bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of polar circumstellar discs in binary star systems
Authors: Smallwood Jeremy L , Martin Rebecca G , Lubow Stephen H
Published: February 2023

We investigate the flow of material from highly misaligned and polar circumbinary discs that feed the formation of circumstellar discs around each binary component. With 3D hydrodynamic simulations we consider equal mass binaries with low eccentricity. We also simulate inclined test particles and highly misaligned circumstellar discs around one binary component for comparison. During Kozai–Lidov (KL) cycles, the circumstellar disc structure is altered through exchanges of disc eccentricity with disc tilt. Highly inclined circumstellar discs and test particles around individual binary components can experience very strong KL oscillations. The continuous accretion of highly misaligned material from the circumbinary disc allows the KL oscillations of circumstellar discs to be long-lived. In this process, the circumbinary material is continuously delivered with a high inclination to the lower inclination circumstellar discs. We find that the simulation resolution is important for modelling the longevity of the KL oscillations. An initially polar circumbinary disc forms nearly polar, circumstellar discs that undergo KL cycles. The gas steams accreting onto the polar circumstellar discs vary in tilt during each binary orbital period, which determines how much material is accreted onto the discs. The long-lived KL cycles in polar circumstellar discs may lead to the formation of polar S-type planets in binary star systems.
The deconvolved distribution estimator: enhancing reionization-era CO line-intensity mapping analyses with a cross-correlation analogue for one-point statistics
Authors: Chung Dongwoo T , Bangari Ishika , Breysse Patrick C , Ihle Håvard T , Bond J Richard , Dunne Delaney A , Padmanabhan Hamsa , Philip Liju , Rennie Thomas J , Viero Marco P ,   COMAP Collaboration
Published: February 2023

We present the deconvolved distribution estimator (DDE), an extension of the voxel intensity distribution (VID), in the context of future observations proposed as part of the CO Mapping Array Project (COMAP). The DDE exploits the fact that the observed VID is a convolution of correlated signal intensity distributions and uncorrelated noise or interloper intensity distributions. By deconvolving the individual VID of two observables away from their joint VID in a Fourier-space operation, the DDE suppresses sensitivity to interloper emission while maintaining sensitivity to correlated components. The DDE thus improves upon the VID by reducing the relative influence of uncorrelated noise and interloper biases, which is useful in the context of COMAP observations that observe different rotational transitions of CO from the same comoving volume in different observing frequency bands. Fisher forecasts suggest that the theoretical sensitivity in the DDE allows significant improvements in constraining power compared to either the cross power spectrum or the individual VID data, and matches the constraining power of the combination of all other one- and two-point summary statistics. Future work should further investigate the covariance and model-dependent behaviour of this novel one-point cross-correlation statistic.
Origin and Evolution of Marsupial-specific Imprinting Clusters Through Lineage-specific Gene Duplications and Acquisition of Promoter Differential Methylation
Authors: Cao Wenqi , Douglas Kory C , Samollow Paul B , VandeBerg John L , Wang Xu , Clark Andrew G
Published: February 2023

Genomic imprinting is a parent-of-origin-specific expression phenomenon that plays fundamental roles in many biological processes. In animals, imprinting is only observed in therian mammals, with ∼200 imprinted genes known in humans and mice. The imprinting pattern in marsupials has been minimally investigated by examining orthologs to known eutherian imprinted genes. To identify marsupial-specific imprinting in an unbiased way, we performed RNA-seq studies on samples of fetal brain and placenta from the reciprocal cross progeny of two laboratory opossum stocks. We inferred allele-specific expression for >3,000 expressed genes and discovered/validated 13 imprinted genes, including three previously known imprinted genes, Igf2r, Peg10, and H19. We estimate that marsupials imprint ∼60 autosomal genes, which is a much smaller set compared with eutherians. Among the nine novel imprinted genes, three noncoding RNAs have no known homologs in eutherian mammals, while the remaining genes have important functions in pluripotency, transcription regulation, nucleolar homeostasis, and neural differentiation. Methylation analyses at promoter CpG islands revealed differentially methylated regions in five of these marsupial-specific imprinted genes, suggesting that differential methylation is a common mechanism in the epigenetic regulation of marsupial imprinting. Clustering and co-regulation were observed at marsupial imprinting loci Pou5f3-Npdc1 and Nkrfl-Ipncr2, but eutherian-type multi-gene imprinting clusters were not detected. Also differing from eutherian mammals, the brain and placenta imprinting profiles are remarkably similar in opossums, presumably due to the shared origin of these organs from the trophectoderm. Our results contribute to a fuller understanding of the origin, evolution, and mechanisms of genomic imprinting in therian mammals.
Jewel Beetle Opsin Duplication and Divergence Is the Mechanism for Diverse Spectral Sensitivities
Authors: Sharkey Camilla R , Blanco Jorge , Lord Nathan P , Wardill Trevor J
Published: February 2023

The evolutionary history of visual genes in Coleoptera differs from other well-studied insect orders, such as Lepidoptera and Diptera, as beetles have lost the widely conserved short-wavelength (SW) insect opsin gene that typically underpins sensitivity to blue light (∼440 nm). Duplications of the ancestral ultraviolet (UV) and long-wavelength (LW) opsins have occurred in many beetle lineages and have been proposed as an evolutionary route for expanded spectral sensitivity. The jewel beetles (Buprestidae) are a highly ecologically diverse and colorful family of beetles that use color cues for mate and host detection. In addition, there is evidence that buprestids have complex spectral sensitivity with up to five photoreceptor classes. Previous work suggested that opsin duplication and subfunctionalization of the two ancestral buprestid opsins, UV and LW, has expanded sensitivity to different regions of the light spectrum, but this has not yet been tested. We show that both duplications are likely unique to Buprestidae or the wider superfamily of Buprestoidea. To directly test photopigment sensitivity, we expressed buprestid opsins from two Chrysochroa species in Drosophila melanogaster and functionally characterized each photopigment type as UV- (356–357 nm), blue- (431–442 nm), green- (507–509 nm), and orange-sensitive (572–584 nm). As these novel opsin duplicates result in significantly shifted spectral sensitivities from the ancestral copies, we explored spectral tuning at four candidate sites using site-directed mutagenesis. This is the first study to directly test opsin spectral tuning mechanisms in the diverse and specious beetles.
IV
Authors: Conrad Joseph
Published: February 2023

This is, imperfectly, what he said—

“It was after the great trouble that broke the alliance of the four states of Wajo.* We fought amongst ourselves, and the Dutch watched from afar till we were weary. Then the smoke of their fire-ships was...
Pecuniary Canons of Taste
Authors: Veblen Thorstein
Published: February 2023

The caution has already been repeated more than once, that while the regulating norm of consumption is in large part the requirement of conspicuous waste, it must not be understood that the motive on which the consumer acts in any given case is this...
Survivals of the Non-Invidious Interest
Authors: Veblen Thorstein
Published: February 2023

In an increasing proportion as time goes on, the anthropomorphic cult, with its code of devout observances, suffers a progressive disintegration through the stress of economic exigencies and the decay of the system of status. As this disintegration proceeds, there come to be associated...
XIX
Authors: Norris Frank
Published: February 2023

One can hold a scrubbing-brush with two good fingers and the stumps of two others even if both joints of the thumb are gone, but it takes considerable practice to get used to it.

Trina became a scrub-woman. She had taken council of Selina, and...
Three-dimensional printing of patient-specific computed tomography lung phantoms: a reader study
Authors: Shapira Nadav , Donovan Kevin , Mei Kai , Geagan Michael , Roshkovan Leonid , Gang Grace J , Abed Mohammed , Linna Nathaniel B , Cranston Coulter P , O'Leary Cathal N , Dhanaliwala Ali H , Kontos Despina , Litt Harold I , Stayman J Webster , Shinohara Russell T , Noël Peter B
Published: February 2023

In modern clinical decision-support algorithms, heterogeneity in image characteristics due to variations in imaging systems and protocols hinders the development of reproducible quantitative measures including for feature extraction pipelines. With the help of a reader study, we investigate the ability to provide consistent ground-truth targets by using patient-specific 3D-printed lung phantoms. PixelPrint was developed for 3D-printing lifelike computed tomography (CT) lung phantoms by directly translating clinical images into printer instructions that control density on a voxel-by-voxel basis. Data sets of three COVID-19 patients served as input for 3D-printing lung phantoms. Five radiologists rated patient and phantom images for imaging characteristics and diagnostic confidence in a blinded reader study. Effect sizes of evaluating phantom as opposed to patient images were assessed using linear mixed models. Finally, PixelPrint's production reproducibility was evaluated. Images of patients and phantoms had little variation in the estimated mean (0.03–0.29, using a 1–5 scale). When comparing phantom images to patient images, effect size analysis revealed that the difference was within one-third of the inter- and intrareader variabilities. High correspondence between the four phantoms created using the same patient images was demonstrated by PixelPrint’s production repeatability tests, with greater similarity scores between high-dose acquisitions of the phantoms than between clinical-dose acquisitions of a single phantom. We demonstrated PixelPrint's ability to produce lifelike CT lung phantoms reliably. These phantoms have the potential to provide ground-truth targets for validating the generalizability of inference-based decision-support algorithms between different health centers and imaging protocols and for optimizing examination protocols with realistic patient-based phantoms.

Classification: CT lung phantoms, reader study
Polarization Eh? Ideological Divergence and Partisan Sorting in the Canadian Mass Public
Authors: Merkley Eric
Published: February 2023

There has been increasing concern among commentators and scholars about polarization in Canada. This note uses the Canadian Election Study from 1993 to 2019 to measure trends in ideological divergence, ideological consistency, and partisan-ideological sorting in the Canadian mass public. It finds only mixed evidence that Canadians are diverging ideologically and becoming more polarized—ideological distributions are unimodal and trends toward more dispersion are slight and driven entirely by the last two election cycles. Canadians are, however, becoming modestly more ideologically consistent and much more sorted—that is, partisanship, ideological identification, and policy beliefs are increasingly interconnected. These findings call for additional research on the causes and consequences of mass polarization in Canada and further efforts to situate these results, along with findings from the United States, in a comparative context.
Strategic Discrimination in the 2020 Democratic Primary
Authors: Green Jon , Schaffner Brian , Luks Sam
Published: February 2023

Primary voters frequently support the candidates they think have a greater chance of winning the general election over the candidates who most closely reflect their policy preferences—a perception referred to as “electability.” While electability is typically taken to mean ideological moderation, recent research highlights the potential for candidates’ demographic characteristics to affect such perceptions. Using a conjoint experiment conducted with a sample of nearly 3,000 likely Democratic primary voters in June 2019, we show that women and candidates of color were seen as less electable than their white, male counterparts despite being preferred more frequently, holding policy stances and general election strategies constant. These effects were independent of respondents’ hostile sexism and racial resentment, and mediation analysis indicates that electability concerns reduced overall support for women and candidates of color. The results replicate and extend recent findings related to “strategic discrimination” in the US electorate.
Screening patients for unintentional carbon monoxide exposure in the Emergency Department: a cross-sectional multi-centre study
Authors: Jarman Heather , Atkinson Richard W , Baramova Desislava , Gant Timothy W , Marczylo Tim , Myers Isabella , Price Shirley , Quinn Tom
Published: February 2023

Background

Low-level exposure to carbon monoxide (CO) is a significant health concern but is difficult to diagnose. This main study aim was to establish the prevalence of low-level CO poisoning in Emergency Department (ED) patients.

Methods

A prospective cross-sectional study of patients with symptoms of CO exposure was conducted in four UK EDs between December 2018 and March 2020. Data on symptoms, a CO screening tool and carboxyhaemoglobin were collected. An investigation of participants’ homes was undertaken to identify sources of CO exposure.

Results

Based on an ED assessment of 4175 participants, the prevalence of suspected CO exposure was 0.62% (95% CI; 0.41–0.91%). CO testing in homes confirmed 1 case of CO presence and 21 probable cases. Normal levels of carboxyhaemoglobin were found in 19 cases of probable exposure and in the confirmed case.

Conclusion

This study provides evidence that ED patients with symptoms suggestive of CO poisoning but no history of CO exposure are at risk from CO poisoning. The findings suggest components of the CO screening tool may be an indicator of CO exposure over and above elevated COHb. Clinicians should have a high index of suspicion for CO exposure so that this important diagnosis is not missed.
Do Corporate Disclosures Constrain Strategic Analyst Behavior?
Authors: Chang Yen-Cheng , Ljungqvist Alexander , Tseng Kevin
Published: February 2023

We show that analyst behavior changes in response to a randomly assigned shock that exogenously varies the timeliness and cost of accessing mandatory disclosures in the cross-section of investors: analysts reduce coverage and issue less optimistic, more accurate, less bold, and less informative forecasts. Our evidence indicates that analysts reduce a strategic component of their behavior: the changes are stronger among analysts with more strategic incentives like affiliated or retail-focused analysts. We conclude that mandatory disclosure can substitute for analyst information production, which is constrained by investors’ ability to verify forecasts using corporate filings.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Joining the International Community
Authors: Ker-Lindsay James , Fabry Mikulas
Published: February 2023

How does recognition happen?

Having gained independence, the priority for any new state is to join the international community. The first step in this process is obtaining recognition from other countries. In terms of the formal act of recognition, this can be done in a...
Specific Liability Questions and Whistleblowing Options
Authors: Nelson J.S. , Stout Lynn A.
Published: February 2023

This chapter discusses what to do when leadership fails employees, and they consider reporting the wrongdoing they observe within the organization to authorities. This chapter describes to whom employees may report and how. Questions include: How should businesses report ethical violations? How should employees report ethical violations? What are the sources of rules and enforcement entities for business ethics violations? What are effective strategies for employee reporting? What are my options if reporting within my organization does not work? What are my options when I report to authorities? What benefits am I entitled to as a whistleblower? What protections will I have as a whistleblower? What else should I know about being a whistleblower?
Designing an Ethical Culture
Authors: Nelson J.S. , Stout Lynn A.
Published: February 2023

This chapter and the previous one focus on the ways that compliance and ethics programs help design ethical organizational culture. Key components of ethical cultures are encouraging employees to “speak up” and preventing retaliation. We also review challenges for certain types of organizations, and we survey some of the best compliance and ethics programs in businesses today. Some questions include: Why does creating a “speak-up culture” matter, and what are some ways to do this? Why does it matter to prevent retaliation against employees who report, and what are some ways to do this? What are some problems that larger companies and supply-side companies face? What are some ideas for these organizations and others in crisis? What are some of the best compliance and ethics programs in businesses today? What are the lessons that businesses and individuals should learn from our discussion of compliance and ethics?
Jihad
Authors: Afsaruddin Asma
Published: February 2023

The word “jihad” is everywhere in the global media. It generally appears in the context of violence waged against the West by militants in or from Muslim-majority societies. This usage overwhelmingly colors popular discourse about Islam and Muslims and it has resulted in highly simplistic, distorted, and ahistorical understandings of the concept of jihad. For most Muslims, jihad refers to the continuous human struggle to promote and implement what is morally good and noble in all walks of life, as well as to resist and prevent what is morally wrong and unjust. This book addresses the great need for a discussion of jihad that explores its various dimensions without fear-mongering or sensationalism. Here it is examined from multiple perspectives: scriptural, theological, moral and ethical, legal and socio-political. Asma Afsaruddin looks at the key questions about jihad and provides concise yet thorough answers. Jihad: What Everyone Needs to Know© provides a historically-grounded, scholarly yet accessible treatment of the meanings of jihad from the formative period of Islam until the contemporary period.
Sanctions
Authors: Jentleson Bruce W.
Published: February 2023

Even before the extensive sanctions imposed on Russia for its 2022 invasion of Ukraine, it was hard to browse the news without seeing reports of yet another set of sanctions. The US has active sanctions against over thirty countries as well as drug traffickers, terrorist organizations, and specially designated individuals. China has long been a target of sanctions and, in recent years, increasingly become a wielder against both countries and companies. Russia also has been a sanctions sender as well as target. The EU has joined some of the American sanctions as well as imposing its own. In some cases, the UN has authorized fully multilateral sanctions. While being used more frequently in recent years, sanctions go back centuries, to such cases as the measures taken by Athens against Sparta in 432 bc and Napoleon’s 1808–1814 Continental System. Given such frequency of use, one would think sanctions were a sure-fire weapon. Yet the record is quite mixed, raising some puzzling questions: Why are economic sanctions used so much? What are the key factors affecting their success? These and related questions are addressed by scholar and senior foreign policy advisor Bruce W. Jentleson in Sanctions: What Everyone Needs to Know. They have long been important among international relations scholars, spanning international security and international political economy subfields. And with sanctions such a recurring foreign policy strategy, they are crucial for policymakers.
Strategies Designed to Improve the Quality of Education
Authors: Kirp David , Macpherson Kevin
Published: February 2023

Chapter 2 explores a range of strategies that are meant to improve the outcomes of pre-K–12 education. The chapter introduces a number of models of schooling—among them homeschooling and community schools—and assesses the research that relates to their effectiveness. Market-based models such as charter schools and school vouchers, which have been the focus of headline-making political debates, are reviewed in similar fashion, including an assessment of the research that relates to their effectiveness. The chapter also analyzes major federal approaches to school reform during the past quarter-century, including the “high-stakes accountability” model introduced in 2002. It concludes with a primer regarding recent federal legislation, as well as the “continuous improvement” and “disruption” strategies that underpin contemporary school reform efforts.
The Changing Investment Landscape
Authors: Baker H. Kent , Holzhauer Hunter M. , Nofsinger John R.
Published: February 2023

Sustainable in-vesting has changed considerably over time. Historically, many viewed it as a form of religious in-vesting that focused mainly on prohibiting “sinful” practices such as usury and excluding “sinful” investments through negative screening. Sustainable investing grew to incorporate a broader range of socially responsible values and practices, in-cluding “socially responsible” investments through positive screening. Sus-tainable investing has now evolved to include a wide array of different approaches that incorpo-rate various investment products and strategies. The most common method is integrating envi-ronmental, social, and governance (ESG) criteria into traditional investment models. Niche ap-proaches like green, impact, and community investing fall under sustainable investing. This chapter explores the evolution of sustainable investing and how it has become one of the most dominant trends in the current investment landscape.
Climate Science Basics
Authors: Romm Joseph
Published: February 2023

This chapter focuses on climate science as it applies to what science can tell us about the changes we have observed to date and what caused them. The goal is to answer the key questions that people ask about the science.
Peptide Analogs of a Trichoderma Peptaibol Effectively Control Downy Mildew in the Vineyard
Authors: Bolzonello Angela , Morbiato Laura , Tundo Silvio , Sella Luca , Baccelli Ivan , Echeverrigaray Sergio , Musetti Rita , De Zotti Marta , Favaron Francesco
Published: February 2023

Plasmopara viticola, the agent of grapevine downy mildew, causes enormous economic damage, and its control is primarily based on the use of synthetic fungicides. The European Union policies promote reducing reliance on synthetic plant protection products. Biocontrol agents such as Trichoderma spp. constitute a resource for the development of biopesticides. Trichoderma spp. produce secondary metabolites such as peptaibols, but the poor water solubility of peptaibols limits their practical use as agrochemicals. To identify new potential bio-inspired molecules effective against P. viticola, various water-soluble peptide analogs of the peptaibol trichogin were synthesized. In grapevine leaf disk assays, the peptides analogs at a concentration of 50 μM completely prevented P. viticola infection after zoosporangia inoculation. Microscopic observations of one of the most effective peptides showed that it causes membrane lysis and cytoplasmic granulation in both zoosporangia and zoospores. Among the effective peptides, 4r was selected for a 2-year field trial experiment. In the vineyard, the peptide administered at 100 μM (equivalent to 129.3 g/ha) significantly reduced the disease incidence and severity on both leaves and bunches, with protection levels similar to those obtained using a cupric fungicide. In the second-year field trial, reduced dosages of the peptide were also tested, and even at the peptide concentration reduced by 50 or 75%, a significant decrease in the disease incidence and severity was obtained at the end of the trial. The peptide did not show any phytotoxic effect. Previously, peptide 4r had been demonstrated to be active against other fungal pathogens, including the grapevine fungus Botrytis cinerea. Thus, this peptide may be a candidate for a broad-spectrum fungicide whose biological properties deserve further investigation.
Identification of a Second Vector for Rose Rosette Virus
Authors: Druciarek Tobiasz , Lewandowski Mariusz , Tzanetakis Ioannis
Published: February 2023

Rose rosette devastates the ornamentals industry in the United States. The disease, caused by rose rosette emaravirus (RRV), is vectored by the eriophyoid mite Phyllocoptes fructiphilus (Acari: Eriophyoidea). In this communication, we investigate two other Phyllocoptes species, P. adalius and P. arcani, for their vector competency and transmission efficiencies in single and multiple mite transfer experiments. P. arcani was identified as a second vector of RRV, a finding of significance for the epidemiology of the disease, as the second vector may be present in plants where P. fructiphilus is absent.
Development and Identification of a Wheat–Rye Breeding Line for Harmonious Improvement Between Powdery Mildew Resistance and High Yield Potential
Authors: Han Guohao , Cao Lijun , Yan Hanwen , Gu Tiantian , Shi Zhipeng , Li Xiuquan , Li Lihui , An Diaoguo
Published: February 2023

Powdery mildew, caused by Blumeria graminis f. sp. tritici, is a devastating disease that seriously threatens wheat yield and quality. To control this disease, host resistance is the preferred measure. However, wheat breeding is a complex process with elusive exchange and recombination of the traits from their parents. Increased resistance often leads to a decline in other key traits, such as yield and quality. Developing breakthrough germplasms with harmonious powdery mildew resistance and other key breeding traits is attractive in wheat breeding. In this study, we developed an ideal wheat breeding line AL46 that pyramided its hexaploid triticale parent-derived desirable yield traits and its wheat parent-derived powdery mildew resistance gene Pm2. Sequential genomic in situ hybridization (GISH), multicolor GISH, multicolor fluorescence in situ hybridization, and molecular marker analyses revealed that AL46 was a wheat–rye T1RS·1BL translocation line. Genetic analysis combined with function marker detection and sequence alignment were used to confirm that AL46 carried the Pm2 gene. Then, we evaluated the powdery mildew resistance and comprehensive traits of AL46, and just as we designed, AL46 showed harmonious powdery mildew resistance with some key breeding traits. This study not only developed an ideal wheat germplasm resource but also provided a successful example for pyramiding breeding, which could be a promising direction for wheat improvement in the future.
Draft Genome Resources of Seven Strains of Tilletia horrida, Causal Agent of Kernel Smut of Rice
Authors: Khanal Sabin , Antony-Babu Sanjay , Zhou Xin-Gen
Published: February 2023

Tilletia horrida, the causal agent of kernel smut of rice, is one of the most economically important diseases in rice. In recent years, increases in the incidence and severity of kernel smut have been reported across the rice-growing regions of the United States. In this study, we report the draft genome sequences of seven strains of T. horrida. Among the seven strains, four were assembled to 26 mb in length and the remaining three to 20 mb in length. These genome sequence datasets will be valuable resources for future studies on the population genomics and fungicide resistance of T. horrida and the host-pathogen interactions.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The transphyseal osteotomy for the slipped proximal tibial epiphysis in tibia vara
Authors: Maré Pieter Herman , Thompson David Mungo , Marais Leonard Charles
Published: February 2023

This study aimed to describe a novel transphyseal osteotomy (TPO) for acute deformity correction in children with bilateral tibia vara and the atraumatic ‘slipped proximal tibial epiphysis’ (SPTE) entity. We described the clinical and radiological findings in five children (10 limbs) with tibia vara that were treated with the TPO. The criteria for the SPTE were met in nine (9/10) cases. The surgical technique and short-term results of the TPO are reported. The median age was 9 years (range, 6–9), with obesity (BMI > 95th centile) present in all children. The medial tibial plateau was not significantly depressed (the median angle of depression of the medial plateau measured 30° (range, 20°–32°). The mean medial proximal tibial angle of 33° (range, 8°–71°) was corrected to 82° (range, 77°–86°), the mean anatomic posterior proximal tibial angle of 48° (range, 32°–70°) was corrected to 72° (range, 61°–86°), and the median internal tibial rotation of 45° (range, 20°–50° internal rotation) was corrected to neutral rotation (range, 10° internal–10° external rotation). There were two complications: one case of recurrent deformity and one case of intra-articular extension of the osteotomy. We describe a novel TPO that aims to simultaneously correct all aspects of the deformity, stabilise the physis, and prevent recurrence through epiphysiodesis. Further research is required to determine its efficacy and safety. The atraumatic SPTE appears to represent a specific morphological presentation in tibia vara. Level of evidence: 4.
Getting personal in metastatic melanoma: neoantigen-based vaccines as a new therapeutic strategy
Authors: D’Alise Anna Morena , Scarselli Elisa
Published: February 2023

Purpose of review

Cancer vaccines are facing renewed interest, thanks to the progress recently achieved in the immunotherapy field, including the success of immune checkpoint inhibitors (CPIs). The advances in understanding the CPI mode of action revealed a central role of neoantigens for the outcome of such treatments. Neoantigens became the preferred antigens for cancer vaccines and have been evaluated in several clinical trials. Here, we review the recent results from neoantigen-based vaccines in melanoma patients and discuss avenues for improvement.

Recent findings

The importance of neoantigens for tumor control comes from the positive correlation between tumor mutational burden (TMB) and response to CPI. Preclinical studies have proved the effectiveness of neoantigen vaccines in models, expediting their clinical testing. Tumor mutations are not shared in most tumor types including melanoma, mandating the need of a personalized approach. Several clinical studies have shown the safety, feasibility, immunogenicity and preliminary evidence of antitumor activity of personalized vaccination. Currently, new trials have been started aiming to both confirm clinical activity and combining vaccines with other immunotherapies for improved efficacy.

Personalized vaccines hold the promise for highly mutated and immunogenic cancers, including melanoma. Continuous efforts are underway to increase their likelihood of success.
Early Detection of Cancers in the Era of Precision Oncology
Authors: Tan Wan Ying , Sharma Anup , Das Paromita , Ahuja Nita
Published: February 2023

Purpose of review

The increasing global incidence of cancer demands innovative cancer detection modalities. The current population-based early cancer detection approaches focus on several major types of cancers (breast, prostate, cervical, lung and colon) at their early stages, however, they generally do not target high-risk individuals at precancerous stages.

Recent findings

Some cancers, such as pancreatic cancer, are challenging to detect in their early stages. Therefore, there is a pressing need for improved, accessible, noninvasive, and cost-effective early detection methods. Harnessing cell-free-based biomarker-driven strategies paves a new era of precision diagnosis for multicancer early detection. The majority of these tests are in the early stages and expensive, but these approaches are expected to become cost sensitive in the near future.

This review provides an overview of early cancer detection strategies, highlighting the methods, challenges, and issues to be addressed to revolutionize and improve global early cancer detection.
Relative Bradycardia in Critically Ill Patients with Novel Coronavirus 19: A Case Series
Authors: Li Qingpeng , Luo Liyun , Tang Wenyi , Chen Jian
Published: February 2023

Severe coronavirus 2019 (COVID-19) infection is associated with myocardial injury and arrhythmia. Bradycardia is a newly recognized consequence of COVID-19. Relative bradycardia and its effects in 4 critically ill patients with COVID-19 was described in this case series. The 4 cases showed the same clinical phenomenon: sinus bradycardia without a compensatory increase in heart rate in response to elevation of body temperature. Typically, heart rate decreases as body temperature rises. The 4 patients were all men with an average age of 67 years. Patient 1 was a 78-year-old man with no major medical history who died from COVID-19 pneumonia. The other 3 patients recovered.
Thoracic epidural analgesia vs. patient-controlled intravenous analgesia for patients undergoing open or laparoscopic colorectal cancer surgery
Authors: Cox P. Boris W. , Pisters Tom P.R.M. , de Korte-de Boer Dianne , Pennings Christoph H. , Melenhorst Jarno , Buhre Wolfgang F.F.A.
Published: February 2023

BACKGROUND

Thoracic epidural analgesia (TEA) is an invasive technique with potential side effects but is widely used in enhanced recovery after surgery (ERAS) programmes in colorectal cancer surgery. The effects of TEA on postoperative length of hospital stay (LOS) or morbidity is still debated.

OBJECTIVES

The main objective was to evaluate the postoperative analgesic effectiveness of TEA compared with patient-controlled intravenous analgesia (PCIA) after open or laparoscopic colorectal surgery, and whether TEA contributes to enhanced recovery.

DESIGN

A retrospective single-centre, observational study.

SETTING

Dutch tertiary-care university hospital.

PATIENTS

All consecutive adult patients undergoing colorectal cancer surgery from 1 January 2014 to 31 December 2016, with ASA status I-IV, were included. Exclusion criteria were hypersensitivity to opioid or local anaesthetic substances, or the use of multiple secondary anaesthetic techniques.

MAIN OUTCOME MEASURES

The primary outcome, postoperative pain assessed with a Numeric Rating Scale on postoperative days 1 to 3 inclusive. Secondary endpoints were LOS, the incidence of epidural related side effects, major complications and the 5-year survival rate. Using linear mixed models, pain scores were compared between patients who received TEA and PCIA.

RESULTS

Of 422 enrolled patients, 110 (32%) received TEA and 234 (68%) PCIA. Patients in the TEA group had lower pain scores: estimated NRS difference at rest; -0.79; 95% CI, -1.1 to -0.49; P < 0.001 and during movement -1.06; 95% CI, -1.39 to -0.73; P < 0.001. LOS, 30-day complication rate and overall survival at 5 years did not differ between the groups.

CONCLUSIONS

TEA in open or laparoscopic colorectal surgery is associated with moderately better postoperative pain control but does not affect LOS, postoperative morbidity, mortality nor long-term survival. The current clinical indication for TEA in colorectal surgery remains unchanged.

TRIAL REGISTRATION

International clinical trial registration number: ISRCTN11426678; retrospectively registered 26 February 2021.
‘Do-not-intubate’ orders in patients assisted by noninvasive respiratory support for acute hypoxaemic failure caused by coronavirus disease 2019; a systematic review and meta-analysis
Authors: Cammarota Gianmaria , Esposito Teresa , Simonte Rachele , Messina Antonio , Cecconi Maurizio , Vaschetto Rosanna , Vetrugno Luigi , Navalesi Paolo , Azzolina Danila , Robba Chiara , Pelosi Paolo , Longhini Federico , Maggiore Salvatore M. , De Robertis Edoardo
Published: February 2023

BACKGROUND

Noninvasive respiratory support (NIRS) has been revealed feasible solutions to cope with the massive request for ventilatory support in patients subjected to ‘do-not-intubate’ order (DNI).

OBJECTIVES

The aims of the present systematic review and meta-analysis was to estimate pooled incidence of DNI orders and the associated in-hospital mortality in patients undergoing NIRS for hypoxaemic acute respiratory failure (ARF) related to coronavirus disease 2019 (COVID-19).

DESIGN

Systematic review of observational studies and randomized-controlled trials with meta-analyses

DATA SOURCES

PUBMED, EMBASE, and Cochrane Controlled Clinical trials register were searched for observational studies and randomised-controlled trials from inception to the end of April 2022.

ELIGIBILITY CRITERIA

Inclusion criteria were: observational studies enrolling ≥50 hospitalised patients with hypoxaemic COVID-19-related ARF requiring NIRS and DNI order application. Two authors independently extracted data from enrolled investigations. Data are presented as proportions with 95% confidence interval.

RESULTS

Thirty-one observational studies were included for a total of 6645 COVID-19 patients undergoing NIRS, of whom 1590 received DNI orders. Among patients assisted by NIRS, a DNI order was expressed in a summary estimate of 25.4% [20.0–31.1] of the cases with a high between-study heterogeneity. The summary estimated of in-hospital mortality was 83.6% [75.3–90.7] for DNI patients and 20.0% [14.2–26.5] for full treatment patients, both with a high between-study heterogeneity.

CONCLUSIONS

In COVID-19 patients assisted through NIRS for hypoxaemic ARF, a DNI order was frequently issued and associated with a high in-hospital mortality

TRIAL REGISTRATION

Prospero registration number: CRD42021271313.
Generalized Difference-in-Differences
Authors: Richardson David B. , Ye Ting , Tchetgen Tchetgen Eric J.
Published: February 2023

Difference-in-differences (DID) analyses are used in a variety of research areas as a strategy for estimating the causal effect of a policy, program, intervention, or environmental hazard (hereafter, treatment). The approach offers a strategy for estimating the causal effect of a treatment using observational (i.e., nonrandomized) data in which outcomes on each study unit have been measured both before and after treatment. To identify a causal effect, a DID analysis relies on an assumption that confounding of the treatment effect in the pretreatment period is equivalent to confounding of the treatment effect in the post treatment period. We propose an alternative approach that can yield identification of causal effects under different identifying conditions than those usually required for DID. The proposed approach, which we refer to as generalized DID, has the potential to be used in routine policy evaluation across many disciplines, as it essentially combines two popular quasiexperimental designs, leveraging their strengths while relaxing their usual assumptions. We provide a formal description of the conditions for identification of causal effects, illustrate the method using simulations, and provide an empirical example based on Card and Krueger’s landmark study of the impact of an increase in minimum wage in New Jersey on employment.
In utero Exposure to Maternal Diabetes and the Risk of Cerebral Palsy: A Population-based Cohort Study
Authors: Ahmed Asma , Rosella Laura C. , Oskoui Maryam , Watson Tristan , Yang Seungmi
Published: February 2023

Background:

Evidence on the effects of in utero exposure to maternal diabetes on cerebral palsy (CP) in offspring is limited. We aimed to examine the effects of pregestational (PGDM) and gestational diabetes (GDM) separately on CP risk and the mediating role of increased fetal size.

Methods:

In a population-based study, we included all live births in Ontario, Canada, between 2002 and 2017 followed up through 2018 (n = 2,110,177). Using administrative health data, we estimated crude and adjusted associations between PGDM or GDM and CP using Cox proportional hazards models to account for unequal follow-up in children. For the mediation analysis, we used marginal structural models to estimate the controlled direct effect of PGDM (and GDM) on the risk of CP not mediated by large-for-gestational age (LGA).

Results:

During the study period, 5,317 children were diagnosed with CP (187 exposed to PGDM and 171 exposed to GDM). Children of mothers with PGDM showed an increased risk (hazard ratio [HR]: 1.84 [95% confidence interval (CI): 1.59, 2.14]) after adjusting for maternal sociodemographic and clinical factors. We found no associations between GDM and CP (adjusted HR: 0.91 [0.77, 1.06]). Our mediation analysis estimated that LGA explained 14% of the PDGM-CP association.

Conclusions:

In this population-based birth cohort study, maternal pregestational diabetes was associated with increased risk of CP, and the increased risk was not substantially mediated by the increased fetal size.
Performance of Multiple Imputation Using Modern Machine Learning Methods in Electronic Health Records Data
Authors: Getz Kylie , Hubbard Rebecca A. , Linn Kristin A.
Published: February 2023

Background:

Missing data are common in studies using electronic health records (EHRs)-derived data. Missingness in EHR data is related to healthcare utilization patterns, resulting in complex and potentially missing not at random missingness mechanisms. Prior research has suggested that machine learning-based multiple imputation methods may outperform traditional methods and may perform well even in settings of missing not at random missingness.

Methods:

We used plasmode simulations based on a nationwide EHR-derived de-identified database for patients with metastatic urothelial carcinoma to compare the performance of multiple imputation using chained equations, random forests, and denoising autoencoders in terms of bias and precision of hazard ratio estimates under varying proportions of observations with missing values and missingness mechanisms (missing completely at random, missing at random, and missing not at random).

Results:

Multiple imputation by chained equations and random forest methods had low bias and similar standard errors for parameter estimates under missingness completely at random. Under missingness at random, denoising autoencoders had higher bias than multiple imputation by chained equations and random forests. Contrary to results of prior studies of denoising autoencoders, all methods exhibited substantial bias under missingness not at random, with bias increasing in direct proportion to the amount of missing data.

Conclusions:

We found no advantage of denoising autoencoders for multiple imputation in the setting of an epidemiologic study conducted using EHR data. Results suggested that denoising autoencoders may overfit the data leading to poor confounder control. Use of more flexible imputation approaches does not mitigate bias induced by missingness not at random and can produce estimates with spurious precision.
Surgical Management of Hidradenitis Suppurativa: Factors Associated with Postoperative Complications and Disease Recurrence
Authors: Skorochod Ron , Margulis Alexander , Adler Neta
Published: February 2023

Background:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder. Treatment of HS remains challenging, and surgical procedures commonly follow attempts of conservative therapy. To date, a consensus regarding the optimal surgical technique has not been reached, and the implications of conservative therapy on future surgical outcomes have yet to be studied.

Methods:

A retrospective cohort study of 65 patients surgically treated for HS at a tertiary care center was conducted. Patients’ medical records were screened for demographical, clinical, and surgical characteristics. Statistical analysis was conducted to determine associations with postoperative complications and disease recurrence.

Results:

Fifty patients (75.8%) were treated with systemic antibiotics before opting for surgical resection. Previous treatment with systemic rifampicin was associated with higher rates of postoperative complications (P = 0.029); however, systemic cephalexin and topical clindamycin were associated with a lower rate of complications (P = 0.007 and 0.040, accordingly). Medical history of smoking and surgical management with split-thickness skin grafts were associated with higher rates of postoperative complications (P = 0.012 and 0.014, accordingly). Patients with a greater number of lesions, and those treated with split-thickness skin graft, had higher rates of disease recurrence (P = 0.0018 and 0.003, accordingly).

In a multivariate analysis a greater number of lesions (P = 0.0498) and the use of autologous split-thickness skin graft (P = 0.022) were independently associated with higher rates of disease recurrence.

Conclusions:

Previous conservative medical therapy bears the potential to modulate postoperative outcomes in HS patients, and should be taken into consideration. Despite reports of reliable results with split-thickness skin grafts, we found them to be associated with increased rates of diseases recurrence and postoperative complications.
Financial Models for an Academic Practice in Plastic Surgery
Authors: Munoz Kathrina , Evans Gregory R. D.
Published: February 2023

Background:

In an attempt to investigate physician compensation in academic practice, financial reimbursement models of departments and/or divisions of plastic surgery within an academic university setting were evaluated.

Method:

Thirteen divisions or departments of plastic surgery were surveyed to obtain information regarding reimbursement models for plastic surgery.

Results:

Of the 13 plastic surgery groups surveyed, 11 were divisions within the department of surgery. The department chairs/chief and/or chief administrative officers were questioned regarding the following areas: (1) total compensation, 2) bonus and incentive compensation models, and (3) cosmetic and cash reimbursement. There were no regional differences that could be identified. As such, we grouped institutions into Western, Midwest, and Eastern regions. COVID-19 did not change any of the financial models that were established before the pandemic.

Discussion:

There is no ideal model for compensation, which varied among the institutions surveyed. All of these financial models were established before COVID-19 and did not significantly change with the pandemic. It appears that within this small sample size, compensation is based mainly on a $/wRVU model. Funding for research and educational teaching remains a challenge, which is not reimbursed well. Although faculty compensation may vary based on the institutions, the decision to enter and remain in academic practice includes a series of decisions. However, compensation is a significant factor, which should not be minimized.