bluuebunny/crossref_metadata_2025 huggingface dataset:
Do persons with intellectual and developmental disabilities prefer to save the best for last in an MSWO? A preliminary investigation
Authors: Castillo Mariana I. , Frank‐Crawford Michelle A. , Liesfeld Jody E. , Doan Trang M. , Newcomb Eli T. , Rooker Griffin W. , Borrero John C.
Published: April 2022

The multiple stimulus without replacement (MSWO) preference assessment is commonly used to identify potential reinforcers. In this arrangement, individuals can choose the order in which they consume edibles or activities. The item selected first is often designated the highest preferred, and the item selected last is often designated the least preferred. Scattered reports suggest that some individuals may save the best for last in an MSWO. Despite these reports, few systematic evaluations of “saving the best for last” in the MSWO have been conducted. We examined this phenomenon using an MSWO and progressive‐ratio‐reinforcer assessment. Evidence of “saving the best for last” was obtained for one of four individuals across assessments involving edibles and leisure activities, respectively.
A novel fluorescent probe with large Stokes shift for the detection of viscosity changes and its imaging in living cells
Authors: Guo Rui , Tang Yonghe , Zhang Liang , Hu Qian , Liu Qing , Cai Shushun , Lin Weiying
Published: April 2022

As an important cellular microenvironmental parameter, viscosity could reflect the status of living cells. Small molecular fluorescent probes are a vital tool to measure the change of viscosity in living cells. A novel fluorescence probe ZL‐1 with a large Stokes shift (in methanol it reached to 153 nm and in glycerol it reached to 125 nm) and excellent sensitivity toward viscosity was developed. The sharp enhancement of the emission intensity for the probe ZL‐1 from low viscous methanol to high viscous glycerol indicated that the probe ZL‐1 could respond to the viscosity variations. Moreover, the probe ZL‐1 has been successfully utilized to detect of the viscosity variations in living cells.
Continuous low pH viral inactivation: Operation and scaling strategy informs viral clearance study
Authors: Brown Matthew , Godfrey Scott , Creasy Arch , Salm Jeffery , Fahrner Robert
Published: April 2022

A continuous viral inactivation (CVI) tubular reactor was designed for low pH viral inactivation within a continuous downstream system across multiple scales of operation. The reactors were designed to provide a minimum residence time of >60 min. The efficacy of this tubular reactor was tested with xenotropic murine leukemia virus (X‐MuLV) through pulse injection experiments. It was determined that the minimum residence time of the small‐scale reactor design, when operated at the target process flow rate, occurred between 63 and 67 min. Inactivation kinetics were compared between continuous operation and standard batch practices using three monoclonal antibodies. The quantification of the virus log reduction values (LRV) was similar between the two modes of operation and most of the acid‐treated samples had virus concentrations below the limit of detection. However, residual infectivity was still present in the endpoint batch samples of two experiments while the continuous samples always remained below the limit of detection. This provides the foundation for leveraging a standard batch‐based model to quantify the LRV for a CVI unit operation.
Integrated continuous biomanufacturing on pilot scale for acid‐sensitive monoclonal antibodies
Authors: Schwarz Hubert , Gomis‐Fons Joaquín , Isaksson Madelène , Scheffel Julia , Andersson Niklas , Andersson Andreas , Castan Andreas , Solbrand Anita , Hober Sophia , Nilsson Bernt , Chotteau Veronique
Published: April 2022

In this study, we demonstrated the first, to our knowledge, integrated continuous bioprocess (ICB) designed for the production of acid‐sensitive monoclonal antibodies, prone to aggregate at low pH, on pilot scale. A high cell density perfusion culture, stably maintained at 100 × 106 cells/ml, was integrated with the downstream process, consisting of a capture step with the recently developed Protein A ligand, ZCa; a solvent/detergent‐based virus inactivation; and two ion‐exchange chromatography steps. The use of a mild pH in the downstream process makes this ICB suitable for the purification of acid‐sensitive monoclonal antibodies. Integration and automation of the downstream process were achieved using the Orbit software, and the same equipment and control system were used in initial small‐scale trials and the pilot‐scale downstream process. High recovery yields of around 90% and a productivity close to 1 g purified antibody/L/day were achieved, with a stable glycosylation pattern and efficient removal of impurities, such as host cell proteins and DNA. Finally, negligible levels of antibody aggregates were detected owing to the mild conditions used throughout the process. The present work paves the way for future industrial‐scale integrated continuous biomanufacturing of all types of antibodies, regardless of acid stability.
Municipal regulation of cannabis and public health in Canada: A comparison of Alberta, Ontario, and Québec
Authors: Gagnon François , Huynh Christophe , Kilborn Michelle , Fry Michelle , Vallée Rachel , Janezic Isidora
Published: April 2022

Canada legalized nonmedical cannabis in October 2018, but significant variations in municipal regulations exist. This study explored the variations that exist and pondered their potential public health consequences. A comparative analysis was completed on the regulations and guidelines that addressed retailers' location and public consumption in the municipalities of Alberta, Ontario, and Québec. Municipal regulations that addressed the location of retailers were more numerous and extensive in Alberta and Ontario (in the context of provincial private retail models) than in Québec (government‐based model). Municipalities in Alberta added more restrictions to public consumption laws as compared to municipalities in Ontario and in Québec. These additions were made to Alberta's and Ontario's provincial‐level smoking and vaping bans which used tobacco‐inspired frameworks, and to Québec's ban on smoking and vaping in all public spaces. The comparative analysis showed the importance of considering municipal cannabis regulations when studying the impact of legalization, given the significant variations that exist. Policy makers should be made aware of these variations in the regulation of cannabis in order to limit health harms and further social inequalities.
Characterization of coagulopathy and outcomes in cancer patients with severe COVID ‐19 illness: Longitudinal changes in hospitalized cancer patients
Authors: Madani Mahsa , Goldstein Drew , Stefanescu Roxana , Woodman Scott E. , Rojas‐Hernandez Cristhiam M.
Published: April 2022

There is a lack of data focused on the specific coagulopathic derangements in COVID‐19 versus non‐COVID‐19 acutely ill cancer patients. Our objective was to characterize features of coagulopathy in cancer patients with active COVID‐19 illness who required hospitalization at MD Anderson in the Texas Medical Center and to correlate those features with thrombotic complications, critical illness, and mortality within the first 30 days after hospital admission for COVID‐19 illness. COVID‐19 and non‐COVID‐19 hospitalized cancer patients, with at least five consecutive measures of PT, PTT, d‐dimer, and CBC during the same period, were matched 1:1 to perform a retrospective analysis. We reviewed complete blood cell counts with differential, PT, PTT, fibrinogen, D‐Dimer, serum ferritin, IL‐6, CRP, and peripheral blood smears. Clinical outcomes were thrombosis, mechanical ventilation, critical illness, and death. Compared with matched hospitalized cancer patients without COVID‐19, we found elevated neutrophil and lower lymphocyte counts in those with critical illness ( p =  0.00) or death ( p =  0.00); only neutrophils correlated with thrombosis. COVID‐19 cancer patients with a platelet count decline during the hospital stay had more frequent critical illness ( p =  0.00) and fatal outcomes ( p =  0.00). Of the inflammatory markers, interleukin‐6 showed consistently higher levels in the COVID‐19 patients with poor outcomes. The findings of unique platelet changes and coagulopathy during severe COVID‐19 illness in the cancer population are of interest to explore disease mechanisms and future risk stratification strategies to help with the management of cancer patients with COVID‐19.
Electrochemical Reduction of CO2 on Au Electrocatalysts in a Zero‐Gap, Half‐Cell Gas Diffusion Electrode Setup: a Systematic Performance Evaluation and Comparison to an H‐cell Setup**
Authors: Alinejad Shima , Quinson Jonathan , Wiberg Gustav K. H. , Schlegel Nicolas , Zhang Damin , Li Yao , Reichenberger Sven , Barcikowski Stephan , Arenz Matthias
Published: April 2022

Based on H‐cell measurements, gold (Au) is one of the most selective catalysts for the CO2 reduction reaction (CO2RR) to CO. To ensure a high dispersion, typically small Au nanoparticles (NPs) are used as a catalyst. However, the preparation of small Au NPs based on conventional synthesis methods often requires the use of surfactants such as polyvinylpyrrolidone (PVP). Here, a systematic evaluation of the performance of laser‐generated, surfactant‐free Au NPs for the CO2RR in a gas diffusion electrode (GDE) setup was presented and the results were compared to investigations in an H‐cell configuration. The GDE setup supplied a continuous CO2 stream at the electrode‐electrolyte interface to circumvent CO2 mass transport limitations encountered in conventional H‐cells. The influence of the catalyst loading and the effect of PVP were investigated. By comparing the two screening methods, that is GDE and H‐cell measurements, it was shown that the performance of the same catalyst could be substantially different in the two environments. In the GDE setup without liquid electrolyte‐catalyst interface a higher reaction rate, but lower faradaic efficiency was determined. Independent of the setup, the presence of PVP favoured the hydrogen evolution reaction (HER). However, in the GDE setup PVP was more detrimental for the performance than in the H‐cell.
Efficient Electrochemical Reduction of CO2 to Formate in Methanol Solutions by Mn‐Functionalized Electrodes in the Presence of Amines**
Authors: Stuardi Francesca Marocco , Tiozzo Arianna , Rotundo Laura , Leclaire Julien , Gobetto Roberto , Nervi Carlo
Published: April 2022

Carbon cloth electrode modified by covalently attaching a manganese organometallic catalyst is used as cathode for the electrochemical reduction of CO2 in methanol solutions. Six different industrial amines are employed as co‐catalyst in millimolar concentrations to deliver a series of new reactive system. While such absorbents were so far believed to provide a CO2 reservoir and act as sacrificial proton source, we herein demonstrate that this role can be played by methanol, and that the adduct formed between CO2 and the amine can act as an effector or inhibitor toward the catalyst, thereby enhancing or reducing the production of formate. Pentamethyldiethylentriamine (PMDETA), identified as the best effector in our series, converts CO2 in wet methanolic solution into bisammonium bicarbonate. Computational studies revealed that this adduct is responsible for a barrierless transformation of CO2 to formate by the reduced form of the Mn catalyst covalently bonded to the electrode surface. As a consequence, selectivity can be switched on demand from CO to formate anion, and in the case of (PMDETA) an impressive TONHCOO− of 2.8×104 can be reached. This new valuable knowledge on an integrated capture and utilization system paves the way toward more efficient transformation of CO2 into liquid fuel.
Exploring the Reactivity of B‐Connected Carboranylphosphines in Frustrated Lewis Pair Chemistry: A New Frame for a Classic System
Authors: Schulz Jan , Sárosi Menyhárt B. , Hey‐Hawkins Evamarie
Published: April 2022

The primary phosphines MesPH2andtBuPH2react with 9‐iodo‐m‐carborane yielding B9‐connected secondary carboranylphosphines 1,7‐H2C2B10H9‐9‐PHR (R=2,4,6‐Me3C6H2(Mes;1 a),tBu (1 b)). Addition of tris(pentafluorophenyl)borane (BCF) to1 a,bresulted in the zwitterionic compounds 1,7‐H2C2B10H9‐9‐PHR(p‐C6F4)BF(C6F5)2(2 a,b) through nucleophilicparasubstitution of a C6F5ring followed by fluoride transfer to boron. Further reaction with Me2SiHCl prompted a H−F exchange yielding the zwitterionic compounds 1,7‐H2C2B10H9‐9‐PHR(p‐C6F4)BH(C6F5)2(3 a,b). The reaction of2 a,bwith one equivalent of R'MgBr (R’=Me, Ph) gave the extremely water‐sensitive frustrated Lewis pairs 1,7‐H2C2B10H9‐9‐PR(p‐C6F4)B(C6F5)2(4 a,b). Hydrolysis of the B−C6F4bond in4 a,bgave the first tertiaryB‐carboranyl phosphines with three distinct substituents, 1,7‐H2C2B10H9‐9‐PR(p‐C6F4H) (5 a,b). Deprotonation of the zwitterionic compounds2 a,band3 a,bformed anionic phosphines [1,7‐H2C2B10H9‐9‐PR(p‐C6F4)BX(C6F5)2]−[DMSOH]+(R=Mes, X=F (6 a), R=tBu, X=F (6 b); R=Mes, X=H (7 a), R=tBu, X=H (7 b)). Reaction of2 a,bwith an excess of Grignard reagents resulted in the addition of R’ at the boron atom yielding the anions [1,7‐H2C2B10H9‐9‐PR(p‐C6F4)BR’(C6F5)2]−(R=Mes, R’=Me (8 a), R=tBu, R’=Me (8 b); R=Mes, R’=Ph (9 a), R=tBu, R’=Ph (9 b)) with [MgBr(Et2O)n]+as counterion. The ability of the zwitterionic compounds3 a,bto hydrogenate imines as well as the Brønsted acidity of3 awere investigated.
Chemo‐ and Regioselective Anionic Fries Rearrangement Promoted by Lithium Amides under Aerobic Conditions in Sustainable Reaction Media
Authors: Ghinato Simone , De Nardi Federica , Bolzoni Paola , Antenucci Achille , Blangetti Marco , Prandi Cristina
Published: April 2022

A straightforward and efficient protocol to promote the metalation/anionic Fries rearrangements of O‐aryl carbamates, using for the first time a lithium amide as metalating agent under aerobic/ambient‐friendly reaction conditions, is reported. This approach enables the sustainable preparation of salicylamide derivatives with high levels of chemoselectivity within ultrafast reaction times, working at room temperature in the presence of air/moisture, and using environmentally responsible cyclopentyl methyl ether as a solvent. Furthermore, the regioselective manipulation of O‐2‐tolyl carbamates has been accomplished using interchangeably alkyllithiums or lithium amides, with an unexpected beneficial contribution from the employment of biorenewable protic eutectic mixtures as non‐innocent reaction media.
Stereochemical switch driven by crystallization: Interplay between stoichiometry and configuration of the products
Authors: Čierna Michaela , Berkeš Dušan , Baran Peter , Šoral Michal , Kolarovič Andrej , Jakubec Pavol
Published: April 2022

An intriguing example of a crystallization‐induced stereochemical switch in the configuration of aza‐Michael reaction products is described. Depending on both the stereochemical purity and stoichiometric ratio of the chiral amine used, the reaction delivers crystalline diastereomers of a different stereochemistry. The optically pure diastereomer smoothly converts to its racemic epimer salt upon the addition of a complementary chiral amine.
2D Homogeneous Holey Carbon Nitride: An Efficient Anode Material for Li‐ion Batteries With Ultrahigh Capacity
Authors: Ghosh Atish , Mandal Sampad , Sarkar Pranab
Published: April 2022

In present day Li‐ion batteries (LIBs) is the most successful and widely used rechargeable batteries. The continuous effort is going on in finding suitable electrode material for LIBs for improved performance in terms of life‐time, storage capacity etc. Computational chemistry plays an important role in identifying suitable electrode materials through electronic structure calculation. By employing state of the art density functional theory we herein explored the electronic structure of homogeneous holey carbon nitride monolayers (CxN3, x=10,19) to understand its suitability as electrode material for rechargeable LIB. The monolayers have shown high negative adsorption energy for Li adsorption and more interestingly the band structure of monolayers reveal Dirac semimetallic character thus would exhibit high electronic conductivity. Meanwhile, monolithiation introduces metallicity in these monolayers. The calculated average open circuit voltages of the monolayers lie in the range of 0.45 to 0.09 V, which are typically observed in high performance anode materials. Moreover, these monolayers achieve ultrahigh theoretical specific capacity upto 2092.01 mAh/g and low diffusion barrier from 0.004 to 0.44 eV. Based on our computational study we suggest that, the CxN3 monolayers could be a promising anode material in search of low‐cost and high performance LIBs.
Perceived and ideal conflict cultures in academe: Creating the conflict cultures survey
Authors: Desrayaud Nathalie
Published: April 2022

Focusing on conflict at the organizational level, this study explores Conflict Culture Theory by (a) conceptualizing perceived and ideal conflict cultures, (b) creating and implementing the Conflict Cultures Survey, and (c) testing Gelfand, Leslie and Keller's (2008) proposed two‐dimensional model. Tenured and tenure‐track faculty at a large, American university (N = 346) completed the survey. Ideal conflict cultures varied little whereas perceived conflict cultures varied across departments, suggesting that ideal and perceived conflict cultures are distinct constructs. Multi‐level modeling and interrater agreement indices for the conflict culture variables provide evidence that conflict cultures exist and vary by department. Results supported the two‐dimensional model rather than one‐ or four‐dimensional models, suggesting that conflict cultures vary along two dimensions: agreeableness and activeness. Practical implications for Conflict Culture Theory and the Conflict Culture Survey include predicting job satisfaction and commitment, identifying bullying or workplace harassment norms, and establishing individual‐organizational fit.
Hydrogen Bond Interaction in the Trade‐Off Between Electrolyte Voltage Window and Supercapacitor Low‐Temperature Performances
Authors: Bu Yongfeng , Jiang Wenya , Liu Haitao , Xu Jiang , Deng Yilin , Sun Tao , Sun Lianshan , Liang Hongyu
Published: April 2022

Liquid electrolyte determines the voltage window and extreme working temperature of supercapacitors. However, the effect of weak interaction between electrolyte species on voltage window and low‐temperature capacitive performance is unclear. Herein, an electrolyte model system with increasing H‐bond interaction was constructed to clarify this concern. The results indicated that strong H‐bond interaction was positively correlated with the number of hydroxyls, which was beneficial to expand voltage window, but deteriorated rate performance; weak H‐bond improved low‐temperature performance. Supercapacitors with an optimized electrolyte presented high voltage and good low‐temperature performance; even at −40 °C, the maximum energy density could be maintained at 7.0 Wh kg−1 (>80 % retention relative to at −20 °C). This study revealed the mechanism of the influence of the H‐bonds on electrolyte voltage window and anti‐freezing capability and provided a new insight for the design of electrolytes with both high working voltage and low‐temperature performance.
Nonisolated high step‐up DC‐DC interleaved SEPIC converter based on voltage multiplier cells
Authors: Salvador Thaís Carvalho , Tofoli Fernando Lessa , de Souza Oliveira Júnior Demercil , Ribeiro Enio Roberto
Published: April 2022

This work presents a nonisolated high step‐up single‐ended primary inductance converter (SEPIC) topology for high‐power, high‐current applications. The converter operation is based on the interleaving principle, and the active switches are driven by gating signals phase shifted by 180°, whereas automatic current sharing is achieved owing to an autotransformer with unity turns ratio. It is possible to extend the voltage gain employing voltage multiplier cells (VMCs) composed of diodes and capacitors. Prominent advantages of the structure include low current and voltage stresses on the semiconductors, inherent modularity, better thermal distribution, and reduced dimensions of the filter elements. A comprehensive theoretical analysis is derived, from which a 1‐kW prototype is designed and thoroughly evaluated.
Interacting effects of cold snaps, rain, and agriculture on the fledging success of a declining aerial insectivore
Authors: Garrett Daniel R. , Pelletier Fanie , Garant Dany , Bélisle Marc
Published: April 2022

Climate change predicts the increased frequency, duration, and intensity of inclement weather periods such as unseasonably low temperatures (i.e., cold snaps) and prolonged precipitation. Many migratory species have advanced the phenology of important life history stages and, as a result, are likely to be exposed to these periods of inclement spring weather more often, therefore risking reduced fitness and population growth. For declining avian species, including aerial insectivores, anthropogenic landscape changes such as agricultural intensification are another driver of population declines. These landscape changes may affect the foraging ability of food provisioning parents and reduce the survival of nestlings exposed to inclement weather through, for example, pesticide exposure impairing thermoregulation and punctual anorexia. Breeding in agro‐intensive landscapes may therefore exacerbate the negative effects of inclement weather under climate change. We observed that a significant reduction in the availability of insect prey occurred when daily maximum temperatures fell below 18.3°C, and thereby defined any day when the maximum temperature fell below this value as a day witnessing a cold snap. We then combined daily information on the occurrence of cold snaps and measures of precipitation to assess their impact on the fledging success of Tree Swallows (Tachycineta bicolor) occupying a nest box system placed across a gradient of agricultural intensification. Estimated fledging success of this declining aerial insectivore was 36.2% lower for broods experiencing 4 cold‐snap days during the 12 days post‐hatching period versus broods experiencing none, and this relationship was worsened when facing more precipitation. We further found that the overall negative effects of a brood experiencing periods of inclement weather was exacerbated in more agro‐intensive landscapes. Our results indicate that two of the primary hypothesized drivers of many avian population declines may interact to further increase the rate of declines in certain landscape contexts.
Is guided self‐help family‐based treatment for parents of adolescents with anorexia nervosa on treatment waitlists feasible? A pilot trial
Authors: Wade Tracey , Byrne Susan , Fursland Anthea , Steele Anna , Wilksch Simon , Anderson Jemma , Zhou Yuan , Datta Nandini , Matheson Brittany , Lock James
Published: April 2022

Objective

The aim of the study was to assess the feasibility (recruitment and retention) of an online 12‐session guided self‐help family‐based treatment (GSH‐FBT) for families on the waitlist for face‐to‐face FBT utilizing trainee psychologists to assist carers of children with anorexia nervosa (AN) or atypical AN.

Method

The primary outcomes were feasibility of GSH‐FBT for families on the waitlist and secondary exploratory outcomes examined improvement of child and parental function.

Results

Of 187 eligible families on the waitlist, 24 (13%) expressed interest in the study; 16 (67%) of these families completed baseline, 13 (54%) completed GSH‐FBT over a 6‐month recruitment period. Children (mean age = 13.92, SD = .86; mean body mass index [BMI] centile = 29.47, SD = 24.80) had an average weight gain of 6 kg (BMI centile effect size = 2.61, 95% CI: 1.77–3.44) and a decrease in eating disorder behaviors (effect size = 1.11, 95% CI: .27–1.95). Improvements also occurred for general mood and behaviors in the child, and the impact of eating disorder symptoms on their functioning. Parents reported improvements in knowledge, skills, and confidence in managing AN.

Discussion

Use of this low‐cost intervention while families are on the waitlist for FBT is engaging and useful but strategies to improve initial recruitment are needed.

Public Significance Statement

Although most eligible families did not enroll in an online 12‐session guided self‐help family‐based treatment for families on the waitlist for face‐to‐face FBT for anorexia nervosa, families who participated found it engaging. The children experienced improvements in BMI centile, eating and behavior. Parents reported increased confidence, knowledge, and skills. We need to examine how families can be encouraged to participate on online training when on waitlists for treatment.
Where did the finch go? Insights from radio telemetry of the medium ground finch (Geospiza fortis)
Authors: Beausoleil Marc‐Olivier , Camacho Carlos , Rabadán‐González Julio , Lalla Kristen , Richard Roxanne , Carrion‐Avilés Paola , Hendry Andrew P. , Barrett Rowan D. H.
Published: April 2022

Movement patterns and habitat selection of animals have important implications for ecology and evolution. Darwin's finches are a classic model system for ecological and evolutionary studies, yet their spatial ecology remains poorly studied. We tagged and radio‐tracked five (three females, two males) medium ground finches (Geospiza fortis) to examine the feasibility of telemetry for understanding their movement and habitat use. Based on 143 locations collected during a 3‐week period, we analyzed for the first time home‐range size and habitat selection patterns of finches at El Garrapatero, an arid coastal ecosystem on Santa Cruz Island (Galápagos). The average 95% home range and 50% core area for G. fortis in the breeding season was 20.54 ha ± 4.04 ha SE and 4.03 ha ± 1.11 ha SE, respectively. For most of the finches, their home range covered a diverse set of habitats. Three finches positively selected the dry‐forest habitat, while the other habitats seemed to be either negatively selected or simply neglected by the finches. In addition, we noted a communal roosting behavior in an area close to the ocean, where the vegetation is greener and denser than the more inland dry‐forest vegetation. We show that telemetry on Darwin's finches provides valuable data to understand the movement ecology of the species. Based on our results, we propose a series of questions about the ecology and evolution of Darwin's finches that can be addressed using telemetry.
In vitro relationships of galactic cosmic radiation and epigenetic clocks in human bronchial epithelial cells
Authors: Nwanaji‐Enwerem Jamaji C. , Boileau Philippe , Galazka Jonathan M. , Cardenas Andres
Published: April 2022

Ionizing radiation is a well‐appreciated health risk, precipitant of DNA damage, and contributor to DNA methylation variability. Nevertheless, relationships of ionizing radiation with DNA methylation‐based markers of biological age (i.e. epigenetic clocks) remain poorly understood. Using existing data from human bronchial epithelial cells, we examined in vitro relationships of three epigenetic clock measures (Horvath DNAmAge, MiAge, and epiTOC2) with galactic cosmic radiation (GCR), which is particularly hazardous due to its high linear energy transfer (LET) heavy‐ion components. High‐LET 56Fe was significantly associated with accelerations in epiTOC2 (β = 192 cell divisions, 95% CI: 71, 313, p‐value = .003). We also observed a significant, positive interaction of 56Fe ions and time‐in‐culture with epiTOC2 (95% CI: 42, 441, p‐value = .019). However, only the direct 56Fe ion association remained statistically significant after adjusting for multiple hypothesis testing. Epigenetic clocks were not significantly associated with high‐LET 28Si and low‐LET X‐rays. Our results demonstrate sensitivities of specific epigenetic clock measures to certain forms of GCR. These findings suggest that epigenetic clocks may have some utility for monitoring and better understanding the health impacts of GCR.
The green total factor productivity and convergence in China
Authors: Zhuang Weiwei , Wang Yujia , Lu Ching‐Cheng , Chen Xiang
Published: April 2022

The green total factor productivity (GTFP) has become an important index of balancing the energy consumptions, economic development, and environmental protections. This study extends the slacks‐based directional distance function (SDDF) of Fare and Grosskopf into the framework of the Malmquist–Luenberger productivity index to estimate the slack‐based GTFP. This SDDF can allow decision‐making units to explore the optimal direction and measure a more precise productivity index. For the empirical study, we employ the new model to measure the slack‐based GTFP for Chinese 30 provinces over the period of 2005–2017. Furthermore, we investigate the effect of the regional differences on the GTFP and the convergence of the Chinese GTFP with β‐converge and σ‐convergence. Our results show that there is a rapid improvement in the GTFP in China, which is attributed to the technical change. However, there exists a significant difference in GTFP for three regions of China. The eastern region performs significantly better than the others. Finally, we find there is a strong convergence in China, and the eastern region has a faster convergence than the other regions.
The importance of implementation: Putting evaluation policy to work
Authors: Fierro Leslie A. , Kinarsky Alana R. , Echeverria‐Estrada Carlos , Sabat Bass Nadia , Christie Christina A.
Published: April 2022

Federal agencies are increasingly expected to write and implement guidance for program evaluation, also known as evaluation policies. The Foundations for Evidence‐Based Policymaking Act required such policies for some federal agencies, and guidance from the White House Office of Management and Budget outlined an expectation that all agencies develop evaluation policies. Before these expectations, many federal agencies were already developing such policies to suit organizational needs and contexts. This chapter details findings from interviews with stakeholders at ten federal agencies and offices that developed and implemented evaluation policies before enacting the Foundations for Evidence‐Based Policymaking Act. These organizations represent early adopters of evaluation policies that can support future guidance and implementation of evaluation frameworks and capacity building in government. The study provides insight into the breadth and depth of the various strategies they used as well as their experiences with implementation.
Impact of the new definition of metabolic dysfunction–associated fatty liver disease on detection of significant liver fibrosis in US adolescents
Authors: Ciardullo Stefano , Carbone Marco , Invernizzi Pietro , Perseghin Gianluca
Published: April 2022

Recently, an expert panel proposed diagnostic criteria for metabolic dysfunction–associated fatty liver disease (MAFLD) in the pediatric population. The aim of this study was to evaluate the prevalence of MAFLD among US adolescents and to investigate whether the new MAFLD definition is able to identify individuals with more advanced liver disease. We analyzed data from participants 12–18 years old included in the 2017–2020 cycles of the National Health and Nutrition Examination Survey, a large survey aimed at including individuals representative of the non‐institutionalized general US population. Participants with a complete vibration‐controlled transient elastography exam were included. Steatosis was evaluated through the median controlled attenuation parameter (CAP) and fibrosis through median liver stiffness measurement (LSM). Recently proposed criteria for the diagnosis of MAFLD were applied. Multivariable logistic regression analysis was performed to evaluate the impact of the new MAFLD definition on the odds of significant liver fibrosis. We included a total of 1446 adolescents (mean age: 14.9 years; 52.0% male; 47.3% overweight or obese). No participant reported a previous history of viral hepatitis. Steatosis (CAP ≥ 248 dB/m) was present in 25.9% (95% confidence interval [CI] 23.3–28.9) of individuals, and among these, 87.7% met the MAFLD criteria. Only 22.9% of patients with steatosis had elevated alanine aminotransferase levels. Among participants with steatosis, prevalence of significant liver fibrosis (LSM ≥ 7.4 kPa) did not differ significantly according to whether they met MAFLD criteria (9.7% vs. 15.2%, p = 0.276). In the multivariable model, odds of significant fibrosis did not differ significantly between these two groups. MAFLD criteria are met by most US adolescents with elastographic evidence of steatosis. Nonetheless, these criteria do not appear to improve detection of subjects with more advanced liver disease. Further longitudinal studies are needed to evaluate whether metabolic dysfunction is associated with faster progression toward inflammation, fibrosis, and liver‐related events.
Combined effects of chlorpyrifos and cyfluthrin on neurobehavior and neurotransmitter levels in larval zebrafish
Authors: Zhang Wanjun , Fan Ruiqi , Luo Sunlin , Liu Ying , Jin Yongpeng , Li Yongchen , Li Bo , Chen Yiqiang , Jia Li , Yuan Xiaoyan
Published: April 2022

Chlorpyrifos and cyfluthrin are insecticides commonly used in agriculture. The mixed residues of chlorpyrifos and cyfluthrin in the aquatic environment may have combined effects on nontarget species. Therefore, studying the combined toxic effects and mechanisms of pesticide mixtures is of great significance to environmental risk assessment. To evaluate the risk of combined exposure, we examined the effects of both compounds, separately and together, on motor activity, acetylcholinesterase (AChE) activity, and neurotransmitter levels in larval zebrafish. Chlorpyrifos exposure significantly reduced functional motor capacity (swim distance and velocity) and enhanced meandering, while cyfluthrin exposure alone had no significant effects on swim parameters. However, combined exposure significantly reduced total swimming distance and mean velocity and increased meandering. Both compounds alone and the combination significantly reduced AChE activity, and the combined effect was antagonistic. Combined exposure also significantly altered the concentrations of serotonin, serotonin precursors, and dopamine precursors, as well as concentrations of the amino acid neurotransmitters glycine, alanine, and aspartic acid. Combined exposure to chlorpyrifos and cyfluthrin exhibited distinct joint action modes in terms of neurobehavior, AChE activity, and neurotransmitter levels, thereby providing an experimental basis for assessing the combined exposure to chlorpyrifos and cyfluthrin's environmental risk.
Two‐layer molecular rotors: A zinc dimer rotating over planar hypercoordinate motifs
Authors: Yu Rui , Yan Gai‐ru , Liu Yu‐qian , Cui Zhong‐hua
Published: April 2022

Multi‐layer molecular rotors represent a class of unique combination of topology and bonding, featuring a barrier‐free rotation of one layer with respect to other layers. This emerging fluxional behavior has been found in a few doped boron clusters. Herein, we strongly enrich this intriguing family followed by an effective design strategy, summarized as essential factors: i) considerable electrostatic interactions originated from a strong charge transfer between layers; ii) the absence of strong covalent bonds between layers; and iii) fully delocalized σ/π electrons from at least one layer. We found that planar hypercoordinate motifs consisting of monocyclic boron rings and metals with σ + π dual aromaticity can be regarded as one promising layer, which can support the suspended X2 (X = Zn, Cd, Hg) dimers. By detailed investigations of thermodynamic and kinetic stabilities of 60 species, eventually, MB7X2− and MB8X2 (X = Zn, Cd; M = Be, Ru, Os; Be works only for Zn‐based cases) clusters were verified to be the global‐minimum two‐layer molecular rotors. Especially, their electronic structure analyses vividly confirm the practicability of the electronic structure requirements mentioned above for designing multi‐layer molecular rotors.
Light‐initiated chemiluminescent assay of 17β‐estradiol metrological traceability system established by manufacturer according to ISO17511:2020 and basic performance evaluation performed by clinical end‐users
Authors: Shang Chenyu , Yuan Xue , Lin Haibiao , Liu Dongdong , Yan Xiaoxin , Ren Xinxin , Lin Xiyang , Di Huang , Li Huiqiang
Published: April 2022

Background

In order to ensure the accuracy of the product, we established 1st model of metrological traceability hierarchy for light‐initiated chemiluminescent assay (LICA) of 17β‐estradiol (E2) at the manufacturer, based on International Organization for Standardization (ISO) 17511:2020. Moreover, we verified/validated the basic performance (such as matrix effect and long‐term stability of end‐user IVD MD calibrator, precision, linearity interval, accuracy/ trueness, and detection capability) at the clinical end‐user.

Methods

Human serum samples were used in this study. E2 was detected by mass spectrometry (MS) and LICA. The metrological traceability of LICA for E2 was established according to ISO 17511: 2020 standards, and pools of human samples were used as the m.3. secondary calibrator. Precision was validated according to Clinical and Laboratory Standards Institute (CLSI) EP05‐A3. The linear interval was verified according to CLSI EP06‐ED2. Comparison of accuracy and trueness of E2 with MS and Roche according to CLSI EP09‐A3. The detection capability was validated according to EP17‐A2. Matrix effect and long‐term stability evaluation of end‐user IVD MD calibrator were carried out according to CLSI EP14‐A2, EP25‐A. Statistical software was used for data analyses.

Results

The use of pools of human samples and fine adjusting calibrators ensured the accuracy of end‐user test results. The metrological traceability of LICA for E2 was established. It showed excellent precision, meeting the requirements of allowable imprecision (7.5%). The allowable deviation from linearity (ADL) of 5% was allowed to show a good linear interval (12.52–4167.25 pg/ml). The accuracy/ trueness was verified, and relative deviation in the medical decision level met the performance specification of 10.03% compared with MS or Roche. The validated limit of blank, limit of detection, and limit of quantitation of E2 were 4.95 pg/ml, 8.93 pg/ml, and 9.88 pg/ml, respectively (the allowed imprecision is 20.00%). The interference rate of E2 ranged from −5.5% to 6.6%.

Conclusion

LICA showed high sensitivity, high specificity, excellent precision, wide linearity interval, IVD MD calibrator has long‐term stability, and no matrix effect. The metrological traceability of E2 established by using pools of human samples as M.3. can deliver accuracy to the end‐user IVD MD and show good consistency with MS and Roche.
Novel findings, mini‐review and dysmorphological characterization of 16p13.11 microduplication syndrome
Authors: Arslan Ahmet Burak , Zamani Ayşe Gül , Yıldırım Mahmut Selman
Published: April 2022

The short arm of chromosome 16 and especially the region 16p13.11 is a chromosome region where many structural variants, especially deletions and duplications, can be observed. Although deletions of this region are clinically well defined, duplications are rare, and so far, there is no established clinical consensus in regard with its clinical picture, and especially the dysmorphic perspective of the disease is far from being clear. A 5‐year‐and‐2‐month‐old patient who presented with epilepsy, autism and late speech onset complaints was evaluated in our genetics department. On physical examination, unilateral preauricular skin tag and upslanting palpebral fissures were noted. Microarray analysis was performed and reported as ([hg19]: 16p13.11 (14.897.804‐16.730.375) x3). The literature review revealed only a few reports about the syndrome, but some dysmorphological findings appear to recur in different reports, which enables a possible characterization. Dysmorphic findings were discussed.
Predictors of growth patterns in children with mucopolysaccharidosis I after haematopoietic stem cell transplantation
Authors: Maier Stefanie , Zivicnjak Miroslav , Grigull Lorenz , Hennermann Julia B. , Aries Charlotte , Maecker‐Kolhoff Britta , Sauer Martin , Das Anibh M. , Beier Rita
Published: April 2022

Mucopolysaccharidosis type I (MPS I) is an autosomal‐recessive metabolic disorder caused by an enzyme deficiency of lysosomal alpha‐l‐iduronidase (IDUA). Haematopoietic stem cell transplantation (HSCT) is the therapeutic option of choice in MPS I patients younger than 2.5 years, which has a positive impact on neurocognitive development. However, impaired growth remains a problem. In this monocentric study, 14 patients with MPS I (mean age 1.72 years, range 0.81–3.08) were monitored according to a standardised follow‐up program after successful allogeneic HSCT. A detailed anthropometric program was carried out to identify growth patterns and to determine predictors of growth in these children. All patients are alive and in outpatient care (mean follow‐up 8.1 years, range 0.1–16.0). Progressively lower standard deviation scores (SDS) were observed for body length (mean SDS −1.61; −4.58 – 3.29), weight (−0.56; −3.19 – 2.95), sitting height (−3.28; −7.37 – 0.26), leg length (−1.64; −3.88 – 1.49) and head circumference (0.91; −2.52 – 6.09). Already at the age of 24 months, significant disproportions were detected being associated with increasing deterioration in growth for age. Younger age at HSCT, lower counts for haemoglobin and platelets, lower potassium, higher donor‐derived chimerism, higher counts for leukocytes and recruitment of a matched unrelated donor (MUD) positively correlated with body length (p ≤ 0.05). In conclusion, this study characterised predictors and aspects of growth patterns in children with MPS I after HSCT, underlining that early HSCT of MUD is essential for slowing body disproportion.
Dermal ultrasound measurements for bone quality assessment : An investigation of advanced glycation endproducts derived from confocal fluorescence microscopy
Authors: Haffer Henryk , Chiapparelli Erika , Moser Manuel , Muellner Maximilian , Dodo Yusuke , Adl Amini Dominik , Zhu Jiaqi , Miller Theodore T. , Han Yi Xin , Donnelly Eve , Shue Jennifer , Sama Andrew A. , Cammisa Frank P. , Girardi Federico P. , Hughes Alexander P.
Published: April 2022

Bone quality is increasingly being recognized in the assessment of fracture risk. Nonenzymatic collagen cross‐linking with the accumulation of advanced glycation end products stiffens and embrittles collagen fibers thus increasing bone fragility. Echogenicity is an ultrasound (US) parameter that provides information regarding the skin collagen structure. We hypothesized that both skin and bone collagen degrade in parallel fashion. Prospectively collected data of 110 patients undergoing posterior lumbar fusion was analyzed. Preoperative skin US measurements were performed in the lumbar region to assess dermal thickness and echogenicity. Intraoperative bone biopsies from the posterior superior iliac spine were obtained and analyzed with confocal fluorescence microscopy for fluorescent advanced glycation endproducts (fAGEs). Pearson's correlation was calculated to examine relationships between  (1) US and fAGEs, and (2) age and fAGEs stratified by sex. Multivariable linear regression analysis with adjustments for age, sex, body mass index (BMI), diabetes mellitus, and hemoglobin A1c (HbA1c) was used to investigate associations between US and fAGEs. One hundred and ten patients (51.9% female, 61.6 years, BMI 29.8 kg/m2) were included in the analysis. In the univariate analysis cortical and trabecular fAGEs decreased with age, but only in women (cortical: r = −0.32, p = 0.031; trabecular: r = −0.32; p = 0.031). After adjusting for age, sex, BMI, diabetes mellitus, and HbA1c, lower dermal (β = 1.01; p = 0.012) and subcutaneous (β = 1.01; p = 0.021) echogenicity increased with increasing cortical fAGEs and lower dermal echogenicity increased with increasing trabecular fAGEs (β = 1.01; p = 0.021). This is the first study demonstrating significant associations between skin US measurements and in vivo bone quality parameters in lumbar fusion patients. As a noninvasive assessment tool, skin US measurements might be incorporated into future practice to investigate bone quality in spine surgery patients.
Adherence to guidelines at the patient‐ and hospital‐levels is associated with improved overall survival in patients with gastric cancer
Authors: Kaslow Sarah R. , Ma Zhongyang , Hani Leena , Prendergast Katherine , Vitiello Gerardo , Lee Ann Y. , Berman Russell S. , Goldberg Judith D. , Correa‐Gallego Camilo
Published: April 2022

Background and Objectives

Adherence to evidence‐based guidelines in gastric cancer is low. We aimed to evaluate adherence to National Comprehensive Cancer Network (NCCN) Guidelines for gastric cancer at both patient‐ and hospital‐levels and examine associations between guideline adherence and treatment outcomes, including overall survival (OS).

Methods

We applied stage‐specific, annual NCCN Guidelines (2004–2015) to patients with gastric cancer treated with curative‐intent within the National Cancer Database and compared characteristics of patients who did and did not receive guideline‐adherent care. Hospitals were evaluated by guideline adherence rate. We identified associations with OS through multivariable Cox regression.

Results

Of 37 659 patients included, 32% received NCCN Guideline‐adherent treatment. OS was significantly associated with both guideline adherence (51 months for patients receiving guideline‐adherent treatment vs. 22 for patients receiving nonadherent treatment, p < 0.001). Treatment at a hospital with higher adherence was associated with longer OS (21 months for patients treated at lowest adherence quartile hospitals vs. 37 months at highest adherence quartile hospitals, p < 0.001), regardless of type of treatment received.

Conclusions

Guideline‐adherent treatment was strongly associated with longer median OS. Guideline adherence should be used as a benchmark for focused quality improvement for physicians taking care of patients with gastric cancer and institutions at large.
Advanced hepatocellular carcinoma: Impact of systemic treatments on health‐related quality of life and patient‐reported outcomes
Authors: Aimar Giacomo , Marino Donatella , Zichi Clizia , Gamba Teresa , Caglio Andrea , De Vita Francesca , Sperti Elisa , Di Maio Massimo
Published: April 2022

In the past years, treatment options for advanced hepatocellular carcinoma (HCC) have thriven. Although globally recognised, the patient‐reported outcomes (PROs) are often underused and quality of life (QoL) results are underreported in many phase III trials. We performed a systematic review to describe the prevalence of QoL inclusion and heterogeneity in QoL reporting in published phase III trials of systemic treatment in advanced HCC. Twenty‐one publications were identified: 12 (57.1%) in first line setting, eight (38.1%) in second line and only one (4.7%) in second and further lines. In 14 trials (66.6%), Qol was included in the analysis as a secondary or tertiary endpoint but only in nine (47.4%) cases Qol results were published in the main paper. QoL data are lacking in a significant proportion of published phase III trials in advanced HCC. The methodology of QoL analysis is heterogeneous for type of instruments, analysis and presentation of results.