bluuebunny/crossref_metadata_2025_split huggingface dataset:
PML and PML-like exonucleases restrict retrotransposons in jawed vertebrates
Authors: Mathavarajah Sabateeshan , Vergunst Kathleen L , Habib Elias B , Williams Shelby K , He Raymond , Maliougina Maria , Park Mika , Salsman Jayme , Roy Stéphane , Braasch Ingo , Roger Andrew J , Langelaan David N , Dellaire Graham 
Published: March 2023

Abstract
We have uncovered a role for the promyelocytic leukemia (PML) gene and novel PML-like DEDDh exonucleases in the maintenance of genome stability through the restriction of LINE-1 (L1) retrotransposition in jawed vertebrates. Although the mammalian PML protein forms nuclear bodies, we found that the spotted gar PML ortholog and related proteins in fish function as cytoplasmic DEDDh exonucleases. In contrast, PML proteins from amniote species localized both to the cytoplasm and formed nuclear bodies. We also identified the PML-like exon 9 (Plex9) genes in teleost fishes that encode exonucleases. Plex9 proteins resemble TREX1 but are unique from the TREX family and share homology to gar PML. We also characterized the molecular evolution of TREX1 and the first non-mammalian TREX1 homologs in axolotl. In an example of convergent evolution and akin to TREX1, gar PML and zebrafish Plex9 proteins suppressed L1 retrotransposition and could complement TREX1 knockout in mammalian cells. Following export to the cytoplasm, the human PML-I isoform also restricted L1 through its conserved C-terminus by enhancing ORF1p degradation through the ubiquitin-proteasome system. Thus, PML first emerged as a cytoplasmic suppressor of retroelements, and this function is retained in amniotes despite its new role in the assembly of nuclear bodies.
Multi-task learning from multimodal single-cell omics with Matilda
Authors: Liu Chunlei , Huang Hao , Yang Pengyi 
Published: March 2023

AbstractMultimodal single-cell omics technologies enable multiple molecular programs to be simultaneously profiled at a global scale in individual cells, creating opportunities to study biological systems at a resolution that was previously inaccessible. However, the analysis of multimodal single-cell omics data is challenging due to the lack of methods that can integrate across multiple data modalities generated from such technologies. Here, we present Matilda, a multi-task learning method for integrative analysis of multimodal single-cell omics data. By leveraging the interrelationship among tasks, Matilda learns to perform data simulation, dimension reduction, cell type classification, and feature selection in a single unified framework. We compare Matilda with other state-of-the-art methods on datasets generated from some of the most popular multimodal single-cell omics technologies. Our results demonstrate the utility of Matilda for addressing multiple key tasks on integrative multimodal single-cell omics data analysis. Matilda is implemented in Pytorch and is freely available from https://github.com/PYangLab/Matilda.
Interaction with the carboxy-terminal tip of SSB is critical for RecG function in E. coli
Authors: Bonde Nina J , Henry Camille , Wood Elizabeth A , Cox Michael M , Keck James L 
Published: March 2023

Abstract
In Escherichia coli, the single-stranded DNA-binding protein (SSB) acts as a genome maintenance organizational hub by interacting with multiple DNA metabolism proteins. Many SSB-interacting proteins (SIPs) form complexes with SSB by docking onto its carboxy-terminal tip (SSB-Ct). An alternative interaction mode in which SIPs bind to PxxP motifs within an intrinsically-disordered linker (IDL) in SSB has been proposed for the RecG DNA helicase and other SIPs. Here, RecG binding to SSB and SSB peptides was measured in vitro and the RecG/SSB interface was identified. The results show that RecG binds directly and specifically to the SSB-Ct, and not the IDL, through an evolutionarily conserved binding site in the RecG helicase domain. Mutations that block RecG binding to SSB sensitize E. coli to DNA damaging agents and induce the SOS DNA-damage response, indicating formation of the RecG/SSB complex is important in vivo. The broader role of the SSB IDL is also investigated. E. coli ssb mutant strains encoding SSB IDL deletion variants lacking all PxxP motifs retain wildtype growth and DNA repair properties, demonstrating that the SSB PxxP motifs are not major contributors to SSB cellular functions.
Colorful hues: insight into the mechanisms of anthocyanin pigmentation in fruit
Authors: Zhao Yun , Sun Juanli , Cherono Sylvia , An Jian-Ping , Allan Andrew C , Han Yuepeng 
Published: March 2023

Abstract
Anthocyanin is a vital indicator for both fruit nutritional and commercial value. Anthocyanin accumulation is a surprisingly complicated process mediated by multiple networks associated with genetic, developmental, hormonal, and environmental factors. Transcriptional regulation along with epigenetic regulation constitutes the dominant molecular framework for anthocyanin biosynthesis. Here, we focus on current knowledge on regulatory mechanisms of anthocyanin accumulation, with emphasis on the latest progress in transcriptional and epigenetic regulation and the crosstalk between various signaling pathways. We present an emerging picture of how various internal and external stimuli control anthocyanin biosynthesis. Additionally, we discuss the synergistic or antagonistic effect of developmental, hormonal and environmental cues on anthocyanin accumulation in fruit.
High-sensitivity cardiac troponin T in infants exposed to anti-Ro antibodies
Authors: Barsalou Julie , Jaeggi Edgar , Grosse-Wortmann Lars , Laskin Carl A , Adeli Khosrow , Silverman Earl D 
Published: March 2023

Abstract

Objectives
Cardiac involvement in neonatal lupus erythematosis (NLE) can present as myocarditis/endocardial fibroelastosis (EFE). It is unknown whether high-sensitivity cardiac troponin T (hs-cTnT) is useful in identifying subclinical myocardial inflammation in infants exposed prenatally to anti-Ro antibodies. This study reports hs-cTnT levels in infants exposed to anti-Ro antibodies with/without cardiac NLE and reports cardiac MRI (CMR) findings in a subset of these children.

Methods
The study included 45 consecutive infants exposed prenatally to anti-Ro antibodies with (n = 7) or without (n = 38) cardiac NLE, who were seen at the SickKids NLE Clinic between 2012 and 2014. Hs-cTnT levels were measured at least once, and those infants with values of ≥30 ng/l were offered the opportunity to undergo CMR. Descriptive statistics were performed.

Results
Of 38 infants without cardiac NLE, 25 had a hs-cTnT level of ≥30 ng/l (including 1 of &gt;113 ng/l); of these, 8 underwent CMR (all without myocarditis/EFE). All 7 infants with cardiac NLE had at least one hs-cTnT level of ≥30 ng/l, but only 2/7 had a level of &gt;113 ng/l; 4/7 infants with cardiac NLE had CMR (all without myocarditis/EFE); 6/7 infants with cardiac NLE had their steroid treatment adjusted based on the trend in their hs-cTnT levels.

Conclusion
Only 3/45 anti-Ro antibodies–exposed infants had hs-cTnT values outside the reference range reported in healthy infants. None of 12 infants who had CMR had subclinical myocarditis/EFE. Routine measurement of hs-cTnT in every anti-Ro antibody–exposed infant is not indicated. Further studies are needed to define the role of hs-cTnT as a biomarker for cardiac NLE.
Pulmonary and neurological health effects associated with exposure to representative composite manufacturing emissions and corresponding alterations in circulating metabolite profiles
Authors: Xia Li , Noh Yoorae , Whelton Andrew J , Boor Brandon E , Cooper Bruce , Lichti Nathanael I , Park Jae Hong , Shannahan Jonathan H 
Published: March 2023

Abstract
Cured-in-place pipe (CIPP) technology is increasingly being utilized to repair aging and damaged pipes, however, there are concerns associated with the public health hazards of emissions. CIPP installation involves the manufacture of a new plastic composite pipe at the worksite and includes multiple variable components including resin material, curing methods, and operational conditions. We hypothesize styrene-based composite manufacturing emissions (CMEs) will induce greater pulmonary inflammatory responses and oxidative stress, as well as neurological toxicity compared with nonstyrene CMEs. Further, these CME-toxicological responses will be sex- and time-dependent. To test the hypothesis, representative CMEs were generated using a laboratory curing chamber and characterized using thermal desorption-gas chromatography-mass spectrometry and photoionization detector. Styrene was released during staying, isothermal curing, and cooling phases of the process and peaked during the cooling phase. Male and female C57BL6/J mice were utilized to examine alterations in pulmonary responses and neurotoxicity 1 day and 7 days following exposure to air (controls), nonstyrene-CMEs, or styrene-CMEs. Serum styrene metabolites were increased in mice exposed to styrene-CMEs. Metabolic and lipid profiling revealed alterations related to CIPP emissions that were resin-, time-, and sex-dependent. Exposure to styrene-CMEs resulted in an influx of lymphocytes in both sexes. Expression of inflammatory and oxidative stress markers, including Tnfα, Vcam1, Ccl2, Cxcl2, Il6, Cxcl1, Tgfβ1, Tgmt2, and Hmox1, displayed alterations following exposure to emissions. These changes in pulmonary and neurological markers of toxicity were dependent on resin type, sex, and time. Overall, this study demonstrates resin-specific differences in representative CMEs and alterations in toxicity endpoints, which can potentially inform safer utilization of composite manufacturing processes.
Perineural and Systemic Dexamethasone and Ulnar Nerve Block Duration: A Randomized, Blinded, Placebo-controlled Trial in Healthy Volunteers
Authors: Maagaard Mathias , Stormholt Emma R. , Nielsen Lasse F. , Bærentzen Finn , Danker Jakob , Zachodnik Josephine , Jæger Pia , Mathiesen Ole , Andersen Jakob H. 
Published: March 2023

Background
The authors hypothesized that both perineural and systemic dexamethasone as adjuncts to bupivacaine increase the duration of an ulnar nerve block compared with bupivacaine alone, and that systemic dexamethasone is noninferior to perineural dexamethasone.

Methods
The authors performed bilateral ulnar nerve blocks with 3 ml bupivacaine 5 mg/ml in 16 healthy volunteers on two trial days. According to randomization, subjects received adjunct treatment with 1 ml dexamethasone 4 mg/ml + 1 ml of saline (perineural condition) in one arm and 2 ml saline in the other arm (systemic condition, through absorption and redistribution of the contralaterally administered perineural dexamethasone) on one trial day; and 2 ml saline in one arm (placebo condition) and 2 ml of lidocaine in the other arm (lidocaine condition) on the other trial day. The primary outcome was the duration of the sensory nerve block assessed by temperature discrimination.

Results
Mean sensory block duration was 706 ± 94 min for the perineural condition, 677 ± 112 min for the systemic condition, and 640 ± 121 min for the placebo condition. The duration of the sensory nerve block was greater with perineural dexamethasone versus placebo (mean difference 66 min (95% CI, 23 to 108). Block duration was similar between systemic dexamethasone and placebo (mean difference 36 min; 95% CI, –30 to 103).

Conclusions
Perineural dexamethasone as an adjunct to bupivacaine in healthy volunteers resulted in a greater duration of an ulnar nerve block when compared with placebo. Systemic dexamethasone resulted in a similar duration as placebo.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Surgical approach affecting long-term urinary continence status after robot-assisted laparoscopic prostatectomy prospectively evaluated using self-reported functional status (Expanded Prostate Cancer Index Composite, EPIC-26)
Authors: Reichert Mathias , Strauß Arne , Voß Joost Wilhelm , von Knobloch Hans Christoph , Neuenhofer Hannah Maria , Uhlig Annemarie , Trojan Lutz , Mohr Mirjam Naomi 
Published: March 2023

Abstract

Purpose
The aim of the study was to examine the influence of the surgical approach for robot-assisted laparoscopic prostatectomy (RALP) on long-term urinary continence status in the era of self-reported functional status measures using the Expanded Prostate Cancer Index Composite 26.

Materials and methods
This is a prospective evaluation of 232 patients undergoing RALP between September, 2019 and September, 2020. Urinary continence status and postoperative incontinence (pad usage) were evaluated 12 months after RALP using Expanded Prostate Cancer Index Composite 26 questionnaires. Patients were categorized according to their surgical approach and outcome into the following groups: successful nerve sparing (NS), primarily without nerve sparing (prim. NNS), and no nerve sparing by secondary resection (NNS by SR). The median levels of their questionnaire outcomes were evaluated and compared using the Wilcoxon rank sum test with continuity correction.

Results
Urinary continence status 12 months after RALP differed significantly between the NS and prim. NNS (p = 0.0071) and the NS and NNS by SR (p = 0.0076) groups. There was no significant difference between the prim. NNS and NNS by SR (p = 0.53) groups. Pad usage 12 months after RALP had no significant difference with regard to SR of the neurovascular bundle (p = 0.14).

Conclusions
Patient-reported outcomes of long-term urinary continence status seem to show no difference in postoperative continence, regardless of whether a non–nerve-sparing result was planned or reached through SR. Instead, preservation of neurovascular bundle seems to lead to better long-term continence rates.
The aging brain: risk factors and interventions for long term brain health in women
Authors: Caldwell Jessica Z.K. , Isenberg Nancy 
Published: March 2023

Purpose of review
Poor cognitive aging and dementia pose a significant public health burden, and women face unique risks compared to men. Recent research highlights the role of genetics, menopause, chronic disease, and lifestyle in risk and resilience in women's cognitive aging. This work suggests avenues for clinical action at midlife that may change the course of brain health in aging.

Recent findings
Studies indicate women's risk for poor cognitive aging relates in part to hormone changes at menopause, a time when memory, brain structure and function, and Alzheimer's pathology may be observed in women and not men. Medical and lifestyle risks including diabetes, hypertension, and low physical activity also contribute to women's unique risks. At the same time, literature on resilience suggests women may benefit from lifestyle and chronic disease intervention, possibly more than men. Current studies emphasize the importance of interacting genetic and lifestyle risks, and effects of social determinants of health.

Summary
Women have greater risk than men for poor cognitive aging; however, by treating the whole person, including genetics, lifestyle, and social environment, clinicians have an opportunity to support healthy cognitive aging in women and reduce the future public health burden of dementia.
Genital tuberculosis, infertility and assisted reproduction
Authors: Mir Nousheen , Pal Lubna 
Published: March 2023

Purpose of review
The goal of this review is to familiarize a global readership on the subtilities of clinical presentation and the mayhem that a missed diagnosis of genital tuberculosis (GTB) is capable of inflicting on the health and wellbeing of infertile women with untreated GTB attempting to conceive with assisted reproductive technology (ART).

Recent findings
Emerging and recent literature relating to the epidemiology and clinical presentation of GTB and reporting of unique risks of ART for maternal and fetal morbidity in untreated cases of GTB are reviewed. Evidence relating to a broadening spectrum of screening methodologies for GTB detection of GTB is additionally considered.

Summary
Genital TB must be considered as a mechanism for couple's infertility in at-risk populations. Attempting to treat female GTB-related infertility with in-vitro fertilization poses unique and potentially life-threatening risks, both to the mother and to the conceptus; these risks can be avoided through vigilance, appropriate screening and timely treatment prior to proceeding with IVF.
HENLE FIBER LAYER THICKNESS AND AREA MEASUREMENT IN TYPE 2 DIABETES MELLITUS WITH AND WITHOUT RETINOPATHY USING A MODIFIED DIRECTIONAL OPTICAL COHERENCE TOMOGRAPHY STRATEGY
Authors: Ersoz M. Giray , Kırık Furkan , Isik Burcu , Ozdemir Hakan 
Published: March 2023

Purpose:
To investigate the thicknesses and areas of Henle fiber layer (HFL), outer nuclear layer, and outer plexiform layer in the eyes of patients with diabetes with no diabetic retinopathy, in eyes with nonproliferative diabetic retinopathy without diabetic macular edema, and in healthy eyes using a modified directional optical coherence tomography strategy.

Methods:
In this prospective study, the no diabetic retinopathy group included 79 participants, the nonproliferative diabetic retinopathy group comprised 68 participants, and the control group had 58 participants. Thicknesses and areas of Henle fiber layer, outer nuclear layer, and outer plexiform layer were measured on a horizontal single optical coherence tomography scan centered on the fovea using directional optical coherence tomography.

Results:
The foveal, parafoveal, and total HFL were significantly thinner in the nonproliferative diabetic retinopathy group than in the no diabetic retinopathy group and the control group (all P < 0.05). The no diabetic retinopathy group had significantly thinner foveal HFL thickness and area compared with the control group (all P < 0.05). The nonproliferative diabetic retinopathy group had significantly thicker outer nuclear layer thickness and area in all regions than the other groups (all P < 0.05). The outer plexiform layer measurements did not differ between the groups (all P > 0.05).

Conclusion:
Directional optical coherence tomography provides isolated thickness and area measurement of HFL. In patients with diabetes, the HFL is thinner, and HFL thinning begins before the presence of diabetic retinopathy.
RISK FACTORS FOR SURGERY OR BLINDNESS IN NEOVASCULAR GLAUCOMA EYES TREATED WITH ANTI-VEGF INJECTIONS BY A RETINA SPECIALIST
Authors: Massenzio Erik , Xu David , Abishek Robert , Wibbelsman Turner D. , Sheng Young , Obeid Anthony , Bhatt Shivani , Zhang Qiang , Sharpe James , Park Carl H. , Spirn Marc J. , Gupta Omesh P. , Chiang Allen , Shukla Aakriti , Shalaby Wesam S. , Myers Jonathan S. , Hsu Jason 
Published: March 2023

Purpose:
To determine baseline patient characteristics that predict the need for glaucoma surgery or blindness in eyes with neovascular glaucoma (NVG) despite intravitreal antivascular endothelial growth factor therapy.

Methods:
This is a retrospective cohort study of patients with NVG who had not previously received glaucoma surgery and were treated with intravitreal antivascular endothelial growth factor injections at the time of diagnosis, from September 8, 2011, to May 8, 2020, at a large, retina subspecialty practice.

Results:
Of 301 newly presenting NVG eyes, 31% required glaucoma surgery and 20% progressed to no light perception vision despite treatment. Patients with intraocular pressure >35 mmHg (P < 0.001), two or more topical glaucoma medications (P = 0.003), worse than 20/100 vision (P = 0.024), proliferative diabetic retinopathy (P = 0.001), eye pain or discomfort (P = 0.010), and new patient status (P = 0.015) at the time of NVG diagnosis were at a higher risk of glaucoma surgery or blindness regardless of antivascular endothelial growth factor therapy. The effect of panretinal photocoagulation was not statistically significant in a subgroup analysis of patients without media opacity (P = 0.199).

Conclusion:
Several baseline characteristics at the time of presentation to a retina specialist with NVG seem to portend a higher risk of uncontrolled glaucoma despite the use of antivascular endothelial growth factor therapy. Prompt referral of these patients to a glaucoma specialist should be strongly considered.
VITREORETINAL LYMPHOMA WITH CENTRAL NERVOUS SYSTEM INVOLVEMENT IN A PATIENT WITH SARCOIDOSIS: A CASE REPORT
Authors: Ramos Michael S. , Mammo Danny A. , Yuan Alex , Sharma Sumit 
Published: March 2023

Background/Purpose:
To describe a case of primary vitreoretinal lymphoma with central nervous system involvement in a patient with sarcoidosis.

Methods:
Single, retrospective chart review.

Patient:
A 59-year-old man with sarcoidosis.

Results:
The patient presented with a 3-year history of bilateral panuveitis thought secondary to his sarcoidosis diagnosed 11 years before. Shortly before presentation, the patient demonstrated recurrent uveitis with a lack of response to aggressive immunosuppression therapy. At presentation, ocular examination showed significant anterior and posterior inflammation. Fluorescein angiography demonstrated hyperfluorescence of the optic nerve with late and small vessel leakage in the right eye. The patient also described a two-month history of memory and word-finding deficits. An inflammatory and infectious disease work-up was unremarkable. A brain MRI showed multiple enhancing periventricular lesions with vasogenic edema, whereas a lumbar puncture was negative for malignant cells. A diagnostic pars plana vitrectomy confirmed a diagnosis of large B-cell lymphoma.

Conclusion:
Sarcoidosis and vitreoretinal lymphoma are known masqueraders. Recurrent inflammation typical of sarcoid uveitis may mask a more sinister diagnosis such as vitreoretinal lymphoma. Furthermore, sarcoid uveitis treatment with corticosteroids may transiently improve symptoms, but further delay a timely diagnosis of primary vitreoretinal lymphoma.
Content Validity of a Collaborative Goal-Setting Pictorial Tool for Children Who Wear Ankle-Foot Orthoses: A Modified Delphi Consensus Study
Authors: Owen Elaine , Rahlin Mary , Kane Kyra Janine 
Published: March 2023

ABSTRACT

Introduction
To determine the optimum prescription and dosage for an ankle-foot orthosis and footwear, clinicians and families need to agree on goals for intervention. To facilitate family-centered collaborative goal setting, a table of potential goals and its pictorial representation had been developed previously. These tools incorporated the International Classification of Functioning, Disability, and Health (ICF) and International Organization for Standardization (ISO) clinical objectives for orthoses and were structured in an approach understandable to families. This study aimed to obtain consensus on the content validity of the Table and Pictorial Tools.

Methods
Seventeen experts from seven countries (orthotists, physical therapists, physicians, surgeons, and engineers) were invited. A modified Delphi technique was used to evaluate and refine the Table Tool (rounds 1 and 2) and Pictorial Tool (rounds 3 and 4). Participants rated their agreement with overall tool structure, content, and feasibility of use on a 4-point Likert scale, and provided open-ended feedback. Consensus was defined as a median score ≥3 (agree) with 75% of responses ≥3. Data were collected using REDCap. After each round, thematic analysis guided document revisions and anonymized feedback.

Results
Ten experts from four countries completed the study. Round 1 (Table Tool): median ratings were all 3; consensus was achieved for 3/5 questions. Round 2: full consensus was achieved. Round 3 (Pictorial Tool): median ratings were ≥3 for 10/11 questions; consensus was achieved for 4/11 questions. Round 4: full consensus was achieved.

Conclusions
The content validity for the Table and Pictorial Tools was established by modified Delphi consensus. These tools represent a comprehensive selection of goals across all ICF components.

Clinical Relevance
These novel tools have the potential to facilitate collaborative goal setting between families and clinicians and aid clinical education. A goal-setting framework specific to orthotic management may improve outcomes within the context of family-centered care.