bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assembly of pH‐Responsive Antibody‐Drug‐Inspired Conjugates
Authors: Raabe Marco , Heck Astrid Johanna , Führer Siska , Schauenburg Dominik , Pieszka Michaela , Wang Tao , Zegota Maksymilian Marek , Nuhn Lutz , Ng David Y. W. , Kuan Seah Ling , Weil Tanja 
Published: November 2021

AbstractWith the advent of chemical strategies that allow the design of smart bioconjugates, peptide‐ and protein‐drug conjugates are emerging as highly efficient therapeutics to overcome limitations of conventional treatment, as exemplified by antibody‐drug conjugates (ADCs). While targeting peptides serve similar roles as antibodies to recognize overexpressed receptors on diseased cell surfaces, peptide‐drug conjugates suffer from poor stability and bioavailability due to their low molecular weights. Through a combination of a supramolecular protein‐based assembly platform and a pH‐responsive linker, the authors devise herein the convenient assembly of a trivalent protein‐drug conjugate. The conjugate should ideally possess distinct features of ADCs such as 1) recognition sites that recognize cell receptor and are arranged on 2) distinct locations on a high molecular weight protein scaffold, 3) a stimuli‐responsive linker, as well as 4) an attached payload such as a drug molecule. These AD‐like conjugates target cancer cells that overexpress somatostatin receptors, can enable controlled release in the microenvironment of cancer cells through a new pH‐responsive biotin linker, and exhibit stability in biological media.
Effect of Bulky Atom Substitution on Backbone Coplanarity and Electrical Properties of Cyclopentadithiophene‐Based Semiconducting Polymers
Authors: Park Sohee , Kim Yejin , Choi Changwon , Ahn Hyungju , Park Taemin , Lee Seoung Ho , Jang Yun Hee , Lee Byoung Hoon 
Published: November 2021

AbstractThe effect of atomic substitution on the optoelectronic properties of a coplanar donor–acceptor (D–A) semiconducting polymer (SPs), prepared using cyclopentadithiophene (CDT) and 2,1,3‐benzothiadiazole (BT) moieties, is investigated. By substituting a carbon atom in the BT unit with CF or C–Cl, two random D–A SPs are prepared, and their optoelectronic properties are thoroughly investigated. Density functional theory calculations demonstrate that the fluorinated polymer has a slightly smaller dihedral angle (ϴ = 0.6°) than the pristine polymer (ϴ = 1.9°) in its lowest‐energy conformation, implying efficient charge transport through the coplanar backbone of the fluorinated polymer. However, the chlorinated polymer shows the lowest energy at a relatively larger dihedral angle (ϴ = 139°) due to the steric hindrance induced by bulky chlorine atoms in the backbone, thereby leading to thin‐film morphology, which is unfavorable for charge transport. Consequently, the fluorinated polymer yields the highest field‐effect mobility (μ) of 0.57 cm2 V−1 s−1, slightly higher than that of the pristine polymer (μ = 0.33 cm2 V−1 s−1), and the extended device lifetime of organic field‐effect transistors over 12 d without any encapsulation layers. The results of this study provide design guidelines for air‐stable D–A SPs.
CDK4/6 inhibitors: A potential therapeutic approach for triple negative breast cancer
Authors: Saleh Lubaid , Wilson Caroline , Holen Ingunn 
Published: November 2021

AbstractTriple negative breast cancer (TNBC) cells lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor‐2 (HER‐2). Thus, TNBC does not respond to hormone‐based therapy. TNBC is also an aggressive subtype associated with poorer prognoses compared to other breast cancers. Conventional chemotherapeutics are used to manage TNBC although systemic relapse is common with limited benefits being reported as well as adverse events being documented. Here, we discuss current therapies for TNBC in the neo‐ and adjuvant settings, as well as recent advancements in the targeting of PD‐L1‐positive tumors and inclusion of PARP inhibitors for TNBC patients with BRCA mutations. The recent development of cyclin‐dependent kinase (CDK) 4/6 inhibitors in ER‐positive breast cancers has demonstrated significant improvements in progression free survival in patients. Here, we review preclinical data of CDK 4/6 inhibitors and describe current clinical trials assessing these in TNBC disease.
Women's perceptions of provider communication on birth options after cesarean: A qualitative study
Authors: Mirabal‐Beltran Roxanne , Hawks‐Cuellar Michelle , Powell Terrinieka W. , Strobino Donna M. 
Published: November 2021

AbstractIn the United States, Hispanic and non‐Hispanic Black women are more likely to have a repeat cesarean birth (RCB) than non‐Hispanic White women. The underrepresentation of Hispanic women and women with previous cesarean births in prior studies has resulted in a limited understanding of the reasons for this disparity. This study used in‐depth interviews to investigate the perceptions of 27 Hispanic and non‐Hispanic Black and White women about the communication that took place with their providers about their birth options after a previous cesarean. The roles of cultural norms and trust in providers in communication about RCBs were also explored. Results suggest that patient–provider communication and trust of providers for Hispanic and non‐Hispanic Black and White women may influence their perception of choice, uptake of information, and ability to make an informed choice regarding birth options. Findings have implications for providers and healthcare management systems who need to account for and attempt to address these differences as they directly affect women's birth outcomes.
Zn‐Induced Interactions Between SARS‐CoV‐2 orf7a and BST2/Tetherin
Authors: Petrosino Maria , Stellato Francesco , Chiaraluce Roberta , Consalvi Valerio , La Penna Giovanni , Pasquo Alessandra , Proux Olivier , Rossi Giancarlo , Morante Silvia 
Published: November 2021

AbstractWe present in this work a first X‐ray Absorption Spectroscopy study of the interactions of Zn with human BST2/tetherin and SARS‐CoV‐2 orf7a proteins as well as with some of their complexes. The analysis of the XANES region of the measured spectra shows that Zn binds to BST2, as well as to orf7a, thus resulting in the formation of BST2‐orf7a complexes. This structural information confirms the the conjecture, recently put forward by some of the present Authors, according to which the accessory orf7a (and possibly also orf8) viral protein are capable of interfering with the BST2 antiviral activity. Our explanation for this behavior is that, when BST2 gets in contact with Zn bound to the orf7a Cys15 ligand, it has the ability of displacing the metal owing to the creation of a new disulfide bridge across the two proteins. The formation of this BST2‐orf7a complex destabilizes BST2 dimerization, thus impairing the antiviral activity of the latter.
Utility of expanded carrier screening in pregnancies with ultrasound abnormalities
Authors: Stevens Blair K. , Nunley Peyton B. , Wagner Chelsea , Murphy Lauren , Wittman Theresa , Ramdaney Aarti , Jones Malorie , Choates Meagan Giles 
Published: November 2021

AbstractObjectiveExplore the utility of expanded carrier screening in evaluating heritable causes of congenital anomalies detected by prenatal ultrasound.MethodA retrospective chart review was conducted to collect structural abnormality and genetic testing data on infants who were evaluated postnatally by a medical geneticist. These were used to determine if expanded carrier screening could have determined the etiology prior to delivery. Additionally, recessive and X‐linked conditions on clinically available carrier screening panels were evaluated to determine the number of conditions associated with abnormal ultrasound findings.ResultsOur retrospective chart review found 222 patients with genetic etiologies, including eight unique autosomal recessive conditions and six X‐linked conditions in the 23% who underwent exome sequencing. Of these 14 unique conditions detected, three were included on a list of 271 conditions for which screening was available in 2019 and five were included on a 500 condition panel available in 2020. A literature review was performed on the list of 271 conditions and 88 were reported to be associated with one or more ultrasound abnormalities.ConclusionThis study demonstrates limited but potential utility for expanded carrier screening to determine the underlying etiology of congenital anomalies.
Population pharmacokinetic modeling of GS‐441524, the active metabolite of remdesivir, in Japanese COVID‐19 patients with renal dysfunction
Authors: Sukeishi Asami , Itohara Kotaro , Yonezawa Atsushi , Sato Yuki , Matsumura Katsuyuki , Katada Yoshiki , Nakagawa Takayuki , Hamada Satoshi , Tanabe Naoya , Imoto Eishi , Kai Shinichi , Hirai Toyohiro , Yanagita Motoko , Ohtsuru Shigeru , Terada Tomohiro , Ito Isao 
Published: November 2021

AbstractRemdesivir, a prodrug of the nucleoside analog GS‐441524, plays a key role in the treatment of coronavirus disease 2019 (COVID‐19). However, owing to limited information on clinical trials and inexperienced clinical use, there is a lack of pharmacokinetic (PK) data in patients with COVID‐19 with special characteristics. In this study, we aimed to measure serum GS‐441524 concentrations and develop a population PK (PopPK) model. Remdesivir was administered at a 200 mg loading dose on the first day followed by 100 mg from day 2, based on the package insert, in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min. In total, 190 concentrations from 37 Japanese patients were used in the analysis. The GS‐441524 trough concentrations were significantly higher in the eGFR less than 60 ml/min group than in the eGFR greater than or equal to 60 ml/min group. Extracorporeal membrane oxygenation in four patients hardly affected the total body clearance (CL) and volume of distribution (Vd) of GS‐441524. A one‐compartment model described serum GS‐441524 concentration data. The CL and Vd of GS‐441524 were significantly affected by eGFR readjusted by individual body surface area and age, respectively. Simulations proposed a dose regimen of 200 mg on day 1 followed by 100 mg once every 2 days from day 2 in patients with an eGFR of 30 ml/min or less. In conclusion, we successfully established a PopPK model of GS‐441524 using retrospectively obtained serum GS‐441524 concentrations in Japanese patients with COVID‐19, which would be helpful for optimal individualized therapy of remdesivir.
Sediment regimes in South Korea
Authors: Yang Chun‐Yao , Kang Woochul , Lee Jai Hong , Julien Pierre Y. 
Published: November 2021

AbstractA comprehensive review of the existing river flow and sediment measurement data of South Korea shows specific sediment yield values ranging from 5 to 1,500 tons/km2·year. The watershed characteristics decisively affect the shape of mass curves for water and sediment, as well as the flow duration and sediment rating curves. In terms of flow regime, small watersheds have flashy hydrographs and high sediment concentrations at a given flow discharge. The sediment rating curve coefficients decrease from 1 to 0.02 as the watershed area increases from 100 to 20,000 km2, while the exponents of these curves remain relatively constant between 1.5 and 2.0. The sediment transport in small watersheds depends on large floods, and the half‐yield discharge decreases with watershed area and typically ranges from 5 to 40 times the mean discharge. This study defines equations to calculate the mean annual flow discharge, flow duration curves, sediment yield, and cumulative water and sediment distribution curves validated with field measurements in South Korea. Additionally, the sediment regime is also presented in a continental perspective.
Design, Characterizations and Host‐Guest Properties of a New Metal‐Organic Cage Based on Half‐Sandwich Rhodium Moieties
Authors: Luo Shi‐Ting , Qiu Feng‐Yi , Shi Hua‐Tian , Yu Weibin 
Published: November 2021

AbstractDespite recent efforts to advance host‐guest systems using discrete metal‐organic cages (MOCs) with non‐trivial topological geometries for molecular recognition, which is often mediated by non‐covalent interactions involving aromatic functional groups, the relative complexation of these so‐called π‐π interaction is still challenges of study, theory and modeling. Specifically, the ability of supramolecular interactions, for an example, π‐π stacking between guest substrates and MOCs as hosts, would easily control the host‐guest assemblies. By the assembly of host‐guest complexations with metal‐coordination driven strategy and π‐π interaction, here we show that the hierarchical combination of the newly metal‐organic cages with nanosized cavity (metallacage 1), which facilitates encapsulating guest molecules through supramolecular forces. Additionally, the electron‐donating (ED)/‐withdrawing (EW) functional groups of pyrene analogues, utilized as guest substrates, can enforce host‐guest assemblies with electron‐donor (D) and electron‐acceptor (A) interactions. We herein demonstrate that ED or EW group can promote host‐guest behaviors. By this new approach, we predict that the more stable host‐guest complexations will be accompanied by stronger D−A interactions. Three guest substrates, including 1‐hydroxypyrene, 1‐pyrenamine, and 1‐pyrenecarboxaldehyde, were chosen to systematically study this host‐guest system within 1, exhibiting well consistent with our hypothesis.
Direct Valorization of Furfural in Primary Alcohols Using Rare‐Earth Metal Salts
Authors: Wang Yufen , Liu Lei , He Liangtu , Wang Yantao , Yang Weiran 
Published: November 2021

AbstractDirect valorization of furfural into alkyl levulinates and γ‐valerolactone in primary alcohols with rare‐earth metal catalysts via transfer hydrogenation was firstly reported. The effects of different rare‐earth metal salts and hydrogen donors, as well as reaction parameters on the conversion of furfural were evaluated. Under optimal conditions, ca. 74 % yield of ethyl levulinate was directly produced from furfural in ethanol with YI3 as the catalyst, and more than 60 % of γ‐valerolactone was yielded using YBr3. And intriguingly, it has been demonstrated that primary alcohols, such as ethanol, n‐propanol etc., have superior catalytic activity than secondary alcohol due to their multiple roles in the reaction. The present study provides a green, simple and efficient way for the valorization of biomass derived furfural.
Inhalation exposure to silver nanoparticles induces hepatic inflammation and oxidative stress, associated with altered renin‐angiotensin system signaling, in Wistar rats
Authors: Nayek Subhayu , Lund Amie K. , Verbeck Guido F. 
Published: November 2021

AbstractSilver nanoparticles (AgNPs) have become increasingly popular in the biomedical field over the last few decades due to its proven antibacterial property. Previous scientific studies have reported that one of the major organs responsible for detoxification of AgNPs is the liver. The liver is also the primary organ responsible for secretion of angiotensinogen (AGT), a key signaling molecule involved in the renin‐angiotensin system (RAS), which plays an important role in maintaining cardiac output and vascular pressure. The aim of this study was to assess any potential changes in the RAS‐associated gene signaling, inflammatory response, and hepatocellular toxicity resulting from AgNP exposure. To do this, 6‐week‐old, male Wistar rats were exposed to a subacute inhalation exposure of AgNP (200 ppb/days over 4 h/days exposure, for 5 d) and their livers were analyzed for alterations in RAS components, inflammation, and oxidative stress. Real time qPCR analysis showed that AgNP‐exposure resulted in a significant increase in hepatic AGT, angiotensin converting enzyme (ACE)‐1, and ACE‐2 mRNA expression. Expression of inflammatory markers interleukin (IL)‐6, IL‐1β, and tumor necrosis factor (TNF)‐α were also upregulated with AgNP‐exposure, compared to controls. Furthermore AgNP‐exposure mediated a significant increase in hepatic expression of catalase, and superoxide dismutase, and oxidative stress, as assessed via 8‐Oxo‐2′‐deoxyguanosine staining. Increased oxidative stress was associated with increased monocyte/macrophage‐2 staining in the liver of AgNP‐exposed rats. Such findings indicate that subacute inhalation exposure to AgNPs mediate increased hepatic RAS signaling, associated with inflammation, macrophage infiltration, and oxidative stress.
Characterization and optimization of the LAC4 upstream region for low‐leakage expression in Kluyveromyces marxianus
Authors: Liu Benxin , Wu Pingping , Zhou Jungang , Yin Anqi , Yu Yao , Lu Hong 
Published: November 2021

AbstractKluyveromyces marxianus is a promising host for the production of heterologous proteins, chemicals, and bioethanol. One superior feature of this species is its capacity to assimilate lactose, which is rendered by the LAC12–LAC4 gene pair encoding a lactose permease and a β‐galactosidase enzyme. Little is known about the regulation of LAC4 in K. marxianus. In this study, we showed the presence of weak glucose repression in the regulation of LAC4 and that might contribute to the leaky expression of LAC4 in the glucose medium. In a mutagenesis screen of 1000‐bp LAC4 upstream region, one mutant region, named H1, drove low‐leakage expression of a URA3 reporter gene in glucose medium. Two mutations inside a polyadenosine stretch (poly(A)) of 5′ UTR were major contributors to the low‐leakage phenotype of H1. H1 directed low‐leakage expression of GFP on a plasmid and that of LAC4 in situ in the glucose medium, which was not due to the reduction of mRNA levels. Meanwhile, H1 did not affect the induction of GFP or LAC4 by lactose. Cre recombinase expressed by H1 caused lower toxicity in the repressive condition and achieved higher yield after induction, compared with that expressed by a wild‐type LAC4 upstream region or a strong INU1 promoter. Our study suggested that poly(A) inside 5′ UTR played a role in regulating the expression of LAC4 in the repressive condition. Meanwhile, H1 provided a base for the development of a strict inducible system for expressing industrial proteins, especially toxic proteins.
Dissoziative Anfälle frühzeitig erkennen
Authors: Opp Joachim , Job Barbara 
Published: November 2021

ZusammenfassungWenn dissoziative Anfälle, also psychogene, nichtepileptische Anfälle als epileptische Anfälle fehlgedeutet werden, führt dies zu frustraner medikamentöser Therapie und verzögert die Einleitung der erforderlichen psychotherapeutischen Maßnahmen. Folgende Anfallssymptome sollten an dissoziative Anfälle denken lassen: unrhythmisches, wildes Hin- und Herbewegen des Kopfes oder der Extremitäten, geschlossene Augen, lange Dauer und undulierender Verlauf. Ein unauffälliges Elektroenzephalogramm (EEG) spricht für dissoziative Anfälle, aber erst ein negativer EEG-Befund während eines Anfalls ist beweisend. Im Arztgespräch ist es entscheidend, dass die Betroffenen die Möglichkeit bekommen, frei zu schildern. Betroffene mit dissoziativen Anfällen zeigen dann Besonderheiten, die als Diagnosekriterien genutzt werden sollten: Sie fokussieren auf Begleitumstände und lassen in ihren Schilderungen den Moment des Bewusstseinsverlusts aus. Sie machen eher allgemeine Angaben und unterscheiden einzelne Anfälle kaum.
On convergence for hybrid models of gene regulatory networks under polytopic uncertainties: a Lyapunov approach
Authors: Pasquini Mirko , Angeli David 
Published: November 2021

AbstractHybrid models of genetic regulatory networks allow for a simpler analysis with respect to fully detailed quantitative models, still maintaining the main dynamical features of interest. In this paper we consider a piecewise affine model of a genetic regulatory network, in which the parameters describing the production function are affected by polytopic uncertainties. In the first part of the paper, after recalling how the problem of finding a Lyapunov function is solved in the nominal case, we present the considered polytopic uncertain system and then, after describing how to deal with sliding mode solutions, we prove a result of existence of a parameter dependent Lyapunov function subject to the solution of a feasibility linear matrix inequalities problem. In the second part of the paper, based on the previously described Lyapunov function, we are able to determine a set of domains where the system is guaranteed to converge, with the exception of a zero measure set of times, independently from the uncertainty realization. Finally a three nodes network example shows the validity of the results.
Long non-coding RNAs: novel regulators of cellular physiology and function
Authors: Oo James A. , Brandes Ralf P. , Leisegang Matthias S. 
Published: November 2021

AbstractLong non-coding RNAs were once considered as “junk” RNA produced by aberrant DNA transcription. They are now understood to play central roles in diverse cellular processes from proliferation and migration to differentiation, senescence and DNA damage control. LncRNAs are classed as transcripts longer than 200 nucleotides that do not encode a peptide. They are relevant to many physiological and pathophysiological processes through their control of fundamental molecular functions. This review summarises the recent progress in lncRNA research and highlights the far-reaching physiological relevance of lncRNAs. The main areas of lncRNA research encompassing their characterisation, classification and mechanisms of action will be discussed. In particular, the regulation of gene expression and chromatin landscape through lncRNA control of proteins, DNA and other RNAs will be introduced. This will be exemplified with a selected number of lncRNAs that have been described in numerous physiological contexts and that should be largely representative of the tens-of-thousands of mammalian lncRNAs. To some extent, these lncRNAs have inspired the current thinking on the central dogmas of epigenetics, RNA and DNA mechanisms.
Spectrum and characterization of bi-allelic variants in MMAB causing cblB-type methylmalonic aciduria
Authors: Forny Patrick , Plessl Tanja , Frei Caroline , Bürer Celine , Froese D. Sean , Baumgartner Matthias R. 
Published: November 2021

AbstractPathogenic variants in MMAB cause cblB-type methylmalonic aciduria, an autosomal-recessive disorder of propionate metabolism. MMAB encodes ATP:cobalamin adenosyltransferase, using ATP and cob(I)alamin to create 5’-deoxyadenosylcobalamin (AdoCbl), the cofactor of methylmalonyl-CoA mutase (MMUT). We identified bi-allelic disease-causing variants in MMAB in 97 individuals with cblB-type methylmalonic aciduria, including 33 different and 16 novel variants. Missense changes accounted for the most frequent pathogenic alleles (p.(Arg186Trp), N = 57; p.(Arg191Trp), N = 19); while c.700C > T (p.(Arg234*)) was the most frequently identified truncating variant (N = 14). In fibroblasts from 76 affected individuals, the ratio of propionate incorporation in the presence and absence of hydroxocobalamin (PI ratio) was associated to clinical cobalamin responsiveness and later disease onset. We found p.(Arg234*) to be associated with cobalamin responsiveness in vitro, and clinically with later onset; p.(Arg186Trp) and p.(Arg191Trp) showed no clear cobalamin responsiveness and early onset. Mapping these and novel variants onto the MMAB structure revealed their potential to affect ATP and AdoCbl binding. Follow-up biochemical characterization of recombinant MMAB identified its three active sites to be equivalent for ATP binding, determined by fluorescence spectroscopy (Kd = 21 µM) and isothermal calorimetry (Kd = 14 µM), but function as two non-equivalent AdoCbl binding sites (Kd1 = 0.55 μM; Kd2 = 8.4 μM). Ejection of AdoCbl was activated by ATP (Ka = 24 µM), which was sensitized by the presence of MMUT (Ka = 13 µM). This study expands the landscape of pathogenic MMAB variants, provides association of in vitro and clinical responsiveness, and facilitates insight into MMAB function, enabling better disease understanding.