bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers for treatment change and radiographic progression in patients with rheumatoid arthritis in remission: a 5 year follow-up study
Authors: Ramírez Julio , Cuervo Andrea , Celis Raquel , Ruiz-Esquide Virginia , Castellanos-Moreira Raul , Narváez José Antonio , Gómez-Puerta José A , Pablos José L , Sanmartí Raimon , Cañete Juan D 
Published: April 2020

Abstract

Objective
To identify biomarkers of treatment change and radiographic progression in patients with RA under remission.

Patients and methods
RA patients in remission (DAS28-ESR &lt;2.6) were selected and followed up for 5 years. An MRI of the dominant hand and an US assessment of knees/hands and serum levels of inflammation/angiogenesis biomarkers were performed at baseline and at 12th month. Synovial biopsies were obtained in patients with Power Doppler signal. Conventional radiographies of hands/feet were taken at baseline and after 5 years. Radiographic progression was defined as the change in the modified Sharp van der Heijde Score at 5 years &gt;10.47 (small detectable change).

Results
Sixty patients were included, 81.6% were ACPA+ and 45% were taking biological DMARDs. At baseline, 66.6% had Power Doppler signal. After 5 years, 73.3% of patients remained in remission. Change of therapy was performed in 20 patients (33.3%) and was associated with BMI [odds ratio (OR) 1.3, 95% CI: 1, 1.7], lack of biological DMARD therapy (OR 24.7, 95% CI: 2.3, 257.2), first-year progression of MRI erosions (OR 1.2, 95% CI: 1, 1.3) and calprotectin serum levels (OR 2.8, 95% CI: 1, 8.2). Radiographic progression occurred in six (10%) patients. These patients had higher first-year progression of MRI erosions (P =  0.03) and bone oedema (P = 0.04). Among 23 patients undergoing synovial biopsy, mast cell density was independently associated with clinical flares.

Conclusions
One-third of RA patients lost clinical remission and changed therapy throughout the 5 years of follow-up, which was independently associated with BMI, lack of biological DMARDs therapy and first-year progression of MRI erosion score and calprotectin serum levels. Significant radiographic progression was uncommon.
Acute severe malnutrition treatment outcomes in children ages 6–59 months admitted to Singa Hospital, Sudan
Authors: Bilal Jalal Ali , Eltahir Hatim G , Al-Nafeesah Abdullah , Al-Wutayd Osama , Adam Ishag 
Published: April 2020

Abstract

Background
Acute malnutrition threatens the lives of 50.5 million children &lt;5 y of age. Consequences of malnutrition include death, among other short-term sequelae. This study was conducted from April to October 2018 to determine the outcomes of children 6–59 months of age with acute severe malnutrition admitted to Singa Hospital in central Sudan.

Methods
Clinical information for children with a mid-upper arm circumference (MUAC) &lt;115 mm were collected. We measured children's weight and height and calculated weight-for-height z-scores. Treatment was offered according to World Health Organization (WHO) guidelines. Outcomes were recorded as recovered, discharged against medical advice or died.

Results
This study included 376 malnourished children. The median age was 18 months (interquartile range [IQR] 12−24). The male:female ratio was 1:1. Among children with weight-for-height Z-scores of −4 and −3, 103 (27.3%) had oedematous malnutrition. There were 131 (34.8%) children with malaria parasites, 33 (8.7%) with pyuria and 24 (6.3%) with intestinal parasites. The recovery rate was 89.1%. The case fatality rate was 3.7%. Mortality was significantly increased with diarrhoea and dermatoses. There were no significant differences in the median of age (17.5 months [IQR 6−24] vs 18 [6−24], p = 0.595), MUAC (110 mm [IQR 104–111] vs 110 [100–111], p = 0.741) or sex (p = 0.991) between children who died and those who recovered.

Conclusions
The case fatality rate was 3.7% and it was associated with diarrhoea and dermatoses.
A revision of the early neotheropod genusSarcosaurusfrom the Early Jurassic (Hettangian–Sinemurian) of central England
Authors: Ezcurra Martín D , Butler Richard J , Maidment Susannah C R , Sansom Ivan J , Meade Luke E , Radley Jonathan D 
Published: April 2020

AbstractNeotheropoda represents the main evolutionary radiation of predatory dinosaurs and its oldest records come from Upper Triassic rocks (c. 219 Mya). The Early Jurassic record of Neotheropoda is taxonomically richer and geographically more widespread than that of the Late Triassic. The Lower Jurassic (upper Hettangian–lower Sinemurian) rocks of central England have yielded three neotheropod specimens that have been assigned to two species within the genus Sarcosaurus, S. woodi (type species) and S. andrewsi. These species have received little attention in discussions of the early evolution of Neotheropoda and recently have been considered as nomina dubia. Here, we provide a detailed redescription of one of these specimens (WARMS G667–690) and reassess the taxonomy and phylogenetic relationships of the genus Sarcosaurus. We propose that the three neotheropod specimens from the Early Jurassic of central England represent a single valid species, S. woodi. The second species of the genus, ‘S. andrewsi’, is a subjective junior synonym of the former. A quantitative phylogenetic analysis of early theropods recovered S. woodi as one of the closest sister-taxa to Averostra and provides new information on the sequence of character state transformations in the lead up to the phylogenetic split between Ceratosauria and Tetanurae.
Early Biomarkers of Muscle Atrophy and of Neuromuscular Alterations During 10‐Day Bed Rest
Authors: Narici Marco Vincenzo , Monti Elena , Franchi Martino , Reggiani Carlo , Toniolo Luana , Giacomello Emiliana , Zampieri Sandra , Simunič Bostjan , Pisot Rado 
Published: April 2020

IntroductionDisuse atrophy may not only arise from a reduction in mechanical loading but also from muscle denervation and neuromuscular junction damage, triggered by inactivity
[1,
2]. The identification of biomarkers of muscle atrophy and of neuromuscular degeneration is therefore needed for an early detection of neuromuscular alterations induced by inactivity. The aim of this study was to investigate the onset of muscle atrophy and of neuromuscular alterations during a short‐term inactivity period.MethodsTen healthy males (aged 23±5 years) participated to a 10‐day bed rest (BR) study, after Ethical approval and informed consent. Blood samples were collected every two days for the assessment of NMJ damage from serum levels of c‐terminal agrin fragment (CAF). Muscle fibre denervation was determined from the expression of neural cell adhesive molecule (N‐CAM) in myofibres obtained from vastus lateralis (VL) muscle biopsies at baseline, 5 and 10 days of BR. Myofibre atrophy was assessed from mean fibre cross‐sectional area (CSA). Whole muscle atrophy was assessed from measurements of muscle architecture (pennation angle and muscle CSA) every two days of BR using ultrasonography. Significance of differences was tested with repeated‐measures Anova, level of significance was set at p<0.05.ResultsAtrophy of whole muscle and of myofibers, represented by decreases of 5.8% in muscle CSA (P<0.0001), 7.3% in pennation angle (P<0.0001), and by a 21% reduction in mean fibre CSA (P<0.01) were detected after 10 days of BR. A 19% increase (p<0.01) in CAF levels was found on BR day 10, together with a 18‐fold increase in N‐CAM positive myofibres. The analysis of myofiber CSA and N‐CAM expression at BR 5 day is in progress.ConclusionsThese findings show a very early onset (within 10 days) of whole muscle and fiber atrophy accompanied by NMJ damage and myofiber denervation in response to chronic inactivity. We suggest that countermeasures against neuromuscular maladaptation to chronic inactivity ought to be implemented as early as possible.Support or Funding InformationFunding by ASI, MARS‐PRE Project, n. DC‐VUM‐2017‐006, is acknowledged.
The effect of dexmedetomidine on postoperative and intensive care unit delirium: A meta‐analysis of randomized controlled trials
Authors: Jiang Fang , Ye Xiaodong , Cai Yin , Xie Xiang , Wang Lin , Hua Lin-lin , Xia Zhengyuan 
Published: April 2020

BackgroundThe present meta‐analysis aimed to assess the efficacy of dexmedetomidine on the occurrence of delirium among critically ill patients in the postoperative and intensive care unit.MethodsPubmed, Embase, Cochrane Library (Central), Web of Science and Clinical Trails databases for randomized controlled trials (RCTs) were searched to compare the effect of dexmedetomidine administration in comparison with control group (normal saline or other anesthetic drugs) on the incidence of delirium in adult patients until April 4, 2019. The sensitivity and subgroup analyses were adopted. Statistical analysis was performed with RevMan software version 5.3 and Stata 12.0. The primary endpoint was the incidence of delirium. The secondary outcome included the occurrence of hypotension, hypertension, bradycardia and tachycardia.Results20 RCTs were finally included in the analysis, with a total of 4,242 adult patients. The results of meta‐analysis showed that dexmedetomidine (odds ratio [OR]=0.47, 95% confidence interval [CI]: 0.35 to 0.64, p < 0.01) could significantly reduce the rate of delirium for the entire patients in the postoperative and intensive care unit when compared with control group. The subgroup analysis indicated that dexmedetomidine reduced the incidence of delirium between groups in cardiac surgery (OR=0.55, 95% CI: 0.30 to 0.98) and non‐cardiac surgery (OR=0.44, 95% CI: 0.31 to 0.64), normal saline (OR=0.47, 95% CI: 0.31 to 0.71) and anesthetic drugs (OR=0.50, 95% CI: 0.30 to 0.81), age ≥ 60 years old (OR=0.50, 95% CI: 0.36 to 0.68) and age < 60 years old (OR=0.34, 95% CI: 0.13 to 0.91), with loading dose (OR=0.38, 95% CI: 0.29 to 0.50) and without loading dose (OR=0.54, 95% CI: 0.44 to 0.67). However, there were no significant difference in delirium among mechanical ventilated patients (OR=0.30, 95% CI: 0.07 to 1.22) and in cardiac surgery patients with age ≥ 60 years old (OR=0.73, 95% CI: 0.44 to 1.22). Additionally, this analysis found that dexmedetomidine administration was associated with an increased incidence of hypertension (OR=0.54, 95% CI: 0.41 to 0.71) and bradycardia (OR=1.59, 95% CI: 1.25 to 2.03), while the incidence of hypotension (OR=0.90, 95% CI: 0.62 to 1.31) and tachycardia (OR=0.73, 95% CI: 0.37 to 1.45) did not differ significantly between dexmedetomidine treated and control groups..ConclusionThe present limited evidence suggests that dexmedetomidine can reduce the incidence of delirium in the postoperative and intensive care unit except in cardiac surgery patients with age ≥ 60. However, the pooled results should be interpreted with more caution due to significant statistical heterogeneity existed. Therefore, future high‐quality, large RCTs should further verify this findings among this population.
Can detrimental mtDNA mutations be under positive selection in the germline?
Authors: Franco Melissa , Pickett Sarah , Fleischmann Zoe , Khrapko Mark , Annis Sofia , Woods Dori , Markuzon Natalya , Turnbull Doug , Khrapko Konstantin 
Published: April 2020

It is conventionally assumed that detrimental mitochondrial DNA (mtDNA) mutations generally are under negative purifying selection in the germline, i.e., that children on average carry a lower burden than mothers. We asked whether, at least for some detrimental mutations, this may not be the case. We chose the infamous 3243G>A mutation, which disrupts mitochondrial function and causes a variety of serious neuromuscular disorders including a severe mitochondrial disease, MELAS. This mutation occurs frequently (detectable in as many as 1 in 500 individuals), and is well studied. To determine whether this mutation is under selection, the mutation level in kids is compared to that in mothers. However, it has been shown that the level of the 3243G>A mutation appears to exponentially decrease with age in blood, where it is commonly measured (~2% per year). This estimation is based on a biologically sensible numerical model that simulates random drift in blood stem cells and removes cells that reach a lethal threshold (Rajasimha, 2008). This model asymptotically converges to an exponential function that describes a decline of 2% heteroplasmy per year. Thus, for fair comparison, kid/mom heteroplasmy ratios need to be corrected for the age difference. With the conventional 2% per year correction, no significant difference between moms and kids could be detected.There are indications, however, that the change of the 3243G>A level with age may be more complex than simple exponent. It may depend on initial heteroplasmy levels and the age. Indeed, we demonstrate that the 2% model predictions are systematically under‐estimates, and that several predictive models that include heteroplasmy and age as variables ensure better fit of the data and decrease this negative bias. One such model is an adaptation of the original numerical model (Rajasimha, 2008). If its asymptotic behavior is not unconditionally assumed, this model explicitly includes heteroplasmy and age as variables. This non‐asymptotic model produces a better fit and corrects the negative bias.We reasoned that a negative bias in prediction might have obscured positive selection on 3243G>A in the germline if it existed. To clarify the issue, we used the non‐asymptotic numerical model to predict the children’s heteroplasmy levels at their mothers’ age. Indeed, in preliminary simulations with this improved correction, a statistically significant positive germline selection of 3243G>A was demonstrated. More analysis is needed to confirm this initial result.We note that, interestingly, if such positive selection of pathogenic mtDNA mutations existed, it might have had an adaptive purpose. Our simulations demonstrate that under realistic conditions, positive selection in the germline may promote removal of detrimental mtDNA mutations at the population level and thus help to evade the dangers of the infamous Muller’s ratchet.
Effect of Angiotensin ll on mouse tracheal reactivity
Authors: Prasad Praveena , Patel Mehaben , Bhavsar Riya , Sheikh Usman , Nahvi Parisa , Ponnoth Dovenia S. 
Published: April 2020

Angiotensin II is a hormone peptide that is primarily generated in the lungs and kidneys. However, effects of Ang ll on airway function is not fully understood. We assessed concentration‐responses to Ang II in isolated mouse trachea by using ex‐vivo organ bath experiments. Western blot data showed that mouse trachea expressed AT1 receptors and AT2 receptors. Our data suggested that Ang II induces concentration‐dependent relaxation in methacholine (MCh)‐precontracted tracheal rings (38.95±0.72% at 10μM; n=4). Use of Ang II type 1 (AT1) receptor antagonist losartan blocked this effect resulting in a small contraction of 3.94±2.83%. nNOS inhibitor also completely blunted the Ang II mediated relaxation resulting in a contraction of 5.17±2.05% in the MCh‐precontracted tracheal rings. Novokinin had a minimal effect on the precontracted tissues, suggesting that AT1 receptors played a main role in mediating Ang ll responses. These data suggest that Ang II mediates tracheal relaxation via AT1‐ receptor activation, through a nitric‐oxide dependent mechanism.Support or Funding InformationSupported by LIU start‐up funds (DSP)
Sexual Dysfunction and Psychopathological Variables Among Tramadol Abusers: An Egyptian Perspective
Authors: Mobasher Maha W. , Hassanin Ahmed M.A. , Elsayed Mohamed A. , Ayoub Doaa R. , El-Makawi Shirin M. 
Published: April 2020

Objectives:
The relationship between tramadol and sexual function seems to be controversial, men with premature ejaculation may benefit from taking tramadol off-label. Yet, these patients are rather sensitive to develop other sexual dysfunctions. To date, rather a limited number of studies investigated this issue. In addition, psychological concerns related to sexual functions in these patients had not enough attention. In this paper we present a new approach which will investigate these concerns

Materials and Methods:
Sixty subjects (30 tramadol-dependent men and 30 matched controls). Patients were assessed by the Mini International Neuropsychiatry Interview (MINI) is to assesses the presence of The Diagnostic and Statistical Manual of Mental Disorder, 4th edition disorders, the Addiction Severity Index (ASI), the International Index of Erectile Function (IIEF), and the Sexuality Scale.

Results:
Tramadol patients were found to have significantly decreased different sexual functions in comparison with controls. Sexual depression scores were significantly higher in tramadol patients compared with controls (P=0.020); while sexual-esteem and sexual preoccupation scores were significantly lower in tramadol patients compared with matched controls (P=0.000 and 0.046). In the patient group, the dose of tramadol used per day showed significant negative correlation with erectile function (P=0.04), orgasmic function (P=0.03), and sexual esteem (P=0.04); while the duration of tramadol dependence showed significant negative correlation with erectile function (P=0.04), intercourse satisfaction (P=0.01), overall satisfaction (P=0.00), and significant positive correlation with sexual preoccupation.

Conclusions:
Tramadol patients indeed suffer from different sexual, emotional, occupational dysfunctions, and sexually related psychopathological aspects.
Muscular Tissue Oxygen Saturation and Posthysterectomy Nausea and Vomiting
Authors: Li Gang , Tian Dan-Dan , Wang Xu , Feng Xiaoxian , Zhang Wenyu , Bao Ju , Wang Dong-Xin , Ai Yan-Qiu , Liu Ya , Zhang Mengyuan , Xu Mingjun , Mu Dong-Liang , Zhao Xu , Dai Feng , Yang Jian-Jun , Che Xiangming , Yanez David , Guo Xiangyang , Meng Lingzhong 
Published: April 2020

Background
Suboptimal tissue perfusion and oxygenation during surgery may be responsible for postoperative nausea and vomiting in some patients. This trial tested the hypothesis that muscular tissue oxygen saturation–guided intraoperative care reduces postoperative nausea and vomiting.

Methods
This multicenter, pragmatic, patient- and assessor-blinded randomized controlled (1:1 ratio) trial was conducted from September 2018 to June 2019 at six teaching hospitals in four different cities in China. Nonsmoking women, 18 to 65 yr old, and having elective laparoscopic surgery involving hysterectomy (n = 800) were randomly assigned to receive either intraoperative muscular tissue oxygen saturation–guided care or usual care. The goal was to maintain muscular tissue oxygen saturation, measured at flank and on forearm, greater than baseline or 70%, whichever was higher. The primary outcome was 24-h postoperative nausea and vomiting. Secondary outcomes included nausea severity, quality of recovery, and 30-day morbidity and mortality.

Results
Of the 800 randomized patients (median age, 50 yr [range, 27 to 65]), 799 were assessed for the primary outcome. The below-goal muscular tissue oxygen saturation area under the curve was significantly smaller in patients receiving muscular tissue oxygen saturation–guided care (n = 400) than in those receiving usual care (n = 399; flank, 50 vs. 140% · min, P < 0.001; forearm, 53 vs. 245% · min, P < 0.001). The incidences of 24-h postoperative nausea and vomiting were 32% (127 of 400) in the muscular tissue oxygen saturation–guided care group and 36% (142 of 399) in the usual care group, which were not significantly different (risk ratio, 0.89; 95% CI, 0.73 to 1.08; P = 0.251). There were no significant between-group differences for secondary outcomes. No harm was observed throughout the study.

Conclusions
In a relatively young and healthy female patient population, personalized, goal-directed, muscular tissue oxygen saturation–guided intraoperative care is effective in treating decreased muscular tissue oxygen saturation but does not reduce the incidence of 24-h posthysterectomy nausea and vomiting.

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The Reemergence of Ketamine for Treatment in Critically Ill Adults
Authors: Hurth Kimberly P. , Jaworski Anthony , Thomas Kristen B. , Kirsch William B. , Rudoni Michael A. , Wohlfarth Kevin M. 
Published: April 2020

Objectives:
To assess the evidence and discuss the risks and clinical relevance of ketamine for the treatment of various disease states impacting the adult critically ill population.

Data Sources:
A literature review was performed using PubMed evaluating primary literature published until August 2018.

Study Selection:
Case reports, observational studies (cohort, case-control), and randomized controlled trials involving patients 18 years and older in a nonperioperative setting using either IV or intramuscular ketamine were included for analysis. Uses of ketamine discussed focused on critically ill patients in the ICU and emergency department settings.

Data Extraction:
Included studies were evaluated for dosing, outcomes, and adverse effects of ketamine. For each study, the design, population, intervention, investigated outcomes, and results were assessed.

Data Synthesis:
The evidence was organized according to use of ketamine, which included pain, sedation, status asthmaticus, alcohol withdrawal syndrome, status epilepticus, and acute behavioral psychologic disturbances. Evaluation of the evidence was based on the included primary literature along with any related guideline recommendations.

Conclusions:
Ketamine has suggested potential benefit in several disease states impacting critically ill patients including pain, alcohol withdrawal syndrome, status epilepticus, and acute agitation. Further supporting evidence is needed to validate its use in the setting of critical illness.