bluuebunny/crossref_metadata_2025 huggingface dataset:
Histologic and Racial/Ethnic Patterns of Appendiceal Cancer among Young Patients
Authors: Gibbs Timothy , Washington Mary K. , Eng Cathy , Idrees Kamran , Davis Jamaine , Holowatyj Andreana N.
Published: April 2021

Background:

Appendiceal cancer incidence among individuals age < 50 years (early-onset appendiceal cancer) is rising with unknown etiologies. Distinct clinicopathologic/demographic features of early-onset appendiceal cancer remain unexplored. We compared patterns of appendiceal cancer among individuals by age of disease-onset.

Methods:

Using the NIH/NCI's Surveillance, Epidemiology, and End Results program data, we identified individuals age 20+ years diagnosed with appendiceal cancer from 2007 to 2016. Cochran–Armitage trend tests and multinomial logistic regression models were used to examine age-related differences in clinicopathologic/demographic features of appendiceal cancer.

Results:

We identified 8,851 patients with appendiceal cancer during the 10-year study period. Histologic subtype, tumor grade, stage, sex and race/ethnicity all significantly differed by age of appendiceal cancer diagnosis. After adjustment for race/ethnicity, sex, stage, insurance status, and tumor grade, young patients were 82% more likely to be Hispanic [OR, 1.82; 95% confidence interval (CI), 1.48–2.25; P < 0.001] and 4-fold more likely to be American Indian or Alaska Native (OR, 4.02; 95% CI, 1.77–9.16; P = 0.0009) compared with late-onset cases. Patients with early-onset appendiceal cancer were also 2- to 3.5-fold more likely to be diagnosed with neuroendocrine tumors of the appendix (goblet cell carcinoid: OR, 1.96; 95% CI, 1.59–2.41; P < 0.0001; carcinoid: OR, 3.52; 95% CI, 2.80–4.42; P < 0.0001) compared with patients with late-onset appendiceal cancer. Among patients with neuroendocrine tumors, early-onset cases were also 45% to 61% less likely to present with high-grade (III–IV) tumors.

Conclusions:

Approximately one in every three patients with appendiceal cancer is diagnosed before age 50 years in the United States. Appendiceal cancer in young patients is classified by distinct histologic and demographic features.

Impact:

Early-onset appendiceal cancer determinants can inform discovery of risk factors and molecular biomarkers of appendiceal cancer in young patients, with implications for appendiceal cancer prevention, detection, and treatment.
Epidemiologic Research of Rare Cancers: Trends, Resources, and Challenges
Authors: Gallicchio Lisa , Daee Danielle L. , Rotunno Melissa , Barajas Rolando , Fagan Sarah , Carrick Danielle M. , Divi Rao L. , Filipski Kelly K. , Freedman Andrew N. , Gillanders Elizabeth M. , Lam Tram K. , Martin Damali N. , Rogers Scott , Verma Mukesh , Nelson Stefanie A.
Published: April 2021

Background:

The goals of this project were to assess the status of NCI's rare cancer–focused population science research managed by the Division of Cancer Control and Population Sciences (DCCPS), to develop a framework for evaluation of rare cancer research activities, and to review available resources to study rare cancers.

Methods:

Cancer types with an overall age-adjusted incidence rate of less than 20 cases per 100,000 individuals were identified using NCI Surveillance, Epidemiology and End Results (SEER) Program data. SEER data were utilized to develop a framework based on statistical commonalities. A portfolio analysis of DCCPS-supported active grants and a review of three genomic databases were conducted.

Results:

For the 45 rare cancer types included in the analysis, 123 active DCCPS-supported rare cancer-focused grants were identified, of which the highest percentage (18.7%) focused on ovarian cancer. The developed framework revealed five clusters of rare cancer types. The cluster with the highest number of grants (n = 43) and grants per cancer type (10.8) was the cluster that included cancer types of higher incidence, average to better survival, and high prevalence (in comparison with other rare cancers). Resource review revealed rare cancers are represented in available genomic resources, but to a lesser extent compared with more common cancers.

Conclusions:

This article provides an overview of the rare cancer–focused population sciences research landscape as well as information on gaps and opportunities.

Impact:

The findings of this article can be used to develop efficient and comprehensive strategies to accelerate rare cancer research.

See related commentary by James V. Lacey Jr, p. 1300
Liquid Biopsy: It's the Bloody Truth!
Authors: Hawkey Nathan M. , Armstrong Andrew J.
Published: April 2021

Liquid biopsy is a promising clinical tool that can provide critical information for prognostication and which may inform treatment decisions in men with metastatic castration-resistant prostate cancer. Here we discuss the Foundation Medicine plasma cell-free circulating tumor DNA assay, its pros and cons, and potential clinical utility.

See related article by Tukachinsky et al., p. 3094
Synthetic Lethality in Cancer Therapeutics: The Next Generation
Authors: Setton Jeremy , Zinda Michael , Riaz Nadeem , Durocher Daniel , Zimmermann Michal , Koehler Maria , Reis-Filho Jorge S. , Powell Simon N.
Published: April 2021

Synthetic lethality (SL) provides a conceptual framework for tackling targets that are not classically “druggable,” including loss-of-function mutations in tumor suppressor genes required for carcinogenesis. Recent technological advances have led to an inflection point in our understanding of genetic interaction networks and ability to identify a wide array of novel SL drug targets. Here, we review concepts and lessons emerging from first-generation trials aimed at testing SL drugs, discuss how the nature of the targeted lesion can influence therapeutic outcomes, and highlight the need to develop clinical biomarkers distinct from those based on the paradigms developed to target activated oncogenes.

Significance:

SL offers an approach for the targeting of loss of function of tumor suppressor and DNA repair genes, as well as of amplification and/or overexpression of genes that cannot be targeted directly. A next generation of tumor-specific alterations targetable through SL has emerged from high-throughput CRISPR technology, heralding not only new opportunities for drug development, but also important challenges in the development of optimal predictive biomarkers.
Cell Phone Selfies: Clinching the Diagnosis of Iris Microhemangiomatosis
Authors: Price Kenneth W. , Gorham John P. , Wells Jill R.
Published: April 2021

Four patients presented with a history of “blood” or a “dark spot” in the eye captured on cell phone photos. These episodes prompted presentation to an ophthalmologist where they all had normal slit lamp exams without a hyphema at initial evaluation. With evidence of a spontaneous hyphema seen on photos, further testing was performed including iris fluorescein angiography which revealed hyperfluorescent iris margin vascular tufts, confirming the diagnosis of iris microhemangiomatosis in each patient. All cases were managed conservatively, and only 1 needed topical antihypertensives. Without these patient-initiated photos, the diagnosis of iris microhemangiomatosis would likely remain elusive as slit lamp exam was normal at the time of initial examination in all 4 cases. Ophthalmologists should be aware of this rare diagnosis in the event a patient comes with a cell phone selfie documenting a spontaneous hyphema, especially when emanating from pupillary border.
Obesity, Blood Pressure, and Intraocular Pressure: A Cross-Sectional Study in Italian Children
Authors: Pileggi Claudia , Papadopoli Rosa , De Sarro Caterina , Nobile Carmelo Giuseppe Angelo , Pavia Maria
Published: April 2021

Introduction: Several studies in the adult population have shown that obesity is an independent risk factor for elevated intraocular pressure (IOP), whereas data in the paediatric population are sparse and controversial. The purpose of the present study is to investigate the relationship between body mass index (BMI), blood pressure (BP), and IOP in healthy school children. Methods: The survey was conducted among a random sample of 8-year-old Italian students. Data were collected on their health status and behaviours related to obesity (physical activity, food and drinking habits, etc.). Physical examinations, conducted at school, included measurements of height, weight, BP, and IOP. Results: Five hundred and seventy-six subjects were recruited (92.8% response rate); 42.4% were overweight or obese, 58.9% consumed inadequate daily servings of fruit and vegetables, and 87.5% were involved in sedentary activities. Elevated BP/hypertension (HTN) affected 3.6% and high IOP was revealed in 12.5% of the children. In the multivariate analysis, elevated BP/HTN was the only significant determinant of ocular HTN (OR 5.36, 95% CI 1.95–14.73, p = 0.001). Conclusions: Our results show that high IOP affects 12.5% of 8-year-old school children and appears to be associated with high BP related to a high BMI.
Penicilliumin B Protects against Cisplatin-Induced Renal Tubular Cell Apoptosis through Activation of AMPK-Induced Autophagy and Mitochondrial Biogenesis
Authors: Shen Weiwei , Jia Nan , Miao Jinhua , Chen Shuangqin , Zhou Shan , Meng Ping , Zhou Xuefeng , Tang Lan , Zhou Lili
Published: April 2021

Introduction: Acute kidney injury (AKI) is at a high prevalence in hospitalized patients, especially in those receiving chemotherapy. Cisplatin is the most widely used chemotherapy drug; however, with its side effects that include nephrotoxicity, it also exhibits a risk of inducing AKI. Importantly, recent studies have shown that autophagy plays a protective role in cisplatin-induced AKI. However, therapeutic strategies and candidate drugs for inducing activation of autophagy remain limited. Methods: In the present study, we adopted a novel candidate drug from a deep sea-derived Penicillium strain, penicilliumin B, to testify its protective role in cisplatin-induced renal tubular cell injury. Results: Penicilliumin B exhibited protection against cisplatin-induced apoptosis in cultured renal tubular epithelial cells and in cisplatin-treated mice. Moreover, penicilliumin B maintained normal mitochondrial morphology and inhibited the production of mitochondrial reactive oxygen species. Further studies demonstrated that penicilliumin B enhanced autophagic flux, promoted the activation of multiple autophagy-related proteins, such as mTOR, Beclin-1, ATG5, PINK1, and LC3B, and induced the degradation of p62. Interestingly, we also found penicilliumin B triggered phosphorylation of adenosine 5‘-monophosphate-activated protein kinase (AMPK), which is an upstream inducer of nearly all autophagy pathways and also an activator of mitochondrial biogenesis. These results suggest that AMPK may represent an activated site of penicilliumin B. Consistently, compound C, an AMPK inhibitor, significantly blocked the protective effects of penicilliumin B on mitochondria and apoptotic inhibition. Conclusion: Taken together, our findings indicate that penicilliumin B represents a novel AMPK activator that may provide protection against renal tubular cell apoptosis through activation of AMPK-induced autophagy and mitochondrial biogenesis.
Expression Analyses of Mediator Complex Subunit 13-Like: A Responsible Gene for Neurodevelopmental Disorders during Mouse Brain Development
Authors: Hamada Nanako , Iwamoto Ikuko , Nishikawa Masashi , Nagata Koh-ichi
Published: April 2021

MED13L (mediator complex subunit 13-like) is a component of the mediator complex, which functions as a regulator for gene transcription. Since gene abnormalities in MED13L are responsible for neurodevelopmental disorders, MED13L is presumed to play an essential role in brain development. In this study, we prepared a specific antibody against MED13L, anti-MED13L, and analyzed its expression profile in mouse tissues with focusing on the central nervous system. In Western blotting, MED13L exhibited a tissue-dependent expression profile in the adult mouse and was expressed in a developmental stage-dependent manner in brain. In immunofluorescence analyses, MED13L was at least partially colocalized with pre- and post-synaptic markers, synaptophysin, and PSD95, in primary cultured hippocampal neurons. Immunohistochemical analyses revealed that MED13L was relatively highly expressed in ventricular zone surface of cerebral cortex, and was also located both in the cytoplasm and nucleus of neurons in the cortical plate at embryonic day 14. Then, MED13L showed diffuse cytoplasmic distribution throughout the cerebral cortex at the postnatal day (P) 30. In addition, MED13L appeared to be localized in cell type- and developmental stage-specific manners in the hippocampus and cerebellum. These results suggest that MED13L is involved in the development of the central nervous system and synaptic function.
A Role for Vasoactive Intestinal Peptide Interneurons in Neurodevelopmental Disorders
Authors: Goff Kevin M. , Goldberg Ethan M.
Published: April 2021

GABAergic inhibitory interneurons of the cerebral cortex expressing vasoactive intestinal peptide (VIP-INs) are rapidly emerging as important regulators of network dynamics and normal circuit development. Several recent studies have also identified VIP-IN dysfunction in models of genetically determined neurodevelopmental disorders (NDDs). In this article, we review the known circuit functions of VIP-INs and how they may relate to accumulating evidence implicating VIP-INs in the mechanisms of prominent NDDs. We highlight recurring VIP-IN-mediated circuit motifs that are shared across cerebral cortical areas and how VIP-IN activity can shape sensory input, development, and behavior. Ultimately, we extract a set of themes that inform our understanding of how VIP-INs influence pathogenesis of NDDs. Using publicly available single-cell RNA sequencing data from the Allen Institute, we also identify several underexplored disease-associated genes that are highly expressed in VIP-INs. We survey these genes and their shared related disease phenotypes that may broadly implicate VIP-INs in autism spectrum disorder and intellectual disability rather than epileptic encephalopathy. Finally, we conclude with a discussion of the relevance of cell type-specific investigations and therapeutics in the age of genomic diagnosis and targeted therapeutics.
The Genetics of Prey Susceptibility to Myxobacterial Predation: A Review, Including an Investigation into Pseudomonas aeruginosa Mutations Affecting Predation by Myxococcus xanthus
Authors: Sydney Natashia , Swain Martin T. , So Jeffery M.T. , Hoiczyk Egbert , Tucker Nicholas P. , Whitworth David E.
Published: April 2021

Bacterial predation is a ubiquitous and fundamental biological process, which influences the community composition of microbial ecosystems. Among the best characterised bacterial predators are the myxobacteria, which include the model organism Myxococcus xanthus. Predation by M. xanthus involves the secretion of antibiotic metabolites and hydrolytic enzymes, which results in the lysis of prey organisms and release of prey nutrients into the extracellular milieu. Due to the generalist nature of this predatory mechanism, M. xanthus has a broad prey range, being able to kill and consume Gram-negative/positive bacteria and fungi. Potential prey organisms have evolved a range of behaviours which protect themselves from attack by predators. In recent years, several investigations have studied the molecular responses of a broad variety of prey organisms to M. xanthus predation. It seems that the diverse mechanisms employed by prey belong to a much smaller number of general “predation resistance” strategies. In this mini-review, we present the current state of knowledge regarding M. xanthus predation, and how prey organisms resist predation. As previous molecular studies of prey susceptibility have focussed on individual genes/metabolites, we have also undertaken a genome-wide screen for genes of Pseudomonas aeruginosa which contribute to its ability to resist predation. P. aeruginosa is a World Health Organisation priority 1 antibiotic-resistant pathogen. It is metabolically versatile and has an array of pathogenic mechanisms, leading to its prevalence as an opportunistic pathogen. Using a library of nearly 5,500 defined transposon insertion mutants, we screened for “prey genes”, which when mutated allowed increased predation by a fluorescent strain of M. xanthus. A set of candidate “prey proteins” were identified, which shared common functional roles and whose nature suggested that predation resistance by P. aeruginosa requires an effective metal/oxidative stress system, an intact motility system, and mechanisms for de-toxifying antimicrobial peptides.
Intravenous Tirofiban Infusion After Angioplasty and Stenting in Intracranial Atherosclerotic Stenosis-Related Stroke
Authors: Baek Byung Hyun , Yoon Woong , Lee Yun Young , Kim Seul Kee , Kim Joon-Tae , Park Man Seok
Published: April 2021

Background and Purpose:

This study aimed to investigate the effectiveness and safety of intravenous infusion of tirofiban after emergent angioplasty with or without stenting in patients with intracranial atherosclerotic stenosis-related large-vessel occlusion stroke.

Methods:

We performed a retrospective case series study of 98 patients who underwent thrombectomy followed by angioplasty with or without stenting to treat intracranial atherosclerotic stenosis-related large-vessel occlusion. Patients were divided into 2 groups: those who received continuous intravenous infusion of tirofiban for 12 hours after procedure (intravenous tirofiban group, n=30) and those who did not receive postprocedural intravenous tirofiban (control group, n=68). The following treatment outcomes in the 2 groups were compared: early reocclusion of treated arteries on computed tomography angiography, parenchymal hematoma, symptomatic hemorrhage, and 90-day functional outcome.

Results:

Early reocclusion occurred in 18 patients (18.4%). The rate of early reocclusion was significantly lower in the intravenous tirofiban group than in the control group (3.3% versus 25%,
P
<0.001). The rates of parenchymal hematoma, symptomatic hemorrhage, 90-day good outcome, and mortality were not significantly different between the 2 groups. In multivariate logistic analysis, the only independent predictor of early reocclusion was no use of intravenous tirofiban (odds ratio, 9.212 [95% CI, 1.155–73.495],
P
=0.036). A good outcome (90-day modified Rankin Scale score of 0–2) was significantly less frequent in patients with early reocclusion than in those without it (16.7% versus 72.5%,
P
<0.001).

Conclusions:

The use of intravenous tirofiban for 12 hours was associated with decreased risk of early reocclusion of treated arteries, with no increased risk of hemorrhage after emergent angioplasty, with or without stenting, in patients with intracranial atherosclerotic stenosis-related large-vessel occlusion stroke. Early reocclusion was associated with a poor outcome in such cases.
Bursaphelenchus paraleoni n. sp. (Tylenchina: Aphelenchoididae) intercepted in Loblolly pine logs imported into China from the USA
Authors: Gu Jianfeng , Fang Yiwu , Liu Lele , Ma Xinxin , Lu Xiaoling
Published: April 2021

Bursaphelenchus paraleoni n. sp. was isolated from Loblolly pine, Pinus taeda, logs from the USA. The new species is characterised by a lateral field with three lines, 13-16 μm long stylet with small basal swellings, and the excretory pore located slightly posterior to the nerve ring. The male spicules are mitten-shaped, the lamina smoothly tapering towards the distal tip. The condylus is broadly rounded, with a small dorsally bent hook, rostrum triangular or conical with finely rounded tip, and cucullus absent. One midventral precloacal papilla, one adcloacal pair and two postcloacal pairs of genital papillae are present. The bursal flap is long and spade-like with the posterior margin truncate or irregular. Females have a small vulval flap 4-6 μm long, a post-vulval uterine sac extending for 34-49% of the vulva to anus distance, a very long tail with slight ventral curvature, mostly filiform and with a finely rounded terminus, occasionally bluntly rounded. Huge variation in the tails of males and females were observed in a culture. It is similar to species of B. eidmanni, B. leoni, and B. silvestris in the leoni-group but detailed phylogenetic analysis based on 18S, ITS and D2-D3 28S sequences confirmed it as a new species.
Reappointment to International Courts and the Case of the EFTA Court
Authors: Tatham Allan F.
Published: April 2021

The independence of judges sitting on international courts is constrained in part by their accountability to the states that appoint them. The interaction between these two principles is particularly stark where judges are able to have their terms of office on the bench renewed, subject to the agreement of states to re-nominate and reappoint them. The present article seeks to examine this interaction, initially in the context more generally of international judicial decision-making bodies, while also considering options designed to reduce the likelihood of the reoccurrence of problems with respect to reappointments. It then provides a more detailed case study of the Norwegian reappointment saga at the EFTA Court and suggests possible ways forward designed to enhance judicial independence in this procedure.
A Narrativist Revival?
Authors: Ankersmit Frank R.
Published: April 2021

Up till the 1980s narrativist philosophers of history were mainly interested in the cognitivist dimension of historical narrative. With Hayden White this interest was exchanged for an exclusive preoccupation with the literary aspects of the historian’s narrative representation of the past. However, it may seem that a revival of pre-Whitean narrativist philosophy of history is at hand. Two recent books suggest as much: one by Chiel van den Akker published in 2018 and one more by Paul Roth that came out in 2020. Obviously, a narrativist revival can take two different forms. It may aim at providing pre-Whitean narrativism with a more up-to-date philosophical basis or at guiding it into new directions. It will be argued in this review-essay that the book by Roth mainly does the former, whereas the book by Van den Akker does both.
Dancing with Greek Vases
Authors: Laferrière Carolyn M.
Published: April 2021

As gods dance, women twirl in choruses, and men leap in kōmos revels on Athenian red-figure vases, their animate bodies must be made to conform to the rounded shape of the vessels. Occasionally, these vases are even included in the images themselves, particularly within the kōmos revel, where the participants incorporate vessels into their dance as props, markers of space, and tools to engage new dance partners. Positioning these scenes within their potential sympotic context, I analyze the vases held by the dancers according to the ancient viewer’s own possible use of these physical vessels. The symposiasts’ own dextrous interaction with the objects echoes the dancers’ behaviors, so that human and ceramic bodies come together in shared movement. The handling of vases thus suggests a tactile, embodied experience shared between dancers and viewers; by evoking viewers’ familiarity with handling similar vessels, the vase-paintings invite viewers to join in the dance.
Vitruvius De Architectura V
Authors: Pöhlmann Egert
Published: April 2021

In Book 5 of De architectura, the main subjects of Vitruvius are the Roman and Greek theatre and their acoustic qualities, explained with the help of several Greek theories. Vitruvius tries to enhance them by introducing a system of assisted resonance. Following the Harmonics of Aristoxenus, he recommends equipping theatre buildings with ἠχεῖα of bronze or earthenware, with the aim of increasing the strength of the voices of actors. Archaeological evidence for such equipment is nonexistent. But in Eastern and Western churches, vessels under the floor and in the walls were found. The Western examples begin in Carolingian times, when De architectura became known again. Thus, there is a debate about whether or not the work of Vitruvius had an influence on Carolingian architecture. The ἠχεῖα of Vitruvius and the resounding vessels in churches work as Helmholtz-Resonators, the sound-absorbing effects of which were used in churches with high internal resonance, while their sound-reinforcing effects were the aim of the ἠχεῖα in theatres.
Recognising Freedom of Thought in Irish Constitutional Law
Authors: Cahill Maria
Published: April 2021

Recent technological advances have made clear that the law needs to take a stance in relation to freedom of thought. Although there is no formal recognition of freedom of thought in the text of the 1937 Constitution of Ireland, I will argue that such a right does exist in Irish law on the basis of both implicit and initial explicit recognition for freedom of thought in the decisions of the superior courts. Part 2 lays out the ways in which freedom of thought is implicitly recognised in the Irish legal system, both through the protection of other constitutional rights and through the place of international law in the Irish legal order. Part 3 takes the analysis a step further, using the doctrine of unenumerated rights (a peculiarity of Irish constitutional law) to spotlight an overlooked Supreme Court judgment in which the right to freedom of thought has been judicially recognised in the absence of a textual mandate in the Constitution. It then proceeds to shore up arguments in favour of such recognition, arguing that protecting freedom of thought is a good thing, because it honours human freedom and human dignity.
Gratitude as the Foundation for Joy
Authors: Emmons Robert A. , Afshar Marc
Published: April 2021

Joy and gratitude are two of the deepest touch points of human existence. Joy is a multi-faceted concept that is best thought of as an emotion-virtue composed of delight in that which is ultimately good. Gratitude is an affirmation of the good and a recognition of where that good is sourced. As self-transcendent, positive emotion dispositions at the heart of many religious and spiritual traditions, these qualities are key components of the flourishing life. Gratitude been object of serious study across many traditions for many centuries; joy has only recently become the focus of investigations in theology and in the human sciences. We explore the connection between the two, and with a special focus on youth thriving, we consider how gratitude practices can potentiate joy.
New species and new distributional record of the genus Broscosoma Rosenhauer, 1846 (Coleoptera, Carabidae, Broscinae) from China
Authors: JIANG RI-XIN , LIU XIAO-FAN , WANG SHUO
Published: April 2021

Two new species of the genus Broscosoma Rosenhauer, 1846 are described from China: Broscosoma guoliangi sp. nov. from Fujian Province and Broscosoma qiului sp. nov. from Chongqing City, respectively. In addition, Broscosoma ribbei rougeriei Deuve & Tian, 2002 is newly recorded from Derung-Nu Autonomous County Gongshan, Yunnan Province, China.
Species delimitation of the praying mantis Hierodula patellifera (Audinet-Serville) based on morphological and molecular characters (Mantodea: Mantidae)
Authors: SHIM JAEIL , PARK HAECHUL , KIM SEONGHYUN , JU HO-JONG , SONG JEONG-HUN
Published: April 2021

An integrative taxonomic analysis of Hierodula patellifera (Audinet-Serville) is presented based on morphological and molecular characters (COI, 28S rDNA). During repeated trips to the Korean peninsula, we collected unusual specimens from Wanju-gun. They were similar to H. patellifera, but can be distinguished by a larger body size, the number and shape of spines on foreleg, and the shape of male genitalia. To examine the phenotypes and delimit H. patellifera from fourteen sampled populations, we used forecoxal spines and male genitalia as key morphological characters, as well as molecular data including gene tree monophyly and genetic divergence data. The molecular analyses (p-distance, neighbor-joining, and parsimony analyses) did not separate the specimens as two distinct species. The diagnostic characters of H. patellifera are illustrated with habitus images.
Prognostic value of measurable residual disease after venetoclax and decitabine in acute myeloid leukemia
Authors: Maiti Abhishek , DiNardo Courtney D. , Wang Sa A. , Jorgensen Jeffrey , Kadia Tapan M. , Daver Naval G. , Short Nicholas J. , Yilmaz Musa , Pemmaraju Naveen , Borthakur Gautam , Bose Prithviraj , Issa Ghayas C. , Ferrajoli Alessandra , Jabbour Elias J. , Jain Nitin , Garcia-Manero Guillermo , Ohanian Maro , Takahashi Koichi , Montalban-Bravo Guillermo , Masarova Lucia , Burger Jan A. , Thompson Philip A. , Verstovsek Srdan , Sasaki Koji , Andreeff Michael , Rausch Caitlin R. , Montalbano Kathryn S. , Pierce Sherry , Qiao Wei , Ning Jing , Kantarjian Hagop M. , Konopleva Marina Y. , Ravandi Farhad
Published: April 2021

Assessment of measurable residual disease (MRD) provides prognostic information in acute myeloid leukemia (AML). However, the utility of MRD with venetoclax-based lower intensity regimens is unknown. We analyzed the prognostic value of achieving a negative MRD in older/“unfit” patients with AML receiving first-line therapy with 10-day decitabine and venetoclax. MRD was evaluated in bone marrow specimens using multicolor flow cytometry (sensitivity 0.1%). Ninety-seven patients achieving either a complete remission (CR) or CR with incomplete hematologic recovery (CRi) or morphologic leukemia-free state were included. Median age was 72 years (interquartile range, 68-78 years), and 64% had adverse-risk AML. Eighty-three patients achieved CR/CRi, and 52 (54%) became MRD negative. Median time to becoming MRD negative was 2.0 months (interquartile range, 0.9-3.1 months). Patients becoming MRD negative by 2 months had longer relapse-free survival (RFS) compared with those remaining MRD positive (median RFS, not reached vs 5.2 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.12-0.78; P = .004), longer event-free survival (EFS) (median EFS, not reached vs 5.8 months; HR, 0.25; 95% CI, 0.12-0.55; P < .001), as well as longer overall survival (OS) (median OS, 25.1 vs 7.1 months; HR, 0.23; 95% CI, 0.11-0.51; P < .001). Patients achieving an MRD-negative CR had longer OS compared with those with an inferior response (median OS, 25.1 vs 11.6 months; HR, 0.33; 95% CI, 0.19-0.58; P < .0005). Patients becoming MRD negative within 1 month had an improved OS compared with MRD-positive patients (median OS, 25.1 vs 3.4 months; HR, 0.15; 95% CI, 0.03-0.64; P < .0001). Differential impact of MRD status on survival outcomes persisted at a later 4-month time point of evaluation. In conclusion, MRD-negative status at 1, 2, and 4 months after starting therapy confers significantly better survival in older/unfit patients with AML receiving first-line therapy with 10-day decitabine and venetoclax. This trial was registered at www.clinicaltrials.gov as #NCT03404193.
COVID-19 in individuals with sickle cell disease/trait compared with other Black individuals
Authors: Singh Ashima , Brandow Amanda M. , Panepinto Julie A.
Published: April 2021

In the United States, COVID-19 has disproportionately affected Black persons. Sickle cell disease (SCD) and sickle cell trait (SCT) are genetic conditions that occur predominantly among Black individuals. It is unknown if individuals with SCD/SCT are at higher risk of severe COVID-19 illness compared with Black individuals who do not have SCD/SCT. The objective of our study was to compare COVID-19 outcomes, including the disease manifestations, hospitalization, and death, among individuals with SCD/SCT vs Black individuals who do not have SCD/SCT. We leveraged electronic health record data from a multisite research network to identify Black patients with COVID-19 who have SCD/SCT and those who do not have SCD/SCT. During the study period of 20 January 2020 to 20 September 2020, there were 312 patients with COVID-19 and SCD and 449 patients with COVID-19 and SCT. There were 45 517 Black persons who were diagnosed with COVID-19 but who did not have SCD/SCT. After 1:1 propensity score matching (based on age, sex, and other preexisting comorbidities), patients with COVID-19 and SCD remained at a higher risk of hospitalization (relative risk [RR], 2.0; 95% CI, 1.5-2.7) and development of pneumonia (RR, 2.4; 95% CI, 1.6-3.4) and pain (RR, 3.4; 95% CI, 2.5-4.8) compared with Black persons without SCD/SCT. The case fatality rates for those with SCD compared with Black persons without SCD/SCT were not significantly different. There also were no significant differences in COVID-19 outcomes between individuals with SCT and Black persons without SCD/SCT within the matched cohorts.
Caloric and nutrient restriction to augment chemotherapy efficacy for acute lymphoblastic leukemia: the IDEAL trial
Authors: Orgel Etan , Framson Celia , Buxton Rubi , Kim Jiyoon , Li Gang , Tucci Jonathan , Freyer David R. , Sun Weili , Oberley Matthew J. , Dieli-Conwright Christina , Mittelman Steven D.
Published: April 2021

Being overweight or obese (OW/OB) during B-cell acute lymphoblastic leukemia (B-ALL) induction is associated with chemoresistance as quantified by minimal residual disease (MRD). We hypothesized that caloric and nutrient restriction from diet/exercise could lessen gains in fat mass (FM) and reduce postinduction MRD. The Improving Diet and Exercise in ALL (IDEAL) trial enrolled patients 10 to 21 years old, newly diagnosed with B-ALL (n = 40), in comparison with a recent historical control (n = 80). Designed to achieve caloric deficits ≥20% during induction, reduce fat intake/glycemic load, and increase activity, IDEAL’s end points were FM gain (primary), MRD ≥0.01%, and adherence/feasibility. Integrated biology explored biomarkers of OW/OB physiology. IDEAL intervention did not significantly reduce median FM change from baseline overall (+5.1% [interquartile range [IQR], 15.8] vs +10.7% [IQR, 16.0]; P = .13), but stratified analysis showed benefit in those OW/OB (+1.5% [IQR, 6.6] vs +9.7% [IQR, 11.1]; P = .02). After accounting for prognostic factors, IDEAL intervention significantly reduced MRD risk (odds ratio, 0.30; 95% confidence interval, 0.09-0.92; P = .02). The trial exceeded its adherence (≥75% of overall diet) and feasibility (≥80% completed visits) thresholds. Integrated biology found the IDEAL intervention increased circulating adiponectin and reduced insulin resistance. The IDEAL intervention was feasible, decreased fat gain in those OW/OB, and reduced MRD. This is the first study in any hematologic malignancy to demonstrate potential benefit from caloric restriction via diet/exercise to augment chemotherapy efficacy and improve disease response. A prospective, randomized trial is warranted for validation. These trials were registered at www.clinicaltrials.gov as #NCT02708108 (IDEAL trial) and #NCT01317940 (historical control).
Advantages of imaging photoplethysmography for migraine modeling: new optical markers of trigemino‐vascular activation in rats
Authors: Sokolov Alexey Y. , Volynsky Maxim A. , Zaytsev Valery V. , Osipchuk Anastasiia V. , Kamshilin Alexei A.
Published: April 2021

Background

Existent animal models of migraine are not without drawbacks and limitations. The aim of our study was to evaluate imaging photoplethysmography (PPG) as a method of assessing intracranial blood flow in rats and its changes in response to electrical stimulation of dural trigeminal afferents.

Methods

Experiments were carried out with 32 anesthetized adult male Wistar rats. Trigeminovascular system (TVS) was activated by means of electrical stimulation of dural afferents through a closed cranial window (CCW). Parameters of meningeal blood flow were monitored using a PPG imaging system under green illumination with synchronous recording of an electrocardiogram (ECG) and systemic arterial blood pressure (ABP). Two indicators related to blood-flow parameters were assessed: intrinsic optical signals (OIS) and the amplitude of pulsatile component (APC) of the PPG waveform. Moreover, we carried out pharmacological validation of these indicators by determining their sensitivity to anti-migraine drugs: valproic acid and sumatriptan. For statistical analysis the non-parametric tests with post-hoc Bonferroni correction was used.

Results

Significant increase of both APC and OIS was observed due to CCW electrical stimulation. Compared to saline (n = 11), intravenous administration of both the sumatriptan (n = 11) and valproate (n = 10) by using a cumulative infusion regimen (three steps performed 30 min apart) lead to significant inhibitory effect on the APC response to the stimulation. In contrast, intravenous infusion of any substance or saline did not affect the OIS response to the stimulation. It was found that infusion of either sumatriptan or valproate did not affect the response of ABP or heart rate to the stimulation.

Conclusions

Imaging PPG can be used in an animal migraine model as a method for contactless assessment of intracranial blood flow. We have identified two new markers of TVS activation, one of which (APC) was pharmacologically confirmed to be associated with migraine. Monitoring of changes in APC caused by CCW electrical stimulation (controlling efficiency of stimulation by OIS) can be considered as a new way to assess the peripheral mechanism of action of anti-migraine interventions.
Fine mapping of two grain chalkiness QTLs sensitive to high temperature in rice
Authors: Yang Weifeng , Liang Jiayan , Hao Qingwen , Luan Xin , Tan Quanya , Lin Shiwan , Zhu Haitao , Liu Guifu , Liu Zupei , Bu Suhong , Wang Shaokui , Zhang Guiquan
Published: April 2021

Background

Grain chalkiness is one of important factors affected rice grain quality. It is known that chalkiness is affected by the high temperature during the seed filling period. Although a larger of QTLs for chalkiness were reported across all 12 chromosomes, only a few of the QTLs were fine mapped or cloned up to now. Here, we fine map two QTLs for chalkiness in two single-segment substitution lines (SSSLs), 11–09 with substitution segment from O. sativa and HP67–11 with substitution segment from O. glaberrima.

Results

The grain chalkiness of SSSLs 11–09 and HP67–11 was significantly lower than that in the recipient Huajingxian 74 (HJX74) in consecutive 8 cropping seasons. The regression correlation analysis showed that percentage of chalky grain (PCG) and percentage of chalky area (PCA) were significantly and positively correlated with percentage of grain chalkiness (PGC). Two QTLs for grain chalkiness were located on two chromosomes by substitution mapping. qPGC9 was mapped on chromosome 9 with an estimated interval of 345.6 kb. qPGC11 was located on chromosome 11 and delimited to a 432.1 kb interval in the O. sativa genome and a 332.9 kb interval in the O. glaberrima genome. qPGC11 is a QTL for grain chalkiness from O. glaberrima and was mapped in a new region of chromosome 11. The effect of two QTLs was incomplete dominance. The additive effects of two QTLs on chalkiness in second cropping season (SCS) were significantly greater than that in first cropping season (FCS).

Conclusions

qPGC11 is a new QTL for grain chalkiness. The two QTLs were fine mapped. The donor alleles of qPGC9 and qPGC11 were sensitive to the high temperature of FCS.
IPCARF: improving lncRNA-disease association prediction using incremental principal component analysis feature selection and a random forest classifier
Authors: Zhu Rong , Wang Yong , Liu Jin-Xing , Dai Ling-Yun
Published: April 2021

Background

Identifying lncRNA-disease associations not only helps to better comprehend the underlying mechanisms of various human diseases at the lncRNA level but also speeds up the identification of potential biomarkers for disease diagnoses, treatments, prognoses, and drug response predictions. However, as the amount of archived biological data continues to grow, it has become increasingly difficult to detect potential human lncRNA-disease associations from these enormous biological datasets using traditional biological experimental methods. Consequently, developing new and effective computational methods to predict potential human lncRNA diseases is essential.

Results

Using a combination of incremental principal component analysis (IPCA) and random forest (RF) algorithms and by integrating multiple similarity matrices, we propose a new algorithm (IPCARF) based on integrated machine learning technology for predicting lncRNA-disease associations. First, we used two different models to compute a semantic similarity matrix of diseases from a directed acyclic graph of diseases. Second, a characteristic vector for each lncRNA-disease pair is obtained by integrating disease similarity, lncRNA similarity, and Gaussian nuclear similarity. Then, the best feature subspace is obtained by applying IPCA to decrease the dimension of the original feature set. Finally, we train an RF model to predict potential lncRNA-disease associations. The experimental results show that the IPCARF algorithm effectively improves the AUC metric when predicting potential lncRNA-disease associations. Before the parameter optimization procedure, the AUC value predicted by the IPCARF algorithm under 10-fold cross-validation reached 0.8529; after selecting the optimal parameters using the grid search algorithm, the predicted AUC of the IPCARF algorithm reached 0.8611.

Conclusions

We compared IPCARF with the existing LRLSLDA, LRLSLDA-LNCSIM, TPGLDA, NPCMF, and ncPred prediction methods, which have shown excellent performance in predicting lncRNA-disease associations. The compared results of 10-fold cross-validation procedures show that the predictions of the IPCARF method are better than those of the other compared methods.
Effects of continuous cropping of sweet potatoes on the bacterial community structure in rhizospheric soil
Authors: Gao Zhiyuan , Hu Yaya , Han Meikun , Xu Junjie , Wang Xue , Liu Lanfu , Tang Zhonghou , Jiao Weijing , Jin Rong , Liu Ming , Guan Zhengjun , Ma Zhimin
Published: April 2021

Background

Continuous cropping obstacles from sweet potatoes are widespread, which seriously reduce the yield and quality, causing certain economic losses. Bacteria of rhizospheric soil are the richest and are associated with obstacles to continuous cropping. However, few studies have examined how continuous sweet potato cropping affects the rhizospheric soil bacterial community structure.

Results

In the study, the Illumina MiSeq method was used to explore the variations in

rhizospheric soil bacterial community structure of different sweet potato varieties after continuous cropping, as well as the correlation between soil characteristics and the bacterial community. The results showed that (1) the dominant bacterial phyla in rhizospheric soils from both Xushu 18 and Yizi 138 were Proteobacteria, Acidobacteria, and Actinobacteria. The most dominant genus was Subgroup 6_norank. The relative abundance of rhizospheric soil bacteria varied significantly between the two sweet potato varieties. (2) The richness and diversity indexes of bacteria were higher in Xushu 18 rhizospheric soil than in Yizi 138 soil after continuous cropping. Moreover, beneficial Lysobacter and Bacillus were more prevalent in Xushu 18, while Yizi 138 contained more harmful Gemmatimonadetes. (3) Soil pH decreased after continuous cropping, and redundancy analysis indicated that soil pH was significantly correlated with the bacterial community. Spearman’s rank correlation coefficient analysis demonstrated that pH was positively associated with Planctomycetes and Acidobacteria, but negatively associated with Actinobacteria and Firmicutes.

Conclusions

After continuous cropping, the bacterial community structure and physicochemical properties of sweet potato rhizospheric soil were changed, and the changes from different sweet potato varieties were different. The contents of Lysobacter and Bacillus were higher in the sweet potato variety resistant to continuous cropping. It provides a basis for developing new microbial fertilizers for sweet potatoes to alleviate the continuous cropping obstacle.
Oesophageal squamous cell carcinoma mimicking submucosal tumour
Authors: Wang Wen , Li Dazhou , Zheng Linfu , Zhan Hongli
Published: April 2021

Background

Oesophageal submucosal tumours are usually benign. We report a rare case of esophageal squamous cell carcinoma presenting as a submucosal tumour.

Case presentation

A 58-year-old man undergoing screening oesophago-gastroduodenoscopy was found to have a smooth-surfaced 0.6-cm sized submucosal tumour in the oesophagus 30 cm from the incisor. Endoscopic ultrasonography showed the tumour to be located in the muscularis mucosa; the lesion was heterogeneously hypoechoic and had a clear boundary. With a provisional diagnosis of leiomyoma, the tumour was removed by endoscopic submucosal dissection. Pathological examination showed it to be a moderately differentiated infiltrating squamous cell carcinoma, with normal overlying squamous epithelium. Immunohistochemistry indicated that it was caused by malignant transformation in mucosal glandular duct epithelium. Positron emission tomography–computer tomography showed no tumour spread to any other site. The patient was treated by oesophageal resection.

Conclusion

The clinician should be aware that oesophageal submucosal tumours with smooth overlying mucosa may not always be benign; malignancy must be ruled out.
Development and testing of the Geriatric Care Assessment Practices (G-CAP) survey
Authors: Giosa Justine L. , Stolee Paul , Holyoke Paul
Published: April 2021

Background

While the Resident Assessment Instrument-Home Care (RAI-HC) tool was designed to support comprehensive geriatric assessment in home care, it is more often used for service allocation and little is known about how point-of-care providers collect the information they need to plan and provide care. The purpose of this pilot study was to develop and test a survey to explore the geriatric care assessment practices of nurses, occupational therapists (OTs) and physiotherapists (PTs) in home care.

Methods

Literature review and expert consultation informed the development of the Geriatric Care Assessment Practices (G-CAP) survey—a 33 question, online, self-report tool exploring assessment and information-sharing methods, attitudes, knowledge, experience and demographic information. The survey was pilot tested at a single home care agency in Ontario, Canada (N = 27). Test-retest reliability (N = 20) and construct validity were explored.

Results

The subscales of the G-CAP survey showed fair to good test-retest reliability within a population of interdisciplinary home care providers [ICC2 (A,1) (M ICC = 0.58) for continuous items; weighted kappa (M kappa = 0.63) for categorical items]. Statistically significant differences between OT, PT and nurse responses [M t = 3.0; M p = 0.01] and moderate correlations between predicted related items [M r = |0.39|] provide preliminary support for our hypotheses around survey construct validity in this population. Pilot participants indicated that they use their clinical judgment far more often than standardized assessment tools. Client input was indicated to be the most important source of information for goal-setting. Most pilot participants had heard of the RAI-HC; however, few used it. Pilot participants agreed they could use assessment information from others but also said they must conduct their own assessments and only sometimes share and rarely receive information from other providers.

Conclusions

The G-CAP survey shows promise as a measure of the geriatric care assessment practices of interdisciplinary home care providers. Findings from the survey have the potential to inform improvements to integrated care planning. Next steps include making adaptations to the G-CAP survey to further improve the reliability and validity of the tool and a broad administration of the survey in Ontario home care.