bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bidirectional modulation of glutamatergic synaptic transmission by metabotropic glutamate type 7 receptors at Schaffer collateral–CA1 hippocampal synapses
Authors: Martín Ricardo , Ferrero José Javier , Collado‐Alsina Andrea , Aguado Carolina , Luján Rafael , Torres Magdalena , Sánchez‐Prieto José 
Published: December 2017

Key points
Neurotransmitter release is inhibited by metabotropic glutamate type 7 (mGlu7) receptors that reduce Ca2+ influx, yet synapses lacking this receptor also produce weaker release, suggesting that mGlu7 receptors may also prime synaptic vesicles for release. Prolonged activation of mGlu7 receptors with the agonist l‐AP4 first reduces and then enhances the amplitude of EPSCs through a presynaptic effect.
The inhibitory response is blocked by pertussis toxin, while the potentiating response is prevented by a phospholipase C inhibitor (U73122) and an inhibitor of diacylglycerol (DAG) binding (calphostin C), suggesting that this receptor also couples to pathways that generate DAG.
Release potentiation is associated with an increase in the number of synaptic vesicles close to the plasma membrane, which was dependent on the Munc13‐2 and RIM1α proteins. The Glu7 receptors activated by the glutamate released following high frequency stimulation provoke a bidirectional modulation of synaptic transmission.
AbstractNeurotransmitter release is driven by Ca2+ influx at synaptic boutons that acts on synaptic vesicles ready to undergo exocytosis. Neurotransmitter release is inhibited when metabotropic glutamate type 7 (mGlu7) receptors provoke a reduction in Ca2+ influx, although the reduced release from synapses lacking this receptor suggests that they may also prime synaptic vesicles for release. These mGlu7 receptors activate phospholipase C (PLC) and generate inositol trisphosphate, which in turn releases Ca2+ from intracellular stores and produces diacylglycerol (DAG), an activator of proteins containing DAG‐binding domains such as Munc13 and protein kinase C (PKC). However, the full effects of mGlu7 receptor signalling on synaptic transmission are unclear. We found that prolonged activation of mGlu7 receptors with the agonist l‐AP4 first reduces and then enhances the amplitude of EPSCs, a presynaptic effect that changes the frequency but not the amplitude of the mEPSCs and the paired pulse ratio. Pertussis toxin blocks the inhibitory response, while the PLC inhibitor U73122, and the inhibitor of DAG binding calphostin C, prevent receptor mediated potentiation. Moreover, this DAG‐dependent potentiation of the release machinery brings more synaptic vesicles closer to the active zone plasma membrane in a Munc13‐2‐ and RIM1α‐dependent manner. Electrically evoked release of glutamate that activates mGlu7 receptors also bidirectionally modulates synaptic transmission. In these conditions, potentiation now occurs rapidly and it overcomes any inhibition, such that potentiation prevails unless it is suppressed with the PLC inhibitor U73122.
Pulsing corals: A story of scale and mixing
Authors: Samson Julia E. , Battista Nicholas A. , Khatri Shilpa , Miller Laura A. 
Published: December 2017

Effective methods of fluid transport vary across scale. A commonly used dimensionless number for quantifying the effective scale of fluid transport is the frequency based Reynolds number, Re, which gives the ratio of inertial to viscous forces in a fluid flow. What may work well for one Re regime may not produce significant flows for another. These differences in scale have implications for many organisms, ranging from the mechanics of how organisms move through their fluid environment to how hearts pump at various stages in development. Some organisms, such as soft pulsing corals, actively contract their tentacles to generate mixing currents that enhance photosynthesis. Their unique morphology and the intermediate Re regime at which they function, where both viscous and inertial forces are significant, make them a unique model organism for understanding fluid mixing. In this paper, 3D fluid-structure interaction simulations of a pulsing soft coral are used to quantify fluid transport and describe fluid mixing across a wide range of Re. The results show that net transport is negligible for Re<10, and continuous upward flow is produced for Reв‰Ґ10. Sustained net transport is necessary to bring in new fluid for sampling and to remove waste. As the Re is increased well above 10, the slow region of mixing necessary for gas exchange between the tentacles is reduced. Since corals live at Re between about 8 and 36, the flows they produce are defined by sustained net transport of fluid away from the coral in a continuous upward jet and a slow region of mixing between the tentacles necessary for gas exchange.Supplementary material:1.В Movie of velocity and vorticity of flow field around pulsing coral at Re = 0.52.В Movie of velocity and vorticity of flow field around pulsing coral at Re = 103.В Movie of velocity and vorticity of flow field around pulsing coral at Re = 80В
Friedreich and dominant ataxias: quantitative differences in cerebellar dysfunction measurements
Authors: Tanguy Melac Audrey , Mariotti Caterina , Filipovic Pierucci Antoine , Giunti Paola , Arpa Javier , Boesch Sylvia , Klopstock Thomas , Müller vom Hagen Jennifer , Klockgether Thomas , Bürk Katrin , Schulz Jörg B , Reetz Kathrin , Pandolfo Massimo , Durr Alexandra , Tezenas du Montcel Sophie 
Published: December 2017

BackgroundSensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction.MethodsWe evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively.ResultsThere were 383 patients with Friedreich’s ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores.ConclusionsCerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated.Trial registration numberClinicalTrials.gov: NCT02069509.
Role of aluminum on the physical and spectroscopic properties of chromium-doped strontium alumino borate glasses
Authors: Ahmed Mohamed Raheem , Sekhar K. Chandra , Hameed Abdul , Chary M. Narasimha , Shareefuddin Md 
Published: December 2017

The glass samples were prepared in accordance with the formula: (30-x)SrO–xAl2O3–69.8B2O3–0.2Cr2O3(0 [Formula: see text]x [Formula: see text] 15 mol %) by melt quenching method. The absence of Bragg’s peaks confirmed the amorphous nature of the prepared glass samples. It was observed that the molar volume was increasing while the density is decreasing with increasing of Al2O3content. Optical absorption study was performed to evaluate the optical bandgap, oxygen packing density, ionic packing density and Urbach energies. The Racah parameters (B and C) and D[Formula: see text]/B ratio have been calculated. Fourier transform infrared (FTIR) spectra recorded in the region from 400–1600 cm[Formula: see text] at room-temperature (RT) confirmed the formation of BO3, BO4and AlO4groups upon the addition of strontium oxide as modifier. The Raman spectra of all the glasses recorded over continuous spectral range 200–1600 cm[Formula: see text] exhibited different spectral bands. The EPR spectra recorded at 9.7 GHz (X-band frequency) have four resonance signals. The signal at g [Formula: see text] 5.33 is due to Cr[Formula: see text] ion sites of rhombic symmetry and signal at g [Formula: see text] 1.97 is due to contribution from Cr[Formula: see text] and Cr[Formula: see text] ion pairs.
Germinal Centers Determine the Prognostic Relevance of Tertiary Lymphoid Structures and Are Impaired by Corticosteroids in Lung Squamous Cell Carcinoma
Authors: Siliņa Karīna , Soltermann Alex , Attar Farkhondeh Movahedian , Casanova Ruben , Uckeley Zina M. , Thut Helen , Wandres Muriel , Isajevs Sergejs , Cheng Phil , Curioni-Fontecedro Alessandra , Foukas Periklis , Levesque Mitchell P. , Moch Holger , Linē Aija , van den Broek Maries 
Published: December 2017

Abstract
In solid tumors, the presence of lymph node–like structures called tertiary lymphoid structures (TLS) is associated with improved patient survival. However, little is known about how TLS develop in cancer, how their function affects survival, and whether they are affected by cancer therapy. In this study, we used multispectral microscopy, quantitative pathology, and gene expression profiling to analyze TLS formation in human lung squamous cell carcinoma (LSCC) and in an experimental model of lung TLS induction. We identified a niche of CXCL13+ perivascular and CXCL12+LTB+ and PD-L1+ epithelial cells supporting TLS formation. We also characterized sequential stages of TLS maturation in LSCC culminating in the formation of germinal centers (GC). In untreated patients, TLS density was the strongest independent prognostic marker. Furthermore, TLS density correlated with GC formation and expression of adaptive immune response–related genes. In patients treated with neoadjuvant chemotherapy, TLS density was similar, but GC formation was impaired and the prognostic value of TLS density was lost. Corticosteroids are coadministered with chemotherapy to manage side effects in LSCC patients, so we evaluated whether they impaired TLS development independently of chemotherapy. TLS density and GC formation were each reduced in chemotherapy-naïve LSCC patients treated with corticosteroids before surgery, compared with untreated patients, a finding that we confirmed in the experimental model of lung TLS induction. Overall, our results highlight the importance of GC formation in TLS during tumor development and treatment.
Significance: Corticosteroid treatment during chemotherapy negatively affects the development of tertiary lymphoid structures and abrogates their prognostic value in patients with lung cancer. Cancer Res; 78(5); 1308–20. ©2018 AACR.
Exploring the Origins of Snow Drought in the Northern Sierra Nevada, California
Authors: Hatchett Benjamin J. , McEvoy Daniel J. 
Published: December 2017

Abstract
The concept of snow drought is gaining widespread interest as the climate of snow-dominated mountain watersheds continues to change. Warm snow drought is defined as above- or near-average accumulated precipitation coinciding with below-average snow water equivalent at a point in time. Dry snow drought is defined as below-average accumulated precipitation and snow water equivalent at a point in time. This study contends that such point-in-time definitions might miss important components of how snow droughts originate, persist, and terminate. Using these simple definitions and a variety of observations at monthly, daily, and hourly time scales, the authors explore the hydrometeorological origins of potential snow droughts in the northern Sierra Nevada from water years 1951 to 2017. This study finds that snow droughts can result from extreme early season precipitation, frequent rain-on-snow events, and low precipitation years. Late-season snow droughts can follow persistent warm and dry periods with effects that depend upon elevation. Many snow droughts were characterized by lower snow fractions and midwinter peak runoff events. These findings can guide improved evaluations of historical and potential future snow droughts, particularly with regards to how impacts on water resources and mountain ecosystems may vary depending on how snow droughts originate and evolve in time.
The Interconnected Global Climate System—A Review of Tropical–Polar Teleconnections
Authors: Yuan Xiaojun , Kaplan Michael R. , Cane Mark A. 
Published: December 2017

AbstractThis paper summarizes advances in research on tropical–polar teleconnections, made roughly over the last decade. Elucidating El Niño–Southern Oscillation (ENSO) impacts on high latitudes has remained an important focus along different lines of inquiry. Tropical to polar connections have also been discovered at the intraseasonal time scale, associated with Madden–Julian oscillations (MJOs). On the time scale of decades, changes in MJO phases can result in temperature and sea ice changes in the polar regions of both hemispheres. Moreover, the long-term changes in SST of the western tropical Pacific, tropical Atlantic, and North Atlantic Ocean have been linked to the rapid winter warming around the Antarctic Peninsula, while SST changes in the central tropical Pacific have been linked to the warming in West Antarctica. Rossby wave trains emanating from the tropics remain the key mechanism for tropical and polar teleconnections from intraseasonal to decadal time scales. ENSO-related tropical SST anomalies affect higher-latitude annular modes by modulating mean zonal winds in both the subtropics and midlatitudes. Recent studies have also revealed the details of the interactions between the Rossby wave and atmospheric circulations in high latitudes. We also review some of the hypothesized connections between the tropics and poles in the past, including times when the climate was fundamentally different from present day especially given a larger-than-present-day global cryosphere. In addition to atmospheric Rossby waves forced from the tropics, large polar temperature changes and amplification, in part associated with variability in orbital configuration and solar irradiance, affected the low–high-latitude connections.
Dominant Circulation Patterns of the Deep Gulf of Mexico
Authors: Pérez-Brunius Paula , Furey Heather , Bower Amy , Hamilton Peter , Candela Julio , García-Carrillo Paula , Leben Robert 
Published: December 2017

AbstractThe large-scale circulation of the bottom layer of the Gulf of Mexico is analyzed, with special attention to the historically least studied western basin. The analysis is based on 4 years of data collected by 158 subsurface floats parked at 1500 and 2500 m and is complemented with data collected by current meter moorings in the western basin during the same period. Three main circulation patterns stand out: a cyclonic boundary current, a cyclonic gyre in the abyssal plain, and the very high eddy kinetic energy observed in the eastern Gulf. The boundary current and the cyclonic gyre appear as distinct features, which interact in the western tip of the Yucatan shelf. The persistence and continuity of the boundary current is addressed. Although high variability is observed, the boundary flow serves as a pathway for water to travel around the western basin in approximately 2 years. An interesting discovery is the separation of the boundary current over the northwestern slope of the Yucatan shelf. The separation and retroflection of the along-slope current appears to be a persistent feature and is associated with anticyclonic eddies whose genesis mechanism remains to be understood. As the boundary flow separates, it feeds into the westward flow of the deep cyclonic gyre. The location of this gyre—named the Sigsbee Abyssal Gyre—coincides with closed geostrophic contours, so eddy–topography interaction via bottom form stresses may drive this mean flow. The contribution to the cyclonic vorticity of the gyre by modons traveling under Loop Current eddies is discussed.
Modeling the Evolution and Life Cycle of Radiative Cold Pools and Fog
Authors: Wilson Travis H. , Fovell Robert G. 
Published: December 2017

Abstract
Despite an increased understanding of the physical processes involved, forecasting radiative cold pools and their associated meteorological phenomena (e.g., fog and freezing rain) remains a challenging problem in mesoscale models. The present study is focused on California’s tule fog where the Weather Research and Forecasting (WRF) Model’s frequent inability to forecast these events is addressed and substantially improved. Specifically, this was accomplished with four major changes from a commonly employed, default configuration. First, horizontal model diffusion and numerical filtering along terrain slopes was deactivated (or mitigated) since it is unphysical and can completely prevent the development of fog. However, this often resulted in unrealistically persistent foggy boundary layers that failed to lift. Next, changes specific to the Yonsei University (YSU) planetary boundary layer (PBL) scheme were adopted that include using the ice–liquid-water potential temperature to determine vertical stability, a reversed eddy mixing K profile to represent the consequences of negatively buoyant thermals originating near the fog (PBL) top, and an additional entrainment term to account for the turbulence generated by cloud-top (radiative and evaporative) cooling. While other changes will be discussed, it is these modifications that create, to a sizable degree, marked improvements in modeling the evolution and life cycle of fog, low stratus clouds, and adiabatic cold pools.
Targeted Tonsillar Biopsy for Unilateral Tonsillar Enlargement
Authors: Pham Truong An , Berkowitz Robert G 
Published: December 2017

Background: Unilateral tonsillar enlargement (UTE) is not an uncommon incidental finding. Lymphoma is the most common malignancy of the tonsils in children and presents with tonsillar enlargement. Methods: This is a retrospective case series of all cases of histopathological analysis of tonsillectomy specimens at a single pediatric tertiary hospital between 1996 and 2015. Patients either had a preoperative indication (n = 53) for pathological testing or indications based on intraoperative findings (n = 88). Of the preoperative group, 17 patients had tonsillectomy for UTE alone. In 72% of cases, the side of perceived unilateral enlargement was confirmed at histopathological assessment. Results: Zero cases of suspected malignancy were identified on testing. Conclusion: There is a very low prevalence of unsuspected and suspected malignancy in routine and targeted examination of tonsillar specimens. It is reasonable to test based on other clinical findings and risk factors such as immunosuppression.
Outcome evaluation of ‘Cool and Clean’, a sports-based substance use prevention programme for young people in Switzerland
Authors: Wicki Matthias , Kuntsche Sandra , Stucki Stephanie , Marmet Simon , Annaheim Beatrice 
Published: December 2017

Aims: The aim of this study was to evaluate the outcomes of Cool and Clean, Switzerland’s largest substance use prevention programme, targeted specifically at 10- to 20-year-olds who belong to a sports club and train as part of a team. Method: Based on a representative sample of young people who belong to a sports club and train as part of a team (both participants and non-participants in ‘cool and clean’), a post-test–only static group comparison was used to analyse data on 1,887 individuals from 179 teams (mean age: 13.8; 33.5% girls). Outcome variables included sports-related aspects (achievement motivation, fair play); attitudes towards tobacco, cannabis and alcohol use, and doping; and substance use (tobacco, cannabis and alcohol use). Results: Cool and Clean participants self-reported beneficial effects of the programme in all outcome areas. They also had a more critical attitude towards doping and substance use in general and had a lower reported frequency of cannabis use than non-participants. We found no significant group differences in terms of sports-related variables, tobacco and alcohol use. However, in each of these areas, better outcomes were found among Cool and Clean participants who trained with teams that implemented the programme more comprehensively. Conclusions: There is cross-sectional evidence for the effectiveness of the Cool and Clean programme. Moreover, the level of impact of the programme depends not only on participation per se but also, and more decisively, on how comprehensively the programme is implemented.
PPD and Flu Vaccine: Don't Get Stuck with this Mix-Up; FDA and the Pharmaceutical Industry must be More Responsive for a Safer Health Care System
Authors: Cohen Michael R. 
Published: December 2017

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them in your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the USP Medication Errors Reporting Program (MERP), which is presented in cooperation with the Institute for Safe Medication Practices. If you have encountered medication errors and would like to report them, you may call USP toll-free, 24 hours a day, at 800-233-7767 (800-23-ERROR). Any reports published by ISMP will be anonymous. Comments are also invited; the writers’ names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported through the ISMP ( www.ismp.org ) or USP ( www.usp.org ) web sites or communicated directly to ISMP by calling 1-800-FAIL SAFE or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters’ wishes as to the level of detail included in publications.
Collaboratively Designed Practice Guidelines Promote Appropriate Use of Intravenous Proton Pump Inhibitors
Authors: Skledar Susan J. , Culley Colleen M. 
Published: December 2017

Objective To determine the effectiveness of practice guidelines for proton pump inhibitor use at an academic medical center. Methods Patients initiated on intravenous (IV) pantoprazole therapy between July 2001 and May 2002 were evaluated prospectively for appropriateness of therapy. Pharmacists assessed clinical use, dosing strategy, administration route, and prescribing patterns. Results A total of 85 patients were evaluated. Only 25% of the patients were prescribed IV pantoprazole according to established institutional guidelines. The majority of therapy meeting guideline criteria were initiated on pantoprazole by the Gastroenterology service. Due to overuse of pantoprazole, prescribing guidelines were revised to specify indications with proven efficacy (erosive GERD, Zollinger-Ellison or other hypersecretory conditions, and upper gastrointestinal bleeding). Patients who received pantoprazole for stress ulcer prophylaxis, an unapproved indication, had therapy automatically switched to a histamine receptor antagonist. For patients who tolerated oral medications or enteral feedings, therapy was automatically converted to the oral dosage form. Conclusions Evaluation of institutional pantoprazole utilization revealed usage extending beyond indications with proven efficacy. Pharmacists and physicians collaboratively developed evidence-based practice guidelines; adherence to appropriate indications showed a 50% improvement.