Autofluorescence-based tissue characterization enhances clinical prospects of light-sheet-microscopy.

Light sheet fluorescence microscopy (LSFM) is a transformative imaging method that enables the visualization of non-dissected specimen in real-time 3D. Optical clearing of tissues is essential for LSFM, typically employing toxic solvents. Here, we test the applicability of a non-hazardous alternative, ethyl cinnamate (ECi). We comprehensively characterized autofluorescence (AF) spectra in diverse murine tissues-ocular globe, knee, and liver-employing LSFM under various excitation wavelengths (405-785 nm) to test the feasibility of unstained samples for diagnostic purposes, in particular regarding percutaneous biopsies, as they constitute to most harvested type of tissue sample in clinical routine. Ocular globe structures were best discerned with 640 nm excitation. Knee tissue showed complex variation in AF spectra variation influenced by tissue depth and structure. Liver exhibited a unique AF pattern, likely linked to vasculature. Hepatic tissue samples were used to demonstrate the compatibility of our protocol for antibody staining. Furthermore, we employed machine learning to augment raw images and segment liver structures based on AF spectra. Radiologists rated representative samples transferred to the clinical assessment software. Learning-generated images scored highest in quality. Additionally, we investigated an actual murine biopsy. Our study pioneers the application of AF spectra for tissue characterization and diagnostic potential of optically cleared unstained percutaneous biopsies, contributing to the clinical translation of LSFM.

Safety of psychological interventions for adult post-traumatic stress disorder: meta-analysis on the incidence and relative risk of deterioration, adverse events and serious adverse events.

BACKGROUND: Attention on harmful effects of psychological interventions for adult post-traumatic stress disorder (PTSD) has increased, yet a comprehensive meta-analysis is lacking. AIMS: To summarise incidences and relative risks of deterioration, adverse events (AEs) and serious adverse events (SAEs) in trials of psychological interventions for adult PTSD. METHOD: We searched MEDLINE, PsycInfo, Web of Science and PTSDpubs from inception to 21 April 2022 for sufficiently large (n ≥ 20) randomised controlled trials (RCTs) reporting on the incidence of harms. RESULTS: We included 56 RCTs (4230 patients). Incidences of harms were generally low (0-5%). Psychological interventions were associated with decreased risk of deterioration relative to passive (RR = 0.21, 95% CI 0.15-0.28) and active control conditions (RR = 0.36, 95% CI 0.14-0.92). Decreased risk was even more pronounced in sensitivity analyses on trials exclusively delivering treatments face to face. When compared with other psychological interventions, trauma-focused cognitive-behavioural therapy (TF-CBT) was associated with decreased risk of SAEs (RR = 0.54, 95% CI 0.31-0.95) and with no differential risk of deterioration and AEs. CONCLUSIONS: The current evidence base suggests that psychological interventions are safe for most adults with PTSD. In none of the analyses were psychological interventions associated with an increased risk of harm compared with control conditions. TF-CBT was found at least as safe as other psychological interventions. Individual face-to-face delivery might be the safest delivery format. However, more data are needed to draw firmer conclusions. We encourage research teams to routinely and thoroughly assess and report the incidence of harms and their causes.

Differential involvement of Hedgehog signaling in butterfly wing and eyespot development.

Butterfly eyespots may have evolved from the recruitment of pre-existent gene circuits or regulatory networks into novel locations on the wing. Gene expression data suggests one such circuit, the Hedgehog (Hh) signaling pathway and its target gene engrailed (en), was recruited from a role in patterning the anterior-posterior insect wing axis to a role patterning butterfly eyespots. However, while Junonia coenia expresses hh and en both in the posterior compartment of the wing and in eyespot centers, Bicyclus anynana lacks hh eyespot-specific expression. This suggests that Hh signaling may not be functioning in eyespot development in either species or that it functions in J. coenia but not in B. anynana. In order to test these hypotheses, we performed functional tests of Hh signaling in these species. We investigated the effects of Hh protein sequestration during the larval stage on en expression levels, and on wing size and eyespot size in adults. Hh sequestration led to significantly reduced en expression and to significantly smaller wings and eyespots in both species. But while eyespot size in B. anynana was reduced proportionately to wing size, in J. coenia, eyespots were reduced disproportionately, indicating an independent role of Hh signaling in eyespot development in J. coenia. We conclude that while Hh signaling retains a conserved role in promoting wing growth across nymphalid butterflies, it plays an additional role in eyespot development in some, but not all, lineages of nymphalid butterflies. We discuss our findings in the context of alternative evolutionary scenarios that led to the differential expression of hh and other Hh pathway signaling members across nymphalid species.

12 MW peak power from a two-crystal Yb:KYW chirped-pulse oscillator with cavity-dumping.

We report on substantial pulse energy increase in Yb:KYW femtosecond laser oscillators by utilizing multiple laser crystals for an enhanced net-gain at higher pump power. The two-crystal oscillator generates pulse energies of 7 µJ at 1 MHz repetition rate which is, to our knowledge the highest energy ever reported from an Yb-doped tungstate fs-laser oscillator. The external pulse compression yields a pulse duration of 416 fs with a peak power of 12 MW being enough for stable white light generation in YAG.

Concept recognition for extracting protein interaction relations from biomedical text.

BACKGROUND: Reliable information extraction applications have been a long sought goal of the biomedical text mining community, a goal that if reached would provide valuable tools to benchside biologists in their increasingly difficult task of assimilating the knowledge contained in the biomedical literature. We present an integrated approach to concept recognition in biomedical text. Concept recognition provides key information that has been largely missing from previous biomedical information extraction efforts, namely direct links to well defined knowledge resources that explicitly cement the concept's semantics. The BioCreative II tasks discussed in this special issue have provided a unique opportunity to demonstrate the effectiveness of concept recognition in the field of biomedical language processing. RESULTS: Through the modular construction of a protein interaction relation extraction system, we present several use cases of concept recognition in biomedical text, and relate these use cases to potential uses by the benchside biologist. CONCLUSION: Current information extraction technologies are approaching performance standards at which concept recognition can begin to deliver high quality data to the benchside biologist. Our system is available as part of the BioCreative Meta-Server project and on the internet http://bionlp.sourceforge.net.