bluuebunny/crossref_metadata_2025 huggingface dataset:
Emulating Control Arms for Cancer Clinical Trials Using External Cohorts Created From Electronic Health Record‐Derived Real‐World Data
Authors: Tan Katherine , Bryan Jonathan , Segal Brian , Bellomo Lawrence , Nussbaum Nate , Tucker Melisa , Torres Aracelis Z. , Bennette Carrie , Capra William , Curtis Melissa , Miksad Rebecca A.
Published: July 2021

Electronic health record (EHR)‐derived real‐world data (RWD) can be sourced to create external comparator cohorts to oncology clinical trials. This exploratory study assessed whether EHR‐derived patient cohorts could emulate select clinical trial control arms across multiple tumor types. The impact of analytic decisions on emulation results was also evaluated. By digitizing Kaplan–Meier curves, we reconstructed published control arm results from 15 trials that supported drug approvals from January 1, 2016, to April 30, 2018. RWD cohorts were constructed using a nationwide EHR‐derived de‐identified database by aligning eligibility criteria and weighting to trial baseline characteristics. Trial data and RWD cohorts were compared using Kaplan–Meier and Cox proportional hazards regression models for progression‐free survival (PFS) and overall survival (OS; individual cohorts) and multitumor random effects models of hazard ratios (HRs) for median endpoint correlations (across cohorts). Post hoc, the impact of specific analytic decisions on endpoints was assessed using a case study. Comparing trial data and weighted RWD cohorts, PFS results were more similar (HR range = 0.63–1.18, pooled HR = 0.84, correlation of median = 0.91) compared to OS (HR range = 0.36–1.09, pooled HR = 0.76, correlation of median = 0.85). OS HRs were more variable and trended toward worse for RWD cohorts. The post hoc case study had OS HR ranging from 0.67 (95% confidence interval (CI): 0.56–0.79) to 0.92 (95% CI: 0.78–1.09) depending on specific analytic decisions. EHR‐derived RWD can emulate oncology clinical trial control arm results, although with variability. Visibility into clinical trial cohort characteristics may shape and refine analytic approaches.
Performance analysis of novel fault‐tolerant multilevel inverter with a pristine methodology for fast and exhaustive real‐time failure of switches
Authors: Anand Vishal , Singh Varsha
Published: July 2021

Multilevel inverter (MLI) provides a high power density, though the number of devices increases the chances of failures increases, reducing the reliability of power converter. It is essential to detect, isolate, and reconfigure the faults which arises in MLI. The research proposed here is capable of accomplishing the complete fault tolerance against single and multiple devices for both open circuit and short circuit faults. The control algorithm for operation of single‐pole‐double‐throw (SPDT) relays. This methodology is capable of completely preserving the normal operating condition in post‐fault condition also. The output voltage waveform matches by voltage sensors connected across load, and the controllers sense the faults originated from the variation in the look‐up‐table (LUT) and also categorize the nature of the faults. Field‐programmable gate array (FPGA)‐based controller sends a command signal through SPDT to isolate the faulty switches by redundant switches. In this way, the output power across the load is preserved. This research article also covers the comparative study that is made with the existing fault‐tolerant structures. The reliability comparison shows the better performance indices over conventional cascaded H‐bridge (CHB) inverter. The simulation and experimental results validate the effectiveness of control methodology to achieve complete fault tolerance.
Hybrid self‐learning controller for restoration of voltage power quality using optimized multilayer neural network
Authors: Kumar Prashant , Arya Sabha Raj , Mistry Khyati D. , Giri Ashutosh K.
Published: July 2021

The main objective of this paper is to develop a hybrid predictor based on intelligence techniques for dynamic voltage restorer (DVR) to estimate the reference load voltage and self‐tuned voltage regulation to enhance voltage power quality issues. The best fitted predictor model is obtained by using the potential merits of metaheuristic algorithms coupled with Antlion Optimization (ALO) and Genetic Algorithm (GA). This article proposes ALO optimized multilayer perceptron (MLP) neural network (NN) control algorithm for appropriate selection of weights and biases to generate the subsequent switching signal with lower error rates for load voltage estimation. The ANFIS‐GA control algorithm is implemented for automatic tuning of fuzzy rules with fewer membership functions (MFs) to obtain the perfect ANFIS (Takagi–Sugeno) predictive models for effective DC and AC link voltage regulation. The proposed hybrid controller counteracts the drawbacks of traditional ANN such as early convergence, slow learning mechanism, less probability of local entrapment, and difficulties to achieve the estimated target under parametric uncertainties, namely, sag, swell, unbalance, and distortion. The accuracy of the prediction model is computed by considering the error indices for the training and testing data set. The result confirms that the hybrid system ALO‐MLP NN establishes satisfactory performance in extracting the reference with the least error values.
Conspecific and congeneric interactions shape increasing rates of breeding dispersal of northern spotted owls
Authors: Jenkins Julianna M. A. , Lesmeister Damon B. , Forsman Eric D. , Dugger Katie M. , Ackers Steven H. , Andrews L. Steven , Gremel Scott A. , Hollen Bruce , McCafferty Chris E. , Pruett M. Shane , Reid Janice A. , Sovern Stan G. , Wiens J. David
Published: July 2021

Breeding dispersal, the movement from one breeding territory to another, is rare for philopatric species that evolved within relatively stable environments, such as the old‐growth coniferous forests of the Pacific Northwest. Although dispersal is not inherently maladaptive, the consequences of increased dispersal on population dynamics in populations whose historical dispersal rates are low could be significant, particularly for a declining species. We examined rates and possible causes of breeding dispersal based on a sample of 4,118 northern spotted owls (Strix occidentalis caurina) monitored in seven study areas over 28 yr, 1990–2017, in Oregon and Washington, USA. Using a multistate mark–resight analysis, we investigated the potential impacts of an emergent congeneric competitor (barred owl Strix varia) and forest alteration (extrinsic factors), and social and individual conditions (intrinsic factors) on 408 successive and 1,372 nonsuccessive dispersal events between years. The annual probability of breeding dispersal increased for individual owls that had also dispersed in the previous year and decreased for owls on territories with historically high levels of reproduction. Intrinsic factors including pair status, prior reproductive success, and experience at a site, were also associated with breeding dispersal movements. The percent of monitored owls dispersing each year increased from ˜7% early in the study to ˜25% at the end of the study, which coincided with a rapid increase in numbers of invasive and competitively dominant barred owls. We suggest that the results presented here can inform spotted owl conservation efforts as we identify factors contributing to changing rates of demographic parameters including site fidelity and breeding dispersal. Our study further shows that increasing rates of breeding dispersal associated with population declines contribute to population instability and vulnerability of northern spotted owls to extinction, and the prognosis is unlikely to change unless active management interventions are undertaken.
Thermal traits predict the winners and losers under climate change: an example from North American ant communities
Authors: Roeder Karl A. , Bujan Jelena , de Beurs Kirsten M. , Weiser Michael D. , Kaspari Michael
Published: July 2021

Across the globe, temperatures are predicted to increase with consequences for many taxonomic groups. Arthropods are particularly at risk as temperature imposes physiological constraints on growth, survival, and reproduction. Given that arthropods may be disproportionately affected in a warmer climate—the question becomes which taxa are vulnerable and can we predict the supposed winners and losers of climate change? To address this question, we resurveyed 33 ant communities, quantifying 20‐yr differences in the incidence of 28 genera. Each North American ant community was surveyed with 30 1‐m2 plots, and the incidence of each genus across the 30 plots was used to estimate change. From the original surveys in 1994–1997 to the resurveys in 2016–2017, temperature increased on average 1°C (range, −0.4°C to 2.5°C) and ~64% of ant genera increased in more than half of the sampled communities. To test Thermal Performance Theory's prediction that genera with higher average thermal limits will tend to accumulate at the expense of those with lower limits, we quantified critical thermal maxima (CTmax: the high temperatures at which they lose muscle control) and minima (CTmin: the low temperatures at which ants first become inactive) for common genera at each site. Consistent with prediction, we found a positive decelerating relationship between CTmax and the proportion of sites in which a genus had increased. CTmin, by contrast, was not a useful predictor of change. There was a strong positive correlation (r = 0.85) between the proportion of sites where a genus was found with higher incidence after 20 yr and the average difference in number of plots occupied per site, suggesting genera with high CTmax values tended to occupy more plots at more sites after 20 yr. Thermal functional traits like CTmax have thus proved useful in predicting patterns of long‐term community change in a dominant, diverse insect taxon.
Redox Charge Transfer Kinetics and Reversibility of VO2 in Aqueous and Non‐Aqueous Electrolytes of Na‐Ion Storage
Authors: Park Sul Ki , Shin Kang Ho , Nakhanivej Puritut , Rana Harpalsinh H. , Park Ho Seok
Published: July 2021

The deep understanding about the electrochemical behavior of the nanostructured electrode in electrolytes provides crucial insights for the rational design of electrode for sodium (Na)‐ion storage system (NIS). Here, we report redox charge transfer kinetics and reversibility of VO2(B) nanorod electrodes in both aqueous and organic electrolytes for NIS. The as‐synthesized VO2(B) nanorods show the reversible redox reaction with the higher specific and rate capacitances at high current density in aqueous electrolytes than in organic electrolytes. Temperature‐dependent impedance measurements demonstrate the more facile interfacial charge transfer of Na ions into VO2(B) nanorods in aqueous electrolytes. The reversible evolution in oxidation state and chemical composition of VO2(B) nanorods is observed in aqueous electrolytes, as confirmed by ex situ XRD and ex situ X‐ray photoelectron spectroscopy analyses. Given by the facile and reversible pseudocapacitive feature, the electrochemical performances of VO2(B) nanorods are further improved by constructing the hierarchical structure of the reduced graphene oxide‐VO2 composite for aqueous Na+ ion storage.
Calorimetric Study of Functionalized Uranyl Peroxide Nanoclusters and Their Monomeric Building Block
Authors: Traustason Hrafn , Caranto Kiana , Burns Peter C.
Published: July 2021

The description of the energy landscape of polyoxometalates (POMs) enriches our understanding of their solution behavior through quantitative information that can be used to predict their existence, stability, and properties. Herein, we report thermodynamic values that describe the energy landscape of four uranyl peroxide nanoclusters (UPCs) (LiRb−U@U24, LiNa−U24Pp12, NaK−U24Pp12, and U60Ox30) and a building block of UPCs, lithium uranyl triperoxide monomer (Li−UT). The results reveal relationships between the affinity of counter cations and the anionic uranyl peroxide units, enthalpy of dissolution, as well as enthalpy of crystallization and cluster solubility. Additionally, the calorimetric measurements of Li−UT allowed us to calculate a favorable enthalpy of formation of Li−U24 and Li−U28 from their monomeric units.
Cyclometallation of Heavier Tetrylenes: Reported Complexes and Applications in Catalysis
Authors: Cabeza Javier A. , García‐Álvarez Pablo
Published: July 2021

Heavier tetrylenes (HTs), which are the heavier analogues of carbenes, have been used as ligands in transition metal chemistry for more than 50 years. Having in mind that cyclometallation is a valuable tool to modify ligand scaffolds, with important implications in inorganic and organic chemistry, this microreview discusses in detail the reactions that have afforded complexes with cyclometallated HTs. To date, eight HT ligands, covering only silylenes and germylenes, have been reported to undergo cyclometallation, all of them on late transition metals. Structural and spectroscopic data of the isolated complexes as well as mechanistic information related to the cyclometallation processes are collected and discussed. Additionally, this minireview also surveys the catalytic applications found so far for cyclometallated HT complexes.
A Scalable High‐Yielding and Selective Oxidative Heck Cross‐Coupling – A Key Step for the Synthesis of trans‐Stilbenes
Authors: Cirillo Davide , Karlsson Staffan , Bjørsvik Hans‐René
Published: July 2021

A selective oxidative Heck cross‐coupling method was developed and optimized as a pivotal step for a synthetic route leading to the trans‐stilbene framework. The developed method and synthesis were needed in a SAR study in progress that concerned design and development of an inhibitor for the human cell xCT antiporter system. The developed oxidative Heck cross‐coupling method was examined with a variety of substrates and reagents to produce a library of different substituted trans‐stilbenes, which revealed the method to hold a very good tolerance for an assortment of functional groups. The final synthetic route was successfully scaled‐up (from mg scale) and performed in a 150 g (>1000×up‐scaled) batch run to obtain an overall yield of 73 % (over three steps), which corresponds to a mean step yield of 90 %. The inhibitor candidate DC10 [(E)‐5‐(2‐([1,1′‐biphenyl]‐4‐yl)vinyl)‐2‐hydroxy‐benzoic acid] was produced in multi‐gram quantities (≈33 g) that subsequently was forwarded for animal efficacy and toxicology studies. The scaled‐up process constitutes the first example of an oxidative Heck cross‐coupling on >100‐gram scale.
Design and operation of magnetophoretic systems at microscale: Device and particle approaches
Authors: Chong Wai Hong , Leong Sim Siong , Lim JitKang
Published: July 2021

Combining both device and particle designs are the essential concepts to be considered in magnetophoretic system development. Researcher efforts are often dedicated to only one of these design aspects and neglecting the interplay between them. Herein, to bring out importance of the idea of integration between device and particle, we reviewed the working principle of magnetophoretic system (includes both device and particle design concepts). Since, the magnetophoretic force is influenced by both field gradient and magnetization volume, hence, accurate prediction of the magnetophoretic force is relying on the availability of information on both parameters. In device design, we focus on the different strategies used to create localized high‐field gradient. For particle design, we emphasize on the scaling between hydrodynamic size and magnetization volume. Moreover, we also briefly discussed the importance of magnetoshape anisotropy related to particle design aspect of magnetophoretic systems. Next, we illustrated the need for integration between device and particle design using microscale applications of magnetophoretic systems, include magnetic tweezers and microfluidic systems, as our working example. On the basis of our discussion, we highlighted several promising examples of microscale magnetophoretic systems which greatly utilized the interplay between device and particle design. Further, we concluded the review with several factors that possibly resulted in the lack of research efforts related to device and particle design integration.
Niobium Carbide as a Promising Pseudocapacitive Sodium‐Ion Storage Anode
Authors: Wang Shige , Shao Lianyi , Yu Lu , Guan Jieduo , Shi Xiaoyan , Sun Zhipeng , Cai Junjie , Huang Haitao , Trukhanov Alex
Published: July 2021

Niobium carbide (NbC) is used as anode material for sodium‐ion batteries for the first time. Ball‐milled NbC delivers an initial charge capacity of 242 mAh g−1 at 0.1 A g−1 and a capacity of 126 mAh g−1 after 1000 cycles at a high current density of 5 A g−1 without carbon coating. Cyclic voltammetry curves demonstrate that the pseudocapacitive Na+ storage behavior dominates the electrochemical reaction, which is responsible for the good rate capability. Ex situ X‐ray diffraction (XRD), transmission electron microscopy (TEM), and density functional theory (DFT) calculations show that the electrochemical reaction between NbC and Na is attributed to an adsorption mechanism.
How much time is enough? Establishing an optimal duration of recording for ambulatory video EEG
Authors: Klein Hans , Pang Trudy , Slater Jeremy , Ramsay Richard Eugene
Published: July 2021

Objective

Ambulatory video EEG allows for extended recording of EEG in the comfort of a patient's home. However, the optimal duration of recording to capture clinical events is yet to be established. The current study uses retrospective analyses to identify an optimal recording duration for at‐home video EEG.

Methods

A retrospective review was performed utilizing an anonymized database of ambulatory video EEG recordings performed between March and September 2020 with a national in‐home EEG provider. Only completed assessments with neurologists' reads of raw data were reviewed, resulting in 3644 unique studies divided into three age cohorts: pediatrics (n = 941), adult (n = 2020), and geriatric (n = 683). Cohorts were characterized by assessment yield and time to first typical clinical event, as well as subsequent typical events over duration of recording.

Results

Frequency distributions reveal over half of first events are captured within 12 hours, but longer recording durations capture a much wider majority of both first typical events, as well as the mean number of subsequent events (5 clinical events). In 72 hours, over 97% of first events were observed in adult and geriatric patients, as well as over 95% of the mean number of subsequent events. In children, time to first event was significantly earlier than either adult or geriatric samples, with 98% of first events, and 92.8% of the mean number of subsequent events being observed in 48 hours.

Significance

These results from a large‐scale, national dataset of patients using in‐home EEG monitoring suggests recording at least 48 hours in duration for children, and at least 72 hours in duration for adult and geriatric samples, is optimal to maximize the likelihood of observing typical clinical events to facilitate diagnosis.
Optimization of combined microwave and hot air drying technology for purple cabbage by Response Surface Methodology (RSM)
Authors: Liu Jing , Li Xiangli , Yang Yanmin , Wei Haixiang , Xue Liping , Zhao Min , Cai Jinxiu
Published: July 2021

Purple cabbage is one of the world's most widely consumed vegetables with high nutritional values containing the antioxidants and anti‐inflammatory activity of anthocyanins, vitamins, and minerals. But due to rapid postharvest quality decay, novel processing techniques including drying are required. In order to determine the conditions of combined microwave and hot air drying for purple cabbage, factors affecting the drying process including microwave density, hot air temperature, and the dry base water content at conversion point were investigated using the anthocyanin content, DPPH antioxidant capacity, chewiness, △E, rehydration ratio, and average drying rate as responses. The combined drying conditions were optimized considering three independent variables at three different levels by response surface methodology. The results showed that the processing parameters of purple cabbage with combined microwave and hot air drying technology were microwave density at 2.5 W/g, moisture content of conversion point at 4.0 g/g, and hot air temperature at 55°C. Under these conditions, the anthocyanin content, DPPH antioxidant capacity, chewiness, △E, rehydration ratio, average drying rate, and overall score of the dried purple cabbage were 175.87 mg/100 g, 87.59%, 4,521.468 g, 26.5, 4.3, 0.76 g/min, and 0.785, respectively. Therefore, combined microwave and hot air drying technology is an effective, suitable method for drying purple cabbage.
Mercury enrichment in anthrosols and adjacent coastal sediments at a Classic Maya site, Marco Gonzalez, Belize
Authors: Turner Simon , Graham Elizabeth , Macphail Richard , Duncan Lindsay , Rose Neil L. , Yang Handong , Whittet Richard , Rosique‐Esplugas Cristina
Published: July 2021

Elevated concentrations of total mercury (THg) are found in the surface soils and flanking wetland sediments at the Classic Maya coastal site of Marco Gonzalez, Belize. Significant concentrations (up to 1.3 µg·g−1dry mass) of THg occur in leaf litter‐rich soils, as well as in the artefact‐rich anthrosol spread over the vegetated mound site of structures and occupation debris. The abundance and spatial pattern of major and trace elements measured in the surface soils indicate both site‐scale controlling factors of topography, structures and vegetation on soil geochemistry as well as local highs in concentration compared with background, due to human activity. Geochemical stratigraphy of wetland sediment cores shows that a shift from carbonate‐reef sediments to mangrove peat in the 13th century AD was attended by an input of allogenic (mineral) elements, including mercury. A THg concentration peak (0.8 μg·g−1) in brackish pool sediment is210Pb‐dated to 1960–1970 AD, but the incorporation of mercury in multiple cores adjacent to the site shows increasing mercury inputs to have occurred before, during Classic‐period Maya occupation and following the sites abandonment. Analysis of element values from site‐scale soil sampling, combined with results from off‐site cores, provides a numerical framework upon which outlier values of THg and other element spatial patterns can be assessed, especially the spatial co‐association of elements related to differences in soil–sediment matrices. Geochemical results from active soils developing from occupation deposits (anthrosols) and sediment cores open up questions concerning contemporary and past mercury accumulation at coastal Mayan sites, and the wider interaction of human and natural biogeochemical processes that occur in human‐modified soils and coastal wetland sediments.
Exploring the relationship between anthropomorphism and theory‐of‐mind in brain and behaviour
Authors: Hortensius Ruud , Kent Michaela , Darda Kohinoor M. , Jastrzab Laura , Koldewyn Kami , Ramsey Richard , Cross Emily S.
Published: July 2021

The process of understanding the minds of other people, such as their emotions and intentions, is mimicked when individuals try to understand an artificial mind. The assumption is that anthropomorphism, attributing human‐like characteristics to non‐human agents and objects, is an analogue to theory‐of‐mind, the ability to infer mental states of other people. Here, we test to what extent these two constructs formally overlap. Specifically, using a multi‐method approach, we test if and how anthropomorphism is related to theory‐of‐mind using brain (Experiment 1) and behavioural (Experiment 2) measures. In a first exploratory experiment, we examine the relationship between dispositional anthropomorphism and activity within the theory‐of‐mind brain network (n = 108). Results from a Bayesian regression analysis showed no consistent relationship between dispositional anthropomorphism and activity in regions of the theory‐of‐mind network. In a follow‐up, pre‐registered experiment, we explored the relationship between theory‐of‐mind and situational and dispositional anthropomorphism in more depth. Participants (n = 311) watched a short movie while simultaneously completing situational anthropomorphism and theory‐of‐mind ratings, as well as measures of dispositional anthropomorphism and general theory‐of‐mind. Only situational anthropomorphism predicted the ability to understand and predict the behaviour of the film's characters. No relationship between situational or dispositional anthropomorphism and general theory‐of‐mind was observed. Together, these results suggest that while the constructs of anthropomorphism and theory‐of‐mind might overlap in certain situations, they remain separate and possibly unrelated at the personality level. These findings point to a possible dissociation between brain and behavioural measures when considering the relationship between theory‐of‐mind and anthropomorphism.
Nickel‐Catalyzed Suzuki‐Miyaura Cross‐Coupling Involving C−O Bond Activation
Authors: Morishige Aoi , Iyori Yasuaki , Chatani Naoto
Published: July 2021

An efficient Suzuki‐Miyaura cross‐coupling reaction of ortho‐phenoxy‐substituted aromatic amides with aryl boronates is described. The use of LiOtBu is crucial for the success of the reaction. An amidate anion, which is formed through deprotonation of the amide NH bond by LiOtBu, functions as a directing group to activate a C−O bond.
Alcohol consumption induces murine osteoporosis by downregulation of natural killer T‐like cell activity
Authors: Naruo Munehiro , Negishi Yasuyuki , Okuda Takahisa , Katsuyama Midori , Okazaki Ken , Morita Rimpei
Published: July 2021

Introduction

Chronic alcohol consumption (CAC) can induce several deleterious effects on the body, including the promotion of osteoporosis; however, the immunological mechanism underlying alcohol‐induced osteoporosis is still unclear.

Methods

We administered alcohol to mice for 4 weeks as the experimental CAC model and analyzed the bone and immune cells that are located in the vicinity of a bone.

Results

IL‐4 is known to be a suppressive factor for osteoclastogenesis, and we found that natural killer T (NKT)‐like cells, which showed NK1.1‐positive, CD3‐positive, and α‐galactosylceramide‐loaded CD1d tetramer‐negative, produced IL‐4 more effectively than CD4+ T and natural killer (NK) cells. The alcohol consumption facilitated a significant decrease of bone mineral density with the upregulation of nuclear factor of activated T cells 1 and receptor activator of NF‐κB ligand expression. Meanwhile, we confirmed that alcohol consumption suppressed the activity of antigen‐presenting cells (APCs) and NKT‐like cells, leading to decreased IL‐4 secretion. Moreover, these harmful effects of alcohol consumption were reduced by simultaneous treatment with a glycolipid antigen OCH.

Conclusions

Our results indicate that the inactivation of innate immune cells, APCs, and NKT‐like cells are likely to be crucial for alcohol‐induced osteoporosis and provide a new therapeutic approach for preventing osteoporosis.
Canadian consensus onTRK‐inhibitortherapy forNTRKfusion‐positive sarcoma
Authors: Simmons Christine , Deyell Rebecca J. , MacNeill Andrea J. , Vera‐Badillo Francisco E. , Smrke Alannah , Abdul Razak Albiruni R. , Banerji Shantanu , McLeod Deanna , Noujaim Jonathan
Published: July 2021

Malignant sarcomas are rare accounting for <1% of all adult solid malignancies and approximately 11% to 13% of all pediatric malignancies. TRK‐inhibitors have demonstrated robust and long‐lasting responses in patients withNTRKfusion‐positive solid tumors, including sarcoma. Access to these agents in many jurisdictions such as Canada remains limited. We undertook a modified Delphi consensus to articulate and convey the clinical importance of these agents for the Canadian sarcoma community. A systematic search of published and presented literature was conducted to identify clinical trials reporting outcomes on the use of TRK‐inhibitors in relapsed/refractoryNTRKfusion‐positive sarcoma. Three main consensus questions were identified: (a) is there currently an unmet clinical need for systemic therapy options in relapsed/refractory sarcoma? (b) do TRK‐inhibitors confer a clinical benefit to patients withNTRKfusion‐positive sarcoma? (c) do phase I/II basket trials provide sufficient evidence to justify funding of TRK‐inhibitors inNTRKfusion‐positive sarcoma? Response rates to the first and second surveys were 57% (n = 30) and 42% (n = 22), respectively. There was strong agreement among the Canadian sarcoma community that there was unmet clinical need for effective systemic therapy options in relapsed/refractory sarcoma, that TRK‐inhibitors are a safe and effective treatment option for patients withNTRKfusion‐positive sarcoma, and that available phase I/II basket trials provide sufficient evidence to support funding of these agents in relapsed/refractoryNTRKfusion‐positive sarcoma. TRK‐inhibitors are a safe and effective systemic therapy option for patients with relapsed/refractoryNTRKfusion‐positive sarcoma.
Do certified cancer centers provide more cost‐effective care? A health economic analysis of colon cancer care in Germany using administrative data
Authors: Cheng Chih‐Yuan , Datzmann Thomas , Hernandez Diego , Schmitt Jochen , Schlander Michael
Published: July 2021

Hospital certification has become an important measure to improve cancer care quality, with the potential effect of prolonging patient survival and reducing medical spending. However, yet to be explored is the cost‐effectiveness of cancer care provided in certified hospitals, considering significant additional costs incurred from certification requirements. We performed a cost‐effectiveness analysis (CEA) using two colon cancer populations (N = 1909) treated in different levels of certified hospitals (CHs) vs noncertified hospitals (NCHs) from a healthcare system's perspective. We matched patient‐level data of incident colon cancer cases, diagnosed between 2008 and 2013 from a large statutory health insurance in Saxony, Germany, to calculate net treatment costs by phase (initial, continuing and terminal phase). The costs were supplemented with extra costs from 31 additional services required for certification. Effectiveness measure was total survival time in life‐years. Outcome of interest was incremental costs per additional life‐year. The annualized net colon cancer treatment costs by phase showed a U shape with high costs in the initial (mean €26 855; 95% CI €25 058‐€28 652) and the terminal phases (mean €30 096; 95% CI €26 199‐€33 993). The base‐case CEA results and all sensitivity analyses consistently demonstrated longer survival and lower costs for the colon cancer cohort treated in CHs vs NCHs. To conclude, we used administrative data to derive the first cost‐effectiveness evidence supporting that colon cancer care delivered in the certified cancer centers in Germany improves survival outcomes and saves costs from a healthcare system's perspective. Generalization of the study results should be exercised with caution.
Does parochial cooperation exist in childhood and adolescence? Ameta‐analysis
Authors: Lazić Aleksandra , Purić Danka , Krstić Ksenija
Published: July 2021

Although previous meta‐analytic evidence supports the existence of parochialism in cooperation among adults, the extent to which children and adolescents are more willing to incur a personal cost to benefit ingroups, compared to outgroups, is not yet clear. We provide the first meta‐analysis on the existence and magnitude of parochialism in cooperation among pre‐adults. Based on 20 experimental economics studies (k = 69,N = 5268, age = 3–19, 12 countries, published 2008–2019), a multilevel meta‐analytic model revealed a small overall effect size indicating that children and adolescents were more cooperative towards ingroups (d = 0.22, 95% CI [0.07, 0.38]). A series of single‐moderator analyses tested for the following conditions: participant age and sex; game type ([mini‐]dictator game, prisoner's dilemma, public goods dilemma, trust game, ultimatum game); outcome interdependence; membership manipulation (between‐ vs. within‐subjects); group type (natural vs. experimental); reward type (monetary vs. non‐monetary); and country of the participant. Parochial cooperation did not vary with participants' age. Parochialism was larger in non‐interdependent (dictator‐type) compared to interdependent (bargaining and social dilemma) games. There were no moderating effects of group type, membership manipulation or reward type. To provide more data on how parochialism develops, primary studies should report age ranges more precisely and use more restricted age groups.
Inhibition of TGF‐β Increases Bone Volume and Strength in a Mouse Model of Osteogenesis Imperfecta
Authors: Greene Benjamin , Russo Ryan J , Dwyer Shannon , Malley Katie , Roberts Errin , Serrielo Joseph , Piepenhagen Peter , Cummings Sheila , Ryan Susan , Zarazinski Christine , Uppuganti Sasidhar , Bukanov Nikolai , Nyman Jeffry S , Cox Megan K , Liu Shiguang , Ibraghimov‐Beskrovnaya Oxana , Sabbagh Yves
Published: July 2021

Osteogenesis imperfecta (OI), is a genetic disorder of bone fragility caused by mutations in collagen I or proteins involved in collagen processing. Previous studies in mice and human OI bones have shown that excessive activation of TGF‐β signaling plays an important role in dominant and recessive OI disease progression. Inhibition of TGF‐β signaling with a murine pan‐specific TGF‐β neutralizing antibody (1D11) was shown to significantly increase trabecular bone volume and long bone strength in mouse models of OI. To investigate the frequency of dosing and dose options of TGF‐β neutralizing antibody therapy, we assessed the effect of 1D11 on disease progression in a dominant OI mouse model (col1a2 gene mutation at G610C). In comparison with OI mice treated with a control antibody, we attempted to define mechanistic effects of 1D11 measured via μCT, biomechanical, dynamic histomorphometry, and serum biomarkers of bone turnover. In addition, osteoblast and osteoclast numbers in histological bone sections were assessed to better understand the mechanism of action of the 1D11 antibody in OI. Here we show that 1D11 treatment resulted in both dose and frequency dependency, increases in trabecular bone volume fraction and ultimate force in lumbar bone, and ultimate force, bending strength, yield force, and yield strength in the femur (p ≤ 0.05). Suppression of serum biomarkers of osteoblast differentiation, osteocalcin, resorption, CTx‐1, and bone formation were observed after 1D11 treatment of OI mice. Immunohistochemical analysis showed dose and frequency dependent decreases in runt‐related transcription factor, and increase in alkaline phosphatase in lumbar bone sections. In addition, a significant decrease in TRACP and the number of osteoclasts to bone surface area was observed with 1D11 treatment. Our results show that inhibition of the TGF‐β pathway corrects the high‐turnover aspects of bone disease and improves biomechanical properties of OI mice. These results highlight the potential for a novel treatment for osteogenesis imperfecta. © 2021 Sanofi‐Genzyme. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
The diverse origin of bone-forming osteoblasts
Authors: Mizoguchi Toshihide , Ono Noriaki
Published: July 2021

Osteoblasts are the only cells that can give rise to bones in vertebrates. Thus, one of the most important functions of these metabolically active cells is mineralized matrix production. Because osteoblasts have a limited lifespan, they must be constantly replenished by preosteoblasts, their immediate precursors. Because disruption of the regulation of bone-forming osteoblasts results in a variety of bone diseases, a better understanding of the origin of these cells by defining the mechanisms of bone development, remodeling, and regeneration is central to the development of novel therapeutic approaches. In recent years, substantial new insights into the origin of osteoblasts—largely owing to rapid technological advances in murine lineage-tracing approaches and other single-cell technologies—have been obtained. Collectively, these findings indicate that osteoblasts involved in bone formation under various physiological, pathological, and therapeutic conditions can be obtained from numerous sources. The origins of osteoblasts include, but are not limited to, chondrocytes in the growth plate, stromal cells in the bone marrow, quiescent bone-lining cells on the bone surface, and specialized fibroblasts in the craniofacial structures, such as sutures and periodontal ligaments. Because osteoblasts can be generated from local cellular sources, bones can flexibly respond to regenerative and anabolic cues. However, whether osteoblasts derived from different cellular sources have distinct functions remains to be investigated. Currently, we are at the initial stage to aptly unravel the incredible diversity of the origins of bone-forming osteoblasts. © 2021 American Society for Bone and Mineral Research (ASBMR).
CCT6A may act as a potential biomarker reflecting tumor size, lymphatic metastasis, FIGO stage, and prognosis in cervical cancer patients
Authors: Ma Jiancai , Yang Liping , Feng Haiqin , Zheng Lulu , Meng Huifang , Li Xuefei
Published: July 2021

Objective

Chaperonin‐containing tailless complex polypeptide subunit 6A (CCT6A) is a critical regulator and newly identified clinical biomarker of several cancers, while its correlation with the clinical characteristics and prognosis of cervical cancer patients is unclear. Therefore, this study aimed to explore this issue.

Methods

Chaperonin‐containing tailless complex polypeptide subunit 6A expression in tumor and tumor‐adjacent tissues from 198 cervical cancer patients who underwent resection were detected by immunohistochemistry assay and reverse transcription‐quantitative polymerase chain reaction. Besides, the clinicopathological features and survival data of cervical cancer patients were collected.

Results

Chaperonin‐containing tailless complex polypeptide subunit 6A protein and mRNA levels were both increased in tumor tissues compared with tumor‐adjacent tissues (both p < 0.001). Receiver operating characteristic curves showed that CCT6A protein (AUC: 0.774, 95% CI: 0.729–0.819) and mRNA levels (AUC: 0.904, 95% CI: 0.874–0.934) well discriminated tumor tissues from tumor‐adjacent tissues. Besides, correlation analyses found that CCT6A protein and mRNA levels were positively correlated with lymph node metastasis and FIGO stage (all p < 0.05), apart from which CCT6A mRNA level was also positively associated with tumor size (p = 0.032). In addition, CCT6A protein and mRNA levels were negatively correlated with accumulating disease‐free survival (both p < 0.05); meanwhile CCT6A mRNA level was negatively associated with accumulating overall survival as well (p = 0.010).

Conclusion

Chaperonin‐containing tailless complex polypeptide subunit 6A is elevated in tumor tissues, and its high expression associates with larger tumor size, lymph node metastasis, higher FIGO stage, and worse prognosis in cervical cancer patients.
The Hologic Aptima SARS‐CoV‐2 assay enables high ratio pooling saving reagents and improving turnaround time
Authors: Newsom Kimberly , Zhang Yuan , Chamala Srikar , Martinez Katherine , Clare‐Salzler Michael , Starostik Petr
Published: July 2021

Background

The Hologic Aptima™ TMA SARS‐CoV‐2 assay was employed to test pooled nasopharyngeal (NP) samples to evaluate the performance of pooled sample testing and characterize variables influencing results.

Methods

Results on 1033 previously tested NP samples were retrieved to characterize the relative light units (RLU) of SARS‐CoV‐2‐positive samples in the tested population. The pooling strategy of combining 10 SARS‐CoV‐2 samples into one pool (10/1) was used in this study. The results were compared with neat sample testing using the same Aptima™ TMA SARS‐CoV‐2 assay and also the CDC RT‐PCR and the Cepheid SARS‐CoV‐2 assays.

Results

The Aptima assay compares favorably with both CDC RT‐PCR and the Cepheid SARS‐CoV‐2 assays. Once samples are pooled 10 to 1 as in our experiments, the resulting signal strength of the assay suffers. A divide opens between pools assembled from strong‐positive versus only weak‐positive samples. Pools of the former can be reliably detected with positive percent agreement (PPA) of 95.2%, while pools of the latter are frequently misclassified as negative with PPA of 40%. When the weak‐positive samples with kRLU value lower than 1012 constitute 3.4% of the total sample profile, the assay PPA approaches 93.4% suggesting that 10/1 pooled sample testing by the Aptima assay is an effective screening tool for SARS‐CoV‐2.

Conclusion

Performing pooled testing, one should monitor the weak positives with kRLU lower than 1012 or quantification cycle (Cq) value higher than 35 on an ongoing basis and adjust pooling approaches to avoid reporting false negatives.
Understanding community violence: A critical realist framework for community psychology
Authors: Malherbe Nick , Seedat Mohamed , Suffla Shahnaaz
Published: July 2021

Critical realism can unsettle a number of orthodoxies that surround the study of community violence within community psychology. This is to say, because critical realism is embraced so rarely by community psychologists, it can institute a parallax shift within the discipline, whereby we are granted alternative ways of perceiving violence within community contexts. Drawing on transdisciplinary thought, we offer in this article a retroductive framework for studying community violence. This framework, we argue, can facilitate an understanding of structurally violent causal mechanisms through interrogating how direct—or observable—violence intersects with epistemic violence (i.e., harmful and inaccurate representation). Demonstrating the efficacy of this framework, we provide an example from our work, where participants from a low‐income South African community produced and screened a documentary film on community violence and collective resistance. Reflecting on the ways by which this film engaged xenophobic violence in particular, we examine how community members used the film to trouble perceptions of community violence and advance a multifaceted antiviolence agenda. By way of conclusion, we consider how our framework can be used to inform a critical realist community psychology, wherein violent social structures are analyzed against the agentic community‐driven initiatives which oppose these structures.
Fibroblast growth factor and kidney disease: Updates for emerging novel therapeutics
Authors: Trivedi Neerja , Kumar Devendra
Published: July 2021

The discovery of fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) provided a profound new insight into physiological and metabolic functions. FGF has a large family by having divergent structural elements and enable functional divergence and specification. FGF and FGFRs are highly expressed during kidney development. Signals from the ureteric bud regulate morphogenesis, nephrogenesis, and nephron progenitor survival. Thus, FGF signaling plays an important role in kidney progenitor cell aggregation at the sites of new nephron formation. This review will summarize the current knowledge about functions of FGF signaling in kidney development and their ability to promote regeneration in injured kidneys and its use as a biomarker and therapeutic target in kidney diseases. Further studies are essential to determine the predictive significance of the various FGF/FGFR deviations and to integrate them into clinical algorithms.
Pathogen and heavy metal contamination in urban agroecosystems of northern Ghana: Influence of biochar application and wastewater irrigation
Authors: Asirifi Isaac , Kaetzl Korbinian , Werner Steffen , Saba Courage K. S. , Abagale Felix K. , Amoah Philip , Marschner Bernd
Published: July 2021

The benefit of biochar as a soil fertility enhancer is well known and has been broadly investigated. Equally, many tropical and subtropical countries use wastewater for irrigation in urban agriculture. To assess the related health risks, we determined pathogen and heavy metal fate associated with biochar application and wastewater irrigation in the urban agriculture of northern Ghana. Rice (Oryza L.) husk biochar (20 t ha−1), N–P–K 15–15–15 fertilizer (212.5 kg ha−1), and their combinations were evaluated in a field‐based experiment. Untreated wastewater and tap water served as irrigation water. Red amaranth (Amaranthus cruentus L.) was used as a test crop and was grown in wet (WS) and dry (DS) cropping seasons. Irrigation water, soil, and vegetables were analyzed for heavy metals, Escherichia coli, fecal coliform, helminth eggs, and Salmonella spp. Unlike the pathogens, analyzed heavy metals from irrigation water and soil were below the FAO/WHO permissible standard for agricultural activities. Wastewater irrigation caused E. coli concentrations ranging from 0.5 to 0.6 (WS) and from 0.7 to 0.8 (DS) log10 colony forming units per gram fresh weight (CFU gFW−1) on vegetables and from 1.7 to 2.1 (WS) and from 0.6 to 1.0 (DS) log10CFU per gram dry weight (gDW−1) in soil. Average log10CFU gFW−1 rates of 6.19 and 3.44 fecal coliform were found on vegetables, whereas in soil, 4.26 and 4.58 log10CFU gDW−1 were observed in WS and DS, respectively. Helminth egg populations were high in wastewater and were transferred to the crops and soil. Biochar did not affect bacteria contamination. Pathogen contamination on vegetables and in soil were directly linked to the irrigation water, with minimal or no difference observed from biochar application.
Lack of correlation between the SARS‐CoV‐2 cycle threshold (Ct) value and clinical outcomes in patients with COVID‐19
Authors: Camargo Jose F. , Lin Rick Y. , Komanduri Krishna V.
Published: July 2021

Problem

The utility of the polymerase chain reaction (PCR) cycle threshold (Ct) values in the management of patients with coronavirus disease 2019 (COVID‐19) remains controversial.

Methods

We assessed the correlation of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Ct values in nasopharyngeal swab samples with the oxygen requirements at the time of sample collection. Specimens were tested with the Simplexa PCR platform, which targets the SARS‐CoV‐2 ORF1ab and S genes.

Results

We identified 23 COVID‐19 patients with 49 Ct values available. While Ct values from ORF1ab and S genes were highly correlated for a given specimen, there was no correlation between Ct values for any of these target genes and the oxygen requirements of the patient at the time of sample collection. We found no differences in the initial nor the nadir Ct values between survivors and non‐survivors or mild/moderate versus severe/critical illness at the maximum point of illness.

Conclusion

SARS‐CoV‐2 Ct values have limited value in the management of COVID‐19.