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Immune checkpoint inhibitors (CPIs) have expanded treatment options for patients with solid tumors. Systemic corticosteroids (CSs) have an indispensable role in cancer care, but CS-related immunosuppression may counteract the CPI-driven antitumor immune response. This retrospective study investigated the association between baseline CS use (bCS; ≤14 days before, ≤30 days after CPI initiation) and clinical outcomes in patients with advanced non-small cell lung cancer (aNSCLC), melanoma (aMel), or urothelial carcinoma (aUC). We analyzed data from the Flatiron Health electronic health record-derived de-identified database for adults diagnosed with aNSCLC, aMel, or aUC between January 2011 and June 2017 who received ≥1 CPI monotherapy in any treatment line. Associations of bCS use with overall survival (OS) and time to next treatment (TTNT) were estimated using multivariable Cox proportional hazards models adjusting for demographic and clinical characteristics (i.e., ECOG performance status, site of metastases). In total, 2,213 patients were diagnosed with aNSCLC (n = 862), aMel (n = 742), or aUC (n = 609) and received ≥1 CPI administration. Most patients (67%-95%) received CSs, many during the baseline period (19%-30%). Patients with bCS use had shorter median OS than those with no bCS use for aNSCLC (6.6 vs 10.6 months; P= .00018), aMel (16.4 vs 21.5; P= .095), and aUC (4.1 vs 7.7; P= .0012). bCS use was associated with shorter OS (not significant for aMel) and TTNT in adjusted multivariable analyses, and clinical outcomes were not explained by prior CS use or other measured confounders. These findings suggest a potential association between bCS use and decreased CPI effectiveness, warranting further investigation.

Aim: In northern environments, periods of isolation during Pleistocene glaciations and subsequent recolonization and secondary contact have had a significant influence on contemporary diversity of many species. The recent advent of high‐resolution genomic analyses allows unprecedented power to resolve genomic signatures of such events in northern species. Here, we provide the highest resolution genomic characterization of Atlantic salmon in North America to date to infer glacial refugia and the geographic scales of post‐glacial secondary contact. Location: North America. Taxon: Atlantic salmon, Salmo salar. Methods: Samples were collected for 5455 individuals from 148 populations, encompassing the majority of the Atlantic salmon's native range in North America, from Labrador to Maine. Individuals were genotyped using a 220K single nucleotide polymorphism array aligned to the Atlantic salmon (Salmo salar) genome. Spatial genetic structure (principal component analysis, k‐means clustering, admixture) was evaluated in conjunction with genomic comparisons of these identified lineages to infer the refugia during the last glacial maximum and regions of secondary contact following recolonization. Results: Spatial genomic analyses identified three phylogeographic groups, consistent with the northward recolonization from two southern glacial refugia in North America (a western Maritime lineage and an eastern Newfoundland and Labrador lineage), with subsequent differentiation of the eastern lineage into two separate groups. Secondary contact among these North American groups was observed within the northern Gulf of St. Lawrence, and evidence of trans‐Atlantic secondary contact was detected within the eastern Newfoundland and Labrador lineage. Comparison of groups from insular Newfoundland with those from mainland Labrador suggests genomic regions displaying high differentiation were characterized by elevated European admixture, suggesting a possible role of European secondary contact in population divergence. Main Conclusions: These findings present the first evidence suggesting that genomic diversity in extant North American Atlantic salmon populations has resulted from allopatric isolation in two glacial refugia followed by both regional and trans‐Atlantic recolonization and secondary contact and demonstrate the power of genomic tools to resolve historical drivers of diversity in wild populations. [ABSTRACT FROM AUTHOR]

In marine species with large populations and high dispersal potential, large-scale genetic differences and clinal trends in allele frequency can provide insight into the evolutionary processes that shape diversity. Lumpfish, Cyclopterus lumpus , is found throughout the North Atlantic and has traditionally been harvested for roe and more recently used as a cleaner fish in salmon aquaculture. We used a 70 K SNP array to evaluate trans-Atlantic differentiation, genetic structuring, and clinal variation across the North Atlantic. Basin-scale structuring between the Northeast and Northwest Atlantic was significant, with enrichment for loci associated with developmental/mitochondrial function. We identified a putative structural variant on chromosome 2, likely contributing to differentiation between Northeast and Northwest Atlantic Lumpfish, and consistent with post-glacial trans-Atlantic secondary contact. Redundancy analysis identified climate associations both in the Northeast (N  = 1269 loci) and Northwest (N  = 1637 loci), with 103 shared loci between them. Clinal patterns in allele frequencies were observed in some loci (15%—Northwest and 5%—Northeast) of which 708 loci were shared and involved with growth, developmental processes, and locomotion. The combined evidence of trans-Atlantic differentiation, environmental associations, and clinal loci, suggests that both regional and large-scale potentially-adaptive population structuring is present across the North Atlantic. [ABSTRACT FROM AUTHOR]

Rehabilitation after primary reverse total shoulder arthroplasty (RTSA) is accepted to be an essential component to successful outcome achievement, but successful rehabilitation approaches have yet to be well described in the literature. This retrospective review documents the outcomes of a cohort of 29 patients undergoing RTSA surgery with rehabilitation following the Upper Limb Treatment and Rehabilitation Advice (ULTRA) guideline (Appendix 1). The Oxford Shoulder Score, Quick Disabilities of the Arm, Shoulder and Hand score, range of movement (degrees of flexion, abduction and external rotation) and numerical rating score for pain were prospectively collected pre-operatively and at one- and two-years post-operatively. Scores were then evaluated to establish whether or not there were any significant changes over time. Statistically significant improvements were seen in all outcome domains from pre-operative to one-year post-operative. All improvements met the threshold for achieving substantial clinical benefit as well as exceeding the minimum clinically important difference, and all improvements were maintained at the two-year post-operative time point. The present study showed that following the ULTRA guideline after elective RTSA can give statistically significant improvements in range of movement, pain score and patient-reported outcome at one-year post-operatively, which can be maintained up to two-years post-operatively. [ABSTRACT FROM AUTHOR]

Complex traits often exhibit complex underlying genetic architectures resulting from a combination of evolution from standing variation, hard and soft sweeps, and alleles of varying effect size. Increasingly, studies implicate both large‐effect loci and polygenic patterns underpinning adaptation, but the extent that common genetic architectures are utilized during repeated adaptation is not well understood. Sea age or age at maturation represents a significant life history trait in Atlantic Salmon (Salmo salar), the genetic basis of which has been studied extensively in European Atlantic populations, with repeated identification of large‐effect loci. However, the genetic basis of sea age within North American Atlantic Salmon populations remains unclear, as does the potential for a parallel trans‐Atlantic genomic basis to sea age. Here, we used a large single‐nucleotide polymorphism (SNP) array and low‐coverage whole‐genome resequencing to explore the genomic basis of sea age variation in North American Atlantic Salmon. We found significant associations at the gene and SNP level with a large‐effect locus (vgll3) previously identified in European populations, indicating genetic parallelism, but found that this pattern varied based on both sex and geographic region. We also identified nonrepeated sets of highly predictive loci associated with sea age among populations and sexes within North America, indicating polygenicity and low rates of genomic parallelism. Despite low genome‐wide parallelism, we uncovered a set of conserved molecular pathways associated with sea age that were consistently enriched among comparisons, including calcium signaling, MapK signaling, focal adhesion, and phosphatidylinositol signaling. Together, our results indicate parallelism of the molecular basis of sea age in North American Atlantic Salmon across large‐effect genes and molecular pathways despite population‐specific patterns of polygenicity. These findings reveal roles for both contingency and repeated adaptation at the molecular level in the evolution of life history variation. [ABSTRACT FROM AUTHOR]

To determine the effect of video and direct laryngoscopy on first-pass success rates for out-of-hospital orotracheal intubation. MEDLINE, Embase, and Cochrane databases were searched from inception to January 2023. Out-of-hospital studies comparing video and direct laryngoscopy on either first-pass or overall intubation success were included. A random effects meta-analysis was performed with a primary outcome of first-pass success stratified by clinician type and laryngoscope blade geometry. The secondary outcomes were overall intubation success stratified by clinician type, and intubation time. All hypotheses and subgroup analyses were determined a priori. Twenty-five studies involving 35,489 intubations met inclusion criteria. Substantial heterogeneity (>75%) precluded reporting point estimates for nearly all analyses. For our primary outcome, video laryngoscopy was associated with improved first-pass success in 3/5 physician studies, 4/6 critical care paramedic/registered nurse studies, and 7/10 paramedic studies. Video laryngoscope devices with Macintosh blade geometry were associated with improved first-pass success in 7/10 studies, while devices with hyperangulated geometry were associated with improved first-pass success in 3/7 studies. Overall intubation success was greater with video laryngoscopy in 2/6 studies in the physician subgroup and 9/10 studies in the paramedic subgroup. Video laryngoscopy was not associated with overall intubation success among critical care paramedics/nurses (OR = 1.89, 0.96 to 3.72, I2 = 34%). Lastly, 4/5 studies found video laryngoscopy to be associated with longer intubation times. We found substantial heterogeneity among out-of-hospital studies comparing video laryngoscopy to direct laryngoscopy on first-pass success, overall success, or intubation time. This heterogeneity was not explained with stratification by study design, clinician type, video laryngoscope blade geometry, or leave-one-out meta-analysis. A majority of studies showed that video laryngoscopy was associated with improved first pass success in all subgroups, but only for paramedics and not physicians when looking at overall success. This improvement was more common in studies that used Macintosh blades than those that used hyperangulated blades. Future research should explore the heterogeneity identified in our analysis with an emphasis on differences in training, clinical milieu, and specific video laryngoscope devices. [ABSTRACT FROM AUTHOR]

Atlantic salmon (Salmo salar) possesses a genome containing 10 genes encoding chitinases, yet their functional roles remain poorly understood. In other fish species, chitinases have been primarily linked to digestion, but also to other functions, as chitinase‐encoding genes are transcribed in a variety of non‐digestive organs. In this study, we investigated the properties of two chitinases belonging to the family 18 glycoside hydrolase group, namely Chia.3 and Chia.4, both isolated from the stomach mucosa. Chia.3 and Chia.4, exhibiting 95% sequence identity, proved inseparable using conventional chromatographic methods, necessitating their purification as a chitinase pair. Biochemical analysis revealed sustained chitinolytic activity against β‐chitin for up to 24 h, spanning a pH range of 2 to 6. Moreover, subsequent in vitro investigations established that this chitinase pair efficiently degrades diverse chitin‐containing substrates into chitobiose, highlighting the potential of Atlantic salmon to utilize novel chitin‐containing feed sources. Analysis of the gastric matrix proteome demonstrates that the chitinases are secreted and rank among the most abundant proteins in the gastric matrix. This finding correlates well with the previously observed high transcription of the corresponding chitinase genes in Atlantic salmon stomach tissue. By shedding light on the secreted chitinases in the Atlantic salmon's stomach mucosa and elucidating their functional characteristics, this study enhances our understanding of chitinase biology in this species. Moreover, the observed capacity to effectively degrade chitin‐containing materials implies the potential utilization of alternative feed sources rich in chitin, offering promising prospects for sustainable aquaculture practices. [ABSTRACT FROM AUTHOR]

Marine protected areas (MPAs) can serve as effective tools for the management and conservation of exploited marine species. The Gilbert Bay MPA in coastal Labrador was created to protect a genetically distinct population of Atlantic cod (Gadus morhua); however, decreases in abundance continue to occur potentially due to exploitation outside the MPA. We developed a single-nucleotide polymorphism (SNP) panel to identify Gilbert Bay cod in areas outside MPA boundaries where mixing with offshore cod occurs. In total, 361 individuals from Gilbert Bay, surrounding areas, and offshore were genotyped for 10 913 SNPs. Using [F.sub.ST] rankings and guided regularized random forest, we selected 23 SNPs that together generate 100% accuracy in individual assignment and accurately estimate the proportion of Gilbert Bay cod in fishery samples from sites outside MPA boundaries: on average, fishery samples included 17.3% Gilbert Bay cod. Estimates of effective population size for the Gilbert Bay population ranged from 655 to 1114. Our findings demonstrate the power of using genomic approaches for management of an exploited marine species and enhancing the design of MPAs. Les aires marines protegees (AMP) peuvent etre des outils efficaces pour la gestion et la conservation des especes marines exploitees. L'AMP de Gilbert Bay, le long des cotes du Labrador, a ete creee pour proteger une population genetiquement distincte de morues de l'Atlantique (Gadus morhua); cependant, des baisses d'abondance ont toujours lieu, possiblement en raison de l'exploitation en dehors de l'AMP. Nous avons developpe une puce pour la detection de polymorphismes mononucleotidiques (puce SNP) pour identifier les morues de Gilbert Bay dans des zones situees a l'exterieur des limites de l'AMP, ou ces morues se melangent a des morues d'origine extracotiere. Au total, 361 individus de Gilbert Bay, de zones environnantes et d'origine extracotiere ont ete genotypes pour 10 913 SNP. En utilisant les indices de differentiation ([F.sub.ST]) et une approche de forets aleatoires regularisee guidee, nous avons selectionne 23 SNP qui, collectivement, produisent des affectations individuelles a 100% exactes et estiment avec exactitude la proportion de morues de Gilbert Bay dans les echantillons de poissons provenant de sites a l'exterieur de l'AMP; en moyenne, les morues de Gilbert Bay constituaient 17,3% des echantillons. Les estimations de la taille effective de la population de Gilbert Bay allaient de 655 a 1 114 morues. Nos resultats demontrent la puissance des approches genomiques pour la gestion d'une espece marine exploitee et Amelioration de la conception d'AMP. [Traduit par la Redaction], Introduction Marine protected areas (MPAs) and marine reserves represent valuable tools for conservation and resource management (Gaines et al. 2010) and can play an important role in protecting marine species [...]