bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining microenvironment normalization strategies to improve cancer immunotherapy
Authors: Mpekris Fotios , Voutouri Chrysovalantis , Baish James W. , Duda Dan G. , Munn Lance L. , Stylianopoulos Triantafyllos , Jain Rakesh K.
Published: February 2020

Significance

Immunotherapy has changed the standard of care in cancer treatment, but an estimated 87% of patients currently do not derive long-term benefit from immune checkpoint blocker monotherapy. Therefore, new therapeutic strategies are needed to improve the response rates in patients who are resistant to immune checkpoint inhibition. We have developed a mathematical framework to determine how tumor microenvironment normalization strategies—specifically, vascular and stroma normalization—might improve immunotherapy efficacy. By incorporating complex interactions among various types of cancer cells, immune cells, stromal cells, and the vasculature, as well as physical mechanisms, we provide guidelines for designing effective combinatorial therapeutic strategies and point out areas for future investigation.
Translating narratives and counter-narratives in Ahmet Ümit’sWhen Pera Trees Whisper
Authors: Tekgül-Akın Duygu
Published: February 2020

This study analyzes the translation of political narratives inBeyoğlu’nun En Güzel Abisi, a 2013 detective novel by the best-selling Turkish author Ahmet Ümit. Translated into English by Elke Dixon asWhen Pera Trees Whisper(2014), the novel addresses the events of 6–7 September 1955 that led to the exodus of non-Muslim communities from Istanbul as well as the Gezi Park protests in 2013. The source text reproduces the competing public narratives on issues including ethnic diversity in Turkey, the public mobilization at Gezi, and police intervention during the protests. These narratives play a crucial role, particularly in light of the framing of the protagonist, Chief Inspector Nevzat, as a “good cop” in previous installments of the detective series. In the target text, Elke Dixon translates narratives and counter-narratives for an international readership, conveying the variety of narrative perspectives and framing choices through explicitations, shifts, and other strategies.
Sign Language in Papua New Guinea
Authors: Kendon Adam
Published: February 2020

This book presents in revised form and as a single monograph three papers on a sign language from the Enga Province of Papua New Guinea. Originally published in 1980, for more than twenty years these papers remained the only report of a sign language from that part of the world. The detailed descriptive analyses that the author provided are still fresh today, and in some respects they anticipate insights into the nature of sign languages that were not further explored until much more recently. The monograph is accompanied by two essays: Sherman Wilcox comments on value and relevance of the author’s work in the light of much more recent work on the linguistics of sign languages. An essay by Lauren Reed and Alan Rumsey provides an up to date survey of what is now known about sign languages in Papua New Guinea. Information about sign languages in the Solomon Island is also included.
Measurement of prosthetic alignment
Authors: Berme N. , Purdey C. R. , Solomonidis S. E.
Published: February 2020

An essential part of alignment description is the position and orientation of the socket relative to the rest of the limb. Repeatable measurements of these parameters is hindered by the non-geometrical shape of the socket. A unique axis system has already been defined to enable such measurements to be carried out. The method however, employs an iterative technique and is time consuming. A simple device to facilitate these measurements has been developed and is reported.
Holocene erosion and deposition within a small catchment of the northeastern Borisoglebsk Upland (Central European Russia)
Authors: Belyaev V R , Garankina E V , Shorkunov I G , Konstantinov E A , Rusakov A V , Shishkina Yu V , Andreev P V , Verlova T A
Published: February 2020

During the Holocene, interfluvial landscapes of European plains have experienced alternating periods of relative stability and significant shifts in climate, soil and geomorphological development. Assumed to be an arena of major transformation their evolutionary model is not entirely resolved yet. Based on lithostratigraphic, geomorphologic and soil survey, new results on the Holocene dynamics of fluvial and related processes including landscape stabilization phases for one of the gully catchments draining the Borisoglebsk Upland northeastern slope towards the Nero Lake are presented. Common absence of the early Holocene deposits can be explained by generally negative sediment budget of the catchment. Nevertheless, continuous erosion was not likely whether rare climatic extremes probably were the case. A series of middle Holocene dates obtained by analyzing total organic carbon from organic-accumulative layers of buried soils, lake gyttja and peats highlights strong evidence of the synchronous phase of landscape stabilization in both upper and lower parts of the Puzhbol catchment accompanied by active infilling of small erosion cuts in its middle part. The upper part of the Puzhbol Gully fan sediment shows clear evidence of synchronous accumulation of agrogenic colluvium and gully alluvium since XIIth Century on top of the lake terrace deposits.
Changes of vegetation in the eastern part of Khanka Plain (south of the Russian Far East) at the transition from the Late Pleistocene cryochron (MIS 2) to the Early Holocene
Authors: Belyanin P S , Belyanina N I
Published: February 2020

Reconstructions of the vegetation in the eastern part of the Khanka Plain have been performed for the time interval at the transition from the Late Pleistocene cryochron (MIS 2) to the Holocene. New evidence of considerable changes in the vegetation structure were provided by the palynological studies supplemented with radiocarbon dates on wood fragments and plant detritus recovered from alluvial, lacustrine and mires sediments. It has been found that at the glacial stage MIS 2 the Khanka Plain was dominated by open birch forests with larch and spruce, alternating with Sphagnum mires with shrub birch. Later, at the interstadial, formations typical of southern boreal dark coniferous (needle-leaved) taiga became widely spread. The Early Holocene was marked by wide expansion of broadleaf trees (and first of all, elm and Mongolian oak) in the Khanka Plain ecosystems. Mixed forests with Korean pine became widely spread in the mountains surrounding the lowland. Mires, patches of dark coniferous forests, and open forests of larch persisted on the plains adjoining the lake and on swampy valley floors.
Diachronic analysis of historical and modern landscapes of the Herakleian peninsula
Authors: Ergina E I , Malashina M C , Ergin S M , Melezhik K A
Published: February 2020

The Herakleian Peninsula has a unique geographical location and a long history of development. The methods of historical and geographical research of this territory have been considered. The historical landscapes development dynamics research of the Peninsula has been conducted with the use of cartographic material, satellite images interpretation and a field observations of the territory within the selected time slices. Map analysis of the economic subsystem of the anthropogenic landscapes of the Herakleian Peninsula has been made. Areas of the South -Western and North-Eastern parts of the Peninsula which preserve the historical features of the modern land use formation have been singled out with regard to the specifics of the arrangement of land allotments (klers) in the ancient system of agriculture.
Archaeological sites in the Katynka river basin (Smolensk Region): Paleogeographic study
Authors: Ershova E G , Krenke N A , Kittel P , Lavrenov N G
Published: February 2020

The first results of paleogeographic study at estuary of the Katynka river allow to reconstruct the dynamics of vegetation in this part of the Dnieper floodplain for about 5 millennia and identify some traces of Neolithic, Early Iron Age and Medieval human activity. The most prominent anthropogenic transformation of landscapes (signs of slash-and-burn agriculture) was associated with the late Holocene «Gnezdovo» buried soil dated 2-5 centuries AD.
Late Holocene malacofauna-based paleoenvironmental reconstruction for the Bazaikha River and Tartat River valleys (Krasnoyark Depression, Central Siberia)
Authors: Makarchuk D E , Yamskikh G Yu , Lebedeva N V , Brungardt V O , Bochka V V
Published: February 2020

The results of malacofauna-based palaeoenvironment reconstructions for the Late Holocene in the valleys of Bazaikha and Tartat rivers (Krasnoyarsk depression) are presented. Palynological analyses of the flood-plain deposits and radiocarbon dating complemented malacofaunal analysis. Biodiversity of malacofauna is represented by 7 freshwater species and 15 land species. Species belonging to the Valloniidae Morse, 1864 and Lymnaeidae Rafinesque, 1815 families are dominant in the fossil assemblages. The finding of Gastrocopta theeli shell in the Late Holocene deposits of the Bazaikha section is the first one in the territory of Krasnoyarsk depression. This finding supports the relic, spotted character of the geographic range of this species. Emploting malacofauna proxies and the Eleneva Cave reference section palynological record enabled reconstructing Late Holocene palaeoenvironmental conditions in the area. Malacofauna in the valleys of Bazaikha and Tartat rivers developed under the conditions of gradual increase in heat availability and decreasing annual precipitation and warm-period precipitation during the last 2500 years. A reduction of malacofauna diversity 950 years ago was caused by a change in the precipitation regime.
A 10 000-year pollen and plant macrofossil record from the Losiny Ostrov National Park (Moscow, Russia)
Authors: Miagkaia A , Ershova E
Published: February 2020

The paper presents the first results of pollen and macrofossil analysis of a peat bog located near the Moscow city within the territory of the Losiny Ostrov National Park. Macrofossil data demonstrate that the bog development started from the stage of a spring calcetrophic fen at the very beginning of the Holocene. After 9.9 ka BP it became a meso-oligotrophic herbaceous-sphagnum bog. Pollen data manifest early spread of spruce in the Moscow region (before 10.2 ka BP). Predominance of broad-leaved temperate deciduous forests is characteristic of the Holocene thermal optimum (8.5-4.8 ka BP). The new spread of spruce forests began after 4.8 ka BP. The first signs of deforestation for agriculture date back to 1.8-1.7 ka BP (Early Iron Age). The next massive deforestation for agriculture was recorded 0.7-0.4 ka BP (Middle Age). After the 17th century, anthropogenic activity decreased, as a result of the establishment of the reserve status.
Holocene vegetation and climate changes in the North-Eastern Caucasus (pollen data from mountains and plain peatlands)
Authors: Ryabogina N E , Nasonova E D , Borisov A V , Idrisov I A
Published: February 2020

Dagestan (North-Eastern part of the Caucasus) is characterized by a unique historical and environment development, however, there is little, if no, data on nature changes throughout the Holocene history of the region. In contrast to the much-studied neighboring Caucasus regions, Dagestan remains mostly unexplored from the standpoint of paleoecology. In 2017, we investigated a detailed radiocarbon-dated 185 cm peat sequence from the Shotota swamp located in the mountainous zone of Dagestan. Peat and soil deposits span most of the Holocene (about 9000 years), and they let us study vegetation history of the Eastern Caucasus for the first time. The results of the study show significant discrepancies in the timing and sequence of the expansion of tree species in the Holocene in comparison with Transcaucasia and the Western Caucasus. The second key study, an examination of a 270 cm peat sequence from Arkida swamp, formed in the second half of the Holocene, also provided new paleoenvironmental data on the south of the Caspian lowland. The vegetation of the flat parts of Dagestan, adjacent to the mountainous zone, has been dry and treeless for the last four thousand years, however, humidification fluctuations and vegetation changes were distinguished.
Dynamics of soil salinization in the Nero Lake depression (Upper Volga) in connection with the latest climate change
Authors: Simonova J V , Rusakov A V , Popov A I
Published: February 2020

Over the last 30–40 years, climate changes have resulted in environmental changes within the Upper Volga basin. In this study, an attempt to analyze the soil record of recent climate changes was made. An example of soil evolution induced by climate change was studied on hydromorphic saline soils in the nature reserve of the Varnicy Saline Spring. In a humid climate, soil salinization occurring in discharge areas can quickly change in response to the changed hydrothermal regime because of close relationships between climatic conditions and groundwater systems. In a poorly drained depression, we could observe an increasing soil salinity and developing hydrogenic accumulation of salts, whereas the groundwater salinity was stable.
Superlubricity in phosphorene identified by means of ab initio calculations
Authors: Losi Gabriele , Restuccia Paolo , Righi M C
Published: February 2020

Phosphorene possesses a great potential for tribological applications due to its layered structure and for the capability of phosphorus to reduce friction and adhesion in steel–steel contacts. Here we present a comprehensive analysis of the static tribological properties of phosphorene based on first principles calculations. The most suitable exchange-correlation functional for describing the structural and electronic properties of multilayer phosphorene is carefully selected. The interlayer binding energy and shear strength are then calculated for two relative orientations of the layers. Layers stacked with the same orientation (armchair–armchair and zigzag–zigzag) are slippery as common solid lubricants, as MoS2 and graphite. While the armchair–zigzag orientation shows a remarkable superlubricity, with a reduction of one order of magnitude for the shear stress. We uncover the microscopic origin of such superlubric phase by analyzing the electronic charge at the layer interface.
Repetitive readout enhanced by machine learning
Authors: Liu Genyue , Chen Mo , Liu Yi-Xiang , Layden David , Cappellaro Paola
Published: February 2020

Single-shot readout is a key component for scalable quantum information processing. However, many solid-state qubits with favorable properties lack the single-shot readout capability. One solution is to use the repetitive quantum-non-demolition readout technique, where the qubit is correlated with an ancilla, which is subsequently read out. The readout fidelity is therefore limited by the back-action on the qubit from the measurement. Traditionally, a threshold method is taken, where only the total photon count is used to discriminate qubit state, discarding all the information of the back-action hidden in the time trace of repetitive readout measurement. Here we show by using machine learning (ML), one obtains higher readout fidelity by taking advantage of the time trace data. ML is able to identify when back-action happened, and correctly read out the original state. Since the information is already recorded (but usually discarded), this improvement in fidelity does not consume additional experimental time, and could be directly applied to preparation-by-measurement and quantum metrology applications involving repetitive readout.
ShinySOM: graphical SOM-based analysis of single-cell cytometry data
Authors: Kratochvíl Miroslav , Bednárek David , Sieger Tomáš , Fišer Karel , Vondrášek Jiří
Published: February 2020

ShinySOM offers a user-friendly interface for reproducible, high-throughput analysis of high-dimensional flow and mass cytometry data guided by self-organizing maps. The software implements a FlowSOM-style workflow, with improvements in performance, visualizations and data dissection possibilities. The outputs of the analysis include precise statistical information about the dissected samples, and R-compatible metadata useful for the batch processing of large sample volumes.

Availability and implementation

ShinySOM is free and open-source, available online at gitlab.com/exaexa/ShinySOM.

Supplementary information

Supplementary data are available at Bioinformatics online.
CPFD simulation on particle behaviour in an entrained-flow gasifier
Authors: Liang Yongshi , Guo Cliff Y , Zhao Xianglong , Qin Qiang , Cheng Yi , He Lixin
Published: February 2020

A computational particle fluid dynamics simulation model for entrained-flow gasification was established in this study. The simulation results agree with the experimental data. The detailed particle information and residence-time distribution were obtained by injecting particle tracers in the simulation. The results show that the particles in the gasifier can be classified into three flowing zones, i.e. a fast-flowing zone, a recirculation zone and a spreading zone. The criterion for this classification was also provided. The rapid gas expansion caused by the fast reactions plays a significant role in forming the particle stream into these three zones. It accelerates the particles in the centre of the gasifier while pushing the particles near the expansion edge into the gas recirculation. Also, the concentrated oxygen distribution in the gasifier results in the formation of high- and low-temperature regions. The particles in the fast-flowing zone flow directly through the high-temperature region and most of these particles in this zone were fully reacted with a short residence time. Since particles in the recirculation zone are in a relatively low-temperature region, most of these particles are not fully gasified, although with a long residence time. The rest of particles in the spreading zone show moderate properties between the above two zones.
Metal-Organic Framework Stationary Phases for One- and Two-Dimensional Micro-Gas Chromatographic Separations of Light Alkanes and Polar Toxic Industrial Chemicals
Authors: Read Douglas H , Sillerud Colin H , Whiting Joshua J , Achyuthan Komandoor E
Published: February 2020

Despite promising advances with metal-organic frameworks (MOFs) as stationary phases for chromatography, the application of MOFs for one- and two-dimensional micro-gas chromatography (μGC and μGC × μGC) applications has yet to be shown. We demonstrate for the first time, μGC columns coated with two different MOFs, HKUST-1 and ZIF-8, for the rapid separation of high volatility light alkane hydrocarbons (natural gas) and determined the partition coefficients for toxic industrial chemicals, using μGC and μGC × μGC systems. Complete separation of natural gas components, methane through pentane, was completed within 1 min, with sufficient resolution to discriminate n-butane from i-butane. Layer-by-layer controlled deposition cycles of the MOFs were accomplished to establish the optimal film thickness, which was validated using GC (sorption thermodynamics), quartz-crystal microbalance gravimetric analysis and scanning electron microscopy. Complete surface coverage was not observed until after ~17 deposition cycles. Propane retention factors with HKUST-1-coated μGC and a state-of-the-art polar, porous-layer open-tubular (PLOT) stationary phase were approximately the same at ~7.5. However, with polar methanol, retention factors with these two stationary phases were 748 and 59, respectively, yielding methanol-to-propane selectivity factors of ~100 and ~8, respectively, a 13-fold increase in polarity with HKUST-1. These studies advance the applications of MOFs as μGC stationary phase.
Pelacarsen for lowering lipoprotein(a): implications for patients with chronic kidney disease
Authors: Fernandez-Prado Raul , Perez-Gomez Maria Vanessa , Ortiz Alberto
Published: February 2020

Chronic kidney disease (CKD) patients are at an increased risk of cardiovascular disease (CVD) and statins may not be protective in advanced CKD. The reasons for the limited efficacy of statins in advanced CKD are unclear, but statins may increase plasma levels of the highly atherogenic molecule lipoprotein(a), also termed Lp(a), as well as PCSK9 (protein convertase subtilisin/kexin type 9) levels. Lp(a) has also been linked to calcific aortic stenosis, which is common in CKD. Moreover, circulating Lp(a) levels increase in nephrotic syndrome with declining renal function and are highest in patients on peritoneal dialysis. Thus, the recent publication of the Phase 2 randomized controlled trial of pelacarsen [also termed AKCEA-APO(a)-LRx and TQJ230], a hepatocyte-directed antisense oligonucleotide targeting the LPA gene messenger RNA, in persons with CVD should be good news for nephrologists. Pelacarsen safely and dose-dependently decreased Lp(a) levels by 35–80% and a Phase 3 trial [Lp(a)HORIZON, NCT04023552] is planned to run from 2020 to 2024. Unfortunately, patients with estimated glomerular filtration rate <60 mL/min or urinary albumin:creatinine ratio >100 mg/g were excluded from Phase 2 trials and those with ‘significant kidney disease’ will be excluded from the Phase 3 trial. Optimized exclusion criteria for Lp(a)HORIZON would provide insights into the role of Lp(a) in CVD in CKD patients.
Ecosystem consequences of multi-trait response to environmental changes in Japanese medaka, Oryzias latipes
Authors: Diaz Pauli Beatriz , Edeline Eric , Evangelista Charlotte
Published: February 2020

Intraspecific trait variation has large effects on the ecosystem and is greatly affected by human activities. To date, most studies focused on single-trait analyses, while considering multiple traits is expected to better predict how an individual interacts with its environment. Here, we used a mesocosm experiment with fish Oryzias latipes to test whether individual growth, boldness and functional traits (feeding rate and stoichiometric traits) formed one functional pace-of-life syndrome (POLS). We then tested the effects of among-individual mean and variance of fish functional POLSs within mesocosms on invertebrate community (e.g. zoobenthos and zooplankton abundances) and ecosystem processes (e.g. ecosystem metabolism, algae stock, nutrient concentrations). Stoichiometric traits correlated with somatic growth and behaviours, forming two independent functional POLS (i.e. two major covariance axes). Mean values of the first syndrome were sex- and environment-dependent and were associated with (i) long-term (10 generations; 4 years) selection for small or large body size resulting in contrasting life histories and (ii) short-term (6 weeks) effects of experimental treatments on resource availability (through manipulation of light intensity and interspecific competition). Specifically, females and individuals from populations selected for a small body size presented fast functional POLS with faster growth rate, higher carbon body content and lower boldness. Individuals exposed to low resources (low light and high competition) displayed a slow functional POLS. Higher mesocosm mean and variance values in the second functional POLS (i.e. high feeding rate, high carbon:nitrogen body ratio, low ammonium excretion rate) were associated to decreased prey abundances, but did not affect any of the ecosystem processes. We highlighted the presence of functional multi-trait covariation in medaka, which were affected by sex, long-term selection history and short-term environmental conditions, that ultimately had cascading ecological consequences. We stressed the need for applying this approach to better predict ecosystem response to anthropogenic global changes.
Tofacitinib for Rescue Therapy in Acute Severe Ulcerative Colitis: A Real-world Experience
Authors: Kotwani Prashant , Terdiman Jonathan , Lewin Sara
Published: February 2020

Background

Acute severe ulcerative colitis is a high stakes event with significant numbers still requiring emergent colectomy, representing a need to establish alternative medical management options. We report a case series of tofacitinib as rescue therapy in biologic-experienced patients with acute severe ulcerative colitis.

Methods

Four patients were identified over a 1-year period at our institution who initiated tofacitinib for acute severe ulcerative colitis. All four had previously failed at least two biologics, including infliximab, and were failing high-dose oral prednisone therapy before admission. All patients had Mayo disease activity index of at least 10 at admission. After no significant improvement despite receiving a minimum of 3 days of intravenous methylprednisolone and based on elevated Ho and Travis indices at Day 3, patients were offered rescue tofacitinib for induction of remission, or colectomy. Standard induction of tofacitinib was used [10 mg twice daily], and one patient was escalated to 15 mg twice daily after inadequate response.

Results

All patients experienced improvement in objective symptoms and laboratory markers, and were discharged without colectomy on tofacitinib as maintenance therapy and prednisone taper; 30-day and 90-day colectomy rates on tofacitinib maintenance therapy were zero and 90-day readmission rate was also zero. Two of four patients achieved steroid-free remission on maintenance tofacitinib monotherapy based on clinical symptoms and follow-up endoscopy. No major adverse reaction was reported during induction or maintenance therapy.

Conclusions

Tofacitinib may be an acceptable rescue agent in biologic-experienced patients with acute severe ulcerative colitis. Tofacitinib may also be safely continued as maintenance therapy once remission has been achieved.
Assessing the supercooling of fresh-cut onions at −5°C using electrical impedance analysis
Authors: Koide Shoji , Yoneyama Ami , Orikasa Takahiro , Uemura Matsuo
Published: February 2020

We supercooled fresh-cut onion at −5°C for 12 h. After supercooling, the electric impedance properties of the samples were evaluated by electrical impedance spectroscopy over the frequency range of 42 Hz − 5 MHz. The time-temperature profiles of samples indicated that the freezing point and supercooling point were −2.3°C ± 0.7°C and −6.9°C ± 1.0°C, respectively. The results indicated that 34 of the 36 supercooled samples exhibited a definite circular arc in the Cole-Cole plot, which suggested that the cell membrane remained intact during supercooling. In the other two samples which did not exhibit a definite circular arc, the cell membrane had sustained serious damage during supercooling. Furthermore, there was large difference in drip loss percentage between supercooled samples exhibited a definite circular arc in the Cole-Cole plot and samples not exhibiting a definite circular arc. Our results suggest that fresh-cut onions can be supercooled at −5°C.
Evolution of cellular HIV DNA levels in virologically suppressed patients switching to dolutegravir/lamivudine versus maintaining a triple regimen: a prospective, longitudinal, matched, controlled study
Authors: Lombardi Francesca , Belmonti Simone , Borghetti Alberto , Fabbiani Massimiliano , Marchetti Simona , Tamburrini Enrica , Cauda Roberto , di Giambenedetto Simona
Published: February 2020

Objectives

To assess the impact of switching to dolutegravir plus lamivudine maintenance therapy on the HIV cellular reservoir size.

Patients and methods

This was a prospective, longitudinal, matched, controlled study. We enrolled virologically suppressed patients on stable three-drug ART who switched at baseline (BL) to dolutegravir/lamivudine (DT group) or maintained triple therapy (TT group); subjects in the TT group were matched 1:1 with those in the DT group according to age, gender, years since HIV diagnosis, years on ART and anchor drug. Total blood-associated HIV DNA levels were assessed by droplet digital PCR at BL and after 48 weeks (T48). Results were expressed as log10 HIV DNA copies/106 leucocytes.

Results

We enrolled 40 patients in the DT group and 40 in the TT group; the two groups were homogeneous for all main characteristics except nadir CD4 cell count. At BL, HIV DNA levels were comparable between the DT and TT groups: 2.27 (IQR 1.97–2.47) and 2.26 (IQR 2.05–2.61) log10 HIV DNA copies/106 leucocytes, respectively. Change in HIV DNA load from BL to T48 was −0.105 (IQR −0.384 to 0.121, P = 0.041) in the DT group and −0.132 (IQR −0.362 to 0.046, P = 0.005) in the TT group, with a comparable decline observed between the two groups (P = 0.821). A higher HIV DNA decline was associated with higher BL CD4/CD8 ratio.

Conclusions

Maintenance therapy with dolutegravir/lamivudine had the same impact as the triple regimen on HIV DNA levels after 48 weeks of treatment. These data seem to support the effectiveness of a dolutegravir/lamivudine dual regimen in controlling the magnitude of the cellular reservoir (www.clinicaltrials.gov, number NCT02836782).
Reproductive Endocrinology Reference Intervals for Transgender Women on Stable Hormone Therapy
Authors: Greene Dina N , Schmidt Robert L , Winston McPherson Gabrielle , Rongitsch Jessica , Imborek Katherine L , Dickerson Jane A , Drees Julia C , Humble Robert M , Nisly Nicole , Dole Nancy J , Dane Susan K , Frerichs Janice , Krasowski Matthew D
Published: February 2020

Background

Transgender women and nonbinary people seeking feminizing therapy are often prescribed estrogen as a gender-affirming hormone, which will alter their reproductive hormone axis. Testosterone, estradiol, and other reproductive hormones are commonly evaluated to assess therapy, but reference intervals specific to transgender women have not been established. The objective of this study was to derive reference intervals for commonly measured analytes related to reproductive endocrinology in a cohort of healthy gender nonconforming individuals on stable feminizing hormone therapy.

Methods

Healthy transgender individuals who had been prescribed estrogen (n = 93) for at least a year were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Total testosterone and estradiol were measured using immunoassay and mass spectrometry; LH, FSH, sex hormone binding globulin, prolactin, progesterone, anti-mullerian hormone (AMH), and dehydroepiandrosterone sulfate (DHEAS) were measured using immunoassay; free testosterone was calculated. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines.

Results

The distribution of results for transgender women was different than what would be expected from cisgender men or women across all measurements. Use of spironolactone was associated with changes in the result distribution of AMH, FSH, LH, and progesterone. Compared to liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS), immunoassay was sufficient for the majority of estradiol and total testosterone measurements; free testosterone added little clinical value beyond total testosterone.

Conclusion

Reference intervals specific to transgender women should be applied when evaluating reproductive endocrine analytes. Spironolactone is a significant variable for result interpretation of some tests.
Disc galaxies formed from major mergers in Illustris
Authors: Peschken Nicolas , Łokas Ewa L , Athanassoula E
Published: February 2020

We show how wet major mergers can create disc galaxies in a cosmological context, using the Illustris simulation. We select a sample of 38 disc galaxies having experienced a major merger in their history with no subsequent significant minor merger, and study how they transform into discs after the merger. In agreement with what was previously found in controlled simulations of such mergers, we find that their disc is built gradually from young stars formed after the merger in the disc region, while the old stars born before the merger form an ellipsoidal component. Focusing on one fiducial case from our sample, we show how the gas was initially dispersed in the halo region right after the merger, but is then accreted on to a disc to form stars, and builds the disc component. We then select a sample of major mergers creating elliptical galaxies, to show that those cases correspond mainly to dry mergers, where the lack of star formation prevents the formation of a disc in the remnant galaxy. The amount of gas in the remnant galaxy after the merger is therefore essential to determine the final outcome of a major merger.
J. SAINSBURY PLC v FROMAGERIES BEL SA
Authors:   Intellectual Property Office
Published: February 2020

H1 Trade marks – Invalidation proceedings – Shape mark with dimension and colour limitations – Assessment of essential characteristics – Effect of limitations - Whether mark consisting exclusively of a shape – Whether shape resulting from the nature of the goods or necessary to achieve a technical result – Whether shape giving substantial value to the goods – Colours – Graphical representation - Requirement of clarity and precision - Whether limitation to “red” sufficient
SYSTEM PRODUCTS UK LTD v TRUSCOTT TERRACE HOLDINGS LLC
Authors:   Appointed Person (Designs)
Published: February 2020

H1 Registered designs – Validity – Bottle shapes – Novelty – Res judicata – Issue estoppel – Clarity of pleading – Whether ground now relied upon could and should have been raised in earlier proceedings – Whether sister companies were “privies” – Use of “Wayback Machine” evidence – Litigants without professional representation – Appeal to Appointed Person
Identification of Hidden Population Structure in Time-Scaled Phylogenies
Authors: Volz Erik M , Carsten Wiuf , Grad Yonatan H , Frost Simon D W , Dennis Ann M , Didelot Xavier
Published: February 2020

Population structure influences genealogical patterns, however, data pertaining to how populations are structured are often unavailable or not directly observable. Inference of population structure is highly important in molecular epidemiology where pathogen phylogenetics is increasingly used to infer transmission patterns and detect outbreaks. Discrepancies between observed and idealized genealogies, such as those generated by the coalescent process, can be quantified, and where significant differences occur, may reveal the action of natural selection, host population structure, or other demographic and epidemiological heterogeneities. We have developed a fast non-parametric statistical test for detection of cryptic population structure in time-scaled phylogenetic trees. The test is based on contrasting estimated phylogenies with the theoretically expected phylodynamic ordering of common ancestors in two clades within a coalescent framework. These statistical tests have also motivated the development of algorithms which can be used to quickly screen a phylogenetic tree for clades which are likely to share a distinct demographic or epidemiological history. Epidemiological applications include identification of outbreaks in vulnerable host populations or rapid expansion of genotypes with a fitness advantage. To demonstrate the utility of these methods for outbreak detection, we applied the new methods to large phylogenies reconstructed from thousands of HIV-1 partial pol sequences. This revealed the presence of clades which had grown rapidly in the recent past and was significantly concentrated in young men, suggesting recent and rapid transmission in that group. Furthermore, to demonstrate the utility of these methods for the study of antimicrobial resistance, we applied the new methods to a large phylogeny reconstructed from whole genome Neisseria gonorrhoeae sequences. We find that population structure detected using these methods closely overlaps with the appearance and expansion of mutations conferring antimicrobial resistance. [Antimicrobial resistance; coalescent; HIV; population structure.]
Effects of supplement amount, with or without calcium salts of fatty acids, on growth performance and intake behavior of grazing Bos indicus bulls
Authors: Cappellozza Bruno I , Velasco André C , Tongu Cintya , Moraes Gustavo , Dib Renato , Cervieri Rafael
Published: February 2020

This study evaluated the effects of 2 supplement dry matter (DM) amounts, with or without calcium salts of fatty acids (CSFA), on growth performance, supplement and water intake behavior of grazing beef bulls. On day 0, 32 Nellore bulls were ranked by initial body weight (BW; 318 ± 11.2 kg), and then, randomly assigned to treatments (n = 8 bulls/treatment), in a 2 × 2 factorial design, which consisted of energy-based supplement DM amount of 0.3 (SP03) or 1.0 (SP1) % of BW with (+) or without (−) CSFA fortification (90 to 100 g/bull daily). During the experiment (98 d), all bulls were managed as single group and rotated between 2 Brachiaria pastures every 9 to 11 d. Each pasture contained an individual electronic data capture system with 2 feed bunks/treatment and 1 water through to determine individual supplement DM and water intake, as well number of visits, time spent at the feeder/waterer, and intake per visit (IPV). A supplement effect was detected (P = 0.02) for final BW. Bulls supplemented at 1.0% of BW, regardless of CSFA inclusion amount, were heavier at the end of the experiment vs. SP03 bulls. Overall average daily gain (ADG) was greater (P = 0.05) for SP03+ vs. SP03− bulls, and did not differ (P = 0.87) between SP1+ vs. SP1− bulls. No supplement amount, CSFA, or supplement amount × CSFA effects were observed (P ≥ 0.13) for supplement and water intake behavior, number of visits to the feeder or IPV. However, SP1 bulls spent (P = 0.05) more time at the feeder than SP1+ bulls, whereas bulls supplemented with CSFA tended (P = 0.10) to consume less water (as % of BW) than cohorts supplemented without CSFA. In summary, CSFA fortification into 0.3% of BW supplements increased ADG when compared with cohorts not offered CSFA. On the other hand, no benefits were observed when CSFA was included into 1.0% of BW supplements, primarily due to the lower than projected supplement, and consequently, CSFA intake. Moreover, CSFA fortification tended to reduced water intake, demonstrating a potential of this technology to increase performance of beef herds, while maintaining the utilization of natural resources.
Nucleos(t)ide analogue continuous therapy associated with reduced adverse outcomes of chronic hepatitis B
Authors: Su Chien-Wei , Wu Chun-Ying , Lin Jaw-Town , Ho Hsiu J. , Wu Jaw-Ching
Published: February 2020

Background:

Nucleos(t)ide analogue (NA) therapy reduces the risk of disease progression in chronic hepatitis B virus-infected patients. However, the risk of liver decompensation, hepatic failure, and mortality after discontinuation of NA therapy remains unknown.

Methods:

Among 51,574 chronic hepatitis B patients who received NAs in the Taiwan National Health Insurance Research Database, we identified 8,631 patients who continued NA therapy (treatment cohort) and 8,631 propensity-score matched patients who stopped NA therapy after their initial 1.5 years treatment (off-therapy cohort) between October 1, 2003 and December 31, 2011. All study subjects were followed up from the index date, that is, the date 1.5 years after the first prescription of NA, until development of liver decompensation and hepatic failure, death or end of 18-month follow-up period.

Results:

Treatment cohort had significantly lower risks of liver decompensation (1.05%; 95% confidence interval [CI], 0.81%–1.30% vs 2.13%; 95% CI, 1.82%–2.45%; p < 0.001), hepatic failure (0.35%; 95% CI, 0.21%–0.49% vs 0.63%; 95% CI, 0.46%–0.80%; p = 0.008) and overall mortality (1.67%; 1.37%–1.98% vs 2.44%; 95% CI, 2.10%–2.77%; p < 0.001) during the 18-month follow-up period. After adjusting for potential confounders, NA continuous therapy was associated with reduced risks of liver decompensation (hazard ratio [HR]: 0.47; 95% CI, 0.36–0.62, p < 0.001), hepatic failure (HR: 0.53; 95% CI, 0.33–0.86, p = 0.01) and overall mortality (HR: 0.67; 95% CI, 0.53–0.84, p = 0.001). The number needed to reduce one less disease progression and mortality was 47. The protective effect of NA continuous therapy was found in nearly all subgroups.

Conclusion:

NA continuous therapy is associated with reduced risks of liver decompensation, hepatic failure, and overall mortality.
Infant anaphylaxis: Diagnostic and treatment challenges
Authors: Shroba Jodi A.
Published: February 2020

Immediate administration of intramuscular epinephrine to a patient experiencing anaphylaxis is the first-line therapy for this life-threatening allergic reaction. Alhough anaphylaxis is generally a rare occurrence, it has dire consequences if left untreated. In infants, anaphylaxis is typically triggered by exposure to egg, cow's milk, or peanuts. The rapid onset of symptoms in multiple organ systems makes an accurate diagnosis in infants difficult because there are numerous ways in which anaphylaxis may present. The symptoms of infant anaphylaxis are often underrecognized or misdiagnosed for less serious illnesses or even normal findings, including drooling, loose stools, and irritability. Because infants are mostly nonverbal—and most pediatric emergency department visits for anaphylaxis cases are the first diagnosis—ascertaining potential exposure to common allergens is difficult; this further complicates diagnosis in these youngest patients for whom the clinical presentation of anaphylaxis varies widely. A key factor in diagnosing anaphylaxis is the temporal profile of symptom development following allergen exposure; however, some children with anaphylaxis develop symptoms that reoccur hours or days after an initial anaphylactic reaction, making diagnosis challenging. Advanced practice nurses are often the first health care provider to encounter a patient who may be experiencing anaphylaxis. Although diagnostic criteria exist for anaphylaxis, specific criteria for the diagnosis of anaphylaxis in infants have not been developed. As such, it is important to understand and recognize the variable presentation of anaphylaxis in infants and to rapidly diagnose and treat with epinephrine.
Small Cell Lung Cancer Neuroendocrine Subtypes are Associated with Different Immune Microenvironment and Checkpoint Molecule Distribution
Authors: Dora David , Rivard Christopher , Yu Hui , Bunn Paul , Suda Kenichi , Ren Shengxiang , Pickard Shivaun Lueke , Laszlo Viktoria , Harko Tunde , Megyesfalvi Zsolt , Moldvay Judit , Hirsch Fred R. , Dome Balazs , Lohinai Zoltan
Published: February 2020

Small cell lung cancer (SCLC) has recently been sub-categorized into neuroendocrine (NE)- high and NE-low subtypes showing ‘immune desert’ and ‘immune oasis’ phenotypes, respectively. We aimed to characterize the immune cell localization and the microenvironment according to immune checkpoints and NE subtypes in human SCLC tissue samples at the protein level. In this cross-sectional study, we included 32 primary tumors and matched lymph node (LN) metastases of resected early-stage, histologically confirmed SCLC patients, which were previously clustered into NE subtypes using NE-associated key RNA genes. Immunohistochemistry (IHC) was performed on FFPE TMAs with antibodies against CD45, CD3, CD8 and immune checkpoints including poliovirus receptor (PVR) and Indoleamine 2,3-dioxygenase (IDO).

According to our results, the stroma was significantly more infiltrated by immune cells both in primary tumors and LN metastases (vs tumor cell nests). Immune (CD45+) cell density was significantly higher in tumor nests (110.6 ± 24.95 vs 42.74 ± 10.30, cell/mm2, p= 0.0048), with increased CD8+ effector T cell infiltration (21.81 ± 5.458 vs 3.16 ± 1.36 cell/mm2, p < 0.001) in NE-low vs NE-high tumors. Furthermore, the expression of IDO was confirmed on stromal and endothelial cells, and it positively correlated (r= 0.755, p<0.01) with higher immune cell density both in primary tumors and LN metastases, regardless of the NE pattern. Expression of IDO in tumor nests was significantly higher in NE-low (vs NE-high) primary tumors. PVR expression was significantly higher in NE-low (vs NE-high) patients both in primary tumors) and LN metastases.

To our knowledge, this is the first human study that demonstrates in situ that NE-low tumors are associated with increased immune cell infiltration compared to NE-high tumors. PVR and IDO are potential new targets in SCLC, with increased expression in the NE-low subtype, providing key insight for further prospective studies on potential biomarkers and targets for SCLC immunotherapies.
Giant African snail genomes provide insights into molluscan whole-genome duplication and aquatic-terrestrial transition
Authors: Liu Conghui , Ren Yuwei , Li Zaiyuan , Hu Qi , Yin Lijuan , Qiao Xi , Zhang Yan , Xing Longsheng , Xi Yu , Jiang Fan , Wang Sen , Huang Cong , Liu Bo , Wang Hengchao , Liu Hangwei , Wan Fanghao , Qian Wanqiang , Fan Wei
Published: February 2020

Whole-genome duplication (WGD) has been observed across a wide variety of eukaryotic groups, contributing to evolutionary diversity and environmental adaptability. Mollusks are the second largest group of animals, and are among the organisms that have successfully adapted to the nonmarine realm through aquatic-terrestrial (A-T) transition, and no comprehensive research on WGD has been reported in this group. To explore WGD and the A-T transition in Mollusca, we assembled a chromosome-level reference genome for the giant African snailAchatina immaculata, a global invasive species, and compared the genomes of two giant African snails (A. immaculataandAchatina fulica) to the other available mollusk genomes. The chromosome-level macrosynteny, colinearity blocks, Ks peak and Hox gene clusters collectively suggested the occurrence of a WGD event shared byA. immaculataandA. fulica. The estimated timing of this WGD event (∼70 MYA) was close to the speciation age of the Sigmurethra-Orthurethra (within Stylommatophora) lineage and the Cretaceous-Tertiary (K-T) mass extinction, indicating that the WGD reported herein may have been a common event shared by all Sigmurethra-Orthurethra species and could have conferred ecological adaptability and genomic plasticity allowing the survival of the K-T extinction. Based on macrosynteny, we deduced an ancestral karyotype containing 8 conserved clusters for the Gastropoda-Bivalvia lineage. To reveal the mechanism of WGD in shaping adaptability to terrestrial ecosystems, we investigated gene families related to the respiration, aestivation and immune defense of giant African snails. Several mucus-related gene families expanded early in the Stylommatophora lineage, functioning in water retention, immune defense and wound healing. The hemocyanins, PCK and FBP families were doubled and retained after WGD, enhancing the capacity for gas exchange and glucose homeostasis in aestivation. After the WGD, zinc metalloproteinase genes were highly tandemly duplicated to protect tissue against ROS damage. This evidence collectively suggests that although the WGD may not have been the direct driver of the A-T transition, it provided an important legacy for the terrestrial adaptation of the giant African snail.