bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population-based incidence and time to classification of systemic lupus erythematosus by three different classification criteria: a Lupus Midwest Network (LUMEN) study
Authors: Duarte-García Alí , Hocaoglu Mehmet , Osei-Onomah Shirley-Ann , Dabit Jesse Y , Giblon Rachel E , Helmick Charles G , Crowson Cynthia S 
Published: October 2021

AbstractObjectiveTo estimate the incidence and time-to-classification of SLE by the 1997 ACR (ACR97) criteria, the SLICC criteria, and the European Alliance of Associations for Rheumatology/ACR (EULAR/ACR) criteria.MethodsWe identified all incident SLE cases from 2000–2018 in the well-defined Olmsted County population. Clinical data included in the ACR97, SLICC and EULAR/ACR criteria were manually abstracted from medical records. All incident cases met at least one of the three classification criteria. Time-to-classification was estimated from the first documented lupus-attributable disease manifestation to the time of criteria fulfilment by each of the three definitions. Annual incidence rates were age or age/sex adjusted to the 2000 US population.ResultsOf 139 incident cases there were 126 cases by the EULAR/ACR criteria, corresponding to an age/sex-adjusted incidence of 4.5 per 100 000 population (95% CI: 3.7, 5.2). The age/sex-incidence was higher than that of the SLICC criteria (113 cases; 4.0 per 100 000 [95% CI: 3.3, 4.7], P = 0.020) and the ACR97 (92 cases; 3.3 per 100 000 [95% CI: 2.6, 3.9], P &lt; 0.001). The median time from first disease manifestation to criteria fulfilment was shorter for the EULAR/ACR criteria (29.4 months) than the ACR97 criteria (47.0 months, P &lt; 0.001) and similar to the SLICC criteria (30.6 months, P = 0.83).ConclusionThe incidence of SLE was higher by the EULAR/ACR criteria compared with the ACR97 and the SLICC criteria, and the EULAR/ACR criteria classified patients earlier that the ACR97 criteria but similar to the SLICC criteria.
Sex differences in the behavioral inhibition system and ventromedial prefrontal cortex connectivity
Authors: Jung Wi Hoon , Lee Tae Young , Kim Minah , Lee Junhee , Oh Sanghoon , Lho Silvia Kyungjin , Moon Sun-Young , Kwon Jun Soo 
Published: October 2021

Abstract
The reinforcement sensitivity theory proposes brain–behavioral systems that underlie individual differences in sensitivity to punishment and reward. Such trait sensitivity is assessed using the behavioral inhibition/activation system (BIS/BAS) scales. Recent studies have reported sex-linked neuroanatomical correlates of the BIS/BAS, especially in the regions belonging to the valuation and salience networks that are associated with the representation of subjective value (SV), whereas less effort has been focused on investigating the neurofunctional aspects associated with sex differences in the BIS/BAS. We tested whether functional connectivity (FC) of the regions associated with the representation of SV mediates the relationship between sex and BIS sensitivity in healthy young adults by using resting-state functional magnetic resonance imaging data and self-reported BIS/BAS measures. Compared with males, females had heightened BIS sensitivity and increased FC between the ventromedial prefrontal cortex (vmPFC) seed and posterior parietal areas; this FC mediated the impact of sex on BIS sensitivity. Given that the observed vmPFC FC maps are considered part of the default-mode network, which is involved in ruminative processes, and that the BIS is associated with rumination and negative affect, our results may have implications for psychiatric disorders such as depression and anxiety, both of which have high incidence in females.
Using factorial mediation analysis to better understand the effects of interventions
Authors: Strayhorn Jillian C , Collins Linda M , Brick Timothy R , Marchese Sara H , Pfammatter Angela Fidler , Pellegrini Christine , Spring Bonnie 
Published: October 2021

Abstract
To improve understanding of how interventions work or why they do not work, there is need for methods of testing hypotheses about the causal mechanisms underlying the individual and combined effects of the components that make up interventions. Factorial mediation analysis, i.e., mediation analysis applied to data from a factorial optimization trial, enables testing such hypotheses. In this commentary, we demonstrate how factorial mediation analysis can contribute detailed information about an intervention’s causal mechanisms. We briefly review the multiphase optimization strategy (MOST) and the factorial experiment. We use an empirical example from a 25 factorial optimization trial to demonstrate how factorial mediation analysis opens possibilities for better understanding the individual and combined effects of intervention components. Factorial mediation analysis has important potential to advance theory about interventions and to inform intervention improvements.
EffectorP 3.0: Prediction of Apoplastic and Cytoplasmic Effectors in Fungi and Oomycetes
Authors: Sperschneider Jana , Dodds Peter N. 
Published: October 2021

Many fungi and oomycete species are devasting plant pathogens. These eukaryotic filamentous pathogens secrete effector proteins to facilitate plant infection. Fungi and oomycete pathogens have diverse infection strategies and their effectors generally do not share sequence homology. However, they occupy similar host environments, either the plant apoplast or plant cytoplasm, and, therefore, may share some unifying properties based on the requirements of these host compartments. Here, we exploit these biological signals and present the first classifier (EffectorP 3.0) that uses two machine-learning models: one trained on apoplastic effectors and one trained on cytoplasmic effectors. EffectorP 3.0 accurately predicts known apoplastic and cytoplasmic effectors in fungal and oomycete secretomes with low estimated false-positive rates of 3 and 8%, respectively. Cytoplasmic effectors have a higher proportion of positively charged amino acids, whereas apoplastic effectors are enriched for cysteine residues. The combination of fungal and oomycete effectors in training leads to a higher number of predicted cytoplasmic effectors in biotrophic fungi. EffectorP 3.0 expands predicted effector repertoires beyond small, cysteine-rich secreted proteins in fungi and RxLR-motif containing secreted proteins in oomycetes. We show that signal peptide prediction is essential for accurate effector prediction, because EffectorP 3.0 recognizes a cytoplasmic signal also in intracellular, nonsecreted proteins. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The acceptability of a novel procedure service run by PAs and NPs
Authors: Kim Nancy , Herbert Tara , Marranca Sheyla , Bergman Eric , Castillo Ronald , Romano Lindsey , Heacock Daniel , Cushing William 
Published: October 2021

ABSTRACT

Background:
Hospitalist physicians are performing fewer procedures because of multiple reasons, including expanded responsibilities beyond their patient panel. A procedure service that offloads hospitalists could expedite these necessary services. An opportunity exists for physician assistants (PAs) and NPs to fill this gap.

Objective:
To describe the implementation of a PA- and NP-run procedure service at a large academic hospital.

Methods:
This is a retrospective cohort study of procedures by the procedure service at one institution from 2015 to 2019.

Results:
Over 5 years, 7,002 procedures were performed, with requests increasing over time. The most frequent procedures were venous access, lumbar puncture, paracentesis, and placement of nasogastric or nasojejunal tubes. Requesting services included hospitalists and residents from internal medicine, surgery, and neurology.

Conclusions:
A PA- and NP-run procedure service is well accepted at a large academic hospital despite the lack of involvement by attending physicians. Future directions are focused on augmenting coverage and procedures offered.
Financial analysis of PA lifetime earnings and debt
Authors: Bruza-Augatis Mirela , Hooker Roderick S. , Coombs Jennifer M. 
Published: October 2021

ABSTRACT
This economic analysis of physician assistant/associate (PA) career earnings sought to assess the increasing effect of student debt, its potential effect on job selection, and whether such financial obligations may influence graduates to select higher-paying specialties. The model was a 30-year-old newly graduated PA who begins working in family medicine. A simulation included wages, student debt, national household expenditures, and real estate statistics. The scenario consisted of a high and middle cost of living in two geographic areas, a family of four, and an average life expectancy. Using a validated economic program, a series of calculations produced the financial effect on moderate-income levels and expenditures based on median PA earnings. On the deficit side is education debt, loan repayment, financing a house, college for children, retirement, and discretionary spending. Weighted variables were used to maximize the sensitivity effect of the simulation. A Monte Carlo probabilistic program predicted the likely outcome of income, expenses, inflation, and investments. Furthermore, the lifetime earnings of a PA who retires at age 67 years and lives to age 85 years falls in the 75th percentile of income of all Americans. The conclusion is that a full-time PA career in any clinical role is as economically rewarding as it is satisfying.
Extended High-frequency Hearing Impairment Despite a Normal Audiogram: Relation to Early Aging, Speech-in-noise Perception, Cochlear Function, and Routine Earphone Use
Authors: Mishra Srikanta K. , Saxena Udit , Rodrigo Hansapani 
Published: October 2021

Objectives:
Humans can hear up to 20 kHz. Emerging evidence suggests that hearing in the extended high frequencies (EHFs; >8 kHz) contributes to speech perception in noise. The objective of the present study was to describe the features of EHF hearing impairment in young adults with normal standard audiograms (0.25–8 kHz). Specifically, the study goals were to: (1) characterize the EHF hearing impairment and identify potential risk factors; (2) elucidate the age-related changes in EHF hearing; (3) determine the effect of EHF hearing impairment on speech-in-noise recognition; and (4) examine the extent to which EHF hearing impairment influences cochlear functioning in the standard frequencies.

Design:
Hearing thresholds at standard frequencies and EHFs (10, 12.5, 14, and 16 kHz), and speech recognition thresholds (SRTs) using digit triplets in multi-talker babble were measured in both ears from 222 participants (19–38 years; n = 444 ears) with normal audiograms (≤20 dB HL at standard frequencies). Test–retest measurement of hearing thresholds was obtained in a subset of 50 participants (100 ears), and clinical distortion product otoacoustic emissions (f
2 frequency = 2, 3, 4, and 5 kHz) were recorded in 49 participants (98 ears).

Results:
Forty-two of 222 participants had EHF hearing impairment (>20 dB HL for at least one EHF in either ear). Only seven individuals with EHF impairment had significant case history and/or listening-in-noise complaints. A breakpoint in the threshold-age function was observed for the EHFs for males but not for females. Linear mixed models revealed a significant effect of age, pure-tone averages for speech frequencies (0.5, 1, 2, and 4 kHz), and EHFs and group (NH versus EHF hearing impairment) independent of each other on the SRTs. Individuals with EHF hearing impairment had less measurable emissions and when present, had a lower magnitude of otoacoustic emissions relative to NH controls. There was no difference in hearing thresholds, SRTs, or otoacoustic emissions between earphone users and nonusers.

Conclusions:
The hearing thresholds for the EHFs exhibit signs of early auditory aging. Age-related deterioration in auditory function can be observed in the third decade of human life. A breakpoint in the threshold-age function suggests that rapid aging processes are operational at a relatively younger age (21 years) for males. The audibility of EHFs contributes to speech-in-noise recognition. EHF hearing impairment independent of age and speech frequencies can affect speech-in-noise recognition. Reduced distortion product otoacoustic emissions in the standard frequencies may suggest preclinical cochlear degeneration in individuals with EHF hearing impairment.
Juvenile open angle glaucoma: current diagnosis and management
Authors: Ciociola Elizabeth C. , Klifto Meredith R. 
Published: October 2021

Purpose of review
The aim of this article is to summarize up-to-date research on the diagnosis and management of juvenile open-angle glaucoma (JOAG).

Recent findings
JOAG can be subclassified into four clinical phenotypes, and faster myopic shift is a risk factor for disease progression. Vessel density is associated with structural damage and worsening visual acuity in JOAG and can be monitored with optical coherence tomography angiography. Genetic studies have revealed molecular causes of JOAG including variants in CPAMD8, MYOC, and CYP1B1. Tube shunt surgeries as well as gonioscopy-assisted transluminal trabeculotomy have been shown to be successful in JOAG.

Summary
Although genetic advances may improve future screening, intraocular pressure monitoring and fundoscopic exam remain the current mainstay of diagnosis. Medical treatment alone for JOAG is typically insufficient with patients requiring surgical management. Selective laser trabeculoplasty may delay or decrease the need for surgery. Trabeculectomy has traditionally been shown to be effective in JOAG, but tube shunt surgery and microinvasive glaucoma surgery are effective alternatives.
American Medical Society for Sports Medicine Position Statement: Principles for the Responsible Use of Regenerative Medicine in Sports Medicine
Authors: Finnoff Jonathan T. , Awan Tariq M. , Borg-Stein Joanne , Harmon Kimberly G. , Herman Daniel C. , Malanga Gerard A. , Master Zubin , Mautner Kenneth R. , Shapiro Shane A. 
Published: October 2021

Abstract:
Many sports medicine physicians are currently considering introducing regenerative medicine into their practice. Regenerative medicine and the subclassification of orthobiologics are a complicated topic and have produced widely varying opinions. Although there is concern by government regulators, clinicians, scientists, patient advocacy organizations, and the media regarding the use of regenerative medicine products, there is also excitement about the potential benefits with growing evidence that certain regenerative medicine products are safe and potentially efficacious in treating musculoskeletal conditions. Sports medicine physicians would benefit from decision-making guidance about whether to introduce orthobiologics into their practice and how to do it responsibly. The purpose of this position statement is to provide sports medicine physicians with information regarding regenerative medicine terminology, a brief review of basic science and clinical studies within the subclassification of orthobiologics, regulatory considerations, and best practices for introducing regenerative medicine into clinical practice. This information will help sports medicine physicians make informed and responsible decisions about the role of regenerative medicine and orthobiologics in their practice.
Bulging of the Oval Window in Common Cavity Deformity: A Possible Predictor of Meningitis
Authors: Manara Renzo , Avato Irene , Uberti Andrea , Trevisi Patrizia , Bovo Roberto , Martini Alessandro , Brotto Davide ,   EU.COM Group, Berettini Stefano , Canzi Pietro , Ciorba Andrea , Cristofari Eliana , Cuda Domenico , Della Volpe Antonio , Frau Giuseppe Nicolò , Genovese Elisabetta , Marsella Pasquale , Murri Alessandra , Sorrentino Flavia , Vincenti Vincenzo , Zanetti Diego 
Published: October 2021

Objective:
To investigate the prevalence-rate of oval window bulging in the common cavity and its association with bacterial meningitis.

Patients:
CT and clinical files of 29 children with preliminary diagnosis of common cavity deformity were collected from 13 Italian centers.

Intervention:
A retrospective case review study was conducted with a centralized evaluation of the temporal bone CT imaging was performed at Azienda Ospedale – Università Padova, Padova, Italy.

Main Outcome Measure:
Diagnosis of common cavity was reviewed; in addition, a fluid protrusion into the middle-ear cavity through the oval window at CT imaging was considered as oval window bulging. Its association with the history of bacterial meningitis was investigated.

Results:
Common cavity deformity was confirmed in 14/29 children (mean-age 11.4 ± 3.8; age-range 5–20; nine females) referred with this diagnosis. In 7/14 patients, the common cavity deformity was bilateral (i.e., 21 common cavities). Oval window bulging was found in 3/19 common cavities (concomitant middle-ear effusive otitis hampered the evaluation in two cases), while the internal acoustic meatus fundus was defective in 10/21 cases. History of bacterial meningitis was found in three children (21%) and two of them had oval window bulging at CT. In the case unrelated to oval window bulging, meningitis occurred late at the age of 12 during acute otitis contralateral to common cavity deformity (ipsilaterally to incomplete partition type 1).

Conclusion:
Patients harboring common cavity deformity have a high risk of meningitis in their first years of life. Oval window bulging seems to be associated with a higher risk of meningitis. This information might be important for appropriate surgical planning.
The potential of microbiome replacement therapies for Clostridium difficile infection
Authors: Buckley Anthony M. , Moura Ines B. , Wilcox Mark H. 
Published: October 2021

Purpose of review
There is a paradox when treating Clostridium difficile infection (CDI); treatment antibiotics reduce C. difficile colonization but cause further microbiota disruption and can lead to recurrent disease. The success of faecal microbiota transplants (FMT) in treating CDI has become a new research area in microbiome restorative therapies but are they a viable long-term treatment option?

Recent findings

C. difficile displays metabolic flexibility to use different nutritional sources during CDI. Using microbiome therapies for the efficient restoration of bile homeostasis and to reduce the bioavailability of preferential nutrients will target the germination ability of C. difficile spores and the growth rate of vegetative cells. Several biotechnology companies have developed microbiome therapeutics for treating CDI, which are undergoing clinical trials.

Summary
There is confidence in using restorative microbiome therapies for treating CDI after the demonstrated efficacy of FMT, where several biotechnology companies are aiming to supply what would be a ‘first in class’ treatment option. Efficient removal of C. difficile from the different intestinal biogeographies should be considered in future microbiome therapies. With the gut microbiota implicated in different diseases, more work is needed to assess the long-term consequences of microbiome therapies.
Diverse functions of long noncoding RNAs in acute myeloid leukemia: emerging roles in pathophysiology, prognosis, and treatment resistance
Authors: Mishra Srishti , Liu Jun , Chai Li , Tenen Daniel G. 
Published: October 2021

Purpose of review
Advancements in the next-generation sequencing technologies have identified rare transcripts of long noncoding RNAs (lncRNAs) in the genome of cancers, including in acute myeloid leukemia (AML). The purpose of this review is to highlight the contribution of lncRNAs in AML pathogenesis, prognosis, and chemoresistance.

Recent findings
Several studies have recently reported that deregulated lncRNAs are novel key players in the development of AML and are associated with AML pathophysiology and may serve as prognostic indicators. A few aberrantly expressed lncRNAs that correlated with the recurrent genetic mutations in AML such as NPM1 and RUNX1 have recently been characterized. Moreover, a few lncRNAs in MLL-rearranged leukemia have been described. Additionally, the involvement of lncRNAs in AML chemoresistance has been postulated.

Summary
Investigating the functional roles of the noncoding regions including lncRNAs, may provide novel insights into the pathophysiology, refine the prognostic schema, and provide novel therapeutic treatment strategies in AML.
Preprint servers in lipidology: current status and future role
Authors: Perera Shehan D. , Muleta Ayana D. , Vlasschaert Caitlyn , Hegele Robert A. 
Published: October 2021

Purpose of review
Preprinting, or the sharing of non-peer reviewed, unpublished scholarly manuscripts, has exploded in all fields of science and medicine over the past 5 years. We searched the literature and evaluated the posting and uptake of preprint publications in the field of lipidology in bioRxiv and medRxiv servers. We also contacted the editorial offices of 20 journals that publish original research in lipidology to gauge their policies on preprints.

Recent findings
All 20 journals contacted indicated that they accepted preprints. As of 31 May 2021, 473 and 231 preprints in lipidology had been submitted to bioRxiv and medRxiv, respectively. About half of all lipidology preprints were related to cardiovascular, cardiometabolic, and/or metabolic diseases (CVMD) and their risk factors, but at least 12 other disease categories were also represented. 16.9% and 1.08% of medRxiv and bioRxiv preprints, respectively, were related to coronavirus disease 2019 (COVID-19).

Summary
All identified journals accept lipidology themed preprints for submission, removing any barriers authors may have had regarding preprinting. Based on growing experience with preprinting, this trend should encourage increased community feedback and facilitate higher quality lipidology research in the future.
Longer Time Intervals From Symptom Onset to Diagnosis Affect the Overall Survival in Children With Acute Lymphoblastic Leukemia
Authors: Dai Qingkai , Liu Rui , Wang Yuefang , Ye Lei , Peng Luyun , Shi Rui , Guo Siqi , He Jiajing , Yang Hao , Zhang Ge , Jiang Yongmei 
Published: October 2021

Background:
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Early diagnosis and timely treatment are essential for effective cancer control and have been widely analyzed in childhood cancer. However, few studies have described the time to diagnosis and treatment in children with ALL. This study investigated delays in diagnosis and treatment initiation and their impact on survival.

Methods:
This retrospective cohort study included 419 patients 0 to 14 years old at a tertiary hospital between 2011 and 2015. The optimal cutoff values for delays were determined by X-tile software. The Kaplan-Meier method and Cox regression models were used to evaluate the impact of delays on survival.

Results:
The median diagnosis, treatment, and total delays were 21 (interquartile range [IQR]: 11-35), 4 (IQR: 2-7), and 26 (IQR: 16-43) days, respectively. The results of multivariate analyses showed that diagnosis delay, risk stratification, and minimal residual disease level were independent predictors for treatment outcome in childhood ALL.

Conclusions:
These findings suggested that a longer time to diagnosis negatively affected the clinical outcome of childhood ALL. Reducing the time to diagnosis could help to improve survival in these patients.