bluuebunny/crossref_metadata_2025 huggingface dataset:
An archaeal Cas3 protein facilitates rapid recovery from DNA damage
Authors: Miezner Guy , Turgeman-Grott Israela , Zatopek Kelly M , Gardner Andrew F , Reshef Leah , Choudhary Deepak K , Alstetter Martina , Allers Thorsten , Marchfelder Anita , Gophna Uri
Published: February 2023

CRISPR-Cas systems provide heritable acquired immunity against viruses to archaea and bacteria. Cas3 is a CRISPR-associated protein that is common to all Type I systems, possesses both nuclease and helicase activities, and is responsible for degradation of invading DNA. Involvement of Cas3 in DNA repair had been suggested in the past, but then set aside when the role of CRISPR-Cas as an adaptive immune system was realized. Here we show that in the model archaeon Haloferax volcanii a cas3 deletion mutant exhibits increased resistance to DNA damaging agents compared with the wild-type strain, but its ability to recover quickly from such damage is reduced. Analysis of cas3 point mutants revealed that the helicase domain of the protein is responsible for the DNA damage sensitivity phenotype. Epistasis analysis indicated that cas3 operates with mre11 and rad50 in restraining the homologous recombination pathway of DNA repair. Mutants deleted for Cas3 or deficient in its helicase activity showed higher rates of homologous recombination, as measured in pop-in assays using non-replicating plasmids. These results demonstrate that Cas proteins act in DNA repair, in addition to their role in defense against selfish elements and are an integral part of the cellular response to DNA damage.
‘Queering the Textual Politics of Alba de Céspedes’s Prima e dopo’
Authors: Gabriele Tommasina
Published: February 2023

Alba de Céspedes’s Prima e dopo (1955) has generally been interpreted within the framework of the Italian Resistance and the subsequent disillusionment of Resistance ideals. While taking this interpretation into account, I argue that the central narrative of desire in Prima e dopo is not Irene’s relationship with her lover, Pietro, but Irene’s subversive desire for her maid, Erminia. I analyse and challenge some of the mechanisms and methodologies of Italian literary historiography that create and reproduce the disregard and devaluation of queer desire, specifically lesbian desire, in Italian narratives, and I identify scholarly, cultural and textual mechanisms that have rendered queer desire in Prima e dopo invisible. In sum, this article contributes to an Italian lesbian archive and lesbian literary historiography and argues that a queer reading of Erminia’s role in Prima e dopo enhances our understanding of the post-Resistance framework of the novel and its radical politics.
Chromosome-level genome and the identification of sex chromosomes in Uloborus diversus
Authors: Miller Jeremiah , Zimin Aleksey V , Gordus Andrew
Published: February 2023

The orb web is a remarkable example of animal architecture that is observed in families of spiders that diverged over 200 million years ago. While several genomes exist for araneid orb-weavers, none exist for other orb-weaving families, hampering efforts to investigate the genetic basis of this complex behavior. Here we present a chromosome-level genome assembly for the cribellate orb-weaving spider Uloborus diversus. The assembly reinforces evidence of an ancient arachnid genome duplication and identifies complete open reading frames for every class of spidroin gene, which encode the proteins that are the key structural components of spider silks. We identified the 2 X chromosomes for U. diversus and identify candidate sex-determining loci. This chromosome-level assembly will be a valuable resource for evolutionary research into the origins of orb-weaving, spidroin evolution, chromosomal rearrangement, and chromosomal sex determination in spiders.
Rationality of Real Conic Bundles With Quartic Discriminant Curve
Authors: Ji Lena , Ji Mattie
Published: February 2023

We study real double covers of $\mathbb P^{1}\times \mathbb P^{2}$ branched over a $(2,2)$-divisor, which are conic bundles with smooth quartic discriminant curve by the second projection. In each isotopy class of smooth plane quartics, we construct examples where the total space is $\mathbb R$-rational. For five of the six isotopy classes, we construct $\mathbb C$-rational examples with obstructions to rationality over $\mathbb R$, and for the sixth class, we show that the models we consider are all rational. Moreover, for three of the five classes with irrational members, we characterize rationality using the real locus and the intermediate Jacobian torsor obstruction of Hassett–Tschinkel and Benoist–Wittenberg. These double cover models were introduced by Frei, Sankar, Viray, Vogt, and the first author, who determined explicit descriptions for their intermediate Jacobian torsors.
Efficacy comparison of 3CL protease inhibitors ensitrelvir and nirmatrelvir against SARS-CoV-2in vitroandin vivo
Authors: Kuroda Takayuki , Nobori Haruaki , Fukao Keita , Baba Kaoru , Matsumoto Kazumi , Yoshida Shinpei , Tanaka Yukari , Watari Ryosuke , Oka Ryoko , Kasai Yasuyuki , Inoue Kae , Kawashima Sho , Shimba Alice , Hayasaki-Kajiwara Yoko , Tanimura Miki , Zhang Qianhui , Tachibana Yuki , Kato Teruhisa , Shishido Takao
Published: February 2023

Objectives

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become established in the human population, making the need to develop safe and effective treatments critical. We have developed the small-molecule antiviral ensitrelvir, which targets the 3C-like (3CL) protease of SARS-CoV-2. This study evaluated the in vitro and in vivo efficacy of ensitrelvir compared with that of another SARS-CoV-2 3CL PI, nirmatrelvir.

Methods

Cultured cells, BALB/cAJcl mice and Syrian hamsters were infected with various SARS-CoV-2 strains, including the ancestral strain WK-521, mouse-adapted SARS-CoV-2 (MA-P10) strain, Delta strain and Omicron strain. Ensitrelvir efficacy was compared with that of nirmatrelvir. Effective concentrations were determined in vitro based on virus-induced cytopathic effects, viral titres and RNA levels. Lung viral titres, nasal turbinate titres, body-weight changes, and animal survival were also monitored.

Results

Ensitrelvir and nirmatrelvir showed comparable antiviral activity in multiple cell lines. Both ensitrelvir and nirmatrelvir reduced virus levels in the lungs of mice and the nasal turbinates and lungs of hamsters. However, ensitrelvir demonstrated comparable or better in vivo efficacy than that of nirmatrelvir when present at similar or slightly lower unbound-drug plasma concentrations.

Conclusions

Direct in vitro and in vivo efficacy comparisons of 3CL PIs revealed that ensitrelvir demonstrated comparable in vitro efficacy to that of nirmatrelvir in cell culture and exhibited equal to or greater in vivo efficacy in terms of unbound-drug plasma concentration in both animal models evaluated. The results suggest that ensitrelvir may become an important resource for treating individuals infected with SARS-CoV-2.
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

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 >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

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

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 < .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

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

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
What’s in a name?
Authors: Otto Philipp , Otto Philipp
Published: February 2023

Does an author’s name affect their chances of being cited? Here, Philipp Otto and Philipp Otto - yes, two researchers with the same name - investigate the impact of academic authorship characteristics on article citations
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

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

Variable 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

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

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

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

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

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 >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 >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 >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

Background

Non-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.

Methods

Demographic, 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.

Results

Among 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 >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 < .01 for all). Median overall survival (OS) was numerically shorter in NAFLD/NASH vs other etiology groups, however, not statistically significant.

Conclusions

Patients 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

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

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 (<3% labeled) and herbivore-induced (<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.
Differentiation of Cool-Virulent Strains in the Ralstonia solanacearum Species Complex by Melt Curve of a DNA Fragment from Effector Gene Rips1
Authors: Schachterle J. K. , Huang Q.
Published: February 2023

The Ralstonia solanacearum species complex ( Rssc) causes bacterial wilt diseases across hundreds of plant species. Phylogenetic analysis of DNA sequences has allowed the grouping of Rssc strains into phylotypes based on genetic relatedness. Although specific phenotypes are associated with corresponding phylotypes, the molecular bases for these differences are not always well understood. The complex trait of cool-virulence that allows several members of phylotype II to cause disease at temperatures below 25°C is one of these poorly understood traits. Here, we report that a 96-bp DNA fragment from a gene encoding the type III secretion system effector protein RipS1, which was recently reported to play a role in the cool-virulence phenotype, has a melting temperature that varies based on the strain of origin. By testing 81 Rssc strains with melt-curve analysis, we found a bimodal distribution with clear separation between the group of strains with a melting temperature below 87.5°C that includes phylotypes I, III, and IV strains and the group with a melting temperature above 87.5°C that includes all 35 tested select agent race 3 biovar 2 (phylotype IIB sequevars 1 and 2) and seven phylotype IIB sequevar 4 strains, previously known to possess cool-virulence capability, with a few exceptions. This provides further support that sequence differences in this effector differentiate cool-virulent strains from non-cool-virulent strains and show potential for use as a marker in continued studies of the cool-virulence phenotype.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2023.
Lateral Mass Screws Versus Pedicle Screws at C7 - Reoperation Rates for Adjacent Segment Disease (Operative ASD) and Nonunions (Operative Nonunions) in Posterior Cervical Fusions
Authors: Brara Harsimran S. , Royse Kathryn E. , Fennessy Jacob , Harris Jessica E. , Guppy Kern H.
Published: February 2023

Study Design.

A retrospective cohort study.

Objective.

To determine if there a difference in reoperation rates for symptomatic adjacent segment disease (operative ASD) and symptomatic nonunions (operative nonunions) in posterior cervical fusions (PCFs) stopping at C7 using either lateral mass screws (LMS) or cervical pedicle screws (CPS) at C7.

Summary of Background Data.

Stopping PCFs at C7 has been controversial because of the risks of adjacent segment disease or nonunions. The two commonly used fixation techniques at the C7 level are LMS and CPS.

Methods.

A retrospective analysis from the Kaiser Permanente Spine Registry identified a cohort of patients with cervical degenerative disc disease who underwent primary PCFs stopping at C7 with either LMS or CPS at C7. Demographic and operative data were extracted from the registry and operative ASD and operative nonunions were adjudicated via chart review. Patients were followed until validated operative ASD or nonunion, membership termination, death, or end of study (03/31/2022). Descriptive statistics and multivariable Cox proportional hazards models were calculated for operative ASDs and operative nonunions.

Results.

We found 481 patients with PCFs stopping at C7 with either LMS (n=347) or CPS (n=134) at C7 with average follow-up time of 5.6 (±3.8) years, time to operative ASD of 3.0 (±2.8) years and to operative nonunion of 1.2 (±0.7) years. There were 11 operative ASDs (LMS=8, CPS=3) and 8 operative nonunions (LMS=4, CPS=4). There was no statistical difference between patients stopping at C7 with LMS versus CPS for operative ASDs (HR: 0.68, 95% CI=0.17-2.77,P=0.60) or operative nonunions (HR: 2.09, 95% CI=0.45-8.58,P=0.37).

Conclusion.

A large cohort of patients with PCFs stopping at C7 with an average follow-up of > 5 years found no statistical difference in reoperation rates for symptomatic ASD (operative ASD) or operative nonunion using either LMS or CPS at C7.
Age Moderates the Effect of Obesity on Mortality Risk in Critically Ill Patients With COVID-19: A Nationwide Observational Cohort Study*
Authors: den Uil Corstiaan A. , Termorshuizen Fabian , Rietdijk Wim J. R. , Sablerolles Roos S. G. , van der Kuy Hugo P. M. , Haas Lenneke E. M. , van der Voort Peter H. J. , de Lange Dylan W. , Pickkers Peter , de Keizer Nicolette F. ,   the Dutch COVID-19 Research Consortium
Published: February 2023

OBJECTIVES:

A high body mass index (BMI) is associated with an unfavorable disease course in COVID-19, but not among those who require admission to the ICU. This has not been examined across different age groups. We examined whether age modifies the association between BMI and mortality among critically ill COVID-19 patients.

DESIGN:

An observational cohort study.

SETTING:

A nationwide registry analysis of critically ill patients with COVID-19 registered in the National Intensive Care Evaluation registry.

PATIENTS:

We included 15,701 critically ill patients with COVID-19 (10,768 males [68.6%] with median [interquartile range] age 64 yr [55–71 yr]), of whom 1,402 (8.9%) patients were less than 45 years.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

In the total sample and after adjustment for age, gender, Acute Physiology and Chronic Health Evaluation IV, mechanical ventilation, and use of vasoactive drugs, we found that a BMI greater than or equal to 30 kg/m2 does not affect hospital mortality (adjusted odds ratio [ORadj] = 0.98; 95% CI, 0.90–1.06; p = 0.62). For patients less than 45 years old, but not for those greater than or equal to 45 years old, a BMI greater than or equal to 30 kg/m2 was associated with a lower hospital mortality (ORadj = 0.59; 95% CI, 0.36–0.96; p = 0.03).

CONCLUSIONS:

A higher BMI may be favorably associated with a lower mortality among those less than 45 years old. This is in line with the so-called “obesity paradox” that was established for other groups of critically ill patients in broad age ranges. Further research is needed to understand this favorable association in young critically ill patients with COVID-19.
Early Fractional Ablative Laser for Skin Cancer Excision Scars: A Randomized Split-Scar Study
Authors: Lin Matthew J. , Dubin Danielle P. , Torbeck Richard L. , Bernstein Daniel M. , Nabatian Adam , Dolan Christopher K. , Bacigalupi Robert , Zade John , Zheng Zhong , Desman Garrett , Khorasani Hooman
Published: February 2023

BACKGROUND

Fractional ablative laser resurfacing has been shown to improve the final cosmetic appearance of surgical scars, but optimal timing is unknown.

OBJECTIVE

To compare surgical scars treated with fractional carbon dioxide (CO2) laser performed on Day 0 and Day 14.

METHODS

Prospective, randomized, split-scar, physician-blinded study of 30 surgical scars on the limbs. Scars halves received fractional CO2 laser on either Day 0 or Day 14. Scar assessment at 6 months evaluated patient preference, physician modified Manchester Scar Scale (MMSS) score, and quantitative scar analysis on histology (fractal dimension [FD] and lacunarity [L] analysis).

RESULTS

There was no significant difference in patient assessment (54% preferred Day 0 side, 46% preferred Day 14 side, p = .58) or physician assessment (mean MMSS 8.4 for Day 0 vs 8.7 for Day 14, p = .28). Fractal dimensions were similar for both interventions (mean 1.778 for Day 0 vs 1.781 for Day 14, p = .80). Lacunarity was similar for both interventions (mean 0.368 for Day 0 vs 0.345 for Day 14, p = .44).

LIMITATIONS

Single-center study with wounds limited to limbs of skin Phototype I-II subjects; 4 of whom were lost to follow-up.

CONCLUSION

Intraoperative CO2 laser is noninferior to Day 14 laser resurfacing for surgical scar treatment.
THREE-DIMENSIONAL HEADS-UP VITRECTOMY VERSUS CONVENTIONAL MICROSCOPIC VITRECTOMY FOR PATIENTS WITH EPIRETINAL MEMBRANE
Authors: Kim Dong Ju , Kim Dong Geun , Park Kyu Hyung
Published: February 2023

Purpose:

To investigate the efficacy and safety of 3D heads-up display (3D-HUD) vitrectomy compared with conventional microscopy (CM) vitrectomy in epiretinal membrane (ERM) surgery.

Methods:

Epiretinal membrane removal with or without internal limiting membrane (ILM) peeling was performed using a 3D-HUD or CM system. The mean changes in best-corrected visual acuity (BCVA) and in central macular thickness (CMT) and postoperative complications were assessed.

Results:

Baseline demographics were comparable except for the follow-up period. Both BCVA and CMT improved at the final visit (all P < 0.05). The ERM recurrence and dissociated optic nerve fiber layer (DONFL) rates were lower in the 3D group (both P < 0.05). conventional microscopic vitrectomy (odds ratio [OR] = 12.86, P = 0.02) and absence of ILM peeling (OR = 45.25, P < 0.05) were associated with ERM recurrence. In the DONFL, CM vitrectomy (OR = 1.98, <0.05) and combined phacovitrectomy (OR = 2.33, P = 0.03) were analyzed as risk factors for DONFL.

Conclusion:

The improvement in BCVA and CMT in ERM surgery using a 3D-HUD is comparable with that of CM vitrectomy, with a significantly low rate of ERM recurrence and DONFL occurrence. Therefore, 3D vitrectomy might have an advantage for ERM surgery.
Comparison of Pre-Descemet Endothelial Keratoplasty and Descemet Membrane Endothelial Keratoplasty in Endothelial Decompensation
Authors: Shanmugam Chandradevi , Agarwal Rinky , Asif Mohamed Ibrahime , Bafna Rahul Kumar , Maharana Prafulla Kumar , Agarwal Tushar , Sinha Rajesh , Titiyal Jeewan Singh , Sharma Namrata
Published: February 2023

Purpose:

The purpose of this study was to compare the outcomes of pre-Descemet endothelial keratoplasty (PDEK) and Descemet membrane endothelial keratoplasty (DMEK) in cases of endothelial decompensation.

Methods:

This was a prospective, randomized, interventional study conducted at a tertiary eye hospital in North India. Thirty eyes of 28 patients with corneal decompensation were randomly subjected to PDEK (n = 15 eyes) and DMEK (n = 15 eyes). Preoperative demographic details, surgical indications, uncorrected distance visual acuity, corrected distance visual acuity, contrast sensitivity, anterior and posterior segment details, intraocular pressure, central corneal thickness, endothelial cell count, and corneal aberrometry tracing on wavefront analysis were recorded. Patients were followed up for 6 months postsurgery. Visual and graft survival outcomes were assessed.

Results:

Intraoperatively, a surgeon reported better ease of preparation and intracameral handling with PDEK grafts. Both groups showed comparable improvement in visual acuity, contrast, and high-order aberrations. A decrease in central corneal thickness was significantly higher in DMEK (196 ± 26 vs. 140 ± 14 μm) patients. DMEK grafts were significantly thinner than PDEK grafts at the 6-month follow-up (16 ± 2.17 vs. 27.2 ± 1.93 μm). Endothelial cell loss (35% in DMEK vs. 33.4% in PDEK, P = 0.48) and rise of intraocular pressure (from 15.33 ± 2.85 mm Hg to 15.53 ± 2.2 mm Hg in the DMEK group vs. from 14.6 ± 1.99 mm Hg to 16.2 ± 1.43 mm Hg in the PDEK group) were comparable. Rebubbling rates were higher in the DMEK group (3/15, 20%) compared with the PDEK group (1/15, 6.66%; P = 0.165).

Conclusions:

DMEK and PDEK were comparable for both quantitative and qualitative visual outcomes and anatomically for graft survival at the 6-month follow-up.
Feasibility Testing of the RT Cardiac Systems Percutaneous Mechanical Circulatory Support Device
Authors: Monreal Gretel , Koenig Steven C. , Taskin Mustafa Ertan , Shambaugh Charles , LaRose Jeffrey A. , Slaughter Mark S.
Published: February 2023

RT Cardiac Systems (RTCS, Raleigh, NC) is developing an intravascular percutaneous mechanical circulatory support (pMCS) device drive system for use during high-risk percutaneous coronary intervention and emergent cardiogenic shock. The proprietary pMCS device (US patent 10,780,206) consists of a miniaturized axial flow pump with an integrated motor connected via a short flexible drive system. This novel flexible drive system creates a flexible pump that is advantageous for percutaneous placement and conforming to anatomy. This design also has the benefit of not requiring a continuous external lubrication source. In this article, we present engineering development and feasibility testing of the prototype pMCS system. Computational fluid dynamics (CFD) modeling was performed to evaluate candidate blade set designs (impeller leading and trailing edges, diffuser) and predict hydrodynamic performance and hemolysis risk. Bench testing of candidate lip seal designs (radial interference, durometer, and seal angle) was evaluated for leak rate. Two 16Fr prototype devices were then fabricated and tested in a static mock flow loop. Experimental testing demonstrated 3 L/min flow against 110 mmHg and 4 L/min flow against 80 mmHg, which matched the CFD-predicted hydrodynamic performance. These results demonstrate feasibility of the engineering design and performance of the prototype devices.
Apixaban Anticoagulation in Children and Young Adults Supported With the HeartMate 3 Ventricular Assist Device
Authors: Kobayashi Ryan L. , Cetatoiu Maria A. , Esteso Paul , Ventresco Courtney , Hawkins Beth , Daly Kevin P. , Blume Elizabeth D. , Fynn-Thompson Francis , VanderPluym Christina
Published: February 2023

There is a growing population of pediatric and adult patients supported with the HeartMate 3 ventricular assist device (HM3 VAD) all of whom require anticoagulation. Apixaban is an anticoagulant requiring less testing than warfarin which has been shown to be effective in other indications. We report five pediatric and young adult patients managed on HM3 VAD with apixaban anticoagulation for 1589 days of VAD support between January 6, 2019 and January 7, 2022. The median age was 17 years and the weight was 69 kg. Four patients had congenital heart disease (2 single-ventricle Fontan circulation, and 2 biventricular circulations) and one had dilated cardiomyopathy. Apixaban was initiated at a median of 7 days postoperatively and doses were titrated based on peak apixaban-specific anti-Xa chromogenic analysis levels (goal 150–250 ng/ml). All patients received aspirin 81 mg daily. There was one major hemocompatibility-related event observed (outflow graft thrombus in the setting of medication nonadherence and chronic VAD infection); there was no major bleeding, death, or stroke. Three patients underwent heart transplantation and two remain on VAD support. In this limited series, apixaban paired with a level-based dosing regimen and low-dose aspirin provided safe and effective antithrombosis with only one hemocompatibility-related event related to medication non-adherence.
Bayesian penalized likelihood PET reconstruction impact on quantitative metrics in diffuse large B-cell lymphoma
Authors: Young Jason R. , Mugu Vamshi K. , Johnson Geoffrey B. , Ehman Eric C. , Packard Annie T. , Homb Andrew C. , Nathan Mark A. , Thanarajasingam Gita , Kemp Bradley J.
Published: February 2023

Evaluate the quantitative, subjective (Deauville score [DS]) and reader agreement differences between standard ordered subset expectation maximization (OSEM) and Bayesian penalized likelihood (BPL) positron emission tomography (PET) reconstruction methods. A retrospective review of 104 F-18 fluorodeoxyglucose PET/computed tomography (CT) exams among 52 patients with diffuse large B-cell lymphoma. An unblinded radiologist moderator reviewed both BPL and OSEM PET/CT exams. Four blinded radiologists then reviewed the annotated cases to provide a visual DS for each annotated lesion. Significant (P < .001) differences in BPL and OSEM PET methods were identified with greater standard uptake value (SUV) maximum and SUV mean for BPL. The DS was altered in 25% of cases when BPL and OSEM were reviewed by the same radiologist. Interobserver DS agreement was higher for OSEM (>1 cm lesion = 0.89 and ≤1 cm lesion = 0.84) compared to BPL (>1 cm lesion = 0.85 and ≤1 cm lesion = 0.81). Among the 4 readers, average intraobserver visual DS agreement between OSEM and BPL was 0.67 for lesions >1cm and 0.4 for lesions ≤1 cm. F-18 Fluorodeoxyglucose PET/CT of diffuse large B-cell lymphoma reconstructed with BPL has higher SUV values, altered DSs and reader agreement when compared to OSEM. This report finds volumetric PET measurements such as metabolic tumor volume to be similar between BPL and OSEM PET reconstructions. Efforts such as adoption of European Association Research Ltd accreditation should be made to harmonize PET data with an aim at balancing the need for harmonization and sensitivity for lesion detection.