bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study
Authors: Lenz Heinz-Josef , Van Cutsem Eric , Luisa Limon Maria , Wong Ka Yeung Mark , Hendlisz Alain , Aglietta Massimo , García-Alfonso Pilar , Neyns Bart , Luppi Gabriele , Cardin Dana B. , Dragovich Tomislav , Shah Usman , Abdullaev Sandzhar , Gricar Joseph , Ledeine Jean-Marie , Overman Michael James , Lonardi Sara 
Published: October 2021

PURPOSE Nivolumab received US Food and Drug Administration approval as a single agent or in combination with ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on CheckMate 142. Presented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate 142 study. PATIENTS AND METHODS Patients with no prior treatment in the metastatic setting for MSI-H/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary end point was objective response rate (investigator assessment; RECIST v1.1). RESULTS Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. Objective response rate and disease control rate were 69% (95% CI, 53 to 82) and 84% (95% CI, 70.5 to 93.5), respectively, with 13% complete response rate. Median duration of response was not reached; 74% of responders had ongoing responses at data cutoff. Median progression-free survival and median overall survival were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumor characteristics, including BRAF or KRAS mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free. Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events. CONCLUSION Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated as a first-line treatment for MSI-H/dMMR mCRC. Based on these promising data, randomized studies are warranted.
Aurora kinase B inhibits aurora kinase A to control maternal mRNA translation in mouse oocytes
Authors: Aboelenain Mansour , Schindler Karen 
Published: October 2021

ABSTRACT
Mammalian oocytes are transcriptionally quiescent, and meiosis and early embryonic divisions rely on translation of stored maternal mRNAs. Activation of these mRNAs is mediated by polyadenylation. Cytoplasmic polyadenylation binding element 1 (CPEB1) regulates mRNA polyadenylation. One message is aurora kinase C (Aurkc), encoding a protein that regulates chromosome segregation. We previously demonstrated that AURKC levels are upregulated in oocytes lacking aurora kinase B (AURKB), and this upregulation caused increased aneuploidy rates, a role we investigate here. Using genetic and pharmacologic approaches, we found that AURKB negatively regulates CPEB1-dependent translation of many messages. To determine why translation is increased, we evaluated aurora kinase A (AURKA), a kinase that activates CPEB1 in other organisms. We find that AURKA activity is increased in Aurkb knockout mouse oocytes and demonstrate that this increase drives the excess translation. Importantly, removal of one copy of Aurka from the Aurkb knockout strain background reduces aneuploidy rates. This study demonstrates that AURKA is required for CPEB1-dependent translation, and it describes a new AURKB requirement to maintain translation levels through AURKA, a function crucial to generating euploid eggs.
Desmosome dualism – most of the junction is stable, but a plakophilin moiety is persistently dynamic
Authors: Fülle Judith B. , Huppert Henri , Liebl David , Liu Jaron , Alves de Almeida Rogerio , Yanes Bian , Wright Graham D. , Lane E. Birgitte , Garrod David R. , Ballestrem Christoph 
Published: October 2021

ABSTRACT
Desmosomes, strong cell–cell junctions of epithelia and cardiac muscle, link intermediate filaments to cell membranes and mechanically integrate cells across tissues, dissipating mechanical stress. They comprise five major protein classes – desmocollins and desmogleins (the desmosomal cadherins), plakoglobin, plakophilins and desmoplakin – whose individual contribution to the structure and turnover of desmosomes is poorly understood. Using live-cell imaging together with fluorescence recovery after photobleaching (FRAP) and fluorescence loss and localisation after photobleaching (FLAP), we show that desmosomes consist of two contrasting protein moieties or modules: a very stable moiety of desmosomal cadherins, desmoplakin and plakoglobin, and a highly mobile plakophilin (Pkp2a). As desmosomes mature from Ca2+ dependence to Ca2+-independent hyper-adhesion, their stability increases, but Pkp2a remains highly mobile. We show that desmosome downregulation during growth-factor-induced cell scattering proceeds by internalisation of whole desmosomes, which still retain a stable moiety and highly mobile Pkp2a. This molecular mobility of Pkp2a suggests a transient and probably regulatory role for Pkp2a in desmosomes.
This article has an associated First Person interview with the first author of the paper.
Neuroligin 1 expression is linked to plasticity of behavioral and neuronal responses to sex pheromone in the male moth Agrotis ipsilon
Authors: Durand Nicolas , Aguilar Paleo , Demondion Elodie , Bourgeois Thomas , Bozzolan Françoise , Debernard Stéphane 
Published: October 2021

ABSTRACT
In the moth Agrotis ipsilon, the behavioral response of males to the female-emitted sex pheromone increases throughout adult life and following a prior exposure to sex pheromone, whereas it is temporally inhibited after the onset of mating. This behavioral flexibility is paralleled with changes in neuronal sensitivity to pheromone signal within the primary olfactory centers, the antennal lobes. In the present study, we tested the hypothesis that neuroligins, post-synaptic transmembrane proteins known to act as mediators of neuronal remodeling, are involved in the olfactory modulation in A. ipsilon males. We cloned a full-length cDNA encoding neuroligin 1, which is expressed predominantly in brain and especially in antennal lobes. The level of neuroligin 1 expression in antennal lobes gradually raised from day-2 until day-4 of adult life, as well as at 24 h, 48 h and 72 h following pre-exposure to sex pheromone, and the temporal dynamic of these changes correlated with increased sex pheromone responsiveness. By contrast, there was no significant variation in antennal lobe neuroligin 1 expression during the post-mating refractory period. Taken together, these results highlight that age- and odor experience-related increase in sex pheromone responsiveness is linked to the overexpression of neuroligin 1 in antennal lobes, thus suggesting a potential role played by this post-synaptic cell-adhesion molecule in mediating the plasticity of the central olfactory system in A. ipsilon.
Regiodivergent Carbene/Alkyne Metathesis in Chromium-Mediated Coupling and Cyclization with 1,6-Enynes
Authors: Murai Masahito , Taniguchi Ryuji , Takai Kazuhiko 
Published: October 2021

Abstract
Regiodivergent carbene/alkyne metathesis for the selective synthesis of 2-alkylidenebicyclo[4.1.0]heptanes and 1-alkenylbicyclo[3.1.0]hexanes from common 1,6-enynes precursors was demonstrated. The cyclization mode could be switched by simple addition of diamine ligands to control the relative orientation of the approaching chromium Schrock carbene equivalents generated in situ from gem-dichromiomethanes toward triple bonds.
Dialogando com Paulo Freire e Marielle Franco: um manifesto poético através de uma performance audiovisual
Authors: Oliveira Danielle Christina do Nascimento , Silva Bianca De Menezes Castro da 
Published: October 2021

Neste artigo, apresentaremos um diálogo subjetivo entre dois personagens emblemáticos na atualidade, com corpos em fricção: Paulo Freire e Marielle Franco, que teve como objetivo a produção artística e cultural através da performance audiovisual com um manifesto poético sobre os pensamentos do primeiro e a vida da segunda, a partir da “metodologia do encontro”. O resultado deste trabalho foi a potência do encontro entre o simbólico de Marielle Franco e a perspectiva de Paulo Freire, nos demonstrando o quanto (sobre)viver é um ato político! Estes personagens deixaram suas vidas e obras como legado, ou melhor dizendo, sementes.
Potential predictors of detrusor underactivity in a urology outpatient clinic: a 5-year single center experience study
Authors: Soefiannagoya Soedarman  , Harrina Erlinati Rahardjo  
Published: October 2021

BACKGROUND Detrusor underactivity (DU) is diagnosed using urodynamics, which caused by a combination of strength and duration of the bladder muscle and resulted in prolonged bladder emptying. Invasive urodynamics, which are limited in many clinical settings, should be performed efficiently in high-risk patients to reduce the risk of emerging complications during and after the procedure. Therefore, this study was aimed to identify the potential predictors of DU for limited clinical settings.
METHODS This retrospective study was retrieved from the medical records of patients who underwent urodynamics in the Department of Urology, Cipto Mangunkusumo Hospital from 2015 to 2020. Age, sex, bladder capacity, bladder compliance, bladder outlet obstruction, history of stroke, diabetes mellitus (DM) status, and neurological abnormalities were analyzed using chi-square and Mann–Whitney to examine the potential predictors of DU. The odds ratio (OR) of each factor was also calculated. Logistic regression was furtherly used for the analysis.
RESULTS A total of 649 patients were included in this study. Male (OR = 1.74, 95% CI = 1.28–2.38) and DM patients (OR = 2.06, 95% CI = 1.36–3.11) had a higher risk of DU, while bladder outlet obstruction (OR = 0.54, 95% CI = 0.39–0.76) was the protective factor of DU. Furthermore, multivariate analysis showed that the potential predictors of DU were male (OR = 1.903, 95% CI = 1.37–2.64), DM (OR= 1.899, 95% CI = 1.22–2.95), and bladder outlet obstruction (OR = 0.32, 95% CI = 0.32–0.65).
CONCLUSIONS Age, sex, bladder outlet obstruction, and history of DM could become the predictors of DU.
3D image reconstruction of terahertz computed tomography at sparse angles by total variation minimization
Authors: Wang Dayong , Ning Ran , Li Gaochao , Zhao Jie , Wang Yunxin , Rong Lu 
Published: October 2021

Continuous-wave terahertz computed tomography (THz-CT) is an important three-dimensional imaging method for probing the profile and inner properties of a sample’s structure. We applied the total variation (TV) minimization iterative algorithm to squeeze 75% data acquisition time of THz-CT without the loss of reconstruction fidelity. The imaging system is built based on a 278.6 GHz avalanche diode source. A zero-order Bessel beam is generated by an axicon, for which the intensity profile remains essentially propagation invariant within the non-diffracting zone. The effectiveness of the proposed method is verified by using three optically opaque objects. The reconstruction results show that the TV-minimization algorithm can effectively suppress noise, artefacts, and shape distortion created in sparse angle reconstruction.
Analysis of antenatal care, intranatal care and postnatal care utilization: Findings from the 2017 Indonesian Demographic and Health Survey
Authors: Istifa Mabda Novalia , Efendi Ferry , Wahyuni Erna Dwi , Ramadhan Kadar , Adnani Qorinah Estiningtyas Sakilah , Wang Jiun-Yi 
Published: October 2021

Background and objectiveMaternal healthcare utilization by young women and adolescent girls is associated with maternal health outcomes and plays a critical role in reducing maternal mortality rates in low- and middle-income countries. This study sought to analyze current data on antenatal care (ANC), intranatal care (INC), and postnatal care (PNC) utilization with a focus on mothers aged 15–24 years in Indonesia.MethodsThis study was a secondary analysis of data from the 2017 Indonesian Demographic and Health Survey. The unit data analyzed 2,584 mothers aged 15–24 years who had delivered babies within the five-year period preceding the survey. Bivariate analysis and multiple logistic regression utilizing descriptive statistics were used to explore correlations between the independent variables and ANC, INC, and PNC visits.ResultsAmong the mothers included in the study, the prevalence of service utilization was 90.9% for ANC, 79.4% for INC, and 68.9% for PNC. Women’s age, education level, number and birth order of children, difference in age between the mother and her husband, her husband’s occupation, wealth index, access to the health service, and regional factors were significantly associated with the utilization of ANC, INC, and PNC services.ConclusionThis study provides insights for policymakers on how to strengthen healthcare policies and laws with the aim to improve maternal healthcare services for mothers aged 15–24 years. To improve maternal healthcare utilization among young mothers, national policy should focus on service equality, accessibility, and reliable implementation.
A novel in vitro assay model developed to measure both extracellular and intracellular acetylcholine levels for screening cholinergic agents
Authors: Tanaka-Kanegae Ryohei , Hamada Koichiro 
Published: October 2021

Background
Cholinergic neurons utilize choline (Ch) to synthetize acetylcholine (ACh) and contain a high-affinity Ch transporter, Ch acetyltransferase (ChAT), ACh receptors, and acetylcholinesterase (AChE). As the depletion or malfunction of each component of the cholinergic system has been reported in patients with dementia, many studies have sought to evaluate whether treatment candidates affect each of the cholinergic components. The associated changes in the cholinergic components may be reflected by intra- or extra-cellular ACh levels, with an increase in extracellular ACh levels occurring following AChE inhibition. We hypothesized that increases in intracellular ACh levels can be more sensitively detected than those in extracellular ACh levels, thereby capturing subtle effects in the cholinergic components other than AChE. The objective of this study was to test this hypothesis.

Methods
We developed an in vitro model to measure both extracellular and intracellular ACh levels using the human cholinergic neuroblastoma cell line, LA-N-2, which have been reported to express Ch transporter, ChAT, muscarinic ACh receptor (mAChR), and AChE. With this model, we evaluated several drug compounds and food constituents reported to improve cholinergic function through various mechanisms. In addition, we conducted western blotting to identify the subtype of mAChR that is expressed on the cell line.

Results
Our cell-based assay system was capable of detecting increases in extracellular ACh levels induced by an AChE inhibitor at relatively high doses, as well as increases in intracellular ACh levels following the administration of lower AChE-inhibitor doses and an mAChR agonist. Moreover, increases in intracellular ACh levels were observed even after treatment with food constituents that have different mechanisms of action, such as Ch provision and ChAT activation. In addition, we revealed that LA-N-2 cells expressed mAChR M2.

Conclusion
The findings support our hypothesis and indicate that the developed assay model can broadly screen compounds from drugs to food ingredients, with varying strengths and mechanisms of action, to develop treatments for ACh-relevant phenomena, including dementia and aging-related cognitive decline.
An 𝔽p2-maximal Wiman sextic and its automorphisms
Authors: Giulietti Massimo , Kawakita Motoko , Lia Stefano , Montanucci Maria 
Published: October 2021

AbstractIn 1895 Wiman introduced the Riemann surface 𝒲 of genus 6 over the complex field ℂ defined by the equationX6+Y6+ℨ6+(X2+Y2+ℨ2)(X4+Y4+ℨ4)−12X2Y2ℨ2= 0, and showed that its full automorphism group is isomorphic to the symmetric groupS5. We show that this holds also over every algebraically closed field 𝕂 of characteristicp≥ 7. Forp= 2, 3 the above polynomial is reducible over 𝕂, and forp= 5 the curve 𝒲 is rational and Aut(𝒲) ≅ PGL(2,𝕂). We also show that Wiman’s 𝔽192-maximal sextic 𝒲 is not Galois covered by the Hermitian curve H19over the finite field 𝔽192.
Protective effect of Lactobacillus-containing probiotics on intestinal mucosa of rats experiencing traumatic hemorrhagic shock
Authors: Wang Lei , Liu Shu-li , Xu Zhi-peng , Song Qi , Li Lei , Qiu Zhao-lei , Wang Zhen-jie 
Published: October 2021

Abstract
This study was conducted to assess whether Lactobacillus-containing probiotics could protect intestinal mucosa in rats during traumatic hemorrhagic shock and to determine its underlying mechanisms. Healthy male Sprague–Dawley rats (300 ± 20 g) were randomly divided into four groups. During the study, reverse transcription polymerase chain reaction, western blotting, and hematoxylin and eosin methods were used. There was a significant increase in the expression of toll-like receptor 4 (TLR4) in the rats that experienced traumatic hemorrhagic shock, along with increased mRNA of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. Pretreatment with Lactobacillus-containing probiotics reduced TLR4 expression, decreased phosphorylation (Ser536) and acetylation (Lys310) of p65, and decreased TNF-α and IL-6 mRNA. The probiotics combined acetate Ringer’s group showed a less severe pathological manifestation compared to the other experimental groups. Lactobacillus-containing probiotics inhibited nuclear factor-kappa B signaling via the downregulation of TLR4, resulting in inflammatory homeostasis, which might be the mechanism whereby Lactobacillus protects the intestinal mucosa from damage caused by the traumatic hemorrhagic shock.
Investigating the Use of Translation Continuation Tasks in Commercial Translation Teaching: A Study on Translating User Manuals
Authors: Xu Qi , Deng Lijun 
Published: October 2021

Abstract
Based on the xu-argument, this study investigated the use of translation continuation tasks in commercial translation instruction. Forty-four second-year Business English majors at a Chinese university participated in the study. They were divided into equal-sized control and experimental groups. Members of the experimental group were asked to read Chinese-English parallel texts from a user manual, while those of the control group were asked to read the Chinese text only. Subsequently, both groups were required to translate the continued Chinese text into English. The results indicated the following: 1) the experimental group’s translated text was of significantly higher quality than that of the control group; and 2) the experimental group’s translations were well-aligned with the original text in their use of terminology, sentence structure, and stylistic features. The study concludes by suggesting that translation continuation tasks can improve commercial translation instruction and hence should be further applied in practice.
Wolfram-like syndrome – another face of a rare disease in children
Authors: Smetek Mariusz , Gadzalska Karolina , Jakiel Paulina , Grzybowska Julia , Mysliwiec Malgorzata , Borowiec Maciej , Zmysłowska Agnieszka 
Published: October 2021

Abstract

Objectives
The presence of two pathogenic variants in the WFS1 gene leads to the occurrence of a rare genetic disease in children – Wolfram syndrome (WFS), which includes insulin-dependent diabetes mellitus (DM), optic atrophy (OA), diabetes insipidus (DI), and deafness (D). However, the presence of a single mutation in the WFS1 gene results in a number of other autosomal dominant inherited diseases, including Wolfram-like syndrome (WFS-like).

Case presentation
A 10-year-old boy was referred to the Genetic Outpatient Clinic with suspected WFS based on the coexistence of D, type 1 DM, short stature, and abnormalities in ophthalmologic examination (astigmatism and OA due to the optical coherence tomography result). The genetic analysis did not confirm WFS syndrome in the boy but identified a single likely pathogenic de novo variant in the WFS1 gene, which confirmed WFS-like syndrome.

Conclusions
Currently, the patient is under the care of an endocrinologist, diabetologist, ophthalmologist, audiologist, and also psychologist because of mood disorders.
Patterns of persistence and diffusibility in the European lexicon
Authors: Gast Volker , Koptjevskaja-Tamm Maria 
Published: October 2021

AbstractThis article investigates to what extent the semantics and the phonological forms of lexical items are genealogically inherited or acquired through language contact. We focus on patterns of colexification (the encoding of two concepts with the same word) as an aspect of lexical-semantic organization. We test two pairs of hypotheses. The first pair concerns the genealogical stability (persistence) and susceptibility to contact-induced change (diffusibility) of colexification patterns and phonological matter in the 40 most genealogically stable elements of the 100-items Swadesh list, which we call “nuclear vocabulary”. We hypothesize that colexification patterns are (a) less persistent, and (b) more diffusible, than the phonological form of nuclear vocabulary. The second pair of hypotheses concerns degrees of diffusibility in two different sections of the lexicon – “core vocabulary” (all 100 elements of the Swadesh list) and its complement (“non-core/peripheral vocabulary”). We hypothesize that the colexification patterns associated with core vocabulary are (a) more persistent, and (b) less diffusible, than colexification patterns associated with peripheral vocabulary. The four hypotheses are tested using the lexical-semantic data from the CLICS database and independently determined phonological dissimilarity measures. The hypothesis that colexification patterns are less persistent than the phonological matter of nuclear vocabulary receives clear support. The hypothesis that colexification patterns are more diffusible than phonological matter receives some support, but a significant difference can only be observed for unrelated languages. The hypothesis that colexification patterns involving core vocabulary are more genealogically stable than colexification patterns at the periphery of the lexicon cannot be confirmed, but the data seem to indicate a higher degree of diffusibility for colexification patterns at the periphery of the lexicon. While we regard the results of our study as valid, we emphasize the tentativeness of our conclusions and point out some limitations as well as desiderata for future research to enable a better understanding of the genealogical versus areal distribution of linguistic features.
New horizons for the synthesis of nanoparticles: Germanium nanoparticles from metastable GeBr-solutions
Authors: Slynchuk Viktoriia , Hodas Martin , Naglav-Hansen Dominik , Schreiber Frank , Schnepf Andreas 
Published: October 2021

Abstract
We present the synthesis and characterization of halide-terminated colloidal Ge nanoparticles of 2–10 nm with a narrow size distribution, synthesized via a novel reaction route. The nanoparticles are prepared by the disproportionation reaction of metastable Ge(I)X solutions and are obtained in a maximum yield of 79%. Control of the nanoparticle size is achieved by varying the aging time and/or temperature. The halide termination of the nanoparticles is a perfect prerequisite for further surface functionalization but also leads to a high sensitivity of the germanium nanoparticles to water and air.