bluuebunny/crossref_metadata_2025 huggingface dataset:
Between Two Chairs: Combination of Theory and Experiment for the Determination of the Conformational Dynamics of Xylosides
Authors: Jaeschke Sven Ole , Lindhorst Thisbe K. , Auer Alexander
Published: June 2022

The conformational properties of monosaccharides constitute fundamental features of oligosaccharides. While the energy landscape of monosaccharides can be altered by a specific biochemical environment or by chemical modifications, the analysis of resulting dynamic conformational equilibria is not feasible by experimental means alone. In this work, a series of β‐d‐xylopyranosides is used to outline how a combination of experimental NMR parameters and computed molecular properties can be used to determine conformers and quantify the composition of conformational equilibria. We demonstrate that identifying the most stable conformers using energy calculations is challenging and computing of NMR shieldings is typically not sensitive enough. On the other hand, computed spin‐spin coupling constants for the xyloside ring can be used to unambiguously assign experimental NMR data of dynamic conformational equilibria and quantify the ratio of different conformers in the mixture. As a proof of principle, this procedure allowed to analyze a hitherto unknown dynamic equilibrium of a diamino‐xyloside as a precursor of a molecular switch.
Carbon‐Based Materials as Lithium Hosts for Lithium Batteries
Authors: Chen Shang , Chen Shuiyin , Han Dengji , Bielawski Christopher W. , Geng Jianxin
Published: June 2022

Lithium (Li) metal has attracted significant attention in areas that range from basic research to various commercial applications due to its high theoretical specific capacity (3860 mA h g−1) and low electrochemical potential (−3.04 vs. standard hydrogen electrode). However, dendrites often form on the surfaces of Li metal anodes during cycling and thus lead to battery failure and, in some cases, raise safety concerns. To overcome this problem, a variety of approaches that vary the electrolyte, membrane, and/or anode have been proposed. Among these efforts, the use of three‐dimensional frameworks as Li hosts, which can homogenize and minimize the current density at the anode surface, is an effective approach to suppress the formation of Li dendrites. Herein, we describe the development of using carbon‐based materials as Li hosts. While these materials can be fabricated into a variety of porous structures, they have a number of intrinsic advantages including low costs, high specific surface areas, high electrical conductivities, and wide electrochemical stabilities. After briefly summarizing the formation mechanisms of Li dendrites, various methods for controlling structural and surface chemistry will be described for different types of carbon‐based materials from the viewpoint of improving their performance as Li hosts. Finally, we provide perspective on the future development of Li host materials needed to meet the requirements for their use in flexible and wearable devices and other contemporary energy storage techniques.
Extending CIECAM02 and CAM16 for the Helmholtz–Kohlrausch effect
Authors: Hellwig Luke , Stolitzka Dale , Fairchild Mark D.
Published: June 2022

Increasing the purity of a visual stimulus increases its brightness, even if the stimulus luminance is held constant. This perceptual phenomenon is known as the Helmholtz–Kohlrausch (H–K) Effect. This paper reviews published experimental data and models of the effect. Using past experimental data, we derive a modification of the CIECAM02 and CAM16 color appearance models to account for the H–K effect and compare the proposed model to other models. Finally, we discuss the need for further experimental data on the H–K effect to refine the proposed model.
Influence of Solvent Properties on Two Individuals Presented in the Excited State – Reverse Fluorosolvatochromism of CNAacDMA**
Authors: Bylińska Irena , Wiczk Wiesław
Published: June 2022

The photophysical behavior of 9‐(2‐(4‐(N,N‐dimethylamino)phenyl)ethynyl)anthracene‐10‐carbonitrile (CNAacDMA) was investigated with absorption and steady‐state fluorometry. Studies have shown extremely interesting properties of the analyzed derivative. The studied molecule is characterized by dual fluorescence and bidirectional fluorescence. These two observed phenomena are interrelated. Dual fluorescence analysis (part 1) explains bidirectional fluorescence. The compound in polar solvents shows only one emission band, however in moderate polar solvents shows dual emission. The appearance of the long‐wavelength CT band in moderate polar solvents and its lack in polar solvents leads to bidirectional solvatofluorochromism. The solvatochrome analysis was performed in a wide range of 24 solvents. To determine the contribution of specific and nonspecific interaction of this compound with solvents linear and multi‐parametric correlation of the solvent polarity were analyzed. The novelty and innovation in this article is to carry out such an analysis separately for two different individuals occurring in the excited state. Single‐parameter scale with ET(30) as a solvent polarity parameter and multi‐parameter scales such as the Catalán four‐parameter solvent scale were used. The excited state dipole moment was determined based on solvatochromic method. The hydrogen bond energy change after excitation in the Franck‐Condon and relaxed excited state were estimated.
Renewable Beta‐Elemene Based Cyclic Carbonates for the Preparation of Oligo(hydroxyurethane)s
Authors: Maquilón Cristina , Brandolese Arianna , Alter Christian , Hövelmann Claas H. , Della Monica Francesco , Kleij Arjan W.
Published: June 2022

Conversion of β‐elemene into new β‐elemene dicarbonates through epoxidation and halide salt‐catalyzed CO2 cycloaddition reactions is reported. Step‐growth polyaddition of this dicarbonate to five different, commercial diamines was investigated under neat conditions at 150 °C yielding non‐isocyanate‐based low molecular weight oligo(hydroxyurethane)s with 1.3≤Mn≤6.3 kDa and 1.3≤Ð≤2.1, and with glass transition temperatures ranging from −59 to 84 °C. The preparation of one selected polyhydroxyurethane material, obtained in the presence of Jeffamine® D‐2010 was scaled‐up to 43 g. The latter, when combined in a formulation using Irgacure® 2100 and Laromer® LR 9000 allowed the preparation of coatings that were analyzed with several techniques showing the potential of these biobased oligourethanes towards the preparation of commercially relevant materials.
Temporal activity patterns of North China leopards and their prey in response to moonlight and habitat factors
Authors: Zaman Muhammad , Roberts Nathan James , Zhu Mengyan , Vitekere Kasereka , Wang Meng , Jiang Guangshun
Published: June 2022

The nocturnal activities of predators and prey are influenced by several factors, including physiological adaptations, habitat quality and, we suspect, corresponds to changes in brightness of moonlight according to moon phase. In this study, we used a dataset from 102 camera traps to explore which factors are related to the activity pattern of North China leopards (Panthera pardus japonensis) in Shanxi Tieqiaoshan Provincial Nature Reserve (TPNR), China. We found that nocturnal activities of leopards were irregular during four different lunar phases, and while not strictly lunar philic or lunar phobic, their temporal activity was highest during the brighter moon phases (especially the last quarter) and lower during the new moon phase. On the contrary, roe deer (Capreolus pygargus) exhibited lunar philic activity, while wild boar (Sus scrofa) and tolai hare (Lepus tolai) were evidently lunar phobic, with high and low temporal activity during the full moon, respectively. In terms of temporal overlap, there was positive overlap between leopards and their prey species, including roe deer and tolai hare, while leopard activity did not dip to the same low level of wild boar during the full moon phase. Human activities also more influenced the temporal activity of leopards and wild boar than other species investigated. Generally, our results suggested that besides moonlight risk index (MRI), cloud cover and season have diverse effects on leopard and prey nocturnal activity. Finally, distinct daytime and nighttime habitats were identified, with leopards, wild boar, and tolai hare all using lower elevations at night and higher elevations during the day, while leopards and roe deer were closer to secondary roads during the day than at night.
Insomnia in patients with acute heart failure: from the KCHF registry
Authors: Seko Yuta , Yamamoto Erika , Kato Takao , Morimoto Takeshi , Yaku Hidenori , Inuzuka Yasutaka , Tamaki Yodo , Ozasa Neiko , Shiba Masayuki , Yoshikawa Yusuke , Yamashita Yugo , Kitai Takeshi , Taniguchi Ryoji , Iguchi Moritake , Nagao Kazuya , Kawai Takafumi , Komasa Akihiro , Nishikawa Ryusuke , Kawase Yuichi , Morinaga Takashi , Toyofuku Mamoru , Furukawa Yutaka , Ando Kenji , Kadota Kazushige , Sato Yukihito , Kuwahara Koichiro , Kimura Takeshi ,   for the KCHF Study Investigators
Published: June 2022

Aims

Insomnia is a known risk factor for heart failure (HF) and a predictor of cardiac events in HF patients, but the clinical significance of insomnia in patients with acute HF (AHF) is not adequately evaluated. This study aimed to investigate the association between insomnia and subsequent clinical outcomes in patients with AHF.

Methods

From the Kyoto Congestive Heart Failure registry, consecutive 3414 patients hospitalized for HF who were discharged alive were divided into the 2 groups at discharge: insomnia group and non‐insomnia group. We compared baseline characteristics and 1 year clinical outcomes according to the presence of insomnia. The primary outcome measure was all‐cause death.

Results

There were 330 patients (9.7%) and 3084 patients (90.3%) with and without insomnia, respectively. In the multivariable logistic regression analysis, brain‐type natriuretic peptide above median value at discharge (OR = 1.50, 95% CI = 1.08–2.10, P = 0.02) and the presence of oedema at discharge (OR = 4.23, 95% CI = 2.95–6.07, P < 0.001) were positively associated with insomnia at discharge, whereas diuretics at discharge (OR = 0.60, 95% CI = 0.39–0.90, P = 0.01) were negatively associated with insomnia at discharge. The cumulative 1 year incidence of all‐cause death was significantly higher in the insomnia group than in the non‐insomnia group (25.1% vs. 16.2%, P < 0.001). Even after adjusting the confounders, the higher mortality risk of patients with insomnia relative to those without insomnia remained significant (HR = 1.55, 95% CI = 1.24–1.94; P < 0.001).

Conclusions

Patients with insomnia at discharge were associated with a higher risk of mortality than those without insomnia at discharge.
Pharmacogenomic study of heart failure and candesartan response from the CHARM programme
Authors: Dubé Marie‐Pierre , Chazara Olympe , Lemaçon Audrey , Asselin Géraldine , Provost Sylvie , Barhdadi Amina , Lemieux Perreault Louis‐Philippe , Mongrain Ian , Wang Quanli , Carss Keren , Paul Dirk S. , Cunningham Jonathan W. , Rouleau Jean , Solomon Scott D. , McMurray John J.V. , Yusuf Salim , Granger Chris B. , Haefliger Carolina , de Denus Simon , Tardif Jean‐Claude
Published: June 2022

Aims

The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) programme consisted of three parallel, randomized, double‐blind clinical trials comparing candesartan with placebo in patients with heart failure (HF) categorized according to left ventricular ejection fraction and tolerability to an angiotensin‐converting enzyme inhibitor. We conducted a pharmacogenomic study of the CHARM trials with the objective of identifying genetic predictors of HF progression and of the efficacy and safety of treatment with candesartan.

Methods

We performed genome‐wide association studies in 2727 patients of European ancestry from CHARM‐Overall and stratified by CHARM study according to preserved and reduced ejection fraction and according to assignment to the interventional treatment with candesartan. We tested genetic association with the composite endpoint of cardiovascular death or hospitalization for heart failure for drug efficacy in candesartan‐treated patients and for HF progression using patients from both candesartan and placebo arms. The safety endpoints for response to candesartan were hyperkalaemia, renal dysfunction, hypotension, and change in systolic blood pressure between baseline and 6 weeks of treatment. To support our observations, we conducted a genome‐wide gene‐level collapsing analysis from whole‐exome sequencing data with the composite cardiovascular endpoint.

Results

We found that the A allele (14% allele frequency) of the genetic variant rs66886237 at 8p21.3 near the gene GFRA2 was associated with the composite cardiovascular endpoint in 1029 HF patients with preserved ejection fraction from the CHARM‐Preserved study (hazard ratio: 1.91, 95% confidence interval: 1.55–2.35; P = 1.7 × 10−9). The association was independent of candesartan treatment, and the genetic variant was not associated with the cardiovascular endpoint in patients with reduced ejection fraction. None of the genome‐wide association studies for candesartan safety or efficacy conducted in patients treated with candesartan passed the significance threshold. We found no significant association from the gene‐level collapsing analysis.

Conclusions

We have identified a candidate genetic variant potentially predictive of the progression of heart failure in patients with preserved ejection fraction. The findings require further replication, and we cannot exclude the possibility that the results may be chance findings.
Clinical characterization and natural history of chemotherapy‐induced dilated cardiomyopathy
Authors: Lalario Andrea , Del Mestre Eva , Lo Casto Michele , Nuzzi Vincenzo , Manca Paolo , Bromage Daniel I. , Barbati Giulia , Merlo Marco , Sinagra Gianfranco , Cannatà Antonio
Published: June 2022

Aims

Chemotherapy‐induced dilated cardiomyopathy (CI‐DCM) is a well‐recognized phenotype of non‐ischemic dilated cardiomyopathy (DCM), characterized by poor outcomes. However, a detailed comparison between idiopathic DCM (iDCM) and CI‐DCM is still lacking.

Methods and results

All consecutive DCM patients enrolled in the Trieste Muscle Heart Disease Registry were analysed. CI‐DCM and iDCM were defined according to current recommendations. The primary study outcome measure was all‐mortality death and secondary outcomes were a) a composite of cardiovascular death/heart‐transplantation/ventricular‐assist‐device implantation, and b) major ventricular arrhythmias. The study included 551 patients (499 iDCM and 52 CI‐DCM). At enrolment, compared with iDCM, CI‐DCM patients were older (51 ± 14 years vs. 58 ± 3 years, respectively, P < 0.001) and had a higher left ventricular ejection fraction (32% ± 9 vs. 35% ± 10, respectively, P = 0.03). Over a median follow‐up of 90 months (IQR 54–140 months), CI‐DCM patients had a higher incidence of all‐cause mortality compared with iDCM (36.5% vs. 8.4% in CI‐DCM and iDCM respectively, P < 0.001), while the incidence of major ventricular arrhythmias was higher in the iDCM group compared with CI‐DCM (4% vs. 0%, in CI‐DCM and iDCM respectively, P = 0.03). The risk of the composite outcome was comparable between the two groups (P = 0.91). At Cox multivariable analysis, the diagnosis of CI‐DCM emerged as independently associated to primary outcome (HR 6.42, 95% C.I. 2.52–16.31, P < 0.001).

Conclusions

In a well‐selected DCM cohort, patients with a chemotherapy‐induced aetiology had a higher incidence of all‐cause mortality compared with iDCM. Conversely, the incidence of life‐threatening ventricular arrhythmic events was higher among patients with iDCM.
Organometallic Chemistry of the Difluorodithiophosphate Anion
Authors: Gaydon Quentin , Bohle David Scott
Published: June 2022

An improved synthetic route of [NnPr4][S2PF2] was devised, and its structure was determined. This unusual dithiophosphate is a good ligand for low valent metal centers and examples of this being hydrolytically stable ruthenium complexes RuH(CO)(S2PF2)(PPh3)2, RuCl(CO)(S2PF2)(PPh3)2 and Ru(S2PF2)2(PPh3)2. Taken together these results give an insight into the bonding of the S2PF2 anion to low oxidation state complexes. A comparison of the structural features and reactivity of the complexes with other known Ru(II) complexes is presented. Ru(S2PF2)2(PPh3)2 was successfully carbonylated to give a complex with monohapto and dihapto S2PF2 ligands, Ru(CO)(η1‐S2PF2)(η2‐S2PF2)(PPh3)2 confirming the lability of the fluorothiophosphate anion. Isomers of this latter complex have been structurally characterized with cis and trans PPh3.
The Nature of the Atypical Kinetic Effects Observed for the Thermally Induced Spin Transition in Ferrous Nitroprussides with Short Organic Pillars
Authors: Avila Yosuan , Scanda Karla , Díaz‐Paneque Luis A. , Cruz‐Santiago Lorenzo A. , González Marlene , Reguera Edilso
Published: June 2022

In pillared 2D ferrous nitroprussides, Fe(L)x[Fe(CN)5NO] where x=1, 2, and L is an appropriate organic molecule, the axial CN and NO groups are dangling ligands found in the interlayer region. These ligands subtract electron density from the iron atom in the nitroprusside building block via π‐back bonding interaction. That electron density appears accumulated at their CN5σ and NOπ* orbitals, and for the case of short pilar molecules, such electron density is responsible for the appearance of a repulsive force between adjacent layers. In the series of ferrous nitroprussides with short pillar molecules herein considered (L=pyrazine, pyridine, and 4‐methylpyridine), that repulsive electrostatic interaction opposes the unit cell volume contraction during the spin transition (HS→LS) on the sample cooling and it favors the cell expansion that accompanies the inverse spin transition (LS→HS) when the sample is warmed. This results in an atypical kinetic behavior for the thermally induced spin transition in these materials. The lower the scan rate, the greater the shift of the HS→LS transition towards low temperatures. The features of this effect are herein discussed. For a large pillar molecule, e. g. 4,4'‐azopyridine, or in the absence of that electrostatic interaction, for instance, in Fe(Pyz)[Pt(CN)4] where Pyz=pyrazine, such an atypical effect is not observed. The results discussed in this contribution illustrate how relevant could be the structural factors on the spin crossover (SCO) in coordination polymers. This study includes an evaluation of the effects of repeated cycles of cooling and warming on the recorded magnetic data, considering that the spin transitions involve nucleation and growth processes of the solid crystallites and structural changes within the solid framework.
Metal‐Organic‐Frameworks and Their Derived Materials in Photo‐Thermal Catalysis
Authors: Khan Il Son , Garzon‐Tovar Luis , Mateo Diego , Gascon Jorge
Published: June 2022

The direct utilization of light to drive chemical reactions has been considered a promising approach to decarbonizing the chemical industry and storing solar energy in the form of chemical bonds. In this regard, photo‐thermal catalysis has emerged as a bright strategy due to the combination of thermal and non‐thermal contributions of sunlight. This enables the whole exploitation of the solar spectrum providing localized heating and thus an enhancement in the productivity rates. In this scenario, MOFs and MOFs‐derived materials offer great opportunities for the rational design of new photo‐thermal catalysts. In this review, we describe the different types of photo‐thermal systems, with a particular consideration on the mechanisms. Further, we describe the recent advances of MOF and MOF‐derived materials as photo‐thermal catalysts for different catalytic reactions, including organic transformations, pollutant degradation or CO2 hydrogenations. Lastly, we present our opinion on the future challenges and perspectives in the field.
Using transition matrices to assess the spatio‐temporal land cover and ecotone changes in fluvial landscapes from historical planimetric data
Authors: Chardon Valentin , Herrault Pierre‐Alexis , Staentzel Cybill , Skupinski Grzegorz , Finance Olivier , Wantzen Karl‐Matthias , Schmitt Laurent
Published: June 2022

Change detection approaches based on historical maps are frequently used in fluvial geomorphology to reconstruct long‐term river trajectories and evaluate the level of functional degradation. On this basis, achievable rehabilitation goals may also be addressed. However, most of these studies explore the changes of land cover over time only through changes in the landscape composition, which is nevertheless not sufficient to assess accurately the river responses to natural and/or man‐made disturbances. In this study, we present that transition matrices and new metrics derived from this approach can be used to evaluate the land cover and ecotone area changes at multispatial scales on a 6 km long reach of the Upper Rhine. This study was based on the historical maps of 1828, 1838 and 1872 and using Open Street Map (OSM) for 2021. Our approach was targeting to assess (i) the composition and configuration of a fluvial landscape over time from pixel to landscape scale, (ii) the accurate location of land cover changes, their nature and their intensities, and (iii) the location, nature and diversity of the ecotone areas and their spatial complexities over time. The results showed that (i) the absence of changes in landscape composition over time cannot be interpreted as stability in the fluvial landscape in all cases, (ii) transition matrices are robust tools to face interpretation biases caused by conventional approaches based on landscape composition, because they allow us to trace the changes of each element of the transformed landscape elements. From this study, we indicate that the Rhine regulation induced a habitat and ecotone homogenization following the river correction works, which was exacerbated by the Rhine by‐passing, mainly due to the degradation of lateral connectivity between the main channel and the floodplain and global loss of the hydrosystem functionality.
A review of transgenerational and multigenerational toxicology in the in vivo model animal Caenorhabditis elegans
Authors: Zhao Yunli , Chen Jingya , Wang Rui , Pu Xiaoxiao , Wang Dayong
Published: June 2022

A large number of pollutants existing in the environment can last for a long time, and their potential toxic effects can transfer from parents to their offspring. Thus, it is necessary to investigate the toxicity of environmental pollutants across multigenerations and the underlying mechanisms in organisms. Due to its short life cycle and sensitivity to environmental exposures, Caenorhabditis elegans is an important animal model for toxicity assessment of environmental pollutants across multigenerations. In this review, we introduced the transgenerational and multigenerational toxicity caused by various environmental pollutants in C. elegans. Moreover, we discussed the underlying mechanisms for the observed transgenerational and multigenerational toxicity of environmental contaminants in C. elegans.
Antiviral efficacy of selective estrogen receptor modulators against SARS‐CoV‐2 infection in vitro and in vivo reveals bazedoxifene acetate as an entry inhibitor
Authors: Miao Gen , Peng Haoran , Tang Hailin , Liu Yangang , Zheng Xu , Liu Bin , Jiang Liangliang , Tang Wanda , He Yanhua , Liu Yan , Ren Hao , Zhao Ping , Qi Zhongtian , Ding Cuiling
Published: June 2022

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the seventh member of the coronavirus family that can infect humans. Recently, more contagious and pathogenic variants of SARS‐CoV‐2 have been continuously emerging. Clinical candidates with high efficacy and ready availability are still in urgent need. To identify potent anti‐SARS‐CoV‐2 repurposing drugs, we evaluated the antiviral efficacy of 18 selective estrogen receptor modulators (SERMs) against SARS‐CoV‐2 infection. Six SERMs exhibited excellent anti‐SARS‐CoV‐2 effects in Vero E6 cells and three human cell lines. Clomifene citrate, tamoxifen, toremifene citrate, and bazedoxifene acetate reduced the weight loss of hamsters challenged with SARS‐CoV‐2, and reduced hamster pulmonary viral load and interleukin‐6 expression when assayed at 4 days postinfection. In particular, bazedoxifene acetate was identified to act on the penetration stage of the postattachment step via altering cholesterol distribution and endosome acidification. And, bazedoxifene acetate inhibited pseudoviruses infection of original SARS‐CoV‐2, Delta variant, Omicron variant, and SARS‐CoV. These results offer critical information supporting bazedoxifene acetate as a promising agent against coronaviruses.
Serpentine‐Inspired Strain Sensor with Predictable Cracks for Remote Bio‐Mechanical Signal Monitoring
Authors: Hu Jie , Ren Penggang , Zhu Guanjun , Yang Junjun , Li Yanhao , Zong Ze , Sun Zhenfeng
Published: June 2022

Flexible strain sensors have attracted intense interest due to their application as intelligent wearable electronic devices. However, it is still a huge challenge to achieve a flexible sensor with simultaneous high sensitivity, excellent durability, and a wide sensing region. In this work, a crack‐based strain sensor with a paired‐serpentine conductive network is fabricated onto flexible film by screen printing. The innovative conductive network exhibits a controlled crack morphology during stretching, which endows the prepared sensor with outstanding sensing characteristics, including high sensitivity (gauge factor up to 2391.5), wide detection (rang up to 132%), low strain detection limit, a fast response time (about 40 ms), as well as excellent durability (more than 2000 stretching/releasing cycles). Benefiting from these excellent performances, full‐range human body motions including subtle physiological signals and large motions are accurately detected by the prepared sensor. Furthermore, wearable electronic equipment integrated with a wireless transmitter and the prepared strain sensor shows great potential for remote motion monitoring and intelligent mobile diagnosis for humans. This work provides an effective strategy for the fabrication of novel strain sensors with highly comprehensive performance.
Gnathodiaphyseal dysplasia with a novel genetic variant in a large family from Iran
Authors: Yassaee Vahid Reza , Khojasteh Arash , Hashemi‐Gorji Farzad , Sadeghi Hossein , Safiaghdam Hannaneh , Mirfakhraie Reza
Published: June 2022

Background

Gnathodiaphyseal dysplasia (GDD) is an ultrarare autosomal dominant bone dysplasia characterized by cementoosseous lesions of the jawbones, bone fragility, frequent bone fractures at the young age, bowing of tubular bones, and diaphyseal sclerosis of long bones associated with generalized osteopenia. GDD is caused by point mutations in anoctamin‐5 (ANO5) on chromosome 11p14.3. For the past few years, next generation sequencing (NGS) technology has facilitated the discovery of causative variants in genetically heterogeneous diseases.

Methods

In this study, exome sequencing (ES) was performed using the DNA sample of the proband. Family histories and clinical information were collected through comprehensive medical examination and genetic counseling.

Results

ES results identified a heterozygous variant, NM_213599.3:c.1078T>C(p.Cys360Arg) in the ANO5 gene. Sanger sequencing was performed to confirm the detected pathogenic variant in DNA samples of the entire family (except deceased individuals), which segregated with the disease within the family. Finally, in silico analysis was applied to test the pathogenicity of the variant using various online software.

Conclusion

In summary, our investigation identified a novel pathogenic variant in the ANO5, responsible for gnathodiaphyseal dysplasia in a large Iranian family. Therefore, based on the present study, this variant can be helpful for diagnosis and effective management of GDD patients.
Accelerating and improving radiochromic film calibration by utilizing the dose ratio in photon and proton beams
Authors: Resch Andreas F. , Padilla Cabal Fatima , Regodic Milovan , Lechner Wolfgang , Heilemann Gerd , Kuess Peter , Georg Dietmar , Palmans Hugo
Published: June 2022

Purpose

Radiochromic films are versatile 2D dosimeters with high‐resolution and near tissue equivalence. To assure high precision and accuracy, a time‐consuming calibration process is required. To improve the time efficiency, a novel calibration method utilizing the ratio of the same dose profile measured at different monitor units (MUs) is introduced and tested in a proton and photon beam.

Methods

The calibration procedure employs the dose ratio of film measurements of the same relative profile for different absolute dose values. Hence, the ratio of the dose is constant at any point of the profile, but the ratio of the net optical densities is not constant. The key idea of the method is to optimize the calibration function until the ratio of the calculated doses is constant. The proposed method was tested in the dose range between 0.25–12 and 1–6 Gy in a proton and photon beam, respectively. A radial symmetric profile and a rectangular profile were created, both having a central plateau region of about 3 cm diameter and a dose falloff of about 1.5 cm at larger distances. The dose falloff region was used as input for the optimization method and the central plateau region served as dose reference points. Only the plateau region of the highest dose entered the optimization as an additional objective. The measured data were randomly split into differently sized training and test sets. The optimization was repeated 1000 times with random start value initialization using the same start values for the standard and the gradient method. Finally, a proton plan with four dose levels was created, which were separated spatially, to test the possibility of a full calibration within a single measurement.

Results

Parameter estimation was possible with as low as one dose ratio used for optimization in both the photon and the proton case, yet exhibiting a high sensitivity on the dose level. The root mean squared deviation (RMSD) of the dose was less than 1% when the dose ratio was in the order of 20, whereas the median RMSD of all optimizations was 1.7%. Using four dose levels for optimization resulted in a median RMSD of 1% when randomly selecting the dose levels. Having at least one dose ratio of about 20 included in the optimization considerably improved the RMSD of the calibration function. Using six or eight dose levels reduced the sensitivity on the dose level selection and the median RMSD was 0.8%. A full calibration was possible in a single measurement having four dose levels in one plan but spatially separated.

Conclusions

The number of measurements required to obtain an EBT3 film calibration function could be reduced using the proposed dose ratio method while maintaining the same accuracy as with the standard method.
The role of local governments in South Korea's COVID‐19 response
Authors: Kim Yunji , Jeong Yeong Ah
Published: June 2022

Research on COVID‐19 responses has largely focused on national governments. Meanwhile, the crisis management literature has noted that such “transboundary crises” require collaborative responses. What role can local governments play? How do citizen perceptions matter? We look for answers in South Korea that has been considered a model case for managing COVID‐19. We use data from policy briefs, news reports, and local government websites to show that local governments successfully implemented national initiatives while modifying them to fit local needs and also actively planned and executed local initiatives to address needs that the central government did not address. Based on 2020 national survey data (N = 16,258), we find that COVID‐19 cases and deaths are linked to citizen perceptions of vulnerability to COVID‐19 and its effect on wellbeing, but not to evaluations of other residents' responses (e.g. following mask mandates, social distancing) or local government responses.
Quantitative analyzing the effect of h‐BN on the thermal conductivity of HDPE‐BN composite through multi‐objective optimization
Authors: Ghobadi Maryam , Rahimzadeh Lotfabad Faraz , Zebarjad Seyed Mojtaba , Ebrahimi Ramin
Published: June 2022

The main focus of this investigation is to quantitatively analyze the opposing effect of filler on the desired properties of fabricated composite specimens. First, the high‐density polyethylene (HDPE) powders with proportions of 0, 2, 4, 6, 8, and 10 wt% of boron nitride (BN) are mixed by the ball mill processes and further hot molded to fabricate HDPE‐BN composites. The density and thermal conductivity of fabricated composites are then measured, and the variation of these properties with the added volume percent of BN is determined. The notions of multi‐objective optimization are employed to obtain the optimum BN content to maximize thermal conductivity while minimizing density. The relative importance of these properties is calculated by applying the entropy method to the variation of thermal conductivity and density with the BN content. It is observed that the positive effect of BN on the thermal conductivity has potentially the same importance as its negative effect on the density. In a more general consideration, various hypothetical fillers with a wide range of thermal conductivities and densities are studied by the same procedure. It is obtained that density has a more determinative rule in the efficiency of a particular filler in circumstances where both thermal conductivity and density have practical importance. While the results of this investigation are presented in terms of thermal conductivity and density, the procedure used here can be applied to any set of properties with practical significance.
DoE‐assisted development and validation of a stability‐indicating HPLC‐DAD method for simultaneous determination of five cannabinoids in Cannabis sativa L. based on analytical quality by design (AQbD) concept
Authors: de Souza Maíra Ribeiro , Koetz Mariana , Limberger Renata Pereira , Henriques Amélia Teresinha
Published: June 2022

Introduction

Medical uses of Cannabis sativa L. have gained interest in recent decades, which highlights the need for defining appropriate quality specifications for Cannabis‐based products. However, the complexity of plant matrices and structural similarity between cannabinoids make analytical development a challenging task. Thus, the application of analytical quality by design (AQbD)‐driven approaches can favour the development of fit‐for‐purpose methods.

Objectives

To develop a high‐performance liquid chromatography diode array detector (HPLC‐DAD) method for simultaneous quantification of cannabidiol, Δ9‐tetrahydrocannabinol, cannabidiolic acid, tetrahydrocannabinolic acid, and cannabinol in C. sativa by applying an AQbD‐driven approach.

Materials and Methods

Critical method attributes (CMA) were established following the analytical target profile. Critical method variables (CMV) were categorised based on risk assessment and literature review. Selected CMV regarding sample preparation and chromatographic conditions were optimised using response surface methodology (RSM). The working point was estimated by multiple response optimisation using Deringer's desirability function. The validity of the optimal conditions was confirmed experimentally. Method validation was performed according to ANVISA and ICH guidelines. Relative response factors (RRFs) were also determined.

Results and Discussion

Baseline resolution of 12 major cannabinoids was achieved in a 35 min chromatographic analysis. All experimental responses obtained during confirmatory analyses were within the prediction intervals (PI95%). Method's selectivity, linearity (10–100 μg/mL), precision, bias, extraction recovery, and ruggedness were satisfactorily demonstrated.

Conclusions

The application of an AQbD‐driven approach allowed for a better understanding of the effects of the ensemble of CMV on the analyte's behaviour, enabling the definition of appropriate conditions to ensure consistent achievement of the intended method's performance.
Approaches and hurdles of implementing pharmacogenetic testing in the psychiatric clinic
Authors: Maruf Abdullah Al , Bousman Chad A.
Published: June 2022

Pharmacogenetic (PGx) testing has emerged as a tool for predicting a person's ability to process and react to drugs. Despite the growing evidence‐base, enthusiasm, and successful efforts to implement PGx testing in psychiatry, a consensus on how best to implement PGx testing into practice has not been established and numerous hurdles to widespread adoption remain to be overcome. In this article, we summarize the most used approaches and commonly encountered hurdles when implementing PGx testing into routine psychiatric care. We also highlight effective strategies that have been used to overcome hurdles. These strategies include the development of user‐friendly clinical workflows for test ordering, use, and communication of results, establishment of test standardization and reimbursement policies, and development of tailored curriculums for educating health‐care providers and the public. Although knowledge and awareness of these approaches and strategies to overcome hurdles alone may not be sufficient for successful implementation, they are necessary to ensure the effective spread, scale, and sustainability of PGx testing in psychiatry and other areas of medicine.
MRI in liver cirrhosis
Authors: Alzoubi Osama , Arar Ahmad , Singh Viraj , Erturk Sukru M. , Mozes Ferenc , Pavlides Michael
Published: June 2022

Liver magnetic resonance imaging (MRI) has seen a massive increase in its use over the last decades. Since its first description in the early 1980s, contrast‐enhanced MRI is now the gold standard for the diagnosis of hepatocellular cancer in patients with liver cirrhosis. Techniques like magnetic resonance (MR) elastography and combinations of multiple MR parameters in single scanning protocols are now available and these are opening new possibilities for the assessment of multiple aspects of disease in patients with liver cirrhosis. In this narrative review, we provide an overview of the use of MRI in patients with cirrhosis for the diagnosis of and screening for liver cancer, for the diagnosis of cirrhosis and prediction of long‐term outcomes, and for the evaluation of portal hypertension. With the multitude of techniques now available and the number of cirrhosis aspects that can be assessed by single scans make the study and application of MRI an attractive target in the search for a technique for use in this group of patients that often have to attend for multiple appointments and multiple tests, including invasive investigations.
DRAGON – The German Thermo‐Chemical Code Based on the Becker‐Kistiakowsky‐Wilson Equation of State
Authors: Arnold Werner , Rottenkolber Ernst , Hartmann Thomas
Published: June 2022

With regard to 100th anniversary of the publication of Richard Becker's famous paper on shock waves and detonation, this article highlights today's relevance of Becker's work on what is known as the BKW EOS. The BKW‐based thermo‐chemical code “Dragon” is presented and the development of the insensitive and blast enhanced PBX “KS23” (RDX/Al/HTPB 58/27/15) is taken as an example to demonstrate the application of Dragon in the design of a modern high explosive. The single experimental development steps of KS23 as well as the underlying and supporting theoretical work are described.
Design, synthesis, and biological evaluation of novel berberine derivatives against phytopathogenic fungi
Authors: Zhou Yong , Yang Cheng‐Jie , Luo Xiong‐Fei , Li An‐Ping , Zhang Shao‐Yong , An Jun‐Xia , Zhang Zhi‐Jun , Ma Yue , Zhang Bao‐Qi , Liu Ying‐Qian
Published: June 2022

BACKGROUND

The abuse of chemical fungicides not only leads to toxic residues and resistance in plant pathogenic fungi, but also causes environmental pollution and side effects on in humans and animals. Based on the antifungal activities of berberine, seven different types of berberine derivatives (A1–G1) were synthesized, and their antifungal activities against six plant pathogenic fungi were evaluated (Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, Phytophthora capsici, Sclerotinia sclerotiorum, and Magnaporthe oryzae).

RESULTS

The results for antifungal activities in vitro showed that berberine derivative E1 displayed good antifungal activity against R. solani with a median effective concentration (EC50) of 1.77 μg ml−1, and berberine derivatives F1 and G1 demonstrated broad‐spectrum antifungal activities with EC50 values ranging from 4.43 to 42.23 μg ml−1 against six plant pathogenic fungi. Berberine derivatives (E2–E29, F2–F18, and G2–G9) were further synthesized to investigate the structure–activity relationship (SAR), and compound E20 displayed significant antifungal activity against R. solani with an EC50 value of 0.065 μg ml−1. Preliminary mechanism studies showed that E20 could cause mycelial shrinkage, cell membrane damage, mitochondrial abnormalities and the accumulation of harmful reactive oxygen species, resulting in cell death in R. solani. Moreover, in vivo experimental results showed that the protective effect of E20 was 97.31% at 5 μg ml−1, which was better than that of the positive control thifluzamide (50.13% at 5 μg ml−1).

CONCLUSION

Berberine derivative E20 merits further development as a new drug candidate with selective and excellent antifungal activity against R. solani. © 2022 Society of Chemical Industry.
Robotic single port anti‐reflux surgery: Initial worldwide experience of two cases with a novel surgical approach to treat gastroesophageal reflux disease
Authors: Cubisino Antonio , Dreifuss Nicolas H. , Schlottmann Francisco , Baz Carolina , Mangano Alberto , Masrur Mario A. , Bianco Francesco M.
Published: June 2022

Introduction

To date, no anti‐reflux operations have been reported with the new da Vinci Single‐Port (single port (SP)) robotic platform. We aimed to describe this novel surgical approach and evaluate its safety and feasibility.

Methods

All robotic SP operations were performed under an Institutional Review Board approved protocol.

Results

Two patients underwent robotic SP anti‐reflux surgery through a single incision of 2.7 cm (one Nissen‐fundoplication and one re‐Redo Nissen‐fundoplication). The mean docking‐time was 2.5 (2–3) minutes and mean console‐time was 147 (119–155) minutes. No additional ports were needed, and no intraoperative complications occurred. Patients tolerated a soft diet on postoperative day 1 and were discharged on POD‐2 and 3.

Conclusion

Robotic SP anti‐reflux surgery appears to be safe and feasible. This platform offers similar advantages to the multiport robotic surgery, while adding lower invasiveness and an improved cosmesis. Further studies are needed to confirm our results and evaluate long‐term outcomes of this surgical approach.
4D Printing of Extrudable and Degradable Poly(Ethylene Glycol) Microgel Scaffolds for Multidimensional Cell Culture
Authors: Miksch Connor E. , Skillin Nathaniel P. , Kirkpatrick Bruce E. , Hach Grace K. , Rao Varsha V. , White Timothy J. , Anseth Kristi S.
Published: June 2022

Granular synthetic hydrogels are useful bioinks for their compatibility with a variety of chemistries, affording printable, stimuli‐responsive scaffolds with programmable structure and function. Additive manufacturing of microscale hydrogels, or microgels, allows for the fabrication of large cellularized constructs with percolating interstitial space, providing a platform for tissue engineering at length scales that are inaccessible by bulk encapsulation where transport of media and other biological factors are limited by scaffold density. Herein, synthetic microgels with varying degrees of degradability are prepared with diameters on the order of hundreds of microns by submerged electrospray and UV photopolymerization. Porous microgel scaffolds are assembled by particle jamming and extrusion printing, and semi‐orthogonal chemical cues are utilized to tune the void fraction in printed scaffolds in a logic‐gated manner. Scaffolds with different void fractions are easily cellularized post printing and microgels can be directly annealed into cell‐laden structures. Finally, high‐throughput direct encapsulation of cells within printable microgels is demonstrated, enabling large‐scale 3D culture in a macroporous biomaterial. This approach provides unprecedented spatiotemporal control over the properties of printed microporous annealed particle scaffolds for 2.5D and 3D tissue culture.
The Effects of Water Temperature and Simulated Angling on the Physiological Stress Response of Largemouth Bass
Authors: Dinken Colin P. , Keretz Kevin R. , Schramm Harold L. , Petrie‐Hanson Lora , Schilling M. Wes , Allen Peter J.
Published: June 2022

The Largemouth Bass Micropterus salmoides, a popular sport fish, is subjected to multiple sublethal stressors during angling, including high water temperature, exercise, handling, live‐well retention, and weigh‐in procedures. Combined effects of ambient and live‐well temperatures on the stress response and recovery from angling‐induced exercise have not been tested in conditions similar to those encountered in tournaments. Therefore, we assessed the effects of ambient temperature (17, 25, and 33°C) and live‐well temperature differential (−4, 0, and +4°C) on the physiological stress response of Largemouth Bass (mean length = 331 mm) at rest, following a simulated angling stressor, and throughout 8 h of recovery in live wells. Stress variables were measured in whole blood (hematocrit, hemoglobin, pH, partial pressure of oxygen [pO2], partial pressure of carbon dioxide [pCO2], Na+, K+, Ca2+, Cl−, and leukocytes) and plasma (cortisol, glucose, lactate, and osmolality). Fish acclimated to 17°C showed the greatest cortisol response after the chasing stressor; however, higher levels of glucose, lactate, pCO2, K+, and monocyte percentage were found at 33°C, and blood pH, Cl−, and lymphocyte percentage were lower at 33°C than at 17°C. When live‐well temperature was manipulated, cortisol levels were highest in fish subjected to the coldest conditions (acclimated to 17°C and retained in 13°C and 17°C live wells) and the warmest condition (acclimated to 33°C and retained in 37°C live wells). However, all fish subjected to the colder extremes survived, whereas 100% mortality occurred in the warmest condition. Besides cortisol, indicators of stress were less pronounced at colder temperatures. Glucose, lactate, and notably K+ concentrations were highest in 37°C live wells, and blood pH, Ca2+, Na+, and Cl− were lowest. Low blood lymphocytes and high monocytes at the warmest conditions indicate reduced immunocompetence or inflammation. Mortality at high temperature may result from exhaustion of aerobic and anaerobic energy sources, failure to recover from metabolic acidosis, and an inability to regain ionic balance.