bluuebunny/crossref_metadata_2025 huggingface dataset:
PD-1 inhibitor sintilimab treated patients with metastatic triple-negative breast cancer
Authors: Jia Yan , Zhang Jie , Shi Yehui , Dong Guolei , Guo Xiaojing , Tong Zhongsheng
Published: October 2024

Purpose

Triple-negative breast cancer (TNBC) is a highly challenging subtype due to a unique tumor microenvironment. Several evidence (IMpassion130 trial and KEYNOTE-355 trial) supported the therapeutic effect of the immune checkpoint inhibitor in TNBC. However, the efficacy and safety of the PD-1 inhibitor sintilimab in breast cancer (BC) has not been well-investigated. So the real-world data on sintilimab-treated patients with metastatic BC were collected and analyzed in this study.

Methods

The patients were eligible according to the requirements included: ages between 18 years and 75 years; recurrent or metastatic TNBC; measurable disease based on RECIST v1.1; no limitation on the prior systemic treatments; and ECOG performance status of 0–1. Patients received sintilimab 200 mg intravenously every 3 weeks until unacceptable toxicity or disease progression.

Results

From 1 June 2019 to 1 October 2022, 40 female patients (median age, 55.5 years) with metastatic TNBC (mTNBC) were enrolled into the study. The median prior lines of systemic therapy for mTNBC was three (range, 1–8), with 60% of cases receiving at least three lines of therapy for metastatic disease. The visceral or brain metastasis was detected in 40.4% or 9.6% of patients, respectively. The median duration of response was 2.8 months (range, 0.7–21.0), and the median number of sintilimab doses administered was 4 (range, 1–30). The ORR and DCR were 22.5% and 72.5%, separately. The median PFS was 3.5 months (range, 1.4–21.0), with a 6-month PFS rate of 15.0% (6/40). The median OS was 52.5 months (range, 9.0–247.0) as of data cut-off. Common adverse effects were acceptable, and fatigue, skin rash, and pruritus were the frequent toxicity observed. Two cases of grade 3 curable adverse events were considered to be treatment-related. PD-L1-positive tumor was found in 40% cases (4/10) of mTNBC. Although statistical difference was not reached, the trend was obvious. Patients with PD-L1-positive tumor gained better treatment response, while the TMB-high carrier received more benefits of PFS and OS.

Conclusion

In our study, preliminary evidence provided the anticancer activity and acceptable adverse effects of sintilimab administered every 3 weeks to pretreated patients with mTNBC. Sintilimab showed its efficacy and safety of immunotherapy for patients with advanced TNBC.
Telocytes of the male reproductive system: dynamic tissue organizers
Authors: Sanches Bruno D. A. , Rocha Lara C. , Neto J. Pimentel , Beguelini Mateus Rodrigues , Ciena Adriano P. , Carvalho Hernandes F.
Published: October 2024

Telocytes are CD34+ interstitial cells that have long cytoplasmic projections (called telopodes), and have been detected in several organs, including those of the male reproductive system. In this brief review we evaluate the role of telocytes in tissue organization of the different organs of the male reproductive system in which these cells were studied. In general terms, telocytes act in the tissue organization through networks of telopodes that separate the epithelia from the stroma, as well as dividing the stroma into different compartments. In addition to this contribution to the structural integrity, there is direct and indirect evidence that such “walls” formed by telocytes also compartmentalize paracrine factors that they or other cells produce, which have a direct impact on morphogenesis and the maintenance of organ cell differentiation, as well as on their normal physiology. Moreover, alterations in telocytes and telopode networks are correlated with pathological conditions in the male reproductive system, in response to profound changes in structural organization of the organs, in inflammation, hyperplasia and cancer. Further studies are necessary to evaluate the molecular pathways telocytes employ in different contexts of physiology and disease.
Design and synthesis of thiahelicenes for molecular electronics
Authors: Baciu Bianca C. , Bronk Pawel J. , Guijarro Albert
Published: October 2024

The conductance of a tunneling electron through a π-conjugated molecule may be affected by the presence of different pathways in the orbital structure of the molecule, resulting in the constructive or destructive interference of the molecular wave function. This quantum interference (QI) directly translates into enhancement or suppression of conductance and offers the possibility of controlling this phenomenon through tailored synthesis. Hence, we set up synthetic methodologies to access a series of thiophene-fused helicenes with a well-defined positioning of the sulfur atoms, which control the occurrence of conducting, linearly conjugated as well as disrupted, cross-conjugated pathways. We describe these synthetic strategies and relate the expected electronic transport through our molecules to three key variables: a) the exo-/endo-topology of the S atom within the ring; b) the parity (odd/even) of the overall number of rings conforming to the helicene; and c) the size of the circuit. This series ranks from [7] to [11] fused rings, having both exo-, endo-, or mixed exo-endo-topology. Comparison of homologous dithiahelicenes with size-tunable highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) energies allows us to isolate the key variable of the bond topology from other electronic properties and face the study of QI in helically conjugated molecules. Understanding and tuning the conductance in such molecular solenoids is the main purpose of this work.
Natural compound-induced downregulation of antimicrobial resistance and biofilm-linked genes in wastewater Aeromonas species
Authors: Judan Cruz Khristina G. , Takumi Okamoto , Bongulto Kenneth A. , Gandalera Emmanuel E. , Kagia Ngure , Watanabe Kozo
Published: October 2024

Addressing the global antimicrobial resistance (AMR) crisis requires a multifaceted innovative approach to mitigate impacts on public health, healthcare and economic systems. In the complex evolution of AMR, biofilms and the acquisition of antimicrobial resistance genes (ARGs) play a pivotal role. Aeromonas is a major AMR player that often forms biofilm, harbors ARGs and is frequently detected in wastewater. Existing wastewater treatment plants (WWTPs) do not have the capacity to totally eliminate antimicrobial-resistant bacteria favoring the evolution of ARGs in wastewater. Besides facilitating the emergence of AMR, biofilms contribute significantly to biofouling process within the activated sludge of WWTP bioreactors. This paper presents the inhibition of biofilm formation, the expression of biofilm-linked genes and ARGs by phytochemicals andrographolide, docosanol, lanosterol, quercetin, rutin and thymohydroquinone. Aeromonas species were isolated and purified from activated sludge samples. The ARGs were detected in the isolated Aeromonas species through PCR. Aeromonas biofilms were quantified following the application of biocompounds through the microtiter plate assay. qPCR analyses of related genes were done for confirmation. Findings showed that the natural compounds inhibited the formation of biofilms and reduced the expression of genes linked to biofilm production as well as ARGs in wastewater Aeromonas. This indicates the efficacy of these compounds in targeting and controlling both ARGs and biofilm formation, highlighting their potential as innovative solutions for combating antimicrobial resistance and biofouling.
Association between weekend admission and in-hospital mortality for patients with ischemic heart disease upon surgery treatment
Authors: Liu Tianzhao , Lin Chuangpeng , Jia Chenyang , Wu Binbin , Liu Hailong , Liang Yan
Published: October 2024

Background

The existence and reasons for the weekend effect in patients with ischemic heart disease (IHD) were not yet fully identified. This study aimed to evaluate whether weekend admission was independently associated with in-hospital mortality and the possible mechanisms associated with the IHD patients.

Methods

The study was a retrospective study, including IHD patients from 2015 to 2023. The International Classification of Diseases, tenth revision (ICD-10) codes were used to identify all admissions with a primary diagnosis of IHD. The sample was divided into weekday and weekend groups. We performed a multivariate logistic regression analysis and a mediation analysis to estimate the effect of weekend admission on hospital mortality.

Results

A total of 18,906 IHD patients were included in the study, with an average age of 63.8 ± 12.7. Of these patients, 21.7% (n = 4,102) were admitted over the weekend. The in-hospital 30-days mortality rate was significantly higher among the patients admitted at weekends compared with those admitted at weekdays (2.0% vs. 1.1%). Respectively, the 30-day mortality rate of patients admitted on weekends was higher compared to patients admitted on weekdays among patients with surgical treatment (2.34% vs. 1.06%, OR = 1.75; 95% CI: 1.23–2.42) and with emergency admission (3.48% vs. 2.59%, OR = 1.56; 95% CI: 1.05–2.28). Mediation analyses showed that the surgical scheduling had significant mediated effects on the associations of admission time with mortality risk.

Conclusions

IHD patients with a surgical therapy or admitted from emergency department had a significantly higher risk of mortality when admitted on weekends compared to weekdays. These findings have potential implications for resource allocation and redistribution of surgery to weekends in hospitals.
Assessing health technology implementation during academic research and early-stage development: support tools for awareness and guidance: a review
Authors: Roosink Meyke , van Gemert-Pijnen Lisette , Verdaasdonk Ruud , Kelders Saskia M.
Published: October 2024

For successful health technology innovation and implementation it is key to, in an early phase, understand the problem and whether a proposed innovation is the best way to solve the problem. This review performed an initial exploration of published tools that support innovators in academic research and early stage development with awareness and guidance along the end-to-end process of development, evaluation and implementation of health technology innovations. Tools were identified from scientific literature as well as in grey literature by non-systematic searches in public research databases and search engines, and based on expert referral. A total number of 14 tools were included. Tools were classified as either readiness level tool (n = 6), questionnaire/checklist tool (n = 5) or guidance tool (n = 3). A qualitative analysis of the tools identified 5 key domains, 5 innovation phases and 3 implementation principles. All tools were mapped for (partially) addressing the identified domains, phases, and principles. The present review provides awareness of available tools and of important aspects of health technology innovation and implementation (vs. non-technological or non-health related technological innovations). Considerations for tool selection include for example the purpose of use (awareness or guidance) and the type of health technology innovation. Considerations for novel tool development include the specific challenges in academic and early stage development settings, the translation of implementation to early innovation phases, and the importance of multi-disciplinary strategic decision-making. A remaining attention point for future studies is the validation and effectiveness of (self-assessment) tools, especially in the context of support preferences and available support alternatives.
Relocation of earthquake clusters show seismogenic transverse structures in the Inner Northern Apennines (Italy)
Authors: Kaerger Lauretta , Del Ventisette Chiara , Vannucchi Paola , Molli Giancarlo , Pagli Carolina , Keir Derek
Published: October 2024

The Inner Northern Apennines (Italy) are a region with a dominant N-S to NNW-SSE fault system, but dissected and offset by several E-W to NE-SW trending structures and lineaments. The knowledge about the nature of these transverse structures, their origin, activity and role in current tectonic motions is limited and debated. To better establish the location, subsurface shape, and kinematics of faults related to the Livorno-Empoli lineament, one of the major transverse structures in the Northern Apennines, we analysed the seismicity in western Tuscany. In the Viareggio Basin we identified and relocated two distinct earthquake clusters as well as calculated 12 new focal mechanisms. The results show that the clusters consisted of several swarms from the years 2006, 2015, 2016 and 2021. The events had a depth between 2 and 15 km and were located along a NE-SW oriented, SE dipping fault system dissecting the Viareggio Basin. Focal mechanisms show oblique normal slip. We interpret the fault system to form a connection between the Viareggio Basin and the Lucca Basin to the east as well as continuing offshore. The results show that the transversal faults of the Inner Northern Apennines are seismogenic, with the length, position and onshore to offshore nature of the fault suggesting reactivation of pre-existing structures.
Tracing links between micronutrients and type 2 diabetes risk: the singular role of selenium
Authors: Zeng Wenxing , Jiang Shan , Cun Dejun , Huang Feng , Jiang Ziwei
Published: October 2024

Background

Type 2 diabetes (T2D) is a growing global health concern. While micronutrients are crucial for physiological functions and metabolic balance, their precise links to T2D are not fully understood.

Methods

We investigated the causal relationships between 15 key micronutrients and T2D risk using both univariate and multivariate Mendelian randomization (MR) methods. Our analysis leveraged data from a large prospective cohort genome-wide association study (GWAS) on these micronutrients and T2D. We employed MR techniques such as inverse variance weighting (IVW), MR Egger, weighted median, and simple models. Multivariate analysis adjusted for diabetes-related factors like body mass index (BMI) and hypertension to assess the independent effects of micronutrients, particularly selenium, on T2D risk.

Results

Selenium intake was associated with an increased risk of T2D, with an odds ratio (OR) of 1.045, a 95% confidence interval (CI) ranging from 1.009 to 1.082, and a P-value of 0.015. This association was consistent in multivariate analyses, suggesting an independent effect of selenium on T2D risk after adjusting for confounders.

Conclusion

Our study presents novel evidence of a positive correlation between selenium intake and T2D risk, underscoring the importance of micronutrients in diabetes prevention and treatment strategies. Further research is necessary to confirm these findings and to clarify the specific biological mechanisms through which selenium influences diabetes risk.
The associations of the triglyceride-glucose index and its combination with blood pressure on cardiovascular and all-cause mortality in hypertension: a national study
Authors: Xu Jun-Peng , Peng Xiong-Qiang , Guo Li-Heng , Zhao Xu-Jie , Chen Mao-Sheng , Mai Xiao-Yi , Tan Jia-Wei , Chen Quanfu , Zeng Rui-Xiang , Zhang Min-Zhou
Published: October 2024

The triglyceride-glucose (TyG) index, a reliable surrogate biomarker of insulin resistance (IR), is highlighted recently as related to cardiac disorders. However, the associations of the TyG index and its combination with blood pressure (BP) on cardiovascular and all-cause mortality in hypertension remain unclear. In this study, we included 9,635 hypertension patients from the National Health and Nutrition Examination Survey 1999–2018. During a median follow-up of 8.00 years, a total number of 853 and 2,489 in cardiovascular and all-cause deaths occurred, respectively. After full adjustments, the individual TyG index was positively associated with cardiovascular and all-cause mortality with J-shaped dose–response relationships. The lowest risk thresholds of the TyG index for cardiovascular and all-cause mortality were 9.5551 and 9.3405, respectively. In joint analyses, the highest risks of cardiovascular and all-cause mortality were observed among those with elevated levels of both BP and IR [1.64 (1.18, 2.28), P = 0.0031; 1.39 (1.14, 1.70), P = 0.0011; respectively]. In sensitivity and subgroup analyses, the results were generally robust. Our data appeal a hypothesis that future treatments for hypertension may require a combination of BP controlled and IR improvement.
Enhanced joint pain in diabetic patients with knee osteoarthritis is associated with increased synovitis, synovial immune cell infiltration, and erythrocyte extravasation
Authors: Eitner Annett , Rutte Veronika , Marintschev Ivan , Hofmann Gunther O. , Schaible Hans-Georg
Published: October 2024

Objective

Diabetes mellitus (DM) is an important risk factor for the development of osteoarthritis (OA), increasing OA progression and OA pain. To gain insight into the underlying mechanisms of how DM exacerbates OA processes and OA pain, this study analyzed histological differences of synovial tissues from non-DM and DM patients with OA and correlated these differences with knee pain severity.

Materials and methods

Synovial tissue was obtained from 12 non-DM and 10 DM patients with advanced knee OA who underwent total knee arthroplasty. Synovial inflammation was assessed using the Synovitis score developed by Krenn. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to assess knee pain intensity and disability in OA patients. The number of mast cells, macrophages, nerve fibers, capillaries, larger vessels and erythrocyte extravasation were analyzed microscopically in histological and immunostained synovial sections from non-DM and DM patients. Association analyses were performed to determine associations between OA knee pain and synovial changes affected by DM.

Results

Synovial tissue from OA patients with DM had a higher synovitis score, more erythrocyte extravasation, and contained higher numbers of mast cells and macrophages compared to non-DM patients. The number of capillaries and vessels in the lining/sublining layer of the synovial tissue was reduced in DM patients. OA patients with DM had more severe knee pain compared to non-DM patients. The KOOS pain score was associated with the synovitis score, the number of tissue macrophages, and the number of mast cells in the synovial tissue (adjusted for age, sex, and BMI). In addition, the erythrocyte extravasation score was associated with the KOOS pain score and with the synovitis score.

Conclusion

The study suggests that increased OA progression and pain severity in patients with DM result from more pronounced synovitis and synovial vascular leakage and increased infiltration of macrophages and mast cells.
Influence mechanism of digital economy development on the supply efficiency of ecological products
Authors: Shao Jingbo
Published: October 2024

Improving the supply efficiency of ecological products (EPSE) is of great significance to protect the ecological environment, promote the development of green industry and the sustainable growth of the economy. This paper focuses on constructing an evaluation index system for EPSE and exploring the relationship between the development level of the digital economy (DE) and EPSE in China. To measure the EPSE, the study employs the Undesirable Slacks-Based Measurement (SBM) Model across 30 provinces, cities and districts in China from 2011 to 2022. Furthermore, the research utilizes spatial econometric models, panel threshold effect models, and other methodologies to investigate the impact mechanism and non-linear relationship between DE and EPSE. The research shows that: (1) The overall level of EPSE in the study area is relatively low, with significant development differences observed; (2) The DE has a nota-ble spatial spillover effect on EPSE, with a significantly negative impact in neighboring areas; (3) The development of the DE promotes EPSE through the upgrading of human capital structure, industrial structure, and increases in local government fiscal revenue and corporate operating profits; (4) Heterogeneity analysis shows that the impact of DE on EPSE varies significantly across eastern, central, and western China, with positive effects pronounced in the eastern and western regions; (5) Regression results of the threshold effect indicate a significant single threshold effect on the impact of DE development level on EPSE. Specifically, when the threshold value is less than 0.1232, DE significantly contributes to the improvement of EPSE. This paper contributes new literature evidence and factual references to the understanding of the causal relationship between DE and EPSE. The findings highlight the importance of considering spatial spillover effects, impact mechanisms, and regional heterogeneity in analyzing the relationship between DE and EPSE. The research also suggests that promoting the development of the digital economy could be a viable strategy to enhance EPSE, especially in regions where the threshold value is below 0.1232
Immune and non-immune mediators in the fibrosis pathogenesis of salivary gland in Sjögren’s syndrome
Authors: Ma Danbao , Feng Yun , Lin Xiang
Published: October 2024

Sjögren’s syndrome (SS) or Sjögren’s disease (SjD) is a systemic autoimmune disease clinically manifested as sicca symptoms. This disease primarily impacts the functionality of exocrine glands, specifically the lacrimal and salivary glands (SG). SG fibrosis, an irreversible morphological change, is a severe consequence that occurs in the later stages of the disease due to sustained inflammation. However, the mechanism underlying SG fibrosis in SS remains under-investigated. Glandular fibrosis may arise from chronic sialadenitis, in which the interactions between infiltrating lymphocytes and epithelial cells potentially contributes to fibrotic pathogenesis. Thus, both immune and non-immune cells are closely involved in this process, while their interplays are not fully understood. The molecular mechanism of tissue fibrosis is partly associated with an imbalance of immune responses, in which the transforming growth factor-beta (TGF-β)-dependent epithelial-mesenchymal transition (EMT) and extracellular matrix remodeling are recently investigated. In addition, viral infection has been implicated in the pathogenesis of SS. Viral-specific innate immune response could exacerbate the autoimmune progression, resulting in overt inflammation in SG. Notably, post-COVID patients exhibit typical SS symptoms and severe inflammatory sialadenitis, which are positively correlated with SG damage. In this review, we discuss the immune and non-immune risk factors in SG fibrosis and summarize the evidence to understand the mechanisms upon autoimmune progression in SS.
Functional role of UNC13D in immune diseases and its therapeutic applications
Authors: Duong Van-Thanh , Lee Dongjun , Kim Yun Hak , Oh Sae-Ock
Published: October 2024

UNC13 family (also known as Munc13) proteins are evolutionarily conserved proteins involved in the rapid and regulated secretion of vesicles, including synaptic vesicles and cytotoxic granules. Fast and regulated secretion at the neuronal and immunological synapses requires multiple steps, from the biogenesis of vesicles to membrane fusion, and a complex array of proteins for each step. Defects at these steps can lead to various genetic disorders. Recent studies have shown multiple roles of UNC13D in the secretion of cytotoxic granules by immune cells. Here, the molecular structure and detailed roles of UNC13D in the biogenesis, tethering, and priming of cytotoxic vesicles and in endoplasmic reticulum are summarized. Moreover, its association with immune diseases, including familial hemophagocytic lymphohistiocytosis type 3, macrophage activation syndrome, juvenile idiopathic arthritis, and autoimmune lymphoproliferative syndrome, is reviewed. Finally, the therapeutic application of CRISPR/Cas9-based gene therapy for genetic diseases is introduced.
Metachronous spinal cord involvement B cell and subcutaneous tissue involvement NK/T cell lymphoid proliferations and lymphomas arising in post-transplantation mimicking general NK/T cell lymphoma: a case report and review of the literature
Authors: Zhu Yingxin , He Lingbo , Zou Heshan , Yao Shuyan , Hu Jinglin , Guo Jing , Wang Yini
Published: October 2024

Lymphoid proliferations and lymphomas arising in post-transplantation are potentially life-threatening complications after solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT). The lymphoid proliferations and lymphomas arising in post-transplantation originating from different cell lineages in the same patient are highly unusual. Herein, we delineate a case of isolated spinal cord involvement with B cell lymphoid proliferations and lymphomas arising in post-transplantation at 11 months post-transplantation, which was successfully treated with chemotherapy and intrathecal injection. Six months later, the patient again developed lymphoma arising in post-transplantation, presenting with predominant subcutaneous tissue involvement deriving from EBV-positive NK/T cells, and received four courses of chemotherapy. Ultimately, she achieved complete remission (CR). The report further contributes to our new insights into the unusual clinical presentations of lymphoid proliferations and lymphomas arising in post-transplantation.
Tenacibaculum maritimum can boost inflammation in Dicentrarchus labrax upon peritoneal injection but cannot trigger tenacibaculosis disease
Authors: Ferreira Inês A. , Santos Paulo , Moxó Javier Sanz , Teixeira Carla , do Vale Ana , Costas Benjamin
Published: October 2024

Introduction

Despite being a bacterial pathogen with devastating consequences, Tenacibaculum maritimum’s pathogenesis is not fully understood. The aim of the present study was to elucidate if different inoculation routes (intraperitoneal - i.p - injection and bath challenge - known to induce mortality) can induce tenacibaculosis (i.e., using the same T. maritimum inoculum), as well as evaluate the short-term immune response of European sea bass (D. labrax). Additionally, the host response against i.p. injection of extracellular products (ECPs) was also studied.

Methods

Fish were i.p. challenged with 5.5 × 105 CFU mL-1 of T. maritimum cells with or without ECPs (BECPs and BWO, respectively), ECPs alone or marine broth (mock). Another group of fish was bath-challenged with 5.5 × 105 CFU mL-1 to confirm the virulence of the bacterial inoculum. Undisturbed specimens were used as controls. The severity of both challenges was determined by following percentage survival. Blood, liver and head-kidney samples were collected at 0, 3, 6, 24 and 48 h post-challenge for assessing immune parameters, oxidative stress and gene expression. Total and differential peritoneal cell counts were performed. The presence of viable bacteria in the blood and peritoneal cavity was studied.

Results

Symptoms of tenacibaculosis, such as skin/fin abrasions, were only observed in the bath-challenged fish, where 0% survival was recorded, whereas 100% survival was observed after i.p. injection of the same bacterial inoculum. An increase in total leukocyte numbers in the peritoneal cavity was observed 3 h post-injection of BECPs when compared to the other treatments. Blood total leukocytes, lymphocytes, and thrombocyte numbers dropped after the challenge, mainly in fish challenged with BECPs. At 48 h post-challenge, bactericidal activity in the plasma increased in fish injected with bacteria (with and without ECPs). The same tendency was seen for some of the oxidative stress parameters.

Discussion/Conclusions

The increased expression of il1β, il6, il8, and hamp1 in fish challenged with ECPs and BECPs suggests a more exacerbated pro-inflammatory response in the head-kidney against these inocula. The infection trial and the observed immune responses showed that the infection route is a determinant factor regarding T. maritimum-induced pathogenesis in European sea bass.
Real-world study and prognostic analysis of angioimmunoblastic T-cell lymphoma
Authors: Li Suxiao , Feng Xiaoyan , Song Yunfei , Fan Mengke , Chen Qingjiang , Zhang Mingzhi , Wu Xiaolong , Dong Meng , Zhang Jieming , Han Lijuan , Zhang Xudong
Published: October 2024

Objective

To analyze the clinical prognostic factors and treatments for angioimmunoblastic T-cell lymphoma (AITL) and develop a novel prognostic model specifically for AITL.

Method

We retrospectively analyzed 231 patients with AITL from the First Affiliated Hospital of Zhengzhou University. Patients were enrolled between January 2014 and July 2023. The primary end points were overall survival (OS) and progression-free survival (PFS).

Result

The patients’ median age was 63 years, with 88.3% at an advanced stage (III/IV). The majority of patients (47.6%) received anthracycline-containing regimens, and there was no significant difference in survival compared with those treated with epigenetic-targeting and gemcitabine- containing regimens. The median PFS and OS were 6 and 17 months, respectively. In multivariate analysis, age >60 years, Eastern Cooperative Oncology Group performance status ≥2, elevated LDH, and splenomegaly were associated with inferior OS. Based on these four factors, a novel prognostic model (AITL model) was constructed that stratified patients into low‐, intermediate‐, and high‐risk groups, with 2-year OS estimates of 63.6%, 42.1%, and 18.6%, respectively.

Conclusion

Currently, there is no consensus on the optimal initial therapy for AITL, and the efficacy of anthracycline-containing regimens remains suboptimal. The novel model developed herein demonstrates predictive significance for both OS and PFS, and exhibits better stratification and discrimination capabilities.
Laboratory study of energy transformation characteristics in breaking wave groups
Authors: Wu Guanglin , He Yanli , Zhang Yizhe , Lin Jinbo , Mao Hongfei
Published: October 2024

The spilling-breaking waves that appear in chirped wave packets are studied in a two-dimensional wave channel. These waves are produced by superposing waves with gradually decreasing frequencies. The analysis focuses on the nonlinear characteristics, energy variation, and energy transformation during the evolution and breaking of wave groups. Ensemble empirical mode decomposition is used to analyze the non-breaking and breaking energy variations of the intrinsic mode functions (IMFs). It is found that the third-order IMF component is a source of non-breaking energy dissipation and the second-order IMF, which represents a short wave group with a relatively higher energy content, is a primary source of the energy loss caused by wave breaking. Additionally, the findings reveal that among the three waves preceding the maximum crest, the wave closest to the maximum crest carried most of the energy. When wave breaking occurs, the energy dissipation caused by the wave breaking primarily originates from that wave. After wave breaking, whether it is the first breaker or subsequent breakers, the main energy dissipation occurs in a frequency range higher than the dominant frequency. This energy loss plays a significant role in increasing the energy of free waves. Moreover, a potential link between the number of carrier waves and wave breaking phenomena has been found. As the number of carrier waves increased, both the nonbreaking and breaking energy dissipation rates exhibited an overall increasing trend. The amount of nonbreaking energy dissipation was generally more than twice the breaking energy dissipation rate. For wave groups with more carrier waves, the modulation instability plays a significant role in generating larger waves. Furthermore, an analysis of the dominant frequency variations of the wave group before wave breaking suggests that wave breaking is not a sufficient condition for a frequency downshift in the wave spectra.
An overview of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in giant cell arteritis
Authors: Thibault Thomas , Alberini Jean-Louis , Billet Anne-Claire , Greigert Hélène , Ramon André , Devilliers Hervé , Cochet Alexandre , Bonnotte Bernard , Samson Maxime
Published: October 2024

PET/CT is an imaging modality that is increasingly being used to diagnose large-vessel vasculitis. In the case of giant cell arteritis, it was first used to demonstrate inflammation of the walls of large arterial trunks such as the aorta and its main branches, showing that aortic involvement is common in this vasculitis and associated with the occurrence of aortic complications such as aneurysms. More recently, with the advent of digital PET/CT, study of the cranial arteries (i.e., temporal, occipital, maxillary and vertebral arteries) has become possible, further increasing the diagnostic interest of this examination for the diagnosis of GCA. Despite these advantages, there are still limitations and questions regarding the use of PET/CT for the diagnosis and especially the follow-up of GCA. The aim of this review is to take stock of currently available data on the use of PET/CT for GCA diagnosis and follow-up.
miR-191-5p suppresses PRRSV replication by targeting porcine EGFR to enhance interferon signaling
Authors: Pan Yu , Zhang Lin , Ma Wenjie , Ibrahim Yassein M. , Zhang Wenli , Wang Mengjie , Wang Xinrong , Xu Yunfei , Gao Caixia , Chen Hongyan , Zhang He , Xia Changyou , Wang Yue
Published: October 2024

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major thread to the global swine industry, lack of effective control strategies. This study explores the regulatory role of a small non-coding RNA, miR-191-5p, in PRRSV infection. We observed that miR-191-5p significantly inhibits PRRSV in porcine alveolar macrophages (PAMs), contrasting with negligible effects in MARC-145 and HEK293-CD163 cells, suggesting a cell-specific antiviral effect. Further investigation unveiled that miR-191-5p directly targets the porcine epidermal growth factor receptor (EGFR), whose overexpression or EGF-induced activation suppresses type I interferon (IFN-I) signaling, promoting PRRSV replication. In contrast, siRNA-or miR-191-5p-induced EGFR downregulation or EGFR inhibitor boosts IFN-I signaling, reducing viral replication. Notably, this miRNA alleviates the suppressive effect of EGF on IFN-I signaling, underscoring its regulatory function. Further investigation revealed interconnections among miR-191-5p, EGFR and signal transducer and activator of transcription 3 (STAT3). Modulation of STAT3 activity influenced IFN-I signaling and PRRSV replication, with STAT3 knockdown countering EGFR activation-induced virus replication. Combination inhibition of STAT3 and miR-191-5p suggests that STAT3 acts downstream in EGFR’s antiviral response. Furthermore, miR-191-5p’s broad efficacy in restricting various PRRSV strains in PAMs was identified. Collectively, these findings elucidate a novel mechanism of miR-191-5p in activating host IFN-I signaling to inhibit PRRSV replication, highlighting its potential in therapeutic applications against PRRSV.
Burkholderia pseudomallei produces 2-alkylquinolone derivatives important for host virulence and competition with bacteria that employ naphthoquinones for aerobic respiration
Authors: Mou Sherry , Savchenko Viktoriia , Filz Verena , Böttcher Thomas , DeShazer David
Published: October 2024

Melioidosis is caused by Burkholderia pseudomallei, an opportunistic Gram-negative pathogen that inhabits soil and water in tropical and subtropical regions. B. pseudomallei infections often occur following contact with contaminated water or soil or by inhalation of contaminated dust and water droplets. There is limited knowledge about how B. pseudomallei is able to survive in harsh environmental conditions and compete with the microbes that inhabit these niches. Previous research demonstrated that 3-methyl-2-alkylquinolones (MAQs), and their corresponding N-oxides (MAQNOs), are produced by B. pseudomallei and provide a competitive advantage when grown in the presence of Gram-positive bacteria. In this study, 39 Gram-negative environmental bacteria in the Pseudomonadota and Bacteroidota phyla were isolated and characterized. Intriguingly, B. pseudomallei inhibited 71% of bacteria in the phylum Bacteroidota in zone of inhibition and coculture competition assays, but no Pseudomonadota isolates were similarly inhibited. Transposon mutagenesis was utilized to identify B. pseudomallei genes required for the inhibition of Sphingobacterium sp. ST4, a representative member of the Bacteroidota. Three mutations mapped to hmqA-G, the locus encoding 2-alkylquinolone derivatives, and two mutations were identified in scmR, a gene encoding a quorum-sensing controlled LysR-type transcriptional regulator. B. pseudomallei strains with deletion mutations in hmqD and scmR were unable to produce 2-alkylquinolone derivatives or inhibit Bacteroidota isolates in competition assays. RAW264.7 murine macrophage cells were infected with B. pseudomallei 1026b and 1026b ΔhmqD and there was a 94-fold reduction in the number of intracellular 1026b ΔhmqD bacteria relative to 1026b. The 50% lethal dose (LD50) of 1026b and 1026b ΔhmqD in BALB/c mice was determined to be 3 x 105 colony forming units (CFU) and > 1 x 106 CFU, respectively. Taken together, the results indicate that the products of the B. pseudomallei hmqA-G locus are important for intracellular replication in murine macrophages, virulence in a mouse model of melioidosis, and competition with bacteria that utilize naphthoquinones for aerobic respiration.
Potential association between COVID-19 and neurological disorders: analysis of common genes and therapeutics
Authors: Chen Wenzhi , Jiang Shishi , Li Cheng , Li Shu , Wang Junling , Xu Renshi
Published: October 2024

As the COVID-19 pandemic persists, the increasing evidences suggest that the patients with COVID-19 may face the risks of the neurological complications and sequelae. To address this issue, we conducted a comprehensive study aimed at exploring the relationship between COVID-19 and various neurological disorders, with a particular focus on the shared dysregulated genes and the potential therapeutic targets. We selected six neurological disorders for investigation, including Alzheimer’s disease, epilepsy, stroke, Parkinson’s disease, and the sleep disorders. Through the bioinformatics analysis of the association between these disorders and COVID-19, we aimed to uncover the common molecular mechanisms and the potential treatment pathways. In this study, we utilized the publicly available RNA-Seq and microarray datasets, and employed tools such as Limma and DESeq2 for the differential gene analysis. Through the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, we explored the common biological features and pathways. Additionally, we focused on analyzing the regulatory roles of miRNA and transcription factors on the shared differentially expressed genes, and predicted the potential drugs interacting with these genes. These analyses contribute to a better understanding of the relationship between COVID-19 and the neurological disorders, and provide a theoretical basis for the future treatment strategies. Through this research, we aim to offer the deeper insights to the scientific community and present the new perspectives for the clinical practice in addressing the challenges of the neurological complications and sequelae faced by the COVID-19 patients.
Exercise effects on neuropsychiatric symptoms and quality of life in mild cognitive impairment: a systematic review and meta-analysis
Authors: Chen Liang , Kim Sung Min
Published: October 2024

Background

Exercise is considered as a cost-efficient option for individuals with mild cognitive impairment (MCI). Although the potential benefits of exercise for improving cognitive function are recognized, its impact on neuropsychiatric symptoms (NPS) and the quality of life (QoL) in individuals with MCI remains unclear.

Objective

This study aims to investigate the effects of exercise interventions on NPS, including depression, anxiety, sleep disorders, and the quality of life in individuals with MCI.

Results

There were 17 randomized controlled trials (RCTs) involving 1,575 participants were included. The findings indicate a small but significant positive effect of exercise on depression (standardized mean difference [SMD] = −0.47, 95% confidence interval [CI]: −0.73 to −0.21), but the quality of the evidence is low. Mind–body exercises were relatively more effective in alleviating depression. No significant improvements were observed in sleep disorders (SMD = −1.27, 95% CI: −2.80 to 0.26). Exercise improved anxiety in one study but had no effect in the other. It also improved quality of life in seven studies, with two showing no effect.

Conclusion

The findings suggest that exercise, particularly mind–body exercises, can improve depression in individuals with MCI. However, the effect of exercise on anxiety, sleep disorders, and quality of life is still uncertain, necessitating additional research. These findings underscore the significance of integrating customized exercise programs in managing MCI to boost quality of life and mitigate NPS.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/. ID: CRD42023445369.
Study on risk factor analysis and model prediction of hyperuricemia in different populations
Authors: Hou Kaifei , Shi Zhongqi , Ge Xueli , Song Xinyu , Yu Congying , Su Zhenguo , Wang Shaoping , Zhang Jiayu
Published: October 2024

Objectives

The purpose of the present study was to explore the influencing factors of hyperuricemia (HUA) in different populations in Shandong Province based on clinical biochemical indicators. A prediction model for HUA was constructed to aid in the early prevention and screening of HUA.

Methods

In total, 705 cases were collected from five hospitals, and the risk factors were analyzed by Pearson correlation analysis, binary logistic regression, and receiver operating characteristic (ROC) curve in the gender and age groups. All data were divided into a training set and test set (7:3). The training set included age, gender, total protein (TP), low-density lipoprotein cholesterol (LDL-C), and 15 other indicators. The random forest (RF) and support vector machine (SVM) methods were used to build the HUA model, and model performances were evaluated through 10-fold cross-validation to select the optimal method. Finally, features were extracted, and the ROC curve of the test set was generated.

Results

TP, LDL-C, and glucose (GLU) were risk factors for HUA, and the area under the curve (AUC) value of the SVM validation set was 0.875.

Conclusion

The SVM model based on clinical biochemical indicators has good predictive ability for HUA, thus providing a reference for the diagnosis of HUA and the development of an HUA prediction model.
Associations of sarcopenia, obesity, and metabolic health with the risk of urinary incontinence in U.S. adult women: a population-based cross-sectional study
Authors: Shao Fei-Xue , Luo Wei-Jia , Lou Li-Qun , Wan Sheng , Zhao Shi-Feng , Zhou Tian-Fan , Zhou Chen-Chen , Yang Ying-Ying , Wu Gui-Zhu , Hua Xiao-Lin
Published: October 2024

Introduction

Urinary incontinence (UI) significantly impairs women’s quality of life. Identifying its risk factors is essential for developing effective interventions. Sarcopenia, characterized by the accelerated loss of muscle mass and function, is an emerging concern often linked to obesity and abnormal metabolic status, exacerbating various adverse health outcomes. This population-based study aimed to explore the independent and joint associations of sarcopenia, obesity, and metabolic health with UI risk, as well as to evaluate the mediating role of metabolic indicators in these associations

Methods

A total of 3,557 women aged ≥20 years from the National Health and Nutrition Examination Survey were included. Sarcopenia was assessed using the appendicular lean mass index (ALMI), and obesity was defined by body mass index and waist circumference. Metabolic health was evaluated using revised criteria from the National Cholesterol Education Program-Adult Treatment Panel III. UI was identified through responses to the “Kidney Conditions-Urology” questionnaire and classified into stress UI (SUI), urgency UI (UUI), and mixed UI (MUI). Multivariable logistic regression and restricted cubic spline models were used to evaluate the associations and visualize the relationship between ALMI and UI. Mediation models were constructed to assess the mediating role of metabolic indicators.

Results

We found that sarcopenia was significantly associated with an increased risk of MUI in the general population. Age-specific analysis revealed that sarcopenia is an independent risk factor for SUI in women aged ≥60, and for MUI in women aged 40–59 years. Sarcopenic obesity, particularly under central obesity criteria, further elevated the risk of UI. Notably, women with the metabolically unhealthy obese phenotype with sarcopenia were at the highest risk for both SUI and MUI. Metabolically unhealthy status, glycohemoglobin, vitamin D, and serum albumin levels were partial mediators of these associations.

Conclusion

Our findings elucidated the complex interactions between sarcopenia, obesity, and metabolic health, underscoring the critical need for integrated therapeutic strategies that address both metabolic health and targeted nutritional interventions, aiming to enhance muscular health and effectively manage and prevent UI.
Modeling epithelial-mesenchymal transition in patient-derived breast cancer organoids
Authors: Bar-Hai Neta , Ben-Yishay Rakefet , Arbili-Yarhi Sheli , Herman Naama , Avidan-Noy Vered , Menes Tehillah , Mansour Aiham , Awwad Fahim , Balint-Lahat Nora , Goldinger Gil , Hout-Siloni Goni , Adileh Mohammad , Berger Raanan , Ishay-Ronen Dana
Published: October 2024

Cellular plasticity is enhanced by dedifferentiation processes such as epithelial-mesenchymal transition (EMT). The dynamic and transient nature of EMT-like processes challenges the investigation of cell plasticity in patient-derived breast cancer models. Here, we utilized patient-derived organoids (PDOs) as a model to study the susceptibility of primary breast cancer cells to EMT. Upon induction with TGF-β, PDOs exhibited EMT-like features, including morphological changes, E-cadherin downregulation and cytoskeletal reorganization, leading to an invasive phenotype. Image analysis and the integration of deep learning algorithms enabled the implantation of microscopy-based quantifications demonstrating repetitive results between organoid lines from different breast cancer patients. Interestingly, epithelial plasticity was also expressed in terms of alterations in luminal and myoepithelial distribution upon TGF-β induction. The effective modeling of dynamic processes such as EMT in organoids and their characteristic spatial diversity highlight their potential to advance research on cancer cell plasticity in cancer patients.
Emerging innovations in neonatal monitoring: a comprehensive review of progress and potential for non-contact technologies
Authors: Krbec Brooke A. , Zhang Xiang , Chityat Inbar , Brady-Mine Alexandria , Linton Evan , Copeland Daniel , Anthony Brian W. , Edelman Elazer R. , Davis Jonathan M.
Published: October 2024

Continuous monitoring of high-risk neonates is essential for the timely management of medical conditions. However, the current reliance on wearable or contact sensor technologies for vital sign monitoring often leads to complications including discomfort, skin damage, and infections which can impede medical management, nursing care, and parental bonding. Moreover, the dependence on multiple devices is problematic since they are not interconnected or time-synchronized, use a variety of different wires and probes/sensors, and are designed based on adult specifications. Therefore, there is an urgent unmet need to enable development of wireless, non- or minimal-contact, and non-adhesive technologies capable of integrating multiple signals into a single platform, specifically designed for neonates. This paper summarizes the limitations of existing wearable devices for neonates, discusses advancements in non-contact sensor technologies, and proposes directions for future research and development.