bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐Collimation and Slow Light‐Based Refractive Index Sensor with a Large Detection Range
Authors: Barough Ali Samadian , Noori Mina , Abbasiyan Amin
Published: May 2021

In this study, a refractive index sensor based on self‐collimation and slow light is presented which operates in the Mid‐IR range (4 µm < λ < 4.133 µm). Here, the square and hexagonal arrays are merged as the background platform and the sensing area, respectively to provide self‐collimation and slow light properties. Three sensors based on slow‐light and self‐collimation are presented in detail which provide Q‐factor, sensitivity, and detection range of 227, 104 nm RIU−1, and 1–1.7, respectively in the best case. Furthermore, the sensor design based on self‐collimation and photonic bandgap phenomena in the background platform and the sensing area, respectively is presented with a single detection unit. The presented sensors are capable of gas or liquid detection with refractive indices in the range of 1–2 with enhanced Q‐factor and sensitivity of over 620 and 123, respectively.
The Desensitized Channelrhodopsin‐2 Photointermediate Contains 13 ‐cis, 15 ‐syn Retinal Schiff Base
Authors: Becker‐Baldus Johanna , Leeder Alexander , Brown Lynda J. , Brown Richard C. D. , Bamann Christian , Glaubitz Clemens
Published: May 2021

Channelrhodopsin‐2 (ChR2) is a light‐gated cation channel and was used to lay the foundations of optogenetics. Its dark state X‐ray structure has been determined in 2017 for the wild‐type, which is the prototype for all other ChR variants. However, the mechanistic understanding of the channel function is still incomplete in terms of structural changes after photon absorption by the retinal chromophore and in the framework of functional models. Hence, detailed information needs to be collected on the dark state as well as on the different photointermediates. For ChR2 detailed knowledge on the chromophore configuration in the different states is still missing and a consensus has not been achieved. Using DNP‐enhanced solid‐state MAS NMR spectroscopy on proteoliposome samples, we unambiguously determined the chromophore configuration in the desensitized state, and we show that this state occurs towards the end of the photocycle.
Limonin as a Starting Point for the Construction of Compounds with High Scaffold Diversity
Authors: Furiassi Lucia , Tonogai Emily J. , Hergenrother Paul J.
Published: May 2021

Structurally complex natural products have been a fruitful source for the discovery and development of new drugs. In an effort to construct a compound collection populated by architecturally complex members with unique scaffolds, we have used the natural product limonin as a starting point. Limonin is an abundant triterpenoid natural product and, through alteration of its heptacyclic core ring system using short synthetic sequences, a collection of 98 compounds was created, including multiple members with novel ring systems. The reactions leveraged in the construction of these compounds include novel ring cleavage, rearrangements, and cyclizations, and this work is highlighted by the discovery of a novel B‐ring cleavage reaction, a unique B/C‐ring rearrangement, an atypical D‐ring cyclization, among others. Computational analysis shows that 52 different scaffolds/ring systems were produced during the course of this work, of which 36 are unprecedented. Phenotypic screening and structure–activity relationships identified compounds with activity against a panel of cancer cell lines.
Highly Soluble Supertetrahedra upon Selective Partial Butylation of Chalcogenido Metalate Clusters in Ionic Liquids
Authors: Peters Bertram , Stuhrmann Gina , Mack Fabian , Weigend Florian , Dehnen Stefanie
Published: May 2021

Supertetrahedral clusters have been reported in two generally different types so far: one type possessing an organic ligand shell, no or low charges, and high solubility, while the other cluster type is ligand‐free with usually high charges and low or no solubility in common solvents. The latter is a tremendous disadvantage regarding further use of the clusters in solution. However, as organic substituents usually broaden the HOMO–LUMO gaps, which cannot be overcompensated by the (limited) cluster sizes, a full organic shielding comes along with drawbacks regarding opto‐electronic properties. We therefore sought to find a way of generating soluble clusters with a minimum number of organic substituents. Here, we present the synthesis and full characterization of two salts of [Sn10O4S16(SBu)4]4− that are high soluble in CH2Cl2 or CH3CN, which includes first NMR and mass spectra obtained from solutions of such salts with mostly inorganic supertetrahedral clusters. The optical absorption properties of this new class of compounds indicates nearly unaffected band gaps. The synthetic approach and the spectroscopic findings were rationalized and explained by means of high‐level quantum chemical studies.
Programmable Dynamic Shapes with a Swarm of Light‐Powered Colloidal Motors
Authors: Chen Meiling , Lin Zhihua , Xuan Mingjun , Lin Xiankun , Yang Mingcheng , Dai Luru , He Qiang
Published: May 2021

We report robust control over the dynamic assembly, disassembly, and reconfiguration of light‐activated molybdenum disulfide (MoS2) colloidal motor swarms with features not possible in equilibrium systems. A photochemical reaction produces chemical gradients across the MoS2 colloidal motors to drive them to move. Under illumination of a gradient light, these colloidal motors display a positive phototactic motion. Mesoscale simulations prove that the self‐diffusiophoresis induced by the locally consumed oxygen gradient across MoS2 colloidal motors dominates the phototactic process. By programming the structured illumination, the collective migration and well‐defined shapes of colloidal motor swarms can be externally regulated. The successful realization of programmable swarm transformation of colloidal motors like the emergent behaviors of living systems in nature provides a direct proof‐of‐concept for active soft materials and systems, with adaptive and interactive functions.
Cucurbituril‐Encapsulating Metal–Organic Framework via Mechanochemistry: Adsorbents with Enhanced Performance
Authors: Liang Jun , Gvilava Vasily , Jansen Christian , Öztürk Secil , Spieß Alex , Lin Jingxiang , Xing Shanghua , Sun Yangyang , Wang Hao , Janiak Christoph
Published: May 2021

The first examples of monolithic crystalline host–guest hybrid materials are described. The reaction of 1,3,5‐benzenetricarboxylic acid (H3BTC) and Fe(NO3)3⋅9 H2O in the presence of decamethylcucurbit[5]uril ammonium chloride (MC5⋅2 NH4Cl⋅4 H2O) directly affords MC5@MIL‐100(Fe) hybrid monoliths featuring hierarchical micro‐, meso‐ and macropores. Particularly, this “bottle‐around‐ship” synthesis and one‐pot shaping are facilitated by a newly discovered Fe‐MC5 flowing gel formed by mechanochemistry. The designed MC5@MIL‐100(Fe) hybrid material with MC5 as active domains shows enhanced CH4and lead(II) uptake performance, and selective capture of lead(II) cations at low concentrations. This shows that host–guest hybrid materials can exhibit synergic properties that out‐perform materials based on individual components.
A Bubble‐Assisted Approach for Patterning Nanoscale Molecular Aggregates
Authors: Min Fanyi , Zhou Peng , Huang Zhandong , Qiao Yali , Yu Changhui , Qu Zhiyuan , Shi Xiaosong , Li Zheng , Jiang Lang , Zhang Zhen , Yan Xuehai , Song Yanlin
Published: May 2021

We demonstrate a new approach to pattern functional organic molecules with a template of foams, and achieve a resolution of sub 100 nm. The bubble‐assisted assembly (BAA) process is consisted of two periods, including bubble evolution and molecular assembly, which are dominated by the Laplace pressure and molecular interactions, respectively. Using TPPS (meso‐tetra(4‐sulfonatophenyl) porphyrin), we systematically investigate the patterns and assembly behaviour in the bubble system with a series of characterizations, which show good uniformity in nanoscale resolution. Theoretical simulations reveal that TPPS's J‐aggregates contribute to the ordered construction of molecular patterns. Finally, we propose an empirical rule for molecular patterning approach, that the surfactant and functional molecules should have the same type of charge in a two‐component system. This approach exhibits promising feasibility to assemble molecular patterns at nanoscale resolution for micro/nano functional devices.
Plastic Waste Conversion over a Refinery Waste Catalyst
Authors: Vollmer Ina , Jenks Michael J. F. , Mayorga González Rafael , Meirer Florian , Weckhuysen Bert M.
Published: May 2021

Polypropylene (PP) makes up a large share of our plastic waste. We investigated the conversion of PP over the industrial Fluid Catalytic Cracking catalyst (FCC‐cat) used to produce gasoline from crude oil fractions. We studied transport limitations arising from the larger size of polymers compared to the crude oil‐based feedstock by testing the components of this catalyst separately. Infrared spectroscopy and confocal fluorescence microscopy revealed the role of the FCC matrix in aromatization, and the zeolite Y domains in coking. An equilibrium catalyst (ECAT), discarded during FCC operation as waste, produced the same aromatics content as a fresh FCC‐cat, while coking decreased significantly, likely due to the reduced accessibility and activity of the zeolite domains and an enhanced cracking activity of the matrix due to metal deposits present in ECAT. This mechanistic understanding provides handles for further improving the catalyst composition towards higher aromatics selectivity.
Anchoring Cu nanoparticles on functionalized multi‐walled carbon nanotube for regioselective synthesis of 1,2,3‐triazoles via click reaction
Authors: Khoshnevis Mahsa , Eshghi Hossein
Published: May 2021

Unique properties of 1,2,3‐triazoles on the one hand and necessity of usage of an efficient catalyst with fidelity in principles of green chemistry on the other hand impelled us to design and synthesis of a novel heterogeneous nanocatalyst (Cu@Arg‐MWCNTs) with simple synthesis, immense power, high regioselectivity, and easy separation and recyclability. The Cu@Arg‐MWCNT structure is characterized by different analyses and used for the synthesis of various triazoles. Its high catalytic activity is confirmed by high yields and short reaction times under mild conditions in click reaction.
Fabrication of halloysite nanotubes embedded thin film nanocomposite membranes for dye removal
Authors: Ormanci‐Acar Turkan , Keskin Basak , Korkut Sevde , Mutlu‐Salmanlı Oyku , Turken Turker , Koseoglu‐Imer Derya Y. , Demir Tugba U. , Menceloglu Yusuf Z. , Unal Serkan , Koyuncu Ismail
Published: May 2021

Environmental friendly Halloysite nanotubes (HNTs) are used to fabricate novel nanofiltration membranes by in situ interfacial polymerization of piperazine and trimesoyl chloride. The removal of excess amine solution from the porous support membrane surface is a critical step to obtain defect free active layer. Hereby, two main removal tools for the excess aqueous amine solution; a rubber roll or air knife are compared to fabricate a defect free thin film nanocomposite (TFN) nanofiltration (NF) membrane. Removal by the rubber roll is eventuated more favorable than air knife in terms of the reproducibility of NF membranes by comparing salt rejections. By determining the removal step of excess amines, various HNTs concentrations are used to fabricate NF membranes and, these membranes are tested with salt and dye solutions at various pH and temperature ranges. R2 membrane (containing 0.02% [w/v] HNTs) performs the best flux results beside higher rejections of MgSO4 (93.0%) and dye (99.5%). To evaluate the extreme conditionals, further performance tests such as pH and temperature resistance are also performed for R2 membrane. Considering the performances of R2 membrane, HNTs can be demonstrated for tailoring the balance between flux and separation performance of NF membranes.
Conventionally facile fabrication of mechanically robust waterborne polyurethane with self‐healing and photoluminescence
Authors: Lei Yuan , Wu Bo , Yuan Anqian , Lei Jingxin , Jiang Liang
Published: May 2021

It is of much importance to synthesize waterborne polyurethane (WPUs) that simultaneously broaden the fields of applications and functions in a green strategy. In this paper, a novel class of WPUs were facilely prepared through the copolymerization between polytetrahydrofuran ether diol (PTMG), isophorone diisocyanate, and 2,2‐bis(hydroxymethyl)propionic acid, which can achieve multiple functions of self‐healing and photoluminescence after incorporating carbon quantum dots (CQs) into the WPUs. The prepared WPUs emulsion showed uniform size distribution from 61.97 nm to171.3 nm with different PTMG molecular weights. Especially, the maximum tensile strength and elongation at break of the WPUs can reach up to 69.78 MPa and 1879.99%, showing superior mechanical performance. After fractured surfaces held contact for 12 h at elevated temperature, the self‐healing efficiency of the pristine WPUs can reach 21.39% for tensile strength and 24.79% for elongation at break. After adding CQs, the synthesized WPUs can also remain nearly the same tensile strength and elongation at break. Significantly, the self‐healing WPUs with CQs can emit a bright orange fluorescence under ultraviolet light, showing outstanding photoluminescence. This kind of designed material takes advantages of simple preparation, no release of organic solvents during use, nontoxicity and harmlessness.
Estrogen‐Induced hsa‐miR‐10b‐5p Is Elevated in T Cells From Patients With Systemic Lupus Erythematosus and Down‐Regulates Serine/Arginine‐Rich Splicing Factor 1
Authors: Ramanujan Suruchi A. , Cravens Elena N. , Krishfield Suzanne M. , Kyttaris Vasileios C. , Moulton Vaishali R.
Published: May 2021

Objective

Autoimmune diseases affect women disproportionately more than men. Estrogen is implicated in immune cell dysfunction, yet its precise molecular roles are not fully known. We recently identified new roles for serine/arginine‐rich splicing factor 1 (SRSF1) in T cell function and autoimmunity. SRSF1 levels are decreased in T cells from patients with systemic lupus erythematosus (SLE) and are associated with active disease and comorbidity. However, the molecular mechanisms that control SRSF1 expression are unknown. Srsf1 messenger RNA (mRNA) has a long 3′‐untranslated region (3′‐UTR), suggesting posttranscriptional control. This study was undertaken to investigate the role of estrogen and posttranscriptional mechanisms of SRSF1 regulation in T cells and SLE.

Methods

In silico bioinformatics analysis of Srsf1–3′‐UTR revealed multiple microRNA (miRNA; miR)–binding sites. Additional screening and literature searches narrowed down hsa‐miR‐10b‐5p for further study. Peripheral blood T cells from healthy individuals and SLE patients were evaluated for mRNA and miRNA expression by quantitative reverse transcription–polymerase chain reaction, and SRSF1 protein levels were assessed by immunoblotting. T cells were cultured with β‐estradiol, and transient transfections were used to overexpress miRNAs. Luciferase assays were used to measure 3′‐UTR activity.

Results

We demonstrated that estrogen increased hsa‐miR‐10b‐5p expression in human T cells, and hsa‐miR‐10b‐5p down‐regulated SRSF1 protein expression. Mechanistically, hsa‐mir‐10b‐5p regulated SRSF1 posttranscriptionally via control of its 3′‐UTR activity. Importantly, hsa‐miR‐10b‐5p expression levels were elevated in T cells from healthy women compared to healthy men and also elevated in T cells from SLE patients.

Conclusion

We identified a previously unrecognized molecular link between estrogen and gene regulation in immune cells, with potential relevance to systemic autoimmune disease.
Influence of mixing height and atmospheric stability conditions on correlation of NO2 columns and surface concentrations in a Mexico‐United States border region
Authors: Flores‐Jiménez David E. , García‐Cueto O. Rafael , Santillán‐Soto Néstor , López‐Velázquez J. Ernesto , Camargo‐Bravo Adriana
Published: May 2021

The objective was to analyze how representative tropospheric NO2 column densities are of surface NO2 measurements under different atmospheric stability conditions in the air basin of two border cities: Calexico, United States, and Mexicali, Mexico. NO2 columns were measured by the Ozone Monitoring Instrument (OMI) on the NASA Aura satellite. NO2 concentrations and meteorological parameters were also measured on the surface for comparison. Specifically, the correlations between OMI and surface NO2 concentrations under different atmospheric stability conditions according to the Pasquill‐Gifford (P‐G) and Monin‐Obukhov (M‐O) classification schemes were determined for 2017 and 2018. During the passage of the satellite through the study area (11:00–13:00 UTC−8), unstable conditions were documented in both years. Good correlation was found between the surface NO2 and OMI NO2 column observations in the second semester of each year, particularly under unstable conditions as diagnosed by the P‐G and M‐O schemes applied in the first and second year, respectively. However, a weakening of these conditions occurs during the autumn–winter period. In both cases, the highest determination coefficients were found for Calexico, with values of 0.48 and 0.36 in 2017 and 2018, respectively; for Mexicali, the determination coefficients were 0.23 and 0.35, respectively. Under each atmospheric stability scheme, the mechanical and convective turbulence caused a decreasing trend in wind speed and solar radiation over the course of second semester of 2017 and in friction velocity, temperature, and sensible heat flux over the course of the same period for 2018. The negative trend of these parameters during the analyzed time frames helped to reduce the influence of unstable atmospheric conditions, favoring better correlations between satellite and surface NO2 measurements. The methodology applied and results obtained herein can enable us to better understand the representativeness of OMI NO2 data in arid border zones with extreme meteorological conditions.
High‐Energy Nickel‐Cobalt‐Aluminium Oxide (NCA) Cells on Idle: Anode‐ versus Cathode‐Driven Side Reactions
Authors: Zülke Alana , Li Yi , Keil Peter , Burrell Robert , Belaisch Sacha , Nagarathinam Mangayarkarasi , Mercer Michael P. , Hoster Harry E.
Published: May 2021

Invited for this month's cover picture is the group of Prof. Harry Hoster at Lancaster University. The cover picture illustrates how state of charge (SoC) influences the capacity fade of a widely employed automotive Li‐ion battery chemistry when idle, e.g. when EVs are parked. The chemical degradation is revealed to be aggravated when devices are kept at around 80 % SoC. Read the full text of the Article at 10.1002/batt.202100046.
Identification of Environmental and Experimental Factors Influencing Human Perception of DC and AC Electric Fields
Authors: Jankowiak Kathrin , Driessen Sarah , Kaifie Andrea , Kimpeler Simon , Krampert Thomas , Kraus Thomas , Stunder Dominik , Kursawe Michael
Published: May 2021

As part of the energy transition in Germany, high‐voltage direct current (HVDC) lines producing DC electric fields (EF) are in planning. Since the human perception of DC EF was rarely investigated in the past, we aimed to identify environmental and experimental factors influencing the human perception of direct current (DC) EF, alternating current (AC) EF, and the co‐exposure of DC EF and AC EF (hybrid EF) under whole‐body exposure. Additionally, first estimates of DC EF and AC EF perception thresholds as well as differences in human perception of DC EF and AC EF concerning the type of sensation experienced and the affected body part were evaluated. A highly sophisticated exposure lab was built to expose participants to various EF strengths and ask for their assessment concerning the presence of an EF. To estimate the individual perception thresholds of 11 participants, the signal detection theory as well as the single‐interval‐adjustment matrix procedure were applied. Relative humidity could be identified as an environmental factor influencing the perception of AC EF and DC EF in different ways. An appropriate ramp slope and an exposure duration for future studies could be elaborated. Additionally, perception thresholds were lower under hybrid EF exposure than under DC EF or AC EF exposure alone. Cutaneous sensations evoked under DC EF and AC EF exposure were individually different and attributed to various parts of the body. Several environmental and experimental factors influencing the human perception of EF could be identified and provide an essential basis for a large‐scale study. © 2021 Bioelectromagnetics Society.
One‐pot synthesis of fluorescent nitrogen and sulfur–carbon quantum dots as a sensitive nanosensor for trimetazidine determination
Authors: Belal Fathalla , Mabrouk Mokhtar , Hammad Sherin , Barseem Aya , Ahmed Hytham
Published: May 2021

Water‐soluble and highly stable N,S‐doped CQDs (N,S‐CQDs) were synthesized using a low‐cost strategy with citric acid and thiosemicarbazide in one step for use as a fluorescent nanosensor. The achieved N,S‐CQDs produced strong emission at 446 nm upon excitation at 370 nm and a high quantum yield of 58.5%. The quenching effect on the prepared N,S‐CQDs was utilized for determination of trimetazidine (TMZ) spectrofluorimetrically over a wide linear range 0.04–0.5 μM (0.0106–0.133 μg ml−1) and a low limit of detection of 0.01 μM (0.002 μg ml−1). Furthermore, CDs were used as a simple and rapid fluorescent probe to determine TMZ in its pharmaceutical formulations as well as in human plasma. The method was tested in compliance with International Council for Harmonisation guidelines. The results obtained were compared statistically with those given for a reported method showing no significant variation regards accuracy and precision.
Microparticles enhance the formation of seven major classes of natural products in native and metabolically engineered actinobacteria through accelerated morphological development
Authors: Kuhl Martin , Rückert Christian , Gläser Lars , Beganovic Selma , Luzhetskyy Andriy , Kalinowski Jörn , Wittmann Christoph
Published: May 2021

Actinobacteria provide a rich spectrum of bioactive natural products and therefore display an invaluable source towards commercially valuable pharmaceuticals and agrochemicals. Here, we studied the use of inorganic talc microparticles (hydrous magnesium silicate, 3MgO·4SiO2·H2O, 10 µm) as a general supplement to enhance natural product formation in this important class of bacteria. Added to cultures of recombinant Streptomyces lividans, talc enhanced production of the macrocyclic peptide antibiotic bottromycin A2 and its methylated derivative Met‐bottromycin A2 up to 109 mg L−1, the highest titer reported so far. Hereby, the microparticles fundamentally affected metabolism. With 10 g L−1 talc, S. lividans grew to 40% smaller pellets and, using RNA sequencing, revealed accelerated morphogenesis and aging, indicated by early upregulation of developmental regulator genes such as ssgA, ssgB, wblA, sigN, and bldN. Furthermore, the microparticles re‐balanced the expression of individual bottromycin cluster genes, resulting in a higher macrocyclization efficiency at the level of BotAH and correspondingly lower levels of non‐cyclized shunt by‐products, driving the production of mature bottromycin. Testing a variety of Streptomyces species, talc addition resulted in up to 13‐fold higher titers for the RiPPs bottromycin and cinnamycin, the alkaloid undecylprodigiosin, the polyketide pamamycin, the tetracycline‐type oxytetracycline, and the anthramycin‐analogs usabamycins. Moreover, talc addition boosted production in other actinobacteria, outside of the genus of Streptomyces: vancomycin (Amycolatopsis japonicum DSM 44213), teicoplanin (Actinoplanes teichomyceticus ATCC 31121), and the angucyclinone‐type antibiotic simocyclinone (Kitasatospora sp.). For teicoplanin, the microparticles were even crucial to activate production. Taken together, the use of talc was beneficial in 75% of all tested cases and optimized natural and heterologous hosts forming the substance of interest with clusters under native and synthetic control. Given its simplicity and broad benefits, microparticle‐supplementation appears as an enabling technology in natural product research of these most important microbes.
Corporate social and environmental disclosure as a sustainable development tool provided by board sub‐committees: Do women directors play a relevant moderating role?
Authors: Pucheta‐Martínez María Consuelo , Gallego‐Álvarez Isabel , Bel‐Oms Inmaculada
Published: May 2021

The aim of this research is to examine the impact of three audit committee characteristics on corporate social and environmental responsibility (CSR) disclosure: the existence of an audit committee, audit committee independence, and audit committee financial expertise. Moreover, this research analyzes the moderating effect of board gender diversity between these audit committees' attributes and CSR reporting. The results of analyzing 13,178 firm‐year observations of non‐financial companies show that the presence of an audit committee and audit committee financial expertise are positively associated with CSR disclosure. However, a higher proportion of non‐executive directors in audit committees has a negative effect on the disclosure of CSR information. These findings suggest that some audit committees' features play an important role in ensuring the reporting of environmental, social, and economic information. Our evidence also indicates that the presence of female directors on boards increases the positive impact of financial expert membership of audit committees on CSR disclosure, while women directors moderate any negative effect of the percentage of independent directors on audit committees on CSR reporting by increasing the latter. In addition, female directors moderate the positive impact of the existence of an audit committee on the disclosure of CSR information by reducing the latter.
Breast cancer in Zimbabwe: patterns of care and correlates of adherence in a national referral hospital radiotherapy center cohort from 2014 to 2018
Authors: Elmore Shekinah Nefreteri Cluff , Mushonga Melinda , Iyer Hari Subramaniam , Kanda Caroline , Chibonda Shirley , Chipidza Fallon , Makunike Mutasa Rudo , Muchuweti David , Muguti Edwin G. , Maunganidze Aspect , Ndlovu Ntokozo , Bellon Jennifer Ruth , Nyakabau Anna Mary
Published: May 2021

Background

Breast cancer is the second most common cancer among women in Zimbabwe. Patients face socioeconomic barriers to accessing oncology care, including radiotherapy. We sought to understand patterns of care and adherence for women with breast cancer in sub‐Saharan Africa (SSA) with radiotherapy access.

Methods

A retrospective cohort was created for women with breast cancer evaluated at the Parirenyatwa Hospital Radiotherapy and Oncology Center (RTC) from 2014 to 2018. Clinical data were collected to define patterns of care. Non‐adherence was modeled as a binary outcome with different criteria for patients with localized versus metastatic disease.

Results

In total, 351 women presented with breast cancer with median age 51 at diagnosis (IQR: 43–61). Receptor status was missing for 71% (248). 199 (57%) had non‐metastatic disease, and 152 (43%) had metastases. Of women with localized disease, 34% received post‐mastectomy radiation. Of women with metastatic disease, 9.7% received radiotherapy. Metastatic disease and missing HIV status were associated with increased odds of study‐defined non‐adherence (aOR: 1.85, 95% CI: 1.05, 3.28; aOR: 2.13, 95% CI: 1.11, 4.05), while availability of ER/PR status was associated with lower odds of non‐adherence (aOR: 0.18, 95% CI: 0.09, 0.36).

Conclusions

Radiotherapy is likely underutilized for women with breast cancer, even in a setting with public sector availability. Exploring patient‐level factors that influence adherence to care may provide clinicians with better tools to support adherence and improve survival. Greater investment is needed in multidisciplinary, multimodality care for breast cancer in SSA.
Cardiovascular adverse events associated with BRAF versus BRAF/MEK inhibitor: Cross‐sectional and longitudinal analysis using two large national registries
Authors: Guha Avirup , Jain Prantesh , Fradley Michael G. , Lenihan Daniel , Gutierrez Jahir M. , Jain Chhavi , de Lima Marcos , Barnholtz‐Sloan Jill S. , Oliveira Guilherme H. , Dowlati Afshin , Al‐Kindi Sadeer
Published: May 2021

Background

Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood.

Methods

This study included all adult patients who received BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) or combinations BRAF/MEK inhibitors (vemurafenib/cobimetinib; dabrafenib/trametinib; encorafenib/binimetinib). We utilized the cross‐sectional FDA’s Adverse Events Reporting System (FAERS) and longitudinal Truven Health Analytics/IBM MarketScan database from 2011 to 2018. Various CVAEs, including arterial hypertension, heart failure (HF), and venous thromboembolism (VTE), were studied using adjusted regression techniques.

Results

In FAERS, 7752 AEs were reported (40% BRAF and 60% BRAF/MEK). Median age was 60 (IQR 49–69) years with 45% females and 97% with melanoma. Among these, 567 (7.4%) were cardiovascular adverse events (mortality rate 19%). Compared with monotherapy, combination therapy was associated with increased risk for HF (reporting odds ratio [ROR] = 1.62 (CI = 1.14–2.30); p = 0.007), arterial hypertension (ROR = 1.75 (CI = 1.12–2.89); p = 0.02) and VTE (ROR = 1.80 (CI = 1.12–2.89); p = 0.02). Marketscan had 657 patients with median age of 53 years (IQR 46–60), 39.3% female, and 88.7% with melanoma. There were 26.2% CVAEs (CI: 14.8%–36%) within 6 months of medication start in those receiving combination therapy versus 16.7% CVAEs (CI: 13.1%–20.2%) among those receiving monotherapy. Combination therapy was associated with CVAEs compared to monotherapy (adjusted HR: 1.56 (CI: 1.01–2.42); p = 0.045).

Conclusions and Relevance

In two independent real‐world cohorts, combination BRAF/MEK inhibitors were associated with increased CVAEs compared to monotherapy, especially HF, and hypertension.
Biosynthesis of [14C]‐11‐De‐O‐Methyltomaymycin, a Precursor of Radiolabelled Antibody Drug Conjugates
Authors: Aubert Catherine , Lavisse Mélanie , Roy Sebastien
Published: May 2021

Antibody drug conjugates (ADCs) are one of the most promising technologies to treat cancer as they combine the specificity of an antibody with the high potency of a cytotoxic molecule such as tomaymycin derivatives, which are DNA‐interactive antitumor antibiotics previously isolated from bacterial broth. The multistep chemical synthesis of some tomaymycin derivatives is complicated because their structures contain a reactive imine bond. Therefore, we turned to biosynthesis to obtain 14C radiolabelled tomaymycin derivative to support ADME studies. Following Hurley's work (J. Antibiotics 1977, 30, 349–370; Antimicrob. Agents Chemother. 1979, 15, 42–45; Acc. Chem. Res. 1980, 13, 263–269), the 14C radiolabel was incorporated efficiently in one step from radiolabelled tyrosine using the strain Streptomyces sp. FH6421. This process has been further optimized by using anthranilic acid as radiolabelled precursor, leading to one of the highest incorporation levels of radiochemical precursors published to date. This biosynthetic strategy is the fastest way to access such radiolabelled precursors.
Toward more efficient locality‐sensitive hashing via constructing novel hash function cluster
Authors: Zhang Shi , Huang Jin , Xiao Ruliang , Du Xin , Gong Ping , Lin Xinhong
Published: May 2021

Locality‐sensitive hashing (LSH) is widely used in the context of nearest neighbor search of large‐scale high‐dimensions. However, there are serious imbalance problems between the efficiency of data index structure construction and the query accuracy of LSH methods. In this article, a novel higher‐entropy‐hyperplane clusters LSH (HEHC‐LSH) algorithm is proposed, which we improve vector quantization to preprocess the data and greatly shortens the preprocessing time; We innovatively integrate the maximum entropy principle into the distribution estimation algorithm to construct a novel hash function cluster method, also incorporate bootstrap aggregating of ensemble learning, and adopt the parallel index dictionary to improve the generalization performance of the index structure. And in the query stage, we realize the comprehensive filtering of index set using integrated learning idea, which not only avoids a lot of distance calculation, but also improves the quality of query results. We also analyze the rationality and effectiveness of the proposed method. Finally, extensive experiment results show that HEHC‐LSH can achieve more higher precision and efficiency simultaneously comparing to current methods, and reflect the strong robustness on different datasets.
The effect of misgendering on body dissatisfaction and dietary restraint in transgender individuals: Testing a Misgendering‐Congruence Process
Authors: Mitchell Linas , MacArthur Heather J. , Blomquist Kerstin K.
Published: May 2021

Objective

Despite research findings that transgender individuals have higher rates of body dissatisfaction and disordered eating than their cisgender peers, reasons for greater eating pathology remain unclear. We propose a Misgendering‐Congruence Process by which being misgendered (i.e., labeled a gender other than that with which one identifies) could lead transgender individuals to feel greater incongruence between their bodies and internal identities, which in turn leads to body dissatisfaction and efforts to bring one's body in line with one's identified gender by engaging in weight and shape control behaviors such as dietary restraint.

Method

One hundred and thirty transgender individuals completed measures of misgendering frequency, transgender congruence, body dissatisfaction, and dietary restraint.

Results

Mediation analyses provided preliminary support for the Misgendering‐Congruence Process when conducted with the overall sample as well as with transgender subgroups: transgender women (n = 41), transgender men (n = 42), and nonbinary transgender individuals (n = 47).

Discussion

Social recognition of transgender people's gender identities appears to play a unique role in their body satisfaction and restrained eating behaviors.
Woodpeckers can act as dispersal vectors for fungi, plants, and microorganisms
Authors: Johansson Niko R. , Kaasalainen Ulla , Rikkinen Jouko
Published: May 2021

Bird‐mediated dispersal is presumed to be important in the dissemination of many different types of organisms, but concrete evidence remains scarce. This is especially true for biota producing microscopic propagules. Tree‐dwelling birds, such as woodpeckers, would seem to represent ideal dispersal vectors for organisms growing on standing tree trunks such as epiphytic lichens and fungi. Here, we utilize bird natural history collections as a novel source of data for studying dispersal ecology of plants, fungi, and microorganisms. We screened freshly preserved specimens of three Finnish woodpecker species for microscopic propagules. Samples were taken from bird feet, and chest and tail feathers. Propagules were extracted using a sonication–centrifugation protocol, and the material obtained was studied using light microscopy. Diverse biological material was recovered from all specimens of all bird species, from all positions sampled. Most abundant categories of discovered biological material included bryophyte fragments, fungal spores, and vegetative propagules of lichens. Also, freshwater diatoms, bryophyte spores, algal cells, testate amebae, rotifers, nematodes, pollen, and insect scales were identified. The method developed here is applicable to living specimens as well, making it a versatile tool for further research. Our findings highlight the potential of bird‐mediated dispersal for diverse organisms and showcase the use of natural history collections in ecological research.
The influence of predators, competitors, and habitat on the use of water sources by a small desert carnivore
Authors: Hall Lucas K. , Larsen Randy T. , Knight Robert N. , McMillan Brock R.
Published: May 2021

Free water can influence the ecology of desert species. While the use of free water is influenced by physiological factors (e.g., species‐specific water requirements, moisture in forage, temperature), nonphysiological factors, such as habitat characteristics and interspecific interactions, are also important. In fact, for species of concern, interspecific interactions and habitat can be important factors influencing their spatial and temporal use of the landscape and its resources. The kit fox (Vulpes macrotis) is a small carnivore considered to be a species of concern over much of its range, and two of the most important conservation challenges it faces are related to (1) habitat and (2) predation/competition by intraguild species. Our objective was to determine the influence of habitat characteristics, predators (bobcats [Lynx rufus], coyotes [Canis latrans]), and potential competitors (badgers [Taxidea taxus], gray foxes [Urocyon cinereoargenteus]) on the use of water by kit foxes. From June to September 2010–2012, we used remote cameras to monitor carnivores at 63 water sources in the Mojave Desert. We used zero‐inflated mixed‐effects models and a two‐stage model selection analysis to evaluate the influence of habitat, predators, and competitors on spatial visits to water by kit foxes. We also assessed temporal avoidance of intraguild predators and competitors by kit foxes at water sources using a coefficient of overlap. We found that visual obscurity, overhead canopy cover, badgers, and coyotes influenced spatial visits of kit foxes. In addition, kit foxes exhibited strong temporal overlap with badgers and bobcats, moderate temporal overlap with gray foxes, and weak temporal overlap with coyotes. Taken together, our study demonstrates that the spatial and temporal use of water sources by kit foxes is dynamic, depending on habitat characteristics and the activity of intraguild predators and competitors.
Rhodium(III)‐Catalyzed Formal Cycloaddition between Thienopyridine/Thienopyrazine Carboxylic Acids and Alkynes, Triggered by C−H Activation
Authors: Rodrigues Juliana M. , Cendón Borja , Gulías Moisés , Mascareñas José Luis , Queiroz Maria‐João R. P.
Published: May 2021

In the last decade, a number of metal‐catalyzed technologies for the functionalization of C−H bonds in carbonaceous aromatic substrates have been developed. However, similar reactions with aza‐heteroaromatic precursors are more challenging and have been much less developed. Herein, we report for the first time catalytic formal cycloadditions of N,S‐heterocycles featuring carboxylic acid substituents, with unsaturated partners (alkynes). The reaction, which works with different symmetrical and unsymmetrical alkynes, produces appealing tricyclic ɑ‐pyrones in a straightforward manner. The optimized conditions established for a model reaction employing thieno[2,3‐b]pyridine‐2‐carboxylic acid as substrate, involved the use of Ag2CO3/AgSbF6 as additives, and proved to be general for different alkynes. Moreover, analogous cycloadditions using thieno[3,2‐b]pyridine‐2‐carboxylic acid and thieno[2,3‐b]pyrazine‐6‐carboxylic acid were successfully developed. Overall, this catalytic technology allows to build, in a single step, an interesting variety of pharmaceutically relevant tricyclic ɑ‐pyrones exhibiting nitrogen and sulfur heteroatoms.
Lagoa do Quari (São Raimundo Nonato, Piauí): Palaeoenvironment and wetland archaeology in Northeastern Brazil
Authors: Parenti Fabio , Aimola Giulia , Candelato Federica , Chaves Sérgio , Faure Martine , Ferrari Sonia , Guérin Claude , Mengoli Davide , Natali Luca , Rioda Vittorio , Scardia Giancarlo , Valli Andrea M. F.
Published: May 2021

Northeastern Brazil has thousands of wetland fossiliferous deposits with megafauna and, in some cases, associated lithic artifacts. The timing of the arrival of humans in South America and the extinction of megafauna is still debated and these sites contribute both to this discussion and to the reconstruction of the Late Pleistocene and Holocene paleoenvironment. Lagoa do Quari, 40 km south of São Raimundo Nonato, Piauí state, is a marsh deposit in the present semiarid caatinga environment, excavated by an interdisciplinary team in 2002–2003. This paper presents the archaeological, palaeontological, geological, chronological, stratigraphical and palynological results and their implications for the Quaternary of northeastern Brazil. The site has a rich megafaunal bonebed at the bottom, dominated by Eremotherium giant sloth remains with poor biodiversity, and a sandy‐silty deposit at the top; two 14C dates constrain this latter layer to 9,944–9,557 and 6,308–6,177 cal. years BP and the associated rich lithic industry of quartz and chert shows a technical continuity throughout the Holocene in the region. Palynology describes an open landscape with periodic wet phases, which could explain the richness of the archaeological occurrences in Holocenic Brazilian prehistory. This study offers a model of interdisciplinary enquiry into the paleoenvironment and prehistory of lowland South America.
Association Between Transient Elastography and Controlled Attenuated Parameter and Liver Ultrasound in Children With Cystic Fibrosis
Authors: Ye Wen , Leung Daniel H. , Molleston Jean P. , Ling Simon C. , Murray Karen F. , Nicholas Jennifer L. , Huang Suiyuan , Karmazyn Boaz W. , Harned Roger K. , Masand Prakash , Alazraki Adina L. , Navarro Oscar M. , Otto Randolph K. , Palermo Joseph J , Towbin Alexander J , Alonso Estella M. , Karnsakul Wikrom W. , Jane Schwarzenberg Sarah , Seidel Glenn F , Siegel Marilyn , Magee John C. , Narkewicz Michael R. , Jay Freeman A.
Published: May 2021

Methods to identify children with cystic fibrosis (CF) at risk for development of advanced liver disease are lacking. We aim to determine the association between liver stiffness measurement (LSM) by vibration‐controlled transient elastography (VCTE) with research ultrasound (US) patterns and conventional hepatic markers as a potential means to follow liver disease progression in children with CF. ELASTIC (Longitudinal Assessment of Transient Elastography in CF) is a nested cohort of 141 patients, ages 7‐21, enrolled in the Prediction by US of Risk of Hepatic Cirrhosis in CF (PUSH) Study. We studied the association between LSM with research‐grade US patterns (normal [NL], heterogeneous [HTG], homogeneous [HMG], or nodular [NOD]) and conventional hepatic markers. In a subgroup (n = 79), the association between controlled attenuation parameter (CAP) and US pattern was explored. Among 133 subjects undergoing VCTE, NOD participants (n = 26) had a significantly higher median (interquartile range) LSM of 9.1 kPa (6.3, 15.8) versus NL (n = 72, 5.1 kPa [4.2, 7.0]; P < 0.0001), HMG (n = 17, 5.9 kPa [5.2, 7.8]; P = 0.0013), and HTG (n = 18, 6.1 kPa [4.7, 7.0]; P = 0.0008) participants. HMG participants (n = 14) had a significantly higher mean CAP (SD) (270.5 dB/m [61.1]) compared with NL (n = 40, 218.8 dB/m [46.5]; P = 0.0027), HTG (n = 10, 218.1 dB/m [60.7]; P = 0.044), and NOD (n = 15, 222.7 dB/m [56.4]; P = 0.041) participants. LSM had a negative correlation with platelet count (rs = 

0.28, P = 0.0071) and positive correlation with aspartate aminotransferase–to‐platelet ratio index (rs = 0.38, P = 0.0002), Fibrosis‐4 index (rs = 0.36, P = 0.0007), gamma‐glutamyltransferase (GGT; rs = 0.35, P = 0.0017), GGT‐to‐platelet ratio (rs = 0.35, P = 0.003), and US spleen size z‐score (rs = 0.27, P = 0.0073). Conclusion: VCTE is associated with US patterns and conventional markers in patients with liver disease with CF.
Gene‐Gene Interactions of Gemcitabine Metabolizing‐Enzyme Genes hCNT3 and WEE1 for Preventing Severe Gemcitabine‐Induced Hematological Toxicity
Authors: Li Juan , Chen Bing , Xi Wen‐Qi , Yang Chen , Zhang Wei‐Xia
Published: May 2021

Most patients experience severe hematological toxicity during treatment with gemcitabine; thus, preventing such toxicity would improve the treatment effects and patient quality of life. We analyzed 13 polymorphisms in the transporters, metabolizing enzymes, targets, and genes involved in DNA damage and the folate pathway among 132 patients treated with gemcitabine and studied their association with the severity of the hematological toxicities. Single‐locus analysis showed that the single‐nucleotide polymorphisms (SNPs) RRM1 rs12806698 and rs11031918 and DCTD rs7663494 were significantly associated with severe neutropenia, hENT1 rs760370 and hCNT3 rs7867504 and rs4877831 were associated with severe leukopenia, CDA rs2072671, DCTD rs7663494, and WEE1 rs3910384 were associated with severe anemia, and MTHFR rs1801133 was associated with severe thrombocytopenia after stringent Bonferroni correction (P < .0038). The gene‐gene interaction analysis identified the overall best models, including a 2‐way interaction model (hCNT3 rs7867504 and dCK rs12648166) for severe leukopenia (P = .0022) and a 3‐locus model (CDA rs207671, DCTD rs7663494, and WEE1 rs3910384) for severe anemia with a strong synergistic effect (P = .0001). The association with hematological toxicity was further strengthened by the results of a haplotype analysis, in which the homozygous genotype combination of rs3910384 CC, rs2072671 AA, rs12648166 GG, rs7867504 CC, and rs7663494 TT conferred high genetic susceptibility to severe thrombocytopenia. Our results suggest that the gene‐gene interaction of gemcitabine metabolic pathway genes and WEE1 contributes to susceptibility to gemcitabine‐induced hematological toxicity. Moreover, we propose a promising data‐mining analysis approach (generalized multifactor dimensionality reduction) to detect and characterize gene‐gene interactions.
Gene expression profiling impacts treatment decision making in newly diagnosed multiple myeloma patients in the prospective PROMMIS trial
Authors: Biran Noa , Dhakal Binod , Lentzsch Suzanne , Siegel David , Usmani Saad Z. , Rossi Adriana , Rosenbaum Cara , Bhutani Divaya , Vesole David H. , Rodriguez Cesar , Nooka Ajay K. , van Rhee Frits , Stork‐Sloots Lisette , de Snoo Femke , Bhattacharyya Pritish K. , Dash Durga Prasad , Zümrütçü Sena , van Vliet Martin H. , Hari Parameswaran , Niesvizky Ruben
Published: May 2021

Multiple myeloma (MM) is a heterogeneous hematologic malignancy associated with several risk factors including genetic aberrations which impact disease response and survival. Thorough risk classification is essential to select the best clinical strategy to optimize outcomes. The SKY92 molecular signature classifies patients as standard‐ or high‐risk for progression. The PRospective Observational Multiple Myeloma Impact Study (PROMMIS; NCT02911571) measures impact of SKY92 on risk classification and treatment plan. Newly diagnosed MM patients had bone marrow aspirates analyzed for SKY92. Physicians completed a questionnaire for each patient capturing risk classification, hypothetical treatment plan, and physician confidence in the treatment plan, before and after unblinding SKY92. One hundred forty seven MM patients were enrolled. Before unblinding SKY92, physicians regarded 74 (50%) patients as clinical standard‐risk. After unblinding SKY92, 16 patients were re‐assigned as high‐risk by the physician, and for 15 of them treatment strategy was impacted, resulting in an escalated treatment plan. For the 73 (50%) clinical high‐risk patients, SKY92 indicated 46 patients to be standard‐risk; for 31 of these patients the treatment strategy was impacted consistent with a de‐escalation of risk. Overall, SKY92 impacted treatment decisions in 37% of patients (p < 0.001). For clinical decision‐making, physicians incorporated SKY92, and the final assigned clinical risk was in line with SKY92 for 89% of patients. Furthermore, SKY92 significantly increased the confidence of the physicians’ treatment decisions (p < 0.001). This study shows potential added value of SKY92 in MM for treatment decision making.