bluuebunny/crossref_metadata_2025_split huggingface dataset:
LONGITUDINAL OVARIAN RESERVE CHANGES IN WOMEN WITH BREAST CANCER RECEIVING ADJUVANT CHEMOTHERAPY OR TAMOXIFEN-ALONE
Authors: Goldfarb Shari B , Turan Volkan , Bedoschi Giuliano , Taylan Enes , Abdo Nadia , Cigler Tessa , Bang Heejung , Patil Sujita , Dickler Maura N , Oktay Kutluk H 
Published: June 2020

ABSTRACTBackgroundTo determine the longitudinal impact of adjuvant chemotherapy and tamoxifen-only treatments on ovarian reserve by serum anti-Mullerian hormone (AMH) levels in women with breast cancer.MethodsOne-hundred-and-forty-two women with a primary diagnosis of breast cancer were prospectively followed with serum AMH assessments before the initiation, and 12, 18 and 24 months after the completion of adjuvant chemotherapy or the start of tamoxifen-only treatment. The chemotherapy regimens were classified into Anthracycline-Cyclophosphamide-based (AC-based) and Cyclophosphamide-Methotrexate+5-Fluorouracil (CMF). Longitudinal data were analyzed by mixed effects model for treatment effects over time, adjusting for baseline age and BMI.ResultsBoth chemotherapy regimens resulted in significant decline in ovarian reserve compared to the tamoxifen-only treatment (p<0.0001 either regimen vs. tamoxifen for overall trend). AMH levels sharply declined at 12 months but did not show a significant recovery from 12 to 18 and 18 to 24 months after the completion of AC-based or CMF regimens. The degree of decline did not differ between the two chemotherapy groups (p=0.53). In contrast, tamoxifen-only treatment did not significantly alter the age-adjusted serum AMH levels over the 24-month follow up. Likewise, the use of adjuvant tamoxifen following AC-based regimens did not affect AMH recovery.ConclusionsBoth AC-based and CMF regimens significantly compromise ovarian reserve, which does not recover during the 12-24-month post-chemotherapy follow up. In contrast, tamoxifen treatment does not seem to alter ovarian reserve. This novel information should be valuable for fertility preservation counselling and in assessing future reproductive potential of breast cancer survivors.
Derivation and Validation of Clinical Prediction Rule for COVID-19 Mortality in Ontario, Canada
Authors: Fisman David N. , Greer Amy L. , Tuite Ashleigh R. 
Published: June 2020

AbstractBackgroundSARS-CoV-2 is currently causing a high mortality global pandemic. However, the clinical spectrum of disease caused by this virus is broad, ranging from asymptomatic infection to cytokine storm with organ failure and death. Risk stratification of individuals with COVID-19 would be desirable for management, prioritization for trial enrollment, and risk stratification. We sought to develop a prediction rule for mortality due to COVID-19 in individuals with diagnosed infection in Ontario, Canada.MethodsData from Ontario’s provincial iPHIS system were extracted for the period from January 23 to May 15, 2020. Both logistic regression-based prediction rules, and a rule derived using a Cox proportional hazards model, were developed in half the study and validated in remaining patients. Sensitivity analyses were performed with varying approaches to missing data.Results21,922 COVID-19 cases were reported. Individuals assigned to the derivation and validation sets were broadly similar. Age and comorbidities (notably diabetes, renal disease and immune compromise) were strong predictors of mortality. Four point-based prediction rules were derived (base case, smoking excluded as a predictor, long-term care excluded as a predictor, and Cox model based). All rules displayed excellent discrimination (AUC for all rules > 0.92) and calibration (both by graphical inspection and P > 0.50 by Hosmer-Lemeshow test) in the derivation set. All rules performed well in the validation set and were robust to random replacement of missing variables, and to the assumption that missing variables indicated absence of the comorbidity or characteristic in question.ConclusionsWe were able to use a public health case-management data system to derive and internally validate four accurate, well-calibrated and robust clinical prediction rules for COVID-19 mortality in Ontario, Canada. While these rules need external validation, they may be a useful tool for clinical management, risk stratification, and clinical trials.
Quantifying Costs of Urbanisation: Wetland Loss and Impacts in a Rapidly Developing Global City
Authors: Gabites Harriet , Spencer Ricky-John 
Published: June 2020

AbstractAs cities grow, natural ecosystems decline through conversion to urban environments. Cities are often viewed as biodiversity wastelands, but they can be hotspots of global biodiversity. Urban biodiversity emphasises two fundamentals. First, people living in cities enjoy wildlife and second, there is virtually no planning for species that co-inhabit our cities. If urban biodiversity was a significant part of planning, then we would be far better at integrating green infrastructure into expanding urban environments.Wetlands are among the most important and productive ecosystems in the world. They are the main suppliers of fresh water for human use and provide habitat to critical fauna and flora. In urban areas they are a vital link to nature and social cohesion. Currently, there is an absence of wetland inventory quantifying loss and changes overtime. Hence the broad impacts of urbanisation on wetland loss are difficult to assess.We explored wetland loss and created a wetland inventory for Western Sydney, Australia, one of the world’s fastest growing urban regions. We used satellite imagery to determine wetland number and type, and calculated changes in wetland surface area from 2010-2017. Broad changes to land use were also quantified. We developed species distribution models of a common urban wetland turtle (Chelodina longicollis) that people interact with regularly or have as pets.Chelodina longicollisutilises both aquatic and terrestrial environments, and we determined if changes in distribution were associated with changes in the wetland inventory and urbanisation.Most local government areas (LGA) experienced a decrease in wetland surface area from 2010-2017, ranging from -1% (Cumberland) to -21% (Blacktown). Majority of LGAs experienced a decrease in wetland density, with wetland densities declining by 25% (Blacktown). All LGAs experienced an increase in urban land use, ranging from 3-12%, which was associated with high rates of wetland loss.Changes in turtle distribution over the decade reflects a southern distribution shift away from where wetland losses were concentrated. We estimated that ∼40,000 individual turtles were displaced or killed due to wetland loss and urbanisation.Urbanisation was the leading cause of wetland loss and degradation in Western Sydney between 2010 and 2017. Wetlands provide critical green infrastructure and significant green space for social cohesion in urban areas. Integration of current wetlands, or the creation of functional wetlands, is key for sustainable development of urban landscapes. Urban wetlands (natural and constructed) may provide “biodiversity arks” for endangered species and facilitate community led conservation programs.
Monitoring the collective behavior of enzymatic nanomotors in vitro and in vivo by PET-CT
Authors: Hortelao Ana C. , Simó Cristina , Guix Maria , Guallar-Garrido Sandra , Julián Esther , Vilela Diana , Rejc Luka , Ramos-Cabrer Pedro , Cossío Unai , Gómez-Vallejo Vanessa , Patiño Tania , Llop Jordi , Sánchez Samuel 
Published: June 2020

AbstractEnzyme powered nanomotors hold great potential for biomedical applications, as they show improved diffusion and navigation within biological environments using endogenous fuels. Yet, understanding their collective behavior and tracking themin vivois paramount for their clinical translation. Here, we report on thein vitroandin vivostudy of swarms of self-propelled enzyme-nanomotors and the effect of collective behavior on the nanomotors distribution within the bladder. For that purpose, mesoporous silica nanomotors were functionalized with urease enzymes and gold nanoparticles. Two radiolabeling strategies, i.e. absorption of124I on gold nanoparticles and covalent attachment of an18F-labeled prosthetic group to urease, were assayed.In vitroexperiments using optical microscopy and positron emission tomography (PET) showed enhanced fluid mixing and collective migration of nanomotors in phantoms containing complex paths. Biodistribution studies after intravenous administration in mice confirmed the biocompatibility of the nanomotors at the administered dose, the suitability of PET to quantitatively track nanomotorsin vivo, and the convenience of the18F-labeling strategy. Furthermore, intravesical instillation of nanomotors within the bladder in the presence of urea resulted in a homogenous distribution after the entrance of fresh urine. Control experiments using BSA-coated nanoparticles or nanomotors in water resulted in sustained phase separation inside the bladder, demonstrating that the catalytic decomposition of urea can provide urease-nanomotors with active motion, convection and mixing capabilities in living reservoirs. This active collective dynamics, together with the medical imaging tracking, constitutes a key milestone and a step forward in the field of biomedical nanorobotics, paving the way towards their use in theranostic applications.
Composite modeling of leaf shape across shoots discriminatesVitisspecies better than individual leaves
Authors: Bryson Abigail E. , Brown Maya Wilson , Mullins Joey , Dong Wei , Bahmani Keivan , Bornowski Nolan , Chiu Christina , Engelgau Philip , Gettings Bethany , Gomezcano Fabio , Gregory Luke M. , Haber Anna C. , Hoh Donghee , Jennings Emily E. , Ji Zhongjie , Kaur Prabhjot , Raju Sunil K. Kenchanmane , Long Yunfei , Lotreck Serena G. , Mathieu Davis T. , Ranaweera Thilanka , Ritter Eleanore J. , Sadohara Rie , Shrote Robert Z. , Smith Kaila E. , Teresi Scott J. , Venegas Julian , Wang Hao , Wilson McKena L. , Tarrant Alyssa R. , Frank Margaret H. , Migicovsky Zoë , Kumar Jyothi , VanBuren Robert , Londo Jason P. , Chitwood Daniel H. 
Published: June 2020

ABSTRACTPremise of studyLeaf morphology is dynamic, continuously deforming during leaf expansion and among leaves within a shoot. We measured leaf morphology from over 200 vines over four years, and modeled changes in leaf shape along the shoot to determine if a composite “shape of shapes” can better capture variation and predict species identity compared to individual leaves.MethodsUsing homologous universal landmarks found in grapevine leaves, we modeled various morphological features as a polynomial function of leaf node. The resulting functions are used to reconstruct modeled leaf shapes across shoots, generating composite leaves that comprehensively capture the spectrum of possible leaf morphologies.ResultsWe found that composite leaves are better predictors of species identity than individual leaves from the same plant. We were able to use composite leaves to predict species identity of previously unassigned vines, which were verified with genotyping.DiscussionObservations of individual leaf shape fail to capture the true diversity between species. Composite leaf shape—an assemblage of modeled leaf snapshots across the shoot—is a better representation of the dynamic and essential shapes of leaves, as well as serving as a better predictor of species identity than individual leaves.
Global analysis of a cancer model with drug resistance due to Lamarckian induction and microvesicle transfer
Authors: Dénes Attila , Röst Gergely 
Published: June 2020

AbstractDevelopment of resistance to chemotherapy in cancer patients strongly effects the outcome of the treatment. Due to chemotherapeutic agents, resistance can emerge by Darwinian evolution. Besides this, acquired drug resistance may arise via changes in gene expression. A recent discovery in cancer research uncovered a third possibility, indicating that this phenotype conversion can occur through the transfer of microvesicles from resistant to sensitive cells, a mechanism resembling the spread of an infectious agent. We present a model describing the evolution of sensitive and resistant tumour cells considering Darwinian selection, Lamarckian induction and microvesicle transfer. We identify three threshold parameters which determine the existence and stability of the three possible equilibria. Using a simple Dulac function, we give a complete description of the dynamics of the model depending on the three threshold parameters. We demonstrate the possible effects of increasing drug concentration, and characterize the possible bifurcation sequences. Our results show that the presence of microvesicle transfer cannot ruin a therapy that otherwise leads to extinction, however it may doom a partially successful therapy to failure.
Keratins couple with the nuclear lamina and regulate proliferation in colonic epithelial cells
Authors: Stenvall Carl-Gustaf A. , Nyström Joel H. , Butler-Hallissey Ciarán , Adam Stephen A. , Foisner Roland , Ridge Karen M. , Goldman Robert D. , Toivola Diana M. 
Published: June 2020

AbstractKeratin intermediate filaments (IFs) convey mechanical stability and protection against stress to epithelial cells, and may participate in nuclear structure and organization. Keratins are important for colon health as observed in keratin 8 knockout (K8−/−) mice, which exhibit colonic inflammation and epithelial hyperproliferation. Here, using a full body and two intestinal epithelial-specific K8−/−knockout mouse models, we determine if cytoplasmic keratins affect the nuclear structure and lamina in epithelial colonocytes. K8−/−colonocytes in vivo and in organoid cultures exhibit significantly decreased levels of the major lamins A/C, B1 and B2 in a colon-specific and cell-intrinsic manner independent of major changes in colonic inflammation or microbiota. Downregulation of K8 by siRNA in Caco-2 cells similarly decreases lamin A levels, which recover after re-expression of K8. K8 loss is associated with reduced plectin, LINC complex proteins and lamin-associated proteins, indicating a dysfunctional keratin-nuclear lamina coupling. Immunoprecipitation identifies complexes of colonocyte keratins with the LINC protein SUN2 and lamin A. Hyperphosphorylation of the lamin A-associated cell cycle regulator pRb in K8−/−colonocytes together with increased nuclear localization of the mechanosensor YAP provide a molecular mechanism for the hyperproliferation phenotype. These findings identify a novel, colonocyte-specific role for K8 in nuclear function.
Evaluation ofstaA,viaBandsopEgenes inSalmonelladetection using conventional polymerase chain reaction (PCR)
Authors: Kariuki Francis , Getanda Pauline , Nyachieo Atunga , Juma Gerald , Kinyanjui Peter , Kamau Joseph 
Published: June 2020

AbstractTyphoid fever is caused by the bacteriaSalmonella entericasubspeciesentericaserovar Typhi (S. Typhi) and remains a significant health problem in many developing countries. The lack of adequate diagnostic capabilities in these poor resource settings have contributed greatly in making typhoid fever endemic in these regions. Reliable and inexpensive diagnostic tests are needed to improve the management of this disease burden. This study evaluated the ability ofstaA, viaBandsopEgenes to detectSalmonellaspp. Conventional polymerase chain reaction (PCR) amplification ofstaA,viaBandsopEgenes ofSalmonellawas used to detect and differentiate between the three most prevalentSalmonellaspp. in Kenya (S. Typhi,S.Typhimurium andS.Enteritidis). ThestaAprimers (StaA-Forward / StaA-Reverse) andviaBprimers (vi-Forward / vi-Reverse) were found to be specific only for the different strains ofS. Typhi, producing PCR products of 585 bp and 540 bp respectively. No amplification was observed withS.Typhimurium,S.Enteritidis,E. coli andS. boydii bacterial strains. ThesopEprimers (SopE-Forward / SopE-Reverse) was demonstrated to be specific for allSalmonellaspp. producing a 465 bp PCR product with no amplification observed with theE. coli andS. boydii bacterial strains. Conventional PCR using thesestaAandviaBprimers for detection ofS. Typhi shows great potential for diagnosis of typhoid fever however, further studies need to be carried out with actual food samples and human samples (blood, stool or saliva) to determine the effectiveness of this method in the detection of common Salmonella spp. in Kenya.Author summaryTyphoid fever is a severe disease caused by the bacteriaSalmonellaTyphi (S. Typhi) and is a significant health problem in many developing countries. The lack of adequate diagnostic capabilities in poor resource settings common in most public health facilities in Kenya and Africa in general, hinder prompt diagnosis of typhoid fever. Currently, the available diagnostic tests are often expensive and more so not readily available in most resource poor endemic areas. This has often led to misdiagnosis of the disease, thereby delaying appropriate treatment and making typhoid fever widespread in most resource poor areas. This study examines the ability of three different genes to detect and differentiate between the three most prevalentSalmonellastrains in Kenya using a readily available and widely used genetic test known as conventional polymerase chain reaction (PCR). This research found thatstaAandviaBgenes were specific only forS. Typhi, while thesopEgene was specific for allSalmonellastrains. Consequently, conventional PCR using thesestaAandviaBgenes for detection ofS. Typhi shows great potential to be used as a readily available diagnostic tool to detect the presence of theS. Typhi organism in individuals or foods sample in Kenya.
MYC regulates ribosome biogenesis and mitochondrial gene expression programs through interaction with Host Cell Factor-1
Authors: Popay Tessa M. , Wang Jing , Adams Clare M. , Codreanu Simona G. , Sherrod Stacy , McClean John A. , Thomas Lance R. , Lorey Shelly L. , Machida Yuichi J. , Weissmiller April M. , Eischen Christine M. , Liu Qi , Tansey William. P. 
Published: June 2020

ABSTRACTThe oncoprotein transcription factor MYC is a major driver of malignancy and a highly-validated but challenging target for development of anti-cancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here, we interrogate how one MYC co-factor, Host Cell Factor (HCF)-1, contributes to MYC activity in a Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets, and demonstrate how modulation of the MYC–HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growthin vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC–HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies.
Somatotopic Arrangement of Eight Distinct Skin Areas in the Human Primary Somatosensory Cortex Derived from Functional Magnetic Resonance Imaging
Authors: Willoughby W. R. , Thoenes Kristina , Bolding Mark 
Published: June 2020

AbstractBlood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to investigate cortical activity associated with peripheral tactile stimuli in a small cohort of healthy humans. MR-safe automated pneumatic stimulators modeled after the Wartenberg pinwheel were used to generate tactile stimuli at regular intervals on eight disparate areas of skin. The phase-encoded BOLD responses of voxels in the cerebral cortex were characterized by the maximal normalized cross-correlation coefficients at time delays between an idealized response and the measure time course. Overall at the group level, the somatotopic organization of the somatosensory cortex (SI) follows the accepted homunculus model, but a noticeable amount of variation was observed between individual study participants. The surface areas of cortical regions in SI activated by tactile stimulation of different body parts were calculated, giving an estimate of cortical magnification factors. Data collected with the participant actively attending the stimuli were compared to data collected before the attention task. No significant attention-related changes were observed in the somatotopic maps or in time courses of voxels well-correlated to stimuli.
Three-dimensional morphodynamics simulations of macropinocytic cups
Authors: Saito Nen , Sawai Satoshi 
Published: June 2020

•AbstractMacropinocytosis is non-specific uptake of the extracellular fluid playing ubiquitous roles in cell growth, immune-surveillance as well as virus entry. Despite its widespread occurrence, it remains unclear how its initial cup-shaped plasma membrane extensions forms without external physical support as in phagocytosis or curvature inducing proteins as in clathrin-mediated endocytosis. Here, by developing a novel computational framework that describes the coupling between bistable reaction-diffusion processes of active signaling patches and membrane deformation, we demonstrate that protrusive force localized to the edge of the patches can give rise to the self-enclosing cup structure without further assumption of local bending or contraction. Efficient uptake requires an appropriate balance between the patch size and the magnitude of protrusive force relative to the cortical tension. Furthermore, our model exhibits a variety of known morphology dynamics including cyclic cup formation, coexistence and competition between multiple cups and cup splitting indicating that these complex morphologies self-organize through mutually dependent dynamics between the reaction-diffusion process and membrane deformation.
A dual role for H2A.Z.1 in modulating the dynamics of RNA Polymerase II initiation and elongation
Authors: Mylonas Constantine , Auld Alexander L. , Lee Choongman , Cisse Ibrahim I. , Boyer Laurie A. 
Published: June 2020

AbstractRNAPII pausing immediately downstream of the transcription start site (TSS) is a critical rate limiting step at most metazoan genes that allows fine-tuning of gene expression in response to diverse signals1–5. During pause-release, RNA Polymerase II (RNAPII) encounters an H2A.Z.1 nucleosome6–8, yet how this variant contributes to transcription is poorly understood. Here, we use high resolution genomic approaches2,9(NET-seq and ChIP-nexus) along with live cell super-resolution microscopy (tcPALM)10to investigate the role of H2A.Z.1 on RNAPII dynamics in embryonic stem cells (ESCs). Using a rapid, inducible protein degron system11combined with transcriptional initiation and elongation inhibitors, our quantitative analysis shows that H2A.Z.1 slows the release of RNAPII, impacting both RNAPII and NELF dynamics at a single molecule level. We also find that H2A.Z.1 loss has a dramatic impact on nascent transcription at stably paused, signal-dependent genes. Furthermore, we demonstrate that H2A.Z.1 inhibits re-assembly and re-initiation of the PIC to reinforce the paused state and acts as a strong additional pause signal at stably paused genes. Together, our study suggests that H2A.Z.1 fine-tunes gene expression by regulating RNAPII kinetics in mammalian cells.