bluuebunny/crossref_metadata_2025 huggingface dataset:
Invited Commentary: Dealing With the Inevitable Deficiencies of Bias Analysis—and All Analyses
Authors: Greenland Sander
Published: March 2021

Lash et al. (Am J Epidemiol. 2021;190(8):1604–1612) have presented detailed critiques of 3 bias analyses that they identify as “suboptimal.” This identification raises the question of what “optimal” means for bias analysis, because it is practically impossible to do statistically optimal analyses of typical population studies—with or without bias analysis. At best the analysis can only attempt to satisfy practice guidelines and account for available information both within and outside the study. One should not expect a full accounting for all sources of uncertainty; hence, interval estimates and distributions for causal effects should never be treated as valid uncertainty assessments—they are instead only example analyses that follow from collections of often questionable assumptions. These observations reinforce those of Lash et al. and point to the need for more development of methods for judging bias-parameter distributions and utilization of available information.
A Randomized Study to Assess the Effect of Including the Graduate Record Examinations Results on Reviewer Scores for Underrepresented Minorities
Authors: Dang Kristina V , Rerolle Francois , Ackley Sarah F , Irish Amanda M , Mehta Kala M , Bailey Inez , Fair Elizabeth , Miller Cecily , Bibbins-Domingo Kirsten , Wong-Moy Eva , Glymour M Maria , Morris Meghan D
Published: March 2021

Whether requiring Graduate Record Examinations (GRE) results for doctoral applicants affects the diversity of admitted cohorts remains uncertain. This study randomized applications to 2 population-health doctoral programs at the University of California San Francisco to assess whether masking reviewers to applicant GRE results differentially affects reviewers’ scores for underrepresented minority (URM) applicants from 2018–2020. Applications with GRE results and those without were randomly assigned to reviewers to designate scores for each copy (1–10, 1 being best). URM was defined as self-identification as African American/Black, Filipino, Hmong, Vietnamese, Hispanic/Latinx, Native American/Alaska Native, or Native Hawaiian/Other Pacific Islander. We used linear mixed models with random effects for the applicant and fixed effects for each reviewer to evaluate the effect of masking the GRE results on the overall application score and whether this effect differed by URM status. Reviewer scores did not significantly differ for unmasked versus masked applications among non-URM applicants (β = 0.15; 95% CI: −0.03, 0.33) or URM applicants (β = 0.02, 95% CI: −0.49, 0.54). We did not find evidence that removing GREs differentially affected URM compared with non-URM students (β for interaction = −0.13, 95% CI: −0.55, 0.29). Within these doctoral programs, results indicate that GRE scores neither harm nor help URM applicants.
Transcriptome differences between Cupriavidus necator NH9 grown with 3-chlorobenzoate and that grown with benzoate
Authors: Moriuchi Ryota , Dohra Hideo , Kanesaki Yu , Ogawa Naoto
Published: March 2021

RNA-seq analysis of Cupriavidus necator NH9, a 3-chlorobenzoate degradative bacterium, cultured with 3-chlorobenzaote and benzoate, revealed strong induction of genes encoding enzymes in degradation pathways of the respective compound, including the genes to convert 3-chlorobenzaote and benzoate to chlorocatechol and catechol, respectively, and the genes of chlorocatechol ortho-cleavage pathway for conversion to central metabolites. The genes encoding transporters, components of the stress response, flagellar proteins, and chemotaxis proteins showed altered expression patterns between 3-chlorobenzoate and benzoate. Gene Ontology enrichment analysis revealed that chemotaxis-related terms were significantly upregulated by benzoate compared with 3-chlorobenzoate. Consistent with this, in semisolid agar plate assays, NH9 cells showed stronger chemotaxis to benzoate than to 3-chlorobenzoate. These results, combined with the absence of genes related to uptake/chemotaxis for 3-chlorobenzoate located closely to the degradation genes of 3-chlorobenzoate, suggested that NH9 has not fully adapted to the utilization of chlorinated benzoate, unlike benzoate, in nature.
SSG-LUGIA: Single Sequence based Genome Level Unsupervised Genomic Island Prediction Algorithm
Authors: Ibtehaz Nabil , Ahmed Ishtiaque , Ahmed Md Sabbir , Rahman M Sohel , Azad Rajeev K , Bayzid Md Shamsuzzoha
Published: March 2021

Background

Genomic Islands (GIs) are clusters of genes that are mobilized through horizontal gene transfer. GIs play a pivotal role in bacterial evolution as a mechanism of diversification and adaptation to different niches. Therefore, identification and characterization of GIs in bacterial genomes is important for understanding bacterial evolution. However, quantifying GIs is inherently difficult, and the existing methods suffer from low prediction accuracy and precision–recall trade-off. Moreover, several of them are supervised in nature, and thus, their applications to newly sequenced genomes are riddled with their dependency on the functional annotation of existing genomes.

Results

We present SSG-LUGIA, a completely automated and unsupervised approach for identifying GIs and horizontally transferred genes. SSG-LUGIA is a novel method based on unsupervised anomaly detection technique, accompanied by further refinement using cues from signal processing literature. SSG-LUGIA leverages the atypical compositional biases of the alien genes to localize GIs in prokaryotic genomes. SSG-LUGIA was assessed on a large benchmark dataset `IslandPick’ and on a set of 15 well-studied genomes in the literature and followed by a thorough analysis on the well-understood Salmonella typhi CT18 genome. Furthermore, the efficacy of SSG-LUGIA in identifying horizontally transferred genes was evaluated on two additional bacterial genomes, namely, those of Corynebacterium diphtheria NCTC13129 and Pseudomonas aeruginosa LESB58. SSG-LUGIA was examined on draft genomes and was demonstrated to be efficient as an ensemble method.

Conclusions

Our results indicate that SSG-LUGIA achieved superior performance in comparison to frequently used existing methods. Importantly, it yielded a better trade-off between precision and recall than the existing methods. Its nondependency on the functional annotation of genomes makes it suitable for analyzing newly sequenced, yet uncharacterized genomes. Thus, our study is a significant advance in identification of GIs and horizontally transferred genes. SSG-LUGIA is available as an open source software at https://nibtehaz.github.io/SSG-LUGIA/.
Burden of in-hospital care in oesophageal cancer: national population-based study
Authors: Linder G , Klevebro F , Edholm D , Johansson J , Lindblad M , Hedberg J
Published: March 2021

Background

Oesophageal cancer management requires extensive in-hospital care. This cohort study aimed to quantify in-hospital care for patients with oesophageal cancer in relation to intended treatment, and to analyse factors associated with risk of spending a large proportion of survival time in hospital.

Methods

All patients with oesophageal cancer in three nationwide registers over a 10-year period were included. In-hospital care during the first year after diagnosis was evaluated, and the proportion of survival time spent in hospital, stratified by intended treatment (curative, palliative or best supportive care), was calculated. Associations between relevant factors and a greater proportion of survival time in hospital were analysed by multivariable logistic regression.

Results

In-hospital care was provided for a median of 39, 26, and 15 days in the first year after diagnosis of oesophageal cancer in curative, palliative, and best supportive care groups respectively. Patients receiving curatively intended treatment spent a median of 12 per cent of their survival time in hospital during the first year after diagnosis, whereas those receiving palliative or best supportive care spent 19 and 23 per cent respectively. Factors associated with more in-hospital care included older age, female sex, being unmarried, and chronic obstructive pulmonary disease.

Conclusion

The burden of in-hospital care during the first year after diagnosis of oesophageal cancer was substantial. Important clinical and socioeconomic factors were identified that predisposed to a greater proportion of survival time spent in hospital.
Multispectral Palm Print and Palm Vein Acquisition Platform and Recognition Method Based on Convolutional Neural Network
Authors: Wang Lei , Zhang Qiang , Qian Qing , Wang Jishuai , Pan Yujun , Yang Renbing , Cheng Wenbo
Published: March 2021

Biometrics recognition takes advantage of feature extraction and pattern recognition to analyze the physical and behavioral characteristics of biological individuals to achieve the purpose of individual identification. As a typical biometric technology, palm print and palm vein have the characteristics of high recognition rate, stable features, easy location and good image quality, which have attracted the attention of researchers. This paper designs and develops a multispectral palm print and palm vein acquisition platform, which can quickly acquire palm spectrum and palm vein multispectral images with seven different wavelengths. We propose a multispectral palm print palmar vein recognition framework, and feature-level image fusion is performed after extracting features of palm print palmar vein images at different wavelengths. Through the multispectral palm print palm vein image fusion experiment, a more feasible multispectral palm print and palm vein image fusion scheme is proposed. Based on the results of image fusion, we further propose an improved convolutional neural network (CNN) for model training to achieve identity recognition based on multispectral palm print palm vein images. Finally, the effects of different CNN network structures and learning rates on the recognition results were analyzed and compared experimentally.
Results of the Seventh Scientific Workshop of ECCO: Precision Medicine in IBD—What, Why, and How
Authors: Fiocchi Claudio , Dragoni Gabriele , Iliopoulos Dimitrios , Katsanos Konstantinos , Ramirez Vicent Hernandez , Suzuki Kohei ,   Scientific Workshop Steering Committee, Verstockt Bram , Fiocchi Claudio , Torres Joana , Scharl Michael
Published: March 2021

Many diseases that affect modern humans fall in the category of complex diseases, thus called because they result from a combination of multiple aetiological and pathogenic factors. Regardless of the organ or system affected, complex diseases present major challenges in diagnosis, classification, and management. Current forms of therapy are usually applied in an indiscriminate fashion based on clinical information, but even the most advanced drugs only benefit a limited number of patients and to a variable and unpredictable degree. This ‘one measure does not fit all’ situation has spurred the notion that therapy for complex disease should be tailored to individual patients or groups of patients, giving rise to the notion of ‘precision medicine’ [PM].

Inflammatory bowel disease [IBD] is a prototypical complex disease where the need for PM has become increasingly clear. This prompted the European Crohn’s and Colitis Organisation to focus the Seventh Scientific Workshop on this emerging theme. The articles in this special issue of the Journal address the various complementary aspects of PM in IBD, including what PM is; why it is needed and how it can be used; how PM can contribute to prediction and prevention of IBD; how IBD PM can aid in prognosis and improve response to therapy; and the challenges and future directions of PM in IBD.

This first article of this series is structured on three simple concepts [what, why, and how] and addresses the definition of PM, discusses the rationale for the need of PM in IBD, and outlines the methodology required to implement PM in IBD in a correct and clinically meaningful way.
Inhibition of NOX1 Mitigates Blood Pressure Increases in Elastin Insufficiency
Authors: Troia Angela , Knutsen Russell H , Halabi Carmen M , Malide Daniela , Yu Zu Xi , Wardlaw-Pickett Amanda , Kronquist Elise K , Tsang Kit Man , Kovacs Attila , Mecham Robert P , Kozel Beth A
Published: March 2021

Elastin (ELN) insufficiency leads to the cardiovascular hallmarks of the contiguous gene deletion disorder, Williams–Beuren syndrome, including hypertension and vascular stiffness. Previous studies showed that Williams–Beuren syndrome deletions, which extended to include the NCF1 gene, were associated with lower blood pressure (BP) and reduced vascular stiffness. NCF1 encodes for p47phox, the regulatory component of the NOX1 NADPH oxidase complex that generates reactive oxygen species (ROS) in the vascular wall. Dihydroethidium and 8-hydroxyguanosine staining of mouse aortas confirmed that Eln heterozygotes (Eln+/−) had greater ROS levels than the wild-types (Eln+/+), a finding that was negated in vessels cultured without hemodynamic stressors. To analyze the Nox effect on ELN insufficiency, we used both genetic and chemical manipulations. Both Ncf1 haploinsufficiency (Ncf1+/−) and Nox1 insufficiency (Nox1−/y) decreased oxidative stress and systolic BP in Eln+/− without modifying vascular structure. Chronic treatment with apocynin, a p47phox inhibitor, lowered systolic BP in Eln+/−, but had no impact on Eln+/+ controls. In vivo dosing with phenylephrine (PE) produced an augmented BP response in Eln+/− relative to Eln+/+, and genetic modifications or drug-based interventions that lower Nox1 expression reduced the hypercontractile response to PE in Eln+/− mice to Eln+/+ levels. These results indicate that the mechanical and structural differences caused by ELN insufficiency leading to oscillatory flow can perpetuate oxidative stress conditions, which are linked to hypertension, and that by lowering the Nox1-mediated capacity for vascular ROS production, BP differences can be normalized.
Long noncoding RNA regulation of spermatogenesis via the spectrin cytoskeleton in Drosophila
Authors: Bouska Mark J , Bai Hua
Published: March 2021

The spectrin cytoskeleton has been shown to be critical in diverse processes such as axon development and degeneration, myoblast fusion, and spermatogenesis. Spectrin can be modulated in a tissue specific manner through junctional protein complexes, however, it has not been shown that long noncoding RNAs (lncRNAs) interact with and modulate spectrin. Here, we provide evidence of a lncRNA CR45362 that interacts with α-Spectrin, is required for spermatid nuclear bundling during Drosophila spermatogenesis. We observed that CR45362 showed high expression in the cyst cells at the basal testis, and CRISPR-mediated knockout of CR45362 led to sterile male, unbundled spermatid nuclei, and disrupted actin cones. Through chromatin isolation by RNA precipitation—mass spectrometry (ChIRP-MS), we identified actin-spectrin cytoskeletal components physically interact with the lncRNA CR45362. Genetic screening on identified cytoskeletal factors revealed that cyst cell-specific knockdown of α-Spectrin phenocopied CR45362 mutants and resulted in spermatid nuclear bundle defects. Consistently, CR45362 knockout disrupted the co-localization of α-Spectrin and spermatid nuclear bundles in the head cyst cells at the basal testis. Thus, we uncovered a novel lncRNA CR45362 that interacts with α-Spectrin to stabilize spermatid nuclear bundles during spermatid maturation.
Robust, flexible, and scalable tests for Hardy–Weinberg equilibrium across diverse ancestries
Authors: Kwong Alan M , Blackwell Thomas W , LeFaive Jonathon , de Andrade Mariza , Barnard John , Barnes Kathleen C , Blangero John , Boerwinkle Eric , Burchard Esteban G , Cade Brian E , Chasman Daniel I , Chen Han , Conomos Matthew P , Cupples L Adrienne , Ellinor Patrick T , Eng Celeste , Gao Yan , Guo Xiuqing , Irvin Marguerite Ryan , Kelly Tanika N , Kim Wonji , Kooperberg Charles , Lubitz Steven A , Mak Angel C Y , Manichaikul Ani W , Mathias Rasika A , Montasser May E , Montgomery Courtney G , Musani Solomon , Palmer Nicholette D , Peloso Gina M , Qiao Dandi , Reiner Alexander P , Roden Dan M , Shoemaker M Benjamin , Smith Jennifer A , Smith Nicholas L , Su Jessica Lasky , Tiwari Hemant K , Weeks Daniel E , Weiss Scott T ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,   TOPMed Analysis Working Group, Scott Laura J , Smith Albert V , Abecasis Gonçalo R , Boehnke Michael , Kang Hyun Min
Published: March 2021

Traditional Hardy–Weinberg equilibrium (HWE) tests (the χ2 test and the exact test) have long been used as a metric for evaluating genotype quality, as technical artifacts leading to incorrect genotype calls often can be identified as deviations from HWE. However, in data sets composed of individuals from diverse ancestries, HWE can be violated even without genotyping error, complicating the use of HWE testing to assess genotype data quality. In this manuscript, we present the Robust Unified Test for HWE (RUTH) to test for HWE while accounting for population structure and genotype uncertainty, and to evaluate the impact of population heterogeneity and genotype uncertainty on the standard HWE tests and alternative methods using simulated and real sequence data sets. Our results demonstrate that ignoring population structure or genotype uncertainty in HWE tests can inflate false-positive rates by many orders of magnitude. Our evaluations demonstrate different tradeoffs between false positives and statistical power across the methods, with RUTH consistently among the best across all evaluations. RUTH is implemented as a practical and scalable software tool to rapidly perform HWE tests across millions of markers and hundreds of thousands of individuals while supporting standard VCF/BCF formats. RUTH is publicly available at https://www.github.com/statgen/ruth.
Robust nonconforming virtual element methods for general fourth-order problems with varying coefficients
Authors: Dedner Andreas , Hodson Alice
Published: March 2021

We present a class of nonconforming virtual element methods for general fourth-order partial differential equations in two dimensions. We develop a generic approach for constructing the necessary projection operators and virtual element spaces. Optimal error estimates in the energy norm are provided for general linear fourth-order problems with varying coefficients. We also discuss fourth-order perturbation problems and present a novel nonconforming scheme which is uniformly convergent with respect to the perturbation parameter without requiring an enlargement of the space. Numerical tests are carried out to verify the theoretical results. We conclude with a brief discussion on how our approach can easily be applied to nonlinear fourth-order problems.
Rapidly Increasing Severe Acute Respiratory Syndrome Coronavirus 2 Neutralization by Intravenous Immunoglobulins Produced From Plasma Collected During the 2020 Pandemic
Authors: Farcet Maria R , Karbiener Michael , Schwaiger Julia , Ilk Reinhard , Kreil Thomas R
Published: March 2021

Immunoglobulin lots (N = 176) released since March 2020 were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies, with first positive results for September 2020 lots (mean, 1.7 IU/mL; 46% of lots positive). From there, values steadily increased, in correlation with the cumulative coronavirus disease 2019 (COVID-19) incidence, to reach a mean of 31.2 IU/mL and 93% of lots positive by January 2021. Extrapolating the correlation, immunoglobulins could reach an anti–SARS-CoV-2 potency of approximately 345 IU/mL by July 2021. At that stage, prophylactic immunoglobulin treatment for primary/secondary immunodeficiency could contain similar doses of anti–SARS-CoV-2 as convalescent plasma that is used for treatment of COVID-19.
Targeting Nrf2-antioxidant signalling reverses acquired cabazitaxel resistance in prostate cancer cells
Authors: Endo Satoshi , Kawai Mina , Hoshi Manami , Segawa Jin , Fujita Mei , Matsukawa Takuo , Fujimoto Naohiro , Matsunaga Toshiyuki , Ikari Akira
Published: March 2021

Prostate cancer is known to have a relatively good prognosis, but long-term hormone therapy can lead to castration-resistant prostate cancer (CRPC). Cabazitaxel, a second-generation taxane, has been used for the CRPC treatment, but its tolerance is an urgent problem to be solved. In this study, to elucidate the acquisition mechanism of the cabazitaxel-resistance, we established cabazitaxel-resistant prostate cancer 22Rv1 (Cab-R) cells, which exhibited ∼sevenfold higher LD50 against cabazitaxel than the parental 22Rv1 cells. Cab-R cells showed marked increases in nuclear accumulation of NF-E2 related factor 2 (Nrf2) and expression of Nrf2-inducible antioxidant enzymes compared to 22Rv1 cells, suggesting that Nrf2 signalling is homeostatically activated in Cab-R cells. The cabazitaxel sensitivity of Cab-R cells was enhanced by silencing of Nrf2, and that of 22Rv1 cells was reduced by activation of Nrf2. Halofuginone (HF) has been recently identified as a potent Nrf2 synthetic inhibitor, and its treatment of Cab-R cells not only suppressed the Nrf2 signalling by decreasing both nuclear and cytosolic Nrf2 protein levels, but also significantly augmented the cabazitaxel sensitivity. Thus, inhibition of Nrf2 signalling may be effective in overcoming the cabazitaxel resistance in prostate cancer cells.
Epigenetic effects induced by the ectopic expression of Pax7 in 3T3-L1
Authors: Elgaabari Alaa , Miyawaki-Kuwakado Atsuko , Tomimatsu Kosuke , Wu Qianmei , Tokunaga Kosuke , Izumi Wakana , Suzuki Takahiro , Tatsumi Ryuichi , Nakamura Mako
Published: March 2021

Although skeletal muscle cells and adipocytes are derived from the same mesoderm, they do not transdifferentiate in vivo and are strictly distinct at the level of gene expression. To elucidate some of the regulatory mechanisms underlying this strict distinction, Pax7, a myogenic factor, was ectopically expressed in 3T3-L1 adipose progenitor cells to perturb their adipocyte differentiation potential. Transcriptome analysis showed that ectopic expression of Pax7 repressed the expression of some adipocyte genes and induced expression of some skeletal muscle cell genes. We next profiled the epigenomic state altered by Pax7 expression using H3K27ac, an activating histone mark, and H3K27me3, a repressive histone mark, as indicators. Our results show that ectopic expression of Pax7 did not result in the formation of H3K27ac at loci of skeletal muscle-related genes, but instead resulted in the formation of H3K27me3 at adipocyte-related gene loci. These findings suggest that the primary function of ectopic Pax7 expression is the formation of H3K27me3, and muscle gene expression results from secondary regulation.
Emergence and Infestation Level of Hypothenemus hampei (Coleoptera: Curculionidae) on Coffee Berries on the Plant or on the Ground During the Post-harvest Period in Brazil
Authors: Pereira Adriano E , Gontijo Pablo C , Fantine Andreza K , Tinoco Ricardo S , Ellersieck Mark R , Carvalho Geraldo A , Zanuncio José C , Vilela Evaldo F
Published: March 2021

The coffee berry borer (CBB), Hypothenemus hampei Ferrari (Coleoptera: Curculionidae), is the most important coffee pest in most of the coffee growing countries. CBB females leave old dry berries after harvest and search for dry noninfested berries on the plant or on the ground to lay eggs or to use as refuge until new berries are available on the coffee trees in the following season. The CBB infestation level and emergence from berries on the ground or on the plants were evaluated in two fields post-harvest in the Spring in Brazil over two seasons. Twenty infested or noninfested berries in separate cages (250 ml plastic cups) were placed on the plants or on the ground under the tree canopy, in each field. The number of infested berries and CBB females that emerged from the infested berries were recorded weekly. CBB emergence was higher from berries on the ground than those on the coffee trees in both seasons, whereas CBB infestation was higher on coffee berries on the plants than those on the ground in season I. Insolation (hours of sunlight) and temperature were the main covariates that affected emergence and infestation by this insect. The results are discussed for monitoring CBB during the time of dispersal with implications on integrated management of this pest.
Breast Cancer–Related Employment Disruption and Financial Hardship in the Sister Study
Authors: Meernik Clare , Sandler Dale P , Peipins Lucy A , Hodgson M Elizabeth , Blinder Victoria S , Wheeler Stephanie B , Nichols Hazel B
Published: March 2021

Background

More than one-half of breast cancer cases are diagnosed among women aged younger than 62 years, which may result in employment challenges. This study examined whether cancer-related employment disruption was associated with increased financial hardship in a national US study of women with breast cancer.

Methods

Women with breast cancer who were enrolled in the Sister or Two Sister Studies completed a survivorship survey in 2012. Employment disruption was defined as stopping work completely or working fewer hours after diagnosis. Financial hardship was defined as: 1) experiencing financial problems paying for cancer care, 2) borrowing money or incurring debt, or 3) filing for bankruptcy because of cancer. Prevalence ratios and 95% confidence intervals for the association between employment disruption and financial hardship were estimated using multivariable Poisson regression with robust variance.

Results

We analyzed data from women employed at diagnosis (n = 1628). Women were a median age of 48 years at diagnosis and 5.6 years from diagnosis at survey completion. Overall, 27.3% of women reported employment disruption (15.4% stopped working; 11.9% reduced hours), and 21.0% experienced financial hardship (16.0% had difficulty paying for care; 12.6% borrowed money or incurred debt; 1.8% filed for bankruptcy). In adjusted analysis, employment disruption was associated with nearly twice the prevalence of financial hardship (prevalence ratio = 1.93, 95% confidence interval = 1.58 to 2.35).

Conclusions

Women experiencing employment disruptions after breast cancer may be more vulnerable to financial hardship. Findings highlight the need to target risk factors for employment disruption, facilitate return to work or ongoing employment, and mitigate financial consequences after cancer.
Light-emitting self-assembled metallacages
Authors: Zhao Jun , Zhou Zhixuan , Li Guangfeng , Stang Peter J , Yan Xuzhou
Published: March 2021

Coordination-driven self-assembly of metallacages has garnered significant interest because of their 3D layout and cavity-cored nature. The well-defined, highly tunable metallacage structures render them particularly attractive for investigating the properties of luminophores, as well as for inducing novel photophysical characters that enable widespread applications. In this review, we summarize the recent advances in synthetic methodologies for light-emitting metallacages, and highlight some representative applications of these metallacages. In particular, we focus on the favorable photophysical properties—including high luminescence efficiency in various physical states, good modularity in photophysical properties and stimulus responsiveness—that have resulted from incorporating ligands displaying aggregation-induced emission (AIE) into metallacages. These features show that the synergy between carrying out coordination-driven self-assembly and using luminophores with novel photophysical characteristics like AIE could stimulate the development of supramolecular luminophores for applications in fields as diverse as sensing, biomedicine and catalysis.
Motor Evoked Potential Recordings During Segmented Deep Brain Stimulation—A Feasibility Study
Authors: Shils Jay , Kochanski Ryan B , Borghei Alireza , Candocia Alexander , Pal Gian D , Afshari Mitra , Verhagen Leonard Metman , Sani Sepehr
Published: March 2021

BACKGROUND

Segmented deep brain stimulation (DBS) leads, which are capable of steering current in the direction of any 1 of 3 segments, can result in a wider therapeutic window by directing current away from unintended structures, particularly, the corticospinal tract (CST). It is unclear whether the use of motor evoked potentials (MEPs) is feasible during DBS surgery via stimulation of individual contacts/segments in order to quantify CST activation thresholds and optimal contacts/segments intraoperatively.

OBJECTIVE

To assess the feasibility of using MEP to identify CST thresholds for ring and individual segments of the DBS lead under general anesthesia.

METHODS

MEP testing was performed during pulse generator implantation under general anesthesia on subjects who underwent DBS lead implantation into the subthalamic nucleus (STN). Stimulation of each ring and segmented contacts of the directional DBS lead was performed until CST threshold was reached. Stereotactic coordinates and thresholds for each contact/segment were recorded along with the initially activated muscle group.

RESULTS

A total of 34 hemispheres were included for analysis. MEP thresholds were recorded from 268 total contacts/segments. For segmented contacts (2 and 3, respectively), the mean highest CST thresholds were 2.33 and 2.62 mA, while the mean lowest CST thresholds were 1.7 and 1.89 mA, suggesting differential thresholds in relation to CST. First dorsal interosseous and abductor pollicis brevis (34% each) were the most commonly activated muscle groups.

CONCLUSION

MEP threshold recording from segmented DBS leads is feasible. MEP recordings can identify segments with highest CST thresholds and may identify segment orientation in relation to CST.
Finding the strongest stable massless column with a follower load and relocatable concentrated masses
Authors: Kirillov Oleg N , Overton Michael L
Published: March 2021

We consider the problem of optimal placement of concentrated masses along a massless elastic column that is clamped at one end and loaded by a nonconservative follower force at the free end. The goal is to find the largest possible interval such that the variation in the loading parameter within this interval preserves stability of the structure. The stability constraint is nonconvex and nonsmooth, making the optimization problem quite challenging. We give a detailed analytical treatment for the case of two masses, arguing that the optimal parameter configuration approaches the flutter and divergence boundaries of the stability region simultaneously. Furthermore, we conjecture that this property holds for any number of masses, which in turn suggests a simple formula for the maximal load interval for $n$ masses. This conjecture is strongly supported by extensive computational results, obtained using the recently developed open-source software package granso (GRadient-based Algorithm for Non-Smooth Optimization) to maximize the load interval subject to an appropriate formulation of the nonsmooth stability constraint. We hope that our work will provide a foundation for new approaches to classical long-standing problems of stability optimization for nonconservative elastic systems arising in civil and mechanical engineering.
Germs, Social Networks, and Growth
Authors: Fogli Alessandra , Veldkamp Laura
Published: March 2021

Does the pattern of social connections between individuals matter for macroeconomic outcomes? If so, where do differences in these patterns come from and how large are their effects? Using network analysis tools, we explore how different social network structures affect technology diffusion and thereby a country’s rate of growth. The correlation between high-diffusion networks and income is strongly positive. But when we use a model to isolate the effect of a change in social networks on growth, the effect can be positive, negative, or zero. The reason is that networks diffuse both ideas and disease. Low-diffusion networks have evolved in countries where disease is prevalent because limited connectivity protects residents from epidemics. But a low-diffusion network in a low-disease environment compromises the diffusion of good ideas. In general, social networks have evolved to fit their economic and epidemiological environment. Trying to change networks in one country to mimic those in a higher-income country may well be counterproductive.
α1-Antitrypsin: Key Player or Bystander in Acute Respiratory Distress Syndrome?
Authors: Hogan Grace , Geoghegan Pierce , Carroll Tomás P. , Clarke Jennifer , McElvaney Oisín F. , McElvaney Oliver J. , McElvaney Noel G. , Curley Gerard F.
Published: March 2021

Acute respiratory distress syndrome is characterized by hypoxemia, altered alveolar–capillary permeability, and neutrophil-dominated inflammatory pulmonary edema. Despite decades of research, an effective drug therapy for acute respiratory distress syndrome remains elusive. The ideal pharmacotherapy for acute respiratory distress syndrome should demonstrate antiprotease activity and target injurious inflammatory pathways while maintaining host defense against infection. Furthermore, a drug with a reputable safety profile, low possibility of off-target effects, and well-known pharmacokinetics would be desirable. The endogenous 52-kd serine protease α1-antitrypsin has the potential to be a novel treatment option for acute respiratory distress syndrome. The main function of α1-antitrypsin is as an antiprotease, targeting neutrophil elastase in particular. However, studies have also highlighted the role of α1-antitrypsin in the modulation of inflammation and bacterial clearance. In light of the current SARS-CoV-2 pandemic, the identification of a treatment for acute respiratory distress syndrome is even more pertinent, and α1-antitrypsin has been implicated in the inflammatory response to SARS-CoV-2 infection.
Outcomes of pediatric anterior cruciate ligament reconstructions in patients with and without bucket handle meniscus repairs
Authors: Kawashima Itaru , Kawai Ryosuke , Tsukahara Takashi , Hiraiwa Hideki , Ishizuka Shinya , Kusaka Yoshiaki , Imagama Shiro
Published: March 2021

The purpose of this study was to report the outcomes of concomitant bucket handle meniscal tear (BHMT) repair and anterior cruciate ligament (ACL) reconstruction and to compare the outcomes with those after isolated ACL reconstruction in patients aged ≤16 years. Patients in our database from 2013 to 2017 were retrospectively analyzed. Patients were assigned to one of two treatment groups based on the presence of BHMTs: no meniscal tear group (group A) and BHMT group (group B). All BHMTs were repaired using the combined inside-out with all-inside technique. This study included 64 knees divided into two groups: 47 knees in group A and 17 knees in group B. There was a significant difference in the interval between ACL injury and surgery between groups A and B (69 vs. 150 days, respectively; P < 0.001). Mean postoperative International Knee Documentation Committee and Lysholm scores in group A were slightly, although significantly, improved compared to those in group B (96.5 vs. 92.6, respectively; P < 0.05, and 98 vs. 95, respectively; P < 0.05). There were no significant differences in postoperative anteroposterior laxity and graft failure rate between the groups. In group B, four patients (23.5%) required surgery for incomplete meniscal healing. Postoperative International Knee Documentation Committee and Lysholm scores of patients with BHMTs were significantly lower than those of patients without any meniscal tear, although with significant improvement in the amount of instability. Level of evidence was Level III.
Characterization of Nocturnal Neuroactive Medication Use and Related Sleep Documentation in Critically Ill Adults
Authors: Hamidi Arzo , Roberts Russel J. , Weinhouse Gerald L. , Szumita Paul M. , Degrado Jeremy R. , Dube Kevin M. , Kovacevic Mary P. , Choi Mia , Sevinsky Regan , Duprey Matthew S. , Devlin John W.
Published: March 2021

We retrospectively characterized scheduled, newly initiated, nocturnal neuroactive medication use, and related clinician documentation, in a cohort of consecutive adults admitted greater than or equal to 24 hours to seven different medical/surgical ICUs at two academic centers who had not received a scheduled nocturnal neuroactive medication prior to admission, over a 5-month period (April 1, 2017, to August 31, 2017). A total of 207 different newly initiated, scheduled nocturnal neuroactive medication orders were written (melatonin agonist 101 [48.8%], antipsychotic 80 [38.6%], antidepressant 17 [8.2%], benzodiazepine 9 [4.3%]) in 189 (9.7%) of the 1,955 patients. Among the 1,553 nights, the 189 patients spent in the ICU, a scheduled nocturnal neuroactive medication was administered on 1,103 (71%), an “as needed” nocturnal neuroactive medication was solely administered on 183 (11.8%), delirium occurred on 736 (47.4%), and nurses were twice as likely as physicians (28.8% vs 11.4%; p < 0.0001) to document a note about sleep quality. Among the 69.8% of patients discharged to the floor, and the 64.5% from the hospital, the scheduled nocturnal neuroactive medication was continued in 85.6% and 87.3%, respectively. Scheduled nocturnal neuroactive medication initiation is common, often continued beyond hospital discharge, and poorly documented.
Models of supportive care in oncology
Authors: Hui David , Hoge Geordyn , Bruera Eduardo
Published: March 2021

Purpose of review

Supportive care services have evolved overtime to meet the growing supportive care need of patients with cancer and their families. In this review, we summarize existing definitions of supportive care, highlight empiric studies on supportive care delivery, and propose an integrated conceptual framework on supportive cancer care.

Recent findings

Supportive care aims at addressing the patients’ physical, emotional, social, spiritual, and informational needs throughout the disease trajectory. Interdisciplinary teams are needed to deliver multidimensional care. Oncology teams have an important role providing supportive care in the front lines and referring patients to supportive care services such as palliative care, social work, rehabilitation, psycho-oncology, and integrative medicine. However, the current model of as needed referral and siloed departments can lead to heterogeneous access and fragmented care. To overcome these challenges, we propose a conceptual model in which supportive care services are organized under one department with a unified approach to patient care, program development, and research. Key features of this model include universal referral, systematic screening, tailored specialist involvement, streamlined care, collaborative teamwork, and enhanced outcomes.

Further research is needed to develop and test innovative supportive care models that can improve patient outcomes.
Anti-PD1 Immunotherapy for Metastatic Renal Cancer Boosted Humoral Immunity In a Hemodialysis Patient
Authors: Eleftheriadis Theodoros , Pissas Georgios , Liakopoulos Vassilios , Stefanidis Ioannis
Published: March 2021

Immune checkpoint inhibitors by blocking specific inhibitory pathways induce T-cell-mediated tumor lysis. However, many remain to be elucidated about their effect on human humoral immunity. We evaluated the effect of the PD1 inhibitor nivolumab on humoral immunity by following the levels of antibodies against hepatitis B surface antigen (anti-HBs) in a hemodialysis patient successfully vaccinated against hepatitis B virus 5 years ago and now starting nivolumab for renal cell carcinoma lung metastases. Anti-HBs kinetics after administration of an extra vaccine dose were also evaluated. Nivolumab increased anti-HBs and facilitated a further increase following an additional vaccine dose. The observed time frame indicates that nivolumab boosts humoral immune response by affecting long-lived plasma cells and at least memory B cells. This may protect cancer patients from pathogens encountered in the past or against which vaccination has been performed and provide information for the emerging immune checkpoint inhibitors administration concept against chronic infectious diseases.
Sarcopenia is a Predictor for Adverse Clinical Outcome in Pediatric Inflammatory Bowel Disease
Authors: Atlan Lilian , Cohen Shlomi , Shiran Shelly , Sira Liat Ben , Pratt Li‐Tal , Yerushalmy‐Feler Anat
Published: March 2021

Objectives:

Inflammatory bowel disease (IBD) has a high impact on nutritional status. Sarcopenia is related to higher risk of surgery and rescue therapy in adults with IBD; however, comparable data in pediatric populations are scarce. We evaluated muscle mass as a predictor of disease outcome in pediatric IBD.

Methods:

All pediatric IBD patients who underwent magnetic resonance enterography (MRE) during 2008 to 2019 were included. Muscle mass was assessed by measuring the area of the psoas muscle at the upper level of L3 on MRE. The psoas area divided by the body surface area (BSA) yielded the psoas index. Clinical and radiological data, including disease location, activity, course, and medications were documented. The control group included non‐IBD children who underwent an MR imaging study.

Results:

We enrolled 101 IBD patients, 69 (68.3%) with Crohn disease (CD) and 32 (31.7%) with ulcerative colitis (UC) (mean age 15.03 ± 3.27 years). The psoas index was significantly lower in the IBD patients compared with the 87 controls (326 vs 528, respectively, P < 0.001). Patients with a psoas index in the lowest quartile had significantly higher risk for biologic therapy (multivariate analysis, hazard ratio [HR] = 12.1, P = 0.046) and disease exacerbation (HR = 9, P = 0.047) independently of body mass index, compared with patients with a psoas index in the uppermost quartile.

Conclusions:

Sarcopenia correlates with the radiological severity of pediatric IBD and serves as a predictor for adverse clinical disease outcome. Muscle mass measurement in MRE studies may serve as a possible marker for disease outcome in this population.
Severe aortic stenosis is associated with perioperative mortality in proximal femur fracture patients
Authors: Cronin Patrick K. , Olson Jeffrey J. , Harris Mitchel B. , Weaver Michael J.
Published: March 2021

Objectives:

Evaluate the correlation between aortic stenosis and perioperative mortality in patients following surgical fixation of proximal femur fractures.

Design:

Retrospectively reviewed case series.

Setting:

Two Academic, Level 1 Trauma Centers.

Patients/Participants:

One hundred fifty-eight patients, definitively diagnosed with aortic stenosis by means of echocardiogram, who underwent surgical fixation for an isolated proximal femur fracture (OTA/AO 31-A, 31-B, 32-A, 32-B, and 32-C fractures) between January 2000 and June 2015. The severity of the aortic stenosis was based upon accepted echocardiographic hemodynamic parameters designated by the 2014 American Heart Association guidelines.

Main Outcome Measures:

Post Injury mortality, 30-day mortality, and 1-year mortality.

Secondary Outcome Measures:

Postoperative mortality stratified by severity of aortic stenosis based on aortic valve area (AVA) and ejection fracture (EF) as determined by preoperative echocardiography.

Results:

One hundred fifty-eight patients were available for final analysis. Kaplan–Meier survival analysis revealed a significantly longer time to mortality among Non-severe aortic stenosis patients compared to Severe aortic stenosis patients, P value .006. Twenty-three percent of patients with Severe aortic stenosis and 10% of patients with Non-severe aortic stenosis died within 30 days of surgery. No significant difference was observed in mean survival among AS patients who underwent surgery within 48 hours of injury (34.5 months) and those delayed more than 48 hours after injury (25.0 months), P value .116. Among the commonly measured hemodynamic parameters of aortic stenosis, only AVA and EF were significantly associated with mortality, P value .015, and P value < .001, respectively. There were no significant effects for Aortic Vmax, Peak ΔP, and Mean ΔP. An AVA of 0.8 cm2 or less is associated with a significantly shorter (22 months) postinjury mortality than patients with an AVA > 0.8 cm2. (37 months), P value .009.

Conclusions:

Severe aortic stenosis is associated with a shorter postoperative time to mortality after surgical fixation of hip fractures compared to patients with Non-severe stenosis. Aortic valve area and Ejection Fraction are the only hemodynamic parameters significantly associated with postoperative mortality.

Level of Evidence: Prognostic Level III
Comparison of reamed long and short intramedullary nail constructs in unstable intertrochanteric femur fractures
Authors: Blum Laura E. , Yee Michael A. , Mauffrey Cyril , Goulet James A. , Perdue Aaron M. , Hake Mark E.
Published: March 2021

Objectives:

There is no definitive evidence to guide clinicians in their decision-making for implant choice regarding long or short intramedullary nails for unstable fracture patterns. Historically short nails were associated with higher rates of perisprothetic fractures which seem to have improved with newer designs. Long intramedullary nails have higher blood loss and time under anesthesia. The purpose of this study was to assess stability of long and short intramedullary nail constructs in unstable intertrochanteric fracture patterns to better elucidate if unstable intertrochanteric fractures are amenable to treatment with short intramedullary nails.

Methods:

This study utilized composite model femurs which were assigned to either a comminuted or reverse obliquity fracture pattern, then subsequently assigned to implantation with either a long or short intramedullary nail. All the samples were reamed to the level of the distal femur and instrumented with the appropriate nail. Axial and torsional stiffness as well as axial load to failure values were determined using a servohydraulic loading system.

Results:

Short nail constructs exhibited significantly greater axial stiffness in A1 fractures and torsional stiffness in A3 fractures when compared with long nails. There was no significant difference between axial load to failure between long nails and short nails.

Discussion:

We found no significant difference in axial load to failure values between long and short intramedullary nail fixation in 2 unstable intertrochanteric fracture patterns in a composite femur model. Short nails exhibited greater stiffness in axial loads in the A1 pattern and torsional stiffness in the A3 pattern. This suggests short or long intramedullary nails could be appropriately employed for fixation of unstable intertrochanteric hip fracture patterns.