bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the timing of second molar bonding on the duration of the mandibular arch levelling: a randomized clinical trial
Authors: Dritsas Konstantinos , Alharbi Majed , Kouvelis Georgios , Kloukos Dimitrios , Gkantidis Nikolaos 
Published: June 2021

SummaryIntroductionThis study investigated the effect of the timing of second molar bonding on the time required for the levelling of the mandibular dental arch.Trial designSingle-centre two-arm parallel randomized clinical trial using random permuted blocks. Allocation concealment was achieved through sealed envelopes. There was blinding in outcome assessment, but not of patient or operator.MethodsThirty-six patients (12–18 years old) with mild to moderate crowding and fully erupted mandibular second molars were assigned randomly (1:1 ratio) in two groups. Group A started fixed orthodontic treatment by bracket bonding in both jaws. Initial wire was 0.014” NiTi. Lower second molar tubes were bonded at the time of 0.016” x 0.022” NiTi wire placement. Group B was same as Group A, but second lower molars were bonded at the first appointment. Placement of the 0.017” x 0.025” stainless steel wire in the mandibular arch was considered the primary endpoint of the trial, indicating the completion of the levelling phase. The days required from bonding to the endpoint comprised the main outcome. Non-parametric statistics were applied.ResultsThere were two dropouts in each group. The compared groups had similar baseline characteristics regarding age, sex, overjet, overbite, space in the dental arch, average Curve of Spee (CoS), and maximum CoS. Group A tended to require more days for levelling (median: 203 days) than Group B (median: 168 days). However, this difference was not statistically significant (P = 0.128). From the tested occlusal factors, only initial overjet was found to be moderately associated with the days required to complete levelling of the mandibular arch (r = 0.45, P = 0.009).ConclusionsIn the frame of the current study, the duration of the levelling phase of orthodontic treatment with fixed appliances was not affected by the timing of second molar inclusion in the appliance. Future research could aim in cases with deep CoS to generalize the present findings and in larger sample sizes.
Clinical Correlates and Implications of the Reliability of the Frailty Index in the Canadian Longitudinal Study on Aging
Authors: Nguyen Quoc Dinh , Moodie Erica M , Keezer Mark R , Wolfson Christina 
Published: June 2021

Abstract

Background
Deficit accumulation frailty indices (FIs) are widely used to characterize frailty. FIs vary in number and composition of items; the impact of this variation on reliability and clinical applicability is unknown.

Method
We simulated 12 000 studies using a set of 70 candidate deficits in 12 080 community-dwelling participants 65 years and older. For each study, we varied the number (5, 10, 15, 25, 35, 45) and composition (random selection) of items defining the FI and calculated descriptive and predictive estimates: frailty score, prevalence, frailty cutoff, mortality odds ratio, predicted probability of mortality for FI = 0.28 (prevalence threshold), and FI cutoff predicting 10% mortality over the follow-up. We summarized the estimates’ medians and spreads (0.025–0.975 quantiles) by number of items and calculated intraclass correlation coefficients (ICCs).

Results
Medians of frailty scores were 0.11–0.12 with decreasing spreads from 0.04–0.24 to 0.10–0.14 for 5-item and 45-item FIs. The median cutoffs identifying 15% as frail was 0.19–0.20 and stable; the spreads decreased with more items. However, medians and spreads for the prevalence of frailty (median: 11%–3%), mortality odds ratio (median: 1.24–2.19), predicted probability of mortality (median: 8%–17%), and FI cutoff predicting 10% mortality (median: 0.38–0.20) varied markedly. ICC increased from 0.19 (5-item FIs) to 0.84 (45-item FIs).

Conclusions
Variability in the number and composition of items of individual FIs strongly influences their reliability. Estimates using FIs may not be sufficiently stable for generalizing results or direct application. We propose avenues to improve the development, reporting, and interpretation of FIs.
Postabortion care availability, facility readiness and accessibility in Nigeria and Côte d’Ivoire
Authors: Bell Suzanne O , Shankar Mridula , Ahmed Saifuddin , OlaOlorun Funmilola , Omoluabi Elizabeth , Guiella Georges , Moreau Caroline 
Published: June 2021

Abstract
Postabortion care (PAC) is an essential component of emergency obstetric care (EmOC) and is necessary to prevent unsafe abortion-related maternal mortality, but we know little regarding the preparedness of facilities to provide PAC services, the distribution of these services and disparities in their accessibility in low-resource settings. To address this knowledge gap, this study aims to describe PAC service availability, evaluate PAC readiness and measure inequities in access to PAC services in seven states of Nigeria and nationally in Côte d’Ivoire. We used survey data from reproductive-age women and the health facilities that serve the areas where they live. We linked facility readiness information, including PAC-specific signal functions, to female data using geospatial information. Findings revealed less than half of facilities provide basic PAC services in Nigeria (48.4%) but greater PAC availability in Côte d’Ivoire (70.5%). Only 33.5% and 36.9% of facilities with the capacity to provide basic PAC and only 23.9% and 37.5% of facilities with the capacity to provide comprehensive PAC had all the corresponding signal functions in Nigeria and Côte d’Ivoire, respectively. With regard to access, while ∼8 out of 10 women of reproductive age in Nigeria (81.3%) and Côte d’Ivoire (79.9%) lived within 10 km of a facility providing any PAC services, significantly lower levels of the population lived &lt;10 km from a facility with all basic or comprehensive PAC signal functions, and we observed significant inequities in access for poor, rural and less educated women. Addressing facilities’ service readiness will improve the quality of PAC provided and ensure postabortion complications can be treated in a timely and effective manner, while expanding the availability of services to additional primary-level facilities would increase access—both of which could help to reduce avoidable abortion-related maternal morbidity and mortality and associated inequities.
Implementation of DoE and Risk-Based Enhanced Analytical Quality by Design Approach to Stability-Indicating RP-HPLC Method for Stability Study of Bosutinib
Authors: Prajapati Pintu B , Bagul Nilesh , Kalyankar Gajanan 
Published: June 2021

Abstract

Background
Bosutinib is a small-molecule BCR-ABL and Src tyrosine kinase inhibitor used for the treatment of chronic myelogenous leukemia. According to published literature, no stability-indicating reversed-phase (RP)-HPLC method has been reported for the estimation of bosutinib.

Objective
A stability-indicating RP-HPLC method has been developed for the stability study of bosutinib, using a risk- and design of experiments (DoE)-based enhanced analytical quality by design (AQbD) approach.

Method
The risk-based AQbD approach was applied by risk parameter identification and risk assessment by risk priority number (RPN) ranking and filtering, as per International Conference on Harmonization (ICH) Q9 guidelines. The DoE-based AQbD approach was implemented by response surface analysis using a central composite design. The risks of critical method risk parameters were mitigated by navigation of design space and framing of control strategy.

Results
Chromatographic separation was performed using a C18 column and acetonitrile–1.0% triethylamine (v/v) in water (pH 7.0, adjusted by ortho-phosphoric acid). The developed method was validated according to ICH Q2 (R1). The developed and validated method was applied for the assay of bosutinib in pharmaceutical dosage forms. The developed method was extended for an oxidative degradation kinetic study of bosutinib at different pH conditions.

Conclusions
The developed RP-HPLC method can be used as an analytical tool for quality control and stability studies of pharmaceutical dosage forms of bosutinib in the pharmaceutical industry.

Highlights
The development and validation of a stability-indicating RP-HPLC method for the estimation of bosutinib by implementation of a DoE- and risk-based enhanced AQbD approach. The method was applied to assay pharmaceutical dosage forms and in an oxidative degradation kinetic study.
Self-Selection into Corrupt Judiciaries
Authors: Gans-Morse Jordan 
Published: June 2021

Abstract
Drawing on experimental games and a survey conducted with university students at an elite legal academy in Ukraine, this study compares the behavioral, attitudinal, and demographic traits of students aspiring to public sector legal careers as judges, prosecutors, and investigators with their counterparts aiming to pursue private sector legal careers as defense attorneys and commercial lawyers. I find evidence that students pursuing public sector legal careers display more willingness to cheat or bribe in experimental games as well as lower levels of altruism. These findings indicate that corruption in some societies may persist in part from the self-selection into government institutions of citizens with a higher propensity to seek profit from illicit activities. Moreover, the findings suggest that such corrupt self-selection can infect a country’s judicial and law enforcement apparatus, with potentially dire implications for the rule of law.
Parents’ Empathic Accuracy: Associations With Type 1 Diabetes Management and Familism
Authors: Main Alexandra , Kho Carmen , Miramontes Maritza , Wiebe Deborah J , Çakan Nedim , Raymond Jennifer K 
Published: June 2021

Abstract

Objective
To (1) test associations between parents’ empathic accuracy for their adolescents’ positive and negative emotions and adolescents’ physical and mental health (HbA1c, diabetes self-care, and depressive symptoms) in a predominantly Latinx sample of adolescents with type 1 diabetes and their parents, and (2) explore how familism values were associated with parent empathic accuracy and adolescent physical and mental health in this population.

Methods
Parents and adolescents engaged in a discussion about a topic of frequent conflict related to the adolescents’ diabetes management. Parents and adolescents subsequently completed a video recall task in which they rated their own and their partner’s emotions once per minute; parents’ empathic accuracy was calculated from an average discrepancy between parent and adolescent ratings of the adolescent’s emotions. Adolescents reported on their depressive symptoms and both parents and adolescents reported on adolescents’ diabetes self-care and their own familism values; HbA1c was obtained from medical records.

Results
Results from structural equation modeling revealed that parents’ empathic accuracy for adolescents’ negative (but not positive) emotions was uniquely associated with adolescents’ HbA1c, self-care, and depressive symptoms. There was limited evidence that familism was related to parent empathic accuracy or adolescent physical and mental health.

Conclusions
Promoting parents’ empathic accuracy for adolescents’ negative emotions in the context of type 1 diabetes management may have important implications for adolescents’ mental and physical health.
Quercetin decreases the antinociceptive effect of diclofenac in an arthritic gout-pain model in rats
Authors: Ventura-Martínez Rosa , Déciga-Campos Myrna , Bustamante-Marquina Araceli , Ángeles-López Guadalupe Esther , Aviles-Herrera José , González-Trujano Maria Eva , Navarrete-Vázquez Gabriel 
Published: June 2021

Abstract

Objective
To analyse the antinociceptive interaction between quercetin (QUER) and diclofenac (DIC) in experimental arthritic gout-pain.

Methods
The antinociceptive effect of DIC and QUER alone and in combination were evaluated using an arthritic gout-pain model. Pain was induced through intra-articular administration of uric acid in the rats and the treatments were administered 2 h later. Additionally, the cyclooxygenase (COX) activity was determined in rats treated with DIC, QUER and their combination.

Key findings
DIC induced a maximal effect of 69.7 ± 2.7% with 3.1 mg/kg; whereas QUER only produced 17.6 ± 2.6% with the maximal dose (316 mg/kg). Ten of twelve DIC + QUER combinations showed a lesser antinociceptive effect than DIC alone did (P &lt; 0.05). Moreover, DIC reduced total-COX (70.4 ± 1.3 versus 52.4 ± 1.8 and 77.4 ± 9.0 versus 56.1 ± 1.3, P &lt; 0.05) and COX-2 (60.1 ± 1.0 versus 42.4 ± 1.8 and 58.1 ± 2.4 versus 48.7 ± 1.3, P &lt; 0.05) activity after 1 and 3 h, respectively. Nevertheless, only the COX-2 activity induced by DIC was prevented in the presence of QUER (63.2 ± 3.0 versus 60.1 ± 1.0 and 56.6 ± 1.3 versus 58.1 ± 2.4 at 1 and 3 h, respectively).

Conclusions
All these data demonstrated that the simultaneous administration of QUER + DIC produces an unfavorable interaction on the antinociceptive effect of DIC. Therefore, this combination might not be recommendable to relieve arthritic gout-pain.
Updating the steady-state model of C4 photosynthesis
Authors: von Caemmerer Susanne 
Published: June 2021

AbstractC4 plants play a key role in world agriculture. For example, C4 crops such as maize and sorghum are major contributors to food production in both developed and developing countries, and the C4 grasses sugarcane, miscanthus, and switchgrass are major plant sources of bioenergy. In the challenge to manipulate and enhance C4 photosynthesis, steady-state models of leaf photosynthesis provide an important tool for gas exchange analysis and thought experiments that can explore photosynthetic pathway changes. Here a previous C4 photosynthetic model developed by von Caemmerer and Furbank has been updated with new kinetic parameterization and temperature dependencies added. The parameterization was derived from experiments on the C4 monocot, Setaria viridis, which for the first time provides a cohesive parameterization. Mesophyll conductance and its temperature dependence have also been included, as this is an important step in the quantitative correlation between the initial slope of the CO2 response curve of CO2 assimilation and in vitro phosphoenolpyruvate carboxylase activity. Furthermore, the equations for chloroplast electron transport have been updated to include cyclic electron transport flow, and equations have been added to calculate the electron transport rate from measured CO2 assimilation rates.
The impact of ionized outflows from z ∼ 2.5 quasars is not through instantaneous in situ quenching: the evidence from ALMA and VLT/SINFONI
Authors: Scholtz J , Harrison C M , Rosario D J , Alexander D M , Knudsen K K , Stanley F , Chen Chian-Chou , Kakkad D , Mainieri V , Mullaney J 
Published: June 2021

ABSTRACT
We present high-resolution (∼2.4 kpc) ALMA band 7 observations (rest-frame λ ∼ 250 $\mu$m) of three powerful z ∼ 2.5 quasars (Lbol = 1047.3–1047.5 erg s−1). These targets have previously been reported as showing evidence for suppressed star formation based on cavities in the narrow H α emission at the location of outflows traced with [O iii] emission. Here, we combine the ALMA observations with a re-analysis of the VLT/SINFONI data to map the rest-frame far-infrared emission, H α emission, and [O iii] emission. In all targets, we observe high velocity [O iii] gas (i.e. W80 ∼ 1000–2000 km s−1) across the whole galaxy. We do not identify any H α emission that is free from contamination from AGN-related processes; however, based on SED analyses, we show that the ALMA data contain a significant dust-obscured star formation component in two out of the three systems. This dust emission is found to be extended over ≈1.5–5.5 kpc in the nuclear regions, overlaps with the previously reported H α cavities and is co-spatial with the peak in surface brightness of the [O iii] outflows. In summary, within the resolution and sensitivity limits of the data, we do not see any evidence for a instantaneous shut down of in situ star formation caused directly by the outflows. However, similar to the conclusions of previous studies and based on our measured star formation rates, we do not rule out that the global host galaxy star formation could be suppressed on longer time-scales by the cumulative effect of quasar episodes during the growth of these massive black holes.
Magnetization of the intergalactic medium in the IllustrisTNG simulations: the importance of extended, outflow-driven bubbles
Authors: Arámburo-García Andrés , Bondarenko Kyrylo , Boyarsky Alexey , Nelson Dylan , Pillepich Annalisa , Sokolenko Anastasia 
Published: June 2021

ABSTRACT
We study the effects of galaxy formation physics on the magnetization of the intergalactic medium (IGM) using the IllustrisTNG simulations. We demonstrate that large-scale regions affected by the outflows from galaxies and clusters contain magnetic fields that are several orders of magnitude stronger than in unaffected regions with the same electron density. Moreover, like magnetic fields amplified inside galaxies, these magnetic fields do not depend on the primordial seed, i.e. the adopted initial conditions for magnetic field strength. We study the volume filling fraction of these strong field regions and their occurrence in random lines of sight. As a first application, we use these results to put bounds on the photon–axion conversion from spectral distortion of the CMB. As photon–axion coupling grows with energy, stronger constraints could potentially be obtained using data on the propagation of gamma-ray photons through the IGM. Finally, we also briefly discuss potential applications of our results to the Faraday Rotation measurements.
Selective cytotoxicity of cyclometalated gold(III) complexes on Caco-2 cells is mediated by G2/M cell cycle arrest
Authors: Abás Elisa , Bellés Andrea , Rodríguez-Diéguez Antonio , Laguna Mariano , Grasa Laura 
Published: June 2021

AbstractNew cyclometalated gold(III) complexes with a general structure [Au(C^N)(SR)2] or [Au(C^N)Cl(SR)], where C^N is a biphenyl ligand such as 2-(p-tolyl)pyridinate (tpy), 2-phenylpyridinate (ppy) and 2-benzylpyridinate (bzp) (SR = Spym, S(Me)2pym, 2-thiouracil (2-TU) and thiourea), and also with ethynyl moieties of the type [Au(C^N)(C≡C-Ar)2] (Ar = p-toluene and 2-pyridine) have been synthesized. All of them have been characterized, including X-ray studies of complex [Au(bzp)Cl(Spym)], and these studies have permitted to elucidate that leaving chloride ligand is trans located to CAr atom. After the full characterization, physicochemical properties were measured by evaluating drug-like water solubility and cell permeability (partition coefficient). All these experiments pointed that our complexes present adequate properties to be used as anticancer drugs. Although not all the complexes showed antiproliferative effects on Caco-2 cells, those that did were more cytotoxic than cisplatin; and complex [Au(tpy)Cl(2-TU)] is even more active than auranofin. In addition to this effectiveness, no evidence of cytotoxic effects was observed on considered normal cells (with the exception of [Au(bzp)Cl(2-TU)]. Further action mechanisms studies were performed using these selective complexes, showing cell cycle arrest on the G2/M phase, a proapoptotic behaviour and also the modification of some genes involved in tumorigenesis. Thus, as a result of this investigation, we present a new family of 17 cyclometalated complexes, 6 of them being selective and possible candidates to be used against colon cancer.
Deep and accurate detection of m6A RNA modifications using miCLIP2 and m6Aboost machine learning
Authors: Körtel Nadine , Rücklé Cornelia , Zhou You , Busch Anke , Hoch-Kraft Peter , Sutandy F X Reymond , Haase Jacob , Pradhan Mihika , Musheev Michael , Ostareck Dirk , Ostareck-Lederer Antje , Dieterich Christoph , Hüttelmaier Stefan , Niehrs Christof , Rausch Oliver , Dominissini Dan , König Julian , Zarnack Kathi 
Published: June 2021

AbstractN6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic mRNAs and influences many aspects of RNA processing. miCLIP (m6A individual-nucleotide resolution UV crosslinking and immunoprecipitation) is an antibody-based approach to map m6A sites with single-nucleotide resolution. However, due to broad antibody reactivity, reliable identification of m6A sites from miCLIP data remains challenging. Here, we present miCLIP2 in combination with machine learning to significantly improve m6A detection. The optimized miCLIP2 results in high-complexity libraries from less input material. Importantly, we established a robust computational pipeline to tackle the inherent issue of false positives in antibody-based m6A detection. The analyses were calibrated with Mettl3 knockout cells to learn the characteristics of m6A deposition, including m6A sites outside of DRACH motifs. To make our results universally applicable, we trained a machine learning model, m6Aboost, based on the experimental and RNA sequence features. Importantly, m6Aboost allows prediction of genuine m6A sites in miCLIP2 data without filtering for DRACH motifs or the need for Mettl3 depletion. Using m6Aboost, we identify thousands of high-confidence m6A sites in different murine and human cell lines, which provide a rich resource for future analysis. Collectively, our combined experimental and computational methodology greatly improves m6A identification.
Rrp1 translocase and ubiquitin ligase activities restrict the genome destabilising effects of Rad51 in fission yeast
Authors: Muraszko Jakub , Kramarz Karol , Argunhan Bilge , Ito Kentaro , Baranowska Gabriela , Kurokawa Yumiko , Murayama Yasuto , Tsubouchi Hideo , Lambert Sarah , Iwasaki Hiroshi , Dziadkowiec Dorota 
Published: June 2021

Abstract
Rad51 is the key protein in homologous recombination that plays important roles during DNA replication and repair. Auxiliary factors regulate Rad51 activity to facilitate productive recombination, and prevent inappropriate, untimely or excessive events, which could lead to genome instability. Previous genetic analyses identified a function for Rrp1 (a member of the Rad5/16-like group of SWI2/SNF2 translocases) in modulating Rad51 function, shared with the Rad51 mediator Swi5-Sfr1 and the Srs2 anti-recombinase. Here, we show that Rrp1 overproduction alleviates the toxicity associated with excessive Rad51 levels in a manner dependent on Rrp1 ATPase domain. Purified Rrp1 binds to DNA and has a DNA-dependent ATPase activity. Importantly, Rrp1 directly interacts with Rad51 and removes it from double-stranded DNA, confirming that Rrp1 is a translocase capable of modulating Rad51 function. Rrp1 affects Rad51 binding at centromeres. Additionally, we demonstrate in vivo and in vitro that Rrp1 possesses E3 ubiquitin ligase activity with Rad51 as a substrate, suggesting that Rrp1 regulates Rad51 in a multi-tiered fashion.