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The increasing release of toxic heavy metals into marine environments poses significant risks due to their persistence and bioaccumulation. Diatoms are ideal bioindicators because of their sensitivity to environmental changes. Despite traditional methods for detecting these persistent pollutants effectively identify composition and concentration, they are time-consuming, they often require the use of harmful reagents, and do not allow a fast assessment of detrimental impacts on marine organisms. To fill this gap, we have successfully investigated the toxicity of different heavy metals in the marine diatom Skeletonema pseudocostatum thanks to a newly developed high-power terahertz (THz) spectrometer. By combining THz spectroscopy, microscopy and ecotoxicological assays, we found that the formation of long diatom chains is significantly inhibited by the presence of lead, copper, and chromium, which disrupt their metabolism. Although the THz absorption and refractive index spectra were not affected by diatom concentration in undoped samples, THz frequencies were highly sensitive to changes in diatom chain length due to heavy metals exposure. These findings suggest that this approach allows to investigate the biochemical processes involved in chain formation in S. pseudocostatum and related algae. THz spectroscopy could therefore provide deeper insights into the microscopic metabolic activity of diatoms, addressing key biochemical questions surrounding these organisms. Furthermore, we propose this novel approach for environmental pollution monitoring, since it could provide a rapid, harmless and sensitive detection method to assess heavy metal toxicity in marine diatoms, key organisms at the basis of the trophic chain., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ruqyyah Mushtaq reports financial support was provided by Italian Ministry of University and Research. Fabio Novelli reports financial support was provided by Deutsche Forschungsgemeinschaft. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Management of central nervous system (CNS) metastases in patients with driver-mutated NSCLC has traditionally incorporated both tyrosine kinase inhibitors (TKIs) and intracranial radiation. Whether next generation, CNS-penetrant TKIs can be used alone without upfront radiation, however, remains unknown. This multi-institutional retrospective analysis aimed to compare outcomes in patients with EGFR- or ALK-positive NSCLC who received CNS-penetrant TKI therapy alone versus in combination with radiation for new or progressing intracranial metastases., Methods: Data were retrospectively collected from three academic institutions. Two treatment groups (CNS-penetrant TKI alone versus TKI + CNS radiation therapy) were compared for both EGFR- and ALK-positive cohorts. Outcome variables included time to progression, time to intracranial progression, and time to treatment failure, measured from the date of initiation of CNS-penetrant TKI therapy., Results: A total of 147 patients were included (EGFR n = 94, ALK n = 52, both n = 1). In patients receiving radiation, larger metastases, neurologic symptoms, and receipt of steroids were more common. There were no significant differences between TKI and CNS radiation therapy plus TKI groups for any of the study outcomes, including time to progression (8.5 versus 6.9 mo, p = 0.13 [EFGR] and 11.4 versus 13.4 mo, p = 0.98 [ALK]), time to intracranial progression (14.8 versus 20.5 mo, p = 0.51 [EGFR] and 18.1 versus 21.8 mo, p = 0.65 [ALK]), or time to treatment failure (13.8 versus 8.6 mo, p = 0.26 [EGFR] and 13.5 versus 23.2 mo, p = 0.95 [ALK])., Conclusions: These results provide preliminary evidence that intracranial activity of CNS-penetrant TKIs may enable local radiation to be deferred in appropriately selected patients without negatively affecting progression., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Bouveret's syndrome is a rare form of gallstone ileus occurring due to obstructing gallstone into the proximal duodenum through a cholecystoduodenal fistula. We report the case of a 72-year-old female presenting with abdominal pain secondary to a large gallstone in the region of the duodenal bulb, causing the upstream gastric obstruction. Here we discuss the clinical features, imaging technologies, and surgical management of Bouveret's syndrome., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The clinicopathologic characteristics, acquired resistance patterns, and outcomes among patients with atypical EGFR mutations and HER2 alterations remain underexplored., Patients and Methods: A single-center retrospective review was conducted. Oncogenes assessed include typical EGFR (t-EGFR; exon 19 del and L858R), atypical EGFR (a-EGFR; G719X, exon 20, L861Q), HER2 (exon 19, exon 20, amplifications), gene fusions (ALK, ROS1, RET), RAS (KRAS, NRAS), and RAF (BRAF V600E). Progression-free survival (PFS), overall survival (OS), disease control rate, and objective response rate (Response Evaluation Criteria in Solid Tumors 1.1) were collected., Results: Among 570 patients, we found 55 a-EGFR mutations (13 G719X, 38 exon 20, 4 L861Q) and 31 HER2 alterations (2 exon 19 mutations, 27 exon 20 insertions, 2 amplifications). Patients with EGFR and HER2 alterations had increased lung and bone metastases relative to patients with gene fusions, RAS/RAF mutations, and no identified driver oncogenes (P < .001). Patients with EGFR exon 20 insertions had a median PFS to EGFR tyrosine kinase inhibitors (TKIs) of 5 months and an OS of 16 months-significantly worse than exon 19 del and L858R (Bonferroni correction; P < .001), but not G719X or L861Q. Relative to t-EGFR mutations, T790M and MET amplification occurred less frequently as acquired resistance mechanisms among a-EGFR samples (P < .001). Ten patients with a-EGFR mutations and HER2 alterations received single-agent immune checkpoint inhibitors (ICIs) with no radiographic responses and a median PFS of 2 months., Conclusion: EGFR and HER2-mutated NSCLC have a high rate of synchronous lung and bone metastases. Patients with a-EGFR mutations have inferior responses to EGFR-directed therapies with lower rates of acquired T790M and MET amplification. Responses to ICIs are uniformly poor. Novel therapeutic approaches are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: This study aims to determine whether advanced ROS1 gene-rearranged NSCLC (ROS1+ NSCLC) has a higher than expected thromboembolic event (TEE) rate., Methods: Venous and arterial TEEs within ±365 days of diagnosis of ROS1+, ALK+, EGFR+, or KRAS+ advanced NSCLC at five academic centers in the United States and China were captured (October 2002-April 2018). The primary endpoint was incidence of TEE in ROS1+ compared to anaplastic lymphoma kinase (ALK)+, EGFR+, and KRAS+ NSCLC within ±90 days of diagnosis. Logistic regression was used to assess if the odds of TEE differed among oncogene drivers., Results: Eligible data from 95 ROS1+, 193 ALK+, 300 EGFR+, and 152 KRAS+ NSCLC patients were analyzed. The incidence rate of TEE was 34.7% (n = 33), 22.3% (n = 43), 13.7% (n = 41), and 18.4% (n = 28), respectively. In univariate analysis, the odds of a TEE in ROS1+ NSCLC were higher than ALK+, EGFR+, and KRAS+ cohorts. In multivariable analysis, the odds of a TEE were significantly higher for ROS1+ compared to EGFR+ and KRAS+ cohorts, the odds ratio (OR) was 2.44, with a 95% confidence interval of 1.31-4.57 (p = 0.005), and OR: 2.62, with a 95% confidence interval of 1.26-5.46 (p = 0.01), respectively. Although numerically superior, the odds for a TEE with ROS1+ compared to ALK+ was not statistically significant (OR: 1.45, p = 0.229). Overall survival was not significantly different in patients with or without TEE within ±90 days of diagnosis in the overall study cohort or within each molecular group., Conclusions: The risk of peridiagnostic TEEs is significantly elevated in patients with advanced ROS+ NSCLC compared to EGFR+ and KRAS+ cases. TEE risk may be similarly elevated in ALK+ NSCLC., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Men with a body mass index (BMI) of 30 or over are more likely to have reduced fertility and fecundity rates. This systematic review and meta-analysis evaluated the effect of male BMI on IVF and intracytoplasmic sperm injection (ICSI) outcome. An electronic search for published literature was conducted in MEDLINE and EMBASE between 1966 and November 2016. Outcome measures were clinical pregnancy rates (CPR) and live birth rates (LBR) per IVF or ICSI cycle. Eleven studies were identified, including 14,372 cycles; nine reported CPR and seven reported LBR. Pooling of data from those studies revealed that raised male BMI was associated with a significant reduction in CPR (OR 0.78, 95% CI 0.63 to 0.98, P = 0.03) and LBR (OR 0.88, 95% CI 0.82 to 0.95, P = 0.001) per IVF-ICSI treatment cycle. Male BMI could be an important factor influencing IVF-ICSI outcome. More robust studies are needed to confirm this conclusion using standardized methods for measuring male BMI, adhering to the World Health Organization definitions of BMI categories, accounting for female BMI, IVF and ICSI cycle characteristics, including the number of embryos transferred and embryo quality, and use the live birth rate per cycle as primary outcome., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)