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Persistent contaminants in ecosystems are often monitored via organisms that bioaccumulate the pollutant of interest. Several published studies have used colonial wading birds to assess contamination by heavy metals in aquatic ecosystems. Using a nonlethal sampling regimen, this study identified chick feathers and guano as tissues that best reflect local contamination. Both cadmium and lead were detected in food samples (0.3-4.3 Mug/g Cd, 0.8-9.3 Mug/g Pb), guano (0.2-3.2 Mug/gCd, 1.0-9.5 Mug/g Pb), and feathers (0.6-25.4 Mug/g Cd, 1.2-16.9 Mug/g Pb) from little blue heron chicks at levels similar to other studies. Chicks exposed to cadmium had significantly slower growth rates than nonexposed chicks, and exposure to lead was correlated with increased nestling mortality. The appropriate scale of comparison necessary to demonstrate these effects and the usefulness of wading birds as bioindicators are discussed. [ABSTRACT FROM AUTHOR]

In Germany, there is currently no official guideline for the submission of placentas for histopathological examination. Placentas are sent for histological examination by obstetricians according to locally defined indications, which leads to different practices in different centers. In this study, two cohorts of placentas were compared to assess the clinical relevance of placental examination. One cohort consisted of placentas with a clinical indication for histologic examination and the other of placentas with a clinically healthy pregnancy and a healthy infant. In this study, a placenta request form based on established international guidelines was used. Placentas from singleton and twin pregnancies with and without clinical indications were histopathologically examined. Clinical information was extracted from the request form and later correlated with histological findings. A total of 236 placentas were examined, including 127 (53.8%) with clinical indications and 109 (46.2%) without. The concordance between submission reasons and histopathological findings was higher in singleton pregnancies with clinical indications (90.9%) compared to twin pregnancies (62.97%). Placentas from singleton and twin pregnancies with clinical indications exhibited significantly more pathological findings than their respective healthy control groups. Histopathological examination of the placenta can confirm or reveal placenta pathologies and therefore improve the care of the mother, child and future pregnancies.

Fibroblast growth factor receptor (FGFR)-2 can be inhibited by FGFR-selective or non-selective tyrosine kinase inhibitors (TKIs). Selective TKIs are approved for cholangiocarcinoma (CCA) with FGFR2 fusions; however, their application is limited by a characteristic pattern of adverse events or evocation of kinase domain mutations. A comprehensive characterization of a patient cohort treated with the non-selective TKI lenvatinib reveals promising efficacy in FGFR2-driven CCA. In a bed-to-bench approach, we investigate FGFR2 fusion proteins bearing critical tumor-relevant point mutations. These mutations confer growth advantage of tumor cells and increased resistance to selective TKIs but remain intriguingly sensitive to lenvatinib. In line with clinical observations, in-silico analyses reveal a more favorable interaction pattern of lenvatinib with FGFR2, including an increased flexibility and ligand efficacy, compared to FGFR-selective TKIs. Finally, the treatment of a patient with progressive disease and a newly developed kinase mutation during therapy with a selective inhibitor results in a striking response to lenvatinib. Our in vitro, in silico, and clinical data suggest that lenvatinib is a promising treatment option for FGFR2-driven CCA, especially when insurmountable adverse reactions of selective TKIs or acquired kinase mutations occur., (© 2024. The Author(s).)

The host microbiome is polymorphic, compartmentalized, and composed of distinctive tissue microbiomes. While research in the field of cancer immunotherapy has provided an improved understanding of the interaction with the gastrointestinal microbiome, the significance of the tumor-associated microbiome has only recently been grasped. This article provides a state-of-the-art review about the tumor-associated microbiome and sheds light on how local tumor microbiota shapes anticancer immunity and influences checkpoint immunotherapy outcome. The direct route of interaction between cancer cells, immune cells, and microbiota in the tumor microenvironment is emphasized and advocates a focus on the tumor-associated microbiome in addition to the spatially separated gut compartment. Since the mechanisms underlying checkpoint immunotherapy modulation by tumor-associated microbiota remain largely elusive, future research should dissect the pathways involved and outline strategies to therapeutically modulate microbes and their products within the tumor microenvironment. A more detailed knowledge about the mechanisms governing the composition and functional quality of the tumor microbiome will improve cancer immunotherapy and advance precision medicine for solid tumors., Competing Interests: Competing interests: MB serves as an advisor for Pantec Biosolutions AG. The other authors have no potential conflicts of interest to declare. No medical writer was involved in the preparation of the manuscript., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The metallization of heterojunction solar cells requires a further reduction of silver consumption to lower production costs and save resources. This article presents how filament stretching of polymer-based low-temperature curing Ag pastes during micro-extrusion enables this reduction while at the same time offering a high production throughput potential. In a series of experiments the relationship between the printing velocity and the filament stretching, thus the reduction of Ag-electrode widths and Ag laydown is evaluated. Furthermore, an existing filament stretching model for the parallel dispensing process is advanced further and utilized to calculate the elongational viscosity. The stretching effect enables a reduction of the Ag-electrode width by down to Δw f  = - 40% rel. depending on the nozzle diameter and paste type. The Ag laydown has been reduced from m Ag,cal.  = 0.84 mg per printed line to only m Ag,cal.  = 0.54 mg per printed Ag-electrode when 30 µm nozzle openings are used, demonstrating the promising potential of parallel dispensing technology for the metallization of silicon heterojunction solar cells., (© 2022. The Author(s).)

Herpes simplex virus 1 (HSV-1) is a frequently unrecognized, yet deadly cause of acute liver failure (ALF). We, therefore, analysed three cases of fatal HSV-1-induced ALF. All patients shared clinical (extremely elevated transaminases, LDH and AST/LDH ratio < 1) and virological characteristics (ratio of viral load in plasma versus throat swabs: 60-700-fold, lack of anti-HSV-1-IgG antibodies or low IgG-avidity during primary infection), which may help to identify patients at risk. Additionally, in vitro chemosusceptibility assays revealed high efficacy of the helicase-primase inhibitors (HPI), pritelivir and drug-candidate IM-250 compared to acyclovir (ACV) using HSV-1-isolates from two patients; hence, ACV/HPI-combinations might offer new therapeutic options for HSV-induced ALF., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background & Aims: Immunotherapy with atezolizumab plus bevacizumab represents the new standard of care in systemic front-line treatment of hepatocellular carcinoma (HCC). However, biomarkers that predict treatment success and survival remain an unmet need., Methods: Patients with HCC put on PD-(L)1-based immunotherapy were included in a training set (n = 190; 6 European centers) and a validation set (n = 102; 8 European centers). We investigated the prognostic value of baseline variables on overall survival using a Cox model in the training set and developed the easily applicable CRAFITY (CRP and AFP in ImmunoTherapY) score. The score was validated in the independent, external cohort, and evaluated in a cohort of patients treated with sorafenib (n = 204)., Results: Baseline serum alpha-fetoprotein ≥100 ng/ml (hazard ratio [HR] 1.7; p = 0.007) and C-reactive protein ≥1 mg/dl (HR, 1.7; p = 0.007) were identified as independent prognostic factors in multivariable analysis and were used to develop the CRAFITY score. Patients who fulfilled no criterion (0 points; CRAFITY-low) had the longest median overall survival (27.6 (95% CI 19.5-35.8) months), followed by those fulfilling 1 criterion (1 point; CRAFITY-intermediate; 11.3 (95% CI 8.0-14.6) months), and patients meeting both criteria (2 points; CRAFITY-high; 6.4 (95% CI 4.8-8.1) months; p <0.001). Additionally, best radiological response (complete response/partial response/stable disease/progressive disease) was significantly better in patients with lower CRAFITY score (CRAFITY-low: 9%/20%/52%/20% vs. CRAFITY-intermediate: 3%/25%/36%/36% vs. CRAFITY-high: 2%/15%/22%/61%; p = 0.003). These results were confirmed in the independent validation set and in different subgroups, including Child-Pugh A and B, performance status 0 and ≥1, and first-line and later lines. In the sorafenib cohort, CRAFITY was associated with survival, but not radiological response., Conclusions: The CRAFITY score is associated with survival and radiological response in patients receiving PD-(L)1 immunotherapy. The score may help with patient counseling but requires prospective validation., Lay Summary: The immunotherapy-based regimen of atezolizumab plus bevacizumab represents the new standard of care in systemic first-line therapy of hepatocellular carcinoma (HCC). Biomarkers to predict treatment outcome are an unmet need in patients undergoing immunotherapy for HCC. We developed and externally validated a score that predicts outcome in patients with HCC undergoing immunotherapy with immune checkpoint blockers., Competing Interests: Conflict of interest B.S. received travel support from AbbVie, Ipsen and Gilead. K.P. nothing to disclose. M.K. received honoraria from BMS and AstraZeneca as consultant and is an investigator for AstraZeneca. F.H. received travel support from Bayer, Abbvie, and Gilead. F.F. received travel support from Abbvie and Novartis, and speaker fees from Abbvie and MSD. O.W. served as consultant for Amgen, Bayer, BMS, Celgene, Eisai, Merck, Novartis, Roche, Servier, and Shire. He served as a speaker for Abbvie, Bayer, BMS, Celgene, Falk, Ipsen, Novartis, Roche, and Shire. He received travel support from Abbvie, BMS, Ipsen, Novartis, and Servier. V.H. has nothing to disclose. K.S. Served as consultant for Ipsen and Bayer, and conducts studies for Bayer, Roche, Lilly, MSD, and BMS. J.v.F. has received advisory board fees from Roche. T.W.F. has nothing to disclose. M.S. has nothing to disclose. H.H. received compensations as a member of a scientific advisory board of Lilly. K.S. has nothing to disclose. S.S. has nothing to disclose. P.R. has nothing to disclose. A.R.S. has served at advisory boards and received consulting honoraria from AMGEN, AAA, Bayer, BMS, IPSEN, Lilly, Merck, MSD, Pfizer, Roche, Sanofi, and Servier. J.C.M. has received consulting honoraria from Abbvie, Astra Zeneca, Bayer, BMS, Eisai, Gilead, Incyte, Intercept, MSD, Sanofi, Vifor for work performed outside the current study. N.N.R. has nothing to disclose. F.K. received speakers' fees from Bayer, Ipsen, MSD, Eisai, Shire, Sirtex and has received travel grants from Eisai, Janssen, Ipsen and Novartis. D.T.W. served as speaker/expert testimony for AstraZeneca, Eisai, BMS, Celgene, Incyte, Ipsen, Falk, Novartis, Roche Pharma AG, Servier, Shire Baxelta, and Sirtex; he received travel support from Bayer Health Pharma, Celgene, Ipsen, Novartis, and SIRTEX, and research grants/funding from Servier. M.P.E. received consulting honoraria from BMS and MSD. A.T. received consulting honoraria and /or lecture fees from Bayer, IPSEN, Lilly, BMS, Eisai Novartis, Roche, Intercept, Falk, AbbVie, and Gilead. He received and travel grants from IPSEN, AbbVie, and Gilead. He is an investigator for IPSEN and GILEAD. S.D.D. received consulting honoraria from Amgen, Bayer, BMS, IPSEN, Lilly, Merck, BMS, Novartis, Pfizer, Roche, Sanofi, and Servier, and travel grants from Amgen, BMS, IPSEN, Roche, and Servier. D.J.P. received lecture fees from ViiV Healthcare, Bayer Healthcare, Falk, BMS, EISAI and Roche; travel expenses from BMS, MSD and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, H3B, Roche, Astra Zeneca, and DaVolterra; research funding (to institution) from MSD, BMS. T.P. received consulting fees from IQVIA and Bayer; and institutional research funding from Lilly, Roche, Bayer. T.M. has nothing to disclose. L.B. has nothing to disclose. C.M. has nothing to disclose. M.M. served as a speaker and/or consultant and/or advisory board member for AbbVie, Bristol-Myers Squibb, Collective Acumen, Gilead, and W. L. Gore & Associates and received travel support from AbbVie, Bristol-Myers Squibb, and Gilead. T.R. received speaker fees from Boehringer Ingelheim, Roche, W.L. Gore and MSD, grant support from Boehringer Ingelheim, Boston Scientific, Cook Medical, Gilead, Guerbet, Abbvie, Phenex Pharmaceuticals, Philips, W.L. Gore, and MSD, served as a consultant for Abbvie, Bayer, Boehringer Ingelheim, Gilead, Intercept and MSD and received travel support from Gilead, Roche, MSD, and Gore. M.T. received speaker fees from Bristol-Myers Squibb (BMS), Falk Foundation, Gilead, Intercept and Merck Sharp & Dohme (MSD); advisory board fees from Abbvie, Albireo, Boehringer Ingelheim, BiomX, Falk Pharma GmbH, GENFIT, Gilead, Intercept, Janssen, MSD, Novartis, Phenex, Regulus and Shire; travel grants from AbbVie, Falk, Gilead, and Intercept; and research grants from Albireo, CymaBay, Falk, Gilead, Intercept, MSD, and Takeda. He is also coinventor of patents on the medical use of norUDCA filed by the Medical University of Graz. N.P. received consulting fees from Amgen, Merck Serono, Servier; lectures fees from AbbVie, Gilead, Lilly; travel fees from Amgen, ArQule; and institutional research funding from Basilea, Merck Serono, Servier. L.R. has received consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Zymeworks; lectures fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi; travel expenses from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks. M.B. received compensations as a member of scientific advisory boards of Bayer, Bristol–Meyers Squibb, EISAI, IPSEN, and MSD. J.T. served as consultant for Amgen, Bayer, BMS, Eisai, Lilly, Merck Serono, MSD, Ipsen, and Roche, received travel support from BMS and Ipsen, and speaking fees from Amgen, Bayer, BMS, Eisai, Lilly, Merck Serono, MSD, Ipsen, and Roche. He is also an investigator for Amgen, Bayer, BMS, Eisai, Lilly, Merck Serono, MSD, Ipsen, and Roche. A.W. received compensations as a member of scientific advisory boards for BMS, Wako, Sanofi and. He served as a speaker for Leo Pharma, Eisai, Ipsen and Roche and received travel support from Merck and Servier. H.W. served as speaker for Bayer, Eisai, Ipsen, and Roche, and as a consultant for Bayer, Eisai, Lilly, BMS, Roche, and Ipsen. He conducts studies for Bayer, Roche, Lilly, MSD, and BMS. J.F.D. received compensations as a member of scientific advisory boards of Abbvie, Bayer, Bristol-Myers Squibb, Falk, Galapagos, Genfit, Genkyotex, Gilead Sciences, HepaRegenix, Intercept, Lilly, Merck, and Novartis. M.P.R. is advisor/consultant for Astra Zeneca, Bayer, BMS, Eisai, Ipsen, Lilly, MSD, and Roche; he served as a speaker for Bayer, Eisai, Ipsen, Lilly, and Roche; he is an investigator for Bayer, BMS, Eisai, Exelixis, Lilly, and Roche. A.V. served as consultant for Roche, Bayer, Lilly, BMS, Eisai, and Ipsen, and received speaking fees form Roche, Bayer, Lilly, BMS, Eisai, and Ipsen. He is also an investigator for Roche, Bayer, Lilly, BMS, Eisai, and Ipsen. M.P. is an investigator for Bayer, BMS, Lilly, and Roche, he received speaker honoraria from Bayer, BMS, Eisai, and MSD, he is a consultant for Bayer, BMS, Ipsen, Eisai, Lilly, Roche, and MSD, and he received travel support from Bayer, BMS, and Roche. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)