bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereoselective Three‐Step One‐Pot Cascade Combining Amino‐ and Biocatalysis to Access Chiral γ‐Nitro Alcohols**
Authors: Ascaso‐Alegre Christian , Herrera Raquel P. , Mangas‐Sánchez Juan
Published: August 2022

The combination of small‐molecule catalysis and enzyme catalysis represents an underexploited area of research with huge potential in asymmetric synthetic chemistry due to both compatibility of reaction conditions and complementary reactivity. Herein, we describe the telescopic synthesis of chiral nitro alcohols starting from commercially available benzaldehyde derivatives through the one‐pot three‐step chemoenzymatic cascade combination of a Wittig reaction, chiral‐thiourea‐catalysed asymmetric conjugate addition, and ketoreductase‐mediated reduction to access the corresponding target compounds in moderate to excellent overall isolated yields (36–80 %) and high diastereomeric and enantiomeric ratios (up to >97 : 3). This represents the first example of the combination of an organocatalysed asymmetric conjugate addition via iminium ion activation and a bioreduction step catalysed by ketoreductases.
Multiple‐Resonance‐Induced Thermally Activated Delayed Fluorescence Materials Based on Indolo[3,2,1‐jk]carbazole with an Efficient Narrowband Pure‐Green Electroluminescence
Authors: Luo Xu‐Feng , Song Shi‐Quan , Ni Hua‐Xiu , Ma Huili , Yang Dezhi , Ma Dongge , Zheng You‐Xuan , Zuo Jing‐Lin
Published: August 2022

Herein, we report two multiple‐resonance thermally activated delayed fluorescence emitters (VTCzBN and TCz‐VTCzBN) based on indolo[3,2,1‐jk]carbazole unit and boron‐nitrogen skeletons, whose emissions peaking at 496 and 521 nm with full width at half maximum of 34 and 29 nm, respectively. Meanwhile, fast rate constants of reverse intersystem crossing of above 106 s−1are obtained due to small singlet‐triplet energy gaps and large spin‐orbital coupling values. Notably, planar molecular structures along the transition dipole moment direction endow them with high horizontal emitting dipole ratios of up to 94 %. Consequently, the corresponding organic light‐emitting diodes (OLEDs) show the maximum external quantum efficiencies of 31.7 % and 32.2 %, respectively. Particularly, OLED with TCz‐VTCzBN display ultra‐pure green emission with Commission Internationale de l′Eclairage coordinates of (0.22, 0.71), consistent with the green display standard of the National Television System Committee.
Less is More: A Shortcut for Anionocages Design Based on (RPO32−)‐Monourea Coordination
Authors: Ma Fen , Qiao Xinrui , Zuo Wei , Tao Yu , Li Anyang , Luo Zhipeng , Liu Yuqi , Liu Xueru , Wang Xiaoqing , Sun Wei , Jia Chuandong
Published: August 2022

Anionocages have been developed as a unique family of hydrogen bonded cages. However, strategies for constructing anionocages are mainly limited to that based on (PO43−)‐bisurea coordination, neither the ligands nor the anions lack the simplicity and diversity of the maturely developed analogues based on metal coordination (i.e. metallocage). We report herein a more simple strategy for anionocages design based on (RPO32−)‐monourea coordination, utilizing monourea rather than bisurea as the hydrogen binding donor, and RPO32−rather than PO43−as the acceptor. Two fluorescent, quadruple helicate anionocages were constructed by a bis‐monourea ligand, and dianions PhOPO32−(H1) or HOPO32−(H1A), respectively, which were capable of encapsulating a series of cation guests. As revealed by molecular modeling,H1features remarkable guest‐adaptive cavity breathing without change of the quadruple helicate topology, which allowed the encapsulation of different sized guests in an “induced fit” manner.
New Benzimidazole‐Based Fe (III) and Cr (III) Complexes: Characterization, Bioactivity Screening, and Theoretical Implementations Using DFT and Molecular Docking Analysis
Authors: Elkanzi Nadia A. A. , Ali Ali M. , Albqmi Mha , Abdou Aly
Published: August 2022

Two new Fe (III) and Cr (III) complexes had been synthesized and structurally characterized. The new complexes were based on 2‐methyl‐benzimidazole (MB) and salicylic acid (H2L). Elemental analyses, Fourier transform infrared spectroscopy, UV‐–Vis, mass spectra, conductivity, magnetic, and thermal measurements were used to formulate the compounds structures. The results revealed octahedral geometry for both of Fe (III) and Cr (III) complexes. Structure elucidation of these complexes was also supported by density functional theory (DFT) along with optimized geometrical parameters. Natural bond orbital analysis and molecular electrostatic potential were also investigated. Electronic absorption spectra were theoretically performed using the time‐dependent TD‐DFT/B3LYP in gas phase and acetonitrtile as a solvent. Furthermore, the bio‐mimicking activity as antimicrobial and anti‐inflammatory activity of the understudy compounds was in vitro screened. The results showed that the Fe (III) and Cr (III) complexes exhibited higher pathogenic action than the free ligands. Molecular docking investigation against 3T88 (E. Coli) and 5IKT (Cyclooxygenase‐2) was carried out to provide deep insights into their role in inhibiting the growth of pathogenic microbes.
Telescopic synthesis and encapsulation of anticancer drugs from Ajuga bracteosa Wall. ex Benth. with zeolitic imidazole framework‐8
Authors: Ahanger Ab Majeed , Kumar Suresh
Published: August 2022

Cancer is one of the world's fastest‐emerging noncommunicable diseases and one of the major causes of death. Zeolitic imidazolate framework‐8 (ZIF‐8) is a subclass of metal–organic frameworks made up of organic linkers and inorganic nodes. Responsive nanocarriers with biocompatibility and precise drug release ability, superior stability under physiological conditions, pH responsiveness, and tunable drug release properties have emerged as prospective properties of ZIF‐8. Among the different options proposed for cancer treatment, natural products are used to find novel hits, which emerge as one of the most successful methods with no adverse effects. Here, we developed a novel nanoscale ZIF‐8 core encapsulated drugs extracted from Ajuga bracteosa extract in its frameworks through a facile and efficient strategy. ZIF‐8@ABE NPs show a sixfold improvement in instability compared with that of free ABE. It can internalize the NPs into cells and present targeted effects of inhibition of growth on the human Caucasian lung carcinoma cell line (A549) (adenocarcinoma). The sustained release behavior of ZIF‐8@ABE has shown a higher efficacy than the free ABE. We envisage that such a biocompatible and biodegradable delivery system may promote the development and translation of hybrid superstructures into smart and personalized delivery platforms, but the limitations imposed by limited loading capacities have stymied the development of innovative multifunctional drug delivery systems.
Protection gaps in Amazon floodplains will increase with climate change: Insight from the world's largest scaled freshwater fish
Authors: Dubos Nicolas , Lenormand Maxime , Castello Leandro , Oberdorff Thierry , Guisan Antoine , Luque Sandra
Published: August 2022

The Amazon floodplains represent important surfaces of highly valuable ecosystems, yet they remain neglected from protected areas. Although the efficiency of the protected area network of the Amazon basin may be jeopardized by climate change, floodplains are exposed to important consequences of climate change but are omitted from species distribution models and protection gap analyses.

The present and future (2070) distribution of the giant bony‐tongue fish Arapaima spp. (Arapaimidae) was modelled accounting for climate and habitat requirements, and with a consideration of dam presence (already existing and planned constructions) and hydroperiod (high‐ and low‐water stages). The amount of suitable environment that falls inside and outside the current network of protected areas was quantified to identify spatial conservation gaps.

We predict that climate change will cause a decline in environmental suitability by 16.6% during the high‐water stage, and by 19.4% during the low‐water stage. About 70% of the suitable environments of Arapaima spp. remain currently unprotected. The gap is higher by 0.7% during the low‐water stage. The lack of protection is likely to increase by 5% with future climate change effects. Both existing and projected dam constructions may hamper population flows between the central, Bolivian and Peruvian parts of the basin.

We highlight protection gaps mostly in the south‐western part of the basin and recommend the extension of the current network of protected areas in the floodplains of the upper Ucayali, Juruà and Purus rivers and their tributaries. This study has shown the importance of integrating hydroperiod and dispersal barriers in forecasting the distribution of freshwater fish species, and stresses the urgent need to integrate floodplains within the protected area networks.
Engineering Escherichia coli asymmetry distribution‐based synthetic consortium for shikimate production
Authors: Ding Qiang , Li Zhendong , Guo Liang , Song Wei , Wu Jing , Chen Xiulai , Liu Liming , Gao Cong
Published: August 2022

Microbial consortia constitute a promising tool for achieving high‐value chemical bio‐production. However, customizing the consortium ratio remains challenging. Herein, an asymmetry distribution‐based synthetic consortium (ADSC) was developed to switch cell phenotypes using shikimate synthesis for proof of concept. First, the cell pole‐organizing protein PopZ was screened as a mediator of asymmetric protein distribution in Escherichia coli. The ADSC was then constructed to incorporate PopZ‐mediated asymmetry distribution and a TetR‐based transcription repression switch to achieve the dynamical control of microbial population ratio. Finally, the ADSC was used to decouple cell growth from shikimate synthesis by effectively coordinating the ratio of growing cells and production cells at the consortium level, thereby increasing shikimate titer to 30.1 g/L in the 7.5‐L bioreactor with a minimal medium. This titer was further improved to 82.5 g/L when using rich medium fermentation. Our results illustrate a novel approach to control consortium structure through ADSC‐mediated regulation, highlighting its potential as an efficient strategy for controlling metabolic state in microbes.
Impact of COVID‐19 on the incidence of localized and metastatic prostate cancer among White and Black Veterans
Authors: Lee Kyung Min , Bryant Alex K. , Alba Patrick , Anglin Tori , Robison Brian , Rose Brent S. , Lynch Julie A.
Published: August 2022

The COVID‐19 pandemic disrupted prostate‐specific antigen (PSA) screening and prostate biopsy procedures. We sought to determine whether delayed screening and diagnostic workup of prostate cancer (PCa) was associated with increased subsequent rates of incident PCa and advanced PCa and whether the rates differed by race. We analyzed data from the Veterans Health Administration to assess the changes in the rates of PSA screening, prostate biopsy procedure, incident PCa, PCa with high‐grade Gleason score, and incident metastatic prostate cancer (mPCa) before and after January 2020. While the late pandemic mPCa rate among White Veterans was comparable to the pre‐pandemic rate (5.4 pre‐pandemic vs 5.2 late‐pandemic, p = 0.67), we observed a significant increase in incident mPCa cases among Black Veterans in the late pandemic period (8.1 pre‐pandemic vs 11.3 late‐pandemic, p < 0.001). Further investigation is warranted to fully understand the impact of the COVID‐19 pandemic on the diagnosis of advanced prostate cancer.
Polyphenols Profile and Enzyme Inhibitory Properties of Blumea lacera (Burm. f.) DC.: A Potential Candidate against Obesity, Aging, and Skin Disorder
Authors: Swaraz A. M. , Sultana Fariha , Shahin Ahmed Khondoker , Satter Mohammed A. , Hossain Hemayet , Raihan Obayed , Brishti Afrina , Khalil Ibrahim , Hua Gan Siew
Published: August 2022

Blumea lacera (Burm. f.) DC. is attracting scientific interest due to the diverse biological activities of its various parts and its use in folk medicine. The present study was undertaken to investigate the tissue‐specific differential expression pattern of its total bioactive compounds. The study was further extended to whole plant phenolics profiling, in vitro enzyme inhibition activities, followed by in silico enzyme inhibition analysis to assess its potential as herbal medicine. The amount of total phenolics in different tissues was followed in decreasing order as old leaf, flower bud, root, young leaf, flower, old stem, and young stem, while that for the flavonoids was old leaf, root, young leaf, flower bud, flower, young stem, and old stem. This study identified rosmarinic acid, quercetin, and kaempferol in this plant for the first time. The solvent extracts demonstrated strong inhibition of lipase and tyrosinase activity, along with varying degrees of inhibition of acetylcholinesterase and butyrylcholinesterase activity. Among the detected compounds, ten displayed strong in silico binding affinities with the tested enzymes. The findings provide a new insight into further investigation of the medicinal potential of this species against obesity, neurological disorders, and aberrant skin color.
Selective Acylation of Proteins at Gly and Lys in His Tags
Authors: Jensen Knud J. , Thygesen Mikkel B. , Sørensen Kasper K. , Wu Shunliang , Treiberg Tuule , Schoffelen Sanne
Published: August 2022

The chemical modification of proteins is of great importance in chemical biology, biotechnology, and for the production of modified biopharmaceuticals, as it enables introduction of fluorophores, biotin, half‐life extending moieties, and more. We have developed two methods that use poly‐His sequences to direct the highly selective acylation of proteins, either at the N‐terminus or at a specific Lys residue. For the former, we used an N‐terminal Gly‐His6 segment (Gly‐His tag) that directed acylation of the N‐terminal Nα‐amine with 4‐methoxyphenyl esters, resulting in stable conjugates. Next, we developed the peptide sequences Hisn‐Lys‐Hism (Lys‐His tags) that direct the acylation of the designated Lys Nϵ‐amine under mild conditions and with high selectivity over native Lys residues. Both the Gly‐His and Lys‐His tags maintain the capacity for immobilized metal ion affinity chromatography. We have demonstrated the robustness of these methods by attaching different moieties such as azides, fluorophores, and biotin to different proteins, including antibodies.
Developments in Downstream Butanol Separation from Acetone, Butanol, and Ethanol Fermentation
Authors: Gonçalves Bruno José Arcanjo , Figueiredo Kátia Cecília de Souza
Published: August 2022

Biobutanol is known for its potential as a biofuel and for having various other industrial applications. However, technical and economic constraints still restrict its commercial application. Biobutanol is produced via acetone, butanol, and ethanol (ABE) fermentation, in which acetone and ethanol are also produced, mainly by Clostridium sp.; however, it is toxic to the cells. Efforts have been made to improve the process by separating butanol from the fermentation broth. This work presents an overview of the main processes reported in ABE separation in the literature, focusing on the pervaporation approach. Some of the latest developments in the field are stated, aiming at comparing the separation processes.
Palladium‐Catalyzed Enantioselective Cyclization of 1,6‐Enynes through Intramolecular Chlorine Transfer as a Novel Strategy for Asymmetric Halopalladation
Authors: Tang Junlong , Zhang Liren , Wu Wanqing , Yang Shaorong , Jiang Huanfeng
Published: August 2022

Palladium‐catalyzed enantioselective cyclization of enynes has contributed significantly to the construction of chiral cyclic molecules. In contrast, the catalytic asymmetric cyclization involving halopalladation remains an unresolved challenge with the inevitable disturbance of the halide ions. Herein, an intramolecular chlorine transfer strategy is used to accomplish the enantioselective chloropalladation cyclization of 1,6‐enynes. This reaction provides a redox‐neutral approach to a variety of chiral α‐chloromethylene‐γ‐butyrolactones with excellent E selectivity and enantioselectivity. The precisely controlled coordination of palladium with both the in situ generated nucleophilic species and the monodentate phosphoramidite ligand is crucial for enantioselectivity.
Research on extraction of Cr(III) by D2EHPA/n‐octanol/sulphonated kerosene
Authors: He Lantao , Zhou Yujie , Zhu Zijun , Luo Jianhong
Published: August 2022

Chromium is an important industrial raw material. As far as China is concerned, chromium is in great demand, which is dependent on imports and large emissions. So recovery of chromium has important economic and environmental protection value. The extraction and back extraction of Cr(III) from solution by the extractant diisooctyl phosphate (di‐2‐ethylhexylphosphoric acid [D2EHPA]) with n‐octanol as assistant and sulphonated kerosene as diluent was studied. The effects of saponification rate, phase ratio, temperature, condensation of extract, aging of extractant, and pH of aqueous phase on extraction equilibrium were discussed, and the formulation of extractant was optimized. The coordination number of the extraction reaction under specific conditions was discussed by the saturation capacity method. The extraction reaction kinetics were mathematically characterized by binary linear regression. The advantages and disadvantages of back extraction with H2SO4 or NaOH were compared. At last, a process to realize the recycling of extractant was obtained.
Noninvasive computed tomography derived fractional flow reserve simulation based on microvascular tree model reconstruction
Authors: Yu Long , He Wei , Qin Wang , Wang Keqiang , Guo Weifeng , Wang Shengzhang
Published: August 2022

To establish a novel method for noninvasive computed tomography derived fractional flow reserve (CT‐FFR) simulation based on microvascular tree model reconstruction and to evaluate the feasibility and diagnostic performance of the novel method in coronary artery disease compared with invasive fractional flow reserve (FFR). Twenty patients (20 vessels) who underwent coronary computed tomography angiography (CCTA) and invasive FFR were retrospectively studied. The anatomic epicardial coronary artery model was reconstructed based on CCTA image, and the microvascular tree model was simulated based on patient‐specific anatomical structures and physiological principles. Numerical simulation was subsequently performed using the CFD method with full consideration of the variation of viscosity in microvascular. Two patients with the FFR value of .80 were selected for adjusting the parameters of the model, while the remaining 18 patients were selected as a validation cohort. After simulation, CT‐FFR was compared with invasive FFR with a threshold of .80. Eleven (55%) patients had an abnormal FFR that was less than or equal to .80. Compared with invasive FFR, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CT‐FFR with an optimal threshold of .80 were 100%, 77.8%, 81.8%, 100%, 88.89%, respectively. There were a good correlation and consistency between CT‐FFR and invasive FFR. Time per patient of CT‐FFR analysis was less than 15 min. CT‐FFR based on microvascular tree model reconstruction is feasible with good diagnostic performance. It requires a short processing time with excellent accuracy. Large multicenter prospective studies are required for further demonstrating the diagnostic performance of this novel model in myocardium ischemia evaluation.
Tunable Naphthalimide/Cinnoline‐Fused (CinNapht) Hybrid Dyes for Fluorescence Imaging in Living Cells
Authors: Hoang Minh‐Duc , Savina Farah , Durand Philippe , Méallet‐Renault Pr. Rachel , Clavier Gilles , Chevalier Arnaud
Published: August 2022

This paper presents the synthesis, photophysical characterization and use for cell imaging of 14 fluorophores derived from a hybrid Naphthalimide/Cinnoline fused backbone called “CinNapht”. Photophysical properties of these fluorophores including absorbance, excitation and emission spectra have been recorded in CHCl3, DMSO and PBS+5 %BSA. They exhibit red emission associated to a large Stokes shift and fluorescence quantum yields up to 52 %. Theoretical calculations have been undertaken in order to provide elements of rationalization for a major part of the results. Some of these analogues have been tuned to enable imaging of cell organelles such as mitochondria, lysosome or lipid droplets. This study comes to confirm that CinNapht dyes can be considered as relevant alternatives to existing tools for cell imaging.
Could Tile Drainage Be Another Form of Crop Insurance in a Changing Climate?
Authors: Sever Megan
Published: August 2022

Tile drainage can prevent fields from being too wet but can also help when fields are too dry. With “controlled tile drainage,” you capture water when there’s too much of it and store it for later use when there’s too little. This article provide a brief primer on tile drainage, what to think about when designing a system, and how to evaluate whether its right for you the producers you advise. Earn 1 CEU in Soil & Water Management by reading the article and taking the quiz at https://web.sciencesocieties.org/Learning‐Center/Courses.
Manipulating adrenergic stress receptor signaling to enhance immunosuppression and prolong survival of vascularized composite tissue transplants
Authors: Kim Minhyung , Fisher Daniel T. , Bogner Paul N. , Sharma Umesh , Yu Han , Skitzki Joseph J. , Repasky Elizabeth A.
Published: August 2022

Background

Vascularized composite tissue allotransplantation (VCA) to replace limbs or faces damaged beyond repair is now possible. The resulting clear benefit to quality of life is a compelling reason to attempt this complex procedure. Unfortunately, the high doses of immunosuppressive drugs required to protect this type of allograft result in significant morbidity and mortality giving rise to ethical concerns about performing this surgery in patients with non‐life‐threatening conditions. Here we tested whether we could suppress anti‐graft immune activity by using a safe β2‐adrenergic receptor (AR) agonist, terbutaline, to mimic the natural immune suppression generated by nervous system‐induced signalling through AR.

Methods

A heterotopic hind limb transplantation model was used with C57BL/6 (H‐2b) as recipients and BALB/c (H‐2d) mice as donors. To test the modulation of the immune response, graft survival was investigated after daily intraperitoneal injection of β2‐AR agonist with and without tacrolimus. Analyses of immune compositions and quantification of pro‐inflammatory cytokines were performed to gauge functional immunomodulation. The contributions to allograft survival of β2‐AR signalling in donor and recipient tissue were investigated with β2‐AR−/− strains.

Results

Treatment with the β2‐AR agonist delayed VCA rejection, even with a subtherapeutic dose of tacrolimus. β2‐AR agonist decreased T‐cell infiltration into the transplanted grafts and decreased memory T‐cell populations in recipient's circulation. In addition, decreased levels of inflammatory cytokines (IFN‐γ, IL‐6, TNF‐α, CXCL‐1/10 and CCL3/4/5/7) were detected following β2‐AR agonist treatment, and there was a decreased expression of ICAM‐1 and vascular cell adhesion molecule‐1 in donor stromal cells.

Conclusions

β2‐AR agonist can be used safely to mimic the natural suppression of immune responses, which occurs during adrenergic stress‐signalling and thereby can be used in combination regimens to reduce the dose needed of toxic immunosuppressive drugs such as tacrolimus. This strategy can be further evaluated for feasibility in the clinic.
Daprodustat for anaemia in patients with heart failure and chronic kidney disease: A randomized controlled study
Authors: Iso Takashi , Matsue Yuya , Mizukami Akira , Tokano Takashi , Isoda Kikuo , Suwa Satoru , Miyauchi Katsumi , Yanagisawa Naotake , Okumura Yasuo , Minamino Tohru
Published: August 2022

Aims

Hypoxia‐inducible factor‐prolyl hydroxylase (HIF‐PH) inhibitors have been developed for the treatment of renal anaemia; however, no study has evaluated the safety and efficacy of HIF‐PH inhibitors in patients with heart failure (HF). This study was designed to evaluate the safety and efficacy of daprodustat, a HIF‐PH inhibitor, in patients with HF and renal anaemia.

Methods and results

We designed a pilot, multi‐centre, open‐label, randomized controlled study, in which 50 patients with HF complicated with chronic kidney disease and anaemia will be randomized 1:1 to either the daprodustat or control group at seven sites in Japan. Study entry requires New York Heart Association Class II HF symptoms or a history of hospitalization due to HF, an estimated glomerular filtration rate of <60 mL/min/1.73 m2, and a haemoglobin level of 7.5 to <11.0 g/dl. Patients randomized to the daprodustat group will be treated with oral daprodustat, and the dose will be uptitrated according to the changes in the haemoglobin level from previous visits. In this study, we will evaluate the impact of HIF‐PH inhibitors on cardiac function using advanced cardiovascular imaging modalities, including cardiac magnetic resonance imaging. The primary outcome is the haemoglobin level at 16 weeks of randomization, and all adverse events will be recorded and evaluated for any association with daprodustat treatment.

Conclusion

Considering the hypothetical upside and downside of using HIF‐PH inhibitors in anaemic patients with HF and chronic kidney disease, and because there are virtually no safe and effective treatments for patients with anaemia not caused by iron deficiency, our study results will contribute significantly to this field.
Solution Structure and Relaxivity of Ln‐DOTXAZA Derivatives
Authors: Holzapfel Malte , Baldau Torben , Kerpa Svenja , Guadalupi Gianmarco , Qi Bing , Liu Yang , Parak Wolfgang J. , Maison Wolfgang
Published: August 2022

Herein we report the synthesis and structural analysis of tunable 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA)‐derivatives bearing azidoethyl side chains. According to the number of azidoethyl side chains, the compounds are termed DOTXAZA (with X=1–4). All derivatives retain the well‐approved DOTA scaffold for metal complexation with 8 coordinating functionalities and are applicable to Cu‐catalyzed alkyne‐azide cycloaddition (CuAAC). They may thus be used to assemble new Gd‐based contrast agents (GBCAs) with tailored pharmacokinetic or MRI properties retaining the high stability of clinically used DOTA‐derived GBCAs. The complex geometry of all DOTXAZA derivatives was investigated in solution with NMR‐spectroscopy of the corresponding Eu‐complexes. A correlation of complex geometry with the longitudinal relaxivity of corresponding Gd‐complexes revealed an increase in relaxivity with increasing substitution number in the DOTXAZA series. Moreover, CuAAC‐modified DOTAZA‐derivatives with neutral, charged, and zwitterionic groups were prepared. Although of similar molecular mass, the corresponding Gd‐complexes revealed pronounced differences in relaxivities from r1=3.9–7.9 mm−1 s−1 in water at 1.5 T and 37 °C. Relaxivities of these complexes were found to be strongly dependent on side chain charge and are most likely determined by second‐sphere water effects.
Reduced‐order models for the seismic assessment of plan‐irregular low‐rise frame buildings
Authors: Ruggieri Sergio , Chatzidaki Akrivi , Vamvatsikos Dimitrios , Uva Giuseppina
Published: August 2022

A procedure is presented for deriving low‐complexity structural models to predict the global response of asymmetric‐plan low‐rise frame buildings for purposes of class‐level assessment. As a compromise between employing a full‐scale multi‐degree‐of‐freedom structural model versus an equivalent single‐degree‐of‐freedom one, the challenge is to create an idealized 3D structure with few degrees‐of‐freedom that can match the inelastic response of a building for which full knowledge of geometrical and mechanical properties is available. Such a 3D reduced‐order model can offset the computational cost related to performing multiple nonlinear dynamic analyses within the framework of Performance‐Based Earthquake Engineering. To this goal, rules and equations are proposed for achieving equivalence among the linear and nonlinear properties (e.g. mass, stiffness, strength) of the building analysed and the related 3D reduced‐order model. The procedure is applied on a sample of 15 existing reinforced‐concrete frame school buildings, from the province of Foggia in Southern Italy, for which the full numerical models are available. Both calibrated and uncalibrated reduced‐order models are created, exploring the limitations of the proposed order‐reduction in a real‐life case study.
A critical review on the practical use of lithium cycle as an upfront nitrogen removal technology from natural gas
Authors: Omar Abdullah , Ibrahim Shadwa , Almomani Fares
Published: August 2022

The increase in energy demand as the world population grows, as well as the competition in the liquefied natural gas (LNG) market, force producers to work hard on developing cost‐effective production technologies. Upfront nitrogen removal (UNR) before the LNG plant's cold section is considered a promising option to save energy that would otherwise be wasted to cool down a large volume of unused nitrogen in the gas stream. In this study, the use of the lithium cycle (Li‐Cy) as a cost‐effective method for UNR is investigated. The Li‐Cy is compromised of three stages: lithium chemisorption of nitrogen (), hydrolysis of lithium nitride (), and electrowinning (Elec.‐w) of the final product to precipitate lithium metal for further reuse. The relevant chemistry, applicability, economic, and future challenges of Li‐Cy as a UNR technology from natural gas (NG) were explored and discussed. The main challenges that required further investigation to apply Li‐Cy to large‐scale applications were highlighted for future works. The literature review revealed that Li‐Cy can spontaneously remove nitrogen from NG even at low temperatures and produces ammonia as a valuable hydrogen storage material. The used lithium can be regenerated via and Elec.‐w and reused again many times. The cost of the Li‐Cy can be compensated by energy savings, the increase in production rate, and by selling the generated ammonia. Calculations showed that selling the produced ammonia from LNG plants with capacity in the range of 1–5 MTPA would not only offset the costs of Li‐Cy but would generate a net profit of $21MM to $103MM, respectively.
The superefficiency direction distance function and total factor energy efficiency: Evidence from the comprehensive and progressive agreement for trans‐pacific partnership (CPTPP) member countries
Authors: Feng Ying , Lu Ching‐Cheng , Lee An‐Guey , Tang Pao‐Yu , Yang An‐Chi , Zhang Leibao
Published: August 2022

This study used the superefficiency direction distance function and total factor energy efficiency to evaluate the changes in energy efficiency and total factor energy efficiency of 11 member countries of the Comprehensive and Progressive Agreement for Trans‐Pacific Partnership (CPTPP) from 2013 to 2017. Based on the results, we consider the policy implications for CPTPP members, and suggest approaches to improve the direction and range of the difference variable for aalyzing energy efficiency performance. In the selection of variables, input variables include labor force, energy consumption, and capital formation; undesirable output variables include the domestic production gross, life expectancy, and PM2.5. The results show that Canada, Japan, and Mexico have the best performance in terms of energy superefficiency and total factor energy efficiency; in contrast, Chile, Malaysia, Peru, and Vietnam would benefit from improved energy efficiency. Energy efficiency can be improved by reducing labor and final energy consumption, increasing gross domestic product, and reducing PM2.5. However, simultaneously improving all three factors is challenging. Countries should first focus on appropriately adjusting energy policies, actively developing new energy use, improving production technology, avoiding waste, reducing PM2.5, and accelerating urban development to achieve optimal energy efficiency.
Congestion centric multi‐objective reptile search algorithm‐based clustering and routing in cognitive radio sensor network
Authors: Sunitha D. , Balmuri Kavitha Rani , de Prado Rocío Pérez , Divakarachari Parameshachari Bidare , Vijayarangan R. , Hemalatha K. L.
Published: August 2022

In recent trends, Cognitive Radio Sensor Networks (CRSNs) are investigated in‐depth and getting momentum in all types of applications. CRSN can make use of the underutilized frequency spectrum in a suitable manner. Due to the above‐mentioned advantage, the scholars have initiated to study of the domain of cognitive radio routing. Network congestion produces transmission delays and packet loss, as well as time and energy wasted on recovery. In order to fulfill the energy efficiency and network lifetime in CRSN, Congestion Centric Multi‐Objective Reptile Search Algorithm (CC‐MORSA)‐based Clustering and Routing are used. The main objective of proposed CC‐MORSA is to improve the lifetime by minimizing the distance among the designated Cluster Head nodes which creates the fitness function by multiple objectives like energy, distance, and load. This technique is appropriate for common sensor nodes in coordinated communications infrastructure and large networks. The simulation results are analyzed through MATALB in terms of remaining energy (999.5 J), average delay (0.36 s), Packet Delivery Ratio (99.8%), Energy Consumption (24.1 J), Throughput (0.98 Mbps), routing overhead (0.54), and Packet Loss Rate (0.2%). From the outcomes, it shows that the presented CC‐MORSA outperformed conventional Stability‐Aware Cluster‐based Routing and Drop Factor‐Based Energy Efficient Routing technique.
How the country context shapes firms' competitive repertoire complexity
Authors: Steinberg Philip J. , Hennig Jan C. , Oehmichen Jana , Heigermoser Judith
Published: August 2022

Research Summary

Recent research has shown that firms' ability to employ complex competitive repertoires can create long‐term competitive advantages. Since research on its determinants has focused on the firm level, we lack an understanding of how country‐level factors impact firms' implementation of complex competitive repertoires. Our cross‐country study addresses this gap by integrating a model of country‐level competitiveness factors with insights from the literature on competitive dynamics and portable governance. We argue that a country context with high‐quality competitiveness factors enables firms to implement complex competitive repertoires. In addition, we hypothesize that firms with foreign investors from countries with high‐quality competitiveness factors can partially compensate for low‐quality factors in firms' domestic context. We found support for our hypotheses in an unbalanced sample containing 1,340 firms from 32 countries.

Managerial Summary

Employing complex competitive repertoires (i.e., diverse and dynamic arrays of competitive actions), such as price reductions or new product introductions, can help firms outcompete their competition. We argue and empirically show that firms' domestic country context, specifically high‐quality governance, factor and demand conditions, related and supporting industries, and strong context for rivalry drive their ability to implement complex repertoires. Moreover, we find that ownership by foreign investors from favorable country backgrounds can partly compensate for firms' weak conditions at home by serving as enabling bridges. Managers who aim to improve their firms' repertoire complexity but are restricted by their domestic country context may consider attracting foreign investors from countries that have what their countries lack.
Bioethics in Community Health
Authors: Berlinger Nancy
Published: August 2022

What keeps community health providers up at night? And how should bioethics evolve to meet the needs of these providers? Hastings Center research scholar Nancy Berlinger introduces a new project and line of research and public‐facing work at The Hastings Center to explore ethical challenges that arise in primary and preventative health care for medically underserved communities, where ethical challenges often reflect the health consequences of social inequalities.
Mask Mandates and Dilemmas of Disability Difference
Authors: Mintz Kevin , Francis Leslie
Published: August 2022

A number of recent legal cases in the United States have considered both disability‐based exceptions to Covid‐19‐related mask mandates and disability‐based claims to stronger masking rules in states restricting the abilities of local governments to enforce mask mandates. We argue that a proper legal and ethical analysis of such cases requires understanding the distinction between disability accommodations and disability modifications. Disability accommodations are individualized adjustments that enable qualified individuals to perform jobs or achieve access on terms comparable to those experienced by others. Disability modifications are programmatic changes to structures or policies that increase accessibility. We contend that in the context of mask mandates, modifications rather than accommodations are ethically desirable because modification‐oriented policies promote disability access in a way that treats all individuals fairly, avoiding the risk of promoting misinformation and uncertainty about the health benefits of masking.
Real‐world evidence in health technology assessment of high‐risk medical devices: Fit for purpose?
Authors: Klein Philip , Blommestein Hedwig , Al Maiwenn , Pongiglione Benedetta , Torbica Aleksandra , Groot Saskia de
Published: August 2022

Health technology assessment (HTA) of medical devices (MDs) increasingly rely on real‐world evidence (RWE). The aim of this study was to evaluate the type and the quality of the evidence used to assess the (cost‐)effectiveness of high risk MDs (Class III) by HTA agencies in Europe (four European HTA agencies and EUnetHTA), with particular focus on RWE. Data were extracted from HTA reports on the type of evidence demonstrating (cost‐)effectiveness, and the quality of observational studies of comparative effectiveness using the Good Research for Comparative Effectiveness principles. 25 HTA reports were included that incorporated 28 observational studies of comparative effectiveness. Half of the studies (46%) took important confounding and/or effect modifying variables into account in the design and/or analyses. The most common way of including confounders and/or effect modifiers was through multivariable regression analysis. Other methods, such as propensity score matching, were rarely employed. Furthermore, meaningful analyses to test key assumptions were largely omitted. Resulting recommendations from HTA agencies on MDs is therefore (partially) based on evidence which is riddled with uncertainty. Considering the increasing importance of RWE it is important that the quality of observational studies of comparative effectiveness are systematically assessed when used in decision‐making.
AIF1+CSF1R+ MSCs, induced by TNF‐α, act to generate an inflammatory microenvironment and promote hepatocarcinogenesis
Authors: Zong Chen , Meng Yan , Ye Fei , Yang Xue , Li Rong , Jiang Jinghua , Zhao Qiudong , Gao Lu , Han Zhipeng , Wei Lixin
Published: August 2022

Background and Aims:

Increasing evidence suggests that mesenchymal stem cells (MSCs) home to injured local tissues and the tumor microenvironment in the liver. Chronic inflammation is regarded as the major trait of primary liver cancer. However, the characteristics of endogenous MSCs in the inflammatory environment and their role in the occurrence of liver cancer remain obscure.

Approach and Results:

Using single‐cell RNA sequencing, we identified a distinct inflammation‐associated subset of MSCs, namely AIF1+CSF1R+ MSCs, which existed in the microenvironment before the occurrence of liver cancer. Furthermore, we found that this MSC subgroup is likely to be induced by TNF‐α stimulation through the TNFR1/SIRT1 (sirtuin 1) pathway. In a rat primary liver cancer model, we showed that MSCs with high SIRT1 expression (Ad‐Sirt1‐MSCs) promoted macrophage recruitment and synergistically facilitated liver cancer occurrence by secreting C‐C motif chemokine ligand (CCL) 5. Interestingly, depletion of macrophages or knockdown of CCL5 expression in Ad‐Sirt1‐MSCs attenuated the promotive effect of Ad‐Sirt1‐MSCs on liver inflammation and hepatocarcinogenesis (HCG). Finally, we demonstrated that SIRT1 up‐regulated CCL5 expression through activation of the AKT/HIF1α signaling axis in MSCs.

Conclusions:

Together, our results show that MSCs, which are mobilized to the injured site, can be educated by macrophages. In turn, the educated MSCs are involved in generating a chronic inflammatory microenvironment and promoting HCG.
Fibroblast growth factor receptor 1/Klothoβ agonist BFKB8488A improves lipids and liver health markers in patients with diabetes or NAFLD: A phase 1b randomized trial
Authors: Wong Chin , Dash Ajit , Fredrickson Jill , Lewin‐Koh Nicholas , Chen Shan , Yoshida Kenta , Liu Yanqiu , Gutierrez Johnny , Kunder Rebecca
Published: August 2022

Background and Aims:

BFKB8488A is a bispecific antibody targeting fibroblast growth factor receptor 1c and Klothoβ. This phase 1b study assessed safety, tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics of BFKB8488A in patients with type 2 diabetes mellitus (T2DM) or NAFLD.

Approach and Results:

Patients were randomized to receive multiple doses of BFKB8488A at various dose levels and dosing intervals (weekly, every 2 weeks, or every 4 weeks) or placebo for 12 weeks. The primary outcome was the safety of BFKB8488A. Overall, 153 patients (T2DM: 91; NAFLD: 62) were enrolled and received at least one dose of treatment. Of these, 102 patients (62.7%) reported at least one adverse event (BFKB8488A: 83 [68.6%]; placebo: 19 [59.4%]). BFKB8488A exhibited nonlinear pharmacokinetics, with greater than dose‐proportional increases in exposure. The treatment‐emergent antidrug antibody incidence was 22.7%. Overall, trends in exposure‐dependent increases in high‐density lipoprotein (HDL) and decreases in triglyceride levels were observed. Decreases in alanine aminotransferase and aspartate aminotransferase were 0.7% and 9.2% for medium exposure and 7.3% and 11.2% for high‐exposure tertiles, compared with increases of 7.5% and 17% in the placebo group, respectively, at Day 85. In patients with NAFLD, the mean decrease from baseline liver fat was 13.0%, 34.5%, and 49.0% in the low‐, medium‐, and high‐exposure tertiles, respectively, compared with 0.1% with placebo at Day 85.

Conclusions:

BFKB8488A was adequately tolerated in patients with T2DM or NAFLD, leading to triglyceride reduction, HDL improvements, and trends in improvement in markers of liver health for both populations and marked liver fat reduction in patients with NAFLD. (ClinicalTrials.gov: NCT03060538).
Cyclohexane and Beyond: Tangled Hexagons and Octahedra
Authors: O'Keeffe Michael , Treacy Michael M. J.
Published: August 2022

Inspired by Dunitz’s treatment of the geometry and flexibility of cyclohexane, we describe some ways in which hexagons and octahedra can become self‐entangled and linked. Connections to topics such as flexibility of frameworks, tensegrity structures, and Borromean rings are indicated.
Distance and health facility choice: Evidence from a health micro insurance program in Punjab, Pakistan
Authors: Latif Dareen , Ahmed Hamna
Published: August 2022

Health micro insurance offers a promising mechanism to protect the poor against risk and vulnerability arising from catastrophic healthcare expenditures. In light of this, we study the relationship between physical distance to hospitals and the choice of healthcare services in the context of a health micro insurance program in Punjab, Pakistan. We address three main research questions; first, how does physical distance affect choice of health facility? Second, is the burden of physical distance greater for women? Third, can the diffusion of information in social networks be a potential mechanism for reducing the burden of distance? We employ a Probit model with administrative data on hospitalisation claims made between 2014 and 2017. Our findings show that distance impedes individuals from making panel (cashless) claims and thus increases the likelihood of out‐of‐pocket expenditures at nearby non‐panel hospitals. This adverse effect is more pronounced for women as compared to men. Dissemination of information in social networks increases the usage of panel facilities, especially by women. Hence, this can be an effective mechanism in reducing the role that distance plays in the choice of health facility.
Development of a multicriteria model for crises in urban water supply and its application to the case of Brasilia, Brazil
Authors: da Silva Welitom T. P. , de Souza Marco A. A.
Published: August 2022

The expansion of urban water supply crisis (UWC) cases, a context characterized by an inadequate ratio between water consumption and supply capacity, has motivated researchers to search for tools to solve the problem. The objective of this study is to develop a multicriteria tool to help select the solution alternative for UWC cases. The tool (called UWC-MCDA) is based on obtaining consensus on various multicriteria methods for selecting alternatives to solve UWC cases. The proposed methodology consists of the following steps: (1) defining the criteria, (2) defining weights, (3) defining the alternative, (4) defining multicriterial decision support methods, (5) coding the UWC solution alternative selection model, (6) evaluation of the model coding, (7) application of the model coding, and (8) sensitivity analysis. The methods PROMETHEE II, TOPSIS, ELECTRE III, and Consensus ranking are used. The case study considered was the Administrative Region of Brasilia, in the Federal District of Brazil. A multicriteria tool to help select the solution alternative for UWC cases was developed in an easy-to-use environment (Visual Basic for Applications, MS Excel). The UWC-MCDA is able to identify and prioritize, among a set of possible alternatives, the most appropriate solution for the case in question. For the case study, the UWC-MCDA indicated the best alternatives for regulating water consumption, strengthening sanitation service operators and good water conservation practices. Integr Environ Assess Manag 2023;19:99–113. © 2022 SETAC