bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ectomycorrhizal fungi and soil enzymes exhibit contrasting patterns along elevation gradients in southern Patagonia
Authors: Truong Camille , Gabbarini Luciano A. , Corrales Adriana , Mujic Alija B. , Escobar Julio M. , Moretto Alicia , Smith Matthew E. 
Published: January 2019

Summary

The biological and functional diversity of ectomycorrhizal (ECM) associations remain largely unknown in South America. In Patagonia, the ECM tree Nothofagus pumilio forms monospecific forests along mountain slopes without confounding effects of vegetation on plant–fungi interactions.

To determine how fungal diversity and function are linked to elevation, we characterized fungal communities, edaphic variables, and eight extracellular enzyme activities along six elevation transects in Tierra del Fuego (Argentina and Chile). We also tested whether pairing ITS1 rDNA Illumina sequences generated taxonomic biases related to sequence length.

Fungal community shifts across elevations were mediated primarily by soil pH with the most species‐rich fungal families occurring mostly within a narrow pH range. By contrast, enzyme activities were minimally influenced by elevation but correlated with soil factors, especially total soil carbon. The activity of leucine aminopeptidase was positively correlated with ECM fungal richness and abundance, and acid phosphatase was correlated with nonECM fungal abundance. Several fungal lineages were undetected when using exclusively paired or unpaired forward ITS1 sequences, and these taxonomic biases need reconsideration for future studies.

Our results suggest that soil fungi in N. pumilio forests are functionally similar across elevations and that these diverse communities help to maintain nutrient mobilization across the elevation gradient.
Oral ribavirin for paramyxovirus infection after alemtuzumab‐containing reduced‐intensity conditioning HCT regimen
Authors: Dreyzin Alexandra , Michaels Marian G. , Vander Lugt Mark T. , Szabolcs Paul 
Published: January 2019

AbstractAerosolized ribavirin has been used in pediatric immunocompromised patients to treat acute respiratory viral infections, but oral ribavirin may be a less expensive alternative that allows for outpatient therapy. Oral ribavirin has compared favorably to aerosolized ribavirin in adult studies, but data on safety are lacking in pediatric populations. Four cases are described in which oral ribavirin was used to treat viral respiratory infections in recipients of allogeneic hematopoietic stem cell transplants at a Children's Hospital, demonstrating safety and feasibility.
NLOphoric Triphenylamine Derived Donor‐π‐Acceptor‐π‐Donor Based Colorants: Synthesis, Spectroscopic, Density Functional Theory and Z‐scan Studies
Authors: Raikwar Manish M. , Mathew Elizabeth , Varghese Manu , Joe Issac H. , Nethi Sekar Nagaiyan 
Published: January 2019

AbstractThree Donor‐π‐Acceptor‐π‐Donor type styryl dyes (5a‐c) with different secondary donors are synthesized and characterized to study their nonlinear and linear optical properties. The structure–property relationships of the dyes are described in the light of systematic photophysical and theoretical investigations. The photophysical characteristics of 5a‐c are influenced by the polarity of the medium, with an appreciable bathochromic shift in emission (5b = 81 nm) and large Stoke shifts (5b = 104–173 nm) in polar solvents. 5a‐c showed intramolecular charge transfer characteristics recognized with the help of emission solvatochromism, solvent polarity graphs, natural bond orbital analysis and HOMO–LUMO energy difference. The optimized geometry and frontier molecular orbitals reveal that the electron donation takes place from secondary donors and not from a fixed donor (triphenylamine) which is more twisted. The nonlinear optical properties obtained using solvent induced spectral shift and computational methods are found within the limiting values. Z‐scan results reveal saturable kind of behavior for 5a, 5b and 5c, whereas 5a and 5b show reverse saturable kind of behavior in acetone and ethanol and hence give optical limiting values. The two‐photon absorption cross section described by two‐level approximation is highest for 5b (251–300 GM).
Photoaging and actinic keratosis in Danish outdoor and indoor workers
Authors: Grandahl Kasper , Olsen Jonas , Friis Kersti Brosbøl Engelund , Mortensen Ole Steen , Ibler Kristina Sophie 
Published: January 2019

AbstractBackgroundThe risk of photoaging and actinic keratosis caused by work related solar ultraviolet radiation exposure has not previously been investigated in Nordic countries. The objectives of this study were to describe the occurrence of photoaging, actinic keratosis, and keratinocyte cancer in a population of Danish outdoor and indoor workers, and investigate the association between these clinical findings and semi‐objective measures of work related solar ultraviolet radiation exposure in the same population.MethodsA clinical cross‐sectional study of the occurrence of facial wrinkles, actinic keratosis, keratinocyte cancer, and melanocytic nevi in a population of Danish outdoor and indoor workers and associations with semi‐objective measures of work related solar ultraviolet radiation exposure based on a combination of dosimetry and self‐report.ResultsWork related solar ultraviolet radiation exposure was significantly positively associated with occurrence of facial wrinkles (α = 0.05). Actinic keratosis was associated to status as outdoor worker (OR = 4.272, CI [1.045‐17.471]) and age (P < 0.001, CI [1.077‐1.262]) and twice as common in outdoor workers (10.3% CI [0.05, 0.15]) compared to indoor workers (5.1% CI [0.00, 0.10]). Only two cases of keratinocyte cancer were diagnosed (<1%). Older age was negatively associated with occurrence of melanocytic nevi.ConclusionOutdoor work in Denmark is associated with increased occurrence of facial wrinkles and actinic keratosis from solar ultraviolet radiation exposure, thus justifying sun safety at Danish workplaces from a clinical perspective.
On the Psychological Function of Nationalistic “Whitelash”
Authors: Sengupta Nikhil K. , Osborne Danny , Sibley Chris G. 
Published: January 2019

A noticeable feature of the political discourse accompanying the rise of nationalism in white‐majority countries is that white people fare worse than other ethnic groups in their societies. However, it is unclear based on the extant literature why group‐based relative deprivation (GRD) would correlate with majority‐group nationalism. Here, we propose that the psychological function of nationalism for majority‐group members lies in its ability to assuage the negative feelings arising from GRD. Accordingly, in a New Zealand national probability sample (N = 15,607), we found that GRD among whites was negatively associated with well‐being. However, we also found anopposingindirect association mediated by nationalism. GRD was associated with higher nationalism, which was in turn associated with higher well‐being. These findings suggest that endorsing beliefs about national superiority is one way a nation’s dominant ethnic group can cope with the negative psychological consequences of perceiving that their group is deprived.
Do cultural orientations moderate the relation between Chinese adolescents’ shyness and depressive symptoms? It depends on their academic achievement
Authors: An Danming , Eggum‐Wilkens Natalie D. 
Published: January 2019

AbstractWe examined the moderating roles of individualistic and collectivistic cultural orientations and academic achievement on the relation between Chinese adolescents’ shyness and depressive symptoms. A sample of Chinese adolescents (N = 492) from an urban school participated in the study during seventh (T1) and eighth (T2) grades. Adolescents self‐reported their shyness, cultural orientations, and depressive symptoms. The school provided records of their academic achievement. Concurrently, shyness and individualism were positively whereas collectivism and academic achievement were negatively, associated with adolescents’ depressive symptoms. Longitudinally, T1 shyness (but not individualism, collectivism, or academic achievement) predicted T2 depressive symptoms after controlling for stability in depressive symptoms. Concurrent relations between shyness and depressive symptoms were moderated by adolescents’ cultural orientations. Specifically, collectivism was protective whereas individualism was harmful, for shy adolescents’ adjustment. Furthermore, collectivism and academic achievement jointly moderated the relations between shyness and depressive symptoms concurrently and longitudinally. The results suggest that cultural orientations may influence shy adolescents’ depression symptoms through individual‐level self‐evaluation, and indicate that cultural factors and academic achievement need to be considered comprehensively for understanding and improving shy Chinese adolescents’ psychological adjustment.
Repeated anodal trans‐spinal direct current stimulation results in long‐term reduction of spasticity in mice with spinal cord injury
Authors: Mekhael Wagdy , Begum Sultana , Samaddar Sreyashi , Hassan Mazen , Toruno Pedro , Ahmed Malik , Gorin Alexis , Maisano Michael , Ayad Mark , Ahmed Zaghloul 
Published: January 2019

Key points
Spasticity is a disorder of muscle tone that is associated with lesions of the motor system. This condition involves an overactive spinal reflex loop that resists the passive lengthening of muscles.
Previously, we established that application of anodal trans‐spinal direct current stimulation (a‐tsDCS) for short periods of time to anaesthetized mice sustaining a spinal cord injury leads to an instantaneous reduction of spasticity. However, the long‐term effects of repeated a‐tsDCS and its mechanism of action remained unknown.
In the present study, a‐tsDCS was performed for 7 days and this was found to cause long‐term reduction in spasticity, increased rate‐dependent depression in spinal reflexes, and improved ground and skill locomotion.
Pharmacological, molecular and cellular evidence further suggest that a novel mechanism involving Na‐K‐Cl cotransporter isoform 1 mediates the observed long‐term effects of repeated a‐tsDCS.
AbstractSpasticity can cause pain, fatigue and sleep disturbances; restrict daily activities such as walking, sitting and bathing; and complicate rehabilitation efforts. Thus, spasticity negatively influences an individual's quality of life and novel therapeutic interventions are needed. We previously demonstrated in anaesthetized mice that a short period of trans‐spinal subthreshold direct current stimulation (tsDCS) reduces spasticity. In the present study, the long‐term effects of repeated tsDCS to attenuate abnormal muscle tone in awake female mice with spinal cord injuries were investigated. A motorized system was used to test velocity‐dependent ankle resistance and associated electromyographical activity. Analysis of ground and skill locomotion was also performed, with electrophysiological, molecular and cellular studies being conducted to reveal a potential underlying mechanism of action. A 4 week reduction in spasticity was associated with an increase in rate‐dependent depression of spinal reflexes, and ground and skill locomotion were improved following 7 days of anodal‐tsDCS (a‐tsDCS). Secondary molecular, cellular and pharmacological experiments further demonstrated that the expression of K‐Cl co‐transporter isoform 2 (KCC2) was not changed in animals with spasticity. However, Na‐K‐Cl cotransporter isoform 1 (NKCC1) was significantly up‐regulated in mice that exhibited spasticity. When mice were treated with a‐tsDCS, down regulation of NKCC1 was detected, and this level did not significantly differ from that in the non‐injured control mice. Thus, long lasting reduction of spasticity by a‐tsDCS via downregulation of NKCC1 may constitute a novel therapy for spasticity following spinal cord injury.
Effect of Recommendations on Serving Content with Unknown Demand
Authors: Gupta Samarth , Moharir Sharayu 
Published: January 2019

We consider the task of content replication in distributed content delivery systems used by Video-on-Demand (VoD) services with large content catalogs. The prior work in this area focuses on the setting where each request is generated independent of all past requests. Motivated by the fact that most popular VoD services offer recommendations to users based on their viewing history, in a departure from existing studies, we study the setting with time-correlation in requests coming from each user.
We use a Markovian process to model each user’s request process. In addition to introducing time-correlation in user requests, our model is consistent with empirically observed properties of the request process for VoD services with recommendation engines. In the setting where the underlying Markov Chain is unknown and has to be learned from the very requests the system is trying to serve, we show that separating the task of estimating content popularity and using the estimates to design a static content replication policy is strictly sub-optimal. To prove this, we show that an adaptive policy, which jointly performs the task of estimation and content replication, outperforms all policies that separate the task of estimation and content replication.
Local Delivery ofOx40l,Cd80, andCd86mRNA Kindles Global Anticancer Immunity
Authors: Haabeth Ole Audun Werner , Blake Timothy R. , McKinlay Colin J. , Tveita Anders A. , Sallets Adrienne , Waymouth Robert M. , Wender Paul A. , Levy Ronald 
Published: January 2019

AbstractLocalized expression of effector molecules can initiate antitumor responses through engagement of specific receptors on target cells in the tumor microenvironment. These locally induced responses may also have a systemic effect, clearing additional tumors throughout the body. In this study, to evoke systemic antitumor responses, we utilized charge-altering releasable transporters (CART) for local intratumoral delivery of mRNA coding for costimulatory and immune-modulating factors. Intratumoral injection of the CART–mRNA complexes resulted in mRNA expression at the site of administration, transfecting a substantial proportion of tumor-infiltrating dendritic cells, macrophages, and T cells in addition to the tumor cells, resulting in a local antitumor effect. Using a two-tumor model, we further show that mRNA therapy locally administered to one tumor stimulated a systemic antitumor response, curing both tumors. The combination of Ox40l-, Cd80-, and Cd86-encoding mRNA resulted in the local upregulation of proinflammatory cytokines, robust local T-cell activation, and migration of immune cells to local draining lymph node or to an anatomically distant tumor. This approach delayed tumor growth, facilitated tumor regression, and cured tumors in both A20 and CT26 tumor models. These results highlight mRNA-CART therapy as a viable approach to induce systemic antitumor immunity from a single localized injection.Significance:The mRNA-CART system is a highly effective delivery platform for delivering immunostimulatory genes into the tumor microenvironment for potential therapeutic development.
A Pragmatic Testing-Eligibility Framework for Population Mutation Screening: The Example of BRCA1/2
Authors: Best Ana F. , Tucker Margaret A. , Frone Megan N. , Greene Mark H. , Peters June A. , Katki Hormuzd A. 
Published: January 2019

Abstract

Background:
Eligibility guidelines for genetic testing may be revisited, given technological advances, plummeting costs, and proposals for population mutation screening. A key property of eligibility criteria is the tradeoff between the number of mutation carriers identified versus population members tested. We assess the fractions of mutation carriers identified, versus women undergoing mutation testing, for BRCA1/2 founder mutation screening in U.S. Ashkenazi-Jewish women.

Methods:
BRCA1/2 carrier probabilities, based on personal/family history, were calculated using the risk-prediction tool BRCAPRO for 4,589 volunteers (102 mutation carriers) in the population-based Washington Ashkenazi Study. For each carrier-probability threshold between 0% and 10%, we compared the percentage of founder mutations detected versus the percentage of women requiring mutation testing. PCR mutation testing was conducted at the NIH for the 3 Ashkenazi-Jewish founder mutations (5382insC and 185delAG in BRCA1, and 6174delT in BRCA2).

Results:
Identifying 90% of BRCA1/2 founder mutations required testing the 60% of Ashkenazi-Jewish women with carrier probabilities exceeding 0.56%, potentially avoiding mutation testing for approximately 0.7 to 1.1 million U.S. Ashkenazi-Jewish women. Alternatively, testing the 44% whose carrier probability exceeded 0.78% identified 80% of mutation carriers, increasing to 89% of mutation carriers when accounting for cascade testing triggered after mutation-positive daughters were identified by screening. We present data on all carrier-probability thresholds, e.g., a 5% threshold identified 46% of mutation carriers while testing 10% of women.

Conclusions:
Different carrier-probability thresholds offered diverse tradeoffs between numbers of identified mutation carriers versus women tested. Low carrier-probability thresholds identified 90% of BRCA1/2 founder mutation carriers, without testing approximately 1 million U.S. Ashkenazi-Jewish women with lowest carrier probabilities.

Impact:
In general, this risk-based framework could provide useful new options to consider during eligibility-criteria development for population mutation screening.
The Mechanism of Action of the Anti-CD38 Monoclonal Antibody Isatuximab in Multiple Myeloma
Authors: Moreno Laura , Perez Cristina , Zabaleta Aintzane , Manrique Irene , Alignani Diego , Ajona Daniel , Blanco Laura , Lasa Marta , Maiso Patricia , Rodriguez Idoia , Garate Sonia , Jelinek Tomas , Segura Victor , Moreno Cristina , Merino Juana , Rodriguez-Otero Paula , Panizo Carlos , Prosper Felipe , San-Miguel Jesus F. , Paiva Bruno 
Published: January 2019

AbstractPurpose:Knowledge about the mechanism of action (MoA) of monoclonal antibodies (mAb) is required to understand which patients with multiple myeloma (MM) benefit the most from a given mAb, alone or in combination therapy. Although there is considerable research about daratumumab, knowledge about other anti-CD38 mAbs remains scarce.Experimental Design:We performed a comprehensive analysis of the MoA of isatuximab.Results:Isatuximab induces internalization of CD38 but not its significant release from MM cell surface. In addition, we uncovered an association between levels of CD38 expression and different MoA: (i) Isatuximab was unable to induce direct apoptosis on MM cells with CD38 levels closer to those in patients with MM, (ii) isatuximab sensitized CD38hi MM cells to bortezomib plus dexamethasone in the presence of stroma, (iii) antibody-dependent cellular cytotoxicity (ADCC) was triggered by CD38lo and CD38hi tumor plasma cells (PC), (iv) antibody-dependent cellular phagocytosis (ADCP) was triggered only by CD38hi MM cells, whereas (v) complement-dependent cytotoxicity could be triggered in less than half of the patient samples (those with elevated levels of CD38). Furthermore, we showed that isatuximab depletes CD38hi B-lymphocyte precursors and natural killer (NK) lymphocytes ex vivo—the latter through activation followed by exhaustion and eventually phagocytosis.Conclusions:This study provides a framework to understand response determinants in patients treated with isatuximab based on the number of MoA triggered by CD38 levels of expression, and for the design of effective combinations aimed at capitalizing disrupted tumor–stroma cell protection, augmenting NK lymphocyte–mediated ADCC, or facilitating ADCP in CD38lo MM patients.See related commentary by Malavasi and Faini, p. 2946
FDA Approval Summary: Ivosidenib for Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation
Authors: Norsworthy Kelly J. , Luo Lola , Hsu Vicky , Gudi Ramadevi , Dorff Sarah E. , Przepiorka Donna , Deisseroth Albert , Shen Yuan-Li , Sheth Christopher M. , Charlab Rosane , Williams Gene M. , Goldberg Kirsten B. , Farrell Ann T. , Pazdur Richard 
Published: January 2019

Abstract
The FDA approved ivosidenib (Tibsovo; Agios), a small-molecule inhibitor of isocitrate dehydrogenase (IDH)1 on July 20, 2018, for treatment of adults with relapsed or refractory acute myeloid leukemia (R/R AML) with susceptible IDH1 mutation as detected by an FDA-approved test. The efficacy of ivosidenib was established on the basis of complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR + CRh, and conversion from transfusion dependence (TD) to transfusion independence (TI) in Study AG120-C-001, a single-arm trial. With median follow-up of 8.3 months for 174 adults with IDH1-mutated R/R AML treated with 500 mg ivosidenib daily, the CR + CRh rate was 33% [95% confidence interval (CI), 26–40], median duration of response was 8.2 (95% CI, 5.6–12) months, and conversion from TD to TI occurred in 37% of patients. These endpoints reflect short-term benefit in patients with an unmet medical need; long-term efficacy outcomes were not assessed. Serious adverse reactions (AR) in ≥5% of patients were differentiation syndrome (10%), leukocytosis (10%), and QT interval prolongation (7%). Common (≥20%) ARs of any grade were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, QT interval prolongation, rash, pyrexia, cough, and constipation. Assessment of long-term safety of ivosidenib is a condition of this approval.
ИСПОЛЬЗОВАНИЕ ЗАЩИТНЫХ НЕЙРОФИЗИОЛОГИЧЕСКИХ РЕАКЦИЙ ГОЛОВНОГО МОЗГА ПРИ ФОРМИРОВАНИИ ПРЕВЕНТИВНОЙ «ИШЕМИЧЕСКОЙ ТОЛЕРАНТНОСТИ» (ПРЕ- И ПОСТКОНДИЦИОНИРОВАНИЕ) В ЦЕЛЯХ ЛЕЧЕНИЯ И РЕАБИЛИТАЦИИ БОЛЬНЫХ С ПОСТИНСУЛЬТНЫМИ ПСИХОПАТОЛОГИЧЕСКИМИ РАССТРОЙСТВАМИ
Authors: Shevchenko-Bitenskyi K. V. , Bitenskyy V. S. 
Published: January 2019

По данным ВОЗ, от инсульта ежегодно страдают более 1 млн человек. Чаще всего встречаются ишемические инсульты (87 %), реже – геморрагические (10 %) или инсульты с кровоизлияниями в субарахно­идальное пространство (3 %).
Феномен «ишемической толерантности» был введен K. Kitagawa в 1990 г. при описании защитного эффекта малых доз церебральных гипертермий (+35 ºС) от действия значительно более выраженных раздражителей. Впервые подобный эффект был предсказан С. П. Боткиным (1867), применен при гипоксии миокарда C. M. Murry et al. в 1986 г.; он получил название «пре- и посткондиционирование».
Цель – исследовать терапевтическую эффективность применения так называемой «ишемической толерантности» у 48 больных с различной психопатологической симптоматикой, возникающей после перенесенного инсульта.
Материал и методы. Было проведено исследование 48 больных мужчин с постинсультными психическими расстройствами в виде различной психопатологической симптоматики.
Выводы. Применение слабой краниоцеребральной гипо- и гипертермии (35 ºС–37,5 ºС) создавало в ткани мозга эффект «ишемической толерантности» и, вместе с ингаляцией ксенона и введением нейропротекторов церебролизина (10,0 мг) и вальпроата (400–800 мг), привело к практическому исчезновению постинсультной психопатологической симптоматики.