bluuebunny/crossref_metadata_2025_split huggingface dataset:
New-Onset Psychosis Associated With a Lesion Localized in the Rostral Tectum: Insights Into Pathway-Specific Connectivity Disrupted in Psychosis
Authors: Koropouli Eleftheria , Melanitis Nikos , Dimitriou Vasileios I , Grigoriou Asimina , Karavasilis Efstratios , Nikita Konstantina S , Tzavellas Elias , Paparrigopoulos Thomas 
Published: February 2020

Abstract

Objective
To investigate pathway-specific connectivity disrupted in psychosis.

Methods
We carried out a case study of a middle-aged patient who presented with new-onset psychosis associated with a space-occupying lesion localized in the right superior colliculus/periaqueductal gray. The study sought to investigate potential connectivity deficits related to the lesion by the use of diffusion tensor imaging and resting-state functional magnetic resonance imaging. To this aim, we generated a functional connectivity map of the patient’s brain, centered on the lesion area, and compared this map with the corresponding map of 10 sex- and age-matched control individuals identified from the Max Planck Institute–Leipzig Mind–Brain–Body database.

Results
Our analysis revealed a discrete area in the right rostral tectum, in the immediate vicinity of the lesion, whose activity is inversely correlated with the activity of left amygdala, whereas left amygdala is functionally associated with select areas of the temporal, parietal, and occipital lobes. Based on a comparative analysis of the patient with 10 control individuals, the lesion has impacted on the connectivity of rostral tectum (superior colliculus/periaqueductal gray) with left amygdala as well as on the connectivity of left amygdala with subcortical and cortical areas.

Conclusions
The superior colliculus/periaqueductal gray might play important roles in the initiation and perpetuation of psychosis, at least partially through dysregulation of left amygdala activity.
Universal loop assembly: open, efficient and cross-kingdom DNA fabrication
Authors: Pollak Bernardo , Matute Tamara , Nuñez Isaac , Cerda Ariel , Lopez Constanza , Vargas Valentina , Kan Anton , Bielinski Vincent , von Dassow Peter , Dupont Chris L , Federici Fernán 
Published: February 2020

Abstract
Standardized type IIS DNA assembly methods are becoming essential for biological engineering and research. These methods are becoming widespread and more accessible due to the proposition of a ‘common syntax’ that enables higher interoperability between DNA libraries. Currently, Golden Gate (GG)-based assembly systems, originally implemented in host-specific vectors, are being made compatible with multiple organisms. We have recently developed the GG-based Loop assembly system for plants, which uses a small library and an intuitive strategy for hierarchical fabrication of large DNA constructs (&gt;30 kb). Here, we describe ‘universal Loop’ (uLoop) assembly, a system based on Loop assembly for use in potentially any organism of choice. This design permits the use of a compact number of plasmids (two sets of four odd and even vectors), which are utilized repeatedly in alternating steps. The elements required for transformation/maintenance in target organisms are also assembled as standardized parts, enabling customization of host-specific plasmids. Decoupling of the Loop assembly logic from the host-specific propagation elements enables universal DNA assembly that retains high efficiency regardless of the final host. As a proof-of-concept, we show the engineering of multigene expression vectors in diatoms, yeast, plants and bacteria. These resources are available through the OpenMTA for unrestricted sharing and open access.
Ensuring the Availability of Clinical Clerkships at U.S. Hospitals: A Tale of 2 States
Authors: Lenhoff Fred , Goldberg Robert B. , Reichgott Michael , Collins Marcia , Jumper Cynthia , Elliott Victoria Stagg 
Published: February 2020

U.S. medical schools are facing growing competition for limited clinical training resources, notably slots for the core clerkships that students most often complete in the third year of their undergraduate medical education. In particular, medical schools in the Caribbean (often referred to as offshore medical schools) are buying clerkship slots at U.S. hospitals for their students, most of whom will be U.S. citizen international medical graduates. For hospitals, especially those that are financially stressed, these payments are an attractive source of revenue. Yet, this practice has put pressure on U.S. medical schools to provide similar remuneration for clerkship slots for their students or to find new clinical training sites.
In this Perspective, the authors outline the scope of the challenge facing U.S. medical schools and the U.S. medical education system. They outline legislative strategies implemented in 2 states (New York and Texas) to address this issue and propose the passage of similar legislation in other states to ensure that students at U.S. medical schools can access the clerkships they need to obtain the requisite clinical experience before entering residency. Such legislation would preserve the availability of clerkships for U.S. medical students and the educational quality of these clinical training experiences and, therefore, preserve the quantity and quality of the future physician workforce in the United States.
Machine Learning Prediction of Postoperative Emergency Department Hospital Readmission
Authors: Mišić Velibor V. , Gabel Eilon , Hofer Ira , Rajaram Kumar , Mahajan Aman 
Published: February 2020

Abstract

Background
Although prediction of hospital readmissions has been studied in medical patients, it has received relatively little attention in surgical patient populations. Published predictors require information only available at the moment of discharge. The authors hypothesized that machine learning approaches can be leveraged to accurately predict readmissions in postoperative patients from the emergency department. Further, the authors hypothesize that these approaches can accurately predict the risk of readmission much sooner than hospital discharge.

Methods
Using a cohort of surgical patients at a tertiary care academic medical center, surgical, demographic, lab, medication, care team, and current procedural terminology data were extracted from the electronic health record. The primary outcome was whether there existed a future hospital readmission originating from the emergency department within 30 days of surgery. Secondarily, the time interval from surgery to the prediction was analyzed at 0, 12, 24, 36, 48, and 60 h. Different machine learning models for predicting the primary outcome were evaluated with respect to the area under the receiver-operator characteristic curve metric using different permutations of the available features.

Results
Surgical hospital admissions (N = 34,532) from April 2013 to December 2016 were included in the analysis. Surgical and demographic features led to moderate discrimination for prediction after discharge (area under the curve: 0.74 to 0.76), whereas medication, consulting team, and current procedural terminology features did not improve the discrimination. Lab features improved discrimination, with gradient-boosted trees attaining the best performance (area under the curve: 0.866, SD 0.006). This performance was sustained during temporal validation with 2017 to 2018 data (area under the curve: 0.85 to 0.88). Lastly, the discrimination of the predictions calculated 36 h after surgery (area under the curve: 0.88 to 0.89) nearly matched those from time of discharge.

Conclusions
A machine learning approach to predicting postoperative readmission can produce hospital-specific models for accurately predicting 30-day readmissions via the emergency department. Moreover, these predictions can be confidently calculated at 36 h after surgery without consideration of discharge-level data.

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Opioid Fills for Lumbar Facet Radiofrequency Ablation Associated with New Persistent Opioid Use
Authors: Southren Daniel L. , Moser Stephanie , Abu-Amara Hasan , Lin Paul , Schack Amanda A. , Gunaseelan Vidhya , Waljee Jennifer F. , Brummett Chad M. 
Published: February 2020

Abstract

Background
Zygapophyseal (facet) joint interventions are the second most common interventional procedure in pain medicine. Opioid exposure after surgery is a significant risk factor for chronic opioid use. The aim of this study was to determine the incidence of new persistent use of opioids after lumbar facet radiofrequency ablation and to assess the effect of postprocedural opioid prescribing on the development of new persistent opioid use.

Methods
The authors conducted a retrospective cohort study using claims from the Clinformatics Data Mart Database (OptumInsight, USA) to identify opioid-naïve patients between 18 and 64 yr old who had lumbar radiofrequency ablation. Patients who had either subsequent radiofrequency ablation 15 to 180 days or subsequent surgery within 180 days after the primary procedure were excluded from the analysis. The primary outcome was new persistent opioid use, defined as opioid prescription fulfillment within the 8 to 90 and 91 to 180 day periods after radiofrequency ablation. The authors then assessed patient-level risk factors for new persistent opioid use.

Results
A total of 2,887 patients met the inclusion criteria. Of those patients, 2,277 (78.9%) had radiofrequency ablation without a perioperative opioid fill, and 610 (21.1%) patients had the procedure with a perioperative opioid fill. The unadjusted rate of new persistent opioid use was 5.6% (34 patients) in the group with a perioperative opioid fill versus 2.8% (63 patients) for those without an opioid fill. Periprocedural opioid prescription fill was independently associated with increased odds of new persistent use (adjusted odds ratio, 2.35; 95% CI, 1.51 to 3.66; P < 0.001).

Conclusions
Periprocedural opioid use after lumbar radiofrequency ablation was associated with new persistent use in previously opioid-naïve patients, suggesting that new exposure to opioids is an independent risk factor for persistent use in patients having radiofrequency ablation for chronic back pain. Opioid prescribing after radiofrequency ablation should be reevaluated and likely discontinued in this population.

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Source-level Cortical Power Changes for Xenon and Nitrous Oxide–induced Reductions in Consciousness in Healthy Male Volunteers
Authors: Pelentritou Andria , Kuhlmann Levin , Cormack John , Mcguigan Steven , Woods Will , Muthukumaraswamy Suresh , Liley David 
Published: February 2020

Abstract

Background
Investigations of the electrophysiology of gaseous anesthetics xenon and nitrous oxide are limited revealing inconsistent frequency-dependent alterations in spectral power and functional connectivity. Here, the authors describe the effects of sedative, equivalent, stepwise levels of xenon and nitrous oxide administration on oscillatory source power using a crossover design to investigate shared and disparate mechanisms of gaseous xenon and nitrous oxide anesthesia.

Methods
Twenty-one healthy males underwent simultaneous magnetoencephalography and electroencephalography recordings. In separate sessions, sedative, equivalent subanesthetic doses of gaseous anesthetic agents nitrous oxide and xenon (0.25, 0.50, and 0.75 equivalent minimum alveolar concentration–awake [MACawake]) and 1.30 MACawake xenon (for loss of responsiveness) were administered. Source power in various frequency bands were computed and statistically assessed relative to a conscious/pre-gas baseline.

Results
Observed changes in spectral-band power (P < 0.005) were found to depend not only on the gas delivered, but also on the recording modality. While xenon was found to increase low-frequency band power only at loss of responsiveness in both source-reconstructed magnetoencephalographic (delta, 208.3%, 95% CI [135.7, 281.0%]; theta, 107.4%, 95% CI [63.5, 151.4%]) and electroencephalographic recordings (delta, 260.3%, 95% CI [225.7, 294.9%]; theta, 116.3%, 95% CI [72.6, 160.0%]), nitrous oxide only produced significant magnetoencephalographic high-frequency band increases (low gamma, 46.3%, 95% CI [34.6, 57.9%]; high gamma, 45.7%, 95% CI [34.5, 56.8%]). Nitrous oxide—not xenon—produced consistent topologic (frontal) magnetoencephalographic reductions in alpha power at 0.75 MACawake doses (44.4%; 95% CI [−50.1, −38.6%]), whereas electroencephalographically nitrous oxide produced maximal reductions in alpha power at submaximal levels (0.50 MACawake, −44.0%; 95% CI [−48.1,−40.0%]).

Conclusions
Electromagnetic source-level imaging revealed widespread power changes in xenon and nitrous oxide anesthesia, but failed to reveal clear universal features of action for these two gaseous anesthetics. Magnetoencephalographic and electroencephalographic power changes showed notable differences which will need to be taken into account to ensure the accurate monitoring of brain state during anaesthesia.

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Insights into the Chemical Discovery of Remifentanil
Authors: Feldman Paul L. 
Published: February 2020

Abstract

Design, Synthesis, and Pharmacological Evaluation of Ultrashort- to Long-acting Opioid Analgetics. By Feldman PL, James MK, Brackeen MF, Bilotta JM, Schuster SV, Lahey AP, Lutz MW, Johnson MR, Leighton HJ. J Med Chem 1991; 34:2202-8. Copyright 1991 American Chemical Society. Reprinted with permission.
In an effort to discover a potent ultrashort-acting µ-opioid analgetic that is capable of metabolizing to an inactive species independent of hepatic function, several classes of 4-anilidopiperidine analgetics were synthesized and evaluated. One series of compounds displayed potent µ-opioid agonist activity with a high degree of analgesic efficacy and an ultrashort to long duration of action. These analgetics, 4-(methoxycarbonyl)-4-[1-oxopropyl)phenylamino]-1-piperidinepropanoic acid alkyl esters, were evaluated in vitro in the guinea pig ileum for µ-opioid activity, in vivo in the rat tail withdrawal assay for analgesic efficacy and duration of action, and in vitro in human whole blood for their ability to be metabolized in blood. Compounds in this series were all shown to be potent µ agonists in vitro, but depending upon the alkyl ester substitution, the potency and duration of action in vivo varied substantially. The discrepancies between the in vitro and in vivo activities and variations in duration of action are probably due to different rates of ester hydrolysis by blood esterase(s). The [structure–activity relationships] with respect to analgesic activity and duration of action as a function of the various esters synthesized is discussed. It was also demonstrated that the duration of action for the ultrashort-acting analgetic, 8, does not change upon prolonged infusion or administration of multiple bolus injections.
Preoperative Cognitive Abnormality, Intraoperative Electroencephalogram Suppression, and Postoperative Delirium
Authors: Fritz Bradley A. , King Christopher R. , Ben Abdallah Arbi , Lin Nan , Mickle Angela M. , Budelier Thaddeus P. , Oberhaus Jordan , Park Daniel , Maybrier Hannah R. , Wildes Troy S. , Avidan Michael S. ,   for the ENGAGES Research Group*
Published: February 2020

Abstract

Background
Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium.

Methods
This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5.

Results
Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs.123 of 683 [18%], P < 0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size (P = 0.078 for moderation).

Conclusions
A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect.

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Single-Center Outcome of Fetoscopic Tracheal Balloon Occlusion for Severe Congenital Diaphragmatic Hernia
Authors: Baschat Ahmet A. , Rosner Mara , Millard Sarah E. , Murphy Jamie D. , Blakemore Karin J. , Keiser Amaris M. , Kearney Jennifer , Bullard Janine , Nogee Lawrence M. , Bembea Melania , Jelin Eric B. , Miller Jena L. 
Published: February 2020

OBJECTIVE:
To assess feasibility and maternal and infant outcome after fetoscopic tracheal balloon occlusion in patients with severe congenital diaphragmatic hernia.

METHODS:
We conducted a prospective cohort study of fetuses with congenital diaphragmatic hernia and observed/expected lung/head ratio less than 30%. Eligible women had planned fetoscopic tracheal balloon occlusion at 26 0/7–29 6/7 weeks of gestation and balloon removal 4–6 weeks later. Standardized prenatal and postnatal care was at a single institution. Fetoscopic tracheal balloon occlusion details, lung growth, obstetric complications, birth outcome, and infant outcome details until discharge were evaluated.

RESULTS:
Of 57 women screened, 14 (25%) were enrolled between 2015 and 2019. The congenital diaphragmatic hernia was left in 12 (86%); the pre–fetoscopic tracheal balloon occlusion observed/expected lung/head ratio was 23.2% (range 15.8–29.0%). At a median gestational age of 28 5/7 weeks (range 27 3/7–29 6/7), fetoscopic tracheal balloon occlusion was successful in all cases, and balloons remained in situ. Removal was elective in 10 (71%) patients, by ultrasound-guided needle puncture in eight (57%), and occurred at a median of 33 4/7 weeks of gestation (range 32 1/7–34 4/7; median occlusion 34 days, range 17–44). The post–fetoscopic tracheal balloon occlusion observed/expected lung/head ratio increased to a median of 62.8% (44.0–108) and fell to a median of 46.6% (range 30–92) after balloon removal (all Mann Whitney U, P<.003). For prevention of preterm birth, all patients received vaginal progesterone; 11 (79%) required additional tocolytics, three (21%) had vaginal pessary placement for cervical shortening, and five (36%) had amnioreduction for polyhydramnios. Median gestational age at birth was 39 2/7 weeks (range 33 6/7–39 4/7), with term birth in eight (57%) patients. Twelve (86%) neonates required high-frequency ventilation, and seven (50%) required extracorporeal membrane oxygenation for a median of 7 days (range 3–19). All neonates needed patch repair. Neonatal survival was 93% (n=13, 95% CI 49–100%), and survival to hospital discharge was 86% (n=12, 95% CI 44–100%).

CONCLUSION:
Fetoscopic tracheal balloon occlusion for severe congenital diaphragmatic hernia was feasible in our single-center setting, with few obstetric complications and favorable infant outcome.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02710968.
Gestation-Specific Vital Sign Reference Ranges in Pregnancy
Authors: Green Lauren J. , Mackillop Lucy H. , Salvi Dario , Pullon Rebecca , Loerup Lise , Tarassenko Lionel , Mossop Jude , Edwards Clare , Gerry Stephen , Birks Jacqueline , Gauntlett Rupert , Harding Kate , Chappell Lucy C. , Watkinson Peter J. 
Published: February 2020

OBJECTIVE:
To estimate normal ranges for maternal vital signs throughout pregnancy, which have not been well defined in a large contemporary population.

METHODS:
We conducted a three-center, prospective, longitudinal cohort study in the United Kingdom from August 2012 to September 2017. We recruited women at less than 20 weeks of gestation without significant comorbidities with accurately dated singleton pregnancies. We measured participants' blood pressure (BP), heart rate, respiratory rate, oxygen saturation and temperature following standardized operating procedures at 4–6 weekly intervals throughout pregnancy.

RESULTS:
We screened 4,279 pregnant women, 1,041 met eligibility criteria and chose to take part. Systolic and diastolic BP decreased slightly from 12 weeks of gestation: median or 50th centile (3rd–97th centile) 114 (95–138); 70 (56–87) mm Hg to reach minimums of 113 (95–136); 69 (55–86) mm Hg at 18.6 and 19.2 weeks of gestation, respectively, a change (95% CI) of −1.0 (−2 to 0); −1 (−2 to −1) mm Hg. Systolic and diastolic BP then rose to a maximum median (3rd–97th centile) of 121 (102–144); 78 (62–95) mm Hg at 40 weeks of gestation, a difference (95% CI) of 7 (6–9) and9 (8–10) mm Hg, respectively. The median (3rd–97th centile) heart rate was lowest at 12 weeks of gestation: 82 (63–105) beats per minute (bpm), rising progressively to a maximum of 91 (68–115) bpm at 34.1 weeks. SpO2 decreased from 12 weeks of gestation: median (3rd–97th centile) 98% (94–99%) to 97% (93–99%) at 40 weeks. The median (3rd–97th centile) respiratory rate at 12 weeks of gestation was 15 (9–22), which did not change with gestation. The median (3rd–97th centile) temperature at 12 weeks of gestation was 36.7 (35.6–37.5)°C, decreasing to a minimum of 36.5 (35.3–37.3)°C at 33.4 weeks.

CONCLUSION:
We present widely relevant, gestation-specific reference ranges for detecting abnormal BP, heart rate, respiratory rate, oxygen saturation and temperature during pregnancy. Our findings refute the existence of a clinically significant BP drop from 12 weeks of gestation.

CLINICAL TRIAL REGISTRATION:
ISRCTN, ISRCTN10838017.