Search Results (253)

Silicon Photomultipliers (SiPMs) are single photon detectors that gained increasing interest in many applications as an alternative to photomultiplier tubes. In the field of space experiments, where volume, weight and power consumption are a major constraint, their advantages like compactness, ruggedness, and their potential to achieve high quantum efficiency from UV to NIR makes them ideal candidates for spaceborne, low photon flux detectors. During space missions however, SiPMs are usually exposed to high levels of radiation, both ionizing and non-ionizing, which can deteriorate the performance of these detectors over time. The goal of this work is to compare process and layout variation of SiPMs in terms of their radiation damage effects to identify the features that helps reduce the deterioration of the performance and develop the next generation of more radiation-tolerant detectors. To do this, we used protons and X-rays to irradiate several Near Ultraviolet High-Density (NUV-HD) SiPMs with small areas (single microcell, 0.2 × 0.2 mm² and 1 × 1 mm²) produced at Fondazione Bruno Kessler (FBK), Italy. We performed online current-voltage measurements right after each irradiation step, and a complete functional characterization before and after irradiation. We observed that the main contribution to performance degradation in space applications comes from proton damage in the form of an increase in primary dark count rate (DCR) proportional to the proton fluence and a reduction in activation energy. In this context, small active area devices show a lower DCR before and after irradiation, and we propose light or charge-focusing mechanisms as future developments for high-sensitivity radiation-tolerant detectors. Full article

We performed a systematic review and meta-analysis to assess the efficacy of EGFR-tyrosine kinase inhibitors (TKI) retreatment in advanced/metastatic non-small-cell lung cancer (NSCLC) patients. We systematically searched PubMed, Embase, Cochrane databases, ASCO, and ESMO websites for studies evaluating EGFR-TKI retreatment in advanced/metastatic NSCLC patients. All analyses were performed using R software (v.4.2.2). We included 19 studies (9 CTs and 10 retrospective cohorts) with a total of 886 patients. In a pooled analysis of all patients during retreatment with TKI, median OS was 11.7 months (95% confidence interval [CI] 10.2–13.4 months) and PFS was 3.2 months (95% CI 2.5–3.9 months). ORR was 15% (95% CI 10–21%) and DCR was 61% (95% CI 53–67%). The subanalysis by generation of TKI in the rechallenge period revealed a slightly better ORR for patients on 3rd generation TKI (p = 0.05). Some limitations include the high heterogeneity of some of the analyses and inability to perform certain subanalyses. Our results unequivocally support the benefit of EGFR-TKI rechallenge in EGFR-mutated NSCLC patients progressing on TKI treatment after a TKI-free interval. These findings may be especially valuable in areas where access to novel therapeutic drugs and clinical trials is limited. Full article

Low-light imaging capabilities are in urgent demand in many fields, such as security surveillance, night-time autonomous driving, wilderness rescue, and environmental monitoring. The excellent performance of SPAD devices gives them significant potential for applications in low-light imaging. This article presents a 64 (rows) × 128 (columns) SPAD image sensor designed for low-light imaging. The chip utilizes a three-dimensional stacking architecture and microlens technology, combined with compact gated pixel circuits designed with thick-gate MOS transistors, which further enhance the SPAD’s photosensitivity. The configurable digital control circuit allows for the adjustment of exposure time, enabling the sensor to adapt to different lighting conditions. The chip exhibits very low dark noise levels, with an average DCR of 41.5 cps at 2.4 V excess bias voltage. Additionally, it employs a denoising algorithm specifically developed for the SPAD image sensor, achieving two-dimensional grayscale imaging under 6 × 10⁻⁴ lux illumination conditions, demonstrating excellent low-light imaging capabilities. The chip designed in this paper fully leverages the performance advantages of SPAD image sensors and holds promise for applications in various fields requiring low-light imaging capabilities. Full article

Background: In endoscopic dacryocystorhinostomy (DCR), surgical landmarks such as the maxillary line (ML) and the axilla of the middle turbinate (MT) guide the surgeon in identifying the lacrimal sac. The primary surgical risk associated with the classical technique, which involves directly opening the lacrimal sac, is the height of the bone drilling on the projection of the lateral wall of the nasal fossa. This poses a significant risk of damaging the orbit, the floor of the frontal sinus, and the anterior skull base. Furthermore, the anatomical variability in size and location of the lacrimal sac poses a risk for difficult and precise surgical identification. Recently, a ‘retrograde’ technique has been introduced to safely identify and expose the lacrimal sac. The aim of this study is to compare the results of retrograde DCR (rDCR) to a classic technique (clDCR), in terms of clinical recurrence and complications. Methods: A retrospective study on a cohort of 35 patients who underwent DCR at the ENT Department of the Modena University Hospital between January 2010 and October 2022 (18 clDCR and 17 rDCR) was performed. Minimum postoperative follow-up for inclusion was 12 months. We used the Fisher’s exact test to compare the two techniques, comparing functional outcomes and clinical recurrence rates. Results: Clinical recurrence of nasolacrimal stenosis in clDCR patients was 50%, compared to 6% in those who underwent rDCR (p-value 0.005). Postoperative surgical complications were not significantly different between the two groups (p > 0.05). Conclusions: rDCR is a safe technique and has been shown to be a statistically more effective surgical technique than clDCR in reducing clinical recurrence rates. Full article

Trastuzumab emtansine (T-DM1) is a mainstay therapy for HER2-positive metastatic breast cancer (mBC). However, identifying patients who will benefit most remains a challenge due to the lack of reliable biomarkers. The recently developed pan-immune-inflammation value (PIV), a novel immune-inflammation marker, could aid in this regard, considering the immunomodulatory effects of T-DM1. Therefore, we aimed to evaluate the association between the PIV and the efficacy of T-DM1 in patients with HER2-positive mBC. A total of 122 HER2-positive mBC patients treated with T-DM1 were included. Receiver operating characteristic (ROC) curve analyses were conducted to determine the optimal PIV threshold value for survival prediction. Kaplan–Meier survival curves and Cox regression analyses were used for univariable and multivariable survival analyses, respectively. The median age was 51 years, and 95.1% of the patients had ECOG PS 0-1. The optimal PIV cutoff value was identified as 338 in ROC analyses (AUC: 0.667, 95% CI: 0.569–0.765, p = 0.002). The multivariate analysis revealed that patients in the high-PIV group had significantly shorter OS (HR: 2.332; 95% CI: 1.408–3.861; p = 0.001) and PFS (HR: 2.423; 95% CI: 1.585–3.702; p < 0.001) than patients in the low-PIV group. Additionally, both ORR and DCR were significantly lower in the high-PIV group (36.6% vs. 61.3%, p = 0.011; 56.1% vs. 76.0%, p = 0.027). Our findings suggest that pre-treatment PIV may be a novel prognostic biomarker for HER2-positive mBC patients receiving T-DM1. A low PIV level is associated with more favorable outcomes. Future prospective studies are warranted to validate these findings and explore the potential utility of PIV in aiding treatment decisions. Full article

The duty-cycle randomness (DCR) of the Bragg grating of the distributed feedback (DFB) lasers introduced by the fabrication process is inevitable, even with state-of-the-art technologies such as electron beam lithography and dry or wet etching.This work investigates the impact of grating DCR on DFB laser performance through numerical simulations. The result reveals that such randomness causes a reduction in the side mode suppression ratio (SMSR), and deteriorates the noise characteristics, i.e., broadens the linewidth and increases the relative intensity noise (RIN). With the grating DCR, the effective grating coupling coefficient decreases as evidenced by the reduced Bragg stopband width. However, the longitudinal spatial hole burning (LSHB) effect in the DFB lasers can somewhat be diminished by the grating DCR. The seriousness of these effects depends on different grating structures and their coupling strengths. Our simulation shows that a degradation of 17 dB can be brought to the SMSR of the uniform grating DFB lasers with their duty cycles taking a deviation of ±25% in a uniformly distributed random fashion. It also broadens the linewidth of the quarter-wavelength phase-shifted DFB lasers by more than 2.5 folds. The impact of this effect on the RIN is moderate—less than 2%. All the performance deteriorations can partially be attributed to the effective reduction in the grating coupling coefficient of around 20% by such a DCR. Full article

Medieval colors used in illuminated manuscripts from the 12th to 15th centuries can be at risk. Knowing the binding media used, the medieval tempera, is fundamental to developing new and greener methodologies to increase sustainability in Cultural Heritage. A closer look at the tempera used in medieval illuminated manuscripts kept in Portuguese collections, namely, the Ajuda Songbook (13th c.), the winter breviary (14th to 15th c.), the books of hours (15th c.), and a Renaissance Charter (1512), shows that most of the paints analyzed used a tempera similar to gum mesquite. Infrared spectra were the basis for the differentiation between the gums used in medieval times originating from Prosopis spp. and Senegalia spp., gum mesquite and gum arabic, respectively. The ethnobotanical uses of gum mesquite further engage the reader. This micro review represents a significant step forward in Heritage Conservation, offering new perspectives for innovative and greener treatments. Our research, focusing on the differentiation of gums used in medieval times and the identification of the binding media, has the potential to revolutionize our understanding and the preservation of illuminated manuscripts in Cultural Heritage. Full article

The integration of Single-Photon Avalanche Diodes (SPADs) in CMOS Fully Depleted Silicon-On-Insulator (FD-SOI) technology under a buried oxide (BOX) layer and a silicon film containing transistors makes it possible to realize a 3D SPAD at the chip level. In our study, a nanostructurated layer created by an optimized arrangement of Shallow Trench Isolation (STI) above the photosensitive zone generates constructive interferences and consequently an increase in the light sensitivity in the frontside illumination. A simulation methodology is presented that couples electrical and optical data in order to optimize the STI trenches (size and period) and to estimate the Photon Detection Probability (PDP) gain. Then, a test chip was designed, manufactured, and characterized, demonstrating the PDP improvement due to the STI nanostructuring while maintaining a comparable Dark Count Rate (DCR). Full article

Waste tire rubber powder-modified asphalt (RMA) has been widely used in road construction, which was traditionally limited by the poor compatibility of RMA, affecting pavement performance. By synthesizing epoxy soybean oil with amide groups (ESO/TETA) and grafting it onto desulfurized rubber powder (DCR) through microwave irradiation, a surface-functionalized rubber powder (MDCR) was produced successfully. The effects of the physical properties, storage stability, thermal stability, and rheological behavior of the modified asphalt were studied. The results show that the MDCR with a polar surface improved the compatibility and adhesive interactions between the modified crumb rubber and the asphalt. The MDCR content could reach 50%, and the phase separation could meet the requirements of 2.2 °C, which has application conditions in engineering for stable storage. Additionally, the inclusion of MDCR in the asphalt formulations significantly mitigated the temperature sensitivity of the modified asphalt. Importantly, when the MDCR constituted from 20% to 50% of the asphalt, there was a noted reduction in the phase angle at temperatures above 70 °C, indicating a significant improvement in the elastic efficiency. The MDCR also led to substantial enhancements in the resistance of the asphalt to high-temperature and high-stress rutting, addressing the crucial limitations in the consumption ability of waste tire rubber powder and improving the overall performance of RMA in pavement applications. Full article

Advanced and metastatic cervical cancer remains a formidable challenge in oncology, with immune checkpoint inhibitors such as the PD-1 inhibitor nivolumab emerging as a potential therapeutic option. This systematic review rigorously assesses the effectiveness and outcomes of various nivolumab treatment regimens within this patient cohort, drawing from clinical trials and real-world evidence up to December 2023. Following a comprehensive search across PubMed, Scopus, and Embase, four studies were deemed eligible, involving a collective total of 80 patients. One preliminary trial data were excluded from the final analysis, as well as four other proceedings and abstracts on the efficacy and safety of nivolumab on advanced cervical cancer. The patients’ average age across these studies was 48 years, with an average of 38% having an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Notably, 64% of all patients were positive for high-risk HPV, and 71% exhibited PD-L1 positivity, indicating a substantial target population for nivolumab. The analysis revealed a pooled objective response rate (ORR) of 48%, with a disease control rate (DCR) averaging 71%. Moreover, progression-free survival (PFS) at 6 months was observed at an average rate of 50%, reflecting the significant potential of nivolumab in managing advanced stages of the disease. The review highlights the influence of PD-L1 status on response rates and underscores the enhanced outcomes associated with combination therapy approaches. By delineating the variability in treatment efficacy and pinpointing key factors affecting therapeutic response and survival, this systematic review calls for further investigations to refine nivolumab’s clinical application, aiming to improve patient outcomes in advanced and metastatic cervical cancer. Full article

Background: Anti-glaucoma eye drops have been investigated due to their production of fibrotic changes on the conjunctival surface, undermining the functioning of the upper lacrimal drainage system. We aimed to assess whether these effects may impair the effectiveness of endoscopic endonasal dacryocystorhinostomy (EE-DCR). Methods: This is a single-center observational retrospective study on EE-DCR via a posterior approach. Resolution of epiphora and dacryocystitis were analyzed after 1 (T1) and 6-months (T2) from surgery. Surgical success was defined as anatomical (patency at irrigation, no recurring dacryocystitis) or complete (zeroing of Munk score). Results: Twenty patients (32 sides) were enrolled. Preoperatively, 93.75% (n = 30/32) presented severe (Munk 3–4) epiphora and 68.75% (n = 22/32) recurrent dacryocystitis. At T1, 50.0% (n = 16/32) were referred with residual epiphora (Munk ≥ 1) and 18.75% (n = 6/32) dacryocystitis. At T2, 31.25% (n = 10/32) still complained of epiphora (Munk ≥ 1) and 6.25% (n = 2/32) dacryocystitis. Difference of outcomes at aggregate and paired timepoints (except for T1 versus T2) resulted in statistical significance (p < 0.05). At T2, 22 (68.75%) complete, 8 (25.0%) anatomical successes and 2 (6.25%) surgical failures were observed. Conclusions: Despite the chronic uptake of anti-glaucoma eye drops, EE-DCR guaranteed high rates of clinical relief from epiphora and remarkable decreases in the rates of recurrent dacryocystitis. Full article

Immune checkpoint inhibitors (ICIs) are at the forefront of advanced non-small-cell lung cancer (NSCLC) treatment. Still, only 27–46% of patients respond to initial therapy with ICIs, and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6–3.1 months and a Disease Control Rate (DCR) of 21.4–41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75–81%, according to post hoc analyses of several clinical trials. Future research on ICI rechallenge for NSCLC should focus on better patient stratification to reflect the underlying biology of immunotherapy resistance more accurately. In this review, we summarize evidence regarding rechallenge immunotherapy efficacy following NSCLC disease progression or relapse, as well as ongoing trials on immunotherapy rechallenge. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of different malignancies. However, their efficacy in advanced adrenocortical carcinoma (ACC) remains uncertain. Thus, we conducted a systematic review and meta-analysis to summarize the efficacy and tolerability of ICIs in patients with advanced ACC. We searched PubMed, Scopus, and CENTRAL for studies that used ICIs in ACC. Studies with more than five patients were included in the meta-analysis of the objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and grade 3/4 adverse events. Twenty studies with 23 treatment arms and 250 patients were included. Single-agent anti-PD1 or anti-PD-L1 treatment was utilized in 13 treatment arms, whereas an anti-PD1 or anti-PD-L1 and anti-CTLA4 combination was used in 4 treatment arms. Other anti-PD1- or anti-PD-L1-based combinations were used in five treatment arms. The ORR was 14% (95% CI = 10–19%, I² = 0%), and the DCR was 43% (95% CI = 37–50%, I² = 13%). The combination anti-PD1- or anti-PD-L1-based treatment strategies did not correlate with higher responses compared with monotherapy. The median OS was 13.9 months (95% CI = 7.85–23.05), and the median PFS was 2.8 months (95% CI = 1.8–5.4). ICIs have a modest efficacy in advanced ACC but a good OS. Further studies are needed to investigate predictive biomarkers for ICI response and to compare ICI-based strategies with the current standard of care. Full article

The Colorado potato beetle (Leptinotarsa decemlineata (Say)) can cause extensive damage to agricultural crops worldwide and is a significant insect pest. This insect is notorious for its ability to evade various strategies deployed to control its spread and is known for its relative ease in developing resistance against different insecticides. Various molecular levers are leveraged by L. decemlineata for this resistance to occur, and a complete picture of the genes involved in this process is lacking. While small non-coding RNAs, including miRNAs, are differentially expressed in insects exposed to insecticides, levels of transcript coding for proteins underlying their synthesis remain to be characterized fully. The overarching objective of this work aims to fill that gap by assessing the expression of such targets in L. decemlineata exposed to cyantraniliprole and thiamethoxam. The expression status of Ago1, Ago2, Ago3, Dcr2a, Dcr2b, Expo-5, Siwi-1 and Siwi-2 transcripts were quantified via qRT-PCR in adult L. decemlineata treated with low and high doses of these compounds for different lengths of time. Variation in Ago1 and Dcr2b expression was notably observed in L. decemlineata exposed to cyantraniliprole, while thiamethoxam exposure was associated with the modulation of Dcr2a and Siwi-1 transcript levels. The down-regulation of Ago1 expression in L. decemlineata using dsRNA, followed by cyantraniliprole treatment, was associated with a reduction in the survival of insects with reduced Ago1 transcript expression. Overall, this work presents the insecticide-mediated modulation of transcripts associated with small non-coding RNA processing and showcases Ago1 as a target to further investigate its relevance in cyantraniliprole response. Full article

Microorganisms colonizing modern water-based metalworking fluids (MWFs) have been implicated in various occupational respiratory health hazards to machinists. An understanding of the exposure risks from specific microbial groups/genera/species (pathogenic or allergenic) and their endotoxins and the need for strategies for effective, timely fluid management warrant real-time extended tracking of the establishment of microbial diversity and the prevailing fluid-related factors. In the current study, the microbial community composition, succession, and dynamics of a freshly recharged industrial semi-synthetic MWF operation was tracked in real-time over a period of 50 weeks, using a combination of microbiological and molecular approaches. Substantial initial bacterial count (both viable and non-viable) even in the freshly recharged MWF pointed to the inefficiency of the dumping, cleaning, and recharge (DCR) process. Subsequent temporal analysis using optimized targeted genus/group-specific qPCR confirmed the presence of Pseudomonads, Enterics, Legionellae, Mycobacteria (M. immunogenum), Actinomycetes, and Fungi. In contrast, selective culturing using commercial culture media yielded non-specific isolates and collectively revealed Gram-negative (13 genera representing 19 isolates) and Gram-positive (2 genera representing 6 isolates) bacteria and fungi but not mycobacteria. Citrobacter sp. and Bacillus cereus represented the most frequent Gram-negative and Gram-positive isolates, respectively, across different media and Nectria haematococca isolation as the first evidence of this fungal pathogen colonizing semi-synthetic MWF. Unbiased PCR-DGGE analysis revealed a more diverse whole community composition revealing 22 bacterial phylotypes and their succession. Surges in the endotoxin level coincided with the spikes in Gram-negative bacterial population and biocide additions. Taken together, the results showed that semi-synthetic MWF is conducive for the growth of a highly diverse microbial community including potential bacterial and fungal pathogens, the current DCR practices are inefficient in combating microbial reestablishment, and the practice of periodic biocide additions facilitates the build-up of endotoxins and non-viable bacterial population. Full article