Search Results (81)

Background: Increasing evidence suggests that the immunogenicity of COVID-19 mRNA vaccines might influence the efficacy of immune checkpoint inhibitors (ICIs). Current studies have not considered the impact of additional vaccinations, which are now recommended as a preventive strategy against SARS-CoV-2 infection for cancer patients receiving active treatments. Consequently, we leveraged the prospective monitoring from the Vax-On-Third study to explore whether periodic mRNA vaccine boosters administered around the start of ICIs could influence the rates of immune-related adverse events (irAEs) and survival outcomes in patients with advanced non-small cell lung cancer (NSCLC). Methods: Our study included patients with a histological diagnosis of metastatic NSCLC and available PD-L1 tumor proportion score (TPS), who had undergone at least two cycles of upfront treatment with pembrolizumab, cemiplimab, or their combination with platinum-based chemotherapy. Patients who received any additional mRNA-based vaccine doses within 60 days before to 30 days after starting ICIs accounted for the exposed cohort. Those who declined further boosters formed the reference cohort. We analyzed differences in irAE frequencies, progression-free survival (PFS), and overall survival (OS) using univariate and multivariate analyses. Results: Between 27 November 2021 and 31 March 2024, we enrolled 226 eligible patients. The exposed cohort consisted of 112 patients who had received either a third or fourth dose of tozinameran or a bivalent booster. Based on PD-L1 expression levels, 93 (41%) and 133 (59%) patients received single-agent ICIs (PD-L1 TPS ≥ 50%) or combination regimens (PD-L1 TPS < 50%), respectively. Propensity-score matching using comprehensive criteria resulted in two cohorts of 102 patients each, with an optimal balance of prognostic factors. A thorough analysis of any grade irAEs showed no significant differences between the cohorts. A longitudinal survival assessment with a median follow-up of 22.8 (95% CI 19.2–26.0) months showed no difference between the cohorts. The median PFS for the reference and exposed cohorts was 7.5 (95% CI 5.9–9.1) and 8.2 (95% CI 6.2–10.2) months, respectively (p = 0.408; HR 0.88 [95% CI 0.66–1.18]). The median OS for the reference and exposed cohorts was 10.5 (95% CI 7.9–13.0) and 13.8 (95% CI 12.0–15.5) months, respectively (p = 0.170; HR 0.81 [95% CI 0.59–1.09]). Multivariate analysis confirmed that receiving additional mRNA vaccine boosters did not significantly affect the risk of disease progression or mortality. Univariate analysis within the subgroup of patients with high PD-L1 TPS who received single-agent ICIs showed a significant OS advantage for patients in the exposed cohort (9.7 [95% CI 8.1–11.2] vs. 18.6 [95% CI 13.5–23.6] months; p = 0.034; HR 0.59 [95% CI 0.36–0.96]). Conclusion: After optimally balancing prognostic factors, regular mRNA vaccine boosters at the onset of ICIs did not impact the safety and survival of patients with advanced NSCLC. The improved outcome observed in patients with high PD-L1 expression levels aligns with previous findings and warrants further investigation. Full article

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, necessitating comprehensive management and prevention strategies. Rehabilitative cardiology, also known as cardiac rehabilitation (CR), is a multidisciplinary approach aimed at enhancing recovery, reducing the risk of recurrent cardiac events, and improving patients’ quality of life. This review explores the critical role of cardiovascular nursing in CR, highlighting its contributions to patient education, psychosocial support, and care coordination. Through an analysis of current evidence, we outline the core components of CR, including exercise training, risk factor modification, and behavioral interventions. Cardiovascular nurses play a pivotal role in optimizing patient outcomes by conducting assessments, providing tailored education, and addressing psychological challenges such as depression and anxiety, which often accompany CVDs. Despite the well-documented benefits of CR, participation rates remain low due to barriers such as inadequate referral systems, accessibility challenges, and socioeconomic disparities. Emerging solutions, including telemedicine and home-based CR, offer promising alternatives to improve adherence and accessibility. The review underscores the need for expanded nursing roles, interdisciplinary collaboration, and policy advancements to bridge existing gaps in CR utilization. By integrating innovative care models, cardiovascular nursing can further enhance the effectiveness of rehabilitative cardiology and contribute to improved long-term patient outcomes. Full article

Background: The arcuate fasciculus (AF) is a critical white matter (WM) tract that connects key cortical language-processing regions, including the so-called Broca’s and Wernicke’s areas. The aim of the present study was to quantitatively assess its radiological–anatomical–morphometric modifications according to different brain tumor histotypes. Methods: A retrospective multicentric Italian study was conducted. AF reconstructions were calculated for both hemispheres for each patient diagnosed with glioblastoma (GBM), low-grade glioma (LGG), brain metastasis, and meningioma using Elements Fibertracking 2.0 software (Brainlab AG, Munich, Germany). A 3D object of each fascicle was evaluated for its volume, average fractional anisotropy (FA), and length. The cerebral healthy hemisphere was compared to the pathological contralateral in different tumor histotypes. Results: In total, 1294 patients were evaluated. A total of 156 met the inclusion criteria. We found a significant difference between healthy hemisphere and the contralateral for AF mean length and volume (p = 0.01 and p < 0.001, respectively). Considering separately the different tumor histotypes, the GBM subgroup (98, 63%) confirmed the results for mean FA and volume (p-value < 0.001); LGG patients (26, 17%) showed no significant difference between healthy and pathological hemisphere for AF mean length, mean FA, and volume (p-value 0.5, p-value 0.3, p-value <0.1, respectively). In patients affected by brain metastasis (18, 12%), Student’s t-test showed a significant difference for FA (p-value 0.003). No differences were found in patients affected by meningiomas (14, 9%) (14). Conclusions: Thorough knowledge of the microscopic anatomy and function of the arcuate fasciculus, as well as the pattern of growth of the different brain tumor histotypes, along with a careful preoperative neuroradiological assessment are mandatory to plan a tailored surgical strategy and perform a safe and effective surgical technique. The AF could be displaced and infiltrated/destructed by the solid component and peritumoral edema, respectively, of GBM. LGG shows a prevalent infiltrative pattern. Metastases account for AF dislocation due to peritumoral edema. Meningiomas do not affect WM anatomy. Full article

The greenhouse effect, responsible for trapping heat in Earth’s atmosphere, has a parallel thermal phenomenon at the indoor scale known as the Room-Level Greenhouse Effect (RGHE), where solar radiation elevates room temperatures and increases energy consumption. The RGHE contributes to indoor temperature increases of 4–10 °C and elevates energy demands by 15–30% in high solar exposure zones, the effect being even worse in tropical zones. To address this problem, an innovative analog microarchitecture is proposed for real-time RGHE detection by sensing the sunlight intensity radiation factor (SIR). A compact analog system is introduced, comprising three stages: a Sensing Circuit Stage (SCS) that isolates the dynamic sunlight signal f (r) from static room condition factors (RCFs), an Amplification Stage (AS) that shifts and boosts the signal, and a Stabilized Peak Detection Stage (SPDS) that captures the peak solar intensity. The microsystem was tested across fixed f (m) levels of 0.75 V, 1.0 V, and 1.5 V, and varying f (r) values of 3 mV, 4 mV, and 5 mV. It successfully detects peak voltages ranging from 1.69 V to 1.92 V, with stabilization achieved within 60 µs, enabling accurate detection of the f (r) signal. The proposed microarchitecture offers a scalable approach to localized thermal monitoring in smart building environments using fully analog circuitry, designed and simulated in Cadence Virtuoso using the TSMC 180 nm technology library. Full article

This paper introduces an innovative low-voltage, low-power current differencing buffered amplifier (CDBA). The proposed CDBA utilizes a bulk-driven MOS transistor operating in the subthreshold region, allowing it to function effectively at low supply voltages while minimizing power consumption, making it suitable for sensor and biomedical applications. To demonstrate the performance of the proposed CDBA, it is incorporated into the design of a current-mode, third-order low-pass filter that is specifically tailored for bio-sensing applications. Both the CDBA and the low-pass filter are designed and simulated in Cadence Virtuoso using the TSMC 0.18 µm CMOS process. The CDBA operates at a supply voltage of 0.3 V, consuming 170 nW of power, while the third-order low-pass filter achieves a dynamic range of 57.2 dB with a total harmonic distortion (THD) of 1%. Full article

This paper presents the integration of memristors into N-path filter architectures to develop reconfigurable N-path filters with a tuneable bandwidth. Two different memristor-based N-path filter designs are proposed and systematically compared. One of the architectures was experimentally validated by interfacing it with a memristor package in a laboratory environment, demonstrating a tuneable bandwidth ranging from 1.5 kHz to 2 kHz at a centre frequency of 1 MHz, corresponding to a tuneable quality factor (Q factor) of between 500 and 667. Additionally, this design enables centre frequency tuning from 0.9 MHz to 1.2 MHz while maintaining a fixed Q factor of 600. The second architecture was evaluated through simulations in the Cadence Virtuoso environment using a memristor model. The results indicate a tuneable bandwidth from 0.99 MHz to 1.38 MHz at a centre frequency of 1 GHz, corresponding to a tuneable Q factor ranging from 730 to 1010. Furthermore, this design allows the centre frequency to be adjusted within the range of 0.99 GHz to 1.38 GHz while preserving a fixed Q factor of 1000. These findings highlight the potential of memristor-based N-path filters in achieving reconfigurable and high-Q filtering capabilities for RF applications. Full article

(1) Background: Clinical evidence has raised concerns regarding a potential link between COVID-19 mRNA-based vaccines and the occurrence of thromboembolic events. So far, no research has explored the effects of this possible interaction in cancer patients undergoing active treatment. We leveraged prospective monitoring from the Vax-On-Third-Profile study to examine the development of venous thromboembolism (VTE) after the third dose of mRNA-BNT162b2 (tozinameran) and its association with antibody and lymphocyte responses. (2) Methods: Patients who had received a third dose of tozinameran and had not experienced any VTE in the previous 30 days were eligible. A serological evaluation was conducted before the booster vaccination (timepoint-1) and four weeks thereafter (timepoint-2) to measure antibody titers against the SARS-CoV-2 spike protein, as well as to determine the absolute counts of T-helper cells, T-cytotoxic cells, B cells, and NK cells. Data were acquired from November 2021 to October 2022 and analyzed from November 2022 to October 2023. (3) Results: The present study involved 429 patients who were given a third dose of tozinameran from 26 September to 30 October 2021. Among the active treatments of interest, 109 (25.4%) patients received targeted therapy, 111 (25.9%) received cytotoxic chemotherapy, 39 (9.1%) received immune checkpoint inhibitors, 21 (4.9%) received endocrine therapy, and 30 (7.0%) received a combination of chemotherapy and targeted agents in the eight weeks preceding the booster dosing. In addition, 119 (27.7%) patients who had discontinued any systemic therapy for at least 12 weeks accounted for the reference subgroup. After a median follow-up time of 10.6 (95% CI 8.1–11.7) months, we observed 31 venous thromboembolic events in the general population, for an overall incidence rate of 7.2% (95% CI 5.0–10.1). The median time to VTE development after booster immunization was 99 (95% CI 85–112) days. In a univariate comparison, patients exposed to targeted therapies (11.3% [95% CI 6.0–18.9]; p = 0.030) or immune checkpoint inhibitors (16.2% [95% CI 6.2–32.0]; p = 0.012) had a significantly higher incidence of VTE than the reference cohort (3.4% [95% CI 0.9–8.5]). Univariate analysis of immune responses showed that only dynamic changes pertaining to NK cell distributions correlated significantly with VTE occurrence. Multivariate regression analysis confirmed only a high-level NK cell response (OR 6.10 [9% CI 2.16–17.21]; p = 0.001), a history of thromboembolic events (OR 9.81 [3.99–24.13]; p < 0.001), and the presence of a central venous catheter (OR 5.02 [95% CI 1.84–13.67]; p = 0.002) as independently associated with an increased risk of VTE. (4) Conclusions: This prospective cohort study provides unprecedented evidence that cancer patients have no increased risk of developing VTE after the third dose of tozinameran, regardless of the type of active therapy. The specific pattern of lymphocyte response appears to increase thromboembolic risk, underlying immune dysregulation as a causal cofactor. These findings emphasize the need for additional monitoring after periodic COVID-19 vaccination in cancer patients. Full article

This paper presents a low-voltage, low-power current differencing transconductance amplifier (CDTA) utilizing the bulk-driven MOS transistor technique in the subthreshold region for reduced voltage and power consumption. The proposed CDTA includes a z-copy terminal, which enhances its functionality in current-mode circuit applications. Designed in the Cadence Virtuoso environment using 0.18 µm CMOS technology from Taiwan Semiconductor Manufacturing Company (TSMC), the amplifier operates with a supply voltage of 0.45 V and consumes 328 nW of power, with a bias current set to 10 nA. The current bandwidth and offset of the CDTA are 35 kHz and 0.3 nA, respectively. To demonstrate its performance, the CDTA is applied in a current-mode universal filter, which can realize low-pass, band-pass, high-pass, band-stop, and all-pass responses within a single topology. This design eliminates issues related to inverting input signals, input signal matching, or the need for multiple input signals. Additionally, the natural frequency of these filtering functions can be electronically controlled. The low-pass filter achieves a dynamic range of 61 dB, with a total harmonic distortion of 0.8%. Full article

The performance of Static Nanomaterials Random-Access Memories (SRAMs) is often degraded in the sub-threshold region as it is susceptible to increased access energy and leakage power. However, the low-power operation of SRAM is very much essential for efficient device functioning. Accordingly, designing robust SRAM cells that maintain stability and minimize power consumption is a key challenge. In this regard, with this ongoing work, the authors present novel designs of SRAMs using memristor technology by mitigating the shortcomings discussed above. This paper proposes a novel SRAM architecture of four transistors and five memristors, by integrating memristor technology to achieve drastic improvement in performance at subthreshold regions. Further, it performs an analysis of the metrics of static noise margin and power consumption to comprehensively evaluate the proposed SRAM designs. Simulation using Cadence Virtuoso for 65 nm technology demonstrates that power consumption for a 4T5M cell is about two and a half times lower than for 4T4M and 1.2 times lower than for 4T3M, hence proving that it will be promising for extremely low-power applications. Full article

Severe obesity is closely associated with an increased risk of comorbidities and alterations in cardiac structure and function. The primary objective of this study was to investigate cardiovascular (CV) risk factors and ventricular remodeling in individuals from an obese population eligible for bariatric surgery. The secondary objective was to evaluate changes in anthropometric, clinical laboratory, and echocardiographic measurements 12 weeks after surgery compared to baseline values. This retrospective observational cohort study involved patients from a single specialized bariatric surgery center. A total of 35 patients were included (mean age 41.5 ± 10.3 years; BMI 43.4 ± 6.6 kg/m²), of whom 34.2% had a family history of coronary artery disease (CAD), 5.7% had a prior history of CAD, 8 had essential hypertension, 11.4% had dyslipidemia, 20% were smokers, and 8.6% were former smokers. Approximately 57% of the patients exhibited concentric left ventricular remodeling, and 14% had grade I diastolic dysfunction. At 12 weeks post-surgery, with an average weight loss of 25 kg and a mean BMI reduction of 8.5 kg/m², 14% of the patients still exhibited concentric left ventricular remodeling, and about 11% had grade I diastolic dysfunction. Bariatric surgery contributes to the improvement of cardiac function and structure over time as a result of significant weight loss. Full article

Baseline thyroid function, as measured by the fT3 to fT4 ratio, has been shown to influence the prognosis of advanced cancer patients receiving active treatments. Although immune checkpoint blockade can alter the balance of thyroid hormones, this interaction has not been thoroughly investigated. The present research sought to determine whether changes in the fT3/fT4 ratio could affect the survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) who were undergoing pembrolizumab-based therapies. This study included patients with metastatic NSCLC who received pembrolizumab as upfront treatment, either alone or in combination with platinum-based chemotherapy. Relevant data were gathered before the start (time point 1) and after 12 weeks (time point 2) of treatment. From April 2018 to May 2023, we enrolled 258 eligible patients, 156 (60.5%) and 102 (39.5%) of whom were treated with single-agent or combination therapy, respectively. We stratified patients into two groups based on baseline fT3 and fT4 values [euthyroid cohort defined by fT3 and fT4 both within the normal range vs. euthyroid sick syndrome cohort defined by low fT3 and/or fT4 levels]. We examined the differences in progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analyses. After applying propensity-score matching, we considered 88 relevant cases in each cohort. Longitudinal comparison of fT3/fT4 ratios showed a significant increase in the median value after pembrolizumab-based therapy (p < 0.001). We computed ROC curves to analyze the correlation between fT3/fT4 ratios and survival outcomes. The relative AUC values were not viable in predicting a positive outcome at the first time point. Conversely, assessment at the second time point revealed a significant association with PFS [AUC 0.82 (95% CI 0.75–0.89), p < 0.001] and OS [AUC 0.81 (95% CI 0.75–0.88), p < 0.001]. After a median follow-up of 20.2 (95% CI 16.2–24.2) months, the median PFS for the low and high fT3/fT4 ratio groups was 4.1 (95% CI 3.0–5.1) and 15.3 (95% CI 10.3–20.1) months, respectively (p < 0.001). The median OS for the low and high fT3/fT4 ratio groups was 6.7 (95% CI 4.9–8.5) and 19.6 (95% CI 16.4–22.8) months, respectively (p < 0.001). The multivariate analysis revealed that a low fT3/fT4 ratio was independently associated with shorter PFS [HR 2.51 (1.66–3.78); p < 0.001] and OS [HR 2.18 (1.43–3.34); p < 0.001]. After the optimal weighting of prognostic factors according to thyroid function impairment, the fT3/fT4 ratio at baseline did not affect the survival of patients receiving immune checkpoint blockade for advanced NSCLC. Patients with an increased fT3/fT4 ratio experienced a significantly decreased risk of disease progression and mortality. The longitudinal assessment of fT3/fT4 ratio may play a predictive role in this specific therapeutic setting. Full article

Glioblastoma is the most fatal and common malignant brain tumor, excluding metastasis and with a median survival of approximately one year. While solid tumors benefit from newly approved drugs, immunotherapy, and prevention, none of these scenarios are opening for glioblastoma. The key to unlocking the peculiar features of glioblastoma is observing its molecular and anatomical features tightly entangled with the host’s central nervous system (CNS). In June 2024, we searched the PUBMED electronic database. Data collection and analysis were conducted independently by two reviewers. Results: A total of 215 articles were identified, and 192 were excluded based on inclusion and exclusion criteria. The remaining 23 were used for collecting divergent molecular pathways and anatomical features of glioblastoma. The analysis of the selected papers revealed a multifaced tumor with extreme variability and cellular reprogramming that are observable within the same patient. All the variability of glioblastoma could be clustered into three pillars to dissect the physiology of the tumor: 1. necrotic core; 2. vascular proliferation; 3. CNS infiltration. These three pillars support glioblastoma survival, with a pivotal role of the neurovascular unit, as supported by the most recent paper published by experts in the field. Full article

The launch of ChatGPT in November of 2022 provides the rare opportunity to consider both what artificial intelligence (AI) is and what human experts are. In the spirit of making the most of this opportunity, we invite the reader to follow a suggestive series of “what if” questions that lead to a plausible settlement in which the human expert and the generative AI system collaborate pedagogically to shape the (human) religious studies student. (1) What if, contrary to the Baconian frame, humans reason primarily by exercising intellectual virtuosity, and only secondarily by means of rules-based inference? (2) What if, even though we train AI models on human-generated data by means of rules-based algorithms, the resulting systems demonstrate the potential for exercising intellectual virtuosity? (3) What if, by deprioritizing mechanistic and algorithmic models of human cognition while being open to the possibility that AI represents a different species of cognition, we open a future in which human and AI virtuosos mutually inspire, enrich, and even catechize one another? Full article

In this work, we introduce the design of a 16-channel in-pixel neural analog front end that employs a current-based summing approach to establish a common-mode feedback loop. The primary aim of this novel structure is to enhance both the system common-mode rejection ratio (SCMRR) and the common-mode interference (CMI) range. Compared to more conventional designs, the proposed front end utilizes DC-coupled inverter-based main amplifiers, which significantly reduce the occupied on-chip area. Additionally, the current-based implementation of the CMFB loop obviates the need for voltage buffers, replacing them with simple common-gate transistors, which, in turn, decreases both area occupancy and power consumption. The proposed architecture is further examined from an analytical standpoint, providing a comprehensive evaluation through design equations of its performance in terms of gain, common-mode rejection, and noise power. A 50 $\mathsf{\mu }$m × 65 $\mathsf{\mu }$m compact layout of the pixel amplifiers that make up the recording channels of the front end was designed using a 180 nm CMOS process. Simulations conducted in Cadence Virtuoso reveal an SCMRR of 80.5 dB and a PSRR of 72.58 dB, with a differential gain of 44 dB and a bandwidth that fully encompasses the frequency range of the bio-signals that can be theoretically captured by the neural probe. The noise integrated in the range between 1 Hz and 7.5 kHz results in an input-referred noise (IRN) of 4.04 $\mathsf{\mu }{V}_{rms}$. Power consumption is also tested, with a measured value of 3.77 $\mathsf{\mu }$W per channel, corresponding to an overall consumption of about 60 $\mathsf{\mu }$W. To test its robustness with respect to PVT and mismatch variations, the front end is evaluated through extensive parametric simulations and Monte Carlo simulations, revealing favorable results. Full article

A crucial component of digital integrated circuits with numerous power domains is the level shifter (LS). The traditional topologies are currently the mirror LS and cross-coupled LS. For full-swing level conversions from extremely low voltage to the nominal voltage of the supply, ahybrid LS is proposed in this paper, which is a combination of the current mirror LS and cross-coupled LS with a swing-aware output inverter. The proposed LS circuit is designed to ensure full swing, static current-free, and limited current-contention level conversions by preserving the benefits of the current mirror and cross-coupled LS, and using them to eliminate each other’s shortcomings. The proposed hybrid LS is designed and implemented by using 45-nm technology in Cadence Virtuoso tool. Pass transistors and current limiters with multiple thresholds are included for the suggested LS. The proposed LS provides voltage conversion from 0.10 V to 1.20 V. At alevel-shifting voltage of 0.20 V, the proposed hybrid LS at 1 MHz input frequency demonstrates a delay of 8.38 ns, an average power consumption of 3.81 µW, and an energy per transition of 26.64 fJ. Additionally, the suggested LS has low delay, good supply voltage scaling, and delay scalability. Full article