bluuebunny/crossref_metadata_2025_split huggingface dataset:
NLRP3 inflammasome as prognostic factor and therapeutic target in primary progressive multiple sclerosis patients
Authors: Malhotra Sunny , Costa Carme , Eixarch Herena , Keller Christian W , Amman Lukas , Martínez-Banaclocha Helios , Midaglia Luciana , Sarró Eduard , Machín-Díaz Isabel , Villar Luisa M , Triviño Juan Carlos , Oliver-Martos Begoña , Parladé Laura Navarro , Calvo-Barreiro Laura , Matesanz Fuencisla , Vandenbroeck Koen , Urcelay Elena , Martínez-Ginés María-Luisa , Tejeda-Velarde Amalia , Fissolo Nicolás , Castilló Joaquín , Sanchez Alex , Robertson Avril A B , Clemente Diego , Prinz Marco , Pelegrin Pablo , Lünemann Jan D , Espejo Carmen , Montalban Xavier , Comabella Manuel 
Published: March 2020

Abstract
Primary progressive multiple sclerosis is a poorly understood disease entity with no specific prognostic biomarkers and scarce therapeutic options. We aimed to identify disease activity biomarkers in multiple sclerosis by performing an RNA sequencing approach in peripheral blood mononuclear cells from a discovery cohort of 44 untreated patients with multiple sclerosis belonging to different clinical forms and activity phases of the disease, and 12 healthy control subjects. A validation cohort of 58 patients with multiple sclerosis and 26 healthy control subjects was included in the study to replicate the RNA sequencing findings. The RNA sequencing revealed an interleukin 1 beta (IL1B) signature in patients with primary progressive multiple sclerosis. Subsequent immunophenotyping pointed to blood monocytes as responsible for the IL1B signature observed in this group of patients. Functional experiments at baseline measuring apoptosis-associated speck-like protein containing a CARD (ASC) speck formation showed that the NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome was overactive in monocytes from patients with primary progressive multiple sclerosis, and canonical NLRP3 inflammasome activation with a combination of ATP plus lipopolysaccharide was associated with increased IL1B production in this group of patients. Primary progressive multiple sclerosis patients with high IL1B gene expression levels in peripheral blood mononuclear cells progressed significantly faster compared to patients with low IL1B levels based on the time to reach an EDSS of 6.0 and the Multiple Sclerosis Severity Score. In agreement with peripheral blood findings, both NLRP3 and IL1B expression in brain tissue from patients with primary progressive multiple sclerosis was mainly restricted to cells of myeloid lineage. Treatment of mice with a specific NLRP3 inflammasome inhibitor attenuated established experimental autoimmune encephalomyelitis disease severity and improved CNS histopathology. NLRP3 inflammasome-specific inhibition was also effective in reducing axonal damage in a model of lipopolysaccharide-neuroinflammation using organotypic cerebellar cultures. Altogether, these results point to a role of IL1B and the NLRP3 inflammasome as prognostic biomarker and potential therapeutic target, respectively, in patients with primary progressive multiple sclerosis.
Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy
Authors: Chatron Nicolas , Becker Felicitas , Morsy Heba , Schmidts Miriam , Hardies Katia , Tuysuz Beyhan , Roselli Sandra , Najafi Maryam , Alkaya Dilek Uludag , Ashrafzadeh Farah , Nabil Amira , Omar Tarek , Maroofian Reza , Karimiani Ehsan Ghayoor , Hussien Haytham , Kok Fernando , Ramos Luiza , Gunes Nilay , Bilguvar Kaya , Labalme Audrey , Alix Eudeline , Sanlaville Damien , de Bellescize Julitta , Poulat Anne-Lise ,   EuroEpinomics-RES consortium AR working group, Helbig Ingo , von Spiczak Sarah , Baulac Stephanie , Barisic Nina , Balling Rudi , Caglayan Hande , Craiu Dana , Guerrini Renzo , Klein Karl Martin , Marini Carla , Muhle Hiltrud , Rosenow Felix , Serratosa Jose M , Sterbova Katalin , Weber Yvonne , Moslemi Ali-Reza , Lerche Holger , May Patrick , Lesca Gaetan , Weckhuysen Sarah , Tajsharghi Homa 
Published: March 2020

Abstract
Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1−/− mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele.
Quantitative Analysis of Taste Bud Cell Numbers in the Circumvallate and Foliate Taste Buds of Mice
Authors: Ogata Takahiro , Ohtubo Yoshitaka 
Published: March 2020

Abstract
A mouse single taste bud contains 10–100 taste bud cells (TBCs) in which the elongated TBCs are classified into 3 cell types (types I–III) equipped with different taste receptors. Accordingly, differences in the cell numbers and ratios of respective cell types per taste bud may affect taste-nerve responsiveness. Here, we examined the numbers of each immunoreactive cell for the type II (sweet, bitter, or umami receptor cells) and type III (sour and/or salt receptor cells) markers per taste bud in the circumvallate and foliate papillae and compared these numerical features of TBCs per taste bud to those in fungiform papilla and soft palate, which we previously reported. In circumvallate and foliate taste buds, the numbers of TBCs and immunoreactive cells per taste bud increased as a linear function of the maximal cross-sectional taste bud area. Type II cells made up approximately 25% of TBCs irrespective of the regions from which the TBCs arose. In contrast, type III cells in circumvallate and foliate taste buds made up approximately 11% of TBCs, which represented almost 2 times higher than what was observed in the fungiform and soft palate taste buds. The densities (number of immunoreactive cells per taste bud divided by the maximal cross-sectional area of the taste bud) of types II and III cells per taste bud are significantly higher in the circumvallate papillae than in the other regions. The effects of these region-dependent differences on the taste response of the taste bud are discussed.
Impact of an Antibiotic Side-Chain–Based Cross-reactivity Chart Combined With Enhanced Allergy Assessment Processes for Surgical Prophylaxis Antimicrobials in Patients With β-Lactam Allergies
Authors: Collins Curtis D , Scheidel Caleb , Anam Kishore , Polega Shikha , Malani Anurag N , Hayward Alexandra , Leo Harvey L , Shankar Tara , Morrin Cheryl , Brockhaus Kara 
Published: March 2020

Abstract

Background
β-Lactam antibiotics are first-line therapy for perioperative prophylaxis; however, patient-reported allergies often lead to increased prescribing of alternative antibiotics that may increase the incidence of surgical site infections. The R-group side chain of the β-lactam ring is responsible for allergic cross-reactivity and experts recommend the use of β-lactams that are structurally dissimilar.

Methods
An internally developed, antibiotic side-chain–based cross-reactivity chart was developed and implemented alongside enhanced allergy assessment processes. This single-center, quasi-experimental study analyzed antibiotic prescribing in all adult patients with a documented β-lactam allergy undergoing an inpatient surgical procedure between quartile (Q) 1 (2012)–Q3 (2014) (historical group) and Q3 (2016)–Q3 (2018) (intervention group). Propensity-weighted scoring analyses compared categorical and continuous outcomes. Interrupted time-series analysis further analyzed key outcomes.

Results
A total of 1119 and 1089 patients were included in the historical and intervention cohorts, respectively. There was a significant difference in patients receiving a β-lactam alternative antibiotic between cohorts (84.9% vs 15.1%; P &lt; .001). There was a decrease in 30-day readmissions in the intervention cohort (7.9% vs 6.3%; P = .035); however, there was no difference in the incidence of SSIs in patients readmitted (14.8% vs 13%; P = .765). No significant differences were observed in allergic reactions (0.5% vs 0.3%; P = .323), surgical site infections, in-hospital and 30-day mortality, healthcare facility–onset Clostridiodes difficile infection, acute kidney injury, or hospital costs.

Conclusions
Implementation of an antibiotic cross-reactivity chart combined with enhanced allergy assessment processes significantly improved the prescribing of β-lactam antibiotics for surgical prophylaxis.
Doxycycline for Prevention of Spirochetal Infections: Status Report
Authors: Wormser Gary P 
Published: March 2020

Abstract
Important human infections caused by spirochetal microorganisms include Lyme disease, syphilis, leptospirosis, and tick-borne relapsing fever. Doxycycline prophylactic regimens have been shown to significantly reduce the risk for developing all of these infections in potentially exposed individuals, which is highly clinically relevant as no vaccines to prevent these infections in humans are currently available. Additional data, however, are needed to define more precisely the level of efficacy of the doxycycline prophylactic regimens, especially for Lyme disease and syphilis, infections that can be potentially prevented by a single 200-mg dose of doxycycline given within 72 hours postexposure.
Improved protein-binding radioassay for plasma cortisol.
Authors: Novacenko H , Halpern F , Sachar E J 
Published: March 2020

Abstract
We describe an improved competitive protein-binding radioassay for total plasma cortisol, which permits rapid analysis of many samples. Plasma, 0.1 mL, is directly applied to a Whatman 3MM filter-paper strip, which is extracted once with dichloromethane. The extract is evaporated and the residue is assayed directly by the micro-method of Murphy (J. Clin. Endocrinol. Metab. 27: 973, 1967). Comparison with the original Murphy method (ethanol extraction) yielded excellent agreement (r = 0.988). One hundred samples, in duplicate, can easily be assayed at a time.
Agricultural land in the Amazon basin supports low bird diversity and is a poor replacement for primary forest
Authors: Neate-Clegg Montague H C , Şekercioğlu Çağan H 
Published: March 2020

Abstract
The Amazon has a long history of disturbance under subsistence agriculture, but slash-and-burn agriculture is small in scale and has relatively low impact on resident avifauna. More recently, the Amazon has suffered extensive deforestation in favor of cattle ranching and other modern systems of agriculture. Cattle pastures, mechanized agriculture, and even tree plantations have detrimental effects on bird communities, greatly lowering diversity, especially that of primary forest interior specialists. A rising threat to the Amazon is the spread of oil palm plantations that retain few bird species and are not viable alternatives to forest. Embedded within the expanding agropastoral mosaic are forest fragments that have experienced a well-documented loss of diversity. Yet, the matrix can mitigate the recovery of fragmented bird communities depending on the type of secondary regrowth. Connectivity via matrix habitats or forest corridors is critical for the maintenance of forest avifauna. With so many types of land use developing across the Amazon, the “tropical countryside” has potential value for bird diversity. However, evidence suggests that the agropastoral mosaic harbors a small, more homogenized avifauna with few forest species, especially when primary forest is absent from the landscape. For the Amazon Basin’s bird life to be conserved into the future, preservation of large tracts of well-connected primary forest is vital. Tropical countryside dominated by agriculture simply cannot sustain sufficient levels of biodiversity.
Relevant issues in tumor regression grading of histopathological response to neoadjuvant treatment in adenocarcinomas of the esophagus and gastroesophageal junction
Authors: Klevebro F , Tsekrekos A , Low D , Lundell L , Vieth M , Detlefsen S 
Published: March 2020

AbstractMultimodality treatment combining surgery and oncologic treatment has become widely applied in curative treatment of esophageal and gastroesophageal junction adenocarcinoma. There is a need for a standardized tumor regression grade scoring system for clinically relevant effects of neoadjuvant treatment effects. There are numerous tumor regression grading systems in use and there is no international standardization. This review has found nine different international systems currently in use. These systems all differ in detail, which inhibits valid comparisons of results between studies. Tumor regression grading in esophageal and gastroesophageal junction adenocarcinoma needs to be improved and standardized. To achieve this goal, we have invited a significant group of international esophageal and gastroesophageal junction adenocarcinoma pathology experts to perform a structured review in the form of a Delphi process. The aims of the Delphi include specifying the details for the disposal of the surgical specimen and defining the details of, and the reporting from, the agreed histological tumor regression grade system including resected lymph nodes. The second step will be to perform a validation study of the agreed tumor regression grading system to ensure a scientifically robust inter- and intra-observer variability and to incorporate the consented tumor regression grading system in clinical studies to assess its predictive and prognostic role in treatment of esophageal and gastroesophageal junction adenocarcinomas. The ultimate aim of the project is to improve survival in esophageal and gastroesophageal adenocarcinoma by increasing the quality of tumor regression grading, which is a key component in treatment evaluation and future studies of individualized treatment of esophageal cancer.
The relation between cardiac 123I-mIBG scintigraphy and functional response 1 year after CRT implantation
Authors: Verschure D O , Poel E , De Vincentis G , Frantellizzi V , Nakajima K , Gheysens O , de Groot J R , Verberne H J 
Published: March 2020

Abstract

Aims
Cardiac resynchronization therapy (CRT) is a disease-modifying therapy in patients with chronic heart failure (CHF). Current guidelines ascribe CRT eligibility on three parameters only: left ventricular ejection fraction (LVEF), QRS duration, and New York Heart Association (NYHA) functional class. However, one-third of CHF patients does not benefit from CRT. This study evaluated whether 123I-meta-iodobenzylguanidine (123I-mIBG) assessed cardiac sympathetic activity could optimize CRT patient selection.

Methods and results
A total of 78 stable CHF subjects (age 66.8 ± 9.6 years, 73% male, LVEF 25.2 ± 6.7%, QRS duration 153 ± 23 ms, NYHA 2.2 ± 0.7) referred for CRT implantation were enrolled. Subjects underwent 123I-mIBG scintigraphy prior to implantation. Early and late heart-to-mediastinum (H/M) ratio and 123I-mIBG washout were calculated. CRT response was defined as either an increase of LVEF to &gt;35%, any improvement in LVEF of &gt;10%, QRS shortening to &lt;150 ms, or improvement in NYHA class of &gt;1 class. In 33 patients LVEF increased to &gt;35%, QRS decreased &lt;150 ms in 36 patients, and NYHA class decreased in 33 patients. Late H/M ratio and hypertension were independent predictors of LVEF improvement to &gt;35% (P = 0.0014 and P = 0.0149, respectively). In addition, early H/M ratio, LVEF, and absence of diabetes mellitus (DM) were independent predictors for LVEF improvement by &gt;10%. No independent predictors were found for QRS shortening to &lt;150 ms or improvement in NYHA class.

Conclusion
Early and late H/M ratio were independent predictors of CRT response when improvement of LVEF was used as measure of response. Therefore, cardiac 123I-mIBG scintigraphy may be used as a tool to optimize selection of subjects that might benefit from CRT.
Progression of ultrasound plaque attenuation and low echogenicity associates with major adverse cardiovascular events
Authors: Shishikura Daisuke , Kataoka Yu , Di Giovanni Giuseppe , Takata Kohei , Scherer Daniel J , Andrews Jordan , Psaltis Peter J , Puri Rishi , Wolski Kathy , Nissen Steven E , Nicholls Stephen J 
Published: March 2020

Abstract

Aims
Intravascular ultrasound (IVUS) imaging can visualize vulnerable plaque features including attenuation (AP) and echolucency (ELP). While IVUS-derived vulnerable plaque features associate with microvascular obstruction during percutaneous coronary intervention, the relationship between these plaque features and clinical outcomes has not been established. This analysis aimed to evaluate the association of AP/ELP with cardiovascular events.

Methods and results
Serial IVUS imaging was reviewed in 1497 patients, followed for 18–24 months, with coronary artery disease from two clinical trials. Attenuated plaque and ELP were identified to measure each characteristics (AP arc, ELP area, and lengths), which permitted calculation of an AP index (API) and ELP volume. Attenuated plaque/ELP progression was defined as patients with any increase of API or ELP volume on serial imaging. The major cardiovascular events (MACEs) were defined as death, myocardial infarction, stroke, and coronary revascularization. AP or ELP was identified in 282 patients (18.8%) at baseline and 160 (10.7%) patients demonstrated an increase in AP or ELP at follow-up. The incidence of MACE was higher in patients with baseline AP/ELP than those without (8.2% vs. 3.9%, P = 0.002). Patients with AP/ELP progression were more likely to be acute coronary syndrome (41.9 vs. 33.2%, P = 0.03) and have greater baseline percent atheroma volume (40.0% vs. 35.8%, P &lt; 0.001) than those without. On multivariable analysis, AP/ELP progression was more strongly associated with MACE [baseline AP/ELP: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.05–2.97, AP/ELP progression: HR 2.19, 95% CI 1.24–3.86].

Conclusion
Attenuation/ELP progression was associated with a higher prevalence of cardiovascular events, supporting a potential role for the identification of high-risk vulnerable plaques in patients with coronary artery disease.
Propulsive nanomachines: the convergent evolution of archaella, flagella and cilia
Authors: Beeby Morgan , Ferreira Josie L , Tripp Patrick , Albers Sonja-Verena , Mitchell David R 
Published: March 2020

ABSTRACTEchoing the repeated convergent evolution of flight and vision in large eukaryotes, propulsive swimming motility has evolved independently in microbes in each of the three domains of life. Filamentous appendages – archaella in Archaea, flagella in Bacteria and cilia in Eukaryotes – wave, whip or rotate to propel microbes, overcoming diffusion and enabling colonization of new environments. The implementations of the three propulsive nanomachines are distinct, however: archaella and flagella rotate, while cilia beat or wave; flagella and cilia assemble at their tips, while archaella assemble at their base; archaella and cilia use ATP for motility, while flagella use ion-motive force. These underlying differences reflect the tinkering required to evolve a molecular machine, in which pre-existing machines in the appropriate contexts were iteratively co-opted for new functions and whose origins are reflected in their resultant mechanisms. Contemporary homologies suggest that archaella evolved from a non-rotary pilus, flagella from a non-rotary appendage or secretion system, and cilia from a passive sensory structure. Here, we review the structure, assembly, mechanism and homologies of the three distinct solutions as a foundation to better understand how propulsive nanomachines evolved three times independently and to highlight principles of molecular evolution.
A method of phase identification for seismic data acquired with the controlled accurate seismic source (CASS)
Authors: Wang Xiaolei , Xue Bing , Cui Rensheng , Gu Guoliang , Peng Chaoyong , Zheng Yu , Yang Jiansi 
Published: March 2020

SUMMARY
With the advantages of the little destruction to the deployment site and high repeatability compared with explosive sources, the controlled accurate seismic source (CASS) has many potential applications with respect to the investigation of the crustal structure and seismic wave velocities. However, the signal generated by the CASS rapidly attenuates with the increasing distance because of its poor signal-to-noise ratio (SNR). Consequently, the difficulties in identifying specific seismic phases from the CASS data limit its application and popularization. The aim of this study is to present a new method to improve the accuracy of traveltime estimation and to identify more seismic phases travelling through the crust. We adopt the global seismic phase scanning algorithms (GSPSA) combined with an optimized narrowband time-varying filter, whose central frequency corresponds to the instantaneous frequency of the linear frequency modulation (LFM) signals produced by the CASS. Using the seismic data from the 40-ton CASS in a field experiment around Xinfengjiang reservoir in southeast China, we attain the seismic phases such as Pg, Sg, PmP and SmS at epicentral distances of more than 200 km with GSPSA. To identify and verify these seismic phases information, we also calculate synthetic waveforms. The results demonstrate that the GSPSA method is an effective tool for seismic phase identification of CASS data.