bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review assessing the state of analytical validation for connected, mobile, sensor-based digital health technologies
Authors: Sharma Yashoda , Djambazova Katerina V. , Marquez Celine D. , Lyden Kate , Goldsack Jennifer C. , Bakker Jessie P. 
Published: May 2023

AbstractBackgroundDespite the recent proliferation of digital health technologies (DHTs), there is a lack of formal, industry-wide standards to evaluate the performance of the product’s algorithm in terms of its ability to measure, detect, or predict a clinical state. The advancement and successful use of DHTs in medicine requires that all stakeholders – clinicians, patients, payers, regulators, pharmaceutical companies, and the medical products industry – have a common understanding of what it means when a DHT has been analytically validated.ObjectiveWe conducted a systematic review to assess the state of the science on analytical validation for DHTs, using the criteria established by the V3 Framework and EVIDENCE checklist.MethodsThe systematic review was conducted according to the PRISMA guidelines. A multi-tier PubMed search identified studies published between April 15, 2020, and April 15, 2023, on analytical validation of DHTs; thereafter, each paper was assessed against the EVIDENCE checklist items specific to analytical validation. All studies were required to report quantitative data collected from a connected, mobile sensor product for the measurement, diagnosis, and/or treatment of a behavioral or physiological function, and compare the outcome measures to an established reference standard.ResultsOf the 1201 papers identified in the literature search, we identified 303 reporting the results of a DHT analytical validation study. The most prevalent therapeutic areas of focus were neurological (26%), cardiovascular (18%), and sleep conditions (17%). Health outcome categories most frequently captured by DHTs were gait (15%), heart rate/rhythm (15%), blood pressure and/or arterial stiffness (11%), sleep staging (10%), and mobility (9%). Only 208 papers (69%) reported all components of the EVIDENCE checklist focused on analytical validation, with the exception of software version and race/ethnicity, thereby meeting our definition of high-quality evidence reporting.ConclusionWe are encouraged by the emerging literature evaluating whether outcome measures assessed by DHTs adequately reflect the physiological or behavioral parameter of interest; however, the quality of reporting is not yet sufficient to ensure the advancement of digital clinical measures that are fit-for-purpose for all members of a defined population and eliminate the need for redundant studies. We recommend that journals publishing analytical validation studies require the use of the EVIDENCE checklist as a reporting standard for these manuscripts.
Age-related phenotypes in breast cancer: a population-based study
Authors: Svanøe Amalie A. , Humlevik Rasmus O.C. , Knutsvik Gøril , Sæle Anna K.M. , Askeland Cecilie , Ingebriktsen Lise M. , Hugaas Ulrikke , Kvamme Amalie B. , Tegnander Amalie F. , Krüger Kristi , Davidsen Benedicte , Hoivik Erling A. , Aas Turid , Stefansson Ingunn M. , Akslen Lars A. , Wik Elisabeth 
Published: May 2023

AbstractBreast cancer in young (<40 years) is associated with a higher frequency of aggressive tumor types and poor prognosis. It remains unclear if there is an underlying age-related biology that contributes to the unfavorable outcome. We aim to investigate the relationship between age and breast cancer biology, with emphasis on proliferation. Clinico-pathologic information, immunohistochemical markers, and follow-up data were obtained for all patients aged <50 (Bergen cohort-1; n=355) and compared to previously obtained information on patients aged 50-69 (Bergen cohort-2; n=540), who participated in the Norwegian Breast Cancer Screening Program. Data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) was applied for validation and for analyses of gene expression signatures. Young breast cancer patients presented more aggressive tumor features such as hormone receptor negativity, HER2 positivity, lymph-node metastasis, the HER2-enriched and triple negative subtypes, and shorter survival. Age <40 was significantly associated with features of stemness and higher proliferation (by Ki67), also in molecular subsets. Ki67 showed weaker prognostic value in young patients. We point to aggressive phenotypes, increased tumor cell proliferation and stem-like features in breast cancer of the young. Hence, tumors of young breast cancer patients may have a unique biology, also when accounting for screen/interval differences, that may open for new clinical opportunities, stratifying treatment by age.
Reduction of retinal ganglion cell death in mouse models of familial dysautonomia using AAV-mediated gene therapy and splicing modulators
Authors: Schultz Anastasia , Cheng Shun-Yun , Kirchner Emily , Costello Stephanann , Miettinen Heini , Chaverra Marta , King Colin , George Lynn , Zhao Xin , Narasimhan Jana , Weetall Marla , Slaugenhaupt Susan , Morini Elisabetta , Punzo Claudio , Lefcort Frances 
Published: May 2023

AbstractFamilial dysautonomia (FD) is a rare neurodevelopmental and neurodegenerative disease caused by a splicing mutation in the Elongator Acetyltransferase Complex Subunit 1 (ELP1) gene. The reduction in ELP1 mRNA and protein leads to the death of retinal ganglion cells (RGCs) and visual impairment in all FD patients. Currently, patient symptoms are managed, but there is no treatment for the disease. We sought to test the hypothesis that restoring levels of Elp1 would thwart the death of RGCs in FD. To this end, we tested the effectiveness of two therapeutic strategies for rescuing RGCs. Here we provide proof-of-concept data that gene replacement therapy and small molecule splicing modifiers effectively reduce the death of RGCs in mouse models for FD and provide pre-clinical data foundation for translation to FD patients.
Bat cellular immunity varies by year and dietary habit in an increasingly fragmented landscape
Authors: DeAnglis Isabella K. , Andrews Benjamin R. , Lock Lauren R. , Dyer Kristin E. , Volokhov Dmitriy V. , Fenton M. Brock , Simmons Nancy B. , Downs Cynthia J. , Becker Daniel J. 
Published: May 2023

AbstractMonitoring the health of wildlife populations is essential in the face of increased agricultural expansion and forest fragmentation. Loss of habitat and habitat degradation can negatively affect an animal’s physiological state, possibly resulting in immunosuppression and increased morbidity or mortality. We sought to determine how fragmentation may differentially impact cellular immunity and infection risk in Neotropical bats species regularly infected with bloodborne pathogens, and to evaluate how effects may vary over time and by dietary habit. We studied common vampire bats (Desmodus rotundus), northern yellow-shouldered bats (Sturnira parvidens), and Mesoamerican mustached bats (Pteronotus mesoamericanus), representing the dietary habits of sanguinivory, frugivory, and insectivory respectively, in northern Belize. We compared estimated total white blood cell counts, leukocyte differentials, and infection status with two blood-borne bacterial pathogens (Bartonellaspp. and hemoplasmas) of 118 bats captured in a broadleaf, secondary forest over a three-year period (2017-2019) of increasing habitat fragmentation. We found evidence for bat species-specific responses of cellular immunity between years, with neutrophil counts increasing inD. rotundus, but decreasing inS. parvidensandP. mesoamericanusfrom 2018 to 2019. However, the odds of infection withBartonellaspp. and hemoplasma spp. between 2017 and 2019 did not differ between bat species, contrary to our prediction that pathogen prevalence may increase with increased fragmentation. We conclude that each bat species invested differently in cellular immunity in ways that changed over years of increasing fragmentation. We recommend further research on the interactions between habitat fragmentation, cellular immunity, and infection across dietary habits of Neotropical bats for informed management and conservation.
Molecular Dynamics studies of Long Neurotoxins against nAChR provide key insights towards design of therapeutic peptides for Dyskinesia
Authors: Pandit Shivam , Saha Gargi , D Jagadeesh Kumar. , Nagendra H.G. 
Published: May 2023

AbstractPeptide-based drugs are widely used as therapeutic products that exhibit strong binding affinities with high specificity and low toxicity. To develop novel therapeutics against severe involuntary muscle movement and trembling disorder (Dyskinesia), the study explored the design of peptides that could target the nicotine acetylcholine receptor (nAChR) as antagonistic leads. The work aimed to suggest that the pharmacological interaction of snake venom toxins and its associated peptides with nAChR’s could be exploited as plausible solutions for PD. Molecular docking and Molecular dynamics exercises were carried out using long chain neurotoxins (α-BTx, 1NTN) to analyze the efficacies of their binding to nAChR’s, with both the entire toxin and short peptide moieties. The study demonstrated that thenovel-peptide (F8J2D7)system appears to possess better affinity with the nAChR than the entire toxin, which is a first step towards designing peptide-based drugs from snake venom proteins that could facilitate further research in the peptide-engineering and drug designing prospects for various neurodegenerative diseases.
Discovering pathways through ribozyme fitness landscapes using information theoretic quantification of epistasis
Authors: Charest Nathaniel , Shen Yuning , Lai Yei-Chen , Chen Irene A. , Shea Joan-Emma 
Published: May 2023

AbstractThe identification of catalytic RNAs is typically achieved through primarily experimental means. However, only a small fraction of sequence space can be analyzed even with high-throughput techniques. Methods to extrapolate from a limited data set to predict additional ribozyme sequences, particularly in a human-interpretable fashion, could be useful both for designing new functional RNAs and for generating greater understanding about a ribozyme fitness landscape. Using information theory, we express the effects of epistasis (i.e., deviations from additivity) on a ribozyme. This representation was incorporated into a simple model of the epistatic fitness landscape, which identified potentially exploitable combinations of mutations. We used this model to theoretically predict mutants of high activity for a self-aminoacylating ribozyme, identifying potentially active triple and quadruple mutants beyond the experimental data set of single and double mutants. The predictions were validated experimentally, with nine out of nine sequences being accurately predicted to have high activity. This set of sequences included mutants that form a previously unknown evolutionary ‘bridge’ between two ribozyme families that share a common motif. Individual steps in the method could be examined, understood, and guided by a human, combining interpretability and performance in a simple model to predict ribozyme sequences by extrapolation.
Towards a definition of unicellular eukaryote phototrophs functional traits via metabolic modelling
Authors: Burel Marie , Régimbeau Antoine , Eveillard Damien , Pelletier Eric 
Published: May 2023

AbstractDefining biological functional traits for unicellular organisms relies on comprehending the set and combination of the biochemical reactions their genomes encode for. This network of biochemical reactions defines the metabolic strategy organisms and communities use. Understanding the functional traits of unicellular organisms involves studying the combination of biochemical reactions encoded in their genomes. These reactions determine the metabolic strategy that organisms and communities use to grow in a specific environment. While prokaryotes have been extensively studied for their metabolic networks, eukaryotes have lagged behind due to the complexity of their genomes and the need for a better understanding of their metabolism. We have createdPhotoEukstein, a meta-metabolic model for unicellular phototrophic eukaryotes. This meta-model enables quick and automated derivation of Genome-Scale Metabolic models directly from genomes. We have used it to analyse 533 environmental genomes and marine eukaryotic unicellular plankton transcriptomes. These models can help predict functional traits that cannot be purely deducted from taxonomic information or the listing of metabolic reactions encoded by the genome. They provide the opportunity to build connections with Earth System Models to pinpoint environmental parameters to capture specific functional traits.
Divergent lineages in a young species: the case of Datilillo (Yucca valida), a broadly distributed plant from the Baja California Peninsula
Authors: Aleman Alberto , Arteaga Maria Clara , Gasca-Pineda Jaime , Bello-Bedoy Rafael 
Published: May 2023

ABSTRACTPremiseGlobally, barriers triggered by climatic changes have caused habitat fragmentation and population allopatric divergence. Across North America, oscillations during the Quaternary have played important roles in the distribution of wildlife. Notably, diverse plant species from the Baja California Peninsula, in western North America, exhibit strong genetic structure and highly concordant divergent lineages across their ranges, as they were isolated during the Pleistocene glacial-interglacial cycles and thus accumulated genetic differentiation in their genomes. A representative plant genus of this Peninsula isYucca, withYucca validahaving the widest range. WhereasY. validais a dominant species, there is an extensive distribution discontinuity between 26° N and 27° N, where no individuals have been identified, suggesting restricted gene flow. Moreover, the historical distribution models indicate the absence of an area with suitable conditions for the species during the Last Interglacial, making it an interesting model for studying genetic divergence.MethodsWe examined the phylogeography ofY. validathroughout its range to identify the number of genetic lineages, quantify their genetic differentiation, reconstruct their demographic history and estimate the species’ age.Key resultsWe assembled 4,411 SNPs from 147 plants, identifying three allopatric lineages. Our analyses support that genetic drift is the driver of genetic differentiation among these lineages. We estimated an age under one million years for the common ancestor ofY. validaand its sister species.ConclusionsHabitat fragmentation caused by climatic changes, low dispersal, and an extensive geographical range gap acted as cumulative mechanisms leading to allopatric divergence inY. valida.
Novel TRPM7 inhibitors with potent anti-inflammatory effectsin vivo
Authors: Busey Gregory W. , Manjegowda Mohan C. , Huang Tao , Iobst Wesley H. , Naphade Shardul S. , Kennedy Joel A. , Doyle Catherine A. , Seegren Philip V. , Lynch Kevin R. , Desai Bimal N. 
Published: May 2023

SummaryTRPM7, a TRP channel with ion conductance and kinase activities, has emerged as an attractive drug target for immunomodulation. Reverse genetics and cell biological studies have already established a key role for TRPM7 in the inflammatory activation of macrophages. Advancing TRPM7 as a viable molecular target for immunomodulation requires selective TRPM7 inhibitors within vivotolerability and efficacy. Such inhibitors have the potential to interdict inflammatory cascades mediated by systemic and tissue-specialized macrophages. FTY720, an FDA-approved drug for multiple sclerosis inhibits TRPM7. However, FTY720 is a prodrug and its metabolite, FTY720-phosphate, is a potent agonist of sphingosine 1-phosphate (S1P) receptors. In this study, we tested non-phosphorylatable FTY720 analogs, which are inert against S1PRs and well toleratedin vivo, for activity against TRPM7 and tissue bioavailability. Using patch clamp electrophysiology, we show that VPC01091.4 and AAL-149 block TRPM7 current at low micromolar concentrations. In culture, they act directly on macrophages to blunt LPS-induced inflammatory cytokine expression, an effect that is predominantly but not solely mediated by TRPM7. We found that VPC01091.4 has significant and rapid accumulation in the brain and lungs, along with direct anti-inflammatory action on alveolar macrophages and microglia. Finally, using a mouse model of endotoxemia, we show VPC01091.4 to be an efficacious anti-inflammatory agent that arrests systemic inflammationin vivo. Together, these findings identify novel small molecule inhibitors that allow TRPM7 channel inhibition independent of S1P receptor targeting. These inhibitors exhibit potent anti-inflammatory properties that are mediated by TRPM7 and likely other molecular targets that remain to be identified.
Detection of mycobacterial pulmonary diseases via breath analysis in clinical practice
Authors: Su Biyi , Feng Yong , Chen Haibin , Zhu Jialou , He Mengqi , Wu Lijuan , Sheng Qing , Guan Ping , Chen Pinru , Kuang Haobin , Li Dexian , Wang Weiyong , Feng Zhiyu , Tan Yigang , Liu Jianxiong , Tan Yaoju 
Published: May 2023

AbstractBackgroundCurrent clinical tests for mycobacterial pulmonary diseases (MPD), such as pulmonary tuberculosis (PTB) and non-tuberculous mycobacteria pulmonary diseases (NTM-PD), are inaccurate, time-consuming, sputum-dependent, and/or costly. We aimed to develop a simple, rapid and accurate breath test for screening and differential diagnosis of MPD patients in clinical settings.MethodsExhaled breath samples were collected from 93 PTB, 68 NTM-PD and 4 PTB&NTM-PD patients, 93 patients with other pulmonary diseases (OPD) and 181 healthy controls (HC), and tested using the online high-pressure photon ionisation time-of-flight mass spectrometer (HPPI-TOF-MS). Machine learning models were trained and blindly tested for the detection of MPD, PTB, NTM-PD, and the discrimination between PTB and NTM-PD, respectively. Diagnostic performance was evaluated by metrics of sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC).ResultsThe breath PTB detection model achieved a sensitivity of 73.5%, a specificity of 85.8%, an accuracy of 82.9%, and an AUC of 0.895 in the blinded test set (n=141). The corresponding metrics for the NTM-PD detection model were 86.4%, 93.2%, 92.1% and 0.972, respectively. For distinguishing PTB from NTM-PD, the model also achieved good performance with sensitivity, specificity, accuracy, and AUC of 85.3%, 81.8%, 83.9% and 0.947, respectively. 22 potential breath biomarkers associated with MPD were putatively identified and discussed, which included 2-furanmethanol, ethanol, 2-butanone, etc.ConclusionsThe developed breathomics-based MPD detection method was demonstrated for the first time with good performance for potential screening and diagnosis of PTB and NTM-PD using a refined operating procedure on the HPPI-TOF-MS platform.
Wiring between close nodes in biological networks evolves more quickly than between distant nodes
Authors: Gil-Gomez Alejandro , Rest Joshua S. 
Published: May 2023

AbstractAs species diverge, a wide range of evolutionary processes lead to changes in protein-protein interaction networks and metabolic networks. The rate at which biological networks evolve is an important question in evolutionary biology. Previous empirical work has focused on interactomes from model organisms to calculate rewiring rates, but this is limited by the relatively small number of species and sparse nature of network data across species. We present a proxy for variation in network topology: variation in drug-drug interactions (DDIs), obtained by studying drug combinations (DCs) across taxa. Here, we propose the rate at which DDIs change across species as an estimate of the rate at which the underlying biological network changes as species diverge. We computed the evolutionary rates of DDIs using previously published data from a high throughput study in gram-negative bacteria. Using phylogenetic comparative methods, we found that DDIs diverge rapidly over short evolutionary time periods, but that divergence saturates over longer time periods. In parallel, we mapped drugs with known targets in protein-protein interaction and co-functional networks. We found that the targets of synergistic DDIs are closer in these networks than other types of DCs and that synergistic interactions have a higher evolutionary rate, meaning that nodes that are closer evolve at a faster rate. Future studies of network evolution may use DC data to gain larger-scale perspectives on the details of network evolution within and between species.
Orthologs of theC. elegansheterochronic genes have divergent functions inC. briggsae
Authors: Ivanova Maria , Moss Eric G. 
Published: May 2023

AbstractThe heterochronic genes ofC. eleganscomprise the best-studied pathway controlling the timing of tissue and organ formation in an animal. To begin to understand the evolution of this pathway and the significance of the relationships among its components, we characterized 11C. briggsaeorthologs ofC. elegansheterochronic genes. Using CRISPR/Cas9, we made a variety of alleles and found that several mutant phenotypes differ in significant ways from those ofC. elegans. Although most mutant orthologs displayed defects in developmental timing, their phenotypes could differ in which stages were affected, the penetrance and expressivity of the phenotypes, or by having additional pleiotropies that were not obviously connected to developmental timing. However, when examining pairwise epistasis and synergistic relationships, we found those paralleled the known relationships between theirC. elegansorthologs, suggesting that the arrangements of these genes in functional modules is conserved, but the modules’ relationships to each other and/or to their targets has drifted since the time of the species’ last common ancestor. Furthermore, our investigation has revealed a relationship to this pathway to other aspects of the animal’s growth and development, including gonad development, that is relevant to both species.
Lean and BIM integration benefits construction management practices in New Zealand
Authors: Likita Ayuba Jerry , Jelodar Mostafa Babaeian , Vishnupriya V , Rotimi James Olabode Bamidele 
Published: May 2023

Purpose
The construction industry is inefficient in terms of quality products, productivity and performance worldwide, including in Australia and New Zealand. The construction industry is becoming more innovative, competitive and complex; and more participants are involved in construction projects. There are new attempts to implement the Lean construction philosophy, integrated project delivery method and building information modelling (BIM) technology in construction industry to improve productivity and efficiency. This paper aims to identify Lean and BIM integration benefits in construction industry globally and in the New Zealand.

Design/methodology/approach
A systematic literature review and case studies were used to identify various benefits of the integrating Lean and BIM in construction industry. It focused on articles published between 1995 and 2021.

Findings
Lean and BIM benefits identified in the study were documented such as benefits over the traditional approach, critically increased efficiency and visualization, better building process, better building performance, mitigating risk and reduce cost. Also, several factors were identified as major benefits such as improved onsite collaboration, better coordination, improve onsite communication, increase productivity, mitigating risk, reducing waste and reduced cost. The study showed integrating Lean and BIM in construction management practice will help reduce several challenges which affect expected goals and customer anticipation. The research outcome ultimately will assist different stakeholders in applying Lean and BIM in construction management practice.

Originality/value
This study practically focused on using the integration of BIM and Lean principles to improve the construction industry productivity and performance.