bluuebunny/crossref_metadata_2025_split huggingface dataset:
A flexible approach for predictive biomarker discovery
Authors: Boileau Philippe , Qi Nina Ting , van der Laan Mark J , Dudoit Sandrine , Leng Ning 
Published: July 2022

Summary
An endeavor central to precision medicine is predictive biomarker discovery; they define patient subpopulations which stand to benefit most, or least, from a given treatment. The identification of these biomarkers is often the byproduct of the related but fundamentally different task of treatment rule estimation. Using treatment rule estimation methods to identify predictive biomarkers in clinical trials where the number of covariates exceeds the number of participants often results in high false discovery rates. The higher than expected number of false positives translates to wasted resources when conducting follow-up experiments for drug target identification and diagnostic assay development. Patient outcomes are in turn negatively affected. We propose a variable importance parameter for directly assessing the importance of potentially predictive biomarkers and develop a flexible nonparametric inference procedure for this estimand. We prove that our estimator is double robust and asymptotically linear under loose conditions in the data-generating process, permitting valid inference about the importance metric. The statistical guarantees of the method are verified in a thorough simulation study representative of randomized control trials with moderate and high-dimensional covariate vectors. Our procedure is then used to discover predictive biomarkers from among the tumor gene expression data of metastatic renal cell carcinoma patients enrolled in recently completed clinical trials. We find that our approach more readily discerns predictive from nonpredictive biomarkers than procedures whose primary purpose is treatment rule estimation. An open-source software implementation of the methodology, the uniCATE R package, is briefly introduced.
The role of sexual selection in flowering plant origin and evolution and the potential significance of female competition and selection in ovules
Authors: Bachelier Julien B 
Published: July 2022

Abstract
Ever since Erasmus and Charles Darwin laid down the foundations of the concept, sexual selection has largely been regarded as a matter of male competition and female selection. While their role in plant evolution and the elusive origin of flowering plants has largely been neglected in contrast to the situation with animals, there is a growing body of evidence accumulated over the past 50 years supporting the hypothesis that, together with the flower and the carpel, increased pollination has led to an intensification of the competition between the fittest (and faster) pollen tubes and their selection by the surrounding maternal tissue. In contrast, the potential role of female competition was historically seldom considered but started to re-emerge a decade ago in both animal and plant evolution. Here, I review a large body of the vast embryological literature to re-evaluate unusual developmental traits in the plant female germline, traditionally considered as teratological occurrences of mere systematic interest, in the light of the current phylogenetic framework for flowering plants. After a summary of the basic tenets of sexual selection and the role of male competition and maternal selection in shaping plant evolution and diversity, I show how recent insights into the deepest nodes of flowering plant phylogeny and confirmation of their systematic relationships over the past 30 years have led to major shifts in our understanding of the reproductive biology of their most recent common ancestor. I also show that a re-evaluation of these unusual developmental traits in the female germline, especially in early-diverging lineages of flowering plants, may potentially be correlated with some floral structural traits. On the basis of these results, I argue that there is circumstantial evidence for mechanisms of female intrasexual competition and selection in individual ovules of flowering plants that are similar to those between pollen tubes competing inside the carpel. I also argue that although they may have evolved independently multiple times in unrelated lineages, they could also be the ‘burning embers’ of plesiomorphic traits that would have been largely selected against after the evolution of their most recent common ancestor.
Implications of leg length for metabolic health and fitness
Authors: Shirley Meghan K , Arthurs Owen J , Seunarine Kiran K , Cole Tim J , Eaton Simon , Williams Jane E , Clark Chris A , Wells Jonathan C K 
Published: July 2022

Abstract

Background and objectives
Several studies have linked longer legs with favorable adult metabolic health outcomes and greater offspring birth weight. A recent Mendelian randomization study suggested a causal link between height and cardiometabolic risk; however, the underlying reasons remain poorly understood.

Methodology
Using a cross-sectional design, we tested in a convenience sample of 70 healthy young women whether birth weight and tibia length as markers of early-life conditions associated more strongly with metabolically beneficial traits like organ size and skeletal muscle mass (SMM) than a statistically derived height-residual variable indexing later, more canalized growth.

Results
Consistent with the ‘developmental origins of health and disease’ hypothesis, we found relatively strong associations of tibia length—but not birth weight—with adult organ size, brain size, SMM and resting energy expenditure measured by magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry and indirect calorimetry, respectively.

Conclusions and implications
Building on prior work, these results suggest that leg length is a sensitive marker of traits directly impacting metabolic and reproductive health. Alongside findings in the same sample relating tibia length and height-residual to MRI-measured pelvic dimensions, we suggest there may exist a degree of coordination in the development of long bone, lean mass and pelvic traits, possibly centered on early, pre-pubertal growth periods. Such phenotypic coordination has important implications for fitness, serving to benefit both adult health and the health of offspring in subsequent generations.
Transcriptomic analysis of deceptively pollinated Arum maculatum (Araceae) reveals association between terpene synthase expression in floral trap chamber and species-specific pollinator attraction
Authors: Szenteczki Mark A , Godschalx Adrienne L , Gauthier Jérémy , Gibernau Marc , Rasmann Sergio , Alvarez Nadir 
Published: July 2022

Abstract
Deceptive pollination often involves volatile organic compound emissions that mislead insects into performing nonrewarding pollination. Among deceptively pollinated plants, Arum maculatum is particularly well-known for its potent dung-like volatile organic compound emissions and specialized floral chamber, which traps pollinators—mainly Psychoda phalaenoides and Psychoda grisescens—overnight. However, little is known about the genes underlying the production of many Arum maculatum volatile organic compounds, and their influence on variation in pollinator attraction rates. Therefore, we performed de novo transcriptome sequencing of Arum maculatum appendix and male floret tissue collected during anthesis and postanthesis, from 10 natural populations across Europe. These RNA-seq data were paired with gas chromatography–mass spectrometry analyses of floral scent composition and pollinator data collected from the same inflorescences. Differential expression analyses revealed candidate transcripts in appendix tissue linked to malodourous volatile organic compounds including indole, p-cresol, and 2-heptanone. In addition, we found that terpene synthase expression in male floret tissue during anthesis significantly covaried with sex- and species-specific attraction of Psychoda phalaenoides and Psychoda grisescens. Taken together, our results provide the first insights into molecular mechanisms underlying pollinator attraction patterns in Arum maculatum and highlight floral chamber sesquiterpene (e.g. bicyclogermacrene) synthases as interesting candidate genes for further study.
Sex-biased admixture and assortative mating shape genetic variation and influence demographic inference in admixed Cabo Verdeans
Authors: Korunes Katharine L , Soares-Souza Giordano Bruno , Bobrek Katherine , Tang Hua , Araújo Isabel Inês , Goldberg Amy , Beleza Sandra 
Published: July 2022

AbstractGenetic data can provide insights into population history, but first, we must understand the patterns that complex histories leave in genomes. Here, we consider the admixed human population of Cabo Verde to understand the patterns of genetic variation left by social and demographic processes. First settled in the late 1400s, Cabo Verdeans are admixed descendants of Portuguese colonizers and enslaved West African people. We consider Cabo Verde’s well-studied historical record alongside genome-wide SNP data from 563 individuals from 4 regions within the archipelago. We use genetic ancestry to test for patterns of nonrandom mating and sex-specific gene flow, and we examine the consequences of these processes for common demographic inference methods and genetic patterns. Notably, multiple population genetic tools that assume random mating underestimate the timing of admixture, but incorporating nonrandom mating produces estimates more consistent with historical records. We consider how admixture interrupts common summaries of genomic variation such as runs of homozygosity. While summaries of runs of homozygosity may be difficult to interpret in admixed populations, differentiating runs of homozygosity by length class shows that runs of homozygosity reflect historical differences between the islands in their contributions from the source populations and postadmixture population dynamics. Finally, we find higher African ancestry on the X chromosome than on the autosomes, consistent with an excess of European males and African females contributing to the gene pool. Considering these genomic insights into population history in the context of Cabo Verde’s historical record, we can identify how assumptions in genetic models impact inference of population history more broadly.
Subjective Age and Falls in Older Age: Evidence From Two Longitudinal Cohorts
Authors: Fundenberger Hervé , Stephan Yannick , Terracciano Antonio , Dupré Caroline , Bongue Bienvenu , Hupin David , Barth Nathalie , Canada Brice 
Published: July 2022

Abstract

Objectives
Falls are a common and serious health problem. The present study examined the association between subjective age (i.e., feeling younger or older than one’s chronological age) and falls in 2 large national samples.

Method
Participants aged 65–105 years old were drawn from the National Health and Aging Trends Study (NHATS) and the Health and Retirement Study (HRS). Data on falls, subjective age, and demographic factors were available from 2,382 participants in HRS and 3,449 in NHATS. Falls were tracked for up to 8 (HRS) and 7 (NHATS) years.

Results
Cox regression analyses that included demographic covariates indicated that older subjective age increased the risk of falling in HRS (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.08–1.27) and in NHATS (HR = 1.06, 95% CI = 1.00–1.13). When compared to people who felt younger, people who reported an older subjective age had a higher risk of fall (HRS: HR = 1.65, 95% CI = 1.33–2.04; NHATS: HR = 1.44, 95% CI = 1.15–1.79). The associations remained significant after accounting for depressive symptoms, handgrip strength, chronic diseases, and cognitive impairment in HRS only.

Discussion
These results confirm the role of subjective age as an important health marker in the aging population. Subjective age assessment can help identify individuals at greater risk of falls.
Talin variant P229S compromises integrin activation and associates with multifaceted clinical symptoms
Authors: Azizi Latifeh , Varela Lorena , Turkki Paula , Mykuliak Vasyl V , Korpela Sanna , Ihalainen Teemu O , Church Joseph , Hytönen Vesa P , Goult Benjamin T 
Published: July 2022

AbstractAdhesion of cells to the extracellular matrix (ECM) must be exquisitely coordinated to enable development and tissue homeostasis. Cell–ECM interactions are regulated by multiple signalling pathways that coordinate the activation state of the integrin family of ECM receptors. The protein talin is pivotal in this process, and talin’s simultaneous interactions with the cytoplasmic tails of the integrins and the plasma membrane are essential to enable robust, dynamic control of integrin activation and cell–ECM adhesion. Here, we report the identification of a de novo heterozygous c.685C&gt;T (p.Pro229Ser) variant in the TLN1 gene from a patient with a complex phenotype. The mutation is located in the talin head region at the interface between the F2 and F3 domains. The characterization of this novel p.P229S talin variant reveals the disruption of adhesion dynamics that result from disturbance of the F2–F3 domain interface in the talin head. Using biophysical, computational and cell biological techniques, we find that the variant perturbs the synergy between the integrin-binding F3 and the membrane-binding F2 domains, compromising integrin activation, adhesion and cell migration. Whilst this remains a variant of uncertain significance, it is probable that the dysregulation of adhesion dynamics we observe in cells contributes to the multifaceted clinical symptoms of the patient and may provide insight into the multitude of cellular processes dependent on talin-mediated adhesion dynamics.
The Expansion of Wage Theft Legislation in Common Law Countries—Should Ireland be Next?
Authors: O’Sullivan Michelle 
Published: July 2022

Abstract
While employment laws exist to protect workers from the unfair exploitation, evidence suggests that wage theft is a prominent practice. Wage theft has received considerable public policy attention in several common law countries leading to the introduction of new legislation on the basis that existing legal regulations were inadequate and because the effects of wage theft are particularly deleterious for low-wage workers. Wage theft though remains underexplored in an Irish policy context. This article examines whether Ireland needs stronger laws to address wage theft by assessing if existing minimum wage and working time employment legislation provide an effective remedy for workers. The analysis finds that Irish laws already contain many provisions which new wage theft laws in other jurisdictions have introduced, suggesting radically new legislation is not needed. Several features of existing laws though obstruct workers in seeking remedy for underpayments and require amendment. Changing legislation, however, will likely be insufficient for an effective enforcement regime and it must be supplemented by statutory support for collective representation and enhancing labour inspectorate capacity to act on workers’ behalf.
The role of the microbiome in pancreatic oncogenesis
Authors: Daley Donnele 
Published: July 2022

Abstract
Bacterial dysbiosis is evolving as an advocate for carcinogenesis and has been associated with pancreatic cancer progression and survival outcomes. The gut and pancreas of cancer patients harbor a unique microbiome that differs significantly from that of healthy individuals. We believe that the pancreatic cancer microbiome regulates tumorigenesis by altering host cell function and modulating immune cells, skewing them toward an immunosuppressive phenotype. Moreover, altering this pathogenic microbiome may enhance the efficacy of current therapies in pancreatic cancer and improve survival outcomes. This review highlights the findings on microbial modulation across various pre-clinical and clinical studies and provides insight into the potential of targeting the microbiome for pancreatic cancer therapy.
CON: Serum biomarker monitoring should not replace primary antifungal chemoprophylaxis in patients with acute leukaemia receiving systemic anti-cancer therapy
Authors: Howard Alex , Hope William 
Published: July 2022

Abstract
Primary antifungal chemoprophylaxis (PAC) is the widespread strategy of choice for the prevention of invasive fungal disease in patients with acute leukaemia (AL). Twice-weekly monitoring of the serum biomarkers (SBM) galactomannan and 1,3-β-d-glucan has been proposed as an alternative prevention strategy to PAC for these patients. This paper outlines the arguments for why PAC should remain as the standard of care in AL, instead of switching to twice-weekly SBM. Arguments put forward in favour of PAC are the strength of evidence for its safety, cost-effectiveness and adaptability, and its adoption by multiple international guidelines as standard of care. The potential implications of PAC for drug interactions and antifungal resistance are also discussed. The drawbacks of twice-weekly SBM are appraised, including missed or delayed diagnoses, unnecessary investigations, deferral of systemic anti-cancer therapy and increased pressure on laboratory services.
Status of Physicochemical and Microbiological Analytical Methods of Gatifloxacin: A Review
Authors: Teixeira Max Well Silva , Dias Cleber Vinicios Barbosa , Kogawa Ana Carolina 
Published: July 2022

Abstract

Background
Gatifloxacin (GAT), an antimicrobial of the fourth generation of fluoroquinolones, has a broad spectrum of action with activity against Gram-positive and Gram-negative, aerobic and anaerobic organisms, including mycobacteria.

Objective
The objective of this review is to discuss about (i) characteristics, (ii) properties, and (iii) analytical methods of gatifloxacin.

Results
Among the methods described in the literature for the evaluation of GAT, the most frequent was HPLC (50%) for both the analysis of pharmaceutical and biological matrixes. GAT has no monograph described in official compendia. Methods for evaluating GAT in pharmaceutical matrixes were the most found in the literature, 79%. Acetonitrile (42%), methanol (20%), and buffer solution (16%) were the most used diluents. GAT, being an antimicrobial, must be analyzed by physical-chemical and microbiological methods, since the evaluation of potency is essential. In this context, the literature is scarce (4%).

Conclusions
There is a gap in the literature for environmentally friendly methods for evaluating GAT. Faster, more optimized and dynamic microbiological methods, as well as physicochemical methods, use less aggressive solvents with fewer steps and less waste. Currently, pharmaceutical analyses require reliable analytical methods, but also safe for both the analyst and the environment.

Highlights
This review shows the status of analytical methods, both physicochemical and microbiological, for the analysis of GAT in pharmaceutical and biological matrixes, also addressing its context in green and sustainable analytical chemistry.
The Role of Vitamin E in Thermal Burn Injuries, Infection, and Sepsis: A Review
Authors: Thompson Marc A , Zuniga Kameel , Sousse Linda , Christy Robert , Gurney Col Jennifer 
Published: July 2022

Abstract
Thermal burn injuries are still a serious public health concern in the United States, due to the initial insult and resulting comorbidities. Burned patients are increasingly susceptible to colonization by endogenous and exogenous microorganisms after having lost skin, which acts as the primary protective barrier to environmental contaminants. Furthermore, the onset of additional pathophysiologies, specifically sepsis, becomes more likely in burned patients compared to other injuries. Despite improvements in the early care of burn patients, infections, and sepsis, these pathophysiologies remain major causes of morbidity and mortality and warrant further investigation of potential therapies. Vitamin E may be one such therapy. We aimed to identify publications of studies that evaluated the effectiveness of vitamin E as it pertains to thermal burn injuries, infection, and sepsis. Several investigations ranging from in vitro bench work to clinical studies have examined the impact on, or influence of, vitamin E in vitro, in vivo, and in the clinical setting. To the benefit of subjects it has been shown that enteral or parenteral vitamin E supplementation can prevent, mitigate, and even reverse the effects of thermal burn injuries, infection, and sepsis. Therefore, a large-scale prospective observational study to assess the potential benefits of vitamin E supplementation in patients is warranted and could result in clinical care practice paradigm changes.
A Pilot Study Testing the Novel Use of a Snake Bite Compression Device for Field Hemostasis and Wound Repair in an Animal Model
Authors: Lindquist David G , Valente Jonathan H , Hack Jason B 
Published: July 2022

ABSTRACT

Introduction
A commercially available snake bite device was pilot tested for novel use as a method of hemostasis and wound repair at a noncompressible site in a live swine model. The device is light, is plastic, uses a hook-and-loop strap attachment, and is easily deployed. The device could offer a method for the field repair of an actively bleeding laceration at a noncompressible site in an austere environment.

Materials and Methods
This was an interventional, prospective, controlled study in a large animal model. The study was approved by the Rhode Island Hospital Institutional Review Board (IRB) and the Animal Welfare Committee/Institutional Animal Care and Use Committee and the Lifespan Research Conflict of Interest Committee. Each animal acted as its own control. Blood loss was measured and compared between repairs of standardized incisions with and without the device’s application. The lacerations were sutured closed. Two proceduralists alternated tasks of wound repair versus blood collection. Blood loss was measured by using gauze sponges to capture the blood during a 30-second free-bleeding period and during the repair itself. Using a one sample t-test (the expected difference in blood loss between the two incision repair methods = 0 if the null hypothesis were true), we calculated the mean difference in the deltas between the repair methods.

Results
The mean delta difference was 3.1 g (SE ± 0.97). The t-test demonstrated that there was a significantly greater blood loss during the standard repair method, t(9) = 3.11, P &lt; 0.01 than during the repair with the device in place (see Fig. 2). A statistical power analysis conducted showed that with a sample size of 10 animals, there was sufficient statistical power to detect this significant effect (β = 0.82, α &lt; 0.05, one-tailed).

Conclusions
There was statistically significantly less blood loss during the repairs with the device’s application. This feasibility experiment demonstrates that a commercially available snakebite device may be useful for hemostasis during laceration repair at anatomic sites not amenable to application of tourniquets or compressive dressings. Strengths of the study include the prospective controlled design, including the use of each animal as its own control; alternating proceduralists to account for any variability in suturing efficiency; and the statistical significance of the results despite the small number of subjects. One weakness is that the time required for each repair was not measured. The device’s portability and reusability suggest applicability in austere medical environments. Future studies could include timing the repairs, using a skin stapler or wound adhesive instead of sutures, applying a hemostatic agent before the repair, and sequentially applying the device to wounds longer than the device.