bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of PD-L1 expression with different clinico-pathological and immunohistochemical features of ovarian surface epithelial tumors
Authors: Shalaby Asem , Shalaby Ola , Abdullah Hazem , Boulassel Mohamed Rachid , Arafa Mohammad
Published: August 2024

Background

Primary carcinoma of the ovary (OCs) are responsible for a significant number of deaths related to cancer, and have the highest rate of death related to cancers of the female reproductive organs. Programmed cell death 1 (PD1) protein, acts as an immune checkpoint, and has an important role in the down-regulation of the immune system by preventing the activation of T-cells, which will weaken the autoimmunity and increases self-tolerance. This study aimed at the evaluation of the immunohistochemical (IHC) expression of PD-L1 in various primary surface ovarian epithelial tumours and to test its correlation with different clinicopathological parameters together with the expression of a panel of P53, ER and PR.

Methods

A set of 102 cases of primary ovarian surface epithelial neoplasms (benign, borderline and malignant) were collected to construct Tissue Microarray (TMA) using 3 tissue cores from each case. IHC for PD-L1, p53, PR and ER was performed. The expression of PD-L1 was evaluated in relation to some clinicopathological parameters and to the expression patterns of other markers.

Results

Expression of PD-L1 was detected in about 51% (n = 36) of malignant tumours. The malignant group significantly showed PD-L1 positivity compared to borderline and benign groups. The malignant tumours significantly showed PD-L1 and total p53 positivity in comparison to borderline group. Also, malignant tumours significantly showed higher combined positivity of PD-L1 and either PR or ER compared to borderline and benign lesions. No significant correlation was appreciated between PD-L1 expression and with any of the studied clinicopathological parameters.

Conclusions

This study showed a significant PD-L1 expression in malignant primary surface epithelial tumours. Construction of a panel of IHC markers, including PD-L1, could have a potential value to define patients those would benefit from the addition of immunotherapy to the treatment plan.
Performance of ChatGPT on basic healthcare leadership and management questions
Authors: Leutz-Schmidt Patricia , Grözinger Martin , Kauczor Hans-Ulrich , Jang Hyungseok , Sedaghat Sam
Published: August 2024

Purpose

ChatGPT is an LLM-based chatbot introduced in 2022. This study investigates the performance of ChatGPT-3.5 and ChatGPT-4 on basic healthcare leadership and management questions.

Methods

ChatGPT-3.5 and -4 (OpenAI, San Francisco, CA, USA) generated answers to 24 pre-selected questions on three different areas of management and leadership in medical practice: group 1) accessing management/leadership training, group 2) management/leadership basics, group 3) department management/leadership. Three readers independently evaluated the answers provided by the two versions of ChatGPT. Three 4-digit scores were developed to assess the quality of the responses: 1) overall quality score (OQS), 2) understandibility score (US), and 3) implementability score (IS). The mean quality score (MQS) was calculated from these three scores.

Results

The interrater agreement was good for ChatGPT-4 (72%) and moderate for ChatGPT-3.5 (56%). The MQS of all questions reached a mean score of 3,42 (SD: 0,64) using ChatGPT-3.5 and 3,75 (SD: 0,47) using ChatGPT-4. ChatGPT-4 showed significantly higher MQS scores in group 2 and 3 questions than ChatGPT-3.5 (p = 0.039 and p < 0.001, respectively). Also, significant differences between ChatGPT-3.5 and ChatGPT-4 regarding OQS, US, and IS in group 3 questions were seen with significances reaching p < 0.001. Significant differences between the two chatbot versions were also present regarding OQS in question groups 1 and 2 (p = 0.035 each). 87.5% of the answers provided by ChatGPT-4 (21 of 24 answers) were considered superior to the answers provided by ChatGPT-3.5 for the same questions. Neither ChatGPT-3.5 nor ChatGPT-4 offered any inaccurate answers.

Conclusion

ChatGPT-3.5 and ChatGPT-4 performed well on basic healthcare leadership and management questions, while ChatGPT-4 was superior.
Hybrid FDG-PET/MRI for Diagnosis and Clinical Management of Patients with Suspected Perihilar Cholangiocarcinoma: A Feasibility Pilot Study
Authors: de Jong D. M. , Chehin K. , Meijering T. L.N. , Segbers M. , van Driel L. M.J.W. , Bruno M. J. , Groot Koerkamp B. , IJzermans J. N.M. , Verburg F. A. , de Lussanet de la Sabloniere Q. G. , Dwarkasing R. S.
Published: August 2024

Purpose

Recently introduced hybrid 2-[18 F]-fluoro-2-deoxy-D-glucose (18 F-FDG) Positron Emission Tomography (PET) combined with Magnetic Resonance Imaging (MRI) may aid in proper diagnosis and staging of perihilar cholangiocarcinoma (pCCA). The aim of this study is to assess the effect of 18 F-FDG PET/MRI on diagnosis and clinical decision making in the pre-operative work up of pCCA.

Methods

In this single-centre pilot study patients with presumed resectable pCCA underwent state-of-the-art 18 F-FDG hybrid PET/MRI using digital silicone photomultiplier detectors integrated within a 3-Tesla bore. Data were collected on several baseline and imaging characteristics. The primary outcome measure was the added diagnostic information and the effect on clinical decision making. Secondary aim was to correlate quantitative PET signal intensity to patient- and tumour characteristics. High and low SUVmax subgroups related to the mean value were made. Significance of lesion- and patient characteristics with the high and low SUVmax subgroups, as well as TLR and TBR, was evaluated with Fisher’s exact test or Mann-Whitney-U test.

Results

In total 14 patients were included (mean age 62.4 years, 64% male). Final diagnosis was pCCA in 10 patients (71.4%), follicular lymphoma in one patient (7.1%) and benign disease in the remaining three patients. FDG-PET/MRI added valuable diagnostic information in six (43%) patients and affected clinical decision making in two of these patients (14%) by increasing confidence for malignancy which lead to the decision for surgery on short term. High SUVmax values were seen in half of cases with pCCA and half of cases with non-cancerous lesions. In addition, high SUVmax values were directly associated with primary sclerosing cholangitis when present (p = 0.03).

Conclusion

Simultaneous 18 F-FDG-PET/MRI added diagnostic information in six of fourteen patients and influenced clinical decision making in two patients (14%) with presumed resectable pCCA.
Systematic Review of Computerised Cognitive Remediation interventions in Early Psychosis: Do we Still Need “Somebody with a Human Touch”?
Authors: Avila Alessia , Novais Filipa
Published: August 2024

Purpose of the Review

Several computerized cognitive remediation (CCR) programs have been developed in recent years, although their efficacy in First Episode Psychosis (FEP) remains unclear, particularly regarding the benefits in terms of functional improvement. This review article provides a systematic evaluation of the efficacy, mechanisms, and implementation characteristics of CCR in FEP and critically reflects on the role of human supervision.

Recent Findings

Studies indicates that CCR is effective in improving neurocognition. Evidence for the effects of CCR in social cognition remain less strong and delivery characteristics do not seem to influence this outcome. CCR showed some effects on both clinical symptoms and functional outcomes, with neurocognition being a strong mediator of improvement in social functioning.

Computer-assisted CR programs can offer standardized, scalable interventions and are effective in improving neurocognition, even with limited supervision from trainers. Human supervision seems, however, crucial to ensuring proper development and transferring of skills to everyday functioning.
Understanding healthy ageing in India: insights from multivariate regression trees
Authors: Das Ayushi , Dhillon Preeti
Published: August 2024

Background

Population ageing represents a significant global challenge, particularly pronounced in countries like India.

Aims

This study aims to explore how factors such as socio-economic status, behaviour, and health influence healthy ageing across the Indian older population.

Methods

In this study, we utilized the Longitudinal Ageing Study in India – wave 1 dataset for analysis purposes. Scores were generated for five dimensions of healthy aging, including physical, functional, mental, cognitive, and social aspects and these scores were treated as the target variables. Multivariate Regression Trees analysis was employed to identify the behavioural and socio-demographic factors associated with each dimension of healthy ageing.

Results

Years of education emerge as crucial across all dimensions, positively impacting cognitive health and mitigating age-related decline in healthy ageing. Marital status, engagement in household activities, spiritual practices, and living arrangements impacts the scores of different aspects of healthy ageing. Gender disparities in healthy aging are noticeable in the 60–74 age group, with women generally having lower scores. Safety of the living environment is a crucial determinant of the mental health of the elderly across all age groups.These findings highlight the complex interplay of factors in healthy ageing outcomes.

Conclusion

Our study emphasizes the pivotal role of education in fostering healthy ageing in India. Factors such as environmental safety and social participation also influence well-being. Targeted interventions addressing education, gender equality, safety, and healthcare access are vital for enhancing the ageing experience and overall well-being of older adults.
Influence of serum uric acid on bone and fracture risk in postmenopausal women
Authors: Gómez-de-Tejada-Romero María-Jesús , Murias-Henríquez Carmen , Saavedra-Santana Pedro , Sablón-González Nery , Abreu Delvys Rodríguez , Sosa-Henríquez Manuel
Published: August 2024

Aims

Uric acid has been associated with several metabolic conditions, including bone diseases. Our objective here was to consider the relationship between serum uric acid levels and various bone parameters (bone mineral density, ultrasonographic parameters, vitamin D, PTH and serum calcium), as well as the prevalence and risk of fragility fracture.

Methods

An observational and cross-sectional study carried out on 679 postmenopausal women, classified into 3 groups according to their serum uric acid levels, in whom bone densitometry, calcaneus ultrasounds, PTH, vitamin D and serum calcium analysis were done. Bone fractures were collected through the clinical history and lateral spinal X-ray.

Results

Higher uric acid levels were found in women with older age, high BMI, diabetes, and high blood pressure. Higher levels of PTH and serum calcium were also observed, but did not effect on vitamin D. Serum uric acid was positively related to densitometric and ultrasonic parameters and negatively associated with vertebral fractures.

Conclusions

In the population of postmenopausal women studied, sUA levels were correlated with BMD, BUA, and QUI-Stiffness, and this correlation was independent of age and BMI. In addition, sUA was associated with a decrease in vertebral fractures. These results imply a beneficial influence of sUA on bone metabolism, with both a quantitative and qualitative positive effect, reflected in the lower prevalence of vertebral fractures.
An exceptionally well-preserved Jurassic plateau-top to marginal escarpment in the Northern Apennines (Central Italy): sedimentological, palaeontological and palaeostructural features
Authors: Santantonio Massimo , Innamorati Giulia , Cipriani Angelo , Antonelli Matteo , Fabbi Simone
Published: August 2024

Submarine palaeo-escarpment tracts at the basin margins commonly border isolated drowned carbonate platforms in the Jurassic rifted margins of the Western Tethys and bear fundamental structural and palaeogeographic significance. These tectonically generated escarpments, rooted in late Hettangian-early Sinemurian master faults, provide key information on the regional architecture of the rift, and on the nature and timespan of activity of the faults which define them. An isolated drowned carbonate platform (the Sabina Plateau) in the Northern Apennines of Central Italy exhibits a wealth of peculiar details on the Jurassic submarine topography. The deposits covering this escarpment host multiple unconformities related to a margin-failure episode, documented by breccias resting on a submarine-scar surface, perched with respect to the basin bottom and draped discontinuously by condensed ammonite-rich pelagites. Thin lenses of graded and laminated oolitic limestones in the condensed pelagic succession of the Sabina Plateau are interpreted as likely produced by the overbanking of turbidity currents, which were shed into the basin by a neighbouring productive carbonate platform. The final leveling of the submarine rift bathymetry occurred in the earliest Cretaceous, as documented by the onlap of the aggrading basinal succession against the palaeo-escarpment, and the burial of the plateau-top condensed succession. This complex onlap surface exhibits a distinctive overprint, such as diffuse silicification driven by the transit of silica-rich diagenetic fluids sourced by the radiolarian-rich basinal units.
CliqueFluxNet: Unveiling EHR Insights with Stochastic Edge Fluxing and Maximal Clique Utilisation Using Graph Neural Networks
Authors: Molaei Soheila , Bousejin Nima Ghanbari , Ghosheh Ghadeer O. , Thakur Anshul , Chauhan Vinod Kumar , Zhu Tingting , Clifton David A.
Published: August 2024

Electronic Health Records (EHRs) play a crucial role in shaping predictive are models, yet they encounter challenges such as significant data gaps and class imbalances. Traditional Graph Neural Network (GNN) approaches have limitations in fully leveraging neighbourhood data or demanding intensive computational requirements for regularisation. To address this challenge, we introduce CliqueFluxNet, a novel framework that innovatively constructs a patient similarity graph to maximise cliques, thereby highlighting strong inter-patient connections. At the heart of CliqueFluxNet lies its stochastic edge fluxing strategy — a dynamic process involving random edge addition and removal during training. This strategy aims to enhance the model’s generalisability and mitigate overfitting. Our empirical analysis, conducted on MIMIC-III and eICU datasets, focuses on the tasks of mortality and readmission prediction. It demonstrates significant progress in representation learning, particularly in scenarios with limited data availability. Qualitative assessments further underscore CliqueFluxNet’s effectiveness in extracting meaningful EHR representations, solidifying its potential for advancing GNN applications in healthcare analytics.
Gene Regulatory Network Analysis of Decidual Stromal Cells and Natural Killer Cells
Authors: Rytkönen Kalle T. , Adossa Nigatu , Zúñiga Norman Sebastián , Lönnberg Tapio , Poutanen Matti , Elo Laura L.
Published: August 2024

Human reproductive success relies on the proper differentiation of the uterine endometrium to facilitate implantation, formation of the placenta, and pregnancy. This process involves two critical types of decidual uterine cells: endometrial/decidual stromal cells (dS) and uterine/decidual natural killer (dNK) cells. To better understand the transcription factors governing the in vivo functions of these cells, we analyzed single-cell transcriptomics data from first-trimester terminations of pregnancy, and for the first time conducted gene regulatory network analysis of dS and dNK cell subpopulations. Our analysis revealed stromal cell populations that corresponded to previously described in vitro decidualized cells and senescent decidual cells. We discovered new decidualization driving transcription factors of stromal cells for early pregnancy, including DDIT3 and BRF2, which regulate oxidative stress protection. For dNK cells, we identified transcription factors involved in the immunotolerant (dNK1) subpopulation, including IRX3 and RELB, which repress the NFKB pathway. In contrast, for the less immunotolerant (dNK3) population we predicted TBX21 (T-bet) and IRF2-mediated upregulation of the interferon pathway. To determine the clinical relevance of our findings, we tested the overrepresentation of the predicted transcription factors target genes among cell type-specific regulated genes from pregnancy disorders, such as recurrent pregnancy loss and preeclampsia. We observed that the predicted decidualized stromal and dNK1-specific transcription factor target genes were enriched with the genes downregulated in pregnancy disorders, whereas the predicted dNK3-specific targets were enriched with genes upregulated in pregnancy disorders. Our findings emphasize the importance of stress tolerance pathways in stromal cell decidualization and immunotolerance promoting regulators in dNK differentiation.
Antibiotic practice and stewardship in the management of neutropenic fever: a survey of US institutions
Authors: Wang Xiao , Arya Swarn V. , Patel Sonal , Saw Stephen , Decena Mary A. , Hirsh Rebecca , Pegues David A. , Ziegler Matthew J.
Published: August 2024

Objective:

To describe neutropenic fever management practices among healthcare institutions.

Design:

Survey.

Participants:

Members of the Society for Healthcare Epidemiology of America Research Network (SRN) representing healthcare institutions within the United States.

Methods:

An electronic survey was distributed to SRN representatives, with questions pertaining to demographics, antimicrobial prophylaxis, supportive care, and neutropenic fever management. The survey was distributed from fall 2022 through spring 2023.

Results:

40 complete responses were recorded (54.8% response rate), with respondent institutions accounting for approximately 15.7% of 2021 US hematologic malignancy hospitalizations and 14.9% of 2020 US bone marrow transplantations. Most entities have institutional guidelines for neutropenic fever management (35, 87.5%) and prophylaxis (31, 77.5%), and first-line treatment included IV antipseudomonal antibiotics (35, 87.5% cephalosporin; 5, 12.5% penicillin; 0, 0% carbapenem).

We observed significant heterogeneity in treatment course decisions, with roughly half (18, 45.0%) of respondents continuing antibiotics until neutrophil recovery, while the remainder having criteria for de-escalation prior to neutrophil recovery. Respondents were more willing to de-escalate prior to neutrophil recovery in patients with identified clinical (27, 67.5% with pneumonia) or microbiological (30, 75.0% with bacteremia) sources after dedicated treatment courses.

Conclusions:

We found substantial variation in the practice of de-escalation of empiric antibiotics relative to neutrophil recovery, highlighting a need for more robust evidence for and adoption of this practice. No respondents use carbapenems as first-line therapy, comparing favorably to prior survey studies conducted in other countries.
Forecasting Inundation of Catastrophic Landslides From Precursory Creep
Authors: Xu Y. , Bürgmann R. , George D. L. , Fielding E. J. , Solis‐Gordillo G. X. , Yanez‐Borja D. B.
Published: August 2024

Forecasting landslide inundation upon catastrophic failure is crucial for reducing casualties, yet it remains a long‐standing challenge owing to the complex nature of landslides. Recent global studies indicate that catastrophic hillslope failures are commonly preceded by a period of precursory creep, motivating a novel scheme to foresee their hazard. Here, we showcase an approach to hindcast landslide inundation by linking satellite‐captured precursory displacements to modeling of consequent granular‐fluid flows. We present its application to the 2021 Chunchi, Ecuador landslide, which failed catastrophically and evolved into a mobile debris flow after four months of precursory creep, destroying 68 homes along its lengthy flow path. Underpinned by uncertainty quantification and in situ validations, we highlight the feasibility and potential of forecasting landslide inundation damage using observable precursors. This forecast approach is broadly applicable for flow hazards initiated from geomaterial failures.
Comprehensive molecular characterization of TFE3-rearranged renal cell carcinoma
Authors: Lee Cho-Rong , Suh Jungyo , Jang Dongjun , Jin Bo-Yeong , Cho Jaeso , Lee Moses , Sim Hyungtai , Kang Minyong , Lee Jueun , Park Ju Hyun , Lee Kyoung-Hwa , Hwang Geum-Sook , Moon Kyung Chul , Song Cheryn , Ku Ja Hyeon , Kwak Cheol , Kim Hyeon Hoe , Cho Sung-Yup , Choi Murim , Jeong Chang Wook
Published: August 2024

TFE3-rearranged renal cell cancer (tRCC) is a rare form of RCC that involves chromosomal translocation of the Xp11.2 TFE3 gene. Despite its early onset and poor prognosis, the molecular mechanisms of the pathogenesis of tRCC remain elusive. This study aimed to identify novel therapeutic targets for patients with primary and recurrent tRCC. We collected 19 TFE3-positive RCC tissues that were diagnosed by immunohistochemistry and subjected them to genetic characterization to examine their genomic and transcriptomic features. Tumor-specific signatures were extracted using whole exome sequencing (WES) and RNA sequencing (RNA-seq) data, and the functional consequences were analyzed in a cell line with TFE3 translocation. Both a low burden of somatic single nucleotide variants (SNVs) and a positive correlation between the number of somatic variants and age of onset were observed. Transcriptome analysis revealed that four samples (21.1%) lacked the expected fusion event and clustered with the genomic profiles of clear cell RCC (ccRCC) tissues. The fusion event also demonstrated an enrichment of upregulated genes associated with mitochondrial respiration compared with ccRCC expression profiles. Comparison of the RNA expression profile with the TFE3 ChIP-seq pattern data indicated that PPARGC1A is a metabolic regulator of the oncogenic process. Cell proliferation was reduced when PPARGC1A and its related metabolic pathways were repressed by its inhibitor SR-18292. In conclusion, we demonstrate that PPARGC1A-mediated mitochondrial respiration can be considered a potential therapeutic target in tRCC. This study identifies an uncharacterized genetic profile of an RCC subtype with unique clinical features and provides therapeutic options specific to tRCC.
A programmable microfluidic platform to monitor calcium dynamics in microglia during inflammation
Authors: Shebindu Adam , Kaveti Durga , Umutoni Linda , Kirk Gia , Burton Michael D. , Jones Caroline N.
Published: August 2024

Neuroinflammation is characterized by the elevation of cytokines and adenosine triphosphate (ATP), which in turn activates microglia. These immunoregulatory molecules typically form gradients in vivo, which significantly influence microglial behaviors such as increasing calcium signaling, migration, phagocytosis, and cytokine secretion. Quantifying microglial calcium signaling in the context of inflammation holds the potential for developing precise therapeutic strategies for neurological diseases. However, the current calcium imaging systems are technically challenging to operate, necessitate large volumes of expensive reagents and cells, and model immunoregulatory molecules as uniform concentrations, failing to accurately replicate the in vivo microenvironment. In this study, we introduce a novel calcium monitoring micro-total analysis system (CAM-μTAS) designed to quantify calcium dynamics in microglia (BV2 cells) within defined cytokine gradients. Leveraging programmable pneumatically actuated lifting gate microvalve arrays and a Quake valve, CAM-μTAS delivers cytokine gradients to microglia, mimicking neuroinflammation. Our device automates sample handling and cell culture, enabling rapid media changes in just 1.5 s, thus streamlining the experimental workflow. By analyzing BV2 calcium transient latency to peak, we demonstrate location-dependent microglial activation patterns based on cytokine and ATP gradients, offering insights contrasting those of non-gradient-based perfusion systems. By harnessing advancements in microsystem technology to quantify calcium dynamics, we can construct simplified human models of neurological disorders, unravel the intricate mechanisms of cell-cell signaling, and conduct robust evaluations of novel therapeutics.
Neuroserpin normalization by mesenchymal stem cell therapy after encephalopathy of prematurity in neonatal rats
Authors: Wang Lan-Wan , Hsiung Chien-Wei , Chang Ching-Ping , Lin Mao-Tsun , Chen Shyi-Jou
Published: August 2024

Background

Hypoxic-ischemia (HI), infection/inflammation and reperfusion injury are pathogenic factors of encephalopathy of prematurity, which involves maturational/neurotrophic disturbances in oligodendrocyte progenitor cells (OPC) and neurons/axons. Mesenchymal stem cells (MSCs) might facilitate neuroserpin production, which is neurotrophic for OPC/neurons. This study investigated MSC effects on developmental disturbances after lipopolysaccharide (LPS)-sensitized HI/reperfusion (LHIR) injury and the relation to neuroserpin expression.

Methods

Postnatal day 2 (P2) rat pups received intraperitoneal LPS (5 µg/kg) injection followed by HI (unilateral common-carotid-artery ligation and 6.5% oxygen exposure for 90 min) and post-HI reperfusion (release of ligation). MSCs (5 × 104 cells) were injected into the left lateral ventricle at 24 h post-LHIR. Neurological tests and brain tissue examinations were performed between P5 and P56.

Results

After LHIR injury, MSC therapy significantly reduced cell death in subplate neurons, attenuated axonal damage, and facilitated synaptophysin synthesis in the cortex. It also alleviated OPC maturation arrest and preserved the complexity of myelinated axons in the white matter, leading to cognitive, motor and behavioral functional improvements. These beneficial effects were linked to restored neuroserpin expression in subplate neurons.

Conclusions

MSC therapy ameliorated developmental disturbances after LHIR injury through protection of neuroserpin expression, serving as a promising approach for treating encephalopathy of prematurity.

Impact

Neuroserpin is secreted by subplate neurons and may regulate the development of neurons and oligodendrocyte-axon contact for myelination in the premature brain.

LPS-sensitized hypoxic-ischemia/reperfusion (LHIR) injury caused the developmental disturbances of neurons/axons and oligodendrocytes, and lowered neuroserpin levels in a neonatal rat model simulating encephalopathy of prematurity.

Mesenchymal stem cell therapy alleviated the developmental disturbances after LHIR injury through protection of neuroserpin expression in subplate neurons, offering a new perspective on potential treatment for encephalopathy of prematurity.
Copy number alterations in metastatic and early breast tumours: prognostic and acquired biomarkers of resistance to CDK4/6 inhibitors
Authors: Sablin Marie-Paule , Gestraud Pierre , Jonas Sarah Flora , Lamy Constance , Lacroix-Triki Magali , Bachelot Thomas , Filleron Thomas , Lacroix Ludovic , Tran-Dien Alicia , Jézéquel Pascal , Mauduit Marjorie , Barros Monteiro Janice , Jimenez Marta , Michiels Stefan , Attignon Valery , Soubeyran Isabelle , Driouch Keltouma , Servant Nicolas , Le Tourneau Christophe , Kamal Maud , André Fabrice , Bièche Ivan
Published: August 2024

Background

Copy number alterations (CNA) are acquired during the evolution of cancers from their early stage to metastatic stage. This study aims at analysing the clinical value of the identified metastasis-associated CNAs both in metastatic breast cancers (mBCs) and early breast cancers (eBCs).

Methods

Single-nucleotide polymorphism (SNP)-array was performed on 926 biopsies from mBC patients, enrolled in SAFIR02-BREAST prospective trial. CNA profiles of eBCs from The Cancer Genome Atlas Breast Invasive Carcinoma (n = 770), Molecular Taxonomy of Breast Cancer International Consortium (n = 1620) and PACS04 trial (n = 243) cohorts were used as references for comparing mBCs and eBCs CNA profiles. Overall survival was the considered survival endpoint.

Results

Among the twenty-one genes frequently altered in ER + /HER2− mBCs: focal amplification of TERT was associated with poor outcome in the ER + /HER2− mBC population. Among the ER + /HER2− mBCs patients for whom CDK4/6 inhibitors information before biopsies collection was available: we identified seven genes on post-treatment biopsies, including the cyclin-dependent kinase 4 (CDK4), which was amplified in 9.8% of the ER + /HER2− mBCs pretreated population, as compared to 1.5% in the ER + /HER2− mBCs unpretreated population (P = 2.82E-04) as well as the 3 eBC populations. CDK4 amplification was associated with poor outcome in the ER + /HER2− eBCs.

Conclusions

This study provides insights into the biology of mBCs and identifies clinically useful genomic features for future improvement of breast cancer patient management.
Oxidative cell death in cancer: mechanisms and therapeutic opportunities
Authors: An Xiaoqin , Yu Wenfeng , Liu Jinbao , Tang Daolin , Yang Li , Chen Xin
Published: August 2024

Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules generated as natural byproducts during cellular processes, including metabolism. Under normal conditions, ROS play crucial roles in diverse cellular functions, including cell signaling and immune responses. However, a disturbance in the balance between ROS production and cellular antioxidant defenses can lead to an excessive ROS buildup, causing oxidative stress. This stress damages essential cellular components, including lipids, proteins, and DNA, potentially culminating in oxidative cell death. This form of cell death can take various forms, such as ferroptosis, apoptosis, necroptosis, pyroptosis, paraptosis, parthanatos, and oxeiptosis, each displaying distinct genetic, biochemical, and signaling characteristics. The investigation of oxidative cell death holds promise for the development of pharmacological agents that are used to prevent tumorigenesis or treat established cancer. Specifically, targeting key antioxidant proteins, such as SLC7A11, GCLC, GPX4, TXN, and TXNRD, represents an emerging approach for inducing oxidative cell death in cancer cells. This review provides a comprehensive summary of recent progress, opportunities, and challenges in targeting oxidative cell death for cancer therapy.
Overcoming ABCB1 mediated multidrug resistance in castration resistant prostate cancer
Authors: Sarwar Sadia , Morozov Viacheslav M. , Newcomb Mallory A. , Yan Bowen , Brant Jason O. , Opavsky Rene , Guryanova Olga A. , Ishov Alexander M.
Published: August 2024

Prostate cancer (PCa) is the second leading cause of cancer-related death in American men. PCa that relapses after hormonal therapies, referred to as castration resistant PCa (CRPC), often presents with metastases (mCRPC) that are the major cause of mortality. The few available therapies for mCRPC patients include taxanes docetaxel (DTX) and cabazitaxel (CBZ). However, development of resistance limits their clinical use. Mechanistically, resistance arises through upregulation of multidrug resistance (MDR) proteins such as MDR1/ABCB1, making ABCB1 an attractive therapeutic target. Yet, ABCB1 inhibitors failed to be clinically useful due to low specificity and toxicity issues. To study taxanes resistance, we produced CBZ resistant C4-2B cells (RC4-2B) and documented resistance to both CBZ and DTX in cell culture and in 3D prostaspheres settings. RNAseq identified increased expression of ABCB1 in RC4-2B, that was confirmed by immunoblotting and immunofluorescent analysis. ABCB1-specific inhibitor elacridar reversed CBZ and DTX resistance in RC4-2B cells, confirming ABCB1-mediated resistance mechanism. In a cell-based screen using a curated library of cytotoxic drugs, we found that DNA damaging compounds Camptothecin (CPT) and Cytarabine (Ara-C) overcame resistance as seen by similar cytotoxicity in parental C4-2B and resistant RC4-2B. Further, these compounds were cytotoxic to multiple PC cells resistant to taxanes with high ABCB1 expression and, therefore, can be used to conquer the acquired resistance to taxanes in PCa. Finally, inhibition of cyclin-dependent kinases 4/6 (CDK4/6) with small molecule inhibitors (CDK4/6i) potentiated cytotoxic effect of CPT or Ara-C in both parental and resistant cells. Overall, our findings indicate that DNA damaging agents CPT and Ara-C alone or in combination with CDK4/6i can be suggested as a new treatment regimen in CRPC patients, including those that are resistant to taxanes.
TNC upregulation promotes glioma tumourigenesis through TDG-mediated active DNA demethylation
Authors: Xu Hongyu , Long Shengrong , Xu Chengshi , Li Zhengwei , Chen Jincao , Yang Bin , He Yongze , Xu Ziyue , Li Zhiqiang , Wei Wei , Li Xiang
Published: August 2024

Gliomas represent the most predominant primary malignant tumor in central nervous system. Thymine DNA glycosylase (TDG) is a central component in active DNA demethylation. However, the specific mechanisms of TDG-mediated active DNA demethylation in gliomas remain unclear. This research indicates TDG expression is overexpressed in gliomas and correlated with poor prognosis. TDG knockdown suppressed the malignant phenotype of gliomas both in vitro and vivo. Notably, RNA-seq analysis revealed a strong association between TDG and tenascin-C (TNC). ChIP-qPCR and MeDIP-qPCR assays were undertaken to confirm that TDG participates in TNC active DNA demethylation process, revealing decreased DNA methylation levels and elevated TNC expression as a result. Silencing TNC expression also suppressed the tumor malignant phenotype in both in vitro and in vivo experiments. Additionally, simultaneous silencing of TNC reduced or even reversed the glioma promotion caused by TDG overexpression. Based on our findings, we conclude that TDG exerts an indispensable role in TNC active DNA demethylation in gliomas. The DNA demethylation process leads to alternations in TNC methylation levels and promotes its expression, thereby contributing to the development of gliomas. These results suggest a novel epigenetic therapeutic strategy targeting active DNA demethylation in gliomas.
Inbreeding depression affects the growth of seedlings of an African timber species with a mixed mating reproductive system, Pericopsis elata (Harms) Meeuwen
Authors: Angbonda Dieu - Merci Assumani , Ilunga-Mulala Crispin M. , Bourland Nils , Beeckman Hans , Boyemba Faustin , Hatakiwe Hulda , Ngongo Jean Pierre , Hardy Olivier J.
Published: August 2024

Selfing or mating between related individuals can lead to inbreeding depression (ID), which can influence the survival, growth and evolution of populations of tree species. As selective logging involves a decrease in the density of congeneric partners, it could lead to increasing biparental inbreeding or self-fertilization, exposing the population to higher ID. We assessed the influence of inbreeding on the growth of a commercial timber species, Pericopsis elata (Fabaceae), which produced about 54% of self-fertilized seedlings in a natural population of the Congo basin. We followed the survival and growth of 540 plants raised in a plantation along a gradient of plant density (0.07–15.9 plants per m2). Parentage analysis allowed us distinguishing selfed and outcrossed seedlings. The annual growth was higher for outcrossed than selfed plants, on average by 10.8% for diameter and 12.9% for height growth. Based on the difference in above ground biomass between selfed and outcrossed seedlings after 41 months, we estimated the level of ID at δ = 0.33, while a lifetime estimate of ID based on the proportions of selfed plants at seedling and adult stages led to δ = 0.7. The level of ID on growth rate did not change significantly with age but tended to vanish under high competition. Pericopsis elata is a particularly interesting model because inbreeding depression is partial, with about 26% of reproducing adults resulting from selfing, contrary to most tropical tree species where selfed individuals usually die before reaching adulthood. Hence, the risks of ID must be considered in the management and conservation of the species.
Nanoscale covalent organic frameworks for enhanced photocatalytic hydrogen production
Authors: Zhao Wei , Luo Liang , Cong Muyu , Liu Xueyan , Zhang Zhiyun , Bahri Mounib , Li Boyu , Yang Jing , Yu Miaojie , Liu Lunjie , Xia Yu , Browning Nigel D. , Zhu Wei-Hong , Zhang Weiwei , Cooper Andrew I.
Published: August 2024

Nanosizing confers unique functions in materials such as graphene and quantum dots. Here, we present two nanoscale-covalent organic frameworks (nano-COFs) that exhibit exceptionally high activity for photocatalytic hydrogen production that results from their size and morphology. Compared to bulk analogues, the downsizing of COFs crystals using surfactants provides greatly improved water dispersibility and light-harvesting properties. One of these nano-COFs shows a hydrogen evolution rate of 392.0 mmol g−1 h−1 (33.3 μmol h−1), which is one of the highest mass-normalized rates reported for a COF or any other organic photocatalysts. A reverse concentration-dependent photocatalytic phenomenon is observed, whereby a higher photocatalytic activity is found at a lower catalyst concentration. These materials also show a molecule-like excitonic nature, as studied by photoluminescence and transient absorption spectroscopy, which is again a function of their nanoscale dimensions. This charts a new path to highly efficient organic photocatalysts for solar fuel production.
Estrogen levels in young women with hormone receptor-positive breast cancer on ovarian function suppression therapy
Authors: Tesch Megan E. , Zheng Yue , Rosenberg Shoshana M. , Poorvu Philip D. , Ruddy Kathryn J. , Tamimi Rulla , Schapira Lidia , Peppercorn Jeffrey , Borges Virginia , Come Steven E. , Snow Craig , Bhasin Shalender , Partridge Ann H.
Published: August 2024

Ovarian function suppression (OFS) benefits young women with hormone receptor (HR)-positive breast cancer but they are at risk for ovarian function breakthrough. We assessed endocrine effects of gonadotropin-releasing hormone agonist (GnRHa) treatment in a prospective cohort of patients aged ≤ 40 years with HR-positive breast cancer. Plasma estradiol (E2), estrone, and follicule-stimulating hormone (FSH) levels were measured from blood samples drawn 1 and 4 years after diagnosis. Patient characteristics, invasive breast cancer-free survival (iBCFS), and overall survival (OS) were compared between those with and without E2 > 2.72 pg/mL during GnRHa treatment. Among eligible patients, 54.7% (46/84) and 60% (15/25) had E2 > 2.72 pg/mL at 1 and 4 years, respectively. Factors associated with E2 > 2.72 pg/mL at 1 year were no prior chemotherapy (P = 0.045) and tamoxifen use (P = 0.009). After a median follow-up of 7 years, among patients with stage I-III breast cancer (N = 74), iBCFS events were seen in 6 (8.1%) with E2 > 2.72 pg/mL and 5 (6.8%) with E2 ≤ 2.72 pg/mL (P = 0.893). Among patients with de novo metastatic breast cancer (N = 12), 6 (50%) with E2 > 2.72 pg/mL and 3 (25%) with E2 ≤ 2.72 pg/mL died during follow-up (P = 0.052). Larger studies exploring the clinical implications of incomplete E2 suppression by GnRHa are needed to ensure optimal OFS treatment strategies are being employed for this population.
Spin-selective transport in a correlated double quantum dot-Majorana wire system
Authors: Majek Piotr , Weymann Ireneusz
Published: August 2024

In this work we investigate the spin-dependent transport through a double quantum dot embedded in a ferromagnetic tunnel junction and side attached to a topological superconducting nanowire hosting Majorana zero-energy modes. We focus on the transport regime when the Majorana mode leaks into the double quantum dot competing with the two-stage Kondo effect and the ferromagnetic-contact-induced exchange field. In particular, we determine the system’s spectral properties and analyze the temperature dependence of the spin-resolved linear conductance by means of the numerical renormalization group method. Our study reveals unique signatures of the interplay between the spin-resolved tunneling, the Kondo effect and the Majorana modes, which are visible in the transport characteristics. In particular, we uncover a competing character of the coupling to topological superconductor and that to ferromagnetic leads, which can be observed already for very low spin polarization of the electrodes. This is signaled by an almost complete quenching of the conductance in one of the spin channels which is revealed through perfect conductance spin polarization. Moreover, we show that the conductance spin polarization can change sign depending on the magnitude of spin imbalance in the leads and strength of interaction with topological wire. Thus, our work demonstrates that even minuscule spin polarization of tunneling processes can have large impact on the transport properties of the system.
Bio-inspired flat optics for directional 3D light detection and ranging
Authors: Majorel Clément , Loucif Amir , Marinov Emil , Juliano Martins Renato , Patoux Adelin , Coulon Pierre-Marie , Brandli Virginie , Antolovic Michel , Bruschini Claudio , Charbon Edoardo , Genevet Patrice
Published: August 2024

The eyes of arthropods, such as those found in bees and dragonflies, are sophisticated 3D vision tools that are composed of an array of directional microlenses. Despite the attempts in achieving artificial panoramic vision by mimicking arthropod eyes with curved microlens arrays, a wealth of issues related to optical aberrations and fabrication complexity have been reported. However, achieving such a wide-angle 3D imaging is becoming essential nowadays for autonomous robotic systems, yet most of the available solutions fail to simultaneously meet the requirements in terms of field of view, frame rate, or resistance to mechanical wear. Metasurfaces, or planar nanostructured optical surfaces, can overcome the limitation of curved optics, achieving panoramic vision and selective focusing of the light on a plane. On-chip vertical integration of directional metalenses on the top of a planar array of detectors enables a powerful bio-inspired LiDAR that is capable of 3D imaging over a wide field of view without using any mechanical parts. Implementation of metasurface arrays on imaging sensors is shown to have relevant industrial applications in 3D sensing that goes beyond the basic usage of metalenses for imaging.
Advancements in electrochemical immunosensors towards point-of-care detection of cardiac biomarkers
Authors: Madhurantakam Sasya , David Bianca Elizabeth , Naqvi Aliya , Lee Zachary J. , Abraham Jacob Thomas , Vankamamidi Trayi Sai , Prasad Shalini
Published: August 2024

Cardiac biomarkers and their connection to cardiovascular diseases.
Advancing catalytic oxidation of lean methane over cobalt-manganese oxide via a phase-engineered amorphous/crystalline interface
Authors: Wang Wei , Qiu Ruishan , Li Chenqi , Zhong Ruixia , Wang Haiwang , Qi Jian
Published: August 2024

A MW-250 W US-300 W catalyst exhibits excellent catalytic activity and stability in the catalytic oxidation of lean methane due to the amorphous/crystalline phase which increases the concentration of oxygen vacancies.
Dehydrogenative cyclization of 2-arylbenzoic acid and 2-arylbenzamide with hydrogen evolution in a photoelectrochemical cell
Authors: Li Haoran , Qiao Kaikai , Jiang Wenfeng , Li Fei , Shi Lei
Published: August 2024

Visible light-driven dehydrogenative cyclization of 2-arylbenzoic acid and 2-arylbenzamide with hydrogen evolution has been developed in a photoelectrochemical cell.
Electronic redistribution induced by interaction between ruthenium nanoparticles and Ni–N(O)–C sites boosts alkaline water electrolysis
Authors: Wang Jiacheng , He Wangtao , Zong Yuyang , Tang Yanfeng , Wang Jin , Ma Ruguang
Published: August 2024

Ru/Ni-CNCT with rich Ni–N(O)–C sites exhibits efficient electrocatalytic activity due to electronic coupling interaction and redistribution.
Orientational anisotropy due to molecular field splitting in sulfur 2p photoemission from CS2 and SF6 – theoretical treatment and application to photoelectron recoil
Authors: Kukk Edwin , Niskanen Johannes , Travnikova Oksana , Berholts Marta , Kooser Kuno , Peng Dawei , Ismail Iyas , Piancastelli Maria Novella , Püttner Ralph , Hergerhahn Uwe , Simon Marc
Published: August 2024

Photoelectron recoil is affected by orientational anisotropy of carbon disulfide molecules emitting high-energy S 2p photoelectrons, due to the effects of molecular field splitting.
Tracking the surface structure and the influence of cations and anions on the double-layer region of a Au(111) electrode
Authors: Adnan Ariba , Behjati Saeid , Félez-Guerrero Núria , Ojha Kasinath , Koper Marc T. M.
Published: August 2024

Electric double-layer capacitance plots on Au(111) are studied to better understand the role of water, cations, and anions, coupled with in situ scanning tunnelling microscopy under electrochemical conditions (ECSTM) to track the mobile surface.
Optimal-tuning of range-separated density functionals to describe the optical and photophysical properties of rhodamine B dimers
Authors: Fanciullo Giacomo , Adamo Carlo , Rivalta Ivan , Ciofini Ilaria
Published: August 2024

Optimally tuned range-separated hybrid functionals are employed to study the excited states of rhodamine B and its H dimer. The impact of range-separation parameters on the description of dimeric charge-transfer states is extensively analyzed.
Unraveling the influence of organic cations on tuning electronic structures and spin-splitting in two-dimensional layered organic–inorganic tin-iodine perovskites
Authors: Jedidi Abdesslem , Alamri Shatha M. , Alotaibi Norah O. , Goumri-Said Souraya , Kanoun Mohammed Benali
Published: August 2024

The solar cell and light-emitting device research community is currently focusing on two-dimensional (2D) hybrid perovskite materials due to their remarkable stability and intriguing optoelectronic characteristics, promising significant advancements in various applications.
Synthesis of iron phthalocyanine/CeO2 Z-scheme nanocomposites as efficient photocatalysts for degradation of 2,4-dichlorophenol
Authors: Chu Xiaoyu , Wang Xinrui , Tian Shuo , Zhao Yongkuo , Liu Shikai , Yan Hong , Shang Yan
Published: August 2024

An FePc/CeO2 heterojunction is constructed by hydrogen bonding induced assembly and follows the Z-scheme mechanism of effective charge separation. Fe2+ in FePc promotes O2 activation, thus enhancing the photocatalytic degradation of 2,4-DCP.
Synthesis, structural characterization, DFT and molecular dynamics simulations of dinuclear (μ-hydroxo)-bridged triethanolamine copper(ii) complexes: efficient candidates towards visible light-mediated photo-Fenton degradation of organic dyes
Authors: Chauhan Chetan , Tanuj  , Kumar Rajesh , Kumar Jitendra , Sharma Subhash , Benmansour Samia , Kumar Santosh
Published: August 2024

Multinuclear (di/tri) copper(ii) complexes bridged through hydroxyl groups are interesting coordination complexes owing to their potential applications in photo-Fenton catalysis and hence in water pollution remediation.
Transient heating synthesis of a highly ordered Ga–Cu intermetallic antiperovskite for efficient ammonia electrosynthesis and ultrastable zinc–nitrate fuel cells
Authors: Wang Peifang , Liu Chongchong , Rao Lei , Tao Weixiang , Huang Rong , Huang Peilin , Zhou Gang
Published: August 2024

Strong p–d intermetallic hybridization was performed to construct an ordered antiperovskite via transient heating strategy, exhibiting high and stable electrochemical activity in both ammonia synthesis and zinc–nitrate battery.
Key factors behind the superior performance of polymer-based NFA blends
Authors: Sağlamkaya Elifnaz , Shadabroo Mohammad Saeed , Tokmoldin Nurlan , Melody Tanner M. , Sun Bowen , Alqahtani Obaid , Patterson Acacia , Collins Brian A. , Neher Dieter , Shoaee Safa
Published: August 2024

Suppressed face-on stacking and crystallinity in ZR1:Y6 reduce charge dissociation, leading to more field-dependent charge generation compared to PM7:Y6, despite similar energy offsets in both blends.