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Leptin is an important regulator of basal metabolism and food intake, with a pivotal role in obesity. Leptin exerts many different actions on various tissues and systems, including cancer, and is considered as a linkage between metabolism and the immune system. During the last decades, obesity and leptin have been associated with the initiation, proliferation and progression of many types of cancer. Obesity is also linked with complications and mortality, irrespective of the therapy used, affecting clinical outcomes. However, some evidence has suggested its beneficial role, called the “obesity paradox”, and the possible antitumoral role of leptin. Recent data regarding the immunotherapy of cancer have revealed that overweight leads to a more effective response and leptin may probably be involved in this beneficial process. Since leptin is a positive modulator of both the innate and the adaptive immune system, it may contribute to the increased immune response stimulated by immunotherapy in cancer patients and may be proposed as a good actor in cancer. Our purpose is to review this dual role of leptin in cancer, as well as trying to clarify the future perspectives of this adipokine, which further highlights its importance as a cornerstone of the immunometabolism in oncology.

In order to improve the management mechanisms of the electric energy transport infrastructures, the smart grid networks have associated data networks that are responsible for transporting the necessary information between the different elements of the electricity network and the control center. Besides, they make possible a more efficient use of this type of energy. Part of these data networks is comprised of the Neighborhood Area Networks (NANs), which are responsible for interconnecting the different smart meters and other possible devices present at the consumers’ premises with the control center. Among the proposed network technologies for NANs, wireless technologies are becoming more relevant due to their flexibility and increasing available bandwidth. In this paper, some general modifications are proposed for the routing protocol of the wireless multi-hop mesh networks standardized by the IEEE. In particular, the possibility of using multiple paths and transmission channels at the same time, depending on the quality of service needs of the different network traffic, is added. The proposed modifications have been implemented in the ns-3 simulator and evaluated in situations of high traffic load. Simulation results show improvements in the network performance in terms of packet delivery ratio, throughput and network transit time.

In recent years, the general interest in routing for vehicular ad hoc networks (VANETs) has increased notably. Many proposals have been presented to improve the behavior of the routing decisions in these very changeable networks. In this paper, we propose a new routing protocol for VANETs that uses four different metrics. which are the distance to destination, the vehicles’ density, the vehicles’ trajectory and the available bandwidth, making use of the information retrieved by the sensors of the vehicle, in order to make forwarding decisions, minimizing packet losses and packet delay. Through simulation, we compare our proposal to other protocols, such as AODV (Ad hoc On-Demand Distance Vector), GPSR (Greedy Perimeter Stateless Routing), I-GPSR (Improvement GPSR) and to our previous proposal, GBSR-B (Greedy Buffer Stateless Routing Building-aware). Besides, we present a performance evaluation of the individual importance of each metric to make forwarding decisions. Experimental results show that our proposed forwarding decision outperforms existing solutions in terms of packet delivery.

Pembrolizumab prolongs progression-free and overall survival among patients with advanced melanoma and recurrence-free survival in resected stage III disease. KEYNOTE-716 assessed pembrolizumab as adjuvant therapy in patients with completely resected, high-risk, stage II melanoma. We report results from the planned first and second interim analyses for recurrence-free survival. In this double-blind, randomised, placebo-controlled phase 3 study, involving 160 academic medical centres and hospitals in 16 countries (Australia, Belgium, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Poland, South Africa, Spain, Switzerland, the UK, and the USA), patients aged 12 years or older with newly diagnosed, completely resected stage IIB or IIC melanoma (TNM stage T3b or T4 with a negative sentinel lymph node biopsy) were recruited. Eligible patients were randomly assigned (1:1), in blocks of four and stratified by T-category (3b, 4a, and 4b) and paediatric status (age 12–17 years vs ≥18 years), using an interactive response technology system to intravenous pembrolizumab 200 mg (2 mg/kg in paediatric patients) or placebo every 3 weeks for 17 cycles or until disease recurrence or unacceptable toxicity. All patients, clinical investigators, and analysts were masked to treatment assignment. The primary endpoint was investigator-assessed recurrence-free survival (defined as time from randomisation to recurrence or death) in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment). The primary endpoint was met if recurrence-free survival was significantly improved for pembrolizumab versus placebo at either the first interim analysis (after approximately 128 patients had events) or second interim analysis (after 179 patients had events) under multiplicity control. Safety was assessed in all patients randomly assigned to treatment who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03553836, and is closed to accrual. Between Sept 23, 2018, and Nov 4, 2020, 1182 patients were screened, of whom 976 were randomly assigned to pembrolizumab (n=487) or placebo (n=489; ITT population). The median age was 61 years (IQR 52–69) and 387 (40%) patients were female and 589 (60%) were male. 874 (90%) of 976 patients were White and 799 (82%) were not Hispanic or Latino. 483 (99%) of 487 patients in the pembrolizumab group and 486 (99%) of 489 in the placebo group received assigned treatment. At the first interim analysis (data cutoff on Dec 4, 2020; median follow-up of 14·4 months [IQR 10·2–18·7] in the pembrolizumab group and 14·3 months [10·1–18·7] in the placebo group), 54 (11%) of 487 patients in the pembrolizumab group and 82 (17%) of 489 in the placebo group had a first recurrence of disease or died (hazard ratio [HR] 0·65 [95% CI 0·46–0·92]; p=0·0066). At the second interim analysis (data cutoff on June 21, 2021; median follow-up of 20·9 months [16·7–25·3] in the pembrolizumab group and 20·9 months [16·6–25·3] in the placebo group), 72 (15%) patients in the pembrolizumab group and 115 (24%) in the placebo group had a first recurrence or died (HR 0·61 [95% CI 0·45–0·82]). Median recurrence-free survival was not reached in either group at either assessment timepoint. At the first interim analysis, grade 3–4 treatment-related adverse events occurred in 78 (16%) of 483 patients in the pembrolizumab groups versus 21 (4%) of 486 in the placebo group. At the first interim analysis, four patients died from an adverse event, all in the placebo group (one each due to pneumonia, COVID-19-related pneumonia, suicide, and recurrent cancer), and at the second interim analysis, one additional patient, who was in the pembrolizumab group, died from an adverse event (COVID-19-related pneumonia). No deaths due to study treatment occurred. Pembrolizumab as adjuvant therapy for up to approximately 1 year for stage IIB or IIC melanoma resulted in a significant reduction in the risk of disease recurrence or death versus placebo, with a manageable safety profile. Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA.

Mosquito-borne viruses are emerging or re-emerging globally, afflicting millions of people around the world. Aedes aegypti, the yellow fever mosquito, is the principal vector of dengue, Zika, and chikungunya viruses, and has well-established populations across tropical and subtropical urban areas of the Americas, including the southern United States. While intense arboviral epidemics have occurred in Mexico and further south in the Americas, local transmission in the United States has been minimal. Here, we study Ae. aegypti and Culex quinquefasciatus host feeding patterns and vertebrate host communities in residential environments of South Texas to identify host-utilization relative to availability. Only 31% of Ae. aegypti blood meals were derived from humans, while 50% were from dogs and 19% from other wild and domestic animals. In Cx. quinquefasciatus, 67% of blood meals were derived from chicken, 22% came from dogs, 9% from various wild avian species, and 2% from other mammals including one human, one cat, and one pig. We developed a model for the reproductive number, R0, for Zika virus (ZIKV) in South Texas relative to northern Mexico using human disease data from Tamaulipas, Mexico. We show that ZIKV R0 in South Texas communities could be greater than one if the risk of human exposure to Ae. aegypti bites in these communities is at least 60% that of Northern Mexico communities. The high utilization of non-human vertebrates and low risk of human exposure in South Texas diminishes the outbreak potential for human-amplified urban arboviruses transmitted by Ae. aegypti.

Although primary percutaneous coronary intervention (pPCI) is the treatment of choice in ST-elevation myocardial infarction (STEMI), challenges may arise in accessing this intervention for certain geodemographic groups. Pharmacoinvasive strategy (PIs) has demonstrated comparable outcomes when delays in pPCI are anticipated, but real-world data on long-term outcomes are limited. The aim of the present study was to compare long-term outcomes among real-world patients with STEMI who underwent either PIs or pPCI. This was a prospective registry including patients with STEMI who received reperfusion during the first 12 hours from symptom onset. The primary objective was cardiovascular mortality at 12 months according to the reperfusion strategy (pPCI vs PIs) and major cardiovascular events (cardiogenic shock, recurrent myocardial infarction, and congestive heart failure), and Bleeding Academic Research Consortium type 3 to 5 bleeding events were also evaluated. A total of 799 patients with STEMI were included; 49.1% underwent pPCI and 50.9% received PIs. Patients in the PIs group presented with more heart failure on admission (Killip-Kimbal >I 48.1 vs 39.7, p = 0.02) and had a lower proportion of pre-existing heart failure (0.2% vs 1.8%, p = 0.02) and atrial fibrillation (0.25% vs 1.2%, p = 0.02). No statistically significant difference was observed in cardiovascular mortality at the 12-month follow-up (hazard ratio for PIs 0.74, 95% confidence interval 0.42 to 1.30, log-rank p = 0.30) according to the reperfusion strategy used. The composite of major cardiovascular events (hazard ratio for PIs 0.98, 95% confidence interval 0.75 to 1.29, p = 0.92) and Bleeding Academic Research Consortium type 3 to 5 bleeding rates were also comparable. A low socioeconomic status, Killip-Kimball >2, age >60 years, and admission creatinine >2.0 mg/100 ml were predictors of the composite end point after multivariate analysis. In conclusion, this prospective real-world registry provides additional support that long-term major cardiovascular outcomes and bleeding are not different between patients who underwent PIs versus primary PCI.

Targeted therapy and immunotherapy have shown intracranial activity in melanoma with CNS metastases, but there remains an unmet need, particularly for patients with symptomatic CNS metastases. We aimed to evaluate atezolizumab in combination with cobimetinib or vemurafenib plus cobimetinib in patients with melanoma with CNS metastases. TRICOTEL was a multicentre, open-label, single-arm, phase 2 study done in two cohorts: a BRAF wild-type cohort and a BRAF mutation-positive cohort, recruited at 21 hospitals and oncology centres in Brazil, France, Germany, Hungary, Italy, Spain, and Switzerland. Eligible patients were aged 18 years or older with previously untreated metastatic melanoma, CNS metastases of 5 mm or larger in at least one dimension, and an Eastern Cooperative Oncology Group performance status of 2 or less. Patients in the BRAF wild-type cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral cobimetinib (60 mg once daily, days 1-21). Patients in the BRAF mutation-positive cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral vemurafenib (720 mg twice daily) plus oral cobimetinib (60 mg once daily, days 1-21); atezolizumab was withheld in cycle 1. Treatment was continued until progression, toxicity, or death. The primary outcome was intracranial objective response rate confirmed by assessments at least 4 weeks apart, as assessed by independent review committee (IRC) using modified Response Evaluation Criteria in Solid Tumours version 1.1. Because of early closure of the BRAF wild-type cohort, the primary endpoint of intracranial objective response rate by IRC assessment was not done in this cohort; intracranial objective response rate by investigator assessment was reported instead. Efficacy and safety were analysed in all patients who received at least one dose of study medication. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT03625141. Between Dec 13, 2018, and Dec 7, 2020, 65 patients were enrolled in the BRAF mutation-positive cohort; the BRAF wild-type cohort was closed early after enrolment of 15 patients. Median follow-up was 9·7 months (IQR 6·3-15·0) for the BRAF mutation-positive cohort and 6·2 months (3·5-23·0) for the BRAF wild-type cohort. Intracranial objective response rate was 42% (95% CI 29-54) by IRC assessment in the BRAF mutation-positive cohort and 27% (95% CI 8-55) by investigator assessment in the BRAF wild-type cohort. Treatment-related grade 3 or worse adverse events occurred in 41 (68%) of 60 patients who received atezolizumab plus vemurafenib plus cobimetinib in the BRAF mutation-positive cohort, the most common of which were lipase increased (15 [25%] of 60 patients) and blood creatine phosphokinase increased (ten [17%]). Eight (53%) of 15 patients treated with atezolizumab plus cobimetinib in the BRAF wild-type cohort had treatment-related grade 3 or worse adverse events, most commonly anaemia (two [13%]) and dermatitis acneiform (two [13%]). Treatment-related serious adverse events occurred in 14 (23%) of 60 patients in the BRAF mutation-positive cohort and two (13%) of 15 in the BRAF wild-type cohort. One death in the BRAF mutation-positive cohort (limbic encephalitis) was considered to be related to atezolizumab treatment. Adding atezolizumab to vemurafenib plus cobimetinib provided promising intracranial activity in patients with BRAF -mutated melanoma with CNS metastases. F Hoffmann-La Roche.

Wireless sensor networks (WSNs) are key enablers of efficient communication in the Internet of Things (IoT) ecosystem. These networks comprise numerous sensor nodes that collaboratively collect and transmit data, requiring adaptive and energy-efficient management. However, high node density and resource limitations introduce challenges such as control overhead, packet collisions, interference, and energy inefficiency. To mitigate these issues, this paper adopts the Hybrid Wireless Mesh Protocol (HWMP), standardized under IEEE 802.11s for wireless mesh networks (WMNs), as the routing protocol in WSNs. HWMP’s hybrid design combining reactive and proactive routing is well-suited for dynamic and mobile environments, making it applicable to WSNs operating under similar conditions. Building on this foundation, we propose a community-aware topology control mechanism that constructs a Connected Dominating Set (CDS) to serve as the network’s energy-efficient backbone. Node selection is guided by centrality metrics and detected community structures to enhance routing efficiency and network longevity. The mechanism is evaluated across six mobility scenarios characterized by realistic movement patterns. Comparative results show that incorporating community structure significantly improves routing performance and reduces energy consumption, validating the approach’s effectiveness in real-world WSN deployments.

Background: Heart failure (HF) is a public health issue. It represents the second most common cause of hospitalization and the leading cause in individuals over 60 years old. Tools that predict adverse outcomes in patients with HF are needed. Objective: This study analyzed the prognostic role of the serum NT-proBNP/chloride ratio as a predictor of major cardiovascular events in patients with acute decompensated HF. Methods: Patients with a confirmed diagnosis of acute decompensated heart failure were retrospectively enrolled in the study; admission NT-proBNP/chloride ratio was used to stratify patients above or below the median (>/<83). The primary composite endpoint consisted of cardiovascular mortality, decompensated HF readmission, and unplanned emergency department visits. Results: A total of 197 individuals were included, of whom 100 (50.7%) were classified above and 97 (49.2%) below the median. Patients showing a high ratio had a lower LVEF (31 vs. 39%), a higher proportion of previous MI (30 vs. 15%), a lower diastolic blood pressure (73 vs. 80 mmHg), and higher BUN (38 vs. 23 mg/dL) and creatinine (1.6 vs. 1.1 mg/dL). After a follow-up period of 92 ± 3 days, 46 patients (23%) presented the primary endpoint; those with a high NT-proBNP/chloride ratio showed an increased risk (HR 3.18, 95% CI 1.55–6.52, p = 0.0015) of the primary endpoint. After multivariate analysis, only serum NT-proBNP/chloride ratio (p = 0.02) and diastolic pressure (0.037) remained significant. The area under the ROC curve for the NT-proBNP/chloride ratio for predicting the primary composite endpoint was significantly superior when compared with AUC for NT-proBNP or chloride alone. Conclusions: The serum NT-proBNP/chloride ratio is a novel, easy to use predictor of short- and medium-term cardiovascular events in patients with acute decompensated HF.