bluuebunny/crossref_metadata_2025 huggingface dataset:
The Call of the Wild: Rethinking Food Production in Ancient Amazonia
Authors: Neves Eduardo G. , Heckenberger Michael J.
Published: August 2019

The Amazon basin is accepted as an independent center of plant domestication in the world. A variety of important plants were domesticated in the Amazon and its surroundings; however, the majority of plants cultivated today in the Amazon are not domesticated, if this descriptor is understood to convey substantial genetic and phenotypic divergence from wild varieties or species. Rather, many domesticates are trees and tubers that occupy an intermediate stage between wild and domesticated, which seems to be a prevailing pattern since at least the middle Holocene, 6,000 years ago. Likewise, basin-wide inventories of trees show a remarkable pattern where a few species, called hyperdominant, are overrepresented in the record, including many varieties that are economically and symbolically important to traditional societies. Cultivation practices among indigenous groups in the Amazon are embedded in other dimensions of meaning that go beyond subsistence, and such entanglement between nature and culture has long been noticed at the conceptual level by anthropologists. This principle manifests itself in ancient and dynamic practices of landscape construction and transformation, which are seriously threatened today by the risks posed by economic development and climate change to Amazonian traditional societies and biomes.
Evidentiality
Authors: San Roque Lila
Published: August 2019

Human societies show a deep concern with how people know things and how relationships to knowledge are constructed and portrayed in talk. The term evidentiality refers to particular linguistic resources for talking about knowledge and especially to grammaticalized markers that indicate knowledge sources. Evidential marking is found in diverse languages around the world. This review discusses cross-linguistic evidential meanings and examines research on evidentials in practice, with a focus on their interpretation as stance markers and deictic elements. Evidentiality is a fascinating accomplishment in language structure, meaning, and use and can tell us about shared and disparate visions of knowledge and sociality across cultures.
Neutrino Emission as Diagnostics of Core-Collapse Supernovae
Authors: Müller B.
Published: August 2019

With myriads of detection events from a prospective Galactic core-collapse supernova, current and future neutrino detectors will be able to sample detailed, time-dependent neutrino fluxes and spectra. This will offer significant possibilities of inferring supernova physics from the various phases of the neutrino signal, ranging from the neutronization burst through the accretion and early explosion phases to the cooling phase. The signal will constrain the time evolution of bulk parameters of the young proto–neutron star, such as its mass and radius, as well as the structure of the progenitor; probe multidimensional phenomena in the supernova core; and constrain the dynamics of the early explosion phase. Aside from further astrophysical implications, supernova neutrinos may also shed light on the properties of matter at supranuclear densities and on open problems in particle physics.
Determination of the Proton's Weak Charge and Its Constraints on the Standard Model
Authors: Carlini Roger D. , van Oers Willem T.H. , Pitt Mark L. , Smith Gregory R.
Published: August 2019

This article discusses some of the history of parity-violation experiments that culminated in the Qweak experiment, which provided the first determination of the proton's weak charge [Formula: see text]. The guiding principles necessary to the success of that experiment are outlined, followed by a brief description of the Qweak experiment. Several consistent methods used to determine [Formula: see text] from the asymmetry measured in the Qweak experiment are explained in detail. The weak mixing angle sin2θw determined from [Formula: see text] is compared with results from other experiments. A description of the procedure for using the [Formula: see text] result on the proton to set TeV-scale limits for new parity-violating semileptonic physics beyond the Standard Model (BSM) is presented. By also considering atomic parity-violation results on cesium, the article shows how this result can be generalized to set limits on BSM physics, which couples to any combination of valence quark flavors. Finally, the discovery space available to future weak-charge measurements is explored.
Future Circular Colliders
Authors: Benedikt M. , Blondel A. , Janot P. , Klein M. , Mangano M. , McCullough M. , Mertens V. , Oide K. , Riegler W. , Schulte D. , Zimmermann F.
Published: August 2019

After 10 years of physics at the Large Hadron Collider (LHC), the particle physics landscape has greatly evolved. Today, a staged Future Circular Collider (FCC), consisting of a luminosity-frontier highest-energy electron–positron collider (FCC-ee) followed by an energy-frontier hadron collider (FCC-hh), promises the most far-reaching physics program for the post-LHC era. FCC-ee will be a precision instrument used to study the Z, W, Higgs, and top particles, and will offer unprecedented sensitivity to signs of new physics. Most of the FCC-ee infrastructure could be reused for FCC-hh, which will provide proton–proton collisions at a center-of-mass energy of 100 TeV and could directly produce new particles with masses of up to several tens of TeV. This collider will also measure the Higgs self-coupling and explore the dynamics of electroweak symmetry breaking. Thermal dark matter candidates will be either discovered or conclusively ruled out by FCC-hh. Heavy-ion and electron–proton collisions (FCC-eh) will further contribute to the breadth of the overall FCC program. The integrated FCC infrastructure will serve the particle physics community through the end of the twenty-first century. This review combines key contents from the first three volumes of the FCC Conceptual Design Report.
Open Heavy-Flavor Production in Heavy-Ion Collisions
Authors: Dong Xin , Lee Yen-Jie , Rapp Ralf
Published: August 2019

The ultrarelativistic heavy-ion programs at the Relativistic Heavy Ion Collider and the Large Hadron Collider have entered an era of quantitative analysis of quantum chromodynamics (QCD) at high temperatures. The remarkable discovery of the strongly coupled quark–gluon plasma (sQGP), as deduced from its hydrodynamic behavior at long wavelengths, calls for probes that can reveal its inner workings. Charm- and bottom-hadron spectra offer unique insights into the transport properties and the microscopic structure of the QCD medium created in these collisions. At low momentum the Brownian motion of heavy quarks in the sQGP gives access to their diffusion constant, at intermediate momentum these quarks give insight into hadronization mechanisms, and at high momentum they are expected to merge into a radiative-energy loss regime. We review recent experimental and theoretical achievements on measuring a variety of heavy-flavor observables, characterizing the different regimes in momentum and extracting pertinent transport coefficients to unravel the structure of the sQGP and its hadronization.
The Role of the Microbiome in Drug Response
Authors: Pryor Rosina , Martinez-Martinez Daniel , Quintaneiro Leonor , Cabreiro Filipe
Published: August 2019

The microbiome is known to regulate many aspects of host health and disease and is increasingly being recognized as a key mediator of drug action. However, investigating the complex multidirectional relationships between drugs, the microbiota, and the host is a challenging endeavor, and the biological mechanisms that underpin these interactions are often not well understood. In this review, we outline the current evidence that supports a role for the microbiota as a contributor to both the therapeutic benefits and side effects of drugs, with a particular focus on those used to treat mental disorders, type 2 diabetes, and cancer. We also provide a snapshot of the experimental and computational tools that are currently available for the dissection of drug–microbiota–host interactions. The advancement of knowledge in this area may ultimately pave the way for the development of novel microbiota-based strategies that can be used to improve treatment outcomes.
A single day of high-fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice
Authors: Kuipers Eline N. , Held Ntsiki M. , in het Panhuis Wietse , Modder Melanie , Ruppert Philip M. M. , Kersten Sander , Kooijman Sander , Guigas Bruno , Houtkooper Riekelt H. , Rensen Patrick C. N. , Boon Mariëtte R.
Published: August 2019

Brown adipose tissue (BAT) catabolizes glucose and fatty acids to produce heat and thereby contributes to energy expenditure. Long-term high-fat diet (HFD) feeding results in so-called ‘whitening’ of BAT characterized by increased lipid deposition, mitochondrial dysfunction, and reduced fat oxidation. The aim of the current study was to unravel the rate and related mechanisms by which HFD induces BAT whitening and insulin resistance. Wild-type mice were fed a HFD for 0, 1, 3, or 7 days. Within 1 day of HFD, BAT weight and lipid content were increased. HFD also immediately reduced insulin-stimulated glucose uptake by BAT, indicating rapid induction of insulin resistance. This was accompanied by a tendency toward a reduced uptake of triglyceride-derived fatty acids by BAT. Mitochondrial mass and Ucp1 expression were unaltered, whereas after 3 days of HFD, markers of mitochondrial dynamics suggested induction of a more fused mitochondrial network. Additionally, HFD also increased macrophage markers in BAT after 3 days of HFD. Counterintuitively, the switch to HFD was accompanied by an acute rise in core body temperature. We showed that a single day of HFD feeding is sufficient to induce the first signs of whitening and insulin resistance in BAT, which reduces the uptake of glucose and triglyceride-derived fatty acids. BAT whitening and insulin resistance are likely sustained by reduced mitochondrial oxidation due to changes in mitochondrial dynamics and macrophage infiltration, respectively. Likely, the switch to HFD swiftly induces thermogenesis in other metabolic organs, which allows attenuation of BAT thermogenesis.
Time Domain Electromagnetic Transient Analysis of Aerial Nonuniform Transmission Lines Excited by an Incident Electromagnetic Field
Authors: Sánchez-Alegría Avisaí , Moreno Pablo , Loo-Yau José R. , Ortega-Cisneros Susana
Published: August 2019

In this paper a model for Nonuniform Transmission Lines for electromagnetic transient analysis that incorporates frequency dependency of electrical parameters, variation of line electrical parameters with respect to distance, and distributed excitations due to incident electromagnetic fields is presented. The model is developed using the Method of Characteristics in the actual physical domain instead of the Modal Domain; this simplifies the mathematical development and the final equations. Moreover, the equations of the resultant model are valid either for two‐conductor lines or for multiconductor lines without any change; this can be an advantage when the computer programming language considers a scalar as a 1x1 matrix. The proposed numerical model is developed under the hypothesis that the dielectric surrounding the conductors is homogenous. It is shown that in this case the characteristic curves of a Nonuniform Transmission Line become straight lines. Finally, the model is validated by comparison with results obtained using the Numerical Laplace Transform method.
Low-RCS, Circular Polarization, and High-Gain Broadband Antenna Based on Mirror Polarization Conversion Metasurfaces
Authors: Zhang Liang , Liu Changqing , Ni Chun , Kong Meng , Wu Xianliang
Published: August 2019

In this paper, a novel slot antenna array that is based on mirror polarization conversion metasurfaces (MPCM) is proposed. It achieves circular polarization (CP) and effectively reduces the radar cross section (RCS) and increases gain in the entire x-band. This design uses the mirrored composition of the polarization conversion metasurfaces (PCM) on the top surface of the substrate. The MPCM covers a 2 × 2 slot antenna array that is fed with by a sequentially rotating network. The CP radiation is realized by the polarization conversion characteristics of the PCM. At the same time, the reduction of RCS is achieved by 180° (±30°) reflection phase difference between two adjacent PCMs. The improvement in gain is achieved by using a Fabry–Perot cavity, which is constituted by the ground of the antenna and the PCM. Simulated and measured results show that approximately 46.4% of the operating bandwidth is in the range of 7.5–12 GHz (AR < 3 dB) and the gain of the antenna with MPCM is at least 5 dB higher than the reference antenna. Moreover, the monostatic RCS is reduced from 8 to 20 GHz.
Dynamic Property Investigation of Sandwich Acoustic Black Hole Beam with Clamped‐Free Boundary Condition
Authors: Du Xiaofei , Huang Dacheng , Zhang Jianrun
Published: August 2019

The geometric parameters of the acoustic black hole (ABH) structure are changed in power exponent, and this feature can be used to control the flexural wave to achieve energy concentration, vibration attenuation, or noise reduction. However, in practice, the ABH structure often has a truncation due to the limitation of manufacturing, which will cause the reflection coefficient to increase significantly and seriously affect the ABH effect. In this paper, a semianalytical model of the sandwich‐truncated ABH beam structure with aluminum in the middle layer and steel in the upper and lower layers is constructed based on the energy principle. The ABH effect of the sandwich beam under the clamped‐free boundary condition is analyzed. Meanwhile, the effects of damping layer parameters, middle layer material, and thickness on the vibrational acceleration response of the ABH region and the uniform beam region of the sandwich beam are also studied. It is observed that, for the sandwich ABH beam structure, the influence of damping layer thickness on the acceleration response peak values of both the ABH region and the uniform region is very obvious in middle and high frequencies and the peaks at about 9 kHz are completely suppressed when the damping layer thickness reaches 3 mm. It also reveals that the use of aluminum as the middle layer material can bring a vibration attenuation at around 9 kHz both for the ABH region and the uniform beam region compared with using steel as the middle layer material. Experiments are carried out to verify the accuracy of simulation analysis.
Dynamic Study of a Predator-Prey Model with Weak Allee Effect and Delay
Authors: Ye Yong , Liu Hua , Wei Yu-mei , Ma Ming , Zhang Kai
Published: August 2019

In this paper, a prey-predator model and weak Allee effect in prey growth and its dynamical behaviors are studied in detail. The existence, boundedness, and stability of the equilibria of the model are qualitatively discussed. Bifurcation analysis is also taken into account. After incorporating the searching delay and digestion delay, we establish a delayed predator-prey system with Allee effect. The results show that there exist stability switches and Hopf bifurcation occurs while the delay crosses a set of critical values. Finally, we present some numerical simulations to illustrate our theoretical analysis.
First-Time Mothers Have a Desire to Be Offered Professional Breastfeeding Support by Pediatric Nurses: An Evaluation of the Mother-Perceived-Professional Support Scale
Authors: Ranch Matilda Möller , Jämtén Sofia , Thorstensson Stina , Ekström-Bergström Anette C.
Published: August 2019

Background. Although the World Health Organization recommends exclusive breastfeeding for six months, the rate of breastfeeding has decreased worldwide. Breastfeeding is the natural way of feeding a baby, but it is a process that has to be learnt. It is not unusual for problems to occur and hence support for breastfeeding is vital. The aim of this study was to explore first-time mothers’ experiences of the breastfeeding support offered by pediatric nurses, as well as to develop and evaluate the Mother Perceived Support from Professionals (MoPPS) scale. Methods. A qualitative design involving both inductive and deductive approaches was chosen. Nine first-time mothers were interviewed regarding their experiences of the breastfeeding support offered by pediatric nurses. Semistructured interviews were conducted. The mothers were also asked to grade their experiences of breastfeeding support on the MoPPS scale. A qualitative content analysis was applied when analyzing the data obtained using both the inductive (interviews) and deductive (MoPPS scale) approaches. Results. The results revealed that the mothers felt the desire to breastfeed, although they all experienced some difficulties. They wanted the pediatric nurses to be perceptive and provide professional support based on their own experiences. When the pediatric nurses took time and booked extra appointments, the mothers felt supported. The inductive analysis resulted in one theme: “When wanting to breastfeed, mothers have a desire to be offered professional breastfeeding support”. Two main categories were identified, namely “Mothers wanted but lacked breastfeeding support” and “Mothers received professional support.” The deductive analysis of the MoPPS scale showed similar results, and the questions were perceived as relevant to the aim. The mothers considered it important that the pediatric nurses had sufficient knowledge about breastfeeding. It was also considered important that the pediatric nurses involved the mothers’ partners in the breastfeeding support. Therefore, we suggest that these areas should be included in the MoPPS scale for pediatric nurses. Conclusions. The MoPPS scale can be a useful tool for helping pediatric nurses to offer mothers professional breastfeeding support. Indeed, when offering breastfeeding support, pediatric nurses can use the items included on the MoPPS scale as guidance.
Identification of Coding and Long Noncoding RNAs Differentially Expressed in Tumors and Preferentially Expressed in Healthy Tissues
Authors: Unfried Juan P. , Serrano Guillermo , Suárez Beatriz , Sangro Paloma , Ferretti Valeria , Prior Celia , Boix Loreto , Bruix Jordi , Sangro Bruno , Segura Víctor , Fortes Puri
Published: August 2019

The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets allow unprecedented gene expression analyses. Here, using these datasets, we performed pan-cancer and pan-tissue identification of coding and long noncoding RNA (lncRNA) transcripts differentially expressed in tumors and preferentially expressed in healthy tissues and/or tumors. Pan-cancer comparison of mRNAs and lncRNAs showed that lncRNAs were deregulated in a more tumor-specific manner. Given that lncRNAs are more tissue-specific than mRNAs, we identified healthy tissues that preferentially express lncRNAs upregulated in tumors and found that testis, brain, the digestive tract, and blood/spleen were the most prevalent. In addition, specific tumors also upregulate lncRNAs preferentially expressed in other tissues, generating a unique signature for each tumor type. Most tumors studied downregulated lncRNAs preferentially expressed in their tissue of origin, probably as a result of dedifferentiation. However, the same lncRNAs could be upregulated in other tumors, resulting in "bimorphic" transcripts. In hepatocellular carcinoma (HCC), the upregulated genes identified were expressed at higher levels in patients with worse prognosis. Some lncRNAs upregulated in HCC and preferentially expressed in healthy testis or brain were predicted to function as oncogenes and were significantly associated with higher tumor burden, and poor prognosis, suggesting their relevance in hepatocarcinogenesis and/or tumor evolution. Taken together, therapies targeting oncogenic lncRNAs should take into consideration the healthy tissue, where the lncRNAs are preferentially expressed, to predict and decrease unwanted secondary effects and increase potency.

Significance:

Comprehensive analysis of coding and noncoding genes expressed in different tumors and normal tissues, which should be taken into account to predict side effects from potential coding and noncoding gene-targeting therapies.
Cellular and Genetic Determinants of the Sensitivity of Cancer to α-Particle Irradiation
Authors: Yard Brian D. , Gopal Priyanka , Bannik Kristina , Siemeister Gerhard , Hagemann Urs B. , Abazeed Mohamed E.
Published: August 2019

Targeted α-particle–emitting radionuclides have great potential for the treatment of a broad range of cancers at different stages of progression. A platform that accurately measures cancer cellular sensitivity to α-particle irradiation could guide and accelerate clinical translation. Here, we performed high-content profiling of cellular survival following exposure to α-particles emitted from radium-223 (223Ra) using 28 genetically diverse human tumor cell lines. Significant variation in cellular sensitivity across tumor cells was observed. 223Ra was significantly more potent than sparsely ionizing irradiation, with a median relative biological effectiveness of 10.4 (IQR: 8.4–14.3). Cells that are the most resistant to γ radiation, such as Nrf2 gain-of-function mutant cells, were sensitive to α-particles. Combining these profiling results with genetic features, we identified several somatic copy-number alterations, gene mutations, and the basal expression of gene sets that correlated with radiation survival. Activating mutations in PIK3CA, a frequent event in cancer, decreased sensitivity to 223Ra. The identification of cellular and genetic determinants of sensitivity to 223Ra may guide the clinical incorporation of targeted α-particle emitters in the treatment of several cancer types.

Significance:

These findings address limitations in the preclinical guidance and prediction of radionuclide tumor sensitivity by identifying intrinsic cellular and genetic determinants of cancer cell survival following exposure to α-particle irradiation.

See related commentary by Sgouros, p. 5479
Synthetic Lethal Interactions for Kinase Deficiencies to DNA Damage Chemotherapeutics
Authors: Robinson-Garcia Lydia , Ferreira da Silva Joana , Loizou Joanna I.
Published: August 2019

Kinases are signaling enzymes that regulate diverse cellular processes. As such, they are frequently mutated in cancer and therefore represent important targets for drug discovery. However, until recently, systematic approaches to identify vulnerabilities and resistances of kinases to DNA-damaging chemotherapeutics have not been possible, partially due to the lack of appropriate technologies. With the advent of CRISPR-Cas9, a comprehensive study has investigated the cellular survival of more than 300 kinase-deficient isogenic cell lines to a diverse panel of DNA-damaging agents, enriched for chemotherapeutics. Here, we discuss how this approach has allowed for the rational development of combination therapies that are aimed at using synthetic lethal interactions between kinase deficiencies and DNA-damaging agents that are used as chemotherapeutics.
Financial Incentives to Promote Colorectal Cancer Screening: A Longitudinal Randomized Control Trial
Authors: Lieberman Alicea , Gneezy Ayelet , Berry Emily , Miller Stacie , Koch Mark , Ahn Chul , Balasubramanian Bijal A. , Argenbright Keith E. , Gupta Samir
Published: August 2019

Background:

Financial incentives may improve health behaviors. We tested the impact of offering financial incentives for mailed fecal immunochemical test (FIT) completion annually for 3 years.

Methods:

Patients, ages 50 to 64 years, not up-to-date with screening were randomized to receive either a mailed FIT outreach (n = 6,565), outreach plus $5 (n = 1,000), or $10 (n = 1,000) incentive for completion. Patients who completed the test were reinvited using the same incentive the following year, for 3 years. In year 4, patients who returned the kit in all preceding 3 years were reinvited without incentives. Primary outcome was FIT completion among patients offered any incentive versus outreach alone each year. Secondary outcomes were FIT completion for groups offered $5 versus outreach alone, $10 versus outreach alone, and $5 versus $10.

Results:

Year 1 FIT completion was 36.9% with incentives versus 36.2% outreach alone (P = 0.59) and was not statistically different for $10 (34.6%; P = 0.31) or $5 (39.2%; P = 0.070) versus outreach alone. Year 2 completion was 61.6% with incentives versus 60.8% outreach alone (P = 0.75) and not statistically different for $10 or $5 versus outreach alone. Year 3 completion was 79.4% with incentives versus 74.8% outreach alone (P = 0.080), and was higher for $10 (82.4%) versus outreach alone (P = 0.033), but not for $5 versus outreach alone. Completion was similar across conditions in year 4 (no incentives).

Conclusions:

Offering small incentives did not increase FIT completion relative to standard outreach.

Impact:

This was the first longitudinal study testing the impact of repeated financial incentives, and their withdrawal, on FIT completion.
Urinary PGE-M Levels and Risk of Ovarian Cancer
Authors: Barnard Mollie E. , Beeghly-Fadiel Alicia , Milne Ginger L. , Akam Eftitan Y. , Chan Andrew T. , Eliassen A. Heather , Rosner Bernard A. , Shu Xiao-Ou , Terry Kathryn L. , Xiang Yong-Bing , Zheng Wei , Tworoger Shelley S.
Published: August 2019

Background:

Regular aspirin use may lower ovarian cancer risk by blocking the cyclooxygenase enzymes, resulting in lower expression of prostaglandins, including prostaglandin E2 (PGE2). We evaluated whether higher prediagnosis PGE-M (a urinary biomarker of PGE2) was associated with increased ovarian cancer risk in three prospective cohorts.

Methods:

We conducted a case–control study nested in the Nurses' Health Study (NHS), NHSII, and Shanghai Women's Health Study. Our analyses included 304 cases of epithelial ovarian cancer diagnosed from 1996 to 2015 and 600 matched controls. We measured urinary PGE-M using LC/MS with normalization to creatinine. Measures from each study were recalibrated to a common standard. We estimated ORs and 95% confidence intervals (CI) using conditional logistic regression, with PGE-M levels modeled in quartiles. Multivariable models were adjusted for ovarian cancer risk factors.

Results:

There was no evidence of an association between urinary PGE-M levels and ovarian cancer risk for women with PGE-M levels in the top versus bottom quartile (OR = 0.80; 95% CI, 0.51–1.27; Ptrend = 0.37). We did not observe heterogeneity by histotype (P = 0.53), and there was no evidence of effect modification by body mass index (Pinteraction = 0.82), aspirin use (Pinteraction = 0.59), or smoking (Pinteraction = 0.14).

Conclusions:

Prediagnosis urinary PGE-M levels were not significantly associated with ovarian cancer risk. Larger sample sizes are needed to consider a more modest association and to evaluate associations for specific tumor subtypes.

Impact:

Systemic prostaglandin levels do not appear strongly associated with ovarian cancer risk. Future research into aspirin use and ovarian cancer risk should consider local prostaglandins and prostaglandin-independent mechanisms.
Assessing Metabolic Intervention with a Glutaminase Inhibitor in Real-Time by Hyperpolarized Magnetic Resonance in Acute Myeloid Leukemia
Authors: Zacharias Niki M. , Baran Natalia , Shanmugavelandy Sriram S. , Lee Jaehyuk , Lujan Juliana Velez , Dutta Prasanta , Millward Steven W. , Cai Tianyu , Wood Christopher G. , Piwnica-Worms David , Konopleva Marina , Bhattacharya Pratip K.
Published: August 2019

Acute myeloid leukemia (AML) is an aggressive hematopoietic disease characterized by glutamine-dependent metabolism. A novel glutaminase (GLS) inhibitor, CB-839, is currently under evaluation for treatment of hematopoietic malignancies and solid tumors. Our purpose was to measure cellular changes in AML associated with CB-839 treatment and to test the ability of hyperpolarized pyruvate for interrogating these changes to OCI-AML3 cells. Our results show that treatment with CB-839 interfered with the citric acid cycle, reduced the NADH/NAD+ ratio and ATP levels, reduced cell proliferation and viability, and reduced the basal and maximal respiratory capacities [oxygen consumption rate (OCR)]. We observed a reduction of the conversion of hyperpolarized pyruvate to lactate in cell lines and in a mouse AML model after CB-839 treatment. Our in vitro and in vivo results support the hypothesis that, in AML, glutamine is utilized to generate reducing equivalents (NADH, FADH2) through the citric acid cycle and that reduction in redox state by GLS inhibition decreases the rate of pyruvate to lactate conversion catalyzed by lactate dehydrogenase. We propose hyperpolarized pyruvate/lactate measurement as a method for direct monitoring of metabolic changes occurring in AML patients receiving CB-839. With further optimization, this method may provide a noninvasive imaging tool to assess the early efficacy of therapeutic intervention with GLS inhibitors.
Effectiveness of Stress-Reducing Interventions on the Response to Challenges to the Immune System: A Meta-Analytic Review
Authors: Schakel Lemmy , Veldhuijzen Dieuwke S. , Crompvoets Paige I. , Bosch Jos A. , Cohen Sheldon , van Middendorp Henriët , Joosten Simone A. , Ottenhoff Tom H.M. , Visser Leo G. , Evers Andrea W.M.
Published: August 2019

Background: There is consistent evidence showing an interplay between psychological processes and immune function in health and disease processes. Objectives: The present systematic review and meta-analysis aims to provide a concise overview of the effectiveness of stress-reducing psychological interventions on the activation of immune responses in both healthy subjects and patients. Methods: Included are 3 types of challenges: in vivo, in vitro, and psychophysiological. Such challenges are designed to mimic naturally occurring immune-related threats. Results: A systematic literature search was conducted using PubMed, EMBASE, and PsychInfo, resulting in 75 eligible studies. The risk of bias was assessed with the Cochrane risk-of-bias tool. Across all studies, a small-to-medium effect size was found for the effects of psychological interventions on optimization of the immune function (g = 0.33; 95% CI 0.22–0.43). While the largest effects were found for in vivo immune-related challenges (g = 0.61; 95% CI 0.34–0.88; especially on studies that incorporated skin tests and wound healing), studies incorporating psychophysiological challenges and in vitro immune-related stimulations similarly suggest more optimal immune responses among those receiving stress-reducing interventions (g = 0.28; 95% CI 0.15–0.42). Conclusion: These findings showed substantial heterogeneity depending on the type of challenge, the study populations, and the intervention types. These data demonstrate support for the effectiveness of stress-reducing psychological interventions in improving immunity in studies that tested immune function by means of incorporating an in vivo,in vitro, or psychophysiological challenge. Future research should more consistently incorporate challenges into the study design to gather more insights in the mechanisms underlying the optimized immune function following a psychological intervention. This is also relevant for clinical practice, as psychological interventions can possibly supplement, or at least partially replace, current drug treatments in various somatic conditions to reduce side effects.
Iron Regulation by Molidustat, a Daily Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, in Patients with Chronic Kidney Disease
Authors: Akizawa Tadao , Macdougall Iain C. , Berns Jeffrey S. , Yamamoto Hiroyasu , Taguchi Megumi , Iekushi Kazuma , Bernhardt Thomas
Published: August 2019

Background/Aims: The current treatment for anemia associated with chronic kidney disease (CKD) includes the administration of erythropoiesis stimulating agents (ESAs) combined with iron supplementation. Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, has potential to treat anemia associated with CKD through increased erythropoietin production and improved iron availability. Here, we report the effect of molidustat on iron metabolism. Method: Parameters of iron metabolism were monitored in three 16-week, randomized, controlled, phase 2 studies assessing the safety and efficacy of molidustat in the treatment of anemia associated with CKD in different populations: treatment-naïve and previously ESA-treated patients not on dialysis, and previously ESA-treated patients on hemodialysis. Iron supplementation was left at the discretion of the investigator. Results: In treatment-naïve patients not on dialysis, transferrin saturation (TSAT), hepcidin, ferritin, and iron concentrations decreased with molidustat, whereas total iron binding capacity (TIBC) increased. Similar results were observed in previously ESA-treated patients not on dialysis, although changes in those parameters were larger in treatment-naïve than in previously ESA-treated patients. In previously ESA-treated patients receiving hemodialysis, hepcidin concentration and TIBC remained stable with molidustat, whereas TSAT and ferritin and iron concentrations increased. Generally, similar trends were observed in secondary analyses of subgroups of patients not receiving iron supplementation. Conclusions: Molidustat is a potential alternative to standard treatment of anemia associated with CKD, with a different mechanism of action. In patients not receiving dialysis, molidustat increases iron availability. In patients receiving hemodialysis, further investigation is required to understand fully the mechanisms underlying iron mobilization associated with molidustat.
Changing the Timing of Enzalutamide Intake from Morning to before Sleep at Night Overcame Enzalutamide-Induced Dysgeusia
Authors: Kawahara Takashi , Miyoshi Yasuhide , Yao Masahiro , Uemura Hiroji
Published: August 2019

Dysgeusia is an adverse effect caused by enzalutamide said to affect 1–5% of patients. The reported management strategies include a temporary drug holiday, the prescription of herbal medicine, and changing the timing of enzalutamide intake from morning to before sleep at night. Case 1: A 72-year-old man developed castration-resistant prostate cancer (CRPC) and was administered enzalutamide. After six weeks of enzalutamide installation, he showed taste alternation, and consequently his dysgeusia increased to grade 2; we therefore changed the medicine intake time from morning to night just before sleep without dose reduction. Four weeks after changing the timing, his dysgeusia had improved. Case 2: A 63-year-old man had developed bone metastatic CRPC, so the combination of Ra-223 and enzalutamide (160 mg/body) was introduced. His serum PSA level had gradually decreased, but dysgeusia appeared, so we changed the timing of enzalutamide intake from morning to night just before sleep without dose reduction. One month after changing the timing, his dysgeusia had improved. We herein report two cases of enzalutamide-induced dysgeusia successfully treated by changing the timing of drug intake from morning intake to just before sleep.
Triple Trouble: A Case of Multiple Resistance Mechanisms after First Generation EGFR-TKI in NSCLC
Authors: Ralki Mike , Maes Brigitte , Pat Karin , Wynants Jokke , Cuppens Kristof
Published: August 2019

Epidermal growth factor receptor (EGFR)-targeted therapy has become standard of care in advanced stages EGFR-mutant non-small cell lung cancer. Acquired resistance to first-line EGFR-tyrosine kinase inhibitor (TKI) and subsequent disease progression is a common problem and mostly due to a secondary mutation (T790M) in EGFR. We report a case of a patient with EGFR-mutated lung adenocarcinoma who developed a complex resistance profile: T790M mutation, HER2 mutation and HER2 amplification after first-line EGFR-TKI. This patient was safely treated with a combination of osimertinib and trastuzumab and achieved a clinically meaningful and clear molecular response.This is the first reported case of acquired resistance to first-line EGFR-TKI based on three resistance mechanisms, treated with molecular targeted combination therapy.
Ceinidae
Authors: COLEMAN CHARLES OLIVER
Published: August 2019

Ceina gerlachae sp. nov. is described. It differs in the habitus from the closely related Ceina carinata (Pirlot) in the rounded anterior process of pereonite 1, an upright carina on pleonite 1, a short process on pleonite 3 and a few characters on the maxillipeds.
Cheluridae
Authors: COLEMAN CHARLES OLIVER , RENZ ADINA
Published: August 2019

Tropichelura insulae (Calman, 1910), a species living in excavations in wooden logs together with limnoriid Isopoda, is redescribed from Lizard Island, Great Barrier Reef Australia. This species has enlarged first gnathopods, three teeth on the posterior margin of pleonite 3 and the peculiar uropods and telson that are characteristic for the family Cheluridae.
Dexaminidae
Authors: MYERS ALAN A. , LECROY SARA E.
Published: August 2019

Four genera and 11 species of dexaminids are reported from the Great Barrier Reef. Of these, three species (Dexaminoculus grobbeni (Spandl, 1923), Guernea ipilya Thomas & Barnard, 1991, G. yamminye Thomas & Barnard, 1991) have been previously encountered on the Reef, seven species (six Paradexamine, one Polycheria) are new to science and one species (Paradexamine micronesicus Ledoyer, 1979) is reported for the first time from Australian waters. All species are described and illustrated.
Hyalidae
Authors: SEREJO CRISTIANA S. , SITTROP DANIELA J.
Published: August 2019

As a result of the Amphipod Lizard Island workshop (2005) three species of Hyalidae were found: two new species are described, Hyachelia lowryi sp. nov. and Lelehua myersi sp. nov. and Parhyale hawaiensis is recorded for the first time for Australia.
Megaluropidae
Authors: HUGHES L. E.
Published: August 2019

This is the first record of the family Megaluropidae in Australian waters. Gibberosus udarus sp. nov. is described here from Lizard Island, Great Barrier Reef.
Phliantidae
Authors: COLEMAN CHARLES OLIVER
Published: August 2019

Pereionotus thomsoni Stebbing is redescribed based on new material from the Great Barrier Reef. This phliantid amphipod has a depressed body. It can be recognized by mid-dorsal hump-like carinae and the typical shape of the basis of pereopod 7 which is constricted posterodistally.
Wandinidae
Authors: LOWRY J. K. , STODDART H. E.
Published: August 2019

One species of wandinid amphipod is reported from the Great Barrier Reef, Queensland, Australia. Wandin griffini Lowry & Stoddart is known from Lizard Island, One Tree Island and reefs on the Outer Barrier, living among rubble usually at the base of living coral. The species is rare in this habitat.
Ampithoidae
Authors: HUGHES L. E. , LOWRY J. K.
Published: August 2019

Five genera and 19 species of ampithoid amphipods are reported from the Great Barrier Reef, Queensland, Australia. Seven species are new to science. The majority of species occur in the genus Cymadusa.
Transfer of Pyrochroa daglariensis to Hemidendroides Ferrari (Coleoptera: Pyrochroidae: Pyrochroinae), with a dichotomous key to the four species of the genus
Authors: YOUNG DANIEL K.
Published: August 2019

Having discovered a primary homonym associated with the pyrochroid species name Dendroides cyanipennis, Young (2004) reviewed the taxonomic history of the species and proposed the replacement name Pyrochroa daglariensis for the junior homonym. This species was previously known solely from the presumed syntype series of two females from the northeastern part of the Turkish province of Hatay, near the Turkey-Syria boarder in the Nur Dağlari mountains. The generic association with Pyrochroa was made in deference to Blair’s (1914) treatment, although Young (2004: 935) added, “Discovery of males would allow better assessment of important characters such as the cranial pit apparatus and genitalia.”
Discovery of Amurinocellia H. Aspöck & U. Aspöck (Raphidioptera: Inocelliidae) in China, with description of two new species
Authors: LIU XINGYUE , ASPÖCK HORST , YANG DING , ASPÖCK ULRIKE
Published: August 2019

The snakefly genus Amurinocellia (Raphidioptera: Inocelliidae) is recorded from China for the first time. Two species are described as new to science: Amurinocellia sinica sp. nov. and Amurinocellia australis sp. nov. A new combination, Amurinocellia calida (H. Aspöck & U. Aspöck) comb. nov. is proposed. A key is provided for the species of Amurinocellia. The generic status and the zoogeography of Amurinocellia are discussed.
Review of the genus Onconeura Andersen et Sæther (Diptera: Chironomidae), with the description of four new species from Brazil
Authors: WIEDENBRUG SOFIA , MENDES HUMBERTO F. , PEPINELLI MATEUS , TRIVINHO-STRIXINO SUSANA
Published: August 2019

Four new species of Onconeura Andersen et Sæther are described from Brazil, O. japi, O. oncovolsella and O. similispina as male, female, pupa and larva, and O. cascatinha as male and pupa. Additionally four pupal morphotypes are included. One new described species has associated COI DNA barcoding gene. The material studied was collected in the States of Mato Grosso, Minas Gerais, Rio de Janeiro, São Paulo and Rio Grande do Sul. Keys to the known species are given for all life stages.
On the poorly known genus Anuvinda Lehtinen, 1967 (Araneae: Titanoecidae)
Authors: ALMEIDA-SILVA LINA M. , BRESCOVIT ANTONIO D. , GRISWOLD CHARLES E.
Published: August 2019

The spider genus Anuvinda includes a single species described from India, Anuvinda escheri (Reimoser), based on a female. The male remained unknown and no other specimens beyond the type specimen are known. In this paper we present the first description of the male of A. escheri and the redescription of the female, based on material recently collected in China, Laos and Thailand. In addition, the distribution range of the species is extended to include these three countries.
Description and comparison of morphological structures of the eggs of Anopheles hyrcanus group and related species (Diptera: Culicidae) from the Republic of Korea
Authors: RUEDA LEOPOLDO M. , BROWN TRACY L. , KIM HEUNG-CHUL , KLEIN TERRY A. , THONGKUKIATKUL AMPORN , SHERWOOD VAN
Published: August 2019

The eggs of six Anopheles Hyrcanus Group (An. sinensis Wiedemann, An. kleini Rueda, An. belenrae Rueda, An. pullus M. Yamada, An. lesteri Baisas and Hu, An. sineroides S. Yamada) and related species (An. koreicus S. Yamada and Watanabe, An. lindesayi japonicus S. Yamada), were described from scanning electron micrographs of specimens collected from different localities of the Republic of Korea. Morphometric measurements of egg samples of the eight species were compared and relationships analyzed by multivariate statistics. About 27 characters were selected and used as a basis for principal and discriminant function analyses. Scanning electron micrographs of various parts of the eggs were selected to illustrate interspecific differences for particular morphological features (e.g. anterior and posterior tubercles, decks, plastron, micropyles, floats).
High haplotype diversity in a microendemic Malagasy gecko species, Lygodactylus mirabilis (Pasteur, 1962)
Authors: CHIARI YLENIA , VIEITES DAVID R. , GUO JERRY , BORA PARFAIT , VENCES MIGUEL
Published: August 2019

Among Malagasy montane reptiles, the diurnal gecko Lygodactylus mirabilis has one of the most restricted distribution ranges, occurring only on the Tsiafajavona mountain on the Ankaratra massif. Here we report data on the current distribution of this species and its genetic diversity. Mitochondrial data based on samples collected in the only previously known distribution area (the Tsiafajavona peak) showed numerous haplotypes at low frequencies, suggesting a past population expansion and a relatively high within-species genetic diversity in an extremely small distribution area. Our field survey also revealed that the range of the species is larger than previously thought, but still is extremely small and restricted to the Ankaratra massif.
On the enigmatic Heterolacurbs ovalis Roewer, 1912 (Opiliones, Laniatores, Biantidae)
Authors: PÉREZ-GONZÁLEZ ABEL , BARROSO AYLIN ALEGRE
Published: August 2019

In the course of conducting a systematic review of the Cuban Stenostygninae (Biantidae), it has been deemed critical to review Heterolacurbs ovalis Roewer, 1912 from Togo. The habitus and the enlarged metatarsus III of males (as shown in Roewer 1912: 185, fig. 42 and 1923: 143, fig. 154) of this species, which is currently placed in the Lacurbsinae, point to a close relationship with the Caribbean Stenostygninae (Pérez-González 2007). The occurrence of taxa with morphological similarities on both sides of the Atlantic Ocean demanded a detailed study of this species, mainly its penis morphology. It needed to be tested whether H. ovalis is in fact a member of an ancestral Gondwanan lineage, or if its morphological similarities with species from the other side of the Atlantic are due to convergence.
Squalius kottelati, a new cyprinid species (Teleostei: Cyprinidae) from Orontes River, Turkey
Authors: TURAN DAVUT , YILMAZ B. TOGAY , KAYA CÜNEYT
Published: August 2019

Squalius kottelati, new species, is described from the Orontes, Ceyhan and Seyhan rivers in Turkey. It belongs to the S. lepidus group, characterized by a projecting lower jaw. It is distinguished from the other species of the genus Squalius in Turkey and adjacent basins by having a conspicuous broad, dark stripe on the upper part of the flank, from the head to the end of the caudal peduncle (vs. absent or very faintly marked, except S. lepidus). It differs from S. lepidus by having a longer head (28.3–30.9, vs. 25.3–27.3 % SL), fewer lateral-line scales (45–47, vs. 48–49) and fewer gill rakers on the first gill arch (9–10, vs. 11–13). It differs from S. anatolicus by having more scales in the lateral line (45–47,mode 46 vs. 43–45, mode 44); a longer caudal fin (length of upper lobe 20.3–22.5, vs. 15.8–19.0 % SL).
A review of the Caligus productus species group, with the description of a new species, new synonymies and supplementary descriptions
Authors: BOXSHALL GEOFF A , EL-RASHIDY HODA H.
Published: August 2019

The productus-group within the sea lice genus Caligus Müller, 1785 is characterised by the loss of two and the reduction or loss of the third of the three plumose setae normally carried on the posterior margin of the distal exopodal segment of the first swimming leg. We describe a new species, Caligus lethrinicola n.sp., from a lethrinid host collected in New Caledonia. We review the group and recognize 15 species as valid, including the new species. The type material of the three varieties of Caligus mauritanicus Brian, 1924 is re-examined and the var. temnodontis is here recognized as a distinct species, Caligus temnodontis Brian, 1924. The typical and miniscula varieties are recognised as synonyms of Caligus dakari van Beneden, 1892 and C. haemulonis Krøyer, 1863 respectively. Additional synonymies are proposed within the group. Supplementary observations are presented on the morphology of C. dakari, C. haemulonis and C. temnodontis. A brief differential diagnosis is presented for each of the 14 previously described valid species and a key to species has been constructed.