bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disseminated Mycoplasma Orale Infection in Patients With Phosphoinositide-3-Kinase Regulatory Subunit 1 Mutations
Authors: Totten Arthur H , Uzel Gulbu , Khil Pavel P , Youn Jung-Ho , Treat Jennifer , Soutar Craig D , Holland Steven M , Dekker John P , Zerbe Christa S 
Published: September 2022

Abstract
Mycoplasma orale is a rare cause of invasive infection in immunodeficient hosts. Phosphatidylinositol 3-kinase, regulatory subunit 1 (PI3KR1) mutations predispose patients to sinopulmonary infections, alongside bronchiectasis autoimmunity and lymphoproliferation. We report 2 cases of PI3KR1 deficiency with invasive M orale and effective treatment options.
Starspots, chromospheric emission lines, and flares of zero-age main-sequence stars
Authors: Yamashita Mai , Itoh Yoichi , Oasa Yumiko 
Published: September 2022

Abstract
Zero-age main-sequence (ZAMS) stars are considered to have enormous starspots and show strong chromospheric emission lines because of their strong surface magnetic field. We discuss the dynamo activities of ZAMS stars with respect to their periodic light variation caused by a starspot and with respect to the strength of the chromospheric emission lines. The light curves of 33 ZAMS stars in IC 2391 and IC 2602 were obtained from TESS (Transiting Exoplanet Survey Satellite) photometric data. The light curves can be grouped into the following four categories: single frequency, possible shape changer, beater, and complex variability. The amplitudes of the light curves are 0.001–0.145 mag, similar to those of ZAMS stars in Pleiades. The starspot coverages are $0.1\%$–$21\%$. We found that the light variations and Ca ii emission line strength of ZAMS stars in IC 2391, IC 2602, and the Pleiades cluster are as large as those of the most active superflare stars and two orders larger than those of the Sun, and are located on the extensions of the superflare stars. These results suggest that superflare stars link the properties of the Sun to those of the ZAMS stars of ages between 30 and 120 Myr. ZAMS stars with a single frequency or possible shape change in the light curve tend to have both large light variation, indicating large spot coverage, and saturated Ca ii emission line strength. ZAMS stars with beat or complex variability have small spot coverage and a faint Ca ii emission line. We also detected 21 flares in the TESS light curves of 12 ZAMS stars in IC 2391 and IC 2602, where most of these stars have saturated chromospheric Ca ii emission lines. The energies of the flares are estimated to be ∼1033–1035 erg, which is comparable with the energy of a superflare.
Mendel: From genes to genome
Authors: Sussmilch Frances C , Ross John J , Reid James B 
Published: September 2022

AbstractTwo hundred years after the birth of Gregor Mendel, it is an appropriate time to reflect on recent developments in the discipline of genetics, particularly advances relating to the prescient friar’s model species, the garden pea (Pisum sativum L.). Mendel’s study of seven characteristics established the laws of segregation and independent assortment. The genes underlying four of Mendel’s loci (A, LE, I, and R) have been characterized at the molecular level for over a decade. However, the three remaining genes, influencing pod color (GP), pod form (V/P), and the position of flowers (FA/FAS), have remained elusive for a variety of reasons, including a lack of detail regarding the loci with which Mendel worked. Here, we discuss potential candidate genes for these characteristics, in light of recent advances in the genetic resources for pea. These advances, including the pea genome sequence and reverse-genetics techniques, have revitalized pea as an excellent model species for physiological–genetic studies. We also discuss the issues that have been raised with Mendel’s results, such as the recent controversy regarding the discrete nature of the characters that Mendel chose and the perceived overly-good fit of his segregations to his hypotheses. We also consider the relevance of these controversies to his lasting contribution. Finally, we discuss the use of Mendel’s classical results to teach and enthuse future generations of geneticists, not only regarding the core principles of the discipline, but also its history and the role of hypothesis testing.
Mosquito tagging using DNA-barcoded nanoporous protein microcrystals
Authors: Stuart Julius D , Hartman Daniel A , Gray Lyndsey I , Jones Alec A , Wickenkamp Natalie R , Hirt Christine , Safira Aya , Regas April R , Kondash Therese M , Yates Margaret L , Driga Sergei , Snow Christopher D , Kading Rebekah C 
Published: September 2022

Abstract
Conventional mosquito marking technology for mark–release–recapture (MRR) is quite limited in terms of information capacity and efficacy. To overcome both challenges, we have engineered, lab-tested, and field-evaluated a new class of marker particles, in which synthetic, short DNA oligonucleotides (DNA barcodes) are adsorbed and protected within tough, crosslinked porous protein microcrystals. Mosquitoes self-mark through ingestion of microcrystals in their larval habitat. Barcoded microcrystals persist trans-stadially through mosquito development if ingested by larvae, do not significantly affect adult mosquito survivorship, and individual barcoded mosquitoes are detectable in pools of up to at least 20 mosquitoes. We have also demonstrated crystal persistence following adult mosquito ingestion. Barcode sequences can be recovered by qPCR and next-generation sequencing (NGS) without detectable amplification of native mosquito DNA. These DNA-laden protein microcrystals have the potential to radically increase the amount of information obtained from future MRR studies compared to previous studies employing conventional mosquito marking materials.
Long Noncoding RNA Lx8-SINE B2 Interacts with Eno1 to Regulate Self-Renewal and Metabolism of Embryonic Stem Cells
Authors: Chen Fuquan , Li Xiaomin , Feng Xiao , Gao Tingting , Zhang Weiyu , Cheng Zhi , Zhao Xuan , Chen Ruiqing , Lu Xinyi 
Published: September 2022

Abstract
Long noncoding RNAs (lncRNAs) emerge as important orchestrators of biological processes in embryonic stem cells (ESCs). LncRNA Lx8-SINE B2 was recently identified as an ESC-specific lncRNA that marks pluripotency. Here, we studied the function of lncRNA Lx8-SINE B2 in ESCs. Depletion of Lx8-SINE B2 disrupted ESC proliferation, repressed the expression of pluripotency genes, activated differentiation genes, and inhibited reprogramming to induced pluripotent stem cells. The reduction of the colony formation ability of ESCs upon Lx8-SINE B2 knockdown was accompanied by the elongation of the G1 phase and the shortening of the S phase. Transcriptome analysis revealed that Lx8-SINE B2 deficiency affected multiple metabolic pathways, particularly glycolysis. Mechanistically, Lx8-SINE B2 functions as a cytoplasmic lncRNA and interacts with the glycolytic enzyme Eno1 as shown by RNA pull-down and RNA localization analysis. Lx8-SINE B2 and Eno1 interact with and regulate each other’s expression, hence promoting the expression of metabolic genes and influencing glycolysis. In conclusion, we have identified lncRNA Lx8-SINE B2 as a novel regulator of ESC proliferation, cell cycle, and metabolism through working with Eno1.
Do Weightbearing Restrictions Cause Excess Weight Gain in Children With LEGG-Calvé-Perthes Disease?
Authors: Novotny Susan A. , Hailer Yasmin D. , Laine Jennifer C. , Wetzel Martha , Gillespie Scott E. , Gilbert Shawn R. , Goldstein Rachel Y. , Kim Harry K.W. , Schrader Tim ,   on behalf of the International Perthes Study Group
Published: September 2022

Background:
Restricted weight bearing is commonly prescribed in Legg-Calvé-Perthes Disease (LCPD), raising concerns of causing overweight or obesity. This study utilizes prospectively collected data to address the following questions: (1) does body mass index (BMI) Z-score increase over the course of LCPD follow-up; (2) is having a BMI category of normal, overweight, or obese at baseline associated with BMI Z-score changes over the course of follow-up; and (3) is the duration of weight bearing restrictions (no restrictions, <3, 3 to <6, 6 to 9, or >9 mo) associated with BMI Z-score changes.

Methods:
Data of 130 children aged 5 to 12 years with unilateral early-stage LCPD were extracted from an international database. Nation-specific BMI Z-scores and percentile-based weight categories were determined, and the duration of follow-up and weight bearing restrictions were calculated. Longitudinal changes in BMI Z-scores were evaluated for the 3 study questions using mixed effects linear regression models with surgery as a covariate. Sensitivity analyses were used to determine the influence of socio-cultural background (USA vs. India) for each study question.

Results:
During the 35.5±15.9 months of follow-up, no statistically significant increase in BMI Z-scores was observed across the entire cohort, or following stratification by baseline weight categories or the duration of the weight bearing restriction. Sensitivity analyses indicated that patients in the USA had no change in their BMI Z-score. When stratified by weight categories, the normal weight of US children had a small increase in their BMI Z-score (0.005 per mo, 95% confidence interval: 0.0002, 0.009), but this was not seen in other BMI categories. The cohort of Indian children had a small but significant decrease in their BMI Z-score (−0.005/mo, 95% CI: −0.009, −0.0002). After stratification by weight categories, a small decrease of the BMI Z-score was observed only in the Indian overweight children (−0.016 per mo, 95% CI: −0.027, −0.005) and no other BMI category.

Conclusions:
Weightbearing restrictions over the course of follow-up for our cohort of children with early-stage LCPD were not associated with clinically meaningful increases of BMI Z-scores. Weight gain is multi-factorial and probably not caused by weight bearing restrictions alone.

Level of Evidence:
III Diagnostic Study.
Temporal Dynamics of Host Immune Response Associated With Disease Severity and Time to Recovery in Patients Hospitalized for COVID-19
Authors: Sophonsri Anthony , Le Diana , Lou Mimi , Ny Pamela , Minejima Emi , Chambliss Allison B. , Nieberg Paul , Shriner Kimberly , Wong-Beringer Annie 
Published: September 2022

OBJECTIVES:
The objective of this study was to compare the temporal dynamics of two viral-induced inflammatory proteins interferon gamma inducible protein-10 (IP-10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as well as C-reactive protein (CRP) among patients hospitalized for COVID-19 and examine their prognostic significance.

DESIGN:
Prospective observational cohort study.

SETTING:
Multicenter, inpatient.

PATIENTS:
Adult patients infected with severe acute respiratory syndrome coronavirus 2 between March 2021 and October 2021.

INTERVENTIONS:
Patient sera were collected on days 1, 3, 5, and 7 of hospitalization. Levels of IP-10, TRAIL, and CRP were measured using a point-of-need diagnostic immunoassay platform (MeMed BV, MeMed, Haifa, Israel) and compared between patients grouped by disease severity (severe vs nonsevere).

MEASUREMENTS AND MAIN RESULTS:
Baseline characteristics were similar regardless of severity except for a higher prevalence of diabetes and heart failure among severe patients. The immune profile at admission was similar between groups; IP-10 and CRP levels generally decreased while TRAIL levels increased over time in all patients. However, the severe group had higher IP-10 (median 713 vs 328 pg/mL; p = 0.045) and lower TRAIL levels (median 21 vs 30 pg/mL; p = 0.003) on day 3 compared with nonsevere patients. A breakpoint IP-10 level of greater than or equal to 570 pg/mL and TRAIL level of less than 25 pg/mL on day 3 were associated with COVID-19 severity. Patients with elevated day 3 IP-10 levels (≥ 570 pg/mL) were more likely to experience prolonged recovery time (median 12 vs 3 d; p < 0.001). The severe group had prolonged use of corticosteroids (12 vs 5 d; p < 0.001) and had a higher rate of secondary infections (20% vs 6%; p = 0.04) and in-hospital mortality (20% vs 0%; p < 0.001) as compared with nonsevere patients.

CONCLUSIONS:
The observed patterns in host immune response revealed a turning point in COVID-19 disease on hospital day 3 and the potential utility of IP-10 and TRAIL as sensitive markers associated with disease severity and time to recovery.
Selecting lymph node–positive patients for adjuvant therapy after radical prostatectomy and extended pelvic lymphadenectomy: An outcome analysis of 100 node-positive patients managed without adjuvant therapy
Authors: Tamhankar Ashwin Sunil , Patil Saurabh , Singh Shanky , Carbin Danny Darlington , Mokal Smruti , Ahluwalia Puneet , Gautam Gagan 
Published: September 2022

Abstract

Objective
The aim of the study is to evaluate the effect of deferred androgen deprivation therapy on biochemical recurrence (BCR) and other survival parameters in node-positive prostate cancer patients after robot-assisted radical prostatectomy with bilateral extended pelvic lymph node dissection (RARP + EPLND).

Materials and methods
Of the 453 consecutive RARP procedures performed from 2011 to 2018, 100 patients with no prior use of androgen deprivation therapy were found to be lymph node (LN) positive and were observed, with initiation of salvage treatment at the time of BCR only. Patients were divided into 1 or 2 LNs (67)—and more than 2 LNs (33)—positive groups to assess survival outcomes.

Results
At a median follow-up of 21 months (1–70 months), the LN group (p < 0.000), preoperative prostate-specific antigen (PSA, p = 0.013), tumor volume (TV, p = 0.031), and LND (p = 0.004) were significantly associated with BCR. In multivariate analysis, only the LN group (p = 0.035) and PSA level (p = 0.026) were statistically significant. The estimated BCR-free survival rates in the one-half LN group were 37.6% (27%–52.2%), 26.5% (16.8%–41.7%), and 19.9% (9.6%–41.0%) at 1, 3, and 5 years, respectively, with a hazard of developing BCR of 0.462 (0.225–0.948) compared with the more than 2 LN-positive group. Estimated 5-year overall survival, cancer-specific, metastasis-free, and local recurrence–free survival rates were 88.4% (73.1%–100%), 89.5% (74%–100%), 65.1% (46.0%–92.1%), and 94.8% (87.2%–100.0%), respectively, for which none of the factors were significant. Based on cutoff values for PSA, TV, and LND of 30 ng/mL, 30%, and 10%, respectively, the 1/2 LN group was substratified, wherein the median BCR-free survival for the low- and intermediate-risk groups was 40 and 12 months, respectively.

Conclusions
Nearly one fourth and one fifth of one-half node-positive patients were BCR-free at 3 and 5 years after RARP + EPLND. Further substratification using PSA, TV, and LN density may help in providing individualized care regarding the initiation of adjuvant therapy.
Practice Patterns for Mohs Surgeons of Varying Clinical Experience: A Cross-Sectional Analysis of a Medicare Claims Database
Authors: Singh Partik , Smith Franki Lambert , Brown Marc D. 
Published: September 2022

BACKGROUND
Use of Mohs micrographic surgery (MMS) is highly prevalent, but little data are available on how surgeon experience affects surgical practice patterns.

OBJECTIVE
To determine differences in use of MMS among surgeons of varying experience.

MATERIALS AND METHODS
This cross-sectional study sampled from clinicians billing ≥200 mean annual Mohs surgery claims from the 2012 to 2018 Medicare Public Use File. The primary outcome was mean annual Mohs surgery claims for clinicians of varying experience. Secondary outcomes included use of flaps/grafts and prescribing of oral antibiotics, benzodiazepines, and opioids.

RESULTS
Among 1,759 unique surgeons, those with 16 to 20 years of experience performed the most mean annual (95% confidence interval) Mohs surgical cases (578.7 [556.7–600.6]). Surgeons with 21 to 25 years of experience prescribed the most antibiotics (240.2 [216.5–263.8] mean annual claims), whereas those with >35 years of experience prescribed the longest courses (15.3 [14.2–16.4] days).

CONCLUSION
Midcareer surgeons performed the most mean annual Mohs surgery cases, whereas later career surgeons prescribed more frequent and longer courses of antibiotics suggesting changing practice patterns with additional years of experience.
Personalized external aortic root support in aneurysm disease
Authors: Treasure Tom , Austin Conal , Kenny Louise Amelia , Pepper John 
Published: September 2022

Purpose of review
To bring together and annotate publications about personalised external aortic reported in the 18 months preceding submission.

Recent findings
The total number of personalised external aortic root support (PEARS) operations is now approaching 700 in 32 centres in Australia, Belgium, Brazil, Czech Republic, Great Britain, Greece, Ireland, Malaysia, Netherlands, New Zealand, Poland and Slovakia. There are continued reports of stability of aortic dimensions and aortic valve function with the only exceptions known being where the surgeon has deviated from the directions for use of the device. The median root diameter of Marfan patients having PEARS was 47 mm suggesting that the existing criterion of 50 mm is due for reconsideration. The peri-operative mortality in the first 200 patients was 0.5% and is currently estimated to be less than 0.2%. The first recipient remains alive and well after 18 years. The use of PEARS as an adjunct to the Ross operation to support the pulmonary autograft is being explored in several centres.

Summary
The operation requires proctoring and adherence to a strict operative protocol and with those precautions excellent results are attained. The evidence and opinions provided in these publications indicate that this is proven and successful prophylactic operation for aortic root aneurysm.
It's not all about ISCHEMIA: the case for coronary artery bypass grafting in stable coronary artery disease
Authors: Yan Weiang , Eikelboom Rachel , Muller Moran Hellmuth R. , Arora Rakesh C. 
Published: September 2022

Purpose of Review
The recent American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions Guidelines for Coronary Artery Revascularization have raised concerns on the survival benefits of coronary artery bypass grafting (CABG) over guideline-directed medical therapy (GDMT) in stable coronary artery disease (CAD) and appropriate conduit selection for CABG. This review summarizes the evidence supporting CABG for stable CAD and use of the radial artery as a conduit for CABG.

Recent Findings
CABG has consistently demonstrated a survival benefit over GDMT for patients with stable multivessel CAD. These benefits were more pronounced in patients with diabetes and/or anatomically complex coronary artery disease. The recently published International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial was not designed to and did not include an appropriate patient population to compare revascularization with CABG to GDMT. These results should thus be viewed in the context of previously published studies. Furthermore, increasing evidence suggests that use of a radial artery in CABG is associated with reduced myocardial infarction and repeat revascularization. This should be considered when selecting the appropriate conduits based on underlying patient factors.

Summary
Readers should be cautious when applying these guidelines broadly. Appropriate consideration of patient and anatomic factors, and in consultation with a multidisciplinary heart team, is important to achieve the best outcomes for patients.
Outcomes of Patients With Thyroid Eye Disease Partially Treated With Teprotumumab
Authors: Ho Tiffany C. , Maamari Robi N. , Kossler Andrea L. , Sears Connie M. , Freitag Suzanne K. , Reshef Edith R. , Shinder Roman , Rootman Daniel B. , Diniz Stefania B. , Kahana Alon , Schlachter Dianne , Do Thai H. , Kally Peter , Turner Sara , Mokhtarzadeh Ali , Harrison Andrew R. , Hwang Christopher J. , Kim Hee Joon , Avila Sarah A. , Thomas Dilip A. , Magazin Maja , Wester Sara T. , Lee Wendy W. , Clauss Kevin D. , Holds John B. , Sniegowski Matthew , Compton Christopher J. , Briggs Christian , Malik Amina I. , Lucarelli Mark J. , Burkat Cat N. , Patel Luv G. , Couch Steven M. 
Published: September 2022

Purpose:
In response to the coronavirus (COVID-19) pandemic, teprotumumab production was temporarily halted with resources diverted toward vaccine production. Many patients who initiated treatment with teprotumumab for thyroid eye disease were forced to deviate from the standard protocol. This study investigates the response of teprotumumab when patients receive fewer than the standard 8-dose regimen.

Methods:
This observational cross-sectional cohort study included patients from 15 institutions with active or minimal to no clinical activity thyroid eye disease treated with the standard teprotumumab infusion protocol. Patients were included if they had completed at least 1 teprotumumab infusion and had not yet completed all 8 planned infusions. Data were collected before teprotumumab initiation, within 3 weeks of last dose before interruption, and at the visit before teprotumumab reinitiation. The primary outcome measure was reduction in proptosis more than 2 mm. Secondary outcome measures included change in clinical activity score (CAS), extraocular motility restriction, margin reflex distance-1 (MRD1), and reported adverse events.

Results:
The study included 74 patients. Mean age was 57.8 years, and 77% were female. There were 62 active and 12 minimal to no clinical activity patients. Patients completed an average of 4.2 teprotumumab infusions before interruption. A significant mean reduction in proptosis (–2.9 mm in active and –2.8 mm in minimal to no clinical activity patients, P < 0.01) was noted and maintained during interruption. For active patients, a 3.4-point reduction in CAS (P < 0.01) and reduction in ocular motility restriction (P < 0.01) were maintained during interruption.

Conclusions:
Patients partially treated with teprotumumab achieve significant reduction in proptosis, CAS, and extraocular muscle restriction and maintain these improvements through the period of interruption.