bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities
Authors: Spring Laura M. , Nakajima Erika , Hutchinson Jennifer , Viscosi Elene , Blouin Gayle , Weekes Colin , Rugo Hope , Moy Beverly , Bardia Aditya 
Published: June 2021

AbstractPatients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate that contains the irinotecan active metabolite, SN-38, linked to a humanized monoclonal antibody targeting trophoblast cell surface antigen 2, which is overexpressed in many solid tumors. In a basket design phase I/II study, sacituzumab govitecan demonstrated promising single-agent therapeutic activity in multiple cancer cohorts, leading to accelerated approval by the U.S. Food and Drug Administration of sacituzumab govitecan-hziy (TRODELVY) for the treatment of patients with metastatic triple-negative breast cancer who had received at least two prior therapies in the metastatic setting. Recently, results of the phase III trial, ASCENT, were confirmatory. There is limited available information on the adverse event management with sacituzumab govitecan needed to maximize the dose and duration of effective therapy while maintaining patient quality of life. This review summarizes the clinical development and the practical management of patients receiving sacituzumab govitecan. Sacituzumab govitecan has a well-defined and manageable toxicity profile, and rapid recognition and appropriate early and proactive management will allow clinicians to optimize sacituzumab govitecan treatment for patients.Implications for PracticeSacituzumab govitecan (TRODELVY) is a novel antibody-drug conjugate composed of the active metabolite of irinotecan (SN-38) conjugated to a monoclonal antibody targeting trophoblast cell surface antigen 2, an epithelial cell surface antigen overexpressed in many cancers. Because of the rapid approval of sacituzumab govitecan, there is limited available information on adverse event (AE) management with this agent. As such, this article reviews the clinical development of the drug, the AE profile, and provides recommendations regarding AE management to help optimize therapy with sacituzumab govitecan.
Locally Recurrent Secretory Carcinoma of the Breast with NTRK3 Gene Fusion
Authors: Mortensen Lindsey , Ordulu Zehra , Dagogo-Jack Ibiayi , Bossuyt Veerle , Winters Loren , Taghian Alphonse , Smith Barbara L. , Ellisen Leif W. , Kiedrowski Lesli A. , Lennerz Jochen K. , Bardia Aditya , Spring Laura M. 
Published: June 2021

Abstract
Enhanced understanding of the molecular events underlying oncogenesis has led to the development of “tumor-agnostic” treatment strategies, which aim to target a tumor's genomic profile regardless of its anatomic site of origin. A classic example is the translocation resulting in an ETV6-NTRK3 gene fusion, a characteristic driver of a histologically diverse array of cancers. The chimeric ETV6-NTRK3 fusion protein elicits constitutive activation of the tropomyosin receptor kinase (TRK) C protein, leading to increased cell survival, growth, and proliferation. Two TRK inhibitors, larotrectinib and entrectinib, are currently approved for use in the metastatic setting for the treatment of advanced solid tumors harboring NTRK fusions. Here we report a rare case of recurrent secretory carcinoma of the breast (SCB) with NTRK3 gene fusion. Whereas most cases of SCB represent slow-growing tumors with favorable outcomes, the case detailed here is the first to the authors' knowledge of recurrence within 1 year of surgery. We review the molecular findings and potential clinical significance.

Key Points
Open intrauterine repair of spina bifida aperta: Historical aspects, current availability, and clinical outcomes from the Latin American Spina Bifida Consortium
Authors: Sepulveda Waldo , Cruz‐Martinez Rogelio , Etchegaray Adolfo , Sanin‐Blair Jose , Ventura Walter , Corral Edgardo , Marquez Rolando 
Published: June 2021

AbstractObjectiveTo determine the historical aspects, current availability, and clinical outcomes of open intrauterine repair of spina bifida aperta (IRSBA) in Spanish‐speaking Latin American countries.MethodsCases were collected from centers with at least 2 years of experience and a minimum of 10 open IRSBA interventions by December 2020. Clinical variables were compared to the results of the Management of Myelomeningocele Study (MOMS) trial.ResultsClinical experience with 314 cases from seven centers was reviewed. Most cases (n = 189, 60.2%) were performed between 24 and 25.9 weeks' gestation. Delivery at less than 30 weeks' gestation occurred in 36 cases (11.5%) and the overall perinatal mortality rate was 5.4% (17 of 314). The rate of maternal complications was low, including the need for blood transfusion (n = 3, 0.9%) and dehiscence or a thin uterine scar (n = 4, 1.3%). No cases of maternal death were recorded. Fifteen neonates required additional surgical repair of the spinal defect (4.8%) and 63 of 167 infants (37.7%) required a cerebrospinal fluid diversion procedure. Only two of the seven centers reported preliminary experience with fetoscopic IRSBA.ConclusionsClinical experience and outcomes were within the expected results reported by the MOMS trial. There is still very limited experience with fetoscopic IRSBA in this part of the world.
Twin chorionicity and zygosity both vary with maternal age
Authors: Yeaton‐Massey Amanda , Sparks Teresa N. , Norton Mary E. , Jelliffe‐Pawlowski Laura , Currier Robert J. 
Published: June 2021

AbstractObjectiveTo determine the ratio of dichorionic (DC) to monochorionic (MC) twins by maternal age.MethodsWe reviewed all twin pregnancies undergoing first trimester screening (FTS) with nuchal translucency from April 2009 to December 2012 with sonographic determination of chorionicity. Cases were linked to newborn screening (NBS) results and zygosity estimated based on rates of fetal sex discordance. The ratio of DC to MC placentation by maternal age was calculated.ResultsWe identified 11,351 twin pregnancies with FTS and documented chorionicity. Among these, 7861 (64.2%) had linked data on FTS and NBS to allow estimation of zygosity based on neonatal sex. Of these, 1464 (18.6%) were MC and 6406 (81.4%) DC. The MC twin rate remained constant while the DC twin rate increased with maternal age until 40 years. At <20 years, 55% of twin pregnancies were monozygotic (MZ), as compared to 29% at > 40 years. Of MZ twins, 38% were DC at < 20years, while 53% were DC at >40 yearsConclusionsOur data suggest a relationship of both zygosity and chorionicity with maternal age. DZ twinning increased with maternal age, while among MZ twins, the proportion that were DC also increased with maternal age.
Is ventriculomegaly and hindbrain herniation seen before and after prenatal neural tube defect repair associated with a worse functional level than anatomical level at birth?
Authors: Corroenne Romain , Zarutskie Alexander , Guimaraes Carolina , Yepez Mayel , Torres Paola , Shetty Anil , Lee Wesley , Espinoza Jimmy , Shamshirsaz Alireza A. , Nassr Ahmed A. , Belfort Michael , Whitehead William , Sanz Cortes Magdalena 
Published: June 2021

AbstractObjectiveTo determine if the evaluation of the fetal ventricular system and hindbrain herniation (HBH) is associated with motor outcome at birth in prenatally repaired open neural tube defect (NTD).MethodsRetrospective cohort study of 47 patients with NTD who underwent prenatal repair (17 fetoscopic; 30 open‐hysterotomy). At referral and 6 weeks postoperatively, the degree of HBH, ventricular atrial widths and ventricular volume were evaluated by MRI. Head circumference and ventricular atrial widths were measured on ultrasound at referral and during the last ultrasound before delivery. Anatomic level of the lesion (LL) was determined based on the upper bony spinal defect detected by ultrasound. We considered the functional level as worse than anatomical level at birth when the motor level was equal or worse than the anatomical LL.Results26% (12/47) of the cases showed worse functional level than anatomical level at birth. Having a HBH below C1 at the time of referral was associated with a worse functional level than anatomical level at birth (OR = 9.7, CI95 [2.2–42.8], p < 0.01). None of the other brain parameters showed a significant association with motor outcomes at birth.ConclusionsHBH below C1 before surgery was associated with a worse functional level than anatomical level at birth.
Modeling of protein complexes in CASP14 with emphasis on the interaction interface prediction
Authors: Dapkūnas Justas , Olechnovič Kliment , Venclovas Česlovas 
Published: June 2021

AbstractThe goal of CASP experiments is to monitor the progress in the protein structure prediction field. During the 14th CASP edition we aimed to test our capabilities of predicting structures of protein complexes. Our protocol for modeling protein assemblies included both template‐based modeling and free docking. Structural templates were identified using sensitive sequence‐based searches. If sequence‐based searches failed, we performed structure‐based template searches using selected CASP server models. In the absence of reliable templates we applied free docking starting from monomers generated by CASP servers. We evaluated and ranked models of protein complexes using an improved version of our protein structure quality assessment method, VoroMQA, taking into account both interaction interface and global structure scores. If reliable templates could be identified, generally accurate models of protein assemblies were generated with the exception of an antibody‐antigen interaction. The success of free docking mainly depended on the accuracy of initial subunit models and on the scoring of docking solutions. To put our overall results in perspective, we analyzed our performance in the context of other CASP groups. Although the subunits in our assembly models often were not of the top quality, these models had, overall, the best‐predicted intersubunit interfaces according to several accuracy measures. We attribute our relative success primarily to the emphasis on the interaction interface when modeling and scoring.
What makes a molecule a pre‐ or a post‐herbicide – how valuable are physicochemical parameters for their design?
Authors: Krähmer Hansjörg , Walter Helmut , Jeschke Peter , Haaf Klaus , Baur Peter , Evans Richard 
Published: June 2021

AbstractPre‐emergence herbicides are taken up by seeds before germination and by roots, hypocotyls, cotyledons, coleoptiles or leaves before emergence, whereas post‐emergence herbicides are taken up primarily by foliage and stems. Most modern pre‐emergence herbicides are lipophilic, but post‐emergence herbicides may be lipophilic or hydrophilic. The metabolic conversion of herbicides to inactive or active metabolites after plant uptake is of major importance for some compound classes. Several herbicides are proherbicides as for example some acetyl‐coenzyme A carboxylase (ACCase)‐inhibitors. The physicochemical characteristics of proherbicides and herbicides are usually unrelated. A major role can be attributed to the site of action at a cellular level. A great number of herbicides such as photosystem II (PS II)‐inhibitors, protoporphyrinogen oxidase (PPO)‐inhibitors or carotenoid biosynthesis inhibitors require light for activity. Others, such as cellulose‐biosynthesis and mitotic inhibitors seem to be primarily active in belowground organs. Several lipophilic barriers against the uptake of xenobiotics exist in aboveground and belowground plant parts. The relevance of these barriers needs, however, further clarification. Uptake and translocation models are valuable tools for the explanation of the potential movement of compounds. Many factors other than uptake and translocation have, however, to be considered for the design of herbicides. For post‐emergence herbicides, ultraviolet (UV) light stability, stability in formulations, and mixability with other agrochemicals have to be kept in mind while, in addition to the aforementioned factors soil interaction plays a major role for pre‐emergence herbicides. In our opinion, general physicochemical characteristics of pre‐ or post‐emergence herbicides do, unfortunately not exist yet. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Characterization of Helicoverpa armigera spatial distribution in pigeonpea crop using geostatistical methods
Authors: Seethalam Malathi , Bapatla Kiran Gandhi , Kumar Murari , Nisa Shabistana , Chandra Puran , Mathyam Prabhakar , Sengottaiyan Vennila 
Published: June 2021

AbstractBACKGROUNDThe gram pod borer, Helicoverpa armigera (Lepidoptera: Noctuidae) is an economically important pest of pigeonpea crop in India. Fixed plot surveys for H. armigera larvae were carried out at 28 pigeonpea fields located in the Southern Plateau and Hills agro‐climatic zone of India for three crop seasons (nine sampling weeks per season). The spatiotemporal dynamics of H. armigera larvae in the experimental area (=Hanamkonda) was analysed using geostatistics tools, namely a variogram and Voronoi diagram, and H. armigera larval distribution patterns were further characterized and mapped.RESULTSA significant difference in H. armigera larval incidence was noticed between sampling weeks, with greater larval incidence observed between 26 November and 2 December. Pod formation phenophase (Meteorological Standard Week 44) of pigeonpea favoured the initial H. armigera larval incidence. Variogram analysis revealed moderate to strong larval aggregation (spatial dependence) of H. armigera in all nine sampling weeks. Based on the range value of the variogram, the average aggregation distance of H. armigera larvae in pigeonpea was estimated to be 2425.48 m. Voronoi diagrams illustrated the spatial heterogeneity of H. armigera larva between sampling weeks, which can be linked to availability of food sources.CONCLUSIONThis study witnessed intrapopulation variability in H. armigera larvae associated with geographical space and temporal patterns. Based on our findings, a sampling distance of 2425.48 m may be used in larger pigeonpea fields (experimental area) to reduce scouting fatigue. The interpolated maps generated in this study may be of value in developing effective H. armigera larva monitoring and management tools in pigeonpea crop.
Resveratrol enhanced mitochondrial recovery from cryopreservation‐induced damages in oocytes and embryos
Authors: Iwata Hisataka 
Published: June 2021

AbstractBackgroundMitochondria play a crucial role in nuclear maturation, fertilization, and subsequent embryo development. Cryopreservation is an important assisted reproductive technology that is used worldwide for humans and domestic animals. Although mitochondrial quantity and quality are decisive factors for successful development of oocytes and embryos, cryopreservation induces mitochondrial dysfunction. Upon thawing, the damaged mitochondria are removed, and de novo synthesis occurs to restore the function of mitochondria. Resveratrol, 3,5,4′‐trihydroxystilbene, is a polyphenolic antioxidant that has versatile target proteins, among which sirtuin‐1 (SIRT1) is a key regulator of in mitochondrial biogenesis and degradation.MethodsThe present study is a literature review focusing on experiments involving the hypothesis that the activation of mitochondrial biogenesis and degradation following cryopreservation and warming by resveratrol may help mitochondrial recovery and improve oocyte and embryo development.Main findings and conclusionResveratrol improves oocyte maturation and development and upregulates mitochondrial biogenesis and degradation. When vitrified‐warmed embryos are treated with resveratrol, it helps in mitochondrial regulation and recovery of embryos from cryopreservation‐induced damage.ConclusionResveratrol treatment is a possible countermeasure against cryopreservation‐induced mitochondrial damage.
Metabolic reprogramming and immune regulation in viral diseases
Authors: Ganesh Goutham V. , Mohanram Ramkumar K. 
Published: June 2021

SummaryThe recent outbreak and transmission of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) worldwide and the ensuing coronavirus disease 2019 (COVID‐19) pandemic has left us scrambling for ways to contain the disease and develop vaccines that are safe and effective. Equally important, understanding the impact of the virus on the host system in convalescent patients, healthy otherwise or with co‐morbidities, is expected to aid in developing effective strategies in the management of patients afflicted with the disease. Viruses possess the uncanny ability to redirect host metabolism to serve their needs and also limit host immune response to ensure their survival. An ever‐increasingly powerful approach uses metabolomics to uncover diverse molecular signatures that influence a wide array of host signalling networks in different viral infections. This would also help integrate experimental findings from individual studies to yield robust evidence. In addition, unravelling the molecular mechanisms harnessed by both viruses and tumours in their host metabolism will help broaden the repertoire of therapeutic tools available to combat viral disease.
Vitamin D supplementation and Covid‐19 outcomes: A systematic review, meta‐analysis and meta‐regression
Authors: Hariyanto Timotius Ivan , Intan Denny , Hananto Joshua Edward , Harapan Harapan , Kurniawan Andree 
Published: June 2021

SummaryVitamin D has many protective properties and potential role against acute lung injury. Low serum vitamin D is associated with high risk of pneumonia and development of acute respiratory distress syndrome. This study sought to analyse the efficacy of vitamin D in improving the outcomes of coronavirus disease 2019 (Covid‐19) patients. Using specific keywords, we comprehensively searched the potential articles on PubMed, Europe PMC and ClinicalTrials.gov database until 8th May 2021. All published studies on Covid‐19 and vitamin D were retrieved. Statistical analysis was conducted using Review Manager 5.4 software. A total of 11 studies with 22,265 Covid‐19 patients were included in the meta‐analysis. Our data suggested that vitamin D supplementation was associated with reduction in intensive care unit admission rate (OR 0.27; 95% CI: 0.09–0.76, p = 0.010, I2 = 70%, random‐effect modelling); reduction of the need for mechanical ventilation (OR 0.34; 95% CI: 0.16–0.72, p = 0.005, I2 = 61%, random‐effect modelling) and reduction of mortality from Covid‐19 (OR 0.37; 95% CI: 0.21–0.66, p < 0.001, I2 = 50%, random‐effect modelling). Further analysis showed that the associations were influenced by age (p = 0.020). Our study suggests that vitamin D supplementation may offer beneficial effects on Covid‐19 outcomes. However, more randomized clinical trials are required to confirm this conclusion.
Fixed‐time cooperative control for robotic manipulators with motion constraints using unified transformation function
Authors: Liu Yang , Zhang Huaguang , Wang Yingchun , Yu Shuhang 
Published: June 2021

AbstractThis article investigates the fixed‐time consensus tracking control problem for multiagent systems composed of uncertain l‐link robotic manipulators with position and velocity constraints. Fuzzy logic systems are employed to model the uncertain dynamic of the robotic manipulators. In order to cope with the asymmetric yet time‐varying constraints, a nonlinear transformation function is introduced. With the help of the nonlinear transformation function, the original constrained manipulator systems are converted into the equivalent systems without constraint. As long as the boundedness of the state variables in the transformed systems is ensured, the constraint conditions of the original systems are not violated. Then, a fixed‐time adaptive fuzzy control scheme is developed. Under the proposed control method, the consensus tracking error can converge into a small neighborhood of origin in fixed‐time, and all the signals in the closed‐loop systems are bounded. Meanwhile, the motion constraints are not violated all the time. Specially, in view of the property of nonlinear transformation function, it is not necessary to change the control structure when the systems are subjected to no state constraint. Finally, a simulation is presented to illustrate the feasibility and effectiveness of implementing the proposed control algorithms.
Hyperkalaemia during two consecutive anaesthetics in an aggressive Bengal cat
Authors: Casoria Vincenzo , Flaherty Derek , Auckburally Adam 
Published: June 2021

AbstractThe development of unanticipated hyperkalaemia during general anaesthesia in healthy veterinary patients is an increasingly recognized phenomenon. Cases have been reported in dogs, cats, horses and non‐domestic felids. However, recurrent hyperkalaemia has not yet been described in domestic cats. We report the development of hyperkalaemia during two consecutive anaesthetics in a 5‐year‐old, Bengal cat, anaesthetised for medial patella luxation repair and 3 months later for implant removal. During both procedures, hyperkalaemia was diagnosed. However, it was only during the first anaesthetic that the hyperkalaemia became life‐threatening, necessitating treatment. The reasons why some animals develop hyperkalaemia during general anaesthesia are still unknown. Considering the apparent increasing frequency of this condition, hyperkalaemia should be considered as a potential cause of intraoperative bradydysrhythmias and must be investigated and treated appropriately.
The Global Economy After the End of Capital Scarcity: A Utopian Proposal
Authors: von Weizsäcker Carl Christian , Krämer Hagen M. 
Published: June 2021

AbstractExtrapolating from List (Das nationale System der politischen Ökonomie. Cotta, Stuttgart, 1841), we explain the paradox of China: A poor country can experience tumultuous growth precisely by exporting more capital on balance than it imports. More growth can be created in developing countries by their running current account surpluses vis-à-vis the OECD plus China region. Public debt in the OECD plus China region would have then to be managed in such a way that full employment is preserved despite the current account deficit. Such a strategy would be beneficial for both groups of countries. For the time being, this is a utopian proposal. Realizing it would mean yet another restructuring, in addition to that associated with digitalization. The opposition of those who could lose their jobs as a result will ensure that this sort of reorientation of global trade policy will remain politically unfeasible for a long time still.
Concluding Remarks on Economic Policy
Authors: von Weizsäcker Carl Christian , Krämer Hagen M. 
Published: June 2021

AbstractThe German debt brake is not compatible with the long-term stability of the euro. “New thinking” requires that public debt and price stability are no longer opponents, but rather allies in the Keynes world of persistently low interest rates. The proposed balanced account agreement is made more concrete here: An appropriate target (real) interest rate on the global capital market is between one and 1.5% per year lower than the growth rate of the OECD plus China region. If the actual interest rate is below the target rate, the countries with current account surpluses undertake to increase their public debt periodD gradually according to a definite formula. In symmetrical fashion, if the real interest rate is “too high,” countries with current account deficits have the duty to reduce their public debt period. The rules of the balanced account agreement replace the debt brake. They are the instruments of soundfiscal policy.