bluuebunny/crossref_metadata_2025_split huggingface dataset:
TPR is required for the efficient nuclear export of mRNAs and lncRNAs from short and intron-poor genes
Authors: Lee Eliza S , Wolf Eric J , Ihn Sean S J , Smith Harrison W , Emili Andrew , Palazzo Alexander F 
Published: October 2020

AbstractWhile splicing has been shown to enhance nuclear export, it has remained unclear whether mRNAs generated from intronless genes use specific machinery to promote their export. Here, we investigate the role of the major nuclear pore basket protein, TPR, in regulating mRNA and lncRNA nuclear export in human cells. By sequencing mRNA from the nucleus and cytosol of control and TPR-depleted cells, we provide evidence that TPR is required for the efficient nuclear export of mRNAs and lncRNAs that are generated from short transcripts that tend to have few introns, and we validate this with reporter constructs. Moreover, in TPR-depleted cells reporter mRNAs generated from short transcripts accumulate in nuclear speckles and are bound to Nxf1. These observations suggest that TPR acts downstream of Nxf1 recruitment and may allow mRNAs to leave nuclear speckles and properly dock with the nuclear pore. In summary, our study provides one of the first examples of a factor that is specifically required for the nuclear export of intronless and intron-poor mRNAs and lncRNAs.
Bidirectional associations between sleep quality or quantity, and dietary intakes or eating behaviors in children 6–12 years old: a systematic review with evidence mapping
Authors: Ward Aimee L , Jospe Michelle , Morrison Silke , Reynolds Andrew N , Kuroko Sarahmarie , Fangupo Louise J , Smith Claire , Galland Barbara C , Taylor Rachael W 
Published: October 2020

Abstract

Context
Although dietary advice has long been a cornerstone of a healthy lifestyle, how sleep quality and quantity may interact with dietary intake or eating behaviors remains unclear.

Objective
To consider a bidirectional relationship between sleep and diet in children aged 6–12 years via a systematic review following PRISMA guidelines.

Data Sources
Relevant trials and observational studies were identified by searching the PubMed, Medline, Embase, and CENTRAL databases up to June 1, 2019, without language or date restrictions and supplemented with hand searching. Recognized procedures and reporting standards were applied.

Data Extraction
Data on participant characteristics, study parameters, diet measures, sleep measures, and findings of study quality assessment criteria were collected.

Data Analysis
Forty-five articles involving 308 332 participants on a diverse range of topics were included. Meta-analyses were planned but were impossible to perform due to high study heterogeneity. Most studies (82%) were cross-sectional, which prevented examining directionality of the observed associations. Risk of bias was assessed for trial, cohort studies, and cross-sectional studies, using the Cochrane Risk of Bias Tool or Newcastle Ottawa Scale.

Results
Of 16 studies in which the effect of sleep on dietary intake was investigated, 81% (n = 13) reported a significant association. All studies (n = 8) of sugar-sweetened or caffeinated beverages reported a negative association with sleep, and in 6 of 7 studies in which eating behaviors were investigated, associations with sleep were reported. The use of objective measures of sleep and diet were scarce, with most trials and studies relying on subjective measures of sleep (68%) or diet (93%).

Conclusion
Because most studies investigating the relationship between sleep and diet in this age group are cross-sectional, temporality could not be determined. Additional randomized controlled trials and long-term cohort studies in middle childhood, particularly those using objective rather than questionnaire measures of sleep, are required to better understand interactions between diet and sleep.

Systematic Review Registration
Prospectively registered with PROSPERO International Prospective Register of Systematic Reviews (CRD42018091647).
The Molecular Function of Plant mTERFs as Key Regulators of Organellar Gene Expression
Authors: Wobbe Lutz 
Published: October 2020

Abstract
The protein family of mTERFs (mitochondrial transcription termination factors) was initially studied in mammalian and insect mitochondria before the first Arabidopsis mTERF mutant was characterized. More than 10 years of research on the function of plant mTERFs in the flowering plants Arabidopsis thaliana, Zea mays and the green microalga Chlamydomonas reinhardtii has since highlighted that mTERFs are key regulators of organellar gene expression (OGE) in mitochondria and in chloroplasts. Additional functions to be fulfilled by plant mTERFs (e.g. splicing) and the fact that the expression of two organellar genomes had to be facilitated have led to a massive expansion of the plant mTERF portfolio compared to that found in mammals. Plant mTERFs are implicated in all steps of OGE ranging from the modulation of transcription to the maturation of tRNAs and hence translation. Furthermore, being regulators of OGE, mTERFs are required for a successful long-term acclimation to abiotic stress, retrograde signaling and interorganellar communication. Here, I review the recent progress in the elucidation of molecular mTERF functions.
Asset-Level Risk and Return in Real Estate Investments
Authors: Sagi Jacob S 
Published: October 2020

Abstract
In stark contrast with liquid asset returns, commercial real estate idiosyncratic return means and variances do not scale with the holding period, even after accounting for all cash flow-relevant events. This puzzling phenomenon survives controlling for vintage effects, systematic risk heterogeneity, and a host of other explanations. To explain the findings, I derive an equilibrium search-based asset-pricing model that, when calibrated, provides an excellent fit to transactions data. A structural model of transaction risk seems crucial to understanding real estate price dynamics. These insights extend to other highly illiquid asset classes, such as private equity and residential real estate.
Early Childhood General Anesthesia and Neurodevelopmental Outcomes in the Avon Longitudinal Study of Parents and Children Birth Cohort
Authors: Walkden Graham J. , Gill Hannah , Davies Neil M. , Peters Alethea E. , Wright Ingram , Pickering Anthony E. 
Published: October 2020

Background
Most common anesthetic agents have been implicated in causing neurodegeneration in the developing animal brain, leading to warnings regarding their use in children. The hypothesis of this study was that exposure to general anesthesia and surgery before 4 yr would associate with adverse neurodevelopmental outcomes at age 7 to 16 yr.

Methods
This cohort study comprised 13,433 children enrolled in the Avon Longitudinal Study of Parents and Children, a prospective, population-based birth cohort born between 1991 and 1993 in southwest England. Children were grouped by none, single, or multiple exposures to general anesthesia and surgery by 4 yr. Motor, cognitive, linguistic, educational, social, and behavioral developmental outcomes were evaluated at 7 to 16 yr using school examination results, validated parent/teacher questionnaires, or clinic assessments. Continuous outcomes were z-scored. P-value thresholds were corrected using false discovery rate procedures.

Results
This study compared 46 neurodevelopmental outcomes in 13,433 children: 8.3% (1,110) exposed singly and 1.6% (212) exposed multiply to general anesthesia and surgery. Of these, the following reached predefined levels of statistical significance (corrected P < 0.00652): dynamic balance scores were 0.3 SD (95% CI, 0.1, 0.5; P < 0.001) lower in multiply exposed children; manual dexterity performance was 0.1 SD (95% CI, 0.0, 0.2; P = 0.006) lower in singly and 0.3 SD (95% CI, 0.1, 0.4; P < 0.001) lower in multiply exposed children; and social communication scores were 0.1 SD (95% CI, 0.0, 0.2; P = 0.001) and 0.4 SD (95% CI, 0.3, 0.5; P < 0.001) lower in singly and multiply exposed children, respectively. General anesthesia and surgery were not associated with impairments in the remaining neurodevelopmental measures including: general cognitive ability; attention; working memory; reading, spelling, verbal comprehension and expression; behavioral difficulties; or national English, mathematics, and science assessments (all ≤0.1 SD; corrected P ≥ 0.00652).

Conclusions
Early childhood general anesthesia and surgery were not associated with a global picture of clinically and statistically significant neurodegenerative effects, providing reassurance about the neurotoxic potential of general anesthesia. Exposure to anesthesia and surgery was associated with significantly lower motor and social linguistic performance.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Hypotension Prediction Index for Prevention of Hypotension during Moderate- to High-risk Noncardiac Surgery
Authors: Maheshwari Kamal , Shimada Tetsuya , Yang Dongsheng , Khanna Sandeep , Cywinski Jacek B. , Irefin Samuel A. , Ayad Sabry , Turan Alparslan , Ruetzler Kurt , Qiu Yuwei , Saha Partha , Mascha Edward J. , Sessler Daniel I. 
Published: October 2020

Background
The Hypotension Prediction Index is a commercially available algorithm, based on arterial waveform features, that predicts hypotension defined as mean arterial pressure less than 65 mmHg for at least 1 min. We therefore tested the primary hypothesis that index guidance reduces the duration and severity of hypotension during noncardiac surgery.

Methods
We enrolled adults having moderate- or high-risk noncardiac surgery with invasive arterial pressure monitoring. Participating patients were randomized to hemodynamic management with or without index guidance. Clinicians caring for patients assigned to guidance were alerted when the index exceeded 85 (range, 0 to 100) and a treatment algorithm based on advanced hemodynamic parameters suggested vasopressor administration, fluid administration, inotrope administration, or observation. Primary outcome was the amount of hypotension, defined as time-weighted average mean arterial pressure less than 65 mmHg. Secondary outcomes were time-weighted mean pressures less than 60 and 55 mmHg.

Results
Among 214 enrolled patients, guidance was provided for 105 (49%) patients randomly assigned to the index guidance group. The median (first quartile, third quartile) time-weighted average mean arterial pressure less than 65 mmHg was 0.14 (0.03, 0.37) in guided patients versus 0.14 (0.03, 0.39) mmHg in unguided patients: median difference (95% CI) of 0 (–0.03 to 0.04), P = 0.757. Index guidance therefore did not reduce amount of hypotension less than 65 mmHg, nor did it reduce hypotension less than 60 or 55 mmHg. Post hoc, guidance was associated with less hypotension when analysis was restricted to episodes during which clinicians intervened.

Conclusions
In this pilot trial, index guidance did not reduce the amount of intraoperative hypotension. Half of the alerts were not followed by treatment, presumably due to short warning time, complex treatment algorithm, or clinicians ignoring the alert. In the future we plan to use a lower index alert threshold and a simpler treatment algorithm that emphasizes prompt treatment.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Oral Dexmedetomidine Promotes Non-rapid Eye Movement Stage 2 Sleep in Humans
Authors: Chamadia Shubham , Hobbs Lauren , Marota Sophia , Ibala Reine , Hahm Eunice , Gitlin Jacob , Mekonnen Jennifer , Ethridge Breanna , Colon Katia M. , Sheppard Kimberly S. , Manoach Dara S. , DiBiasio Alan , Nguyen Sarah , Pedemonte Juan C. , Akeju Oluwaseun 
Published: October 2020

Background
The administration of dexmedetomidine is limited to highly monitored care settings because it is only available for use in humans as intravenous medication. An oral formulation of dexmedetomidine may broaden its use to all care settings. The authors investigated the effect of a capsule-based solid oral dosage formulation of dexmedetomidine on sleep polysomnography.

Methods
The authors performed a single-site, placebo-controlled, randomized, crossover, double-blind phase II study of a solid oral dosage formulation of dexmedetomidine (700 mcg; n = 15). The primary outcome was polysomnography sleep quality. Secondary outcomes included performance on the motor sequence task and psychomotor vigilance task administered to each subject at night and in the morning to assess motor memory consolidation and psychomotor function, respectively. Sleep questionnaires were also administered.

Results
Oral dexmedetomidine increased the duration of non-rapid eye movement (non-REM) stage 2 sleep by 63 (95% CI, 19 to 107) min (P = 0.010) and decreased the duration of rapid eye movement (REM) sleep by 42 (5 to 78) min (P = 0.031). Overnight motor sequence task performance improved after placebo sleep (7.9%; P = 0.003) but not after oral dexmedetomidine–induced sleep (–0.8%; P = 0.900). In exploratory analyses, we found a positive correlation between spindle density during non-REM stage 2 sleep and improvement in the overnight test performance (Spearman rho = 0.57; P = 0.028; n = 15) for placebo but not oral dexmedetomidine (Spearman rho = 0.04; P = 0.899; n = 15). Group differences in overnight motor sequence task performance, psychomotor vigilance task metrics, and sleep questionnaires did not meet the threshold for statistical significance.

Conclusions
These results demonstrate that the nighttime administration of a solid oral dosage formulation of dexmedetomidine is associated with increased non-REM 2 sleep and decreased REM sleep. Spindle density during dexmedetomidine sleep was not associated with overnight improvement in the motor sequence task.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
A Pharmacokinetic and Pharmacodynamic Study of Oral Dexmedetomidine
Authors: Chamadia Shubham , Pedemonte Juan C. , Hobbs Lauren E. , Deng Hao , Nguyen Sarah , Cortinez Luis I. , Akeju Oluwaseun 
Published: October 2020

Background
Dexmedetomidine is only approved for use in humans as an intravenous medication. An oral formulation may broaden the use and benefits of dexmedetomidine to numerous care settings. The authors hypothesized that oral dexmedetomidine (300 mcg to 700 mcg) would result in plasma concentrations consistent with sedation while maintaining hemodynamic stability.

Methods
The authors performed a single-site, open-label, phase I dose-escalation study of a solid oral dosage formulation of dexmedetomidine in healthy volunteers (n = 5, 300 mcg; followed by n = 5, 500 mcg; followed by n = 5, 700 mcg). The primary study outcome was hemodynamic stability defined as lack of hypertension, hypotension, or bradycardia. The authors assessed this outcome by analyzing raw hemodynamic data. Plasma dexmedetomidine concentrations were determined by liquid chromatograph–tandem mass spectrometry. Nonlinear mixed effect models were used for pharmacokinetic and pharmacodynamic analyses.

Results
Oral dexmedetomidine was associated with plasma concentration–dependent decreases in heart rate and mean arterial pressure. All but one subject in the 500-mcg group met our criteria for hemodynamic stability. The plasma concentration profile was adequately described by a 2-compartment, weight allometric, first-order absorption, first-order elimination pharmacokinetic model. The standardized estimated parameters for an individual of 70 kg was V1 = 35.6 [95% CI, 23.8 to 52.8] l; V2 = 54.7 [34.2 to 81.7] l; CL = 0.56 [0.49 to 0.64] l/min; and F = 7.2 [4.7 to 14.4]%. Linear models with effect sites adequately described the decreases in mean arterial pressure and heart rate associated with oral dexmedetomidine administration. However, only the 700-mcg group reached plasma concentrations that have previously been associated with sedation (>0.2 ng/ml).

Conclusions
Oral administration of dexmedetomidine in doses between 300 and 700 mcg was associated with decreases in heart rate and mean arterial pressure. Despite low oral absorption, the 700-mcg dose scheme reached clinically relevant concentrations for possible use as a sleep-enhancing medication.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Does participation in a multicenter study group affect physician treatment preference? A survey of participants
Authors: Martin Benjamin D. , Kelly Derek M. , Nolan Vikki G. , Matthews Allison , Flournory Jolecia , Kim Harry K.W. 
Published: October 2020

Background:
Our purpose was to determine if participation in a prospective, multicenter study group will influence surgeons’ treatment preferences despite no new evidence reported by the group.

Methods:
Surveys of treatment preferences in patients with Legg-Calve-Perthes (LCPD) disease and four cases with radiographs were sent to the International Perthes Study Group participants just before the inaugural meeting in 2012 and after the fifth annual meeting in 2016, and results were compared. A treatment change was a move from operative to nonoperative treatment or vice versa, surgeon experience was number of years in practice; the number of annual meetings attended served as a proxy study group participation.

Results:
Survey responses from 47 surgeons were analyzed. Participation in the study group ranged from one to five meetings, and the average clinical experience was 15 yr. On each survey question, some surgeons changed their response, highlighting changes in treatment preferences over time; however, no association was noted between treatment changes and number of meetings attended or length of surgeon experience. The more meetings attended, the more likely the surgeon used lateral extrusion on radiograph, lateral pillar or Catterall classification, or perfusion MRI as an indication to operate on certain age groups. For one of the four clinical cases, surgeons were 1.8 times more likely to change treatment preference with each meeting attended, and surgeons with less than 15 yr of experience were 8.5 times more likely to change.

Conclusions:
Although treatment preferences varied, study group participation did not impact decisions for operative versus nonoperative treatment, except in one case.

Level of Evidence:
Level IV.
Convalescent Plasma Therapy in Four Critically Ill Pediatric Patients With Coronavirus Disease 2019: A Case Series
Authors: Schwartz Stephanie P. , Thompson Peyton , Smith Melissa , Lercher Daniel M. , Rimland Casey A. , Bartelt Luther , Park Yara A. , Weiss Susan , Markmann Alena Janda , Raut Rajendra , Premkumar Lakshmanane , Kuruc JoAnn , Willis Zachary 
Published: October 2020

Background:
Coronavirus disease 2019 is a pandemic with no specific therapeutic agents or vaccination. Small published case series on critically ill adults suggest improvements in clinical status with minimal adverse events when patients receive coronavirus disease 2019 convalescent plasma, but data on critically ill pediatric patients are lacking. We report a series of four critically ill pediatric patients with acute respiratory failure who received coronavirus disease 2019 convalescent plasma as a treatment strategy for severe disease.

Case Summary:
Patients ranged in age from 5 to 16 years old. All patients received coronavirus disease 2019 convalescent plasma within the first 26 hours of hospitalization. Additional disease modifying agents were also used. All patients made a full recovery and were discharged home off of oxygen support. No adverse events occurred from the coronavirus disease 2019 convalescent plasma transfusions.

Conclusion:
Coronavirus disease 2019 convalescent plasma is a feasible therapy for critically ill pediatric patients infected with severe acute respiratory syndrome coronavirus 2. Well-designed clinical trials are necessary to determine overall safety and efficacy of coronavirus disease 2019 convalescent plasma and additional treatment modalities in pediatric patients.
Prevention of atelectasis by continuous positive airway pressure in anaesthetised children
Authors: Acosta Cecilia M. , Lopez Vargas María Paz , Oropel Facundo , Valente Lisandro , Ricci Lila , Natal Marcela , Suarez Sipmann Fernando , Tusman Gerardo 
Published: October 2020

BACKGROUND
Continuous positive airway pressure (CPAP) prevents peri-operative atelectasis in adults, but its effect in children has not been quantified.

OBJECTIVE
The aim of this study was to evaluate the role of CPAP in preventing postinduction and postoperative atelectasis in children under general anaesthesia.

DESIGN
A randomised controlled study.

SETTING
Single-institution study, community hospital, Mar del Plata. Argentina.

PATIENTS
We studied 42 children, aged 6 months to 7 years, American Society of Anesthesiologists physical status class I, under standardised general anaesthesia.

INTERVENTIONS
Patients were randomised into two groups: Control group (n = 21): induction and emergence of anaesthesia without CPAP; and CPAP group (n = 21): 5 cmH2O of CPAP during induction and emergence of anaesthesia. Lung ultrasound (LUS) imaging was performed before and 5 min after anaesthesia induction. Children without atelectasis were ventilated in the same manner as the Control group with standard ventilatory settings including 5 cmH2O of PEEP. Children with atelectasis received a recruitment manoeuvre followed by standard ventilation with 8 cmH2O of PEEP. Then, at the end of surgery, LUS images were repeated before tracheal extubation and 60 min after awakening.

MAIN OUTCOME MEASURES
Lung aeration score and atelectasis assessed by LUS.

RESULTS
Before anaesthesia, all children were free of atelectasis. After induction, 95% in the Control group developed atelectasis compared with 52% of patients in the CPAP group (P < 0.0001). LUS aeration scores were higher (impaired aeration) in the Control group than the CPAP group (8.8 ± 3.8 vs. 3.5 ± 3.3 points; P < 0.0001). At the end of surgery, before tracheal extubation, atelectasis was observed in 100% of children in the Control and 29% of the CPAP group (P < 0.0001) with a corresponding aeration score of 9.6 ± 3.2 and 1.8 ± 2.3, respectively (P < 0.0001). After surgery, 30% of children in the Control group and 10% in the CPAP group presented with residual atelectasis (P < 0.0001) also corresponding to a higher aeration score in the Control group (2.5 ± 3.1) when compared with the CPAP group (0.5 ± 1.5; P < 0.01).

CONCLUSION
The use of 5 cmH2O of CPAP in healthy children of the studied age span during induction and emergence of anaesthesia effectively prevents atelectasis, with benefits maintained during the first postoperative hour.

TRIAL REGISTRY
Clinicaltrials.gov NCT03461770.