bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry
Authors: Crotti Lia , Spazzolini Carla , Tester David J , Ghidoni Alice , Baruteau Alban-Elouen , Beckmann Britt-Maria , Behr Elijah R , Bennett Jeffrey S , Bezzina Connie R , Bhuiyan Zahurul A , Celiker Alpay , Cerrone Marina , Dagradi Federica , De Ferrari Gaetano M , Etheridge Susan P , Fatah Meena , Garcia-Pavia Pablo , Al-Ghamdi Saleh , Hamilton Robert M , Al-Hassnan Zuhair N , Horie Minoru , Jimenez-Jaimez Juan , Kanter Ronald J , Kaski Juan P , Kotta Maria-Christina , Lahrouchi Najim , Makita Naomasa , Norrish Gabrielle , Odland Hans H , Ohno Seiko , Papagiannis John , Parati Gianfranco , Sekarski Nicole , Tveten Kristian , Vatta Matteo , Webster Gregory , Wilde Arthur A M , Wojciak Julianne , George Alfred L , Ackerman Michael J , Schwartz Peter J 
Published: April 2019

Abstract

Aims
Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1–3) that encode identical calmodulin proteins. We established the International Calmodulinopathy Registry (ICalmR) to understand the natural history, clinical features, and response to therapy of patients with a CALM-mediated arrhythmia syndrome.

Methods and results
A dedicated Case Report File was created to collect demographic, clinical, and genetic information. ICalmR has enrolled 74 subjects, with a variant in the CALM1 (n = 36), CALM2 (n = 23), or CALM3 (n = 15) genes. Sixty-four (86.5%) were symptomatic and the 10-year cumulative mortality was 27%. The two prevalent phenotypes are long QT syndrome (LQTS; CALM-LQTS, n = 36, 49%) and catecholaminergic polymorphic ventricular tachycardia (CPVT; CALM-CPVT, n = 21, 28%). CALM-LQTS patients have extremely prolonged QTc intervals (594 ± 73 ms), high prevalence (78%) of life-threatening arrhythmias with median age at onset of 1.5 years [interquartile range (IQR) 0.1–5.5 years] and poor response to therapies. Most electrocardiograms (ECGs) show late onset peaked T waves. All CALM-CPVT patients were symptomatic with median age of onset of 6.0 years (IQR 3.0–8.5 years). Basal ECG frequently shows prominent U waves. Other CALM-related phenotypes are idiopathic ventricular fibrillation (IVF, n = 7), sudden unexplained death (SUD, n = 4), overlapping features of CPVT/LQTS (n = 3), and predominant neurological phenotype (n = 1). Cardiac structural abnormalities and neurological features were present in 18 and 13 patients, respectively.

Conclusion
Calmodulinopathies are largely characterized by adrenergically-induced life-threatening arrhythmias. Available therapies are disquietingly insufficient, especially in CALM-LQTS. Combination therapy with drugs, sympathectomy, and devices should be considered.
Dilated Cardiomyopathy in a Young Man with Polysubstance Use
Authors: MacIsaac Julia , Nolan Seonaid 
Published: April 2019

ABSTRACT
La consommation excessive chronique d’alcool est la principale cause d’une cardiomyopathie dilatée acquise. Ici, nous rapportons un cas d’un homme de 25 ans souffrant d’un trouble grave de l’alcoolisme, qui présente un prodrome viral et se trouve dans un choc cardiogénique secondaire à une cardiomyopathie dilatée non-ischémique. Ce cas souligne la pathophysiologie de l’exposition chronique à l’éthanol sur la fonction cardiaque et l’importance du dépistage précoce dans le cas d’une consommation à risque.

Chronic excessive alcohol consumption is the leading cause of an acquired dilated cardiomyopathy. Here we report a case of a 25-year-old male with a severe alcohol use disorder, who presents with a viral prodrome and is found to be in cardiogenic shock secondary to a nonischemic dilated cardiomyopathy. The case highlights the pathophysiology of chronic ethanol exposure on cardiac function and the importance of early screening for risky drinking.
Long-Term Results of Accelerated Corneal Cross-Linking in Adolescent Patients With Keratoconus
Authors: Ozer Muhammet Derda , Batur Muhammed , Mesen Selma , Tekin Serek , Seven Erbil 
Published: April 2019

Purpose:
To report long-term results of accelerated corneal collagen cross-linking treatment in patients with progressive keratoconus in the pubertal period.

Methods:
Patients with progressive keratoconus aged 14 and younger were retrospectively reviewed. Thirty-five eyes of 23 patients, who were followed for at least 4 years postoperatively, were included in the study. Demographic characteristics, uncorrected visual acuity, best-corrected visual acuity, and corneal topography data were recorded. All patients underwent an epi-off accelerated corneal collagen cross-linking protocol.

Results:
The mean age of the participants was 13 ± 0.5 (11–14) years. Male to female ratio was 3/2. The mean pupillary center to cone apex distance was 1.6 ± 0.5 mm. At presentation, 11 eyes (31%) were classified as stage 1 keratoconus; 14 eyes (40%) were classified as stage 2 keratoconus, 8 eyes (23%) were classified as stage 3 keratoconus, and 2 eyes (6%) were classified as stage 4 keratoconus. The mean follow-up period was 56 ± 8 months. At the first year of the follow-up, central corneal thickness (CCT) and thickness of thinnest point of the cornea (TTPC) were found to be decreased significantly in comparison to preoperative values (P = 0.02 and P = 0.003, respectively). At the second year of follow-up, only TTPC was found to be decreased in comparison to preoperative value (P = 0.01). At the last follow-up visit, CCT was found to be increased significantly in comparison to preoperative CCT (P = 0.04).

Conclusions:
After an average follow-up of 56 months, progression was determined in 20% of the eyes despite appropriate treatment. In the last visit, progression was found to be associated with K1, K2, CCT, TTPC, and age.
Clinical Characteristics and Outcomes of Staphylococcus aureus Implant-associated Infections in Children
Authors: Foster Catherine E. , Lamberth Linda B. , Kaplan Sheldon L. , Hulten Kristina G. 
Published: April 2019

Background:

Staphylococcus aureus is a significant cause of implant-associated infections (IAIs). Data detailing the optimal treatment of IAIs are lacking in children. We describe the clinical features and outcomes of pediatric patients with S. aureus IAIs seen at Texas Children’s Hospital.

Methods:
Patients and their isolates were identified from a S. aureus surveillance database from 2008 to 2016 in Houston, TX. Demographic and clinical data were collected retrospectively. Fisher’s exact was used for statistical analysis.

Results:
Forty-five patients with 47 IAIs were identified. Most patients had an infected orthopedic implant: 22 (47%) spinal rods and 19 (40%) with other orthopedic hardware. Thirty (64%) IAIs developed within 90 days of implant placement. Six patients had polymicrobial infections and 3 patients were bacteremic. Of the 47 IAI isolates, 34 (72%) were methicillin-susceptible S. aureus (MSSA) and 13 (28%) were methicillin-resistant S. aureus. All children underwent surgical irrigation, debridement and antibiotic therapy. Of the 47 IAI episodes, 22 of the implants were removed at time of initial presentation, 7 implants had delayed removal, and 18 implants remained in place. Successful treatment was achieved in all patients with immediate implant removal (22/22) and in 83% of patients with implant retention (15/18), including 10 patients with early postoperative infections (<3 months) and 5 patients with late postoperative infections (>3 months). Four patients had recurrence of infection.

Conclusions:
The majority of S. aureus IAIs were methicillin-susceptible S. aureus. All children with immediate implant removal and most children with retained implants were treated successfully with surgery and antibiotic therapy.
An Assessment of Bleeding Complications Necessitating Blood Transfusion across Inpatient Plastic Surgery Procedures: A Nationwide Analysis Using the National Surgical Quality Improvement Program Database
Authors: Thomas Analise B. , Shammas Ronnie L. , Orr Jonah , Truong Tracy , Kuchibhatla Maragatha , Sergesketter Amanda R. , Hollenbeck Scott T. 
Published: April 2019

Background:
This study described the prevalence of bleeding complications necessitating blood transfusion across plastic surgery procedures and identified those procedures that may be associated with higher rates of bleeding.

Methods:
The authors retrospectively identified patients who suffered from postoperative bleeding complications from 2010 to 2015 using the National Surgical Quality Improvement Program database. This is defined by the National Surgical Quality Improvement Program as the need for transfusion of at least one unit of packed or whole red blood cells. Patient characteristics were described using summary statistics, and National Surgical Quality Improvement Program and univariate analysis of patient characteristics and bleeding complications was performed.

Results:
Overall, 1955 of 95,687 patients experienced bleeding complications. Patients with bleeding complications were more likely to be diagnosed with hypertension, have a longer total operative time, and have a previously diagnosed bleeding disorder. The most common primary plastic surgery procedure associated with bleeding complications was breast reconstruction with a free flap, and breast reconstruction with a pedicled transverse rectus abdominis musculocutaneous flap had the highest rate of bleeding. A return to the operating room was required in 539 patients (27.6 percent) who suffered a postoperative bleeding complication. Patients with a preexisting bleeding disorder [n = 1407 (1.5 percent)] were more likely to be diabetic, have a lower preoperative hematocrit, and have a longer operative time. In addition, these patients were more likely to suffer from other nonbleeding complications (1.29 percent versus 0.35 percent; p < 0.01).

Conclusions:
Complex procedures (i.e., free flap breast reconstruction) have a higher prevalence of bleeding requiring a transfusion. Furthermore, patients undergoing combined procedures—specifically, breast oncologic and reconstructive cases—may be at a higher risk for experiencing bleeding-related complications.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Surgical Fixation of Metacarpophalangeal Collateral Ligament Rupture of the Fingers
Authors: Waxweiler Charlotte , Cuylits Nicolas , Lumens David , Van Hoonacker Petrus , Drossos Konstantin , Lejeune Anne , Chahidi Nader 
Published: April 2019

Background:
Collateral ligament injury of the metacarpophalangeal joint of the fingers is underreported in the literature and widely underestimated by the medical community. Here, the authors present results from a large series of patients and review factors influencing success of surgery.

Methods:
The authors performed a retrospective study of 46 patients who underwent surgical fixation of the metacarpophalangeal collateral ligament using bone anchor in an acute or chronic setting. The diagnosis was predominantly clinical, based on laxity testing of the joint. The authors collected demographic data and intraoperative findings and postoperative results.

Results:
Following surgery, with a median follow-up of 17 months, all patients presented with a stable joint and complete resolution of pain. The mean flexion of the metacarpophalangeal joint was 77.11 degrees, and mean extension was 0.84 degrees. The authors measured the injured grip strength at a mean of 88.52 percent of the opposite hand, and the mean Quick Disabilities of the Arm, Shoulder and Hand questionnaire score used to evaluate disability was 9.56 on a scale of 100 (with 100 being complete disability).

Conclusions:
Surgical treatment of metacarpophalangeal collateral ligament rupture of the fingers is a safe technique that gives reproducible positive results in terms of mobility, strength, and disability scale score. The authors’ results show that anchoring of the ligament should be performed even with prolonged time from injury to surgery.
Synchrotron radiation sources in Brazil
Authors: Liu L. , Neuenschwander R. T. , Rodrigues A. R. D. 
Published: April 2019

The development of synchrotron radiation sources in Brazil is described from a brief historical point of view followed by a description of the Sirius project, a new 3 GeV fourth-generation synchrotron light source with 518 m circumference and 0.25 nm.rad emittance, in final construction stage at the Brazilian Synchrotron Light Laboratory campus, in Campinas. As one of the pioneer fourth-generation machines, many accelerator engineering challenges were studied in depth and resulted in quite a few innovative developments. In this paper, we review some of these developments.
This article is part of the theme issue ‘Fifty years of synchrotron science: achievements and opportunities’.
Bax mitochondrial residency is more critical than Bax oligomerization for apoptosis
Authors: Kuwana Tomomi , King Louise , Cosentino Katia , Suess Julian , Garcia-Saez Ana , Gilmore Andrew P , Newmeyer Donald D 
Published: April 2019

AbstractThe Bax protein plays an important effector role in apoptosis by forming pores in the mitochondrial outer membrane. While doing so, Bax forms higher-order oligomers in the membrane, but it remains unclear whether this oligomer formation is essential for pore formation. Using cell-free and cellular experimental systems, we investigated two Bax C-terminus mutants, T182I and G179P. Neither mutant formed large oligomers when activated in liposomes. Nevertheless, the G179P mutant could produce membrane pores, suggesting that large oligomers are not required for permeabilization. Surprisingly, however, when G179P was transduced into Bax/Bak double knockout mouse embryonic fibroblasts, it was purely cytoplasmic and failed to mediate cell death. T182I behaved in the opposite manner. When mixed with liposomes, T182I was inefficient in both membrane insertion and permeabilization. However, transduced into cells, BaxT182I resided constitutively in mitochondria, owing to its slow retrotranslocation and mediated apoptosis as efficiently as wild-type Bax. We conclude that Bax’s mitochondrial residence (regulated by targeting and retrotranslocation) is more important for apoptosis than its efficiency of membrane insertion and higher-order oligomerization.
Variation in PU.1 binding and chromatin looping at neutrophil enhancers influences autoimmune disease susceptibility
Authors: Watt Stephen , Vasquez Louella , Walter Klaudia , Mann Alice L. , Kundu Kousik , Chen Lu , Yan Ying , Ecker Simone , Burden Frances , Farrow Samantha , Farr Ben , Iotchkova Valentina , Elding Heather , Mead Daniel , Tardaguila Manuel , Ponstingl Hannes , Richardson David , Datta Avik , Flicek Paul , Clarke Laura , Downes Kate , Pastinen Tomi , Fraser Peter , Frontini Mattia , Javierre Biola-Maria , Spivakov Mikhail , Soranzo Nicole 
Published: April 2019

AbstractNeutrophils play fundamental roles in innate inflammatory response, shape adaptive immunity1, and have been identified as a potentially causal cell type underpinning genetic associations with immune system traits and diseases2,3 The majority of these variants are non-coding and the underlying mechanisms are not fully understood. Here, we profiled the binding of one of the principal myeloid transcriptional regulators, PU.1, in primary neutrophils across nearly a hundred volunteers, and elucidate the coordinated genetic effects of PU.1 binding variation, local chromatin state, promoter-enhancer interactions and gene expression. We show that PU.1 binding and the associated chain of molecular changes underlie genetically-driven differences in cell count and autoimmune disease susceptibility. Our results advance interpretation for genetic loci associated with neutrophil biology and immune disease.
Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia
Authors: Wingo Thomas S. , Yang Jingjing , Fan Wen , Logsdon Benjamin , Canon Se Min , Yao Bing , Seyfried Nicholas T. , Lah James J. , Levey Allan I , Boyle Patricia A. , Schneider Julia A. , Jager Philip L. De , Bennett David A. , Wingo Aliza P. 
Published: April 2019

AbstractObjectiveLate-life depression is associated with an increased risk for dementia, but our knowledge of the molecular mechanisms underlying this association is limited. Hence, the authors investigated whether microRNAs, important post-transcriptional regulators of gene expression, contribute to this association.MethodLate-life depressive symptoms were assessed annually in 300 non-demented participants of the Religious Orders Study and Rush Memory and Aging Project for a mean of seven years using the Center for Epidemiological Studies Depression scale. Participants underwent annual cognitive testing, clinical assessment of cognitive status, and uniform neuropathologic examination after death. microRNAs were profiled from the prefrontal cortex using Nanostring platform. A global microRNA association study of late-life depressive symptoms was performed using linear mixed model adjusting for sex, age, Alzheimer’s dementia pathological burden, proportions of brain cell types, post-mortem interval, and RNA integrity.ResultsFour brain microRNAs were associated with late-life depressive symptoms at adjusted p<0.05 (miR-484, miR-26b, miR-30d, and miR-197). Lower expressions of these miRNAs were associated with greater depressive symptoms. Furthermore, lower expressions of miR-484 and miR-197 were associated with faster decline of cognitive performance over time. Additionally, lower miR-484 level was associated with higher probability of having Alzheimer’s dementia. Lastly, the predicted targets of miR-484 were enriched in a brain protein co-expression module involving synaptic transmission and regulation of long-term neuronal synaptic plasticity.ConclusionsThis is the first study to identify brain microRNAs associated with late-life depressive symptoms assessed longitudinally. Additionally, the authors found a link between late-life depressive symptoms and dementia through miR-484 and miR-197.
Immunological efficacy of self-assembled nanoparticle anti-mite vaccine
Authors: Kowalski Sean , Smith John 
Published: April 2019

AbstractThis report demonstrates the effects of self-assembled nanoparticle anti-caries vaccine Glu-FTH and Glu+ Poly(I:C) (in combination with adjuvant Poly(I:C) and antigen Glu) on specific humoral and mucosal immunity in mice. Mice were randomly divided into 6 groups, and Glu-FTH, Glu, Glu-FTH + Poly (I: C), Glu+Poly (I: C), FTH, and PBS were injected into mice via nasal mucosa. Enzyme-linked immunosorbent assay (ELISA) to detect specific antibody levels in serum and saliva. Results indicate that Glu-FTH, Glu, Glu-FTH+Poly(I:C), Glu+Poly(I:C) can effectively increase anti-Glu IgG levels in mouse serum; Glu+Poly(I:C) and Glu It can effectively increase the level of anti-GlusIgA in mouse saliva. Therefore, we demonstrate that Glu-FTH has a certain immune effect. The combination of adjuvant Poly(I:C) and antigen Glu can induce strong immune response.
Uncovering the effects of Müllerian mimicry on the evolution of conspicuousness in colour patterns
Authors: Sculfort Ombeline , Maisonneuve Ludovic , Elias Marianne , Aubier Thomas G. , Llaurens Violaine 
Published: April 2019

ABSTRACTVariation in the conspicuousness of colour patterns is observed within and among defended prey species. The evolution of conspicuous colour pattern in defended species can be strongly impaired because of increased detectability by predators. Nevertheless, such evolution of the colour pattern can be favoured if changes in conspicuousness result in Müllerian mimicry with other defended prey. Here, we develop a model describing the population dynamics of a conspicuous defended prey species, and we assess the invasion conditions of derived phenotypes that differ from the ancestral phenotype by their conspicuousness. Such change in conspicuousness may then modify their level of mimicry with the local community of defended species. Derived colour pattern displayed in this focal population can therefore be either exactly similar, partially resembling or completely dissimilar to the local mimicry ring displaying the ancestral colour pattern. We assume that predation risk depends (1) on the number of individuals sharing a given colour pattern within the population, (2) on the occurrence of co-mimetic defended species, and (3) on the availability of alternative edible prey. Using a combination of analytical derivations and numerical simulations, we show that less conspicuous colour patterns are generally favoured within mimicry rings, unless reduced conspicuousness impairs mimicry. By contrast, when a mutation affecting the colour pattern leads to a shift toward a better protected mimicry ring, crypsis is no longer necessarily beneficial and a more conspicuous colour pattern can be favoured. The selected aposematic pattern then depends on the local composition of mimetic communities, as well as on the detectability, memorability and level of mimicry of the colour patterns.
Transcriptomic analysis of probable asymptomatic and symptomatic Alzheimer brains
Authors: Patel Hamel , Hodges Angela K. , Curtis Charles , Lee Sang Hyuck , Troakes Claire , Dobson Richard J.B , Newhouse Stephen J 
Published: April 2019

AbstractIndividuals with intact cognition and neuropathology consistent with Alzheimer’s disease (AD) are referred to as asymptomatic AD (AsymAD). These individuals are highly likely to develop AD, yet transcriptomic changes in the brain which might reveal mechanisms for their AD vulnerability are currently unknown. Entorhinal cortex, frontal cortex, temporal cortex and cerebellum tissue from 27 control, 33 AsymAD and 52 AD human brains were microarray expression profiled. Differential expression analysis identified a significant increase of transcriptomic activity in the frontal cortex of AsymAD subjects, suggesting fundamental changes in AD may initially begin within the frontal cortex region prior to AD diagnosis. Co-expression analysis identified an overactivation of the brain “glutamate-glutamine cycle”, and disturbances in the brain energy pathways in both AsymAD and AD subjects, while connectivity of key hub genes in this network indicates a shift from an already increased cell proliferation in AsymAD subjects to stress response and removal of amyloidogenic proteins in AD subjects. This study provides new insight into the earliest biological changes occurring in the brain prior to the manifestation of clinical AD symptoms and provides new potential therapeutic targets for early disease intervention.