bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractActinobacteria 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

AbstractThe 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

AbstractBackgroundBreast 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.MethodsA 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.ResultsIn 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).ConclusionsRadiotherapy 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

AbstractBackgroundCardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood.MethodsThis 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.ResultsIn 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 RelevanceIn 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

AbstractAntibody 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

AbstractLocality‐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

AbstractObjectiveDespite 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.MethodOne hundred and thirty transgender individuals completed measures of misgendering frequency, transgender congruence, body dissatisfaction, and dietary restraint.ResultsMediation 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).DiscussionSocial 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

AbstractBird‐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

AbstractFree 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

AbstractIn 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

AbstractNortheastern 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.