bluuebunny/crossref_metadata_2025_split huggingface dataset:
HMOX1 pathway signature predicts clinical benefit from immunotherapy plus tyrosine kinase inhibitor therapy in advanced renal cell carcinoma
Authors: Xu Xianglai , Zhang Sihong , Wang Ying , Zhu Yanjun , Wang Jiajun , Guo Jianming 
Published: April 2023

AbstractBackgroundImmunotherapy (IO) plus tyrosine kinase inhibitor (TKI) emerged as standard first‐line therapy for advanced renal cell carcinoma (RCC). The heme Oxygenase 1 (HMOX1) pathway is involved in tumor development and treatment resistance, which may affect the efficacy of TKI + IO.MethodsTwo cohorts from our center (ZS‐MRCC, ZS‐HRRCC), one cohort from clinical trial (JAVELIN Renal 101) and the Cancer Genome Atlas (TCGA‐KIRC) were enrolled. HMOX1 pathway signatures were determined for each sample by RNA‐sequencing and gene set enrichment analysis. Immune infiltration was evaluated by flow cytometry. Response and progression‐free survival (PFS) were set as primary endpoints.ResultsPatients of low‐HMOX1 signature showed higher objective response rate (43.5% vs. 27.3%) in ZS‐MRCC cohort and longer PFS in both cohorts (ZS‐MRCC cohort, p = 0.019; JAVELIN‐101 cohort, p = 0.036). Patients in the high‐HMOX1 signature arm also showed greater clinical benefit from TKI + IO, rather than TKI monotherapy (p < 0.001). In high‐HMOX1 signature RCC tissues, CD8+ T cells showed a dysfunctional phenotype with decreased GZMB expression (Spearman's ρ = −0.32, p = 0.045). A risk score based on HMOX1 signature was further constructed by random forest approach, involving HMOX1 signature and immunologic features. In patients with a low risk level, TKI + IO combination therapy demonstrated longer PFS than TKI monotherapy (p < 0.001), however in individuals with a high risk score group, these two regimens did not give different advantages.ConclusionsOur study identified the HMOX1 pathway signature was a potential prognostic factor of progression‐free survival for TKI + IO combination therapy in the advanced RCC in different cohort, especially in first‐line management of mRCC in the Javelin 101 cohort. Moreover, HMOX1 signature was associated with T‐cell function in tumor environment.
Postoperative chemotherapy significantly improves survival of elderly patients with stage IB‐II non‐small cell lung cancer: A population‐based study
Authors: Liu Wujianhong , Ma Shangshang , Shi Pingfan , Zhang Yanfei , Li Ming 
Published: April 2023

AbstractBackgroundThere is scant evidence‐based information about survival benefits of postoperative chemotherapy in elderly patients with early‐stage non‐small cell lung cancer (NSCLC). The purpose of this study is to compare the overall survival (OS) and cancer‐specific survival (CSS) rates of surgery alone versus postoperative chemotherapy in patients aged ≥70 years with stage I‐II NSCLC.MethodsElderly patients aged ≥70 years diagnosed with stage I‐II NSCLC were selected from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010 to December 31, 2015. OS and CSS were compared between the two groups utilizing overlap weighting analysis, inverse probability of treatment weight (IPTW), and propensity score matching (PSM).ResultsOf the 7193 included patients with stage I‐II NSCLC who are more than 70 years old, 681 patients (9.5%) received postoperative chemotherapy and 6512 patients (90.5%) received surgery‐alone. Median OS was 77 months in postoperative chemotherapy group versus 79 months in surgery‐alone group (p = 0.89). The result of IPTW analysis showed the similar results. The probability of patients choosing chemotherapy increased with the AJCC stage and Grade increasing (p < 0.001) and decreased with the growth of age (p < 0.001). The results of subgroup analysis showed that the survival rate of stage IA patients decreased significantly after postoperative chemotherapy (p < 0.01) while the survival rate of stage IB‐II patients increased significantly (p < 0.01). At the same time, we found that patients in the postoperative chemotherapy group tended to have better OS than those in the surgery‐alone group with the grade and tumor size increasing.ConclusionThe results of this study indicated that postoperative chemotherapy could significantly improve the survival of stage IB‐II NSCLC patients aged ≥70 years, and decrease the survival of stage IA patients.
A pilot study: Metabolic profiling of plasma and saliva samples from newly diagnosed glioblastoma patients
Authors: Muller Bark Juliana , Karpe Avinash V. , Doecke James D. , Leo Paul , Jeffree Rosalind L. , Chua Benjamin , Day Bryan W. , Beale David J. , Punyadeera Chamindie 
Published: April 2023

AbstractBackgroundDespite aggressive treatment, more than 90% of glioblastoma (GBM) patients experience recurrences. GBM response to therapy is currently assessed by imaging techniques and tissue biopsy. However, difficulties with these methods may cause misinterpretation of treatment outcomes. Currently, no validated therapy response biomarkers are available for monitoring GBM progression. Metabolomics holds potential as a complementary tool to improve the interpretation of therapy responses to help in clinical interventions for GBM patients.MethodsSaliva and blood from GBM patients were collected pre and postoperatively. Patients were stratified conforming their progression‐free survival (PFS) into favourable or unfavourable clinical outcomes (>9 months or PFS ≤ 9 months, respectively). Analysis of saliva (whole‐mouth and oral rinse) and plasma samples was conducted utilising LC‐QqQ‐MS and LC‐QTOF‐MS to determine the metabolomic and lipidomic profiles. The data were investigated using univariate and multivariate statistical analyses and graphical LASSO‐based graphic network analyses.ResultsAltogether, 151 metabolites and 197 lipids were detected within all saliva and plasma samples. Among the patients with unfavourable outcomes, metabolites such as cyclic‐AMP, 3‐hydroxy‐kynurenine, dihydroorotate, UDP and cis‐aconitate were elevated, compared to patients with favourable outcomes during pre‐and post‐surgery. These metabolites showed to impact the pentose phosphate and Warburg effect pathways. The lipid profile of patients who experienced unfavourable outcomes revealed a higher heterogeneity in the abundance of lipids and fewer associations between markers in contrast to the favourable outcome group.ConclusionOur findings indicate that changes in salivary and plasma metabolites in GBM patients can potentially be employed as less invasive prognostic biomarkers/biomarker panel but validation with larger cohorts is required.
RNA analysis of intronic variants in the LAMA2 gene detected by whole genome sequencing confirms a rare dual diagnosis of incontinentia pigmenti with limb‐girdle muscular dystrophy
Authors: Washington Camerun , Stolerman Elliot S. , Cooley‐Coleman Jessica A. , Jones Julie R. , Chen‐Deutsch Xiangwen 
Published: April 2023

AbstractWe see that a multiple methods approach to diagnosis remains necessary in the era of whole genome sequencing. We also observe that reproductive risk genetic counseling can be a motivating factor for further testing along the diagnostic odyssey.
The anesthetic consideration of a gravid patient with osteogenesis imperfecta undergoing cesarean section: A case report.
Authors: Hu Tao , Chen Tao , Luo Lin , Zhou Ying , Zhang Yu , Fu Qiang 
Published: April 2023

AbstractOsteogenesis imperfecta (OI) is a rare disorder of bone fragility. Gravid patients with OI usually need cesarean and may present multiple challenges. We present a case of an OI patient with severe scoliosis and an anticipated difficult airway undergoing cesarean section, with details on perioperative assessment and strategy of anesthesia.
Postprogression treatment of lenvatinib plus PD‐1 inhibitor in advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy
Authors: An Chao , Fu Yan , Li Wang , Zuo Mengxuan , Wu Peihong 
Published: April 2023

AbstractPurposeThis study compares the efficacy and safety of lenvatinib and programmed cell death protein (PD)‐1 versus lenvatinib alone for advanced hepatocellular carcinoma (Ad‐HCC) refractory to hepatic arterial infusion chemotherapy (HAIC).MethodsFrom April 2016 to September 2021, 145 patients with Ad‐HCC refractory to HAIC based on modified Response Evaluation Criteria in Solid Tumors criteria were enrolled by two radiologists and classified into the HAIC‐lenvatinib group (H‐L, n = 87) and HAIC‐lenvatinib‐PD‐1 group (H‐L‐P, n = 58). A propensity score‐matching method was used to reduce selective bias. The overall survival (OS) and postprogression‐free survival (PPS) rates were compared using the Kaplan–Meier method with log‐rank test. Multivariable analyses of independent prognostic factors were evaluated by means of the forward stepwise Cox regression model.ResultsAfter propensity score matching 1:1, the median OS was 43.6 months in the H‐L‐P group and was significantly longer than that (18.9 months) of the H‐L group (p = .009). The median PPS was 35.6 months in the H‐L‐P group and was significantly longer than that (9.4 months) of the H‐L group (p = .009). Multivariate analyses showed that the factors that ‎significantly affected the OS were‎ α‐fetoprotein (hazard ratio [HR], 2.14; 95% CI, 1.26–3.98; p = .006), early response to HAIC (HR, 0.44; 95% CI, 1.20–3.85; p = .009), and H‐L treatment (HR, ‎0.52; 95% CI, 0.30–0.86; p = .012). Modified albumin‐bilirubin grade (HR, 1.32; 95% CI, 1.03–1.70; p = .026), early response to HAIC (HR, 0.44; 95% CI, 0.25–0.77; p = .004), and H‐L (HR, ‎0.47‎; 95% CI, 0.28–0.78; p = .003) significantly affected the PPS.ConclusionsThis combination therapy of PD‐1 inhibitors plus lenvatinib has promising survival benefits in the management of patients with Ad‐HCC refractory to HAIC.Plain Language Summary

Lenvatinib plus programmed death 1 inhibitor is an effective and safe postprogression treatment and improved significantly overall survival and postprogression‐free survival compared with lenvatinib alone in patients with advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.
The chromatic atmosphere of Chilean Patagonia: The color of vastness
Authors: Cordero‐Jahr Elisa , Cerda‐Brintrup Gonzalo 
Published: April 2023

AbstractThis text proposes exploring the relationship between color, landscape, and architecture. It refers to the interrelation between the color of the landscape and architecture of one of the world's southernmost regions, Patagonia, at the southernmost tip of Chile. It is suggested that the chromatic atmosphere of this territory is marked by the vastness of the landscape, incorporating its architecture. The study is approached from an exploratory and chromatic observation perspective, through photographs and watercolors, supported by a historical and planimetric (plans and maps) literature review. The results show a complex territory, whose chromatic atmosphere evinces a deep and indissoluble link between color, landscape, and architectural heritage, concluding that the colors found onsite form an intrinsic part of this territory's identity.
The WNK1–ERK5 route plays a pathophysiological role in ovarian cancer and limits therapeutic efficacy of trametinib
Authors: Sánchez‐Fdez Adrián , Matilla‐Almazán Sofía , Montero Juan Carlos , Del Carmen Sofía , Abad Mar , García‐Alonso Sara , Bhattacharya Somshuvra , Calar Kristin , de la Puente Pilar , Ocaña Alberto , Pandiella Atanasio , Esparís‐Ogando Azucena 
Published: April 2023

AbstractBackgroundThe dismal prognosis of advanced ovarian cancer calls for the development of novel therapies to improve disease outcome. In this regard, we set out to discover new molecular entities and to assess the preclinical effectiveness of their targeting.MethodsCell lines, mice and human ovarian cancer samples were used. Proteome profiling of human phosphokinases, in silico genomic analyses, genetic (shRNA and CRISPR/Cas9) and pharmacological strategies as well as an ex vivo human preclinical model were performed.ResultsWe identified WNK1 as a highly phosphorylated protein in ovarian cancer and found that its activation or high expression had a negative impact on patients’ survival. Genomic analyses showed amplification of WNK1 in human ovarian tumours. Mechanistically, we demonstrate that WNK1 exerted its action through the MEK5–ERK5 signalling module in ovarian cancer. Loss of function, genetic or pharmacological experiments, demonstrated anti‐proliferative and anti‐tumoural effects of the targeting of the WNK1–MEK5–ERK5 route. Additional studies showed that this pathway modulated the anti‐tumoural properties of the MEK1/2 inhibitor trametinib. Thus, treatment with trametinib activated the WNK1–MEK5–ERK5 route, raising the possibility that this effect may limit the therapeutic benefit of ERK1/2 targeting in ovarian cancer. Moreover, in different experimental settings, including an ex vivo patient‐derived model consisting of ovarian cancer cells cultured with autologous patient sera, we show that inhibition of WNK1 or MEK5 increased the anti‐proliferative and anti‐tumour efficacy of trametinib.ConclusionsThe present study uncovers the participation of WNK1–MEK5–ERK5 axis in ovarian cancer pathophysiology, opening the possibility of acting on this pathway with therapeutic purposes. Another important finding of the present study was the activation of that signalling axis by trametinib, bypassing the anti‐tumoural efficacy of this drug. That fact should be considered in the context of the use of trametinib in ovarian cancer.
Quantifying phenological landmarks of migration shows nonuniform use of the Caribbean by shorebirds
Authors: Cañizares Jessica Rozek , Edwards Collin B. , Reed J. Michael 
Published: April 2023

AbstractOf the boreal‐ and Arctic‐breeding North American shorebirds that migrate south through the Caribbean, most individuals continue farther south. However, for many species, some individuals remain beyond the southbound migration period (i.e., throughout the temperate winter and/or summer). This variation among individuals adds complexity to observation data, obscures migration patterns, and could prevent the examination of the use of different Caribbean regions by various shorebird species during migration and in the nonmigratory seasons. Here, we present a novel method that leverages a well‐established statistical approach (generalized additive models) to systematically identify migration phenology even for complex passage migrant species with individuals that remain beyond migration. Our method identifies the active migration period using derivatives of a fitted GAM and then calculates phenology metrics based on quantiles of that migration period. We also developed indices to quantify oversummering and overwintering patterns with respect to migration. We analyzed eBird data for 16 North American shorebird species as they traveled South through the insular Caribbean, identifying separate migratory patterns for Cuba, Puerto Rico, Guadeloupe, Aruba, Bonaire, Curaçao, and Trinidad and Tobago. Our results confirm past reports and provide additional detail on shorebird migration in the Caribbean, and identify several previously unpublished regional patterns. Despite Puerto Rico being farther north and closer to continental North America, most species reached Puerto Rico later than other regions, supporting a long‐standing hypothesis that migration strategy (transcontinental vs. transoceanic) leads to geographic differences in migration timing. We also found distinct patterns of migration curves, with some regions and species consistently having either symmetrical or skewed curves; these differences in migration curve shape reflect different migration processes. Our novel method proved reliable and adaptable for most species and serves as a valuable tool for identifying phenological patterns in complex migration data, potentially unlocking previously intractable data.
Species richness drives selection of individuals within wetlands based on traits related to acquisition and utilization of light
Authors: Deschamps Lucas , Proulx Raphaël , Rheault Guillaume , Gross Nicolas , Watson Christopher , Maire Vincent 
Published: April 2023

AbstractSelection within natural communities has mainly been studied along large abiotic gradients, while the selection of individuals within populations should occur locally in response to biotic filters. To better leverage the role of the latter, we considered the hierarchal nature of environmental selection for the multiple dimensions of the trait space across biological levels, that is, from the species to the community and the ecosystem levels. We replicated a natural species richness gradient where communities included from two to 16 species within four wetlands (bog, fen, meadow, and marsh) contrasting in plant productivity. We sampled functional traits from individuals in each community and used hierarchical distributional modeling in order to analyze the independent variation of the mean and dispersion of functional trait space at ecosystem, community, and species levels. The plant productivity gradient observed between wetlands led to species turnover and selection of traits related to leaf nutrient conservation/acquisition strategy. Within wetlands, plant species richness drove trait variation across both communities and species. Among communities, variation of species richness correlated with the selection of individuals according to their use of vertical space and leaf adaptations to light conditions. Within species, intraspecific light‐related trait variation in response to species richness was associated with stable population density for some species, while others reached low population density in more diverse communities. Within ecosystems, variation in biotic conditions selects individuals along functional dimensions that are independent of those selected across ecosystems. Within‐species variations of light‐related traits are related to demographic responses, linking biotic selection of individuals within communities to eco‐evolutionary dynamics of species.
Plastic loss of motile cilia in the gills of Polypterus in response to high CO2 or terrestrial environments
Authors: Kimura Yuki , Nakamuta Nobuaki , Nikaido Masato 
Published: April 2023

AbstractThe evolutionary transition of vertebrates from water to land during the Devonian period was accompanied by major changes in animal respiratory systems in terms of physiology and morphology. Indeed, the fossil record of the early tetrapods has revealed the existence of internal gills, which are vestigial fish‐like traits used underwater. However, the fossil record provides only limited data on the process of the evolutionary transition of gills from fish to early tetrapods. This study investigated the gills of Polypterus senegalus, a basal ray‐finned/amphibious fish which shows many ancestral features of stem Osteichthyes. Based on scanning electron microscopy observations and transcriptome analysis, the existence of motile cilia in the gills was revealed which may create a flow on the gill surface leading to efficient ventilation or remove particles from the surface. Interestingly, these cilia were observed to disappear after rearing in terrestrial or high CO2 environments, which mimics the environmental changes in the Devonian period. The cilia re‐appeared after being returned to the original aquatic environment. The ability of plastic changes of gills in Polypterus revealed in this study may allow them to survive in fluctuating environments, such as shallow swamps. The ancestor of Osteichthyes is expected to have possessed such plasticity in the gills, which may be one of the driving forces behind the transition of vertebrates from water to land.
Evaluating the evolutionary mechanisms maintaining alternative mating strategies in a simulated bull trout (Salvelinus confluentus) population
Authors: Bernos Thaïs A. , Chang Sarah L. , Giglio Rachael M. , Davenport Kaeli , Fisher Jeff , Lowery Erin , Bearlin Andrew , Simmons Ryan , Fortin Marie‐Josée , Day Casey C. , Landguth Erin L. 
Published: April 2023

AbstractThe coexistence of distinct alternative mating strategies (AMS) is often explained by mechanisms involving trade‐offs between reproductive traits and lifetime fitness; yet their relative importance remains poorly understood. Here, we used an established individual‐based, spatially explicit model to simulate bull trout (Salvelinus confluentus) in the Skagit River (Washington, USA) and investigated the influence of female mating preference, sneaker‐specific mortality, and variation in age‐at‐maturity on AMS persistence using global sensitivity analyses and boosted regression trees. We assumed that two genetically fixed AMS coexisted within the population: sneaker males (characterized by younger age‐at‐maturity, greater AMS‐specific mortality, and lower reproductive fitness) and territorial males. After 300 years, variation in relative sneaker success in the system was explained by sneaker males' reproductive fitness (72%) and, to a lesser extent, the length of their reproductive lifespan (21%) and their proportion in the initial population (8%). However, under a wide range of parameter values, our simulated scenarios predicted the extinction of territorial males or their persistence in small, declining populations. Although these results do not resolve the coexistence of AMS in salmonids, they reinforce the importance of mechanisms reducing sneaker's lifetime reproductive success in favoring AMS coexistence within salmonid populations but also limit the prediction that, without any other selective mechanisms at play, strong female preference for mating with territorial males and differences in reproductive lifespan allow the stable coexistence of distinct AMS.
What causes bird‐building collision risk? Seasonal dynamics and weather drivers
Authors: Scott Kara M. , Danko Attilla , Plant Paloma , Dakin Roslyn 
Published: April 2023

AbstractBird‐building collisions are a major source of wild bird mortality, with hundreds of millions of fatalities each year in the United States and Canada alone. Here, we use two decades of daily citizen science monitoring to characterize day‐to‐day variation in building collisions and determine the factors that predict the highest risk times in two North American cities. We use these analyses to evaluate three potential causes of increased collision risk: heightened migration traffic during benign weather, increased navigational and flight errors during inclement weather, and increased errors in response to highly directional sunlight that enhances reflected images. The seasonal phenology of collisions was consistent across sites and years, with daily collision rates approximately twofold higher in autumn as compared to spring. During both migration seasons, collision risk was best predicted by the weather conditions at dawn. In spring, peak collision risk occurs on days with warm temperatures, south winds, and a lack of precipitation at dawn. In autumn, peak collision occurs on days with cool temperatures, north winds, high atmospheric pressure, a lack of precipitation, and clear conditions with high visibility. Based on these results, we hypothesize that collisions are influenced by two main weather‐driven mechanisms. First, benign weather at dawn and winds that are favorable for migration cause an increase in migration traffic in both spring and autumn, creating greater opportunity for collisions to occur. Second, for autumnal migrants, cold clear conditions may cause an additional increase in collision risk. We propose that these conditions may be particularly hazardous in autumn because of the high abundance of naïve and diurnal migrants at that time of year. Our analysis also establishes that a relatively small proportion of days (15%) are responsible for 50% of the total collision mortality within a season, highlighting the importance of targeting mitigation strategies to the most hazardous times.