bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Germline Genetic Testing Before and After a Medical Policy Covering Universal Testing Among Patients With Colorectal Cancer
Authors: Moretz Chad , Byfield Stacey DaCosta , Hatchell Kathryn E. , Dalton Joline , Onglao Peter Nicholas , Hang Lillian , Hansen Pamela , Radford Cristi , Nielsen Sarah M. , Heald Brandie , Munro Sandra B. , Nussbaum Robert L. , Esplin Edward D. 
Published: October 2022

ImportanceIn 2020, some health insurance plans updated their medical policy to cover germline genetic testing for all patients diagnosed with colorectal cancer (CRC). Guidelines for universal tumor screening via microsatellite instability and/or immunohistochemistry (MSI/IHC) for mismatch repair protein expression for patients with CRC have been in place since 2009.ObjectivesTo examine whether uptake of MSI/IHC screening and germline genetic testing in patients with CRC has improved under these policies and to identify actionable findings and management implications for patients referred for germline genetic testing.Design, Setting, and ParticipantsThe multicenter, retrospective cohort study comprised 2 analyses of patients 18 years or older who were diagnosed with CRC between January 1, 2017, and December 31, 2020. The first analysis used an insurance claims data set to examine use of MSI/IHC screening and germline genetic testing for patients diagnosed with CRC between 2017 and 2020 and treated with systemic therapy. The second comprised patients with CRC who had germline genetic testing performed in 2020 that was billed under a universal testing policy.Main Outcomes and MeasuresPatient demographic characteristics, clinical information, and use of MSI/IHC screening and germline genetic testing were analyzed.ResultsFor 9066 patients with newly diagnosed CRC (mean [SD] age, 64.2 [12.7] years; 4964 [54.8%] male), administrative claims data indicated that MSI/IHC was performed in 6645 eligible patients (73.3%) during the study period, with 2288 (25.2%) not receiving MSI/IHC despite being eligible for coverage. Analysis of a second cohort of 55 595 patients with CRC diagnosed in 2020 and covered by insurance found that only 1675 (3.0%) received germline genetic testing. In a subset of patients for whom germline genetic testing results were available, 1 in 6 patients had pathogenic or likely pathogenic variants, with most of these patients having variants with established clinical actionability.Conclusions and RelevanceThis nationwide cohort study found suboptimal rates of MSI/IHC screening and germline genetic testing uptake, resulting in clinically actionable genetic data being unavailable to patients diagnosed with CRC, despite universal eligibility. Effective strategies are required to address barriers to implementation of evidence-based universal testing policies that support precision treatment and optimal care management for patients with CRC.
Reimagining Children’s Rights in the US
Authors: Barnert Elizabeth , Wright Joseph , Choi Charlene , Todres Jonathan , Halfon Neal ,   Reimagining Children’s Rights Steering Committee, Advisory Committee, and Project Team, Abaya Miriam A , Adedokun Lola A , Akl Abdullah , Alexander David T , Alvarez Mayra E , Aron Laudan Y , Auerswald Colette L , Barbosa Gabriella , Battle Gabrielle C , Bunnett Dana M , Chow Giselle , Christakis Dimitri A , Counts Nathaniel Z , El-Amin Champion Tezzaree S , Engman Mark G , Ewing Toby J , Gentile-Montgomery Chloe R , Godoy Blanca , Goldhagen Jeffrey L , Gran Brian , Hernandez Giovanni , Iyer Puja , Jones-Taylor Myra , Kemp Jasmin M , Kirsch Kayla A , Lansdown Gerison , Lazarus Wendy , Lesley Bruce , Lombardi Joan , López Hernández Guadalupe , Mejia-Garzaro Brianna N , Michael Brown Keaun , Morales Xavier , Moulton Melissa K , Peiffer Matthew B , Peńa Andrea R , Pitre Nikki , Porayouw William F , Poterek Lauren A , Santana Sandy , Sayed Rimsha S , Schotland Marieka S , Thomas III Bernard L , Togi Dashuri (Dash) L , Woodhouse Barbara , Zhang Adrianna 
Published: October 2022

ImportanceThe US faces a pivotal moment of opportunity and risk regarding issues affecting children (aged 0-17 years). Although the US remains the only United Nations member state to not have ratified the Convention on the Rights of the Child (CRC), a child rights framework is essential for child health professionals seeking to advance many issues affecting children in the US. The Reimagining Children’s Rights project (2020-2021) conducted an in-depth environmental scan of relevant literature and policy analysis using the Three Horizons design process to assess strategies that could advance the rights and well-being of children in the US. The project was overseen by a steering committee and informed by an advisory committee composed of youth leaders and experts in children’s rights, advocacy, health, law, and a range of child-specific issues (eg, youth justice, early childhood development), who provided expert input on strategic considerations for advancing children’s rights.ObservationsSeven findings about advancing children’s rights in the US are notable, all reflecting current gaps and opportunities for using a whole-child rights framework in the US, even without formal adoption of the CRC. Actionable strategies, tactics, and tools to leverage sustainable change in the multitude of issue areas can advance the current state of children’s rights. High-potential strategies for catalyzing advancement of children’s rights include youth activism, innovations in governance and accountability, legislative action, impact litigation, place-based initiatives, education and public awareness, alignment with other children’s movements, and research. The child rights framework is unifying and adaptive to future unforeseen challenges.Conclusions and RelevanceChildren’s rights provide a powerful, synergistic framework for child health professionals—in partnership with youth and other leaders—to increase equity and protect the rights and well-being of all children in the US.
Flowsheet generation through hierarchical reinforcement learning and graph neural networks
Authors: Stops Laura , Leenhouts Roel , Gao Qinghe , Schweidtmann Artur M. 
Published: October 2022

AbstractProcess synthesis experiences a disruptive transformation accelerated by artificial intelligence. We propose a reinforcement learning algorithm for chemical process design based on a state‐of‐the‐art actor‐critic logic. Our proposed algorithm represents chemical processes as graphs and uses graph convolutional neural networks to learn from process graphs. In particular, the graph neural networks are implemented within the agent architecture to process the states and make decisions. We implement a hierarchical and hybrid decision‐making process to generate flowsheets, where unit operations are placed iteratively as discrete decisions and corresponding design variables are selected as continuous decisions. We demonstrate the potential of our method to design economically viable flowsheets in an illustrative case study comprising equilibrium reactions, azeotropic separation, and recycles. The results show quick learning in discrete, continuous, and hybrid action spaces. The method is predestined to include large action‐state spaces and an interface to process simulators in future research.
[3+2] Cycloaddition Reactions of 2‐Ylidene Acenaphthylenones with 3‐Benzylidene Succinimides and 1,4‐Benzoxazinone Derivatives
Authors: Dahiya Pooja , Yadav Anoop , Rawat Megha , Peddinti Rama Krishna 
Published: October 2022

AbstractA base‐catalyzed novel [3+2] cycloaddition reaction between arylidene‐1‐phenyl succinimides and alkylidene acenaphthylenones is carried out to access succinimide substituted spiro[acenaphthylenone‐cyclopentane]fused scaffolds with high regio‐ and stereo‐selectivity under mild conditions. The reaction of alkylidene acenaphthylenones with 1,4‐benzoxazinone derivatives under the influence of environmentally benign iodine afforded polyheterocyclic compounds embedded with pyrrole moiety. This metal‐free synthesis is highly efficient and atom economic and the protocol obviates column chromatography. The products are isolated by simple decantation followed by washing with solvent.
Reflections of manual labor in the hand entheses of early industrial women workers with extensively documented life histories
Authors: Karakostis Fotios Alexandros , Hotz Gerhard 
Published: October 2022

AbstractObjectivesSex‐based occupational variability constitutes a fundamental component of human behavior and a major focus of research focusing on biocultural evolution. However, the reliability of reconstructing physical activity in past women is often compromised by the lack of female skeletal collections with adequately documented lifetime occupations, domestic living conditions, medical records, and socioeconomic status. Here, we attempt to reconstruct habitual manual activity in a skeletal sample of early industrial women with uniquely archived life histories.Materials and MethodsWe rely on the application of our “Validated Entheses‐based Reconstruction of Activity” method on the hand skeletons of 38 extensively documented individuals from the Basel‐Spitalfriedhof collection. Our comparisons also include 40 documented males from the same collection.ResultsAs expected, we found evidence of increased entheseal variability among women sharing the same unspecialized occupation (maids and factory workers). Moreover, certain entheseal patterns were almost exclusive to the men involved in occupations not associated with the female sex (mainly construction workers). Importantly, all six women known to have practiced more specific occupational activities (e.g., seamstresses) showed distinctive entheseal patterns, seemingly associated with more demanding physical practices. This within‐sex variation was not correlated with differences in biological age, estimated body size, socioeconomic status, relatedness, or the presence of reported children.DiscussionOur findings directly reflect the rich historical sources on the working lives of low‐status women in early industrial Basel. These results highlight the high potential value of our documented sample as a reference basis for reconstructing the division of labor in bioarchaeological contexts.
Was there a need for high carbohydrate content in Neanderthal diets?
Authors: Klement Rainer J. 
Published: October 2022

AbstractObjectivesIn a recent paper, Hardy et al. (2022, Journal of Human Evolution 162: 103105) claim that the physiological Neanderthal requirement for plant carbohydrates may have reached 50%–60% of caloric intake, inferred from modern dietary guidelines and a putative need for high carbohydrate intake in pregnant/breastfeeding women and athletes. The aim of this article is to critically re‐examine these arguments under the premise that hominins could adapt to hypercarnivorous diets and low carbohydrate consumption.Materials and MethodsLiterature on ketogenic and carnivore diets was retrieved. A case report of a male rugby player voluntarily undertaking a carnivore diet under medical supervision is presented.ResultsHuman metabolism is highly flexible towards adapting to long‐term low carbohydrate intakes by producing and utilizing ketone bodies. The evidence base of dietary guidelines is weak, and carbohydrate intake recommendations for athletes and during pregnancy/lactation are uncertain, making a translation to Neanderthal diets questionable. The studied rugby player maintained his sports performance and health over a 4‐months period despite minimal carbohydrate intake.DiscussionHuman physiology appears to have an extraordinary ability to utilize ketone bodies as a fuel for the brain and skeletal muscle, in particular also during exercise. The translation of dietary guidelines to Neanderthals and interpretation of studies in subjects not adapted to ketosis may be biased by a “glucocentric” perspective supposing that high carbohydrate intake is necessary for maintaining health. Allowing for the possibility of keto‐adaption leads to a more coherent integration of archeological and physiological data.
Spectro‐Microscopic Techniques for Studying Nanoplastics in the Environment and in Organisms
Authors: Mandemaker Laurens D. B. , Meirer Florian 
Published: October 2022

AbstractNanoplastics (NPs), small (<1 μm) polymer particles formed from bulk plastics, are a potential threat to human health and the environment. Orders of magnitude smaller than microplastics (MPs), they might behave differently due to their larger surface area and small size, which allows them to diffuse through organic barriers. However, detecting NPs in the environment and organic matrices has proven to be difficult, as their chemical nature is similar to these matrices. Furthermore, as their size is smaller than the (spatial) detection limit of common analytical tools, they are hard to find and quantify. We highlight different micro‐spectroscopic techniques utilized for NP detection and argue that an analysis procedure should involve both particle imaging and correlative or direct chemical characterization of the same particles or samples. Finally, we highlight methods that can do both simultaneously, but with the downside that large particle numbers and statistics cannot be obtained.
An Electrochemical Method for Deborylative Hydroxylation of Arylboronic Acids under Metal‐free Conditions
Authors: Fu Zhengjiang , Yi Xuezheng , Fang Ziqi , Zhong Tingting , He Dongdong , Guo Shengmei , Cai Hu 
Published: October 2022

AbstractAn electrochemical method for the synthesis of (poly)phenols via deborylative hydroxylation of arylborons has been well established under metal‐free conditions, whose practicability and advantage has been highlighted by the preparation of drug molecules and preformation of scalable transformation. Mechanistic studies have demonstrated that superoxide anion radical was involved in the conversion followed by the reaction with arylboronic acid substrate.
Implementation of a method for a clinical biochemistry lesson plan based on the flowchart
Authors: Haeri Mohammad Reza 
Published: October 2022

AbstractBiochemistry is believed to be a difficult subject to understand for most life science and medical students. This article explains an experience with a flowchart‐based teaching approach that is applicable to different kinds of biochemistry courses (basic, medical, and clinical) for undergraduate and postgraduate students. After preparing the flowcharts, they were given to the students at the beginning of the semester, and the flowchart‐based teaching was performed for a whole semester. At the end of the semester, they were asked about the effectiveness and facilitation of learning using flowchart‐based teaching. This survey was performed for several semesters. Approximately, 95% stated that it facilitates learning and understanding.
Optimized therapeutic strategy for patients with refractory or relapsed acute myeloid leukemia: long‐term clinical outcomes and health‐related quality of life assessment
Authors: Yan Chen‐hua , Wang Yu , Sun Yu‐qian , Cheng Yi‐fei , Mo Xiao‐dong , Wang Feng‐rong , Chen Yu‐hong , Zhang Yuan‐yuan , Han Ting‐ting , Chen Huan , Xu Lan‐ping , Zhang Xiao‐hui , Liu Kai‐yan , Huang Xiao‐jun 
Published: October 2022

AbstractBackgroundPatients with refractory or relapsed acute myeloid leukemia (AML) have poor survival, necessitating the exploration of optimized therapeutic strategy. Here, we aimed to investigate clinical outcomes and health‐related quality of life (HR‐QoL) after total therapy, which included allogeneic hematopoietic stem cell transplantation (allo‐HSCT), and prophylactic donor lymphocyte infusion (DLI) in the early phase after transplantation, followed by multiple measurable residual disease (MRD) and graft‐versus‐host disease (GvHD)‐guided DLIs.MethodsConsecutive patients who had refractory or relapsed AML and had received non‐T‐cell‐depleted allo‐HSCT at Peking University Institute of Hematology were included in the study. If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse, severe infection, organ failure, and active GvHD at the time of planned DLI, prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen (HLA)‐matched related HSCT or at 45‐60 days after transplantation for haploidentical or unrelated HSCT. Subsequently, multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation.ResultsA total of 105 patients were eligible. Eighty‐seven patients received prophylactic DLI (group B), while 18 did not receive prophylactic DLI (group A). Among 105 patients, the cumulative incidence of grade 2‐4 acute GvHD and chronic GvHD was 40.6% (95% confidence interval [CI] = 30.6%‐50.6%) and 73.3% (95% CI = 67.4%‐79.2%), respectively. The cumulative incidence of relapse (CIR), transplant‐related mortality (TRM), and leukemia‐free survival (LFS) at 5 years after transplantation were 31.5% (95% CI = 21.9%‐41.1%), 22.1% (95% CI = 11.3%‐32.9%), and 46.4% (95% CI = 36.8%‐56.0%), respectively. In group B, the CIR, TRM, and LFS at 5 years after transplantation were 27.6% (95% CI = 17.6%‐37.6%), 21.6% (95% CI = 11.2%‐32.0%), and 50.8% (95% CI = 40.0%‐61.6%), respectively. At the end of follow‐up, 48 patients survived, and more than 90% of survivors had satisfactory recoveries of HR‐QoL.ConclusionsOur study indicated that total therapy is not only associated with decreased CIR, comparable TRM, and better long‐term LFS, but also with satisfactory HR‐QoL for refractory or relapsed AML, compared with those of standard of care therapy reported previously. Therefore, total therapy may be an optimized therapeutic strategy for refractory or relapsed AML.
Chemical Variability of Hexane Extracts from Five Subspecies of Calendula suffruticosa from Spain
Authors: Ohse Silvana , Marques Mariza B. , Silveira Paulo C. , Válega Mónica S. G. A. , Silva Artur M. S. , Pinto Diana C. G. A. 
Published: October 2022

AbstractThe chemical profile of the hexane extracts of the subspecies carbonellii, greuteri, marginata, trialata, and vejerensis of Calendula suffruticosa growing in Spain, herein described for the first time, were studied to access their value as a chemo taxonomical tool and search for potentially useful compounds. The subsp. greuteri and carbonellii showed higher extract yields. Terpenoids were the most abundant chemical class in subsp. carbonellii, greuteri, trialata, and vejerensis, while alkanes were the most abundant in subsp. marginata. Differences in chemical constituents were identified among the subspecies of C. suffruticosa analysed, which the PCA can prove. The subsp. trialata and greuteri showed more significant phytochemical similarity, which might indicate genetic proximity between these two subspecies. C. suffruticosa subsp. marginata presented the fewest number of compounds and in the smallest quantities, and C. suffruticosa subsp. vejerensis presented the largest number, however, both showed no alcohols. Furthermore, some of the compounds found in significant amounts are known for their pharmacological and nutraceutical properties, denoting potential use.
The HD Reaction of Nitrogenase: a Detailed Mechanism
Authors: Dance Ian 
Published: October 2022

AbstractNitrogenase is the enzyme that converts N2 to NH3 under ambient conditions. The chemical mechanism of this catalysis at the active site FeMo‐co [Fe7S9CMo(homocitrate)] is unknown. An obligatory co‐product is H2, while exogenous H2 is a competitive inhibitor. Isotopic substitution using exogenous D2 revealed the N2‐dependent reaction D2+2H++2e−→2HD (the ‘HD reaction’), together with a collection of additional experimental characteristics and requirements. This paper describes a detailed mechanism for the HD reaction, developed and elaborated using density functional simulations with a 486‐atom model of the active site and surrounding protein. First D2 binds at one Fe atom (endo‐Fe6 coordination position), where it is flanked by H−Fe6 (exo position) and H−Fe2 (endo position). Then there is synchronous transfer of these two H atoms to bound D2, forming one HD bound to Fe2 and a second HD bound to Fe6. These two HD dissociate sequentially. The final phase is recovery of the two flanking H atoms. These H atoms are generated, sequentially, by translocation of a proton from the protein surface to S3B of FeMo‐co and combination with introduced electrons. The first H atom migrates from S3B to exo‐Fe6 and the second from S3B to endo‐Fe2. Reaction energies and kinetic barriers are reported for all steps. This mechanism accounts for the experimental data: (a) stoichiometry; (b) the N2‐dependence results from promotional N2 bound at exo‐Fe2; (c) different N2 binding Km for the HD reaction and the NH3 formation reaction results from involvement of two different sites; (d) inhibition by CO; (e) the non‐occurrence of 2HD→H2+D2 results from the synchronicity of the two transfers of H to D2; (f) inhibition of HD production at high pN2 is by competitive binding of N2 at endo‐Fe6; (g) the non‐leakage of D to solvent follows from the hydrophobic environment and irreversibility of proton introduction.
Optical Manipulation of Gb3 Enriched Lipid Domains: Impact of Isomerization on Gb3‐Shiga Toxin B Interaction
Authors: Socrier Larissa , Ahadi Somayeh , Bosse Mathias , Montag Cindy , Werz Daniel B. , Steinem Claudia 
Published: October 2022

AbstractThe plasma membrane is a complex assembly of proteins and lipids that can self‐assemble in submicroscopic domains commonly termed “lipid rafts”, which are implicated in membrane signaling and trafficking. Recently, photo‐sensitive lipids were introduced to study membrane domain organization, and photo‐isomerization was shown to trigger the mixing and de‐mixing of liquid‐ordered (lo) domains in artificial phase‐separated membranes. Here, we synthesized globotriaosylceramide (Gb3) glycosphingolipids that harbor an azobenzene moiety at different positions of the fatty acid to investigate light‐induced membrane domain reorganization, and that serve as specific receptors for the protein Shiga toxin (STx). Using phase‐separated supported lipid bilayers on mica surfaces doped with four different photo‐Gb3 molecules, we found by fluorescence microscopy and atomic force microscopy that liquid disordered (ld) domains were formed within lo domains upon trans‐cis photo‐isomerization. The fraction and size of these ld domains were largest for Gb3 molecules with the azobenzene group at the end of the fatty acid. We further investigated the impact of domain reorganization on the interaction of the B‐subunits of STx with the photo‐Gb3. Fluorescence and atomic force micrographs clearly demonstrated that STxB binds to the lo phase if Gb3 is in the trans‐configuration, whereas two STxB populations are formed if the photo‐Gb3 is switched to the cis‐configuration highlighting the idea of manipulating lipid‐protein interactions with a light stimulus.