bluuebunny/crossref_metadata_2025_split huggingface dataset:
The interaction between RPAP3 and TRBP reveals a possible involvement of the HSP90/R2TP chaperone complex in the regulation of miRNA activity
Authors: Abel Yoann , Charron Christophe , Virciglio Camille , Bourguignon-Igel Valérie , Quinternet Marc , Chagot Marie-Eve , Robert Marie-Cécile , Verheggen Céline , Branlant Christiane , Bertrand Edouard , Manival Xavier , Charpentier Bruno , Rederstorff Mathieu 
Published: January 2022

Abstract
MicroRNAs silence mRNAs by guiding the RISC complex. RISC assembly occurs following cleavage of pre-miRNAs by Dicer, assisted by TRBP or PACT, and the transfer of miRNAs to AGO proteins. The R2TP complex is an HSP90 co-chaperone involved in the assembly of ribonucleoprotein particles. Here, we show that the R2TP component RPAP3 binds TRBP but not PACT. The RPAP3-TPR1 domain interacts with the TRBP-dsRBD3, and the 1.5 Å resolution crystal structure of this complex identifies key residues involved in the interaction. Remarkably, binding of TRBP to RPAP3 or Dicer is mutually exclusive. Additionally, we found that AGO(1/2), TRBP and Dicer are all sensitive to HSP90 inhibition, and that TRBP sensitivity is increased in the absence of RPAP3. Finally, RPAP3 seems to impede miRNA activity, raising the possibility that the R2TP chaperone might sequester TRBP to regulate the miRNA pathway.
The intrinsically disordered TSSC4 protein acts as a helicase inhibitor, placeholder and multi-interaction coordinator during snRNP assembly and recycling
Authors: Bergfort Alexandra , Hilal Tarek , Kuropka Benno , Ilik İbrahim Avşar , Weber Gert , Aktaş Tuğçe , Freund Christian , Wahl Markus C 
Published: January 2022

Abstract
Biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and their recycling after splicing require numerous assembly/recycling factors whose modes of action are often poorly understood. The intrinsically disordered TSSC4 protein has been identified as a nuclear-localized U5 snRNP and U4/U6-U5 tri-snRNP assembly/recycling factor, but how TSSC4’s intrinsic disorder supports TSSC4 functions remains unknown. Using diverse interaction assays and cryogenic electron microscopy-based structural analysis, we show that TSSC4 employs four conserved, non-contiguous regions to bind the PRPF8 Jab1/MPN domain and the SNRNP200 helicase at functionally important sites. It thereby inhibits SNRNP200 helicase activity, spatially aligns the proteins, coordinates formation of a U5 sub-module and transiently blocks premature interaction of SNRNP200 with at least three other spliceosomal factors. Guided by the structure, we designed a TSSC4 variant that lacks stable binding to the PRPF8 Jab1/MPN domain or SNRNP200 in vitro. Comparative immunoprecipitation/mass spectrometry from HEK293 nuclear extract revealed distinct interaction profiles of wild type TSSC4 and the variant deficient in PRPF8/SNRNP200 binding with snRNP proteins, other spliceosomal proteins as well as snRNP assembly/recycling factors and chaperones. Our findings elucidate molecular strategies employed by an intrinsically disordered protein to promote snRNP assembly, and suggest multiple TSSC4-dependent stages during snRNP assembly/recycling.
A multi-institutional pilot clinical trial of spectroscopic MRI-guided radiation dose escalation for newly diagnosed glioblastoma
Authors: Ramesh Karthik , Mellon Eric A , Gurbani Saumya S , Weinberg Brent D , Schreibmann Eduard , Sheriff Sulaiman A , Goryawala Mohammed , de le Fuente Macarena , Eaton Bree R , Zhong Jim , Voloschin Alfredo D , Sengupta Soma , Dunbar Erin M , Holdhoff Matthias , Barker Peter B , Maudsley Andrew A , Kleinberg Lawrence R , Shim Hyunsuk , Shu Hui-Kuo G 
Published: January 2022

Abstract

Background
Glioblastomas (GBMs) are aggressive brain tumors despite radiation therapy (RT) to 60 Gy and temozolomide (TMZ). Spectroscopic magnetic resonance imaging (sMRI), which measures levels of specific brain metabolites, can delineate regions at high risk for GBM recurrence not visualized on contrast-enhanced (CE) MRI. We conducted a clinical trial to assess the feasibility, safety, and efficacy of sMRI-guided RT dose escalation to 75 Gy for newly diagnosed GBMs.

Methods
Our pilot trial (NCT03137888) enrolled patients at 3 institutions (Emory University, University of Miami, Johns Hopkins University) from September 2017 to June 2019. For RT, standard tumor volumes based on T2-FLAIR and T1w-CE MRIs with margins were treated in 30 fractions to 50.1 and 60 Gy, respectively. An additional high-risk volume based on residual CE tumor and Cho/NAA (on sMRI) ≥2× normal was treated to 75 Gy. Survival curves were generated by the Kaplan–Meier method. Toxicities were assessed according to CTCAE v4.0.

Results
Thirty patients were treated in the study. The median age was 59 years. 30% were MGMT promoter hypermethylated; 7% harbored IDH1 mutation. With a median follow-up of 21.4 months for censored patients, median overall survival (OS) and progression-free survival were 23.0 and 16.6 months, respectively. This regimen appeared well-tolerated with 70% of grade 3 or greater toxicity ascribed to TMZ and 23% occurring at least 1 year after RT.

Conclusion
Dose-escalated RT to 75 Gy guided by sMRI appears feasible and safe for patients with newly diagnosed GBMs. OS outcome is promising and warrants additional testing. Based on these results, a randomized phase II trial is in development.
Predictive accuracy of T2-FLAIR mismatch sign for the IDH-mutant, 1p/19q noncodeleted low-grade glioma: An updated systematic review and meta-analysis
Authors: Do Yoon Ah , Cho Se Jin , Choi Byung Se , Baik Sung Hyun , Bae Yun Jung , Sunwoo Leonard , Jung Cheolkyu , Kim Jae Hyoung 
Published: January 2022

Abstract

Background
The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, has been considered a highly specific imaging biomarker of IDH-mutant, 1p/19q noncodeleted low-grade glioma. This systematic review and meta-analysis aimed to evaluate the diagnostic performance of T2-FLAIR mismatch sign for prediction of a patient with IDH-mutant, 1p/19q noncodeleted low-grade glioma, and identify the causes responsible for the heterogeneity across the included studies.

Methods
A systematic literature search in the Ovid-MEDLINE and EMBASE databases was performed for studies reporting the relevant topic before November 17, 2020. The pooled sensitivity and specificity values with their 95% confidence intervals were calculated using bivariate random-effects modeling. Meta-regression analyses were also performed to determine factors influencing heterogeneity.

Results
For all the 10 included cohorts from 8 studies, the pooled sensitivity was 40% (95% confidence interval [CI] 28–53%), and the pooled specificity was 100% (95% CI 95–100%). In the hierarchic summary receiver operating characteristic curve, the difference between the 95% confidence and prediction regions was relatively large, indicating heterogeneity among the studies. Higgins I2 statistics demonstrated considerable heterogeneity in sensitivity (I2 = 83.5%) and considerable heterogeneity in specificity (I2 = 95.83%). Among the potential covariates, it seemed that none of factors was significantly associated with study heterogeneity in the joint model. However, the specificity was increased in studies with all the factors based on the differences in the composition of the detailed tumors.

Conclusions
The T2-FLAIR mismatch sign is near-perfect specific marker of IDH mutation and 1p/19q noncodeletion.
Management of severe renal disease in anti-neutrophil-cytoplasmic-antibody-associated vasculitis: the place of rituximab and plasma exchange?
Authors: Morel Pauline , Karras Alexandre , Porcher Raphaël , Belenfant Xavier , Audard Vincent , Rafat Cédric , Hanouna Guillaume , Beaudreuil Séverine , Vilain Cédric , Hummel Aurélie , Terrier Benjamin , Pillebout Evangeline , Groh Matthieu , Jouenne Romain , Dhote Robin , Fain Olivier , Ponsoye Matthieu , Noel Nicolas , Limal Nicolas , Puéchal Xavier , Le Jeunne Claire , Guillevin Loïc , Mouthon Luc , Régent Alexis 
Published: January 2022

Abstract

Objective
The optimal induction therapy for severe glomerulonephritis of ANCA-associated vasculitis (AAV) is debated. We compared the efficacy of glucocorticoid and rituximab (RTX) or CYC induction therapy for severe AAV-related glomerulonephritis and evaluated the potential benefit of plasma exchange (PE) as adjunct therapy to CYC.

Methods
This retrospective, multicentre study included AAV patients with severe renal active disease (serum creatinine level ≥350 µmol/l and/or estimated glomerular filtration ratio ≤15 ml/min/1.73 m2). Propensity-score analysis was used to adjust for potential confounders.

Results
Between 2005 and 2017, 153 patients with AAV-related glomerulonephritis were studied (96 [60%] men; mean [s.d.] age 63 [13.1] years): 19 (12%) were treated with RTX and 134 (88%) with CYC. Remission rates did not differ between RTX- and CYC-treated groups. Although more patients with RTX than CYC were dialysis-free at month (M) 12 (79% vs 68%), the difference was not significant after adjustment. Among 134 patients with CYC-treated glomerulonephritis, 76 (57%) also had PE. M3 and M6 remission rates were comparable for weighted CYC groups with or without PE. For weighted groups, the dialysis-free survival rate with CYC was higher with than without PE at M6 (72% vs 64%; odds ratio 2.58) and M12 (74% vs 60%; odds ratio 2.78) reaching statistical significance at M12.

Conclusion
We could not find any difference between RTX and CYC as induction therapy for patients with severe AAV-related glomerulonephritis. In patients receiving CYC induction regimen, the addition of PE conferred short-term benefits with higher dialysis-free rate at M12.
Prospective epidemiological study of juvenile-onset systemic lupus erythematosus in the UK and Republic of Ireland
Authors: Lythgoe Hanna , Smith Eve M D , Killeen Orla G , Murphy Ruth , Pilkington Clarissa , Pain Clare E , Beresford Michael W ,   in association with the British Paediatric Surveillance Unit, Lynn Richard , McDonagh Janet , Tizard Jane , Ioannou Yiannis 
Published: January 2022

Abstract

Objectives
The primary objective was to define the incidence of JSLE in children &lt;16 years of age in the UK and Republic of Ireland (ROI). The secondary objective was to describe presenting features, classification criteria, initial management and disease damage in newly presenting JSLE patients.

Methods
A prospective JSLE epidemiological study was undertaken between September 2017 and September 2019 with support of the British Paediatric Surveillance Unit and other professional groups involved in diagnosis and management of JSLE patients. Treating consultants reported all cases of JSLE seen. A follow-up study at 1 year examined management and progression of disease and treatment.

Results
There were 124 incident cases included in the final analysis. Incidence was estimated using ACR-1997 classification criteria (0.36/100 000), SLICC-2012 classification criteria (0.41/100 000) and clinician expert opinion (0.46/100 000). A high disease burden was seen, with 71.0% of patients requiring ongoing systemic CS treatment at 1 year; 98.2% receiving immunomodulatory treatment; and 20.4% accruing damage in the year following diagnosis (predominantly neuropsychiatric-related), with substantial involvement from multiple speciality teams.

Conclusions
The minimum UK and ROI incidence of JSLE is between 0.36 and 0.46/100 000, depending on the case definition used. Challenges in classification of patients with JSLE are highlighted, but overall this study supports the use of SLICC-2012 classification criteria. The high levels of disease damage and ongoing CS use 1 year after diagnosis is concerning, highlighting the need for further interventions to improve outcomes in JSLE.
ACTIVITY RATIO OF URANIUM IN FUKUSHIMA SOIL SAMPLES USING MULTI-COLLECTOR INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
Authors: Murugan Rajamanickam , Sahoo Sarata Kumar , Sorimachi Atsuyuki , Omori Yasutaka , Aono Tatsuo 
Published: January 2022

Abstract
The Fukushima soils have been collected from Namie and Futaba areas for the radiocaesium and uranium isotope ratio studies. The 137Cs activity concentration of soil samples ranged from 6 ± 1 to 756 ± 14 kBq/kg. The uranium isotope ratios are measured using multi collector inductively coupled plasma mass spectrometry. The activity ratio (234U/238U) of the Fukushima soils is calculated from the measured 234U/238U isotope ratio. Activity ratio varied from 0.98 to 1.02 which indicates that 234U and 238U are in secular equilibrium. The 235U/238U atomic ratio of the Fukushima soils did not show any heterogeneity compared with the natural terrestrial ratio even with high level of 137Cs in soils.
Primary Nonadherence to Antipsychotic Treatment Among Persons with Schizophrenia
Authors: Lieslehto Johannes , Tiihonen Jari , Lähteenvuo Markku , Tanskanen Antti , Taipale Heidi 
Published: January 2022

AbstractIt has remained unclear what factors relate to primary nonadherence to antipsychotic treatment and whether specific agents and routes of administration differ in how patients adhere to them. We collected electronic prescriptions and their dispensings from the Finnish electronic prescription database for 29 956 patients with schizophrenia prescribed antipsychotics via electronic prescription during 2015–2016. We defined primary nonadherence as being prescribed an antipsychotic, which was not dispensed from the pharmacy within one year from prescription. Using logistic regression, we analyzed whether several sociodemographic and clinical factors related to nonadherence. We found that 31.7% (N = 9506) of the patients demonstrated primary nonadherence to any of their prescribed antipsychotics. We found that young age (OR = 1.77, 95%CI = 1.59–1.96), concomitant benzodiazepines (OR = 1.47, 95%CI = 1.40–1.55) and mood stabilizers (OR = 1.29, 95%CI = 1.21–1.36), substance abuse (OR = 1.26 95%CI = 1.19–1.35), previous suicide attempt (OR = 1.21, 95%CI = 1.11–1.31), diabetes (OR = 1.15, 95%CI = 1.06–1.25), asthma/COPD (OR = 1.14, 95%CI = 1.04–1.25), and cardiovascular disease (OR = 1.12, 95%CI = 1.05–1.19), were related to primary nonadherence to antipsychotic treatment. Patients using clozapine showed the lowest nonadherence (4.77%, 95%CI = 4.66–4.89), and patients using long-acting injectables were more adherent to treatment (7.27%, 95%CI = 6.85–7.71) when compared to respective oral agents (10.26%, 95%CI = 10.02–10.49). These results suggest that selection between different pharmacological agents and routes of administration while taking into account patients’ concomitant medications (benzodiazepines in particular) and comorbidities play a key role in primary nonadherence to antipsychotic treatment.
Experimental methods to study sleep disruption and immune balance in urban children with asthma
Authors: Koinis-Mitchell Daphne , Marshall Gailen D , Kopel Sheryl J , Belanger Nicole M S , Ayala-Figueroa Jesús , Echevarria Sofia , Millman Richard , Zheng Tao , Weathers Jessica , Gredvig Caroline A , Carskadon Mary A 
Published: January 2022

AbstractStudy ObjectivesWe describe research methods developed to examine effects of sleep disruption on changes in immune balance, lung function, and cognitive performance in a sample of urban, ethnically diverse children with persistent asthma. Two case examples (8- and 10-year-old males) are presented to highlight methods of the current study and illustrate effects of experimentally disrupted sleep on the immune balance profile (Th1/Th2 cytokines), key sleep variables from polysomnography data, and lung function in our sample.MethodsChildren follow an individualized structured sleep schedule consistent with their habitual sleep need (≥9.5 hours’ time in bed) for six days before a laboratory-based experimental sleep protocol. Children then spend two successive nights in the sleep lab monitored by polysomnography: a baseline night consisting of uninterrupted sleep, and a disruption night, during which they are awoken for 2 minutes between 20-minute intervals of uninterrupted sleep. Evening and morning blood draws bracket baseline and disruption nights for immune biomarker assessment.ResultsA shift towards immune imbalance following the sleep disruption protocol was observed in these illustrative cases.ConclusionsData from these case examples provide evidence that the experimental protocol caused disruptions in sleep as observed on polysomnography and had the hypothesized downstream effects on immune balance associated with clinical asthma control. Documenting the effects of sleep disruption on immune function in children with persistent asthma is a crucial step towards understanding associations between sleep, immune balance, and asthma outcomes and provides important information for developing novel interventions for youth with asthma and suboptimal sleep.Clinical TrialsNot applicable.
Suicide risk and prevention in LGBTQ+ youth
Authors: Cottrell Damon B. , Gonzalez John D. , Atchison Phillip T. , Evans Stephanie C. , Stokes Alyssa 
Published: January 2022

Abstract:
Lesbian, gay, bisexual, transgender, questioning (or queer), and other sexual and gender minority (LGBTQ+) youth face various forms of bullying and mistreatment that may lead to suicide. Nurses can help recognize, address, and mitigate challenges associated with suicide among LGBTQ+ youth.
Dementia care in the age of COVID-19
Authors: Nelson Andrea , Rosenberg Paul B. , Cotter Valerie T. 
Published: January 2022

Abstract:
The COVID-19 pandemic and related measures, such as social distancing, have adversely impacted persons with dementia (PWD) and their caregivers. Nurses must be able to identify the care needs of PWD and their caregivers and intervene with relevant resources.
Association between blood metals mixtures concentrations and cognitive performance, and effect modification by diet in older US adults
Authors: Laouali Nasser , Benmarhnia Tarik , Lanphear Bruce P. , Weuve Jennifer , Mascari Michael , Boutron-Ruault Marie-Christine , Oulhote Youssef 
Published: January 2022

Background:
Chronic exposure to heavy metals has been associated with adverse neurological outcomes in older adults. Inflammatory processes are suspected as an underlying pathway by which metals exert their neurotoxicity. In parallel, a diet rich in antioxidant and anti-inflammatory components may protect against chronic inflammation.

Objectives:
We examined the associations of blood concentrations of lead, cadmium, and manganese as a mixture with cognitive performance in older US adults and potential modification of these associations by diet as measured by the Healthy Eating Index 2015 (HEI-2015) and the Adapted Dietary Inflammatory Index (ADII).

Methods:
We used data on 1,777 adults ≥60 years old from the US National Health and Nutrition Examination Survey (NHANES; 2011–2014). We derived the ADII and the HEI-2015 from two nonconsecutive 24-hour diet recalls. Cognitive performance was measured by the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word Learning subtest, the animal fluency test, and the Digit Symbol Substitution Test (DSST). We also constructed a composite z-score reflecting overall cognitive performance. We used quantile g-computation to evaluate the joint associations of a mixture of metals with cognitive performance test scores. We also evaluated effect modification by sex and diet quality indices using Cochran Q tests.

Results:
The median (interquartile range) of blood metals were 0.38 μg/L (0.35), 14.70 μg/L (11.70), and 8.74 μg/L (4.06) for cadmium, lead, and manganese, respectively. Increasing blood concentrations of all metals by one quartile was associated with a decrease in overall cognitive performance (–0.04; 95% confidence interval [CI] = –0.09, 0.02), CERAD (–0.04; 95% CI = –0.12, 0.03), animal fluency (–0.02; 95% CI, –0.11, 0.06), and DSST (–0.05; 95% CI = –0.11, 0.02) test scores. These associations were more pronounced in adults with high pro-inflammatory or low-diet quality and null or positive though imprecise associations in participants with a high anti-inflammatory. These associations also varied by sex with inverse associations in men and positive associations in women.

Conclusions:
Our findings suggest that adherence to an antioxidant and anti-inflammatory diet may prevent blood metals adverse cognitive effects among older adults. If confirmed, strategies based on diet could provide a potential complementary and efficient approach to counteract effects of environmental pollutants.
Bilateral Finger Morton Neuroma after Primary Fingertip Amputation
Authors: Mogl Adrian Georg , Gualdi Alessandro , Kamolz Lars-Peter , Sarocchi Francesca , Cambiaso-Daniel Janos 
Published: January 2022

Summary:
Morton’s neuroma (MN) is a painful, proliferative fibrosis of perineural tissue caused by pressure or recurrent irritation that was previously thought to affect only the common interdigital nerve of the foot. We present a case of a bilateral MN of both the ulnar and radial proper digital nerves of the fifth finger in a 30-year-old patient, following multiple surgeries on the aforementioned finger. The patient was referred to our center by a peripheral hospital after traumatic fingertip amputation distal the DIP joint, where the fingertip was initially simply sutured. Because of progressive neuropathic pain, he underwent two revision surgeries, in which the distal phalanx was removed, two neuromas were excised, and the nerve stumps were shortened, but both were unsuccessful. A final, more extensive revision surgery was then carried out, in which two club-like enlargements were excised and the nerve stumps coadapted to form a loop. Histopathological examination of the excised specimen revealed perineural fibrosis in the context of a Morton’s neuroma. This is, to our knowledge, the first documented case of a bilateral MN of the hand, which may have resulted from an inadequate primary finger and nerve shortening, resulting in high pressure from the surrounding soft tissue. Finally, this report emphasizes the significance of optimal treatment for finger amputation injuries, as well as the fact that for neuromas, simple nerve resection should be avoided whenever possible, because of the high recurrence rates.
Structured Mammoplasty (Breast Reduction and Mastopexy with Silicone Implants): Standardization of Technique for Predictable Results
Authors: Sakai Rafael L. , Sakai Graciela M.G.A. , Pacheco Lucas C. , Rezende Aline P. , Montenegro Bruno H. 
Published: January 2022

Background:
Several methods have been developed for the treatment of ptosis and breast hypertrophy, with good early results but with dissatisfaction in the long term, due to loss of volume and projection of the upper pole and recurrence of ptosis. In the face of this adversity, the purposes of the present study were to describe a surgical technique of breast reduction and mastopexy with silicone implants, named structured mammoplasty, and to present the outcomes of patients who underwent this technique.

Methods:
The structured mammoplasty technique with round silicone prostheses (surgical marking and stages), performed on 100 patients who were operated on between 2017 and 2020 and were followed up for a minimum of 12 months, was described. Postoperative and patient satisfaction assessments were made.

Results:
No major complications were observed in an average of 18 months of follow-up (ranging from 12 to 30 months). The maintenance of the outcome with a projected upper pole and rounded breasts resulted in a high level of satisfaction.

Conclusions:
Structured mammoplasty with silicone implants is a safe and predictable option, ensuring a long-lasting shape. It can be applied to any breast that has surplus skin, making it a more reliable option in the arsenal of the plastic surgeon.