bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Correlations of Positive Herpes Simplex PCR in Cerebrospinal Fluid
Authors: Alessandro Lucas , Wilken Miguel , Farez Mauricio F. , Arias Cebollada Eugenia , Mora Andrea C. , Cammarota Ángel , Del Castillo Marcelo 
Published: October 2018

Objectives:
Herpes simplex viruses (HSV) can produce encephalitis (HSE), which requires early detection, typically using polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). However, other neurological conditions not directly caused by HSV may also present with a positive HSV PCR in the CSF (NCNHPCR+). We aimed to analyze the clinical features of both groups of patients (HSE vs. NCNHPCR+) and to consider the potential relevance of this finding in the latter.

Methods:
A retrospective analysis of clinical presentation, workup (CSF, EEG, and MRI) and outcome of patients with an HSV+ result in CSF was conducted from Jan-2007 to Sep-2015 in our institution. Patients under 18 years and those with nonencephalitic HSV associated disorders were excluded. Group comparison between HSE and NCNHPCR+ patients was conducted using parametric and nonparametric tests accordingly.

Results:
Sixteen HSE and 23 NCNHPCR+ patients were included. Patients with HSE presented a higher incidence of headache (87.5% vs. 43.5%; P=0.008), meningeal symptoms (50% vs. 17.4%; P=0.04), pleocytosis (75% vs. 18%; P=0.001), EEG abnormalities (46.67% vs. 22%; P=0.02) and typical MRI findings (50% vs. 0%; P<0.001), whereas 35% of patients with NCNHPCR+ had an underlying immunologic disorder (35% vs. 0%; P=0.012).

Conclusions:
The pathogenic role of HSV in NCNHPCR+ is uncertain. This finding must be interpreted in the appropriate clinical, EEG, and neuroimaging context. Immunocompromise and neuroinflammation states could be related to a higher presence of HSV in CSF.
Iron: an essential nutrient for Aspergillus fumigatus and a fulcrum for pathogenesis
Authors: Matthaiou Efthymia I. , Sass Gabriele , Stevens David A. , Hsu Joe L. 
Published: October 2018

Purpose of review

Aspergillus fumigatus is a ubiquitous saprophytic fungus that can cause life-threatening invasive aspergillosis in immunocompromised patients. Apart from the immune status of the host only a few characterized virulence factors have been identified. In this review, we describe the role of iron in the manifestation of A. fumigatus virulence.

Recent findings
We gathered recent clinical evidence suggesting that tissue iron overload increases the risk of invasive aspergillosis occurrence. Furthermore, we summarize the mechanisms that A. fumigatus employs to achieve iron homeostasis and their importance in A. fumigatus proliferation in vitro. We describe two recent in-vivo models that clearly demonstrate the importance of iron in A. fumigatus growth and invasion.

Summary
Based on these recent findings, therapy aimed at managing A. fumigatus iron homeostasis locally could make conditions more favorable to the host.
Improved Quality of Life for Children With Beckwith–Wiedemann Syndrome Following Tongue Reduction Surgery
Authors: Harada Takeshi , Yamanishi Tadashi , Kurimoto Takayuki , Nishio Juntaro 
Published: October 2018

Abstract
Macroglossia is observed in the majority of patients with Beckwith–Wiedemann syndrome (BWS), a congenital condition with characteristic anomalies. In addition, sleep disordered breathing (SDB) associated with macroglossia has occasionally been noted in BWS patients, for which tongue reduction surgery is generally performed. However, macroglossia is related to various health problems, such as eating and articulation disorders, attention deficit disorder, enuresis, and thorax deformation, as well as aesthetic issues. Therefore, in addition to treating airway obstruction, tongue reduction surgery can also exert favorable effects on the overall quality of life (QOL) of patients. However, surgical indications for tongue reduction have yet to be established and reports on QOL assessments after surgery are rare. The OSA-18 questionnaire is used for screening SDB and is also useful for assessing the effect of tongue reduction surgery on QOL. We report a patient whose QOL was improved by tongue reduction surgery. On the basis of our patient's results, we recommend tongue reduction surgery in early childhood not only to treat SDB but also to improve QOL.
Aesthetic and Functional Evaluation of Large Full-Thickness Vermilion and Lower Lip Defects Reconstruction
Authors: Jun Guo , Wei Fei , Tong Liu , Yi Huang , Hao Zhou , Jun Li Shuang 
Published: October 2018

Background:
It is hardly to reconstruct a huge defect of lower lip by using of partial flap which brings no mouth closing functional problem. In this study, we would like to introduce our experience in large full-thickness vermilion and lower lip/chin defects reconstruction, and also focus on the evaluation of the surgery effects.

Methods:
The large lower lip and chin (include vermilion) reconstruction were performed in Sichuan Provincial People's Hospital (2012–2015). The surgery experience was introduced in this study first. In the following section, after a statement of these basic problems, various situations involving are investigated, such as the surgical effects of aesthetic and function that were evaluated through a visual analogue scale (VAS) by doctors and patients separately. The VAS score assessments of 2 kinds of surgery were collected and compared.

Results:
A total of 7 patients use the tongue flap alone. Four patients use the combination of the free forearm flap and the anterior ventral tongue flap (COMBO flap). The VAS score of doctors group was significantly lower than the patients group (P < 0.05), and the aesthetic appearance was excellent (>90 points). Language features were not affected (>90 points). Slight mouth opening problems exist on these patients who were used COMBO flaps (>80 points; <90 points). The drooling and drumming gas problems were not observed. These 11 patients had no recurrence within 12 months after the operation.

Conclusion:
The 1:1 ratio between upper and lower lip is crucial to the design of anterior ventral tongue flap which brings with an excellent 3-dimensional morphologic and anatomic structure outcome. The bite block might become an essential operation step for vermilion reconstruction by using of tongue flap. And the COMBO flap may enhance the facial aesthetics and oral function for the reconstruction.
Tranexamic acid mediates proinflammatory and anti-inflammatory signaling via complement C5a regulation in a plasminogen activator–dependent manner
Authors: Barrett Christopher D. , Moore Hunter B. , Kong Yi-Wen , Chapman Michael P. , Sriram Ganapathy , Lim Dan , Moore Ernest E. , Yaffe Michael B. 
Published: October 2018

BACKGROUND
Both tissue plasminogen activator (tPA) in the circulation and urokinase (uPA) in tissues cleave plasminogen (PLG) to plasmin to promote clot lysis. Tranexamic acid (TXA) blocks both the tPA-dependent generation of plasmin on blood clots as well as active plasmin binding to polymerized fibrin, and is commonly administered for bleeding in trauma to limit fibrinolysis. In addition to lysing clots, however, active plasmin also cleaves complement proteins, potentially enhancing inflammation. Because TXA does not block uPA-dependent plasmin generation from PLG and instead augments it, we hypothesized that administration of TXA could enhance or inhibit proinflammatory C5a formation in a PLG activator–dependent manner.

METHODS
Citrate platelet-poor plasma (PPP) and PPP depleted of complement protein C3 or PLG were obtained from healthy donors and commercial sources. Platelet-poor plasma was treated ex vivo with or without TXA and either with or without tPA or with or without uPA. Clotting was then induced by calcium and thrombin in clotted PPP experiments, while unclotted PPP experiments were treated with vehicle controls. C5a levels were measured via enzyme–linked immunosorbent assay. Data were expressed as mean ± SEM.

RESULTS
Plasmin-mediated fibrinolysis by tPA in clotted PPP led to an approximately threefold increase in C5a production (p < 0.0001), which was significantly inhibited by TXA (p < 0.001). Paradoxically, when fibrinolysis was induced by uPA, TXA treatment led to further increases in C5a production beyond uPA alone (p < 0.0001). Furthermore, clotting was not required for C5a generation from uPA + TXA. C3 depletion had no effect on C5a production, while depletion of PLG eliminated it.

CONCLUSIONS
Tranexamic acid administration can have proinflammatory or anti-inflammatory effects through regulating C5a generation by plasmin, depending on the predominating PLG activator. Tranexamic acid may cause significant inflammatory C5a elevations in injured tissues by augmenting uPA-mediated plasmin generation in a fibrin-independent manner. In contrast, TXA reduces C5a generation during tPA-mediated fibrinolysis that may reduce inflammatory responses. In vivo validation of these novel ex vivo findings is warranted and may have important clinical consequences.
Massive transfusion protocols in nontrauma patients: A systematic review and meta-analysis
Authors: Sommer Nora , Schnüriger Beat , Candinas Daniel , Haltmeier Tobias 
Published: October 2018

BACKGROUND
Massive bleeding is a major cause of death both in trauma and nontrauma patients. In trauma patients, the implementation of massive transfusion protocols (MTP) led to improved outcomes. However, the majority of patients with massive bleeding are nontrauma patients.

OBJECTIVES
To assess if the implementation of MTP in nontrauma patients with massive bleeding leads to improved survival.

DATA SOURCES
National Library of Medicine's Medline database (PubMed).

STUDY ELIGIBILITY CRITERIA
Original research articles in English language investigating MTP in nontrauma patients.

PARTICIPANTS
Nontrauma patients with massive bleeding 18 years or older.

INTERVENTION
Transfusion according to MTP versus off-protocol.

STUDY APPRAISAL AND SYNTHESIS METHODS
Systematic literature review using PubMed. Outcomes assessed were mortality and transfused blood products. Studies that compared mortality of MTP and non-MTP groups were included in meta-analysis using Mantel-Haenszel random effect models.

RESULTS
A total of 252 abstracts were screened. Of these, 12 studies published 2007 to 2017 were found to be relevant to the topic, including 2,475 patients. All studies were retrospective and comprised different patient populations. Most frequent indications for massive transfusion were perioperative, obstetrical and gastrointestinal bleeding, as well as vascular emergencies. Four of the five studies that compared the number of transfused blood products in MTP and non-MTP groups revealed no significant difference. Meta-analysis revealed no significant effect of MTP on the 24-hour mortality (odds ratio 0.42; 95% confidence interval 0.01–16.62; p = 0.65) and a trend toward lower 1-month mortality (odds ratio 0.56; 95% confidence interval 0.30–1.07; p = 0.08).

LIMITATIONS
Heterogeneous patient populations and MTP in the studies included.

CONCLUSION
There is limited evidence that the implementation of MTP may be associated with decreased mortality in nontrauma patients. However, patient characteristics, as well as the indication and definition of MTP were highly heterogeneous in the available studies. Further prospective investigation into this topic is warranted.

LEVEL OF EVIDENCE
Systematic review and meta-analysis, level III.
Favorable Outcome of an Exclusively Posttransplant Prophylactic Strategy After Heart Transplantation in Recipients With High Immunological Risk
Authors: Coutance Guillaume , d’Orio Virginie , Belin Lisa , Bréchot Nicolas , Saheb Samir , Lebreton Guillaume , Bouglé Adrien , Rouvier Philippe , Gautreau Chantal , Ouldammar Salima , Chamillard Xavier , Huot Mélanie , Amour Julien , Combes Alain , Leprince Pascal , Varnous Shaida 
Published: October 2018

Background.
Management of the increasing number of sensitized heart transplant candidates has become a recurrent issue. Rather than using pretransplant desensitization therapies, we used a posttransplant prophylactic strategy. Our aim was to describe outcomes in transplant recipients with preformed donor-specific anti-HLA antibodies (pfDSA) managed with this strategy.

Methods.
A posttransplant protocol was applied to patients transplanted with pfDSA, consisting of perioperative management of DSA (polyvalent immunoglobulins +/− perioperative plasmapheresis sessions, according to DSA level, as well as induction therapy) and systematic treatment of subsequent antibody-mediated rejection (AMR), even when subclinical. We performed a retrospective analysis of this prospective protocol. The study included all consecutive first recipients of a noncombined heart transplant performed between 2009 and 2015 at our center. The primary endpoint was all-cause mortality. Secondary endpoints included primary graft dysfunction, early posttransplant bleeding, rejection, and cardiac allograft vasculopathy-free survival.

Results.
A total of 523 patients were studied, including 88 (17%) and 194 (37%) transplanted with DSA mean fluorescence intensity (MFI) of 500 to 1000 and greater than 1000, respectively. The median follow-up period was 4.06 years. Survival was not significantly different between groups. Rejection-free survival was worse in patients with pfDSA MFI >1000, evidenced by a fourfold increase in the risk of antibody-mediated rejection. The incidence of primary graft dysfunction and cardiac allograft vasculopathy-free survival did not significantly differ between groups. Perioperative plasmapheresis increased the risk for transfusion of packed red blood cells.

Conclusions.
This exclusively posttransplant prophylactic strategy achieved favorable outcomes in heart transplant recipients with pfDSA.
Version 3 of the National Alzheimer’s Coordinating Center’s Uniform Data Set
Authors: Besser Lilah , Kukull Walter , Knopman David S. , Chui Helena , Galasko Douglas , Weintraub Sandra , Jicha Gregory , Carlsson Cynthia , Burns Jeffrey , Quinn Joseph , Sweet Robert A. , Rascovsky Katya , Teylan Merilee , Beekly Duane , Thomas George , Bollenbeck Mark , Monsell Sarah , Mock Charles , Zhou Xiao Hua , Thomas Nicole , Robichaud Elizabeth , Dean Margaret , Hubbard Janene , Jacka Mary , Schwabe-Fry Kristen , Wu Joylee , Phelps Creighton , Morris John C. 
Published: October 2018

Introduction:
In 2015, the US Alzheimer’s Disease Centers (ADC) implemented Version 3 of the Uniform Data Set (UDS). This paper describes the history of Version 3 development and the UDS data that are freely available to researchers.

Methods:
UDS Version 3 was developed after years of coordination between the National Institute on Aging-appointed Clinical Task Force (CTF), clinicians from ∼30 ADCs, and the National Alzheimer’s Coordinating Center (NACC). The CTF recognized the need for updates to align with the state of the science in dementia research, while being flexible to the diverse needs and diseases studied at the ADCs. Version 3 also developed a nonproprietary neuropsychological battery.

Results:
This paper focuses on the substantial Version 3 changes to the UDS forms related to clinical diagnosis and characterization of clinical symptoms to match updated consensus-based diagnostic criteria. Between March 2015 and March 2018, 4820 participants were enrolled using UDS Version 3. Longitudinal data were available for 25,337 of the 37,568 total participants using all UDS versions.

Discussion:
The results from utilization of the UDS highlight the possibility for numerous research institutions to successfully collaborate, produce, and use standardized data collection instruments for over a decade.
New molecular targets in meningiomas: the present and the future
Authors: Venur Vyshak Alva , Santagata Sandro , Galanis Eva , Brastianos Priscilla K. 
Published: October 2018

Purpose of reviewMeningiomas, the most common primary brain tumor, have historically been managed with surgery and radiation. Traditional chemotherapy has not been effective. Fortunately, recent advances in genetic sequencing have led to an improved understanding of the molecular drivers in meningioma. This article aims to discuss the diagnostic and therapeutic implications of recently discovered genetic alterations in meningiomas.Recent findingsMany of the recently discovered genetic alterations correlate with distinct clinical phenotypes.SMO,AKTandPIK3CAmutations are enriched in the anterior skull base.KLF4mutations are specific for secretory histology, andBAP1alterations are common in progressive rhabdoid meningiomas. Alterations inTERT,DMDandBAP1correlate with poor clinical outcomes. Importantly, the discovery of clinically actionable alterations in a number of genes, includingSMO,AKT1andPIK3CA,has opened up novel potential avenues for therapeutic management of meningiomas. Overexpression of PD-L1 in higher grade meningiomas also provides preclinical support for the investigation of checkpoint blockade.SummaryThe discovery of genetic alterations has improved our understanding of the natural history and classification of meningiomas. Clinical trials with several novel agents targeting driver mutations are currently accruing patients and they can lead to better treatment strategies.
Kinematic and biomechanical analyses in Drosophila suggests that most legged locomotion in insects can be understood within a single framework
Authors: Chun Chanwoo , Biswas Tirthabir , Bhandawat Vikas 
Published: October 2018

AbstractDespite the fact that all insects have six legs, they display considerable differences in their legged locomotion. Are these differences irreconcilable, or simply different domains of the same system? In this study, we investigate walking inDrosophila. We find that despite the fact that flies walk extremely slowly relative to their size, they predominantly employ an alternating tripod gait, a gait typically associated with high-speed locomotion. The kinematics of their center of mass (CoM) is diametrically opposite to the CoM kinematics observed in insect runners such as cockroach. We resolve this tension between similar gaits, and differing kinematics in slow and high-speed locomotion by showing that the mechanics of a tripod gait naturally reduces to a simple biomechanical model which can support a range of kinematic patterns including both fly-like and cockroach-like patterns. These findings suggest that legged locomotion in different insects might represent different domains of the same system.
Early detection of cryostorage tank failure using a weight-based monitoring system
Authors: Michaelson Zahava P. , Bondalapati Sai T. , Amrane Selma , Prosser Robert W. , Hill Daniel M. , Gaur Pallavi , Recio Matt , Travassos David E. , Wolfkamp Mikaela D. , Sadowy Sasha , Thomas Colin , Forman Eric J. , Williams Zev 
Published: October 2018

AbstractObjectTo study the ability of custom-built, web-enabled scales to monitor liquid nitrogen (LN2) levels in cryostorage dewars.DesignLaboratory studySettingA large academic fertility center in New York City.InterventionsCryostorage dewars were placed on top of the custom-engineered scales with continuous real-time monitoring, and weight and temperature data were recorded in the setting of slow, medium, and fast rate-loss of LN2 designed to mimic models of tank failures.Main Outcome MeasuresWeights were continuously monitored and recorded, with a calculated alarm trigger set at 10% weight loss. Temperature within the tanks was simultaneously monitored with probes placed near the top of the tanks, with calculated alarms using a −185 °C as the threshold. For the “slow rate-loss” simulations, tanks were left intact and closed in usual operating conditions, and LN2 was allowed to evaporate at the normal rate. For the “medium rate-loss” simulation, the foam core of the tank neck was removed and the insulating vacuum was eliminated by making a 1/16 inch hole in the outer tank wall. For the “fast rate-loss” simulation, a 1/16” hole was made through the outer tank wall and LN2 was released at a rate of 0.15 L/second. All simulations were performed in duplicate.ResultsWith an intact and normally functioning tank, a 10% loss in LN2 occurred in 4.2-4.9 days. Warming to −185 °C occurred in 37.8 - 43.7 days, over 30 days after the weight-based alarm was triggered. Full evaporation of LN2required 36.8 days. For the medium rate-loss simulation, a 10% loss in LN2 occurred in 0.8 h. Warming to −185 °C occurred in 3.7 - 4.8 hours, approximately 3 hours after the weight-based alarm was triggered. For the fast rate-loss simulation, a 10% weight loss occurred within 15 seconds and tanks were completely depleted in under 3 minutes. Tank temperatures began to rise immediately and at a relatively constant rate of 43.9 °C/hour and 51.6 °C/hour. Temperature alarms would have sounded within 0.37 and 0.06 hours after the breech.ConclusionsThis study demonstrates that a weight-based, automated alarm system can detect tank failures prior to a temperature-based alarm system, in some cases over a month in advance. In combination with existing safety mechanisms such as temperature probes, a weight-based monitoring system could serve as a redundant safety mechanism for added protection of cryopreserved reproductive tissues.
Brain tissue segmentation based on MP2RAGE multi-contrast images in 7 T MRI
Authors: Choi Uk-Su , Kawaguchi Hirokazu , Matsuoka Yuichiro , Kober Tobias , Kida Ikuhiro 
Published: October 2018

AbstractWe proposed a method for segmentation of brain tissues––gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF)—using multi-contrast images, including a T1 map and a uniform T1-weighted image, from a magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE) sequence at 7 Tesla. The proposed method was evaluated with respect to the processing time and the similarity of the segmented masks of brain tissues with those obtained using FreeSurfer, FSL, and SPM12. The processing time of the proposed method (28 ± 0 s) was significantly shorter than those of FSL and SPM12 (444 ± 4 s and 159 ± 2 s for FSL and SPM12, respectively). In the similarity assessment, the tissue mask of the brain obtained by the proposed method showed higher consistency with those obtained by FSL than with those obtained by SPM12. The proposed method misclassified the subcortical structures and large vessels since it is based on the intensities of multi-contrast images obtained using MP2RAGE, which uses a similar segmentation approach as FSL but is not based on a template image or a parcellated brain atlas, which are used for FreeSurfer and SPM12, respectively. However, the proposed method showed good segmentation in the cerebellum and WM in the medial part of the brain in comparison with the other methods. Thus, because the proposed method using different contrast images of MP2RAGE sequence showed the shortest processing time and similar segmentation ability as the other methods, it may be useful for both neuroimaging research and clinical diagnosis.
capC-MAP : A Software Package for Analysis of Capture-C data
Authors: Buckle Adam , Gilbert Nick , Marenduzzo Davide , Brackley Chris A. 
Published: October 2018

AbstractWe present capC-MAP, a software package for the analysis of Capture-C data. Capture-C is a “many-to-all” chromosome-conformation-capture method. We summarise the method, then detail capC-MAP, the first software specifically designed and optimised for Capture-C data. capC-MAP has been developed with ease-of-use and flexibility in mind: the entire pipe-ine can be run with a single command, or the component programs can be run individually for custom data processing, in a strategy that will suit computational as well as experimental researchers. Finally, we compare and benchmark capC-MAP against another package which can perform (though is not optimised for) analysis of Capture-C data.