Search Results (4,626)

B7-H3 (CD276), a member of the B7 family of proteins, is known to play a key role in the progression of a number of cancers. This protein is selectively expressed in both tumor cells and immune cells within the tumor microenvironment. Various investigations, including a number of clinical trials, have reported high levels of expression of this protein in cancerous tissues compared to their healthy counterparts. This difference in expression attracted various research efforts to establish whether such a difference can be linked to the therapeutic potential of this molecule. It is worth noting that B7-H3 is not the only immune checkpoint expressed at different levels in cancerous and healthy cells. Therapeutic strategies, based on different levels of expression, have been tested with other checkpoints. To inhibit the expression of some checkpoints, immune checkpoint inhibitors (ICIs) were developed. The introduction of these inhibitors for the treatment of some forms of advanced-stage tumors has been justly described as an important milestone in the landscape of immune therapy. Years after the launch of these inhibitors, numerous clinical trials revealed that these inhibitors benefit a narrow subset of patients suffering from advanced-stage tumors, while the majority of patients treated with these inhibitors either did not respond positively or simply did not respond at all (refractory patients). Other clinical trials showed that this form of treatment can provoke serious immune-related adverse events (irAEs). It is fair to state that changes in the expression level of a given protein in diseased tissue is an important parameter to take into account in the assessment of such a protein as a therapeutic target. However, the last ten years have demonstrated that taking the level of expression of a given checkpoint within a cancerous tissue is not sufficient to consider such expression a reliable predictive biomarker for the investigated disease. On the other hand, to establish a solid base for a given therapeutic strategy, these varying levels of expression have to be combined with a deep understanding of the biology of the molecule under investigation, as well as the identification and thorough analysis of the relevant signaling pathways, particularly those communicating with both the investigated molecule and the immune system. Recently, a number of pharmaceutical and biotechnology firms have suggested that B7-H3 is a highly promising therapeutic target for the development of immune therapeutics. In this review, we ask why hopes of better therapeutic performance are attached to this immune checkpoint. A partial answer to this question is provided through the careful consideration of the available data generated by various clinical trials. The contribution of mass spectrometry-based proteomics to this area of research is highlighted. Full article

This study presents a novel methodology that integrates Transformer-based textual analysis from professional networking platforms with traditional demographic variables within a survival analysis framework to predict turnover. Using a dataset comprising 4087 work events from Maimai (a leading professional networking platform in China) spanning 2020 to 2022, our approach combines sentiment analysis and deep learning semantic representations to enhance predictive accuracy and interpretability for HR decision-making. Methodologically, we adopt a hybrid feature-extraction strategy combining theory-driven methods (sentiment analysis and TF-IDF) with a data-driven Transformer-based technique. Survival analysis is then applied to model time-dependent turnover risks, and we compare multiple models to identify the most predictive feature sets. Results demonstrate that integrating textual and demographic features improves prediction performance, specifically increasing the C-index by 3.38% and the cumulative/dynamic AUC by 3.43%. The Transformer-based method outperformed traditional approaches in capturing nuanced employee sentiments. Survival analysis further boosts model adaptability by incorporating temporal dynamics and also provides interpretable risk factors for turnover, supporting data-driven HR strategy formulation. This research advances turnover prediction methodology by combining text analysis with survival modeling, offering small and medium-sized enterprises a practical, data-informed approach to workforce planning. The findings contribute to broader labor market insights and can inform both organizational talent retention strategies and related policy-making. Full article

Background/Objectives: Pleural mesothelioma (PM) frequently recurs despite multimodal therapy. Here, we aimed to retrospectively evaluate the safety and potential clinical benefit of radiofrequency ablation (RFA) for recurrent PM. Methods: Fourteen consecutive patients underwent CT-guided RFA between July 2019 and June 2025. The cohort comprised 13 men and 1 woman, with a median age of 69 (range, 54–77) years. All patients had previously received systemic therapy, and 12 had undergone surgery. Seven patients (50%) presented with multiple lesions, and 25 tumors (median diameter 1.8 cm; range, 0.5–7.0 cm) were treated in 23 sessions. Outcomes assessed were local tumor control, complications, and survival. Local progression and overall survival were estimated using Kaplan–Meier analysis. Adverse events were classified according to the Society of Interventional Radiology guidelines. Results: Technical success was achieved in all sessions. Two tumors showed local recurrence, corresponding to 1- and 2-year local progression rates of 10.6%. Seven patients showed distant metastases, most of whom subsequently received systemic therapy. Three patients died, two from disease progression and one from treatment-related gastrointestinal perforation during therapy for an unrelated cancer. The overall survival rates were 100%, 100%, and 60% at 1, 3, and 5 years, respectively. Major and minor complications occurred in one case each (4.3%): a refractory skin ulcer and retroperitoneal hematoma, respectively. Conclusions: RFA was technically feasible and generally well tolerated and helped achieve encouraging local control and survival in patients with recurrent PM, warranting further evaluation of RFA as a complementary approach in multimodal treatment strategies. Full article

Background: Pain management in patients with severe burns remains one of the most complex challenges in perioperative care. Burn-related pain is multifactorial, resulting from tissue destruction, intense inflammation, surgical procedures, and repeated dressing changes. Opioids remain the cornerstone of analgesia; however, prolonged use is associated with tolerance, dependence, adverse effects, and prolonged hospitalization. Multimodal and opioid-sparing strategies, including regional anesthesia, may improve postoperative outcomes by enhancing analgesia while reducing systemic drug exposure. This study aimed to evaluate the effectiveness of a standardized regional anesthesia protocol in reducing postoperative pain and opioid requirements in burn patients undergoing lower-limb escharectomy and autologous skin grafting. Methods: We conducted a retrospective, single-center analysis of 25 adult patients with deep thermal burns of the lower limbs who underwent escharectomy and split-thickness skin grafting. All patients received a combined ultrasound-guided sciatic popliteal block and adductor canal block on both the burned limb and the donor site. Ropivacaine 0.375% with clonidine was administered without exceeding a total dose of 3.0 mg/kg. Postoperative pain was assessed using the Numerical Rating Scale (NRS), and opioid consumption was recorded as rescue doses in intravenous morphine equivalents. Secondary outcomes included perioperative complications and 30-day hospital readmission. Results: Regional anesthesia provided effective postoperative pain control. Thirty-two percent of patients reported no pain (NRS 0), 52% reported mild pain (NRS 1–3), and 16% reported moderate pain (NRS 4–6). No patient reported severe pain (NRS 7–10). Only four patients (16%) required rescue opioids. No perioperative complications or block-related adverse events occurred, and no patient required hospital readmission within 30 days. Conclusions: In this cohort, regional anesthesia was associated with satisfactory postoperative analgesia and minimal opioid requirements. By reducing opioid exposure, this approach may help improve patient comfort and potentially limit opioid-related adverse effects. Larger prospective studies are needed to confirm these findings and to assess long-term outcomes. Full article

As a critically important global food crop, wheat has been increasingly threatened by the frequent occurrence of extreme high-temperature events, which impairs its growth and development, resulting in reduced seed-setting rate, compromised grain quality and diminished yield. Therefore, identifying heat-tolerant genes and enhancing thermotolerance through molecular breeding are essential strategies for wheat improvement. In this study, we retrieved spatial transcriptomic data from the public database PRJNA427246, which captured gene expression profiles in flag leaves and grains of the heat-sensitive wheat cultivar Chinese Spring (CS) under 37 °C heat stress at time points of 0 min, 5 min, 10 min, 30 min, 1 h, and 4 h. Weighted Gene Co-expression Network Analysis (WGCNA) was used to construct co-expression networks for flag leaf and grain transcriptomes. One highly significant module was identified in each tissue, along with 35 hub genes that showed a strong temporal association with heat stress progression. Notably, both modules contained the previously characterized thermotolerance gene TaMBF1c, suggesting that additional heat-responsive genes may be present within these modules. Simultaneous analysis of the expression data from four groups (encompassing different tissues and high-temperature treatments) for the 35 core genes revealed that genes from the TaHSP20 family, TaMBF1c family, and other related genes exhibit coordinated expression patterns in terms of the temporal dynamics and tissue distribution of stress responses. Additionally, 27 genes of the small heat shock protein (HSP20) family are predicted to be involved in the endoplasmic reticulum-associated degradation (ERAD) pathway. They assist in clearing misfolded proteins induced by stress, thereby helping to maintain endoplasmic reticulum homeostasis and cellular functions under stress conditions. Finally, the expression levels of three core genes, TaHSP20-1, TaPCDP4, and TaMBF1c-D, were validated by qRT-PCR in two wheat cultivars with distinct thermotolerance: S116 (Zhehuamai 2008) and S128 (Yangmai 33). These findings provide new insights into the molecular mechanisms underlying heat tolerance in wheat and offer valuable genetic resources for breeding thermotolerant varieties. Full article

Today, machine learning (ML) is generally considered a potent and efficient tool for addressing studies in various diverse domains, including image processing and event prediction on a timescale. ML represents complex relations between features, and these mappings between such features may be applied in simulations of time-dependent events, such as the behavior of animals. Still, ML inherently strongly depends on extensive and consistent datasets, a fact that reveals both the benefits and drawbacks of ML. In the use of ML, insufficient or skewed data can limit the ability of algorithms to accurately predict or generalize possible states. To overcome this limitation, this work proposes an integrated hybrid approach that combines machine learning with methods from cognitive science, here especially inspired by the ACT-R model to approach cases of missing or unbalanced data. By incorporating cognitive processes such as memory, perception, and attention, the model accounts for the internal mechanisms of decision-making and environmental interaction where traditional ML methods fall short. This approach is particularly useful in representing states that are not directly observable or are underrepresented in the data, such as rare behavioral responses for animals, or adaptive strategies. Experimental results show that the combination of machine learning for data-driven analysis and cognitive ‘rule-based’ frameworks for filling in gaps provides a more comprehensive model of animal behavior. The findings suggest that this hybrid approach to simulation models can offer a more robust and consistent way to study complex, real-world phenomena, especially when data is inherently incomplete or unbalanced. Full article

Introduction: The addition of immunotherapy to neoadjuvant treatment for early triple-negative breast cancer (TNBC) has been adopted in clinical practice in France since March 2022, with little real-world data published on the topic. The aim of this study was to evaluate real-world data on treatment feasibility, efficacy, and related toxicities, with a specific focus on immune-related adverse events (irAEs). Methods: We conducted a retrospective analysis of patients who completed at least the neoadjuvant sequence of pembrolizumab combined with chemotherapy for early-stage TNBC at Montpellier Cancer Institute from April 2022 to July 2024. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The pathological complete response (pCR) was defined as the absence of residual invasive disease in the breast and axillary lymph nodes (ypT0/Tis ypN0). Results: We reviewed data from 92 patient records. The median age at diagnosis was 50 years (range: 27–76). The history of autoimmune disease was noted in 3.2% of patients. Grade 3–4 irAEs were observed in 20% of patients and included hepatitis (8.6%), colitis (3.3%), skin toxicity (2.1%), myocarditis (2%), arthralgia (1%), autoimmune hemolytic anemia (1%), hypothyroidism (1%), and adrenal insufficiency (1%). No treatment-related deaths were reported. Immunotherapy was discontinued due to irAEs in 29.3% of patients in the study population. The pCR rate was 61,1%, with no significant association between the number of neoadjuvant pembrolizumab cycles and the pCR rate (p = 0.7). Patients experiencing grade 3–4 irAEs had a pCR rate of 80%, compared to 56.7% in those without such toxicities (p = 0.079). Initial positivity of antinuclear antibodies (ANA) was not associated with an increased incidence of irAEs. Conclusions: The immune-related adverse events and efficacy data observed in our cohort were broadly comparable to those reported in the KEYNOTE-522 trial, with no treatment-related deaths. Patients with grade 3–4 irAEs tended to have higher pCR rates. Full article

Background/Objectives: Venovenous extracorporeal membrane oxygenation (VV ECMO) supports reversible respiratory failure when mechanical ventilation fails. Technological advances and specialized teams now enable ECMO initiation at referring centers, even for high-risk transports. This study aimed to evaluate the safety of pediatric patients on ECMO support during medical transfer, based on a single-center experience and a systematic review of the literature. Methods: A retrospective analysis was conducted on all pediatric patients supported with ECMO transferred from regional hospitals to our university hospital (January 2023–September 2025), focusing on transport-related mortality and morbidity. We also performed a systematic review of original articles (2015–2025) using the PubMed, Embase, and Cochrane databases. Results: Fourteen critically ill children with a median age of 16 months (range: 2 months to 11 years) and acute respiratory failure were transferred to our hospital’s Intensive Therapy Unit. All transported patients in the local cohort were supported with VV ECMO. Transport distances ranged from 5 to 520 km (median: 151 km). No mortality or serious adverse events occurred during transfer. Two technical issues were noted. In the systematic review, 14 articles met the inclusion criteria, reporting a total of 900 transfers, mainly primary ECMO initiations (779–86.6%). The number of ground transports was 337, which accounted for 37.4%. Adverse events were reported in 252 out of 900, which was 28%. One death during transport was reported (mortality: 1‰). Conclusions: All transports were safely performed by our experienced multidisciplinary mobile ECMO team. Both our experience and literature review confirmed low mortality in pediatric ECMO transport, despite potential life-threatening adverse events. Full article

Influenza has long been a well-documented contributor to cardiovascular morbidity and mortality, particularly among high-risk groups. COVID-19 has notably altered the seasonality and natural history of pandemic influenza, with broad implications for related cardiac complications. This review examines the interaction between influenza and cardiovascular illness, especially myocardial infarction, congestive heart failure, stroke, and other acute cardiac events. We review the impact of the COVID-19 pandemic on influenza transmission dynamics, public health policy, and the evolving burden of cardiovascular complications. New evidence indicates that both diseases exacerbate endothelial dysfunction, systemic inflammation, and prothrombotic states, thereby increasing cardiovascular risk. A comparative analysis of pre- and post-COVID-19 influenza-related cardiac complications clarifies evolving trends and guides future preventive strategies. In light of the recent resurgence of influenza following the relaxation of COVID-19 mitigation measures, maximizing vaccine coverage and collaborating to manage viral infections in patients with cardiovascular disease are critical. This review focuses on key research needs to understand long-term cardiac consequences and the urgent requirement for targeted public health strategies to counter viral-mediated cardiovascular threats. In the post-COVID era, integrating influenza and COVID-19 vaccination strategies into cardiovascular risk management may represent a critical opportunity to reduce virus-triggered cardiovascular morbidity and mortality. Full article

Postsocialist peri-urban spaces are characterized by a chaotic development as a result of the transition from communism to capitalism. Recent research has highlighted that liveability in peri-urban spaces encounters challenges of adaptation to the peri-urban areas. The aim of the present study is to identify and analyze patterns and contrasts that occur between age groups and gender in relation to the level of liveability as well as to better understand the daily mobility practices and commuting dependencies and how mobility shapes key contrasts and emerging tensions within Timișoara’s postsocialist peri-urban spaces. As liveability relates to local development, commuting, and accessibility to service facilities in the residential environment, the identification of patterns and differences is imperative when considering the perception of local residents on potential (un)sustainable liveability in peri-urban areas. This study utilizes a quantitative analysis, informed by a survey of considerable size (N = 954) conducted in peri-urban settlements of Timisoara, Romania, with a view to elucidating the distinctions and commonalities in the perceptions held by the local populace. The findings indicate that the elderly population exhibits a greater reluctance to adapt to the emerging peri-urban environment. In contrast, the younger and more educated demographic demonstrates a higher degree of adaptability to the contemporary challenges posed by peri-urban expansion and hazardous development. Daily mobility, including commuting, is directly influenced by the effects of dispersed and chaotic development (e.g., more than 79% of respondents rely on private cars for commuting), as well as the lack of facilities and services (e.g., 2.21 level of satisfaction regarding cultural events). This highlights Timisoara’s dependence on external services, as well as the significant role of personal vehicles in providing access to the city center and its neighborhoods. Therefore, we can observe the peri-urban area undergoing a transitional phase as it navigates the initial stages of sustainable urban development and pursues an enhanced quality of life. Finally, we propose several policy recommendations for local authorities, offering solutions for enhancing liveability in peri-urban areas. Full article

Through a comprehensive analysis of urban vegetation summer seasonal and interannual patterns in the Bucharest metropolis in Romania, this study explored the response of urban vegetation to heat waves’ (HWs) impact in relation to multi-climatic parameters variability from a spatiotemporal perspective during 2000–2024, with a focus on summer HWs periods (June–August), and particularly on the hottest summer 2024. Statistical correlation, regression, and linear trend analysis were applied to multiple long-term MODIS Terra/Aqua and MERRA-2 Reanalysis satellite and in situ climate data time series. To support the decline in urban vegetation during summer hot periods due to heat stress, this study found strong negative correlations between vegetation biophysical observables and urban thermal environment parameters at both the city center and metropolitan scales. In contrast, during the autumn–winter–spring seasons (September–May), positive correlations have been identified between vegetation biophysical observables and a few climate parameters, indicating their beneficial role for vegetation growth from 2000 to 2024. The recorded decreasing trend in evapotranspiration from 2000 to 2024 during summer HW periods in Bucharest’s metropolis was associated with a reduction in the evaporative cooling capacity of urban vegetation at high air temperatures, diminishing vegetation’s key function in mitigating urban heat stress. The slight decline in land surface albedo in the Bucharest metropolis due to increased urbanization may explain the enhanced air temperatures and the severity of HWs, as evidenced by 41 heat wave events (HWEs) and 222 heat wave days (HWDs) recorded during the summer (June–August) period from 2000 to 2024. During the severe 2024 summer heat wave episodes in the south-eastern part of Romania, a rise of 5.89 °C in the mean annual land surface temperature and a rise of 6.76 °C in the mean annual air temperature in the Bucharest metropolitan region were observed. The findings of this study provide a refined understanding of heat stress’s impact on urban vegetation, essential for developing effective mitigation strategies and prioritizing interventions in vulnerable areas. Full article

Parametric tropical cyclone models are widely used to generate large wind field ensembles for assessing extreme storm tides and wave heights. The radius of maximum wind (RMW) is a key model parameter and is commonly estimated using empirical formulas. This study shows that uncertainty introduced by the choice of RMW formulas has been largely overlooked in tropical cyclone risk assessments. Using the Pearl River Estuary as a case study, historical wind fields (1981–2024) were generated with a parametric tropical cyclone model combined with eight empirical RMW formulas. Storm tides and wave heights during tropical cyclone events were simulated using a coupled wave–current model (ROMS–SWAN) and analyzed with extreme value theory. The results indicate that, for estuarine nearshore zones, the 100-year return period of water level and significant wave height vary by up to 1.26 m and 1.54 m, respectively, across all the selected RMW formulas. Joint probability analysis further shows that RMW uncertainty can shift the joint return period of the same compound storm tide and wave event from 100 years to 10 years. For an individual extreme event, differences in the RMW formula alone can produce deviations up to 2.11 m in peak storm tide levels and 3.8 m in significant wave heights. Such differences can also change the duration of extreme sea states by 13 h. These results highlight that RMW formula selection is a critical uncertainty factor, and related uncertainty should be considered in large-sample tropical cyclone hazard assessment and engineering design. Full article

The cryptochromes (CRYs) perceive blue light to regulate various developmental and metabolic events. However, the role of CRYs in flavonoid biosynthesis and flower pigmentation in safflower (Carthamus tinctorius L.) remains unknown. In this study, we determined flower color diversity among 485 safflower genotypes using the integrated CIELAB color space parameters and cluster analysis. On this basis, distinct colors were categorized into four groups, namely white (WW), yellow (YY), orange–red (OR), and yellow–red (YR). A genome-wide association study (GWAS) via 933,444 high-quality SNPs showed CtCRY2 as a flower color variation gene. Subsequently, genomic analysis identified three genes of the CRY family, including CtCRY1.1, CtCRY1.2, and CtCRY2. In silico analysis, such as gene structure, phylogeny and cis-acting elements, suggested CtCRY1.1 as a key candidate in pigment biosynthesis and was, therefore, selected for functional validation. Overexpression of CtCRY1.1 in Arabidopsis accumulated a high flavonoid content, particularly upregulating the expression of CHS, FLS, and ANS, proving its role as a positive regulator of flavonoid biosynthesis in safflower. These findings provide insights into the molecular mechanisms underlying flower color regulation in safflower and highlight CtCRY1.1 as a new target to enhance pigment-related traits in plants. Full article

Significant differences in reproductive performance exist between meat-type ducks (e.g., Qiangying Duck, QD) and laying-type ducks (e.g., Shaoxing Duck, SD). The molecular mechanisms underlying these differences, particularly concerning ovarian development and function, remain incompletely understood. This study aimed to comprehensively characterize the ovarian transcriptomes of these two duck types, focusing on differential gene expression and post-transcriptional regulatory events. We performed an integrated full-length transcriptome analysis of ovarian tissues from these two breeds using PacBio SMRT and Illumina sequencing. Bioinformatic analyses, including functional annotation, differential expression analysis, and the identification of APA events, were used. We discovered substantial breed-specific differences in alternative polyadenylation (APA), with SD ducks exhibiting significant 3′UTR shortening in 3799 genes and 3′UTR lengthening in 1626 genes compared to QD. The integrated analysis of differential gene expression and APA events highlighted key genes related to steroid hormone synthesis (HMGCS1, DHCR24), lipid metabolism (SCD), signal transduction (HRAS), and antioxidant defense (SOD1). The functional enrichment implicated critical pathways such as mitochondrial energy metabolism, oxidative phosphorylation, and fatty acid degradation. Our study provides a comprehensive atlas of post-transcriptional regulation in the duck ovary and reveals APA as a crucial process of gene regulation. APA may contribute to the differential ovarian function and egg-laying capacity between meat and laying ducks, thus offering valuable targets for genetic selection. Full article

Family-implemented interventions are evidence-based practices used to support a range of developmental outcomes, including social communication. Social communication is a broad construct that encompasses a variety of skills, from foundational abilities such as joint attention (i.e., two people attending to the same object or event) to more advanced behaviors like triadic interactions (i.e., responding to or initiating conversation that involves reciprocal interactions). In a previous study, we examined the effects of a brief, parent-implemented Naturalistic Developmental Behavioral Intervention (NDBI), delivered over telepractice with video feedback coaching. The intervention resulted in increased strategy use by all mothers and the frequency of communication for three young children. In the current study, we conducted a secondary analysis of those data to explore whether the communication-focused intervention produced a collateral effect on activity-engaged triadic interactions (i.e., mother–child–mother or child–mother–child exchanges while simultaneously engaging in a joint activity). Although a functional relation was not established, critical theoretical implications are posed. These findings highlight the need for future research to break apart complex skills into subskills to detect any subtle changes in child outcomes. Limitations and directions for future research are discussed. Full article