bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly Sensitive Blocker Displacement Amplification for Detection of Low-Level JAK2V617F Variant
Authors: Wang Zhen , Weller Cailin , Pinto Alessandro , Zhang David Yu , Mularo Frank , Tu Zheng Jin , Cheng Yu-Wei 
Published: February 2023

Abstract

Background
Key criteria in the diagnostic workup and risk stratification for myeloproliferative neoplasms (MPN) include molecular testing for JAK2V617F and other mutant alleles. Multiple methods for quantitatively detecting nucleotide sequence changes exist, but the lower limit of detection can limit identification of the low-level allele fraction of a variant. We evaluated a recently developed blocker displacement amplification (BDA)-based quantitative PCR platform for detection and quantitation of JAK2V617F variant allele fraction (VAF).

Methods
Clinical samples were tested using BDA, next-generation sequencing (NGS), and droplet digital PCR (ddPCR) in a head-to-head comparison of sensitivity and specificity in detecting the JAK2V617F variant. In total, 112 human genomic DNA specimens previously tested for JAK2V617F gene mutation status with NGS were analyzed, including 12 samples with low-level variants with VAF ≤2%, 6 samples with VAF &gt;2%, and 94 samples with no variant previously identified by NGS.

Results
BDA and ddPCR results correlated well across a range of VAFs, with both methods identifying the JAK2V617F variant down to at least 0.05% VAF. NGS of routine sequencing depth was less sensitive, identifying JAK2V617F only at 0.6% VAF.

Conclusions
BDA can provide a cost-effective alternative means to identify low-level variants using instrumentation commonly found in laboratories.
Utility of Direct Specimen Sequencing in Addition to Conventional Testing in Management of Infections in an Urban Referral Health Center
Authors: Saini Vikram , Como James , Abdulmassih Rasha , Min Zaw , Bhanot Nitin 
Published: February 2023

Abstract

Background
Direct specimen sequencing (DSS) offers the promise of enhanced pathogen detection and disease diagnosis.

Methods
A single healthcare network, retrospective chart review over a 3-year period was completed for all cases in which DSS was submitted, in addition to conventional testing (CT) for workup of an infectious disease. We sought to compare results (concordance and discordance) from these 2 techniques in order to evaluate any additional yield from DSS over CT. Additionally, we calculated mean turnaround time (TAT) and average cost for obtaining DSS on all specimens.

Results
A total of 23 patients’ specimens were sent for DSS. DSS and CT concordance occurred in 91% (21/23) of cases. DSS testing was able to identify specific pathogens in 17.4% (4/23) of patients, out of which 4% (1/23) were discordant. The respective mean TAT and total cost per specimen for DSS were 6 days and $821.52 (range $573–$1590), respectively.

Conclusions
In our limited cohort of patients, there was significant concordance between the 2 testing modalities primarily due to negative tests. DSS did not provide significant additional yield in the infectious diagnosis in our cohort compared to CT. Short TAT may provide advantage in the detection of fastidious organisms, but high cost remains a limitation. Larger sample size may reveal a clinically meaningful difference.
Toxicity risk score and clinical decline after adjuvant chemotherapy in older breast cancer survivors
Authors: Ji Jingran , Sun Can-Lan , Cohen Harvey J , Muss Hyman B , Bae Marie , Sedrak Mina S 
Published: February 2023

Abstract

Background
Chemotoxicity risk scores were developed to predict grade 3-5 chemotherapy toxicity in older women with early breast cancer. However, whether these toxicity risk scores are associated with clinically meaningful decline in patient health remains unknown.

Methods
In a prospective study of women aged 65 years and older with stage I-III breast cancer treated with chemotherapy, we assessed chemotoxicity risk using the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score (categorized as low, intermediate, and high). We measured patient health status before (T1) and after (T2) chemotherapy using a clinical frailty index (Deficit Accumulation Index, categorized as robust, prefrail, and frail). The population of interest was robust women at T1. The primary outcome was decline in health status after chemotherapy, defined as a decline in Deficit Accumulation Index from robust at T1 to prefrail or frail at T2. Multivariable logistic regression was used to examine the association between T1 CARG-BC score and decline in health status, adjusted for sociodemographic and clinical characteristics.

Results
Of the 348 robust women at T1, 83 (24%) experienced declining health status after chemotherapy, of whom 63% had intermediate or high CARG-BC scores. After adjusting for sociodemographic and clinical characteristics, women with intermediate (odds ratio = 3.14, 95% confidence interval = 1.60 to 6.14, P &lt; .001) or high (odds ratio = 3.80, 95% confidence interval = 1.35 to 10.67, P = .01) CARG-BC scores had greater odds of decline in health status compared with women with low scores.

Conclusions
In this cohort of older women with early breast cancer, higher CARG-BC scores before chemotherapy were associated with decline in health status after chemotherapy independent of sociodemographic and clinical risk factors.
A celebration of the writing and professional work of Paul Hirst: an introduction
Authors: White Patricia , Bridges David 
Published: February 2023

Abstract
This paper introduces this Special Issue celebrating the writing and professional work of Paul Hirst. The international range of contributors include scholars who knew him and his work in his heyday, as well as younger generations of philosophers of education. In this Introduction the editors, in conversation, first introduce the papers on Hirst’s early work on liberal education and the nature of knowledge, and then go on to discuss his later turn to advocacy of an education centred on social practices and his discussions of the nature of educational theory and teacher education. They consider those papers that refer to his work on the place of the arts in education and those involving detailed exploration of his work in moral and religious education. The extensive nature of his high-level administrative work in London and Cambridge, as well as nationally, is also recognized. A paper based on his personal correspondence reveals the lively man behind the work. An Appendix to this Introduction includes two extensive bibliographies, of Hirst’s writings and of critical discussions of his work.
Earth’s CO2 battle: a view from space
Authors: Cressie Noel , Zammit-Mangion Andrew , Jacobson Josh , Bertolacci Michael 
Published: February 2023

Abstract
Our environment is undergoing rapid change as greenhouse gases warm the planet. Noel Cressie, Andrew Zammit-Mangion, Josh Jacobson, and Michael Bertolacci use WOMBAT, a Bayesian hierarchical statistical framework, to infer the spatio-temporal distribution of CO2 surface fluxes
Meteorin-like Protein and Asprosin Levels in Children and Adolescents with Obesity and Their Relationship with Insulin Resistance and Metabolic Syndrome
Authors: Moradi Nariman , Fadaei Reza , Roozbehkia Maryam , Nourbakhsh Mitra , Nourbakhsh Mona , Razzaghy-Azar Maryam , Larijani Bagher 
Published: February 2023

Abstract

Objective
Two newly discovered adipokines, including Meteorin-like protein (Metrnl) and asprosin, have been implicated in glucose and insulin metabolism. This study aimed to investigate the associations of these adipokines with obesity in children and adolescents.

Methods
This study was performed on 35 normal-weight children and 35 children with obesity. Anthropometric and biochemical parameters were determined. Serum concentrations of Metrnl, asprosin, and insulin were measured using enzyme-linked immunosorbent assay.

Results
Metrnl level was significantly lower in obese children than normal-weight children. Additionally, Metrnl was negatively correlated with body mass index (BMI), insulin, waist-to-hip ratio, and homeostatic model assessment of insulin resistance (HOMA-IR). Our results also revealed that circulating asprosin levels were significantly increased in obese children compared to the control subjects and were positively correlated with BMI, insulin, HOMA-IR, cholesterol, and LDL-C.

Conclusion
Obesity is accompanied by significant alterations in Metrnl and asprosin and therefore these adipokines, especially Metrnl, are suggested as new promising therapeutic targets for obesity and its associated metabolic imbalances.
Fluctuation Electron Microscopy on Amorphous Silicon and Amorphous Germanium
Authors: Radić Dražen , Peterlechner Martin , Posselt Matthias , Bracht Hartmut 
Published: February 2023

AbstractVariable resolution fluctuation electron microscopy experiments were performed on self-ion implanted amorphous silicon and amorphous germanium to analyze the medium-range order. The results highlight that the commonly used pair-persistence analysis is influenced by the experimental conditions. Precisely, the structural correlation length Λ, a metric for the medium-range order length scale in the material, obtained from this particular evaluation varies depending on whether energy filtering is used to acquire the data. In addition, Λ depends on the sample thickness. Both observations can be explained by the fact that the pair-persistence analysis utilizes the experimentally susceptible absolute value of the normalized variance obtained from fluctuation electron microscopy data. Instead, plotting the normalized variance peak magnitude over the electron beam size offers more robust results. This evaluation yields medium-range order with an extent of approximately (1.50 ± 0.50) nm for the analyzed amorphous germanium and around (1.10 ± 0.20) nm for amorphous silicon.
Low-frequency quasi-periodic oscillation in MAXI J1820+070: Revealing distinct Compton and reflection contributions
Authors: Gao Chenxu , Yan Zhen , Yu Wenfei 
Published: February 2023

ABSTRACT
X-ray low-frequency quasi-periodic oscillations (LFQPOs) of black hole X-ray binaries, especially those type-C LFQPOs, are representative timing signal of black hole low/hard state and intermediate state, which has been suspected as to originate due to Lense-Thirring precession of the accretion flow. Here we report an analysis of one of the Insight-HXMT observations of the black hole transient MAXI J1820+070 taken near the flux peak of its hard spectral state during which strong type-C LFQPOs were detected in all three instruments up to photon energies above 150 keV. We obtained and analysed the short time-scale X-ray spectra corresponding to high- and low-intensity phases of the observed LFQPO waveform with a spectral model composed of Comptonization and disc reflection components. We found that the normalization of the spectral model is the primary parameter that varied between the low and high-intensity phases. The variation in the LFQPO flux at the hard X-ray band (≳100 keV) is from the Compton component alone, while the energy-dependent variation in the LFQPO flux at lower energies (≲30 keV) is mainly caused by the reflection component with a large reflection fraction in response to the incident Compton component. The observed X-ray LFQPOs thus should be understood as manifesting the original timing signals or beats in the hard Compton component, which gives rise to additional variability in softer energies due to disc reflection.
Adaptation of Antarctic Icefish Vision to Extreme Environments
Authors: Castiglione Gianni M , Hauser Frances E , Van Nynatten Alexander , Chang Belinda S W 
Published: February 2023

Abstract
Extreme environments, such as Antarctic habitats, present major challenges for many biological processes. Antarctic icefishes (Crynotothenioidea) represent a compelling system to investigate the molecular basis of adaptation to cold temperatures. Here, we explore how the sub-zero habitats of Antarctic icefishes have impacted rhodopsin (RH1) function, the temperature-sensitive dim-light visual pigment found in rod photoreceptors. Using likelihood models and ancestral reconstruction, we find that accelerated evolutionary rates in icefish RH1 underlie unique amino acid mutations absent from other deep-dwelling fishes, introduced before (S160A) and during (V259M) the onset of modern polar conditions. Functional assays reveal that these mutations red-shift rhodopsin spectral absorbance, consistent with spectral irradiance under sea ice. These mutations also lower the activation energy associated with retinal release of the light-activated RH1, and accelerate its return to the dark state, likely compensating for a cold-induced decrease in kinetic rates. These are adaptations in key properties of rhodopsin that mediate rod sensitivity and visual performance in the cold dark seas of the Antarctic.
Using single cell atlas data to reconstruct regulatory networks
Authors: Song Qi , Ruffalo Matthew , Bar-Joseph Ziv 
Published: February 2023

Abstract
Inference of global gene regulatory networks from omics data is a long-term goal of systems biology. Most methods developed for inferring transcription factor (TF)–gene interactions either relied on a small dataset or used snapshot data which is not suitable for inferring a process that is inherently temporal. Here, we developed a new computational method that combines neural networks and multi-task learning to predict RNA velocity rather than gene expression values. This allows our method to overcome many of the problems faced by prior methods leading to more accurate and more comprehensive set of identified regulatory interactions. Application of our method to atlas scale single cell data from 6 HuBMAP tissues led to several validated and novel predictions and greatly improved on prior methods proposed for this task.
Target search by an imported conjugative DNA element for a unique integration site along a bacterial chromosome during horizontal gene transfer
Authors: Arbel-Goren Rinat , McKeithen-Mead Saria A , Voglmaier Dominik , Afremov Idana , Teza Gianluca , Grossman Alan D , Stavans Joel 
Published: February 2023

Abstract
Integrative and conjugative elements (ICEs) are mobile genetic elements that can transfer by conjugation to recipient cells. Some ICEs integrate into a unique site in the genome of their hosts. We studied quantitatively the process by which an ICE searches for its unique integration site in the Bacillus subtilis chromosome. We followed the motion of both ICEBs1 and the chromosomal integration site in real time within individual cells. ICEBs1 exhibited a wide spectrum of dynamical behaviors, ranging from rapid sub-diffusive displacements crisscrossing the cell, to kinetically trapped states. The chromosomal integration site moved sub-diffusively and exhibited pronounced dynamical asymmetry between longitudinal and transversal motions, highlighting the role of chromosomal structure and the heterogeneity of the bacterial interior in the search. The successful search for and subsequent recombination into the integration site is a key step in the acquisition of integrating mobile genetic elements. Our findings provide new insights into intracellular transport processes involving large DNA molecules.
Association of eGFR and mortality with use of a joint model: results of a nationwide study in Iceland
Authors: Jonsson Arnar J , Lund Sigrun H , Eriksen Bjørn O , Palsson Runolfur , Indridason Olafur S 
Published: February 2023

ABSTRACT

Objectives
Prior studies on the association of estimated glomerular filtration rate (eGFR) and mortality have failed to include methods to account for repeated eGFR determinations. The aim of this study was to estimate the association between eGFR and mortality in the general population in Iceland employing a joint model.

Methods
We obtained all serum creatinine and urine protein measurements from all clinical laboratories in Iceland in the years 2008–16. Clinical data were obtained from nationwide electronic medical records. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and categorized as follows: 0–29, 30–44, 45–59, 60–74, 75–89, 90–104 and &gt;104 mL/min/1.73 m2. A multiple imputation method was used to account for missing urine protein data. A joint model was used to assess risk of all-cause mortality.

Results
We obtained 2 120 147 creatinine values for 218 437 individuals, of whom 84 364 (39%) had proteinuria measurements available. Median age was 46 (range 18–106) years and 47% were men. Proteinuria associated with increased risk of death for all eGFR categories in persons of all ages. In persons ≤65 years, the lowest risk was observed for eGFR of 75–89 mL/min/1.73 m2 without proteinuria. For persons aged &gt;65 years, the lowest risk was observed for eGFR of 60–74 mL/min/1.73 m2 without proteinuria. eGFR of 45–59 mL/min/1.73 m2 without proteinuria did not associate with increased mortality risk in this age group. eGFR &gt;104 mL/min/1.73 m2 associated with increased mortality.

Conclusions
These results lend further support to the use of age-adapted eGFR thresholds for defining chronic kidney disease. Very high eGFR needs to be studied in more detail with regard to mortality.
Resection of NAFLD/NASH-related Hepatocellular Carcinoma (HCC): Clinical Features and Outcomes Compared with HCC Due to Other Etiologies
Authors: Pal Chaudhary Surendra , Reyes Stephanie , Chase Matthew L , Govindan Aparna , Zhao Lei , Luther Jay , Bhan Irun , Bethea Emily , Franses Joseph W , Paige Walsh Elizabeth , Anne Dageford Leigh , Kimura Shoko , Elias Nahel , Yeh Heidi , Markman James , Bozorgzadeh Adel , Tanabe Kenneth , Ferrone Cristina , Zhu Andrew X , Andersson Karin , Thiim Michael , Antonio Catalano Onofrio , Kambadakone Avinash , Vagefi Parsia A , Qadan Motaz , Pratt Daniel , Hashemi Nikroo , Corey Kathleen E , Misdraji Joseph , Goyal Lipika , Clark Jeffrey W 
Published: February 2023

AbstractBackgroundNon-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the leading causes of hepatocellular carcinoma (HCC) worldwide. Limited data exist on surgical outcomes for NAFLD/NASH-related HCC compared with other HCC etiologies. We evaluated differences in clinicopathological characteristics and outcomes of patients undergoing surgical resection for NAFLD/NASH-associated HCC compared with other HCC etiologies.MethodsDemographic, clinicopathological features, and survival outcomes of patients with surgically resected HCC were collected. NAFLD activity score (NAS) and fibrosis score were assessed by focused pathologic review in a subset of patients.ResultsAmong 492 patients screened, 260 met eligibility (NAFLD/NASH [n = 110], and other etiologies [n = 150]). Median age at diagnosis was higher in the NAFLD/NASH HCC cohort compared with the other etiologies cohort (66.7 vs. 63.4 years, respectively, P = .005), with an increased percentage of female patients (36% vs. 18%, P = .001). NAFLD/NASH-related tumors were more commonly &gt;5 cm (66.0% vs. 45%, P = .001). There were no significant differences in rates of lymphovascular or perineural invasion, histologic grade, or serum AFP levels. The NAFLD/NASH cohort had lower rates of background liver fibrosis, lower AST and ALT levels, and higher platelet counts (P &lt; .01 for all). Median overall survival (OS) was numerically shorter in NAFLD/NASH vs other etiology groups, however, not statistically significant.ConclusionsPatients with NAFLD/NASH-related HCC more commonly lacked liver fibrosis and presented with larger HCCs compared with patients with HCC from other etiologies. No differences were seen in rates of other high-risk features or survival. With the caveat of sample size and retrospective analysis, this supports a similar decision-making approach regarding surgical resection for NAFLD/NASH and other etiology-related HCCs.
The Effects of Partial Employment Protection Reforms: Evidence from Italy
Authors: Daruich Diego , Di Addario Sabrina , Saggio Raffaele 
Published: February 2023

Abstract
We combine matched employer–employee data with firms’ financial records to study a 2001 Italian reform that lifted constraints on the employment of temporary contract workers while maintaining rigid employment protection regulations for employees hired under permanent contracts. Exploiting the staggered implementation of the reform across different collective bargaining agreements, we find that this policy change led to an increase in the share of temporary contracts but failed to raise employment. The reform had both winners and losers. Firms are the main winners as the reform was successful in decreasing labor costs, leading to higher profits. By contrast, young workers are the main losers since their earnings were substantially depressed following the policy change. Rent-sharing estimates show that temporary workers receive only two-thirds of the rents shared by firms with permanent workers, helping explain most of the labor costs and earnings reductions caused by the reform.
Drought impairs herbivore-induced volatile terpene emissions by ponderosa pine but not through constraints on newly assimilated carbon
Authors: Malone Shealyn C , Simonpietri Austin , Knighton Walter B , Trowbridge Amy M 
Published: February 2023

Abstract
Volatile terpenes serve multiple biological roles including tree resistance against herbivores. The increased frequency and severity of drought stress observed in forests across the globe may hinder trees from producing defense-related volatiles in response to biotic stress. To assess how drought-induced physiological stress alters volatile emissions alone and in combination with a biotic challenge, we monitored pre-dawn water potential, gas-exchange, needle terpene concentrations and terpene volatile emissions of ponderosa pine (Pinus ponderosa) saplings during three periods of drought and in response to simulated herbivory via methyl jasmonate application. Although 3-, 6- and 7-week drought treatments reduced net photosynthetic rates by 20, 89 and 105%, respectively, the magnitude of volatile fluxes remained generally resistant to drought. Herbivore-induced emissions, however, exhibited threshold-like behavior; saplings were unable to induce emissions above constitutive levels when pre-dawn water potentials were below the approximate zero-assimilation point. By comparing compositional shifts in emissions to needle terpene concentrations, we found evidence that drought effects on constitutive and herbivore-induced volatile flux and composition are primarily via constraints on the de novo fraction, suggesting that reduced photosynthesis during drought limits the carbon substrate available for de novo volatile synthesis. However, results from a subsequent 13CO2 pulse-chase labeling experiment then confirmed that both constitutive (&lt;3% labeled) and herbivore-induced (&lt;8% labeled) de novo emissions from ponderosa pine are synthesized predominantly from older carbon sources with little contribution from new photosynthates. Taken together, we provide evidence that in ponderosa pine, drought does not constrain herbivore-induced de novo emissions through substrate limitation via reduced photosynthesis, but rather through more sophisticated molecular and/or biophysical mechanisms that manifest as saplings reach the zero-assimilation point. These results highlight the importance of considering drought severity when assessing impacts on the herbivore-induced response and suggest that drought-altered volatile metabolism constrains induced emissions once a physiological threshold is surpassed.