bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain-wide visual habituation networks in wild type and fmr1 zebrafish
Authors: Marquez-Legorreta Emmanuel , Constantin Lena , Piber Marielle , Favre-Bulle Itia A. , Taylor Michael A. , Blevins Ann S. , Giacomotto Jean , Bassett Dani S. , Vanwalleghem Gilles C. , Scott Ethan K.
Published: February 2022

Habituation is a form of learning during which animals stop responding to repetitive stimuli, and deficits in habituation are characteristic of several psychiatric disorders. Due to technical challenges, the brain-wide networks mediating habituation are poorly understood. Here we report brain-wide calcium imaging during larval zebrafish habituation to repeated visual looming stimuli. We show that different functional categories of loom-sensitive neurons are located in characteristic locations throughout the brain, and that both the functional properties of their networks and the resulting behavior can be modulated by stimulus saliency and timing. Using graph theory, we identify a visual circuit that habituates minimally, a moderately habituating midbrain population proposed to mediate the sensorimotor transformation, and downstream circuit elements responsible for higher order representations and the delivery of behavior. Zebrafish larvae carrying a mutation in the fmr1 gene have a systematic shift toward sustained premotor activity in this network, and show slower behavioral habituation.
A non-catalytic scaffolding activity of hexokinase 2 contributes to EMT and metastasis
Authors: Blaha Catherine S. , Ramakrishnan Gopalakrishnan , Jeon Sang-Min , Nogueira Veronique , Rho Hyunsoo , Kang Soeun , Bhaskar Prashanth , Terry Alexander R. , Aissa Alexandre F. , Frolov Maxim V. , Patra Krushna C. , Brooks Robey R. , Hay Nissim
Published: February 2022

Hexokinase 2 (HK2), which catalyzes the first committed step in glucose metabolism, is induced in cancer cells. HK2’s role in tumorigenesis has been attributed to its glucose kinase activity. Here, we describe a kinase independent HK2 activity, which contributes to metastasis. HK2 binds and sequesters glycogen synthase kinase 3 (GSK3) and acts as a scaffold forming a ternary complex with the regulatory subunit of protein kinase A (PRKAR1a) and GSK3β to facilitate GSK3β phosphorylation and inhibition by PKA. Thus, HK2 functions as an A-kinase anchoring protein (AKAP). Phosphorylation by GSK3β targets proteins for degradation. Consistently, HK2 increases the level and stability of GSK3 targets, MCL1, NRF2, and particularly SNAIL. In addition to GSK3 inhibition, HK2 kinase activity mediates SNAIL glycosylation, which prohibits its phosphorylation by GSK3. Finally, in mouse models of breast cancer metastasis, HK2 deficiency decreases SNAIL protein levels and inhibits SNAIL-mediated epithelial mesenchymal transition and metastasis.
CRISPR-assisted rational flux-tuning and arrayed CRISPRi screening of an l-proline exporter for l-proline hyperproduction
Authors: Liu Jiao , Liu Moshi , Shi Tuo , Sun Guannan , Gao Ning , Zhao Xiaojia , Guo Xuan , Ni Xiaomeng , Yuan Qianqian , Feng Jinhui , Liu Zhemin , Guo Yanmei , Chen Jiuzhou , Wang Yu , Zheng Ping , Sun Jibin
Published: February 2022

Development of hyperproducing strains is important for biomanufacturing of biochemicals and biofuels but requires extensive efforts to engineer cellular metabolism and discover functional components. Herein, we optimize and use the CRISPR-assisted editing and CRISPRi screening methods to convert a wild-typeCorynebacterium glutamicumto a hyperproducer ofl-proline, an amino acid with medicine, feed, and food applications. To facilitatel-proline production, feedback-deregulated variants of key biosynthetic enzyme γ-glutamyl kinase are screened using CRISPR-assisted single-stranded DNA recombineering. To increase the carbon flux towardsl-proline biosynthesis, flux-control genes predicted by in silico analysis are fine-tuned using tailored promoter libraries. Finally, an arrayed CRISPRi library targeting all 397 transporters is constructed to discover anl-proline exporter Cgl2622. The final plasmid-, antibiotic-, and inducer-free strain producesl-proline at the level of 142.4 g/L, 2.90 g/L/h, and 0.31 g/g. The CRISPR-assisted strain development strategy can be used for engineering industrial-strength strains for efficient biomanufacturing.
Effects of early-life antibiotics on the developing infant gut microbiome and resistome: a randomized trial
Authors: Reyman Marta , van Houten Marlies A. , Watson Rebecca L. , Chu Mei Ling J. N. , Arp Kayleigh , de Waal Wouter J. , Schiering Irene , Plötz Frans B. , Willems Rob J. L. , van Schaik Willem , Sanders Elisabeth A. M. , Bogaert Debby
Published: February 2022

Broad-spectrum antibiotics for suspected early-onset neonatal sepsis (sEONS) may have pronounced effects on gut microbiome development and selection of antimicrobial resistance when administered in the first week of life, during the assembly phase of the neonatal microbiome. Here, 147 infants born at ≥36 weeks of gestational age, requiring broad-spectrum antibiotics for treatment of sEONS in their first week of life were randomized 1:1:1 to receive three commonly prescribed intravenous antibiotic combinations, namely penicillin + gentamicin, co-amoxiclav + gentamicin or amoxicillin + cefotaxime (ZEBRA study, Trial Register NL4882). Average antibiotic treatment duration was 48 hours. A subset of 80 non-antibiotic treated infants from a healthy birth cohort served as controls (MUIS study, Trial Register NL3821). Rectal swabs and/or faeces were collected before and immediately after treatment, and at 1, 4 and 12 months of life. Microbiota were characterized by 16S rRNA-based sequencing and a panel of 31 antimicrobial resistance genes was tested using targeted qPCR. Confirmatory shotgun metagenomic sequencing was executed on a subset of samples. The overall gut microbial community composition and antimicrobial resistance gene profile majorly shift directly following treatment (R2 = 9.5%, adjustedp-value = 0.001 and R2 = 7.5%, adjustedp-value = 0.001, respectively) and normalize over 12 months (R2 = 1.1%, adjustedp-value = 0.03 and R2 = 0.6%, adjustedp-value = 0.23, respectively). We find a decreased abundance ofBifidobacteriumspp. and increased abundance ofKlebsiellaandEnterococcusspp. in the antibiotic treated infants compared to controls. Amoxicillin + cefotaxime shows the largest effects on both microbial community composition and antimicrobial resistance gene profile, whereas penicillin + gentamicin exhibits the least effects. These data suggest that the choice of empirical antibiotics is relevant for adverse ecological side-effects.
Population antibody responses following COVID-19 vaccination in 212,102 individuals
Authors: Ward Helen , Whitaker Matthew , Flower Barnaby , Tang Sonja N. , Atchison Christina , Darzi Ara , Donnelly Christl A. , Cann Alexandra , Diggle Peter J. , Ashby Deborah , Riley Steven , Barclay Wendy S. , Elliott Paul , Cooke Graham S.
Published: February 2022

Population antibody surveillance helps track immune responses to COVID-19 vaccinations at scale, and identify host factors that may affect antibody production. We analyse data from 212,102 vaccinated individuals within the REACT-2 programme in England, which uses self-administered lateral flow antibody tests in sequential cross-sectional community samples; 71,923 (33.9%) received at least one dose of BNT162b2 vaccine and 139,067 (65.6%) received ChAdOx1. For both vaccines, antibody positivity peaks 4-5 weeks after first dose and then declines. At least 21 days after second dose of BNT162b2, close to 100% of respondents test positive, while for ChAdOx1, this is significantly reduced, particularly in the oldest age groups (72.7% [70.9–74.4] at ages 75 years and above). For both vaccines, antibody positivity decreases with age, and is higher in females and those with previous infection. Antibody positivity is lower in transplant recipients, obese individuals, smokers and those with specific comorbidities. These groups will benefit from additional vaccine doses.
Structure, mechanism and lipid-mediated remodeling of the mammalian Na+/H+ exchanger NHA2
Authors: Matsuoka Rei , Fudim Roman , Jung Sukkyeong , Zhang Chenou , Bazzone Andre , Chatzikyriakidou Yurie , Robinson Carol V. , Nomura Norimichi , Iwata So , Landreh Michael , Orellana Laura , Beckstein Oliver , Drew David
Published: February 2022

The Na+/H+ exchanger SLC9B2, also known as NHA2, correlates with the long-sought-after Na+/Li+ exchanger linked to the pathogenesis of diabetes mellitus and essential hypertension in humans. Despite the functional importance of NHA2, structural information and the molecular basis for its ion-exchange mechanism have been lacking. Here we report the cryo-EM structures of bison NHA2 in detergent and in nanodiscs, at 3.0 and 3.5 Å resolution, respectively. The bison NHA2 structure, together with solid-state membrane-based electrophysiology, establishes the molecular basis for electroneutral ion exchange. NHA2 consists of 14 transmembrane (TM) segments, rather than the 13 TMs previously observed in mammalian Na+/H+ exchangers (NHEs) and related bacterial antiporters. The additional N-terminal helix in NHA2 forms a unique homodimer interface with a large intracellular gap between the protomers, which closes in the presence of phosphoinositol lipids. We propose that the additional N-terminal helix has evolved as a lipid-mediated remodeling switch for the regulation of NHA2 activity.
Activation of the NLRP3 inflammasome and elevation of interleukin-1β secretion in infection by sever fever with thrombocytopenia syndrome virus
Authors: Li Zhifeng , Hu Jianli , Bao Changjun , Gao Chengfeng , Zhang Nan , Cardona Carol J. , Xing Zheng
Published: February 2022

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging phlebovirus that causes a hemorrhagic fever known as the severe fever with thrombocytopenia syndrome (SFTS). Inflammasomes are a molecular platform that are assembled to process pro-caspase 1 and subsequently promote secretion of interleukin (IL)-1β/IL-18 for proinflammatory responses induced upon infection. We hypothesize that inflammasome activation and pyroptosis induced in SFTS results in elevated levels of IL-1β/IL-18 responsible for high fever and hemorrhage in the host, characteristic of SFTS. Here we report that IL-1β secretion was elevated in SFTS patients and infected mice and IL-1β levels appeared to be reversibly associated to disease severity and viral load in patients’ blood. Increased caspase-1 activation, IL-1β/IL-18 secretion, cell death, and processing of gasdermin D were detected, indicating that pyroptosis was induced in SFTSV-infected human peripheral blood monocytes (PBMCs). To characterize the mechanism of pyroptosis induction, we knocked down several NOD-like receptors (NLRs) with respective shRNAs in PBMCs and showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome was critical for processing pro-caspase-1 and pro-IL-1β. Our data with specific inhibitors for NLRP3 and caspase-1 further showed that activation of the NLRP3 inflammasome was key to caspase-1 activation and IL-1β secretion which may be inhibitory to viral replication in PBMCs infected with SFTSV. The findings in this study suggest that the activation of the NLPR3 inflammasome and pyroptosis, leading to IL-1β/IL-18 secretion during the SFTSV infection, could play important roles in viral pathogenesis and host protection. Pyroptosis as part of innate immunity might be essential in proinflammatory responses and pathogenicty in humans infected with this novel phlebovirus.
Mathematical model analysis and numerical simulation for codynamics of meningitis and pneumonia infection with intervention
Authors: kotola Belela Samuel , Mekonnen Temesgen Tibebu
Published: February 2022

In this paper, we have considered a deterministic mathematical model to analyze effective interventions for meningitis and pneumonia coinfection as well as to make a rational recommendation to public healthy, policy or decision makers and programs implementers. We have introduced the epidemiology of infectious diseases, the epidemiology of meningitis, the epidemiology of pneumonia, and the epidemiology of infection of meningitis and pneumonia. The positivity and boundedness of the sated model was shown. Our model elucidate that, the disease free equilibrium points of each model are locally asymptotically stable if the corresponding reproduction numbers are less than one and globally asymptotically stable if the corresponding reproduction numbers are greater than one. Additionally, we have analyzed the existence and uniqueness of the endemic equilibrium point of each sub models, local stability and global stability of the endemic equilibrium points for each model. By using standard values of parameters we have obtained from different studies, we found that the effective reproduction numbers of meningitis $${\mathcal{R}}_{eff(m)}=9$$

R

e
f
f
(
m
)

=
9

and effective reproduction numbers of pneumonia $${\mathcal{R}}_{eff(p)}=11$$

R

e
f
f
(
p
)

=
11

that lead us to the effective reproduction number of the meningitis and pneumonia co-infected model is $$max\left\{ {\mathcal{R}}_{eff\left(m\right)}, {\mathcal{R}}_{eff(p)} \right\}=9$$

m
a
x

R

e
f
f

m

,

R

e
f
f
(
p
)

=
9

. Applying sensitivity analysis, we identified the most influential parameters that can change the behavior of the solution of the meningitis pneumonia coinfection dynamical system are $${\alpha }_{1} , {\alpha }_{2}$$

α
1

,

α
2

and $$\pi$$
π
. Biologically, decrease in $${\alpha }_{1}$$

α
1

and increasing in $$\pi$$
π
is a possible intervention strategy to reduce the infectious from communities. Finally, our numerical simulation has shown that vaccination against those diseases, reducing contact with infectious persons and treatment have the great effect on reduction of these silent killer diseases from the communities.
Chemical properties of the coffee grounds and poultry eggshells mixture in terms of soil improver
Authors: Tombarkiewicz Barbara , Antonkiewicz Jacek , Lis Marcin W. , Pawlak Krzysztof , Trela Magdalena , Witkowicz Robert , Gorczyca Olga
Published: February 2022

Spent coffee grounds (SCG) as well as chicken (CES) or duck eggshells (DES) left over from the artificial hatching technology are proposed as potential soil improver and/or organic-mineral fertiliser components. Therefore, it seems interesting and necessary to evaluate the chemical composition of these wastes and their mixtures in terms of their possible use for that purpose. The study was conducted under the incubation experiment conditions using a mixture of SCG and eggshells (10:1 ratio). Macronutrients, i.e. C, N, S, were determined by the catalytic combustion method, while P, K, Mg, Ca, Na by atomic spectrometry. It was found that SCG were rich in C, N, P, and K, while eggshells in Ca, Mg, Na, and S. However, CES compared to DES were richer in deacidifying components (i.e. Ca, Mg, K). At the same time, the content of macronutrients in eggshells decreased gradually along with the embryo development. For this reason, the mixture of SCG and shells of unembryonated chicken eggs (CES I) had the best chemical and usable proprieties. To conclude, the chemical properties of the mixtures of spent coffee grounds and eggshells indicate their possible application in soil bioengineering.
Quantitative determination of cation–π interactions between metal ions and aromatic groups in aqueous media by a hydrogel Donnan potential method
Authors: Fan Hailong , Guo Honglei , Kurokawa Takayuki , Gong Jian Ping
Published: February 2022

The binding ratios of various metal ions to aromatic groups by cation–π interactions in aqueous media have been quantitatively calculated by using Donnan potential measurements.
Cationic peptides template the assembly of polyoxometalates into ultrathin nanosheets with in-plane ordered arrangements
Authors: Xie Xiaoming , Liu Xiaohuan , Ma Zhiyuan , Zhao He , Li Wen
Published: February 2022

2D POM nanosheets with an in-plane alignment were constructed using β-sheet peptides as versatile templates, and different POMs varying in topology, size, and charges could be templated into ordered nanostructures.
Bioactivity-guided isolation of the major anthocyanin fromLycium ruthenicumMurr. fruit and its antioxidant activity and neuroprotective effectsin vitroandin vivo
Authors: Chen Shasha , Hu Na , Wang Honglun , Wu Yongning , Li Guoliang
Published: February 2022

Pn3G5G was isolated fromLycium ruthenicumMurr. fruit. It exerted neuroprotective effects by suppressing oxidative stress-mediated inflammation and apoptosis in CML-induced Neuro-2a cells andd-galactose-induced aging mice.
Excitation and ionization processes of chlorine in molybdenum dichloride dioxideflakesusing the glow discharge mass spectrometry technique
Authors: Mushtaq Sohail
Published: February 2022

This article reports a novel observation of enhanced ionization of chlorine in MoCl2O2and provides an interesting explanation for this enhancement that involves an asymmetric charge exchange in the presence of oxygen.
Undifferentiated destruction of mitochondria by photoacoustic shockwave to overcome chemoresistance and radiation resistance in cancer therapy
Authors: Liu Liming , Zeng Fanchu , Li Yujie , Li Wenjing , Yu Hui , Zeng Qingxing , Chen Qun , Qin Huan
Published: February 2022

The nanoparticle ICG/DSPE-PEG-TPP efficiently targeted the mitochondria in both parental and its corresponding resistant tumor cells.
A molecular simulation study into the stability of hydrated graphene nanochannels used in nanofluidics devices
Authors: Williams Christopher D. , Wei Zixuan , Shaharudin Mohd Rafie bin , Carbone Paola
Published: February 2022

Molecular dynamics simulations were used to assess the stability of hydrated graphene nanochannels, revealing the presence of liquid monolayer inside the narrowest channels.
Multivalent non-covalent interactions lead to strongest polymer adhesion
Authors: Lallemang Max , Yu Leixiao , Cai Wanhao , Rischka Klaus , Hartwig Andreas , Haag Rainer , Hugel Thorsten , Balzer Bizan N.
Published: February 2022

Multivalent interactions are quantified using AFM-based single molecule force spectroscopy showing that non-covalent interactions are ideal candidates to mediate robust adhesion.
Magnetic field responsive microspheres with tunable structural colors by controlled assembly of nanoparticles
Authors: Shang Shenglong , Zhang Kaiqi , Hu Huifang , Sun Xiaoran , Liu Jie , Ni Yanpeng , Zhu Ping
Published: February 2022

An efficient strategy was used for the preparation of magneto-chromatic microspheres with tunable structural color.
Ion beam-induced bending of TiO2 nanowires with bead-like and prismatic shapes
Authors: Razaghi Zhina , Xie Dong Yue , Lin Ming-hui , Zhu Guo-zhen
Published: February 2022

TiO2 nanowires with prismatic shape, show significant bending under an ion beam, compared to those with a bead-like shape.
Fabrication and functionalization of biocompatible carboxymethyl chitosan/gelatin membranesviaanodic electrophoretic deposition
Authors: Wang Fushi , Qiao Weiwei , Guo Weiting , Li Zhiwen , Cai Xinjie
Published: February 2022

A biocompatible CMC/G membrane for titanium substrates has been fabricated in an eco-friendly manner and could be a promising carrier for negatively charged agents.
Self-supported amorphous TaNx(Oy)/nickel foam thin film as an advanced electrocatalyst for hydrogen evolution reaction
Authors: Thiyagarajan Ganesh Babu , Mukkavilli Raghunath Sharma , Graf David , Fischer Thomas , Wilhelm Michael , Christiansen Silke , Mathur Sanjay , Kumar Ravi
Published: February 2022

Enhanced electrocatalytic hydrogen evolution attributed to the synergistic effect between the amorphous TaNx(Oy) film (Volmer–Hevroysky Reaction, VHR) and the nickel foam (Volmer Reaction, VR).
Dynamical component exchange in a model phase separating system: an NMR-based approach
Authors: Pantoja Christian F. , Zweckstetter Markus , Rezaei-Ghaleh Nasrollah
Published: February 2022

NMR-based exchange spectroscopy enables monitoring the partitioning of scaffold and client molecules during liquid–liquid phase separation (LLPS) of triethylamine.
Designing for simplicity: lessons from Mesa Biotech for microfluidic entrepreneurs and early-stage companies
Authors: Greenleaf Morgan N. , Damhorst Gregory L. , Ku David N. , Nehl Eric J. , Tyburski Erika A. , Brand Oliver , Martin Greg S. , Lam Wilbur A.
Published: February 2022

The COVID-19 pandemic has proven the need for point-of-care diagnosis of respiratory diseases and microfluidic technology has risen to the occasion.
Correction: Thermal response and thermochromism of methyl red-based copolymer systems – coupled responsiveness in critical solution behaviour and optical absorption properties
Authors: Jaik Thorben Gwydion , Ciubini Betty , Frascella Francesca , Jonas Ulrich
Published: February 2022

Correction for ‘Thermal response and thermochromism of methyl red-based copolymer systems – coupled responsiveness in critical solution behaviour and optical absorption properties’ by Thorben Gwydion Jaik et al., Polym. Chem., 2022, DOI: 10.1039/D1PY01361K.
Correction: Thermal, mechanical investigation and neutron shielding analysis for Gd-MOF/polyimide materials
Authors: Hu Chen , Huang Qunying , Zhai Yutao
Published: February 2022

Correction for ‘Thermal, mechanical investigation and neutron shielding analysis for Gd-MOF/polyimide materials’ by Chen Hu et al., RSC Adv., 2021, 11, 40148–40158. DOI: 10.1039/D1RA07500D.
Mixing fraction in classical novae
Authors: Guo Yunlang , Wu Chengyuan , Wang Bo
Published: February 2022

Context. Classical novae are powered by thermonuclear runaways occurring on the surface of accreting white dwarfs (WDs). In the observations, the enrichments of heavy elements in nova ejecta have been detected, indicating a mixing process between the accreted matter and the matter from the outer layers of the underlying WDs prior to nova outbursts. However, the mixing fraction in classical novae is still uncertain.

Aims. The purpose of this article is to investigate some elemental abundance ratios during nova outbursts that can be used to estimate the WD mixing fraction in classical novae.

Methods. By considering different WD mixing fractions with the stellar evolution code Modules for Experiments in Stellar Astrophysics, we carried out a series of simulations of nova outbursts, in which the initial CO WD masses range from 0.7−1.0 M⊙.

Results. We identified four elemental abundance ratios (i.e. (H + He)/∑CNO, (H + He)/Ne, ∑CNO/Mg, and ∑CNO/Si) that satisfy the conditions for determining the WD mixing fraction, in which (H + He)/∑CNO is the most suitable mixing meter. We also estimated the WD mixing fraction in some representative classical novae. Additionally, we found that a higher metallicity (i.e. higher WD mixing fraction) is preferentially accompanied by a longer t2 (the time of decline by two magnitudes from peak luminosity) during nova outbursts. Our results can be used to constrain the mixing process in classical novae.
Magnetic field evolution around a fast-moving pore emerging from the quiet Sun
Authors: Xu Zhe , Ji Haisheng , Hong Junchao , Ji Kaifan , Yang Jiayan
Published: February 2022

Context. Solar pores are intense concentrations of magnetic fields on the solar surface and plasma flows have always played a key role in spurring the evolution of the pores.

Aims. In this study, we present the evolution of the magnetic field and plasma velocity around a fast-moving pore. The target pore expands into the quiet Sun area with a sufficiently fast speed after its emergence, while the background magnetic fields around the pore are simple. These characteristics provide us with an excellent opportunity to study the interaction between plasma motions and ambient magnetic fields.

Methods. We analyzed the Helioseismic and Magnetic Imager (HMI) vector magnetograms with a pixel size of 0.5″ and a temporal cadence of 12 min across a duration of 11 h. We also adopted he HMI dopplergrams present the line-of-sight velocities. The horizontal flow fields were obtained using the Differential Affine Velocity Estimator for Vector Magnetograms method.

Results. Pure horizontal magnetic fields are generated in the moving frontwards when the pore is subject to fast movement. The generated magnetic fields occur outside the emerging site and thus can be ruled out as the emerging flux from the interior. Instead, they are highly correlated with the broader downflows and expanding horizontal plasma motions in front of the pore. A magnetic gap can be observed between the magnetic fields inside and outside the pore. The temporal evolution of the generated magnetic fields is related to the speed of the pore, which is also distinguished from the original fields within the pore.

Conclusions. The observations suggest that the plasma flows driven by the fast proper motion of the pore compress and stretch the local magnetic field to a horizontal non-radial direction, ultimately leading to the magnetic field amplification in the front part of the moving pore.
Research progress on granulation process of iron and steel slag
Authors: Lin WenLong , Wang Hui , Liu DongHui , Xing HongWei , Liu Chao , Zhang YuZhu , Li Shuo
Published: February 2022

Efficient utilization of iron and steel slag is one of the important measures to achieve peak carbon emissions and carbon neutrality in the iron and steel industry. Improving the recycling rate of iron and steel slag has become an urgent problem to be solved by scholars and enterprises at home and abroad. Therefore, it is of great significance to continuously optimize the recycling process of iron and steel slag and waste heat recovery technology. By comparing and analyzing the advantages and disadvantages of different granulation processes for iron and steel slag, the disadvantages of using dry or wet granulation processes alone for iron and steel slag are pointed out in this paper. Then, a combined granulation process mode combining dry and wet processes is proposed to improve the processing efficiency of molten slag. The increase in resource conversion rate and the quality of granulated slag after primary granulating of iron and steel slag contribute to reducing the amount of slag to be treated secondarily. Furthermore, the energy consumption and pollutant emissions of slag secondary treatment will be decreased as well. It is intended to provide a reference for slag treatment technology and slag utilization rate expansion in iron and steel enterprises.
Tätowierung durch intradermale Hauttests mit farbstoffhaltigen Medikamenten
Authors: Bircher Andreas J. , Scherer Hofmeier Kathrin
Published: February 2022

Bei zwei Individuen, einem 72-jährigen Patienten und einer 20-jährigen Kontrollprobandin, wurde bei der Durchführung von Hauttests mit farbigen Medikamenten eine iatrogene Tätowierung verursacht. Der Patient hatte eine anaphylaktische Reaktion auf ein Eisenpräparat erlitten, und es bestand die zwingende Indikation für eine erneute intravenöse Eisensubstitution. Deshalb wurden weiterführende Abklärungen inklusive Hauttests durchgeführt. Die zweite Tätowierung erfolgte im Rahmen einer Studie zur Evaluation des irritativen Potenzials von Intradermaltests mit Isosulfanblau, einem diagnostischen Farbstoff. In beiden Fällen war vorab eine Einverständniserklärung bzw. ein Ethikvotum eingeholt worden, sodass es zu keinen weiteren rechtlichen Konsequenzen kam.
Desires and attitudes of outpatients and physicians regarding the use of teleurology during the pandemic: a prospective survey study
Authors: Karabulut Ibrahim , Demirdogen Saban Oguz , Ramazanoglu Mehmet Akif , Sam Emre , Cinislioglu Ahmet Emre , Al Salih , Altay Mehmet Sefa , Yilmazel Fatih Kursat , Bicaklioglu Fatih , Aydin Hasan Riza , Adanur Senol
Published: February 2022

Objective: It is not known to date how many patients admitted to
urology outpatient clinics are willing to use telemedicine. We aimed to investigate knowledge
levels and attitudes concerning the utilization of teleurology by patients applying to urology
outpatient clinics.

Methods: This prospective multicentre survey study included 334 patients aged 18–65
years who applied to an urology outpatient clinics. The patients were asked questions about
their attitudes and expectations regarding teleurology. Diseases were divided into seven
subgroups due to the broad spectrum of diagnoses. Physicians’ and patients’ opinions on
whether it was possible to manage the current medical condition via teleurology were recorded.

Results: 69.5% of patients stated that they had sufficient technical skills to use teleurology
by themselves for medical examination. 55.4% of patients and 78.4% of physicians responded
that the existing complaints were suitable for teleurology. Both patients and physicians
deemed genital system diseases and urinary tract infections suitable for teleurology
(p<0.001, p<0.001 for physicians, and p<0.001, p<0.001 for patients), whereas
urine transport, storage and emptying disorders (p=0.003) and benign prostatic hyperplasia
(p=0.029) were deemed to be suitable for teleurology only by the physicians.

Conclusion: Our
study shows that (i) the majority of our patient population has a telecommunications
infrastructure suitable for teleurology, (ii) teleurology has aroused interest among patients,
particularly during the pandemic period, and (iii) physicians and patients have high
expectations that the problem can be solved with teleurology in suitable patients.
Psychotherapeutische
Aspekte psychoemotionaler
Störungen
Authors: Pelz Holger
Published: February 2022

Psychoemotionale Störungen, v. a. nach ICD 10 F45, werden
psychotherapeutisch behandelt. Für stresserzeugende somatoforme
Verarbeitungsmodi von Betroffenen bieten sich multimodale leiborientierte Konzepte
und nicht nur rein körperpsychotherapieorientierte Vorgehensweisen in der
Behandlung an, damit dysfunktionale emotionale Ausdrücke psychisch
kohärent mit Emotionen neu verknüpft werden können.
Liebe Leserinnen, liebe Leser,
Authors: Kamp Rainer
Published: February 2022

auch wenn wir wissen, dass die Tage wieder länger werden, so hat sie uns doch
noch voll im Griff: die dunkle Jahreszeit. Irgendwie schlägt sie uns aufs
Gemüt – dem einen mehr, dem anderen weniger. Deshalb kommen wir
gerne dem Wunsch nach, just zu diesem Zeitpunkt das Thema der emotionalen
Störungen in der AkupunkturPraxis von verschiedenen Seiten aus zu
beleuchten.
Kurzzeiteffekte und Akzeptanz einer Intervention für
drogenabhängige Eltern: Das „SHIFT PLUS“
Elterntraining
Authors: Dyba Janina , Moesgen Diana , Grimmig Luisa , Köhler Thorsten , Klein Michael
Published: February 2022

Hintergrund Eltern mit einer Drogenabhängigkeit sind
häufig in ihren elterlichen Kompetenzen eingeschränkt. Die
Lebenswelt von Kindern, die in suchtbelasteten Familien aufwachsen, ist oft
prekär, insbesondere wenn diese von der Drogensubkultur geprägt
ist. Gleichzeitig stehen für Mütter und Väter mit
Drogenproblemen in Deutschland keine evidenzbasierten, standardisierten
Interventionen zur Verfügung.

Methode Mit SHIFT PLUS wurde ein modularisiertes Gruppenprogramm
für drogenabhängige Eltern mit Kindern bis 8 Jahren entwickelt,
welches ihre Elternkompetenzen und die Familienresilienz stärken sowie
ihre Bereitschaft bzw. Fähigkeit zur Abstinenz fördern soll. Das
Training basiert auf dem bestehenden „SHIFT“-Elterntraining
für Crystal Meth-konsumierende Eltern und wurde für den gesamten
Bereich der Abhängigkeit von illegalen Substanzen erweitert sowie um
Module für Angehörige ergänzt. Die Umsetzung des
Programms erfolgte an acht Praxisstandorten im Bundesgebiet in Kooperation von
Sucht- und Jugendhilfeeinrichtungen mit N=87 teilnehmenden Eltern. Zur
Evaluation der kurzzeitigen Wirkeffekte wurde ein quasi-experimentelles
Forschungsdesign mit Interventions- und Wartekontrollgruppe zu zwei
Messzeitpunkten realisiert. Ergänzend wurden Akzeptanz und
Praktikabilität durch Teilnehmende und Trainer/innen
bewertet.

Ergebnisse Das SHIFT PLUS-Elterntraining zeigte sich als praktikabel und
hoch akzeptiert von teilnehmenden Müttern und Vätern, die
berichteten familiäre Herausforderungen subjektiv besser
bewältigen zu können. Die Wirksamkeitsevaluation zeigte zudem
eine signifikante Reduktion depressiver Symptome in der IG sowie einen
signifikant besseren Umgang mit dem Thema Sucht in der Familie.
Ergänzend verbesserten sich beide Gruppen hinsichtlich psychischer
Belastungen, Substanzkonsum und Elternkompetenz.

Schlussfolgerung Die Intervention bietet eine innovative Ergänzung
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elterlicher Fähigkeiten und familiärer Resilienz unter
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Hilfesystem.
Chrysene-Cored Fluorescent Dendrimers as Nondoped Deep-Blue Emitters for Solution-Processable Electroluminescent Devices
Authors: Promarak Vinich , Chatsirisupachai Jirat , Sudyoadsuk Taweesak , Namuangrak Supawadee
Published: February 2022

New solution-processable chrysene-basked deep-blue fluorescent dendrimers consisting of chrysene as a core end-capped by carbazole dendrons were designed, synthesized, and characterized. These dendrimers exhibit strong deep-blue emissions in solution or thin-film states with decent hole mobility and high thermal and electrochemical stability. They can be effectively used as nondoped emitters in organic light-emitting diodes (OLEDs). The nondoped OLEDs, which have a simple structure, showed good electroluminescence (EL) performance (luminance: 2334–2400 cd m–2; external quantum efficiency: 1.88-2.51%; turn-on voltage: 3.8–4.0 V) and deep-blue EL spectra (CIE y: 0.065–0.075) with a narrow full width at half maximum of 61–65 nm.
Katacine Is a New Ligand of CLEC-2 that Acts as a Platelet Agonist
Authors: Morán Luis A. , Di Ying , Sowa Marcin A. , Hermida-Nogueira Lidia , Barrachina María N. , Martin Eleyna , Clark Joanne C. , Mize Todd H. , Eble Johannes A. , Moreira David , Pollitt Alice Y. , Loza María I. , Domínguez Eduardo , Watson Steve P. , García Ángel
Published: February 2022

Background CLEC-2 is a platelet receptor with an important role in thromboinflammation but a minor role in hemostasis. Two endogenous ligands of CLEC-2 have been identified, the transmembrane protein podoplanin and iron-containing porphyrin hemin, which is formed following hemolysis from red blood cells. Other exogenous ligands such as rhodocytin have contributed to our understanding of the role of CLEC-2.

Objectives To identify novel CLEC-2 small-molecule ligands to aid therapeutic targeting of CLEC-2.

Methods ALPHA screen technology has been used for the development of a high-throughput screening (HTS) assay recapitulating the podoplanin–CLEC-2 interaction. Light transmission aggregometry was used to evaluate platelet aggregation. Immunoprecipitation and western blot were used to evaluate direct phosphorylation of CLEC-2 and downstream protein phosphorylation. Autodock vina software was used to predict the molecular binding site of katacine and mass spectrometry to determine the polymeric nature of the ligand.

Results and Conclusion We developed a CLEC-2–podoplanin interaction assay in a HTS format and screened 5,016 compounds from a European Union-open screen library. We identified katacine, a mixture of polymers of proanthocyanidins, as a novel ligand for CLEC-2 and showed that it induces platelet aggregation and CLEC-2 phosphorylation via Syk and Src kinases. Platelet aggregation induced by katacine is inhibited by the anti-CLEC-2 monoclonal antibody fragment AYP1 F(ab)′2. Katacine is a novel nonprotein ligand of CLEC-2 that could contribute to a better understanding of CLEC-2 activation in human platelets.
Asymmetric Total Synthesis of Ventilanones A and B, Two Naturally Occurring Pyranonaphthoquinones from Ventilago harmandiana
Authors: Reutrakul Vichai , Deelertpaiboon Pramchai , Kongsriprapan Sopanat , Krajangsri Suppachai , Betterley Nolan M. , Kuhakarn Chutima
Published: February 2022

The asymmetric synthesis of the novel pyranonaphthoquinones ventilanone A and ventilanone B, isolated from the Thai endemic plant Ventilago harmandiana, is accomplished by employing l-rhamnose and gallic acid as the starting materials. The key reactions are the utilization of a newly introduced reagent, PhSCF2H/SnCl4, for the formyl­ation of sterically hindered aromatics containing an electron-withdrawing methyl ester, and the efficient Hauser annulation of phenyl­thiophthalides with optically active C-1 glycals derived from l-rhamnose. The developed synthetic methodologies solve the long-standing problem of the formylation of sterically hindered aromatics containing electron-withdrawing groups, and are applicable for the synthesis of other analogues with substituents on the aromatic and pyran rings.
Palladium-Catalyzed Intermolecular Carbonylation-Based Difunctionalization of Alkenes
Authors: Liu Guosheng , Tian Bing , Chen Pinhong
Published: February 2022

The palladium(II)-catalyzed carbonylation of alkenes presents one of most efficient methods for the synthesis of alkyl-substituted carbonyls and has received much attention. In this Account, we summarize our recent studies on the palladium-catalyzed intermolecular carbonylation-based 1,2-difunctionalization of alkenes, in which two strategies were involved: (1) a cooperative strategy involves the sequential iodine(III)-mediated alkene activation and palladium-catalyzed carbonylation, leading to the intermolecular β-oxy-, fluoro-, and azidocarbonylation of alkenes; (2) the classic strategy initiated by intermolecular nucleopalladation and carbonylation, including the asymmetric oxycarbonylation of alkenes. These methods provide a series of efficient approaches to synthesize β-functionalized aliphatic carboxylic derivatives.

1 Introduction

2 A Cooperative Strategy Involving Iodine(III)-Mediated Alkene Activation and Palladium-Catalyzed Carbonylation

2.1 Intermolecular Oxycarbonylation of Alkenes

2.2 Intermolecular Fluorocarbonylation of Alkenes

2.3 Intermolecular Azidocarbonylation of Alkenes

3 Intermolecular Aminocarbonylation of Alkenes Initiated by Aminopalladation

4 Intermolecular Arylcarbonylation of Alkenes Initiated by Arylpalladation

5 Intermolecular Enantioselective Oxycarbonylation of Alkenes Initiated by Oxypalladation

6 Conclusion
Survey of New, Small-Molecule Isatin-Based Oxindole Hybrids as Multi-Targeted Drugs for the Treatment of Alzheimer’s Disease
Authors: Marques Carolina S. , López Óscar , Leitzbach Luisa , Fernández-Bolaños José G. , Stark Holger , Burke Anthony J.
Published: February 2022

In the last decade, our group has been very active at developing and assaying complex libraries of scaffolds with a focus on their potential to identify bioactive drug candidates for neurodegenerative diseases, particularly Alzheimer’s disease (AD). Attention has been focused on isatin-based oxindole scaffolds, for which promising results concerning butyrylcholinesterase (BuChE) inhibitory activity have previously been obtained. Considering some published reports and detailed analysis of the pharmacophores of commercially available drugs for AD (powerful cholinesterase (ChE) inhibitors), we performed a strategic structural modification of the isatin core and generated a new family of isatin-based oxindole hybrids (27 new compounds) possessing crucial key functional units in their framework. The syntheses were accomplished using multiple approaches, including simple N-alkylation reactions, copper-catalyzed amination reactions, and click chemistry. The resulting library was evaluated on ChE and MAO enzymes, both of which are involved in the pathophysiology of neurodegeneration. IC50 values of 1.6 and 2.6 μM (BuChE assays), were achieved for the best inhibitors.
Soft Tissue Sarcomas with Special Reference to Molecular Aberration, Chemotherapy, and Recent Advances: A Review Article
Authors: Jacob Linu Abraham , A. Sreevalli , Ninutha Shwetha , Dasappa Lokanatha , MC Suresh Babu , KN Lokesh , AH Rudresha , LK Rajeev , Saldanha Smitha
Published: February 2022

Soft tissue sarcomas (STS) are a diverse group of rare solid tumors of mesenchymal cell origin with distinct clinical and pathological features. They account for less than 1% of all adult malignancies and 15% of pediatric neoplasms. They include over hundreds of different histological subtypes. Many of these subtypes can occur at any age and are not confined to a specific site. Each subtype displays variable clinical behavior. Low incidence, variable presentation, behavior, and long-term outcomes further make it challenging to treat. There are multiple ongoing trials that focus on the anatomic site and histologic subtype to tailor the treatment. Further rarity of each histotype is a major barrier to recruit patients to randomized controlled trials. A multidisciplinary approach is mandatory in all cases of soft tissue sarcomas.

The purpose of this review is to thoroughly understand the existing literature on history, incidence, epidemiology, etiology, histology, pathogenesis, diagnostic modalities, prognosis, management, and post treatment surveillance of STS. Uterine sarcomas, gastrointestinal stromal tumors (GIST), and pediatric sarcomas are not included here. It briefly highlights various molecular aberrations, changes in staging as per the American Joint Committee on Cancer (AJCC) 8, drugs that are used off-label in specific subtypes of sarcoma along with the recent advances. The classification of STS is undergoing continuous evolution. A wide variety of subtypes can only be diagnosed accurately with sophisticated molecular diagnostic tests and with the involvement of expert geneticists and pathologists to interpret it.

There is no clarity on tailoring the treatment of STS to date. There is always a question on how best we can incorporate chemotherapy and radiotherapy along with surgery as a part of multimodality treatment. The heterogeneity of STS has hindered the development of robust, evidence-based treatment strategies, and our therapeutic approach is neither histology-specific nor widely standardized. Increased knowledge about sarcoma biology could help to discover new and more effective treatment strategies and help overcome the therapeutic challenge imposed by this deadly disease. Continued collaboration among various sarcoma centers globally will be of prime importance to optimize STS management. This will allow studies to be both sufficiently large and reasonably focused to generate evidence that is clinically meaningful in specific STS patient populations.
A Graphical Toolkit for Longitudinal Dataset Maintenance and Predictive Model Training in Health Care
Authors: Bai Eric , Song Sophia L. , Fraser Hamish S. F. , Ranney Megan L.
Published: February 2022

Background Predictive analytic models, including machine learning (ML) models, are increasingly integrated into electronic health record (EHR)-based decision support tools for clinicians. These models have the potential to improve care, but are challenging to internally validate, implement, and maintain over the long term. Principles of ML operations (MLOps) may inform development of infrastructure to support the entire ML lifecycle, from feature selection to long-term model deployment and retraining.

Objectives This study aimed to present the conceptual prototypes for a novel predictive model management system and to evaluate the acceptability of the system among three groups of end users.

Methods Based on principles of user-centered software design, human-computer interaction, and ethical design, we created graphical prototypes of a web-based MLOps interface to support the construction, deployment, and maintenance of models using EHR data. To assess the acceptability of the interface, we conducted semistructured user interviews with three groups of users (health informaticians, clinical and data stakeholders, chief information officers) and evaluated preliminary usability using the System Usability Scale (SUS). We subsequently revised prototypes based on user input and developed user case studies.

Results Our prototypes include design frameworks for feature selection, model training, deployment, long-term maintenance, visualization over time, and cross-functional collaboration. Users were able to complete 71% of prompted tasks without assistance. The average SUS score of the initial prototype was 75.8 out of 100, translating to a percentile range of 70 to 79, a letter grade of B, and an adjective rating of “good.” We reviewed persona-based case studies that illustrate functionalities of this novel prototype.

Conclusion The initial graphical prototypes of this MLOps system are preliminarily usable and demonstrate an unmet need within the clinical informatics landscape.
Diagnosis and Management of Invasive Candida Infections in Critically Ill Patients
Authors: Zakhem Aline El , Istambouli Rachid , Jabbour Jean-Francois , Hindy Joya-Rita , Gharamti Amal , Kanj Souha S.
Published: February 2022

Invasive candidiasis (IC) has become a serious problem in the intensive care unit patients with an attributable mortality rate that can reach up to 51%. Multiple global surveillance studies have shown an increasing incidence of candidemia. Despite their limited sensitivity (21–71%), cultures remain the gold standard for the diagnosis of IC associated with candidemia. Many adjunct laboratory tests exist to support or rule out the diagnosis, each with its indications and limitations, including procalcitonin, 1,3-β-D-glucan, mannan and anti-mannan antibodies, and Candida albicans germ tube antibody. In addition, polymerase chain reaction-based methods could expedite species identification in positive blood cultures, helping in guiding early empirical antifungal therapy. The management of IC in critically ill patients can be classified into prophylactic, preemptive, empiric, and directed/targeted therapy of a documented infection. There is no consensus concerning the benefit of prophylactic therapy in critically ill patients. While early initiation of appropriate therapy in confirmed IC is an important determinant of survival, the selection of candidates and drug of choice for empirical systemic antifungal therapy is more controversial. The choice of antifungal agents is determined by many factors, including the host, the site of infection, the species of the isolated Candida, and its susceptibility profile. Echinocandins are considered initial first-line therapy agents. Due to the conflicting results of the various studies on the benefit of preemptive therapy for critically ill patients and the lack of robust evidence, the Infectious Diseases Society of America (IDSA) omitted this category from its updated guidelines and the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) do not recommend it.