bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quercetin as an innovative therapeutic tool for cancer chemoprevention: Molecular mechanisms and implications in human health
Authors: Rather Rafiq A. , Bhagat Madhulika 
Published: October 2019

AbstractCancer is a life‐threatening disease afflicting human health worldwide. Recent advances in drug discovery infrastructure and molecular approaches have helped a lot in identifying the novel drug targets for therapeutic intervention. Nevertheless, the morbidity and mortality rates because of this disease keep on rising at an alarming rate. Recently, the use of natural and synthetic molecules as innovative therapeutic tools for cancer prevention has lead to the development of cancer chemoprevention. Cancer chemoprevention is a prophylactic strategy that involves the chronic administration of one or more natural or synthetic agents to block, to inhibit, or to suppress the process of cancer development before it becomes an invasive disease. Quercetin, a dietary bioflavonoid, can specifically retard the growth of cancer cells and behaves as a potent cancer chemopreventive agent. Quercetin has multiple intracellular targets in a cancer cell. Therefore, many mechanisms have been postulated to explain its chemopreventive action. The chemopreventive effects elicited by this natural molecule in different model systems are believed to include antioxidant/pro‐oxidant action, regulation of redox homeostasis, apoptosis, cell cycle arrest, anti‐inflammatory action, modulation of drug metabolizing enzymes, alterations in gene expression patterns, inhibition of Ras gene expression, and modulation of signal transduction pathways. However, cell signaling networks have recently garnered attention as common molecular target for various chemopreventive effects of quercetin. In this review, we made an attempt to critically summarize the emerging knowledge on the role of quercetin in cancer chemoprevention and the underlying molecular mechanisms implicated in its chemopreventive and therapeutic effects.
Response‐adapted treatment with rituximab, bendamustine, mitoxantrone, and dexamethasone followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma after first‐line immunochemotherapy: Results of the RBMDGELTAMO08 phase II trial
Authors: Peñalver Francisco‐Javier , Márquez José‐Antonio , Durán Soledad , Giraldo Pilar , Martín Alejandro , Montalbán Carlos , Sancho Juan‐Manuel , Ramírez María‐José , Terol María‐José , Capote Francisco‐Javier , Gutiérrez Antonio , Sánchez Blanca , López Andrés , Salar Antonio , Rodríguez‐Caravaca Gil , Canales Miguel , Caballero María‐Dolores ,   on behalf of GELTAMO (The Spanish Lymphoma Cooperative Group)
Published: October 2019

AbstractBackgroundConsensus is lacking regarding the optimal salvage therapy for patients with follicular lymphoma who relapse after or are refractory to immunochemotherapy.MethodsThis phase II trial evaluated the efficacy and safety of response‐adapted therapy with rituximab, bendamustine, mitoxantrone, and dexamethasone (RBMD) in follicular lymphoma patients who relapsed after or were refractory to first‐line immunochemotherapy. Sixty patients received three treatment cycles, and depending on their response received an additional one (complete/unconfirmed complete response) or three (partial response) cycles. Patients who responded to induction received rituximab maintenance therapy for 2 years.ResultsThirty‐three (55%) and 42 (70%) patients achieved complete/unconfirmed complete response after three cycles and on completing induction therapy (4‐6 cycles), respectively (final overall response rate, 88.3%). Median progression‐free survival was 56.4 months (median follow‐up, 28.3 months; 95% CI, 15.6‐51.2). Overall survival was not reached. Progression‐free survival did not differ between patients who received four vs six cycles (P = .6665), nor between patients who did/did not receive rituximab maintenance after first‐line therapy (P = .5790). Median progression‐free survival in the 10 refractory patients was 25.5 months (95% CI, 0.6‐N/A) and was longer in patients who had shown progression of disease after 24 months of first‐line therapy (median, 56.4 months; 95% CI, 19.8‐56.4) than in those who showed early progression (median, 42.31 months; 95% CI, 24.41–NA) (P = .4258). Thirty‐six (60%) patients had grade 3/4 neutropenia. Grade 3/4 febrile neutropenia and infection were recorded during induction (4/60 [6.7%] and 5/60 [8.3%] patients, respectively) and maintenance (2/43 [4.5%] and 4/43 [9.1%] patients, respectively).ConclusionsThis response‐adapted treatment with RBMD followed by rituximab maintenance is an effective and well‐tolerated salvage treatment for relapsed/refractory follicular lymphoma following first‐line immunochemotherapy.Clinical trial registrationClinicalTrials.gov # NCT01133158.
Clinical candidate and genistein analogue AXP107‐11 has chemoenhancing functions in pancreatic adenocarcinoma through G protein‐coupled estrogen receptor signaling
Authors: Mesmar Fahmi , Dai Bingbing , Ibrahim Ahmed , Hases Linnea , Jafferali Mohammed Hakim , Jose Augustine Jithesh , DiLorenzo Sebastian , Kang Ya'an , Zhao Yang , Wang Jing , Kim Michael , Lin Chin‐Yo , Berkenstam Anders , Fleming Jason , Williams Cecilia 
Published: October 2019

AbstractDespite advances in cancer therapeutics, pancreatic cancer remains difficult to treat and often develops resistance to chemotherapies. We have evaluated a bioavailable genistein analogue, AXP107‐11 which has completed phase Ib clinical trial, as an approach to sensitize tumor cells to chemotherapy. Using organotypic cultures of 14 patient‐derived xenografts (PDX) of pancreatic ductal adenocarcinoma, we found that addition of AXP107‐11 indeed sensitized 57% of cases to gemcitabine treatment. Results were validated using PDX models in vivo. Further, RNA‐Seq from responsive and unresponsive tumors proposed a 41‐gene treatment‐predictive signature. Functional and molecular assays were performed in cell lines and demonstrated that the effect was synergistic. Transcriptome analysis indicated activation of G‐protein‐coupled estrogen receptor (GPER1) as the main underlying mechanism of action, which was corroborated using GPER1‐selective agonists and antagonists. GPER1 expression in pancreatic tumors was indicative of survival, and our study proposes that activation of GPER1 may constitute a new avenue for pancreatic cancer therapeutics.
Should clinical suspicion shift to ampicillin resistance organisms in certain preterm premature rupture of membranes scenarios?: Case of early‐onset sepsis caused by E coli
Authors: Bandu Anirudh , Barone Anthony , Parab Santosh , Lakhi Nisha 
Published: October 2019

AbstractThis case highlights the importance antibiotic stewardship, including reexamining current regimens use for intrapartum antibiotic prophylaxis, which may be accountable for the shift in organism responsible for some cases of early‐onset sepsis.
Anaplastic multiple myeloma resembling dysplastic megakaryocytes
Authors: Xie Wei , Tang Guilin , Li Shaoying , Yin C. Cameron , Xu Jie 
Published: October 2019

AbstractAnaplastic multiple myeloma (AMM) is a very rare morphologic variant of multiple myeloma with extremely poor prognosis. The anaplastic morphology of AMM may pose a diagnostic challenge. A thorough workup is critical in reaching the correct diagnosis.
Muscular hypotonia as an onset manifestation of Tuberculosis meningitis in an HIV‐negative patient
Authors: Daghmouri Mohamed Aziz , Cherni Imen , Rebai Lotfi , Ghouibi Cheima , Ghedira Salma , Houissa Mohamed 
Published: October 2019

AbstractMuscular hypotonia is considered as one of the rarest forms of initial onset signs of TBM, in addition to aphasia and hyponatremia, the awareness of those rare onset signs, a well‐conducted diagnostic approach and early treatment can improve the outcome.
High areal capacitance of Fe3O4‐decorated carbon nanotubes for supercapacitor electrodes
Authors: Nawwar Mohamed , Poon Ryan , Chen Ri , Sahu Rakesh P. , Puri Ishwar K. , Zhitomirsky Igor 
Published: October 2019

AbstractA conceptually new approach has been developed for the fabrication of magnetite (Fe3O4)‐decorated carbon nanotubes (M‐CNTs) for negative electrodes of electrochemical supercapacitors. M‐CNTs were prepared by an ultrasonic‐assisted chemical synthesis method, which involved dispersion of functionalized CNTs in water, Fe3O4 formation on the CNTs surface, and particle extraction through liquid‐liquid interface (PELLI). Palmitic acid was found to be an efficient new extractor for PELLI. The slurries produced after drying and redispersing M‐CNTs and slurries obtained using PELLI were used for electrode fabrication. The electrodes prepared using PELLI showed superior performance due to reduced particle agglomeration. Testing results provided an insight into the influence of Fe3O4/CNTs mass ratio on the capacitance and capacitance retention at high charge‐discharge rates. A capacitance of 5.82 F cm−2 (145.4 F g−1) was achieved in Na2SO4 electrolyte using electrodes with high active mass of 40 mg cm−2 and ratio of active mass to current collector mass of 0.6. Good electrochemical performance was achieved at low impedance. The capacitance of the negative M‐CNTs electrodes was comparable with capacitance of advanced positive MnO2‐CNTs electrodes, which was beneficial for the fabrication of asymmetric devices. The asymmetric device has been fabricated, which showed promising performance in a voltage window of 1.6 V.
Room‐Temperature Phosphorescence from a Series of 3‐Pyridylcarbazole Derivatives
Authors: Sasabe Hisahiro , Kato Yuki , Watanabe Yuichiro , Ohsawa Tatsuya , Aizawa Naoya , Fujiwara Wataru , Pu Yong‐Jin , Katagiri Hiroshi , Kido Junji 
Published: October 2019

AbstractExploration of pure metal‐free organic molecules that exhibit strong room‐temperature phosphorescence (RTP) is an emerging research topic. In this regard, unveiling the design principles for an efficient RTP molecule is an essential, but challenging, task. A small molecule is an ideal platform to precisely understand the fundamental role of each functional component because the parent molecule can be easily derivatized. Here, the RTP behaviors of a series of 3‐pyridylcarbazole derivatives are presented. Experimental studies in combination with theoretical calculations reveal the crucial role of the n orbital on the central pyridine ring in the dramatic enhancement of the intersystem crossing between the charge‐transfer‐excited singlet state and the locally excited triplet states. Single‐crystal X‐ray crystallographic studies apparently indicate that both the pyridine ring and fluorine atom contribute to the enhancement of the RTP because of the restricted motion owing to weak C−H⋅⋅⋅N and H⋅⋅⋅F hydrogen‐bonding interactions. The single crystal of the fluorine‐substituted derivative shows an ultra‐long phosphorescent lifetime (τP) of 1.1 s and a phosphorescence quantum yield (ΦP) of 1.2 %, whereas the bromine‐substituted derivative exhibits τP of 0.15 s with a ΦP of 7.9 %. We believe that this work provides a fundamental and universal guideline for the generation of pure organic molecules exhibiting strong RTP.
Identification of key residues that regulate the interaction of kinesins with microtubule ends
Authors: Belsham Hannah R. , Friel Claire T. 
Published: October 2019

AbstractKinesins are molecular motors that use energy derived from ATP turnover to walk along microtubules, or when at the microtubule end, regulate growth or shrinkage. All kinesins that regulate microtubule dynamics have long residence times at microtubule ends, whereas those that only walk have short end‐residence times. Here, we identify key amino acids involved in end binding by showing that when critical residues from Kinesin‐13, which depolymerises microtubules, are introduced into Kinesin‐1, a walking kinesin with no effect on microtubule dynamics, the end‐residence time is increased up to several‐fold. This indicates that the interface between the kinesin motor domain and the microtubule is malleable and can be tuned to favour either lattice or end binding.
Improving on‐time colorectal cancer screening through lead time messaging
Authors: Jones Whitney F. , Ahnen Dennis J. , Schroy Paul C. 
Published: October 2019

Screening rates for colorectal cancer have increased steadily in recent years among individuals aged 55 years and older but remain unacceptably low for younger individuals, especially those at an increased risk due to family history. Herein, the authors describe a novel lead time messaging program aimed at increasing on‐time screening for both average‐risk individuals and those at increased risk because of a family history of colorectal cancer or advanced adenomas.
Nonconsumptive predator effects modify crayfish‐induced bioturbation as mediated by limb loss: Field and mesocosm experiments
Authors: Dunoyer Luc A. , Coomes Dakota , Crowley Philip H. 
Published: October 2019

Abstract

We addressed the implications of limb loss and regeneration for multispecies interactions and their impacts on ecosystem engineering in freshwater stream environments.

We included regenerative and nonregenerative crayfish as well as fish predators in a 2 × 2 factorial design to assess the effects on water turbidity of interactions between crayfish ecosystem engineers differing in regenerative status and their fish predators.

We demonstrated that crayfish limb loss and predation risks lead to more turbidity in field and mesocosm conditions. Moreover, ongoing regeneration of crayfish increased turbidity, while fish presence seemed to hinder crayfish turbidity‐inducing behaviors (such as tail‐flipping and burrowing) in the mesocosm experiment.

We confirmed that greater numbers of crayfish produce a greater amount of turbidity in situ in streams.

Although mechanical burrowing crayfish capacities may depend on crayfish burrowing classification (primary, secondary, or tertiary), our work emphasizes the implication for turbidity levels of crayfish autotomy in freshwater streams.
Novel insights into how the mean and heterogeneity of abiotic conditions together shape forb species richness patterns in the Allegheny plateau ecoregion
Authors: Catella Samantha A. , Eysenbach Sarah R. , Abbott Karen C. 
Published: October 2019

AbstractWhile plant community theory tends to emphasize the importance of abiotic heterogeneity along niche axes, much empirical work seeks to characterize the influence of the absolute magnitude of key abiotic variables on diversity. Both magnitude (as reflected, e.g., by a mean) and heterogeneity (variance) in abiotic conditions likely contribute to biodiversity patterns in plant communities, but given the large number of putative abiotic drivers and the fact that each may vary at different spatiotemporal scales, the challenge of linking observed biotic patterns with the underlying environment remains acute. Using monitoring data from a natural resource agency, we compared how well statistical models of the mean, heterogeneity, and both the mean and heterogeneity combined of 17 abiotic factor variables explained patterns of forb species richness in Northeast Ohio, USA. We performed our analyses at two spatial scales, repeated in spring and summer across four forest types. Although all models explained a great deal of the variance in species richness, models including both the mean and heterogeneity of different abiotic factors together outperformed models including either the mean or the heterogeneity of abiotic factors alone. Variability in forb species richness was mostly due to changes in mean calcium levels regardless of forest type. After accounting for forest type, we were able to attribute variation in forb species richness to changes in the heterogeneity of different abiotic factors as well. Our results suggest that multiple mechanisms act simultaneously according to different aspects of the abiotic environment to structure forb communities, and this underscores the importance of considering both the magnitude of and heterogeneity in multiple abiotic factors when looking for links between the abiotic environment and plant community patterns. Finally, we identify novel patterns across spatial scales, forest types, and seasons that can guide future research in this vein.OPEN RESEARCH BADGES

This article has earned an Open Data Badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. The data is available at https://doi.org/10.5061/dryad.kp3cb17.
Rewiring and indirect effects underpin modularity reshuffling in a marine food web under environmental shifts
Authors: D'Alelio Domenico , Hay Mele Bruno , Libralato Simone , Ribera d'Alcalà Maurizio , Jordán Ferenc 
Published: October 2019

AbstractSpecies are characterized by physiological and behavioral plasticity, which is part of their response to environmental shifts. Nonetheless, the collective response of ecological communities to environmental shifts cannot be predicted from the simple sum of individual species responses, since co‐existing species are deeply entangled in interaction networks, such as food webs. For these reasons, the relation between environmental forcing and the structure of food webs is an open problem in ecology. To this respect, one of the main problems in community ecology is defining the role each species plays in shaping community structure, such as by promoting the subdivision of food webs in modules—that is, aggregates composed of species that more frequently interact—which are reported as community stabilizers.In this study, we investigated the relationship between species roles and network modularity under environmental shifts in a highly resolved food web, that is, a “weighted” ecological network reproducing carbon flows among marine planktonic species. Measuring network properties and estimating weighted modularity, we show that species have distinct roles, which differentially affect modularity and mediate structural modifications, such as modules reconfiguration, induced by environmental shifts.Specifically, short‐term environmental changes impact the abundance of planktonic primary producers; this affects their consumers’ behavior and cascades into the overall rearrangement of trophic links. Food web re‐adjustments are both direct, through the rewiring of trophic‐interaction networks, and indirect, with the reconfiguration of trophic cascades. Through such “systemic behavior,” that is, the way the food web acts as a whole, defined by the interactions among its parts, the planktonic food web undergoes a substantial rewiring while keeping almost the same global flow to upper trophic levels, and energetic hierarchy is maintained despite environmental shifts. This behavior suggests the potentially high resilience of plankton networks, such as food webs, to dramatic environmental changes, such as those provoked by global change.
Dual Amperometric Immunosensor for Improving Cancer Metastasis Detection by the Simultaneous Determination of Extracellular and Soluble Circulating Fraction of Emerging Metastatic Biomarkers
Authors: Valverde Alejandro , ben Hassine Amira , Serafín Verónica , Muñoz‐San Martín Cristina , Pedrero María , Garranzo‐Asensio María , Gamella Maria , Raouafi Noureddine , Barderas Rodrigo , Yáñez‐Sedeño Paloma , Campuzano Susana , Pingarrón José M. 
Published: October 2019

AbstractThis paper reports the development of a dual immunosensor using magnetic microcarriers (MBs) and amperometric transduction at dual screen‐printed carbon electrodes (SPdCEs) for the simultaneous determination of two biomarkers: interleukin‐13 receptor α2 (IL‐13Rα2) and E‐cadherin (E‐CDH), with both extracellular and soluble fraction; oncogenic and tumor suppressor markers, respectively, of great relevance in metastatic processes. The implemented methodology involved the formation of sandwich‐type immunocomplexes using specific capture antibodies immobilized onto carboxylic acid magnetic microbeads (HOOC‐MBs), and biotinylated detector antibodies labeled with streptavidin−horseradish peroxidase conjugates (Strep‐HRP). The amperometric detection was performed by addition of hydrogen peroxide in the presence of hydroquinone (HQ) as the redox mediator. The dual immunosensing platform provided linear calibration ranges suitable for the determination of both biomarkers in liquid and solid clinical specimens as well as excellent selectivity against other cancer biomarkers. This simple handling dual bioplatform was applied to the determination of the soluble and extracellular fraction of the target biomarkers in serum and paraffined‐embedded tissues from colorectal cancer (CRC) patients diagnosed at different tumor grade. The obtained results reveal great potential of this configuration to improve the reliability in diagnosing metastatic CRC.
Do the concepts of “life course approach” and “developmental origins of health and disease” underpin current maternity care? Study protocol
Authors: Jacob Chandni Maria , Lawrence Wendy T. , Inskip Hazel M. , McAuliffe Fionnuala M. , Killeen Sarah Louise , Hanson Mark 
Published: October 2019

AbstractObjectiveTo explore the knowledge of Developmental Origins of Health and Disease (DOHaD) concepts among midwives and obstetricians and to identify barriers and facilitators for clinicians to engage women and their partners before or early in pregnancy on risk factors associated with DOHaD, and thus to embed the concept of DOHaD in routine clinical practice.MethodsA qualitative study using semi‐structured interviews will be conducted in Ghana, India, Pakistan, Brazil, the UK, and USA in collaboration with the International Confederation of Midwives and the International Federation of Obstetricians and Gynecologists. Participants will be contacted via email and telephone interviews will be conducted until data saturation followed by inductive thematic analysis.ResultsFindings from this exploratory study will provide new knowledge about the perspectives of midwives and obstetricians on DOHaD and their role in preventing the intergenerational passage of non‐communicable disease (NCD) risk and improving preconception care.ConclusionThis study will help us understand the current use of DOHaD principles in international maternity care and how this can be improved. Bringing DOHaD to clinical practice will help healthcare practitioners adopt a long‐term approach in the prevention of NCDs and childhood obesity and will help women to enter pregnancy in optimum health.