bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Meta-analysis of Structural and Functional Brain Abnormalities in Early-Onset Schizophrenia
Authors: Ioakeimidis Vasileios , Haenschel Corinna , Yarrow Kielan , Kyriakopoulos Marinos , Dima Danai 
Published: March 2020

AbstractEarly-onset schizophrenia (EOS) patients demonstrate brain changes that are similar to severe cases of adult-onset schizophrenia. Neuroimaging research in EOS is limited due to the rarity of the disorder. The present meta-analysis aims to consolidate MRI and functional MRI findings in EOS. Seven voxel-based morphometry (VBM) and 8 functional MRI studies met the inclusion criteria, reporting whole-brain analyses of EOS vs healthy controls. Activation likelihood estimation (ALE) was conducted to identify aberrant anatomical or functional clusters across the included studies. Separate ALE analyses were performed, first for all task-dependent studies (Cognition ALE) and then only for working memory ones (WM ALE). The VBM ALE revealed no significant clusters for gray matter volume reductions in EOS. Significant hypoactivations peaking in the right anterior cingulate cortex (rACC) and the right temporoparietal junction (rTPJ) were detected in the Cognition ALE. In the WM ALE, consistent hypoactivations were found in the left precuneus (lPreC), the right inferior parietal lobule (rIPL) and the rTPJ. These hypoactivated areas show strong associations with language, memory, attention, spatial, and social cognition. The functional co-activated networks of each suprathreshold ALE cluster, identified using the BrainMap database, revealed a core co-activation network with similar topography to the salience network. Our results add support to posterior parietal, ACC and rTPJ dysfunction in EOS, areas implicated in the cognitive impairments characterizing EOS. The salience network lies at the core of these cognitive processes, co-activating with the hypoactivating regions, and thus highlighting the importance of salience dysfunction in EOS.
Differential activating effects of thyrotropin-releasing hormone and its analog taltirelin on motor output to the tongue musculature in vivo
Authors: Liu Wen-Ying , Liu Hattie , Aggarwal Jasmin , Huang Zhi-Li , Horner Richard L 
Published: March 2020

Abstract
Thyrotropin-releasing hormone (TRH) is produced by the hypothalamus but most brain TRH is located elsewhere where it acts as a neuromodulator. TRH-positive neurons project to the hypoglossal motoneuron pool where TRH receptor RNA shows a high degree of differential expression compared with the rest of the brain. Strategies to modulate hypoglossal motor activity are of physiological and clinical interest given the potential for pharmacotherapy for obstructive sleep apnea (OSA), a common and serious respiratory disorder. Here, we identified the effects on tongue motor activity of TRH and a specific analog (taltirelin) applied locally to the hypoglossal motoneuron pool and systemically in vivo. Studies were performed under isoflurane anesthesia and across sleep–wake states in rats. In anesthetized rats, microperfusion of TRH (n = 8) or taltirelin (n = 9) into the hypoglossal motoneuron pool caused dose-dependent increases in tonic and phasic tongue motor activity (both p &lt; 0.001). However, the motor responses to TRH were biphasic, being significantly larger “early” in the response versus at the end of the intervention (p ≤ 0.022). In contrast, responses to taltirelin were similar “early” versus “late” (p ≥ 0.107); i.e. once elicited, the motor responses to taltirelin were sustained and maintained. In freely behaving conscious rats (n = 10), microperfusion of 10 μM taltirelin into the hypoglossal motoneuron pool increased tonic and phasic tongue motor activity in non-rapid-eye-movement (REM) sleep (p ≤ 0.038). Intraperitoneal injection of taltirelin (1 mg/kg, n = 16 rats) also increased tonic tongue motor activity across sleep–wake states (p = 0.010). These findings inform the studies in humans to identify the potential beneficial effects of taltirelin for breathing during sleep and OSA.
Topiramate reduces nocturnal eating in sleep-related eating disorder
Authors: Winkelman John W , Wipper Benjamin , Purks Julia , Mei Leslie , Schoerning Laura 
Published: March 2020

Abstract

Study Objectives
Sleep-related eating disorder (SRED) is a parasomnia characterized by partial arousals from sleep with compulsive consumption of food with impaired level of awareness and memory for the event. Small case series’ have demonstrated efficacy of topiramate in SRED. We conducted a placebo-controlled randomized clinical trial of topiramate to assess efficacy in SRED.

Methods
Thirty-four participants with an ICSD-2/ICSD-3 diagnosis of SRED with &gt;6 months of symptoms and ≥3 sleep-related eating episodes per week were randomized to placebo or topiramate with flexible dosing to a maximum dosage of 300 mg for 13 weeks. Primary outcomes were percentage of nights with eating and Clinician Global Impression-Improvement (CGI-I). Intention-to-treat last observation carried forward (ITT LOCF) analysis was conducted.

Results
Mean age was 39.5 years, 74% were female, with mean duration of sleep-related eating of 13.7 years. SRED symptoms were significantly reduced with topiramate (74.7% to 33.2% nights/week; n = 15) compared to placebo (77.0% to 57.4%; n = 17) (p = 0.035). There were significantly more CGI-I responders on topiramate (71%) than placebo (27%) (p = 0.016). Level of wakefulness (r = −0.49) and memory for nighttime eating (r = −0.58) at baseline predicted topiramate response. The topiramate group lost significantly more weight than the placebo group (−8.5 lbs vs. +1.0 lbs, p = 0.001). The most common side effects were paresthesias and cognitive dysfunction.

Conclusions
This first randomized controlled trial demonstrating efficacy for treatment of SRED supports preliminary data on the use of topiramate for SRED. Side effects were prominent for topiramate. Limitations include a small sample size and a high drop-out rate in both study groups.

Clinical Trial Information
NCT00606411
New insights into the cognitive effects of sleep deprivation by decomposition of a cognitive throughput task
Authors: Honn Kimberly A , Halverson T , Jackson M L , Krusmark M , Chavali V P , Gunzelmann G , Van Dongen H P A 
Published: March 2020

Abstract

Study Objectives
A cognitive throughput task known as the Digit Symbol Substitution Test (DSST) (or Symbol Digit Modalities Test) has been used as an assay of general cognitive slowing during sleep deprivation. Here, the effects of total sleep deprivation (TSD) on specific cognitive processes involved in DSST performance, including visual search, spatial memory, paired-associate learning, and motor response, were investigated through targeted task manipulations.

Methods
A total of 12 DSST variants, designed to manipulate the use of specific cognitive processes, were implemented in two laboratory-based TSD studies with N = 59 and N = 26 subjects, respectively. In each study, the Psychomotor Vigilance Test (PVT) was administered alongside the DSST variants.

Results
TSD reduced cognitive throughput on all DSST variants, with response time distributions exhibiting rightward skewing. All DSST variants showed practice effects, which were however minimized by inclusion of a pause between trials. Importantly, TSD-induced impairment on the DSST variants was not uniform, with a principal component analysis revealing three factors. Diffusion model decomposition of cognitive processes revealed that inter-individual differences during TSD on a two-alternative forced choice DSST variant were different from those on the PVT.

Conclusions
While reduced cognitive throughput has been interpreted to reflect general cognitive slowing, such TSD-induced impairment appears to reflect cognitive instability, like on the PVT, rather than general slowing. Further, comparisons between task variants revealed not one, but three distinct underlying processes impacted by sleep deprivation. Moreover, the practice effect on the task was found to be independent of the TSD effect and minimized by a task pacing manipulation.
Effects of low dose radiation on immune cells subsets and cytokines in mice
Authors: Liu Xiaochang , Liu Zheng , Wang Duo , Han Yang , Hu Sai , Xie Ying , Liu Yike , Zhu Maoxiang , Guan Hua , Gu Yongqing , Zhou Ping-Kun 
Published: March 2020

Abstract
Whole-body exposure to low-dose radiation due to diagnostic imaging procedures, occupational hazards and radiation accidents is a source of concern. In this study, we analyzed the effects of single and long-term low-dose irradiation on the immune system. Male Balb/c mice received a single whole-body dose of irradiation (0.01, 0.05, 0.2, 0.5 or 1 Gy). For long-term irradiation, mice were irradiated 10 times (total dose of 0.2, 0.5 or 1 Gy) over a period of 6 weeks. Two days after single or long-term irradiation, the numbers of splenic macrophages, natural killer cells and dendritic cells were reduced, and the spleen organ coefficient was decreased. At 2 Days after long-term low-dose irradiation, the number of white blood cells in the peripheral blood of the mice decreased. Between 7 and 14 Days after long-term low-dose irradiation, the number of immune cells in the thymus and spleen began to increase and then stabilized. Th1/Th2 cytokines and reactive oxygen species-related proteins first decreased and then increased to a plateau. Our results show a significant difference in the effects of single and long-term low-dose irradiation on the immune system.
Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19)
Authors: Alhazzani Waleed , Møller Morten Hylander , Arabi Yaseen M. , Loeb Mark , Gong Michelle Ng , Fan Eddy , Oczkowski Simon , Levy Mitchell M. , Derde Lennie , Dzierba Amy , Du Bin , Aboodi Michael , Wunsch Hannah , Cecconi Maurizio , Koh Younsuck , Chertow Daniel S. , Maitland Kathryn , Alshamsi Fayez , Belley-Cote Emilie , Greco Massimiliano , Laundy Matthew , Morgan Jill S. , Kesecioglu Jozef , McGeer Allison , Mermel Leonard , Mammen Manoj J. , Alexander Paul E. , Arrington Amy , Centofanti John E. , Citerio Giuseppe , Baw Bandar , Memish Ziad A. , Hammond Naomi , Hayden Frederick G. , Evans Laura , Rhodes Andrew 
Published: March 2020

Background:The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.Methods:We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using theGrading of Recommendations, Assessment, Development and Evaluation(GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.Results:The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy.Conclusion:The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.
Relationship Between Contact Lens Sensor Output Parameters and Visual Field Progression in Open-angle Glaucoma: Assessment of a Practical Tool to Guide Clinical Risk-assessment
Authors: Gillmann Kevin , Young Cara C. , Stanley Jordan , Seibold Leonard K. , Hoskens Kirsten , Midha Neha , Kahook Malik Y. , Mansouri Kaweh 
Published: March 2020

Purpose:
In recent years, new technologies have emerged to better analyze and interpret intraocular pressure (IOP) fluctuations. Among them is the progression report (PR), an algorithm based on continuous contact lens sensor (CLS) readings to estimate the likelihood of fast visual field (VF) glaucomatous progression. The objective of this study is to validate the PR.

Methods:
In this retrospective study, 30 open-angle glaucoma patients were enrolled. Twenty-four hours IOP-related variations were recorded using a CLS. Recordings were used to generate PR. The likelihood of fast VF progression (<−1 dB/y mean deviation) was estimated by 2 masked assessors based on clinical parameters. At least 3 VF were performed over the 2 years following the initial assessment, to determine actual progression.

Results:
Mean age was 65.9±10.45 years, with a mean baseline mean deviation of −5.4±5.1. After a mean follow-up of 29.5±12.9 months, 26.7% of eyes were assessed as fast progressors (−2.9±1.9 dBs/y). The average risk-score attributed by the PR was 42% [41% (slow) vs. 44% (fast); P=0.035]. Correlations between the 2 assessors were good (r=0.59), and identical to that between PR and the averaged assessors’ gradings. Correlations between mean deviation progression rates and PR, Assessor 1 and Assessor 2’s gradings were, r=0.57, 0.31, and 0.43, respectively.

Conclusions:
PR provided comparable predictions of the risk of fast VF progression as did physician estimates based on all available clinical data. With their relationship to the eye’s biomechanical properties and the ocular tissues’ response to pressure variations, CLS recordings may offer new information that complements conventional examinations.
Reversible Corneal Endothelial Abnormalities With Netarsudil
Authors: Tanna Angelo P. , Esfandiari Hamed , Teramoto Kyla 
Published: March 2020

Purpose:
To report a case of reversible corneal endothelial abnormalities after treatment with netarsudil.

Observation:
A 68-year-old woman presented with the complaint of blurred vision soon after starting treatment with the fixed-dose combination of netarsudil and latanoprost (FC-netarsudil-latanoprost). She had been receiving the fixed-dose combination of dorzolamide and timolol and latanoprost for primary open-angle glaucoma until her ophthalmologist switched latanoprost to FC-netarsudil-latanoprost 2 months before referral to our center.
Best-corrected visual acuity was 20/20-1 in the right eye and 20/20-3 in the left eye. The slit-lamp biomicroscopic examination was remarkable for a guttata-like abnormality of the corneal endothelium of both eyes. The intraocular pressure was 10 mm Hg in both eyes. Specular microscopy revealed irregularly shaped corneal endothelial cells with indistinct borders between cells. FC-netarsudil-latanoprost was replaced with latanoprost in the left eye but continued in the right eye. Nine weeks later, best-corrected visual acuity remained 20/20-1 in the right eye but it improved to 20/20 in the left eye. Repeat specular microscopy was unchanged in the right eye and was normal in the left eye.

Conclusion and Importance:
Topical therapy with netarsudil can result in guttata-like changes of the corneal endothelium and corneal endothelial cell abnormalities that can be detected with specular microscopy. These abnormalities seem to be transient and resolved upon the cessation of netarsudil. Ophthalmologists should consider the possibility of a corneal endothelial abnormality in patients treated with netarsudil who develop blurred vision.
Hip fracture care and national systems: Australia and Asia
Authors: Tarrrant Seth M. , Ajgaonkar Amit , Babhulkar Sushrut , Cui Zhiyong , Harris Ian A. , Kulkarni Sunil , Minehara Hiroaki , Miyamoto Takashi , Oppy Andrew , Shigemoto Kenji , Tian Yun , Balogh Zsolt J. 
Published: March 2020

Abstract
The Asia-Pacific region includes countries with diverse cultural, demographic, and socio-political backgrounds. Countries such as Japan have very high life expectancy and an aged population. China and India, with a combined population over 2.7 billion, will experience a huge wave of ageing population with subsequent osteoporotic injuries. Australia will experience a similar increase in the osteoporotic fracture burden, and is leading the region by establishing a national hip fracture registry with governmental guidelines and outcome monitoring. While it is impossible to compare fragility hip fracture care in every Asia-Pacific country, this review of 4 major nations gives insight into the challenges facing diverse systems. They are united by the pursuit of internationally accepted standards of timely surgery, combined orthogeriatric care, and secondary fracture prevention strategies.
Surgical timing for open fractures
Authors: You Daniel Z. , Schneider Prism S. 
Published: March 2020

Abstract
Controversy exists over the optimal management of open fractures as new clinical studies question open fracture management dogma. Open fractures are complex injuries requiring the orthopaedic surgeon to consider both the bone injury as well as associated soft tissue injury. Early intravenous antibiotics and tetanus prophylaxis remain instrumental in infection prevention. However, the “six-hour rule” for initial open fracture debridement and revascularization has come into question. New evidence supports initial debridement within 24 hours with the appropriate surgical team. Additionally, orthopaedic surgeons and vascular surgeons should collaborate on the sequence of management of open fractures with associated vascular injury. Whereas debates on the optimal irrigation pressure and solution have been answered by multicenter randomized controlled trials, further research is required to determine the optimal irrigation volume and timing of wound closure. With advances in management of open fractures, the utility of well-known classification systems including the Gustilo-Anderson classification and Mangled Extremity Severity Score need to be re-evaluated in favor of up-to-date classification systems which better guide management and predict prognosis.
It Is Time to Reconsider Factorial Designs: How Bradford Hill and R. A. Fisher Shaped the Standard of Clinical Evidence
Authors: Neuhauser Duncan , Provost Shannon M. , Provost Lloyd P. 
Published: March 2020

Objectives:
Could medical research and quality improvement studies be more productive with greater use of multifactor study designs?

Methods:
Drawing on new primary sources and the literature, we examine the roles of A. Bradford Hill and Ronald A. Fisher in introducing the design of experiments in medicine.

Results:
Hill did not create the randomized controlled trial, but he popularized the idea. His choice to set aside Fisher's advanced study designs shaped the development of clinical research and helped the single-treatment trial to become a methodological standard.

Conclusions:
Multifactor designs are not widely used in medicine despite their potential to make improvement initiatives and health services research more efficient and effective. Quality managers, health system leaders, and directors of research institutes could increase productivity and gain important insights by promoting a broader use of factorial designs to study multiple interventions simultaneously and to learn from interactions.
Timeliness of Care for Injured Patients Initially Seen at Freestanding Emergency Departments: A Pilot Quality Improvement Project
Authors: Birmingham Lauren E. , Richner Gwendolyn , Moran Mary , Hatridge Kindra M. , George Richard L. 
Published: March 2020

Background:
The impact of freestanding emergency departments (FSEDs) on timeliness of care for trauma patients is not well understood. This quality improvement project had 2 objectives: (1) to determine whether significant delays in definitive care existed among trauma patients initially seen at FSEDs compared with those initially seen at other outlying sites prior to transfer to a level I trauma center; and (2) to determine the feasibility of identifying differences in time-to-definitive care and emergency department length of stay (ED LOS) based on initial treatment location.

Methods:
Trauma registry data from January 1, 2017, through December 31, 2017, from a verified level I trauma center were analyzed by location of initial presentation. Appropriate statistical tests are used to make comparisons across transport groups.

Results:
Patients initially seen at non-FSEDs experienced ED LOS that were, on average, 24.5 minutes greater than patients seen initially at FSEDs, although the difference was not statistically significant (P = .3112). Several challenges were identified in the feasibility analysis that will inform the design for a larger study including large quantities of missing time stamp data and potential selection bias. Prospective solutions were identified.

Conclusion:
This project found that there were not significant differences in ED LOS for injured patients presenting initially to FSEDs or other non-FSED facilities, suggesting that timeliness of care was similar across location types.
Resources Utilization After Liver Transplantation in Patients With and Without Hepatopulmonary Syndrome: Cleveland Clinic Experience
Authors: Cywinski Jacek B. , Makarova Natalya , Arney Andrea , Liu Qiang , Fujiki Masato , Menon K. V. Narayanan , Quintini Cristiano 
Published: March 2020

Background.Patients with hepatopulmonary syndrome (HPS) reportedly experience posttransplant morbidity and require more resources to care during perioperative period. The exact incremental increase of resources utilization compared with non-HPS population remains unknown.Methods.In this single-center retrospective investigation, we compared the perioperative resources utilization of HPS patients undergoing orthotopic liver transplant (n = 28) to cohort without HPS (n = 739). Potential confounding variables were adjusted in the analysis and the multivariable log-linear regression were used.Results.The overall hospital costs for HPS patients were about 27% higher compared with non-HPS patients (the ratio of geometric means, 1.27; 98.3% confidence interval, 1.09-1.47;P < 0). HPS diagnosis was independently associated with both longer intensive care unit stay (P < 0.001) and hospital stay (P < 0.001). The odds of being discharged to extended care facility were about 15 times higher for HPS patients comparing to non-HPS patients (odds ratio, 14.9; 97.5% confidence interval, 4.98-44.29;P < 0.001). There were no differences observed in odds of being readmitted to the hospital within 6 mo after the transplant (P = 0.75).Conclusions.HPS diagnosis was associated with longer intensive care unit stay, hospital stay, and increased hospital cost, together with higher odds of being discharged to extended care facility compared with non-HPS patients.