoidosis is an infiltrative cardiomyopathy that results from granulomatous inflammation of the myocardium and may present with high-grade conduction disease, ventricular arrhythmias, and right or left ventricular dysfunction. Over the past several decades, the prevalence of cardiac sarcoidosis has increased. Definitive histological confirmation is often not possible, so clinicians frequently face uncertainty about the accuracy of diagnosis. Hence, the likelihood of cardiac sarcoidosis should be thought of as a continuum (definite, highly probable, probable, possible, low probability, unlikely) rather than in a binary fashion. Treatment should be initiated in individuals with clinical manifestations and active inflammation in a tiered approach, with corticosteroids as first-line treatment. The lack of randomized clinical trials in cardiac sarcoidosis has led to treatment decisions based on cohort studies and consensus opinions, with substantial variation observed across centers. This scientific statement is intended to guide clinical practice and to facilitate management conformity by providing a framework for the diagnosis and management of cardiac sarcoidosis.
The “Mr. and Mrs. Ghat crab”, Ghatiana dvirupa sp. nov. (Decapoda: Brachyura: Gecarcinucidae) from the Central Western Ghats of India
Authors: PATI SAMEER KUMAR , BAJANTRI PARASHURAM PRABHU , HEGDE GOPALKRISHNA DATTATRAYA
Published: April 2024

A new species of gecarcinucid freshwater crab, Ghatiana dvirupa sp. nov., is described herein from the Kali Tiger Reserve of the Uttara Kannada district, Karnataka state, India. The Kali Tiger Reserve is a protected area, which is situated in the Central Western Ghats. The new species superficially most resembles Ghatiana sanguinolenta Pati, Thackeray & Pawar, 2023, from Karnataka but can easily be distinguished mainly by its ultimate article of the male first gonopod, which is distally gently curved inwards against the gently outwardly curved distal portion of the ultimate article in the latter species. Ghatiana dvirupa sp. nov. is also compared with the remaining species of the genus from Karnataka and some morphologically related species from Maharashtra. The difference in colour in life has been noticed between males and females of G. dvirupa sp. nov.; as such the common name of the new species is proposed as “Mr. and Mrs. Ghat Crab”. Ghatiana Pati & Sharma, 2014, is now known for 13 species, all from the Western Ghats of India. Karnataka currently possesses six species of Ghatiana, and many new species are yet to be described.
Smoothing effects of two-dimensional materials
Authors: Wang Xiaodong , Wang Hanlin , Peng Jiahao , Zhou Jun , Tao Chen , Zheng Xin , Ren Shuai , Zhou Peng , Chen Bo
Published: April 2024

Rippling in graphene, which is an out-of-plane corrugation induced by thermal fluctuations, plays a fundamental role in supporting the material’s stable existence. These ripples have also been instrumental in explaining various unconventional electronic and chemical properties
of graphene. Previous experimental findings have indicated that graphene exhibits smoothing effects on underlying substrates in the high-spatial-frequency regime. To explain this phenomenon, we employed a force balance model that considered both van der Waals forces and strain forces. By utilizing
traditional film-growth theory, our model successfully predicted experimental results.
Ultralight reduced graphene oxide based foam with excellent electromagnetic interference shielding and superior mechanical properties
Authors: Zheng He-Ping , Pan Ji-Lin , Tang Jian-Hua , Niu Jia-Hong , Lin Hao , Xu Ling
Published: April 2024

Reduced graphene oxide/carboxymethyl cellulose (RGO/CMC) foams with ultra-lightweight, excellent EMI shielding and mechanical robustness are fabricated based on a facile solution method and regulation of thermal reduction conditions. Results indicate that the two-step heating mode is
good to obtain better EMI shielding properties. By introducing only 10 wt% of CMC, high electrical conductivity up to 34.7 S/m and EMI shieling effectiveness (SE) up to 34.6 dB are obtained. In addition, due to the connection effect of CMC, superior compressive strength and modulus as high
as 8.3 KPa and 29.2 KPa are achieved, corresponding to an increase of 388.2% and 378.7%, respectively, compared to that of the RGO foam without CMC. Moreover, due to the ultralow density (∼4.1 mg/cm3) and high EMI SE of RGO/CMC, excellent specific shielding efficiency as high
as 42195 dB.cm2/g is obtained, way much superior to that of other metal-, graphene-, and CNT-based carbon foams. This work will have great significance for facile fabricating efficient EMI shielding materials towards electronics and aerospace applications.
Facilitating Holistic Nursing Through the Development of Mindfulness: A Model for Student Nurses
Authors: Matshaka Lerato , Downing Charlene , Ntshingila Nompumelelo
Published: April 2024

Holistic nursing should be a goal for all nurses. Patients that receive holistic nursing feel acknowledged, valued, and appreciated. Caring for patients holistically requires student nurses to possess and display attributes of mindfulness and Ubuntu. Student nurses therefore need to be supported and taught how to provide caring holistically to patients while being aware, being present, and conscious in the caring moment. The purpose of this article was to describe the model developed as a frame of reference to facilitate holistic nursing through developing mindfulness and Ubuntu. A theory generative, exploratory, and contextual research design was followed. A diagrammatic structure was constructed after the concept analysis was conducted. The model consisted of three phases with an outcome of a student nurse who is caring holistically and mindfully. The model provides a framework of reference to facilitate holistic nursing through the development of mindfulness. This study adds a model of mindfulness and a lens of looking at mindfulness through an African philosophy of Ubuntu.
Analysis of unsteady flow and pressure pulsation of multistage centrifugal pump based on actual size
Authors: Cui Baoling , Zhang Yingbin , Huang Yakun , Zhu Zuchao
Published: April 2024

In this paper, the unsteady flow and pressure pulsation in 11-stage centrifugal pump were analyzed based on large eddy simulation. The performances from the numerical simulation agreed with the ones from the experiment. The numerical results show that large pressure gradient area appears on trailing edge of blade pressure surface, and large vorticity intensity area appears on blade suction surface and trailing edge. The vortexes in the impeller passage decrease obviously with the increase of flow rate from 0.4 Q to 1.2 Q. As the stage increase, there is a local high pressure area at the tongue and it affects the fluid backflow. The main frequency of the pulsation at the impeller inlet is the blade passing frequency ( fBPF), and the main frequency at the impeller outlet and the interface is 2 fBPF. Due to interstage interference, the main frequency of the second impeller includes blade passing frequency of the first stage impeller (5 fn) and its own blade passing frequency (7 fn). With the increase of the stages, the rule of pulsation gradually tends to be consistent.
Dynamic fluctuations of salivary CGRP levels during migraine attacks: association with clinical variables and phenotypic characterization
Authors: Alpuente Alicia , Gallardo Victor J. , Asskour Laila , Caronna Edoardo , Torres-Ferrus Marta , Pozo-Rosich Patricia
Published: April 2024

Background

Migraine is a complex neurological disorder with significant heterogeneity in its clinical presentation and molecular mechanisms. Calcitonin gene-related peptide (CGRP) has emerged as a key player in migraine pathophysiology, but challenges remain in its utilization as a biomarker. This study aimed to investigate salivary CGRP levels during migraine attacks across the frequency spectrum and explore associations with clinical variables.

Methods

A prospective longitudinal pilot study was conducted, recruiting migraine patients from an outpatient headache clinic. Salivary CGRP levels were measured at interictal, onset, post-2 h of onset and end-of-attack. Using generalized linear mixed models, we explored the effect of CGRP changes over the attack in presence of depressive symptoms (DS), acute attack treatment, and after three-months of erenumab treatment. Finally, patients were classified and compared according to their CGRP phenotype.

Results

A total of 44 migraine patients were included (90.9% women), with 80 migraine attacks analyzed. Salivary CGRP levels increased at the onset of migraine attacks. We observed statistically significant interactions between DS and both the linear (Est. [SE]: 19.4 [5.8], p = 0.001) and quadratic terms of time (-19.1 [6.0], p = 0.002). Additionally, a significant three-way interaction within the use of acute treated attack (linear-term: -18.5 [6.2], p = 0.005; quadratic-term: 19.2 [6.8], p = 0.005) was also found. Molecular phenotyping revealed that 72.7% (32/44) of patients presented only CGRP-dependent attacks, while 27.3% (12/44) presented non-CGRP-dependent migraine attacks. Patients with only CGRP-dependent attacks were associated with younger age, shorter disease evolution time, a higher proportion of aura, and fewer monthly headache days (p < 0.05). Exploratory analysis of erenumab treatment effects did not result in changes in CGRP levels during migraine attacks.

Conclusions

Our study underscores the dynamic nature of migraine at a molecular level and emphasizes the importance of integrating clinical variables, such as depressive symptoms, in understanding its pathophysiology. The identification of distinct migraine subtypes based on CGRP dependence suggests potential opportunities for personalized treatment approaches.
Factors associated with plans for early retirement among Ontario family physicians during the COVID-19 pandemic: a cross-sectional study
Authors: Walsh Rachel , Telner Deanna , Butt Debra A. , Krueger Paul , Fleming Karen , MacDonald Sarah , Pyakurel Aakriti , Greiver Michelle , Jaakkimainen Liisa
Published: April 2024

Background

Higher numbers of family physicians (FPs) stopped practicing or retired during the COVID-19 pandemic, worsening the family doctor shortage in Canada. Our study objective was to determine which factors were associated with FPs’ plans to retire earlier during the COVID-19 pandemic.

Methods

We administered two cross-sectional online surveys to Ontario FPs asking whether they were “planning to retire earlier” as a result of the pandemic during the first and third COVID-19 pandemic waves (Apr-Jun 2020 and Mar-Jul 2021). We used logistic regression to determine which factors were associated with early retirement planning, adjusting for age.

Results

The age-adjusted proportion of FP respondents planning to retire earlier was 8.2% (of 393) in the first-wave and 20.5% (of 454) in the third-wave. Planning for earlier retirement during the third-wave was associated with age over 50 years (50–59 years odds ratio (OR) 5.37 (95% confidence interval (CI):2.33–12.31), 60 years and above OR 4.18 (95% CI: 1.90-10.23)), having difficulty handling increased non-clinical responsibilities (OR 2.95 (95% CI: 1.79–4.94)), feeling unsupported to work virtually (OR 1.96 (95% CI: 1.19–3.23)) or in-person (OR 2.70 (95% CI: 1.67–4.55)), feeling unable to provide good care (OR 1.82 (95% CI: 1.10–3.03)), feeling work was not valued (OR 1.92 (95% CI: 1.15–3.23)), feeling frightened of dealing with COVID-19 (OR 2.01 (95% CI: 1.19–3.38)), caring for an elderly relative (OR 2.36 (95% CI: 1.69–3.97)), having difficulty obtaining personal protective equipment (OR 2.00 (95% CI: 1.16–3.43)) or difficulty implementing infection control practices in clinic (OR 2.10 (95% CI: 1.12–3.89)).

Conclusions

Over 20% of Ontario FP respondents were considering retiring earlier by the third-wave of the COVID-19 pandemic. Supporting FPs in their clinical and non-clinical roles, such that they feel able to provide good care and that their work is valued, reducing non-clinical (e.g., administrative) responsibilities, dealing with pandemic-related fears, and supporting infection control practices and personal protective equipment acquisition in clinic, particularly in those aged 50 years or older may help increase family physician retention during future pandemics.
Prenatal ultrasound findings and clinical outcomes of uniparental disomy: a retrospective study
Authors: Wu Cui-Yi , Zhou Yi , Yin Xia , Peng Ruan , Xie Hong-Ning
Published: April 2024

Background

Uniparental disomy is the inheritance of a homologous chromosome pair or part of homologous chromosomes from only one parent. However, the clinical significance of uniparental disomy and the difference among the prognosis of involvement of different chromosomes remain unclear.

Objective

To assess the associated prenatal ultrasound presentations and clinical outcomes of uniparental disomy on different chromosomes and to analyze the relationship between prenatal ultrasound markers and clinical outcomes.

Study design

We retrospectively analyzed data from fetuses with uniparental disomy diagnosed using chromosome microarray analysis with the Affymetrix CytoScan HD array at our institution between January 2013 and September 2022. The relationship between prenatal ultrasound findings, the involved chromosome(s), and clinical outcomes was evaluated.

Results

During the study period, 36 fetuses with uniparental disomy were diagnosed, and two cases were excluded for non-available postnatal data. Finally, 34 fetuses were included in our study, of which 30 (88.2%) had uniparental disomy occurring on a single chromosome, while four (11.8%) were identified with uniparental disomy on different chromosomes. The most frequently involved chromosomes were chromosomes 16, X and 2, which presented in 8 (23.5%), 5 (14.7%) and 4 (11.8%), respectively. Prenatal ultrasound abnormalities were detected in 21 fetuses, with the most common category being multiple abnormalities (12 (57.1%)). Fetal growth restriction was identified in 14 (41.2%) fetuses, all of which coexisted with other abnormal findings. The rate of adverse perinatal outcomes in patients with uniparental disomy and fetal abnormalities was significantly higher than those without abnormalities (76.2% versus 15.4%, P = 0.002). The incidence of fetal or neonatal death was significantly higher in fetuses with fetal growth restriction than those without (85.7% versus 30.0%, P = 0.004).

Conclusions

The prognosis of fetuses with uniparental disomy combined with fetal abnormalities, especially fetal growth restriction, was much poorer than those without.
UBE2C promotes the proliferation of acute myeloid leukemia cells through PI3K/AKT activation
Authors: Wang Li , Zhao Shuqin , Wang Yongling , Liu Jianying , Wang Xiaoli
Published: April 2024

This study aims to investigate the role and mechanism of tubiquitin-conjugating enzyme E2 C (UBE2C) in acute myeloid leukemia (AML). Initially, UBE2C expression in leukemia was analyzed using the Cancer Genome Atlas database. Further, we silenced UBE2C expression using small-hairpin RNA (sh-RNA). UBE2C expression was detected via the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis. Apoptotic events and reactive oxygen species (ROS) levels were detected by flow cytometry. A xenograft model of leukemia cells were established, and the protein levels of UBE2C, KI-67, and cleaved-caspase 3 were detected by immunohistochemistry. We reported an overexpression of UBE2C in leukemia patients and cell lines (HL60, THP-1, U937, and KG-1 cells). Moreover, a high expression level of UBE2C was correlated with a dismal prognosis in AML patients. UBE2C knockdown inhibited the viability and promoted apoptosis in AML cells by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Furthermore, UBE2C knockdown increased cellular Fe2+ and ROS levels, and enhanced erastin-induced ferroptosis in a proteasome-dependent manner. UBE2C knockdown also suppressed the tumor formation of AML cells in the mouse model. In summary, our findings suggest that UBE2C overexpression promotes the proliferation and inhibits ferroptosis in AML cells by activating the PI3K/AKT pathway.
Interstitial round needles should not be used for cervical cancer patient treated with intracavitary/ interstitial brachytherapy using a Venezia applicator : a case report
Authors: Takagawa Yoshiaki , Izumi Sachiko , Takahashi Eiichi , Kita Midori
Published: April 2024

Background

Image-guided adaptive brachytherapy (IGABT) demonstrates an excellent local control rate and low toxicity while treating cervical cancer. For intracavitary/interstitial (IC/IS) brachytherapy (BT), several applicators are commercially available. Venezia (Elekta, Sweden), an advanced gynecological applicator, is designed for IC/IS BT for treating locally advanced cervical cancer. There are two types of interstitial needles for the Venezia applicator: the round needle and sharp needle. Generally, a round needle is safer because it has less risk of damaging the organ at risk than a sharp needle. However, there is currently no evidence to suggest that a round needle is better than a sharp needle for the Venezia applicator in IC/IS BT. Herein, we documented our experience of using both round and sharp needles with the Venezia applicator in IC/IS BT for cervical cancer.

Case presentation

A 71-year-old woman was diagnosed with clinical stage T2bN0M0 and the International Federation of Gynecology and Obstetrics stage IIB cervical squamous cell carcinoma. Definitive therapy, including a high-dose-rate BT boost, was planned using a round needle with the Venezia applicator in IC/IS BT. After inserting four interstitial round needles during the first and second BT sessions, an unexpectedly large gap (1.5 cm) was detected between the cervix and ovoid. We therefore used a sharp needle with the Venezia applicator for IC/IS BT during the third and fourth BT sessions. Three sharp needles were firmly inserted during the third and fourth BT sessions.

Conclusions

The study findings suggest that the interstitial round needle should not be used for cervical cancer patients undergoing IC/IS BT using the Venezia applicator.
Development and application of a deep learning-based comprehensive early diagnostic model for chronic obstructive pulmonary disease
Authors: Zhu Zecheng , Zhao Shunjin , Li Jiahui , Wang Yuting , Xu Luopiao , Jia Yubing , Li Zihan , Li Wenyuan , Chen Gang , Wu Xifeng
Published: April 2024

Background

Chronic obstructive pulmonary disease (COPD) is a frequently diagnosed yet treatable condition, provided it is identified early and managed effectively. This study aims to develop an advanced COPD diagnostic model by integrating deep learning and radiomics features.

Methods

We utilized a dataset comprising CT images from 2,983 participants, of which 2,317 participants also provided epidemiological data through questionnaires. Deep learning features were extracted using a Variational Autoencoder, and radiomics features were obtained using the PyRadiomics package. Multi-Layer Perceptrons were used to construct models based on deep learning and radiomics features independently, as well as a fusion model integrating both. Subsequently, epidemiological questionnaire data were incorporated to establish a more comprehensive model. The diagnostic performance of standalone models, the fusion model and the comprehensive model was evaluated and compared using metrics including accuracy, precision, recall, F1-score, Brier score, receiver operating characteristic curves, and area under the curve (AUC).

Results

The fusion model exhibited outstanding performance with an AUC of 0.952, surpassing the standalone models based solely on deep learning features (AUC = 0.844) or radiomics features (AUC = 0.944). Notably, the comprehensive model, incorporating deep learning features, radiomics features, and questionnaire variables demonstrated the highest diagnostic performance among all models, yielding an AUC of 0.971.

Conclusion

We developed and implemented a data fusion strategy to construct a state-of-the-art COPD diagnostic model integrating deep learning features, radiomics features, and questionnaire variables. Our data fusion strategy proved effective, and the model can be easily deployed in clinical settings.

Trial registration

Not applicable. This study is NOT a clinical trial, it does not report the results of a health care intervention on human participants.
Effects of quercetin on polycystic ovary syndrome in animal models: a systematic review and meta-analysis
Authors: Su Pingping , Chen Chao , Pang Liang , Wu Kai , Sun Yun
Published: April 2024

Background

Metformin is an insulin sensitizer that is widely used for the treatment of insulin resistance in polycystic ovary syndrome patients. However, metformin can cause gastrointestinal side effects.

Purpose

This study showed that the effects of quercetin are comparable to those of metformin. Therefore, this study aimed to systematically evaluate the efficacy of quercetin in treating PCOS.

Methods

The present systematic search of the Chinese National Knowledge Infrastructure (CNKI), Wanfang Data Information Site, Chinese Scientific Journals Database (VIP), SinoMed, Web of Science, and PubMed databases was performed from inception until February 2024. The methodological quality was then assessed by SYRCLE’s risk of bias tool, and the data were analyzed by RevMan 5.3 software.

Results

Ten studies were included in the meta-analysis. Compared with those in the model group, quercetin in the PCOS group had significant effects on reducing fasting insulin serum (FIS) levels (P = 0.0004), fasting blood glucose (FBG) levels (P = 0.01), HOMA-IR levels (P < 0.00001), cholesterol levels (P < 0.0001), triglyceride levels (P = 0.001), testosterone (T) levels (P < 0.00001), luteinizing hormone (LH) levels (P = 0.0003), the luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (P = 0.01), vascular endothelial growth factor (VEGF) levels (P < 0.00001), malondialdehyde (MDA) levels (P = 0.03), superoxide dismutase (SOD) levels (P = 0.01) and GLUT4 mRNA expression (P < 0.00001).

Conclusion

This meta-analysis suggested that quercetin has positive effects on PCOS treatment. Quercetin can systematically reduce insulin, blood glucose, cholesterol, and triglyceride levels in metabolic pathways. In the endocrine pathway, quercetin can regulate the function of the pituitary-ovarian axis, reduce testosterone and luteinizing hormone (LH) levels, and lower the ratio of LH to follicle-stimulating hormone (FSH). Quercetin can regulate the expression of the GLUT4 gene and has antioxidative effects at the molecular level.
Role of imbalanced gut microbiota in promoting CRC metastasis: from theory to clinical application
Authors: Fan Shiying , Zhou Lujia , Zhang Wenjie , Wang Daorong , Tang Dong
Published: April 2024

Metastasis poses a major challenge in colorectal cancer (CRC) treatment and remains a primary cause of mortality among patients with CRC. Recent investigations have elucidated the involvement of disrupted gut microbiota homeostasis in various facets of CRC metastasis, exerting a pivotal influence in shaping the metastatic microenvironment, triggering epithelial-mesenchymal transition (EMT), and so on. Moreover, therapeutic interventions targeting the gut microbiota demonstrate promise in enhancing the efficacy of conventional treatments for metastatic CRC (mCRC), presenting novel avenues for mCRC clinical management. Grounded in the “seed and soil” hypothesis, this review consolidates insights into the mechanisms by which imbalanced gut microbiota promotes mCRC and highlights recent strides in leveraging gut microbiota modulation for the clinical prevention and treatment of mCRC. Emphasis is placed on the considerable potential of manipulating gut microbiota within clinical settings for managing mCRC.
The development of chimeric antigen receptor T-cells against CD70 for renal cell carcinoma treatment
Authors: Xiong Qinghui , Wang Haiying , Shen Qiushuang , Wang Yan , Yuan Xiujie , Lin Guangyao , Jiang Pengfei
Published: April 2024

In this study, we investigated CD70 as a promising target for renal cell carcinoma (RCC) therapy and developed a potent chimeric antigen receptor T (CAR-T) cells for potential clinical testing. CD70, found to be highly expressed in RCC tumors, was associated with decreased survival. We generated CAR-T cells expressing VHH sequence of various novel nanobodies from immunized alpaca and a single-chain variable fragment (scFv) derived from human antibody (41D12). In our in vitro experiments, anti-CD70 CAR-T cells effectively eliminated CD70-positive tumor cells while sparing CD70-negative cells. The nanobody-based CAR-T cells demonstrated significantly higher production of cytokines such as IL-2, IFN-γ and TNF-ɑ during co-culture, indicating their potential for enhanced functionality. In xenograft mouse model, these CAR-T cells exhibited remarkable anti-tumor activity, leading to the eradication of RCC tumor cells. Importantly, human T cell expansion after infusion was significantly higher in the VHH groups compared to the scFv CAR-T group. Upon re-challenging mice with RCC tumor cells, the VHH CAR-T treated group remained tumor-free, suggesting a robust and long-lasting anti-tumor response. These findings provide strong support for the potential of nanobody-based CD70 CAR-T cells as a promising therapeutic option for RCC. This warrants further development and consideration for future clinical trials and applications.
Discovery of a novel and highly selective JAK3 inhibitor as a potent hair growth promoter
Authors: Hossain Md Mehedi , Khalid Arfan , Akhter Zaheen , Parveen Sabra , Ayaz Mir Owais , Bhat Aadil Qadir , Badesra Neetu , Showket Farheen , Dar Mohmmad Saleem , Ahmed Farhan , Dhiman Sumit , Kumar Mukesh , Singh Umed , Hussain Razak , Keshari Pankaj , Mustafa Ghulam , Nargorta Amit , Taneja Neha , Gupta Somesh , Mir Riyaz A. , Kshatri Aravind Singh , Nandi Utpal , Khan Nooruddin , Ramajayan P. , Yadav Govind , Ahmed Zabeer , Singh Parvinder Pal , Dar Mohd Jamal
Published: April 2024

JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC50 of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under in vivo and in vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.
Mesothelin-based CAR-T cells exhibit potent antitumor activity against ovarian cancer
Authors: Guo Jing , Zeng Xiaozhu , Zhu Yongjie , Yang Dong , Zhao Xudong
Published: April 2024

Background

Ovarian cancer (OC) is characterized by its rapid growth and spread which, accompanied by a low 5-year survival rate, necessitates the development of improved treatments. In ovarian cancer, the selective overexpression of Mucin-16 (MUC16, CA125) in tumor cells highlights its potential as a promising target for developing anti-tumor therapies. However, the potential effectiveness of CAR-T cell therapy that targets MUC16 in ovarian cancer cells is unknown.

Methods

The expression of MUC16 in viable OC cells was detected using immunofluorescence and flow cytometry techniques. A MSLN-CAR construct, comprising the MUC16-binding polypeptide region of mesothelin (MSLN), a CD8 hinge spacer and transmembrane domain, 4-1BB, and CD3ζ endo-domains; was synthesized and introduced into T cells using lentiviral particles. The cytotoxicity of the resultant CAR-T cells was evaluated in vitro using luciferase assays. Cytokine release by CAR-T cells was measured using enzyme-linked immunosorbent assays. The anti-tumor efficacy of the CAR-T cells was subsequently assessed in mice through both systemic and local administration protocols.

Results

MSLN-CAR T cells exhibited potent cytotoxicity towards OVCAR3 cells and their stem-like cells that express high levels of MUC16. Also, MSLN-CAR T cells were inefficient at killing SKOV3 cells that express low levels of MUC16, but were potently cytotoxic to such cells overexpressing MUC16. Moreover, MSLN-CAR T cells delivered via tail vein or peritoneal injection could shrink OVCAR3 xenograft tumors in vivo, with sustained remission observed following peritoneal delivery of MSLN-CAR T cells.

Conclusions

Collectively, these results suggested that MSLN-CAR T cells could potently eliminate MUC16- positive ovarian cancer tumor cells both in vitro and in vivo, thereby providing a promising therapeutic intervention for MUC16-positive patients.
Microbiota-derived acetate attenuates neuroinflammation in rostral ventrolateral medulla of spontaneously hypertensive rats
Authors: Yin Xiaopeng , Duan Changhao , Zhang Lin , Zhu Yufang , Qiu Yueyao , Shi Kaiyi , Wang Sen , Zhang Xiaoguang , Zhang Huaxing , Hao Yinchao , Yuan Fang , Tian Yanming
Published: April 2024

Background

Increased neuroinflammation in brain regions regulating sympathetic nerves is associated with hypertension. Emerging evidence from both human and animal studies suggests a link between hypertension and gut microbiota, as well as microbiota-derived metabolites short-chain fatty acids (SCFAs). However, the precise mechanisms underlying this gut-brain axis remain unclear.

Methods

The levels of microbiota-derived SCFAs in spontaneously hypertensive rats (SHRs) were determined by gas chromatography-mass spectrometry. To observe the effect of acetate on arterial blood pressure (ABP) in rats, sodium acetate was supplemented via drinking water for continuous 7 days. ABP was recorded by radio telemetry. The inflammatory factors, morphology of microglia and astrocytes in rostral ventrolateral medulla (RVLM) were detected. In addition, blood-brain barrier (BBB) permeability, composition and metabolomics of the gut microbiome, and intestinal pathological manifestations were also measured.

Results

The serum acetate levels in SHRs are lower than in normotensive control rats. Supplementation with acetate reduces ABP, inhibits sympathetic nerve activity in SHRs. Furthermore, acetate suppresses RVLM neuroinflammation in SHRs, increases microglia and astrocyte morphologic complexity, decreases BBB permeability, modulates intestinal flora, increases fecal flora metabolites, and inhibits intestinal fibrosis.

Conclusions

Microbiota-derived acetate exerts antihypertensive effects by modulating microglia and astrocytes and inhibiting neuroinflammation and sympathetic output.
Targeting brain-peripheral immune responses for secondary brain injury after ischemic and hemorrhagic stroke
Authors: Duan Mingxu , Xu Ya , Li Yuanshu , Feng Hua , Chen Yujie
Published: April 2024

The notion that the central nervous system is an immunologically immune-exempt organ has changed over the past two decades, with increasing evidence of strong links and interactions between the central nervous system and the peripheral immune system, both in the healthy state and after ischemic and hemorrhagic stroke. Although primary injury after stroke is certainly important, the limited therapeutic efficacy, poor neurological prognosis and high mortality have led researchers to realize that secondary injury and damage may also play important roles in influencing long-term neurological prognosis and mortality and that the neuroinflammatory process in secondary injury is one of the most important influences on disease progression. Here, we summarize the interactions of the central nervous system with the peripheral immune system after ischemic and hemorrhagic stroke, in particular, how the central nervous system activates and recruits peripheral immune components, and we review recent advances in corresponding therapeutic approaches and clinical studies, emphasizing the importance of the role of the peripheral immune system in ischemic and hemorrhagic stroke.
Massive retroperitoneal hematoma caused by intercostal artery bleeding after blunt trauma: a case report
Authors: Zhu Ran , Liu Xiangtian , Li Xiaoli , Ye Liping
Published: April 2024

Background

The occurrence of massive retroperitoneal hematoma caused by intercostal artery bleeding is exceedingly uncommon.

Case presentation

A middle-aged male presented to the hospital after a fall. Computed tomography scan revealed a massive retroperitoneal hematoma without any evidence of organ or major vessel rupture. The angiogram revealed extravasation from a branch of the twelfth intercostal artery, and successful transcatheter arterial embolization was performed on this specific artery.

Conclusions

The possibility of intercostal artery rupture should be considered in cases of retroperitoneal hematomas, and accurate diagnosis can be achieved through imaging studies. Transcatheter arterial embolization represents an effective treatment modality.
To repair or to replace in mitral valve infective endocarditis? an updated meta-analysis
Authors: Awad Ahmed K. , Wilson Karim , Elnagar Mahmoud A. , Elbadawy Merihan A. , Fathy Mohamed H.
Published: April 2024

Background

Valve infective endocarditis (IE) is a potentially life-threatening condition that affects patients’ livelihoods. Current surgical options in mitral valve IE include mitral valve repair (MVr) or replacement (MVR). While each procedure boasts its merits, doubt remains as to which type of surgery is superior.

Methods

We searched PubMed, Scopus, Web of Science, and Cochrane literature databases for studies comparing MVR and MVr in mitral valve IE. Any randomized controlled trial (RCT) or observational studies that compare MVR vs. MVr in mitral valve IE were eligible. Our dichotomous outcomes were extracted in the form of event and total, and risk and hazard ratio (RR)(HR) with 95% confidence interval (CI) and were pooled and calculated using RevMan 5.0.

Results

Our study included 23 studies with a total population of 11,802 patients. Compared to MVR, MVr had statistically significant lower risks of both early mortality with RR [0.44; 95% CI, 0.38–0.51; p < 0.001] and long-term follow-up mortality with HR [0.70; 95% CI, 0.58–0.85; p = 0.0004]. Moreover, MVr was associated with a statistically significant lower risk of IE recurrence with RR [0.43; 95% CI, 0.32–0.58; p < 0.001]; however, no statistically significant differences between both groups in terms of re-operations with RR [0.83; 95% CI, 0.41–1.67; p = 0.60].

Conclusion

Our results suggest that MVr was superior in terms of in-hospital mortality, long-term survival, and risk of recurrence without significance in valve reoperation. Therefore, MVr is appropriate as a primary treatment choice and should be considered whenever possible in most IE patients.
Recent advances in nanomaterial-based biosensor for periodontitis detection
Authors: Hooshiar Mohammad Hosseini , Moghaddam Masoud Amiri , Kiarashi Mohammad , Al-Hijazi Athraa Y. , Hussein Abbas Fadel , A.Alrikabi Hareth , Salari Sara , Esmaelian Samar , Mesgari Hassan , Yasamineh Saman
Published: April 2024

Periodontitis, a chronic inflammatory condition caused by bacteria, often causes gradual destruction of the components that support teeth, such as the alveolar bone, cementum, periodontal ligament, and gingiva. This ultimately results in teeth becoming loose and eventually falling out. Timely identification has a crucial role in preventing and controlling its progression. Clinical measures are used to diagnose periodontitis. However, now, there is a hunt for alternative diagnostic and monitoring methods due to the progress of technology. Various biomarkers have been assessed using multiple bodily fluids as sample sources. Furthermore, conventional periodontal categorization factors do not provide significant insights into the present disease activity, severity and amount of tissue damage, future development, and responsiveness to treatment. In recent times, there has been a growing utilization of nanoparticle (NP)-based detection strategies to create quick and efficient detection assays. Every single one of these platforms leverages the distinct characteristics of NPs to identify periodontitis. Plasmonic NPs include metal NPs, quantum dots (QDs), carbon base NPs, and nanozymes, exceptionally potent light absorbers and scatterers. These find application in labeling, surface-enhanced spectroscopy, and color-changing sensors. Fluorescent NPs function as photostable and sensitive instruments capable of labeling various biological targets. This article presents a comprehensive summary of the latest developments in the effective utilization of various NPs to detect periodontitis.

Graphical Abstract
The correlation between ultrasonographic findings and clinical symptoms of pelvic endometriosis
Authors: Mostafavi Seyed Reza Saadat , Kor Elham , Sakhaei Seyyed Mohammad , Kor Anis
Published: April 2024

Objective

Considering the importance of endometriosis and its relatively high prevalence among women, this study sought to investigate clinical and Transrectal and transvaginal ultrasounds (TVS) findings of disease.

Methods

This descriptive-analytical study was performed based on medical records of 155 women with endometriosis admitted to Rasool-e Akram Hospital in Tehran for a TVS. All the sonography data and patients’ information were collected into checklists and analyzed in SPSS-25 software (IBM).

Results

The mean age of participants was 32.4 ± 6.1 years, ranging from 18 to 50 years. Endometrioma was prevalent in 129 patients (84.8%). Size of endometrioma (diameter) was more than 3 cm in 79.9% of patients, and 3 cm or fewer in 20.1% of cases. Bladder, intestinal, vaginal, and rectosigmoid involvements with endometriosis implants were observed in 4 (2.6%), 54 (35.5), 3 (0.2%), and 51 (33.5) of patients, respectively. A total of 64.5% of patients were diagnosed with incomplete stenosis of the Douglas pouch and 35.5% had complete stenosis. Deep infiltrating endometriosis (DIE) was less than 1 cm in 20.7%, 1 to 3 cm in 42.3%, and over 3 cm in 37% of patients. The most common manifestations of endometriosis Obliteration of the Douglas pouch, endometrioma, and DIE. In addition, imaging modalities have shown promising results, indicating the necessity to use transvaginal ultrasound as the first line of diagnosis in patients with clinically suspected endometriosis.
Genomic Landscape of Circulating Tumor DNA in Patients With Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor-2–Negative Metastatic Breast Cancer Treated With Abemaciclib: Data From the SCRUM-Japan Cancer Genome Screening Project
Authors: Hattori Masaya , Serelli-Lee Victoria , Naito Yoichi , Yamanaka Takashi , Yasojima Hiroyuki , Nakamura Rikiya , Fujisawa Takao , Imai Mitsuho , Nakamura Yoshiaki , Bando Hideaki , Kawaguchi Tsutomu , Yoshino Takayuki , Iwata Hiroji
Published: April 2024

PURPOSE

To understand the mutational landscape of circulating tumor DNA (ctDNA) and tumor tissue of patients with hormone receptor–positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) metastatic breast cancer (MBC) treated with abemaciclib + endocrine therapy (ET).

METHODS

Blood samples for ctDNA and/or tissue samples were collected from abemaciclib-treated patients with HR+/HER2– MBC enrolled in the SCRUM-Japan MONSTAR-SCREEN project. Blood samples were collected before abemaciclib initiation (baseline) and at disease progression/abemaciclib discontinuation (post abemaciclib treatment). Clinical and genomic characteristics including neoplastic burden (measured by shedding rate and maximum variant allele frequency [VAF]) were assessed at baseline. Genomic alterations in ctDNA were compared in paired baseline and post abemaciclib treatment samples.

RESULTS

All patients (N = 97) were female (median age, 57 years [IQR, 50-67]). In baseline ctDNA (n = 77), PIK3CA (37%), TP53 (28%), ESR1 (16%), and GATA3 (11%) were the most frequently mutated genes. Baseline tissue samples (n = 79) showed similar alteration frequencies. Among patients with baseline ctDNA data, 30% had received previous ET. ESR1 alteration frequency (35% v 8%; P < .01), median shedding rate (3 v 2), and maximum somatic VAF (4 v 0.8; both P < .05) were significantly higher in ctDNA from patients with previous ET than those without previous ET. In paired ctDNA samples (n = 33), PIK3CA and ESR1 alteration frequencies were higher after abemaciclib treatment than at baseline, though not statistically significant. Among the post-treatment alterations, those newly acquired were detected most frequently in FGF3/4/19 (18%); PIK3CA, TP53, CCND1, and RB1 (all 15%); and ESR1 (12%).

CONCLUSION

We summarized the ctDNA and cancer tissue mutational landscape, including overall neoplastic burden and PIK3CA and ESR1 hotspot mutations in abemaciclib-treated patients with HR+/HER2– MBC. The data provide insights that could help optimize treatment strategies in this population.