bluuebunny/crossref_metadata_2025_split huggingface dataset:
One Key and Multiple Locks: Substrate Binding in Structures of Tryptophan Dioxygenases and Hydroxylases
Authors: Mammoli Andrea , Riccio Alessandra , Bianconi Elisa , Coletti Alice , Camaioni Emidio , Macchiarulo Antonio 
Published: June 2021

AbstractSince its discovery at the beginning of the past century, the essential nutrient l‐Tryptophan (l‐Trp) and its catabolic pathways have acquired an increasing interest in an ever wider scientific community for their pivotal roles in underlying many important physiological functions and associated pathological conditions. As a consequence, enzymes catalyzing rate limiting steps along l‐Trp catabolic pathways ‐ including IDO1, TDO, TPH1 and TPH2 ‐ have turned to be interesting drug targets for the design and development of novel therapeutic agents for different disorders such as carcinoid syndrome, cancer and autoimmune diseases. This article provides a fresh comparative overview on the most recent advancements that crystallographic studies, biophysical and computational works have brought on structural aspects and molecular recognition patterns of these enzymes toward l‐Trp. Finally, a conformational analysis of l‐Trp is also discussed as part of the molecular recognition process governing the binding of a substrate to its cognate enzymes.
Hyper‐CVAD plus ofatumumab versus hyper‐CVAD plus rituximab as frontline therapy in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia: A propensity score analysis
Authors: Sasaki Koji , Kantarjian Hagop M. , Morita Kiyomi , Short Nicholas J. , Konopleva Marina , Jain Nitin , Ravandi Farhad , Garcia‐Manero Guillermo , Wang Sa , Khoury Joseph D. , Jorgensen Jeffrey L. , Champlin Richard E. , Khouri Issa F. , Kebriaei Partow , Schroeder Heather M. , Khouri Maria , Garris Rebecca , Takahashi Koichi , O’Brien Susan M. , Jabbour Elias J. 
Published: June 2021

BackgroundThe outcome of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone plus ofatumumab hyper‐CVAD + ofatumumab (hyper‐CVAD + ofatumumab) has not been compared with the outcome of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone plus ofatumumab hyper‐CVAD plus rituximab (hyper‐CVAD + Rituximab) in Philadelphia chromosome–negative acute lymphoblastic leukemia (ALL) in a randomized clinical trial.MethodsThe authors compared the outcomes of 69 patients treated with hyper‐CVAD + ofatumumab and 95 historical‐control patients treated with hyper‐CVAD + Rituximab. Historical‐control patients were treated with hyper‐CVAD + Rituximab if they had CD20 expression ≥ 20%. Ofatumumab (day 1 of course 1, 300 mg intravenously; subsequent doses, 2000 mg intravenously) was administered on days 1 and 11 of courses 1 and 3 and on days 1 and 8 of courses 2 and 4 for a total of 8 doses. A propensity score analysis with inverse probability of treatment weighting (IPTW) was performed to adjust for baseline covariates between groups.ResultsThe median event‐free survival with stem cell transplantation (SCT) censoring was 33 and 65 months with hyper‐CVAD + Rituximab and hyper‐CVAD + ofatumumab, respectively (crude P = .064; IPTW P = .054). The median overall survival with SCT censoring was 52 months and not reached, respectively (crude P = .087; IPTW P = .097).ConclusionsHyper‐CVAD + ofatumumab was associated with better outcomes than hyper‐CVAD + Rituximab among patients with newly diagnosed Philadelphia chromosome–negative ALL.
First line immunotherapy extends brain metastasis free survival, improves overall survival, and reduces the incidence of brain metastasis in patients with advanced melanoma
Authors: Wang Xuechen , Haaland Benjamin , Hu‐Lieskovan Siwen , Colman Howard , Holmen Sheri L. 
Published: June 2021

AbstractBackgroundRecent advances in targeted therapy and immunotherapy have improved the prognosis of melanoma patients but brain metastasis remains a major challenge. Currently, it is unclear how existing therapies can be best used to prevent or treat brain metastasis in melanoma patients.AimsWe aimed to assess brain metastasis free survival (BMFS), overall survival (OS), incidence of brain metastases, and sequencing strategies of immunotherapy and targeted therapy in patients with BRAF‐mutated advanced melanoma.Methods and resultsWe retrospectively analyzed 683 patients with BRAF‐mutated advanced melanoma treated with first line (1L) immunotherapy (N = 266) or targeted therapy (N = 417). The primary outcome was BMFS. Secondary outcomes included OS of all patients and incidence of brain metastases in patients without documented brain metastases prior to 1L therapy. The median BMFS was 13.7 months [95% confidence interval (CI): 12.4–16.0] among all patients. The median BMFS for patients receiving 1L immunotherapy was 41.9 months [95% CI: 22.8–not reached (NR)] and targeted therapy was 11.0 months (95% CI: 8.8–12.5). Median OS results were qualitatively similar to BMFS results. The cumulative incidence of brain metastases for patients receiving 1L targeted therapy was higher than for patients receiving 1L immunotherapy (P < .001). Patients receiving 1L anti‐CTLA4 plus anti‐PD1 combination immunotherapy only or followed by second line (2L) targeted therapy had better BMFS (HR 0.40, 95% CI: 0.24–0.67,P = .001), improved OS (HR 0.49, 95% CI: 0.30–0.81,P = .005), and reduced incidence of brain metastases (HR 0.47, 95% CI: 0.24–0.67,P = .047) than patients receiving 1L combination BRAF and MEK targeted therapy followed by 2L immunotherapy.ConclusionPatients with advanced BRAF mutant melanoma treated with 1L immunotherapy have significantly longer BMFS and OS, and reduced incidence of brain metastases, compared with those treated with 1L targeted therapy. Further studies evaluating the ability of immunotherapy and targeted therapy to improve OS and prevent brain metastases are warranted
Quantifying the impact of the COVID‐19 pandemic on gastrointestinal cancer care delivery
Authors: Perkons Nicholas R. , Kim Casey , Boedec Chris , Keele Luke J. , Schneider Charles , Teitelbaum Ursina R. , Ben‐Josef Edgar , Gabriel Peter E. , Plastaras John P. , Shulman Lawrence N. , Wojcieszynski Andrzej P. 
Published: June 2021

AbstractBackground and AimThis study quantifies how changes in healthcare utilization and delivery during the first months of the COVID‐19 pandemic have altered the presentation, treatment, and management of patients with gastrointestinal (GI) malignancies within an academic health system.Methods and resultsPatients diagnosed with a GI malignancy (ICD10: C15‐C26) who received medical care within the health system during the observation period (first 44 weeks of 2019 and 2020) were identified for a retrospective cohort study. Deidentified patient encounter parameters were collected for this observation period and separated into pre‐pandemic (weeks 1–10) and early pandemic (weeks 11–20) study periods. Difference‐in‐difference analyses adjusted for week‐specific and year‐specific effects quantified the impact of the COVID‐19 pandemic on care delivery between pre‐pandemic and early pandemic study periods in 2020. Across all GI malignancies, the COVID‐19 pandemic has been associated with a significant decline in the number of patients with new patient visits (NPVs) (p = 1.2 × 10−4), Radiology encounters (p = 1.9 × 10−7), Surgery encounters (p = 1.6 × 10−3), Radiation Oncology encounters (p = 4.1 × 10−3), and infusion visits (6.1 × 10−5). Subgroup analyses revealed cancer‐specific variations in changes to delivery. Patients with colorectal cancer (CRC) had the most significant decrease in NPVs (p = 7.1 × 10−5), which was significantly associated with a concomitant decrease in colonoscopies performed during the early pandemic period (r2 = 0.722, p = 2.1 × 10−10).ConclusionsThe COVID‐19 pandemic has been associated with significant disruptions to care delivery. While these effects were appreciated broadly across GI malignancies, CRC, diagnosed and managed by periodic screening, has been affected most acutely.
Survivors of childhood cancer in Latin America: Role of foundations and peer groups in the lack of transition processes to adult long‐term follow‐up
Authors: Rossell Nuria , Olarte‐Sierra María Fernanda , Challinor Julia 
Published: June 2021

AbstractBackgroundOver the last decade, the population of childhood cancer survivors has rapidly increased in Latin America, opening a long chapter of challenges for healthcare providers in these countries to provide follow‐up and adult care.AimIn the process of exploring childhood cancer parent and patient engagement in resource‐limited settings, we highlight the challenges faced by Latin American survivors from El Salvador, Mexico, and Peru as they transitioned from receiving cancer treatment to life as a cancer survivors.Methods and ResultsFocus group discussions and interviews were performed as part of a larger qualitative study involving 10 low and middle‐income countries in four continents regarding patient and caregiver engagement in childhood cancer treatment. We present the results of the Latin‐American survivors and their experiences finishing treatment and life outside the pediatric oncology follow‐up system. Themes regarding a) losing eligibility for pediatric surveillance and care, b) the importance of peer survivors, and c) the need for giving back were part of their stories.ConclusionWe suggest that given the lack of organized support from healthcare systems and providers for survivors' proper transition into adult‐centered care, foundations and non‐governmental organizations can provide transitional support, offer space for guidance/information, and work towards collaboration among systems for future integrated programs.
High‐quality steganography scheme using hybrid edge detector and Vernam algorithm based on hybrid fuzzy neural network
Authors: Dhawan Sachin , Gupta Rashmi 
Published: June 2021

SummaryThere has been a developing extension in the utilization of steganography, because of the advancement in utilizing web innovation and interactive media innovation. Subsequently, these days, the data are not made sure about adequately while transmitting it over the system. Data are the most significant resource for the current electronic communication framework. Thus the data security has played a significant job to give protection from unapproved people. Steganography is the technique that provides the solution for this challenge. This article proposes a novel type of steganography strategy in which it uses the hybrid algorithm for higher security and a hybrid fuzzy neural network is utilized for the good quality of stego images. For higher security, this article utilizes the Sobel and Kirsch edge identifier and then the Vernam algorithm utilized for encrypting the secret image. Thereafter this article utilizes the combination of fuzzy logic and neural network for enhancing the quality of stego images. There are various advantages of this technique that it can be utilized in various areas, for example, confidential data communication in the defense sector, medical, electronic governance, banking, communication, and so on.
Long‐Term Generation of Longitudinal Spin Order Controlled by Ammonia Ligation Enables Rapid SABRE Hyperpolarized 2D NMR
Authors: Vaneeckhaute Ewoud , De Ridder Sophie , Tyburn Jean‐Max , Kempf James G. , Taulelle Francis , Martens Johan A. , Breynaert Eric 
Published: June 2021

AbstractThe front cover artwork front cover artwork is provided by NMRCoRe, the Flemish NMR/X‐Ray platform for Convergence Research and was designed by Ir. Ewoud Vaneeckhaute and Dr. Eric Breynaert. The image shows the reciprocity between parahydrogen, deuterated ammonia and iridium allowing for hyperpolarized 2D NMR via long‐term availability of longitudinal spin order. Read the full text of the Article at 10.1002/cphc.202100079.
Exploring the problems and potential of curriculum‐making for social learning: Implications for policy and practice
Authors: Restad Frode 
Published: June 2021

AbstractAlthough enhancing students’ social and emotional learning is a central concern in curriculum‐making at the policy level, little is still known about how curriculum‐making in the classroom can support such outcomes. Building on interviews and observations of students and teachers in lower secondary education in Norway, this study investigates how teachers support their students social learning through subject teaching in language and science, and explores the challenges related to such practices. The study identifies four main ways that teachers support social learning by; framing personal experiences as meaningful contents, facilitating community through peer assessment, using group work to develop shared practices and extending purpose to influence students’ identities through their subject teaching. The study concludes that curriculum‐making for social learning has potential as a strategy to support students’ social and academic learning in a more sustainable and meaningful way. Realising this potential, however, will require addressing the problems related to such practices and providing better guidance and support to avoid overburdening teachers and marginalising students.
Stages of embryonic development in the live‐bearing fish, Gambusia holbrooki
Authors: Mousavi Seyed Ehsan , Patil Jawahar G. 
Published: June 2021

AbstractBackgroundDivergent morphology and placentation of Poeciliids make them suitable model for investigating how evolutionary selection has altered and conserved the developmental mechanisms. However, there is limited description of their embryonic staging, despite representing a key evolutionary node that shares developmental strategy with placental vertebrates. Here, we describe the embryonic developmental stages of Gambusia holbrooki from zygote to parturition using freshly harvested embryos.ResultsWe defined 40 embryonic stages using a numbered (stages 0‐39; zygote to parturition, respectively) and named (grouped into seven periods, ie, zygote, cleavage, blastula, gastrula, segmentation, pharyngula, and parturition) staging system. Two sets of quantitative (ie, egg diameter, embryonic total length, otic vesicle closure index, heart rates, the number of caudal fin rays and elements) and qualitative (ie, three‐dimensional analysis of images and key morphological criteria) data were acquired and used in combination to describe each stage. All 40 stages are separated by well‐defined morphological traits, revealing developmental novelties that are influenced by narrow perivitelline space, placentation, internal gestation, and sex differentiation.ConclusionsThe principal diagnostic features described are quick, reliable, and easy to apply. This system will benefit researchers investigating molecular ontogeny, particularly sexual differentiation mechanisms in G. holbrooki.
Modes of drought climatization: A frame analysis of drought problematization in Germany across policy fields
Authors: Müller Wibke , Kruse Sylvia 
Published: June 2021

AbstractSince 2003, droughts have been problematized within a climate change frame in Germany. Scholars describe this framing process as climatization. In our research, we conduct a qualitative content analysis of sector journal articles to investigate the climatization of drought within the three most affected policy fields in Germany: agriculture, water management, and forestry. The research objectives are to investigate how climatization processes evolve and take place within a specific policy field, and what different modes of climatization can be identified. The results are based on a framing analysis of 267 articles from journals published by political associations of farmers, water managers, and foresters at both the national and a state level, covering drought problematization relating to two major drought events in 2003 and 2011–2012. The article shows that four modes of climatization can be distinguished: scientification, securitization, technocratization, and transformation. With this empirically based heuristic, we contribute to advancing the concept of climatization by operationalizing it into a more profound, empirically grounded analytical concept that can be applied to critically investigate policymaking processes related to reducing disaster risks and achieving climate adaptation.
The Quest for Optimal 3 d Orbital Splitting in Tetrahedral Cobalt Single‐Molecule Magnets Featuring Colossal Anisotropy and Hysteresis
Authors: Legendre Christina M. , Damgaard‐Møller Emil , Overgaard Jacob , Stalke Dietmar 
Published: June 2021

AbstractOnly a few four‐coordinated Co2+‐complexes show single‐molecule magnet (SMM) properties without an applied dc field. Common for those is a large magnetic anisotropy generated by the close proximity of the
and
orbitals. This type of magnetic anisotropy is strongly correlated with the extent of structural distortion from ideal tetrahedral towards linear coordination. Quantification of the governing magneto‐structural correlations is hence crucial for the development of better SMMs. For this purpose, we synthesized and analyzed four significantly distorted tetrahedral cobalt complexes that exhibit extremely large magnetic anisotropies and slow relaxation of magnetization in zero field. The N−Co−N bite angles vary from 70.8 to 72.7°, and magnetic measurements show strong anisotropy with D‐values in the range from
75 to
114 cm−1. Ab initio calculations supported the experimental results and highlighted a significant increase of D up to
141 cm−1, correlated with the reduction of the energy difference between the
and
orbitals. Based on these magneto‐structural correlations and in contrast to the current assumption that the smaller bite angle is the better, we predict that with an ideal bite angle in the range from 76–78° in distorted Co(N2R)2 complexes, the energy difference between the two important d‐orbitals is at a minimum and hence the magnetic anisotropy is maximized.
Ipragliflozin Improves the Hepatic Outcomes of Patients With Diabetes with NAFLD
Authors: Takahashi Hirokazu , Kessoku Takaomi , Kawanaka Miwa , Nonaka Michihiro , Hyogo Hideyuki , Fujii Hideki , Nakajima Tomoaki , Imajo Kento , Tanaka Kenichi , Kubotsu Yoshihito , Isoda Hiroshi , Oeda Satoshi , Kurai Osamu , Yoneda Masato , Ono Masafumi , Kitajima Yoichiro , Tajiri Ryo , Takamori Ayako , Kawaguchi Atsushi , Aishima Shinichi , Kage Masayoshi , Nakajima Atsushi , Eguchi Yuichiro , Anzai Keizo 
Published: June 2021

Sodium glucose cotransporter‐2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon‐like peptide‐1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, −0.41%, P < 0.01; BMI, −1.06 kg/m2, P < 0.01), whereas these did not change in the CTR group (n = 26). Liver pathology was evaluated in 21/25 participants in the IPR/CTR groups, and hepatic fibrosis was found in 17 (81%) and 18 (72%) participants in the IPR and CTR groups at baseline. This was ameliorated in 70.6% (12 of 17) of participants in the IPR group and 22.2 % (4 of 18) of those in the CTR group (P < 0.01). Nonalcoholic steatohepatitis (NASH) resolved in 66.7% of IPR‐treated participants and 27.3% of CTR participants. None of the participants in the IPR group developed NASH, whereas 33.3% of the CTR group developed NASH. Conclusion: Long‐term ipragliflozin treatment ameliorates hepatic fibrosis in patients with NAFLD. Thus, ipragliflozin might be effective for the treatment and prevention of NASH in patients with diabetes, as well as improving glycemic control and obesity. Therefore, SGLT2is may represent a therapeutic choice for patients with diabetes with NAFLD, but further larger studies are required to confirm these effects.
Redox‐Neutral Syntheses and Electrochemical Studies of 10‐Bromo‐Substituted Light‐Stable Antivitamin B12 Candidates
Authors: Brenig Christopher , Mosberger Leila , Baumann Katja , Blacque Olivier , Zelder Felix 
Published: June 2021

AbstractThis publication describes the straightforward and redox‐neutral synthesis of 10‐bromophenylethynylcobalamin and its facile conversion to 10‐bromoaquacobalamin. In this approach, the phenylethynyl ligand acts as convenient light‐stable protecting group that is removed in quantitative yield under acidic conditions. The proteolytic cleavage at pH 2.0 was studied under pseudo‐first‐order conditions and is 1.5 times slower than that of phenylethynylcobalamin with a hydrogen instead of a bromine at C(10). Preliminary electrochemical studies of organometallic ethynyl‐Cbls (Cbl=cobalamin) are reported for the first time. A reduction potential
of −0.94 V vs. Ag/AgCl was determined for the CoIII/CoI reduction of 10‐bromophenylethynylcobalamin. The positive potential shift of 180 mV compared to phenylethynylcobalamin is in agreement with earlier electrochemical studies of related cyanocobalamins.
Enantioselective Total Synthesis of (+)‐Nordasycarpidone, (+)‐Dasycarpidone, and (+)‐Uleine
Authors: Delayre Bastien , Fung Cédric , Wang Qian , Zhu Jieping 
Published: June 2021

AbstractThe structure of uleine type alkaloids is characterized by the presence of a bridged tetracyclic hexahydro‐1H‐1,5‐methanoazocino[4,3‐b]indole ring system 1. Various strategies have been developed to access this polycyclic structural motif. We report herein a one‐step conversion of appropriately functionalized 1,3,4‐trisubstituted cyclopent‐1‐ene to 1 by way of an integrated oxidation/reduction/cyclization (iORC) process. This domino sequence, initiated by oxidative cleavage of cyclopentene ring, generated subsequently a cyclohexenone, an indole and a 1,3‐bridged piperidine ring through formation of one C−C and two C−N bonds. Compound 1 is subsequently converted to nordasycarpidone, dasycarpidone and uleine. The chirality of the molecule was introduced by enzymatic desymmetrization of commercially available meso cis‐3,5‐diacetoxy‐1‐cyclopentene.