bluuebunny/crossref_metadata_2025 huggingface dataset:
Nurse Practitioners Rising to the Challenge During the Coronavirus Disease 2019 Pandemic in Long-Term Care Homes
Authors: McGilton Katherine S , Krassikova Alexandra , Boscart Veronique , Sidani Souraya , Iaboni Andrea , Vellani Shirin , Escrig-Pinol Astrid
Published: February 2021

Background and Objectives

There is an urgency to respond to the longstanding deficiencies in health human resources in the long-term care (LTC) home sector, which have been laid bare by the coronavirus disease 2019 (COVID-19) pandemic. Nurse practitioners (NPs) represent an efficient solution to human resource challenges. During the current pandemic, many Medical Directors in LTC homes worked virtually to reduce the risk of transmission. In contrast, NPs were present for in-person care. This study aims to understand the NPs’ roles in optimizing resident care and supporting LTC staff during the pandemic.

Research Design and Methods

This exploratory qualitative study employed a phenomenological approach. A purposive sample of 14 NPs working in LTC homes in Ontario, Canada, was recruited. Data were generated using semistructured interviews and examined using thematic analysis.

Results

Four categories relating to the NPs’ practices and experiences during the pandemic were identified: (a) containing the spread of COVID-19, (b) stepping in where needed, (c) supporting staff and families, and (d) establishing links between fragmented systems of care by acting as a liaison.

Discussion and Implications

The findings suggest that innovative models of care that include NPs in LTC homes are required moving forward. NPs embraced a multitude of roles in LTC homes, but the need to mitigate the spread of COVID-19 was central to how they prioritized their days. The pandemic clearly accentuated that NPs have a unique scope of practice, which positions them well to act as leaders and build capacity in LTC homes.
Rewarding Subjective Effects of the NMDAR Antagonist Nitrous Oxide (Laughing Gas) Are Moderated by Impulsivity and Depressive Symptoms in Healthy Volunteers
Authors: Kamboj Sunjeev K , Zhao Hannah , Troebinger Luzia , Piazza Giulia , Cawley Emma , Hennessy Vanessa , Iskandar Georges , Das Ravi K
Published: February 2021

Background

Nitrous oxide (N2O) is an anesthetic gas with both therapeutic and abuse potential. Because N2O is an NMDA receptor (NMDAR) antagonist, its effects are expected to resemble those of the prototypical NMDAR antagonist, ketamine. In this study, we examined the subjective rewarding effects of N2O using measures previously employed in studies of ketamine. We also tested for moderation of these effects by bipolar phenotype, depressive symptoms, and impulsivity.

Methods

Healthy volunteers were randomly assigned to either 50% N2O (n = 40) or medical air (n = 40). Self-reported rewarding (liking and wanting), and alcohol-like effects were assessed pre-, peri- and post inhalation.

Results

Effect sizes for the various rewarding/alcohol-like effects of N2O were generally similar to those reported in studies of moderate-dose ketamine. Impulsivity moderated the subjective reinforcing (liking) effects of inhaled gas, while depressive symptoms moderated motivational (wanting [more]) effects. However, depression and impulsivity had opposite directional influences, such that higher impulsivity was associated with higher N2O liking, and higher depression, with lower N2O wanting.

Conclusion

To the extent that static (versus longitudinal) subjective rewarding effects are a reliable indicator of future problematic drug use, our findings suggests that impulsivity and depression may predispose and protect, respectively, against N2O abuse. Future studies should examine if these moderators are relevant for other NMDAR antagonists, including ketamine, and novel ketamine-like therapeutic and recreational drugs. Similarities between moderate-dose N2O and moderate-dose ketamine in the intensity of certain subjective effects suggest that N2O may, at least to some extent, serve as substitute for ketamine as a safe and easily implemented experimental tool for probing reward-related NMDAR function and dysfunction in humans.
Real-World Outcomes of Direct-Acting Antiviral Treatment and Retreatment in United Kingdom–Based Patients Infected With Hepatitis C Virus Genotypes/Subtypes Endemic in Africa
Authors: Aranday-Cortes Elihu , McClure C Patrick , Davis Christopher , Irving William L , Adeboyejo Kazeem , Tong Lily , da Silva Filipe Ana , Sreenu Vattipally , Agarwal Kosh , Mutimer David , Stone Benjamin , Cramp Matthew E , Thomson Emma C , Ball Jonathan K , McLauchlan John
Published: February 2021

Background

Chronic hepatitis C virus (HCV) infection affects 71 million individuals, mostly residing in low- and middle-income countries (LMICs). Direct-acting antivirals (DAAs) give high rates of sustained virological response (SVR) in high-income countries where a restricted range of HCV genotypes/subtypes circulate.

Methods

We studied United Kingdom–resident patients born in Africa to examine DAA effectiveness in LMICs where there is far greater breadth of HCV genotypes/subtypes. Viral genome sequences were determined from 233 patients.

Results

Full-length viral genomic sequences for 26 known subtypes and 5 previously unidentified isolates covering 5 HCV genotypes were determined. From 149 patients who received DAA treatment/retreatment, the overall SVR was 93%. Treatment failure was associated primarily with 2 subtypes, gt1l and gt4r, using sofosbuvir/ledipasvir. These subtypes contain natural resistance-associated variants that likely contribute to poor efficacy with this drug combination. Treatment failure was also significantly associated with hepatocellular carcinoma.

Conclusions

DAA combinations give high SVR rates despite the high HCV diversity across the African continent except for subtypes gt1l and gt4r, which respond poorly to sofosbuvir/ledipasvir. These subtypes are widely distributed across Western, Central, and Eastern Africa. Thus, in circumstances where accurate genotyping is absent, ledipasvir and its generic compounds should not be considered as a recommended treatment option.
Hospital nurses’ intention to report near misses, patient safety culture and professional seniority
Authors: Toren Orly , Dokhi Mohanad , Dekeyser Ganz Freda
Published: February 2021

Objectives

To determine the extent nurses reported near miss events; to describe the relationship between patient safety culture, professional seniority and intention to report near misses; and to determine predictors of intention to report near miss events.

Design

This was a descriptive cross-sectional correlational study.The sampling method was cluster convenience sampling. Surveys were based on the Hospital Survey on Patient Safety (HSOPS).

Setting

Three general Hospitals (a small, large and a tertiary center) located in the north and center of Israel.

Participants

ICU and inpatient ward nurses working in general hospitals.

Main outcome measures

Patient safety culture, reporting medical errors and near miss events, intention to report near miss events, professional seniority.

Results

The sample included 227 nurses. Most nurses rated the patient safety culture components as moderately positive. Approximately 80% stated their intention to report a near miss, however 52.4% indicated that they did not report a near miss event in the past year. A positive correlation was found between all components of the patient safety culture and the intention to report a near miss event. Professional seniority was not related to any safety culture components or intention to report a near-miss event. Three variables predicted intention to report: team work, feedback and communication about errors, and the amount of near misses reported in the last year.

Conclusions

There is a discrepancy between what nurses describe as their intent to report a near miss event and their actual reporting of an event. Components of safety culture, especially communication openness, teamwork and reported near misses in the last year are significant predictors of the intent to report. Therefore, reinforcement of these components should be encouraged at the policy level to enable nurses to report near misses and thus improve patient safety.
Impact of pre-existing drug resistance on risk of virological failure in South Africa
Authors: Li Jonathan Z , Stella Natalia , Choudhary Manish C , Javed Aneela , Rodriguez Katherine , Ribaudo Heather , Moosa Mahomed-Yunus , Brijkumar Jay , Pillay Selvan , Sunpath Henry , Noguera-Julian Marc , Paredes Roger , Johnson Brent , Edwards Alex , Marconi Vincent C , Kuritzkes Daniel R
Published: February 2021

Objectives

There is conflicting evidence on the impact of pre-existing HIV drug resistance mutations (DRMs) in patients infected with non-B subtype virus.

Methods

We performed a case–cohort substudy of the AIDS Drug Resistance Surveillance Study, which enrolled South African patients initiating first-line efavirenz/emtricitabine/tenofovir. Pre-ART DRMs were detected by Illumina sequencing of HIV pol and DRMs present at <20% of the viral population were labelled as minority variants (MVs). Weighted Cox proportional hazards models estimated the association between pre-ART DRMs and risk of virological failure (VF), defined as confirmed HIV-1 RNA ≥1000 copies/mL after ≥5 months of ART.

Results

The evaluable population included 178 participants from a randomly selected subcohort (16 with VF, 162 without VF) and 83 additional participants with VF. In the subcohort, 16% of participants harboured ≥1 majority DRM. The presence of any majority DRM was associated with a 3-fold greater risk of VF (P = 0.002), which increased to 9.2-fold (P < 0.001) in those with <2 active drugs. Thirteen percent of participants harboured MV DRMs in the absence of majority DRMs. Presence of MVs alone had no significant impact on the risk of VF. Inclusion of pre-ART MVs with majority DRMs improved the sensitivity but reduced the specificity of predicting VF.

Conclusions

In a South African cohort, the presence of majority DRMs increased the risk of VF, especially for participants receiving <2 active drugs. The detection of drug-resistant MVs alone did not predict an increased risk of VF, but their inclusion with majority DRMs affected the sensitivity/specificity of predicting VF.
Do specific antimicrobial stewardship interventions have an impact on carbapenem resistance in Gram-negative bacilli? A multicentre quasi-experimental ecological study: time-trend analysis and characterization of carbapenemases
Authors: Álvarez-Marín Rocío , López-Cerero Lorena , Guerrero-Sánchez Francisca , Palop-Borras Begoña , Rojo-Martín María Dolores , Ruiz-Sancho Andrés , Herrero-Rodríguez Carmen , García María Victoria , Lazo-Torres Ana María , López Inmaculada , Martín-Hita Lina , Nuño-Álvarez Enrique , Sánchez-Yebra Waldo , Galán-Sánchez Fátima , Reguera-Iglesias José María , Lepe José Antonio , Peñalva Germán , Pascual Álvaro , Cisneros José Miguel ,   the CarbaPIRASOA team, Rodríguez-Mateos María Eugenia , Gallego-Fernández Carmen , Rueda Félix Gómez-de , Soria Raquel Saldaña , Pérez-Moreno María Antonia , Fernández-Cuenca Felipe , Guindo Pablo Nieto , Peña Alejandro , Márquez-Gómez Ignacio , Valiente Lucía , Ferra-Murcia Sergio , Rodríguez Miguel Ángel , Gea-Lázaro Isabel , Bermejo José Molina-Gil
Published: February 2021

Background

Carbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB.

Methods

We conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends.

Results

A decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) −1.5%, P < 0.001] and a −8.170 (−16.064 to −0.277) level change following the intervention were observed. The ID of CR-Acinetobacter baumannii decreased (AQPC −3.5%, P = 0.02) and the overall ID of CR-GNB remained stable (AQPC −0.4%, P = 0.52). CR-GNB, CR-Pseudomonas aeruginosa and CR-A. baumannii IDs per hospital correlated with the local consumption of carbapenems. The most prevalent carbapenem resistance mechanisms were OXA-23 for CR-A. baumannii (76.1%), OXA-48 for CR-Klebsiella pneumoniae (66%) and no carbapenemases for CR-P. aeruginosa (91.7%). The epidemiology of carbapenemases was heterogeneous throughout the study, especially for carbapenemase-producing Enterobacteriaceae.

Conclusions

In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.
Optimal initial antibiotic regimen for the treatment of acute appendicitis: a systematic review and network meta-analysis with surgical intervention as the common comparator
Authors: Wang Chih-Hung , Yang Chi-Chun , Hsu Wan-Ting , Qian Frank , Ding Julia , Wu Han-Ping , Tsai Jih-Jin , Yang Chia-Jui , Su Ming Yang , Chen Shyr-Chyr , Lee Chien-Chang
Published: February 2021

Background

The optimal antibiotic regimen for the medical management of acute appendicitis remains unknown due to a lack of head-to-head comparisons between different antibiotic regimens.

Methods

We systematically searched the PubMed, EMBASE, Scopus and Cochrane Central Register of Controlled Trials databases from their inception through to August 2020. We selected randomized controlled trials (RCTs) or observational studies comparing antibiotic therapy and appendectomy as the initial treatment for adult or paediatric patients with acute appendicitis. We performed a Bayesian network meta-analysis (NMA) to obtain the indirect comparison results between different antibiotic regimens by employing the group managed by surgery as a common comparator. Antibiotic regimens were classified into three categories: those including a carbapenem; those including a cephalosporin; and those including a β-lactam/β-lactamase inhibitor combination.

Results

A total of 9 RCTs (adults, n = 8; paediatrics, n = 1) and 12 observational studies (adults, n = 3; paediatrics, n = 9) were included in the NMA, with a total of 4551 patients. The most commonly administered regimen was a β-lactam/β-lactamase inhibitor combination (9/21; 43%), followed by a cephalosporin (7/21; 33%) or a carbapenem (5/21; 24%). The NMA indicated that surgery significantly increased 1 year treatment success, compared with cephalosporins [OR: 16.79; 95% credible interval: 3.8–127.64] or β-lactam/β-lactamase inhibitor combinations (OR: 19.99; 95% credible interval: 4.87–187.57), but not carbapenems (OR: 3.50, 95% credible interval: 0.55–38.63). In contrast, carbapenems were associated with fewer treatment-related complications compared with surgery (OR: 0.12; 95% credible interval: 0.01–0.85).

Conclusions

Carbapenems might be recommended as the initial antibiotic regimen for the non-operative management of adult patients with acute appendicitis. Nevertheless, due to the imprecise estimates in our NMA, additional RCTs are needed to corroborate these findings, especially for paediatric patients.
Changing the way we think: competition, platforms and ecosystems
Authors: Jenny Frederic
Published: February 2021

Many of the traditional tools used by competition authorities to assess relevant markets or the intensity of competition between firms are difficult to use or inadequate to assess competition issues between ecosystems in the digital world. Further economic thinking and an understanding of the business models of ecosystems are required to allow competition authorities to make informed and relevant decisions about competition on digital markets. This article reviews some of the challenges they face.
Dronedarone HCl–Quercetin Co-Amorphous System: Characterization and RP-HPLC Method Development for Simultaneous Estimation
Authors: Navya Sree K S , Dengale Swapnil J , Mutalik Srinivas , Bhat Krishnamurthy
Published: February 2021

Background

Dronedarone HCl (DRN) is an anti-arrhythmic drug indicated for atrial fibrillation. DRN has a low solubility of 2 µg/mL and 4% bioavailability, thus it is formulated as a co-amorphous system to enhance its solubility by using quercetin (QCT) as a co-former. A sensitive, accurate, and economic method for the simultaneous quantification of DRN and QCT in formulation is not found in the literature.

Objective

To develop a Reverse Phase -HPLC method for the simultaneous estimation of DRN and QCT in a DRN–QCT co-amorphous system.

Method

The co-amorphous system was prepared using a solvent evaporation technique with DRN and QCT in a 1:1 molar ratio. The separation was achieved on a Purospher® STAR C18 (250 mm × 4.6 mm × 5 μm id (internal diameter)) column with the mobile phase comprising of acetonitrile and a 25 mM phosphate buffer pH 3.6 (60:40%, v/v).

Results

DRN and QCT were retained on the column for 6.7 and 3.5 min, respectively. For both molecules, the method was developed with a wide linearity range of 0.2–500 µg/mL. The LOD for DRN was found to be 0.0013 µg/mL and for QCT it was found to be 0.0026 µg/mL. The LOQ for DRN was found to be 0.0041 µg/mL, and for QCT it was 0.0078 µg/mL.

Conclusions

The method was validated as per International Conference on Harmonization (ICH) guidelines for linearity, precision, accuracy, and robustness. The method was used in simultaneous quantification of DRN and QCT in co-amorphous samples.

Highlights

The method developed was used for the analysis of content uniformity and solubility samples of co-amorphous system, where the method was able to successfully quantify DRN and QCT. Low detection and quantification limits contribute to the sensitivity of the method and wide linearity range assures the robust and precise quantification of molecules.
Pertuzumab and trastuzumab as adjuvant treatment for HER2-positive early breast cancer: outcomes in Chinese patients in the APHINITY study
Authors: Shao Zhimin , Tseng Ling-Ming , Huang Chiun-Sheng , Pang Da , Yang Youngsen , Li Wei , Liao Ning , Geng Cuizhi , Zhang Qingyuan , Xu Binghe , Liu Donggeng , Kwong Ava ,   et al (continued in the appendix)
Published: February 2021

Background

The addition of pertuzumab to trastuzumab plus standard chemotherapy as adjuvant therapy following surgery significantly improved invasive disease-free survival (IDFS) in patients with HER2-positive early breast cancer in the multinational randomized APHINITY trial (NCT01358877, BIG 4–11/BO25126/TOC4939G). We analyzed clinical outcomes in the subgroup of patients recruited at Chinese sites.

Methods

Patients were randomized to standard adjuvant chemotherapy plus 1 year of trastuzumab with pertuzumab or placebo. Patients recruited in mainland China, Hong Kong and Taiwan are included in this descriptive analysis.

Results

Chinese patients had similar demographic characteristics to the global population, but a higher proportion had nodal involvement. Although this subgroup analysis was not powered to detect statistical significance, a numerical improvement in IDFS was observed with the addition of pertuzumab to trastuzumab in Chinese patients (hazard ratio, 0.69; 95% confidence interval: 0.39–1.19; 3-year IDFS event-free estimates 92.5% [pertuzumab] and 91.7% [placebo]), which was consistent with the primary analysis of the global population. Further subgroup analyses showed numerical improvements in the Chinese node-positive, hormone receptor-negative and -positive subgroups, although confidence intervals were wide due to the low number of events. The incidence of diarrhea was higher in the pertuzumab arm, and no primary cardiac events occurred in Chinese patients in either arm.

Conclusions

Pertuzumab, used in combination with trastuzumab and chemotherapy in APHINITY, is effective as an adjuvant treatment regimen for Chinese patients with HER2-positive early breast cancer in a setting with curative intent. The safety profile in Chinese patients was consistent with that of the global population.
Patient-Reported Outcomes and Long-Term Nonadherence to Aromatase Inhibitors
Authors: Hershman Dawn L , Neugut Alfred I , Moseley Anna , Arnold Kathryn B , Gralow Julie R , Henry N Lynn , Hillyer Grace Clarke , Ramsey Scott D , Unger Joseph M
Published: February 2021

Background

Nonadherence to aromatase inhibitors (AIs) is common and increases risk of breast cancer (BC) recurrence. We analyzed factors associated with nonadherence among patients enrolled in S1105, a randomized trial of text messaging.

Methods

At enrollment, patients were required to have been on an adjuvant AI for at least 30 days and were asked about financial, medication, and demographic factors. They completed patient-reported outcomes (PROs) representing pain (Brief Pain Inventory), endocrine symptoms (Functional Assessment of Cancer Therapy–Endocrine Symptoms), and beliefs about medications (Treatment Satisfaction Questionnaire for Medicine; Brief Medication Questionnaire). Our primary endpoint was AI nonadherence at 36 months, defined as urine AI metabolite assay of less than 10 ng/mL or no submitted specimen. We evaluated the association between individual baseline characteristics and nonadherence with logistic regression. A composite risk score reflecting the number of statistically significant baseline characteristics was examined.

Results

We analyzed data from 702 patients; median age was 60.9 years. Overall, 35.9% patients were nonadherent at 36 months. Younger patients (younger than age 65 years) were more nonadherent (38.8% vs 28.6%, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.05 to 2.16; P = .02). Fourteen baseline PRO scales were each statistically significantly associated with nonadherence. In a composite risk model categorized into quartile levels, each increase in risk level was associated with a 46.5% increase in the odds of nonadherence (OR = 1.47, 95% CI =1.26 to 1.70; P < .001). The highest-risk patients were more than 3 times more likely to be nonadherent than the lowest-risk patients (OR = 3.14, 95% CI = 1.97 to 5.02; P < .001).

Conclusions

The presence of multiple baseline PRO-specified risk factors was statistically significantly associated with AI nonadherence. The use of these assessments can help identify patients for targeted interventions to improve adherence.
Repurposing of sildenafil as antitumour; induction of cyclic guanosine monophosphate/protein kinase G pathway, caspase-dependent apoptosis and pivotal reduction of Nuclear factor kappa light chain enhancer of activated B cells in lung cancer
Authors: AboYoussef Amira M , Khalaf Marwa M , Malak Marina N , Hamzawy Mohamed A
Published: February 2021

Objectives

Lung cancer is one of the most frequent types of cancers that lead to death. Sildenafil is a potent inhibitor of phosphodiesterase-5 and showed potential anticancer effects, which has not yet been fully evaluated. Thus, this study aims to investigate the potential anticancer effect of sildenafil in urethane-induced lung cancer in BALB/c mice.

Methods

Five-week-old male BALB/c mice were treated with either (i) normal saline only, (ii) sildenafil only 50 mg kg-1/ P.O every other day for the last four successive weeks, (iii) urethane 1.5 gm kg-1 i.p (at day 1 and day 60), (iv) carboplatin after urethane induction, or (v) sildenafil after urethane induction.

Key findings

It was shown that sildenafil significantly increased the levels of cGMP and Caspase-3 with a reduction of NF-κB, Bcl-2, Cyclin D1, intercellular adhesion molecule 1, matrix metalloproteinase-2 levels and normalisation of Nrf2 along with pronounced improvement in the histological patterns.

Conclusions

These results indicated that sildenafil markedly induces cell cycle arrest, apoptosis and inhibits the metastatic activity through activation of cyclic guanosine monophosphate/protein kinase G pathway and down-regulation of cyclin D1 and nuclear factor kappa light chain enhancer of activated B cells with downstream anti-apoptotic gene Bcl-2, which underscores the critical importance of future using sildenafil in the treatment of lung cancer.
Mechanisms exploration of Xiaojin Pills on lung cancer based on metabolomics and network pharmacology
Authors: Cao Bo , Lin Junzhi , Wu Zhenfeng , Liu Huimin , Zhang Dingkun , Xu Hong , Xu Runchun , Han Li
Published: February 2021

Objectives

This study was designed to evaluate the pharmacological activity and therapeutic mechanism of Xiaojin Pills (XJW) on lung cancer.

Methods

Mice were orally administered with Xiaojin Pills for 21 days. Tumour samples were collected to evaluate the antilung cancer effect, and blood samples were collected to identify differential metabolites with metabolomics. Through the analysis of network pharmacology, the active ingredients and targets related to XJW therapy for lung cancer were filtered.

Key findings

Different expression of seven metabolites related to seven pathways, including Arachidonic acid metabolism, Citrate cycle, tryptophan metabolism, glyoxylate and dicarboxylate metabolism, arginine and proline metabolism, primary bile acid biosynthesis and nicotinate and nicotinamide metabolism, were demonstrated to explain the efficacy of XJW in the treatment of lung cancer. Furthermore, a total of 19 active ingredients (ursolic acid, α-thujone, pelargonidin, succinic acid, boswellic acid, muscone, daidzein, xanthorrhizol, isoeugenol, oleic acid, β-caryophyllene, vanillin, β-sitosterol, lupeol, palmitic acid, eugenol, methylbutenol, β-elemene and quercetin) acted directly on 9 targets (CAT, PTGS2, PTGS1, CTH, ABTA, ALT1, ME2, AGXT and AGXT 2) and regulated 3 out of 7 metabolites (3-Hydroxyanthranilic acid, Pyruvate and Prostaglandin G2).

Conclusions

Through metabolomics and network pharmacology analyses, this study demonstrated that the major metabolites of XJW in treating lung cancer were regulated by multitarget and multicomponent interaction network.
Splenic artery aneurysm, case series of seven patients
Authors: Salimi Javad , Omrani Zahra , Cheraghali Roozbeh
Published: February 2021

Splenic artery aneurysms (SAA) account for 46–60% of all visceral artery aneurysms. Small SAAs are usually asymptomatic, but giant aneurysms are more likely to cause symptoms and can result in life-threatening complications. Treatment of a splenic artery aneurysms includes laparotomy, laparoscopy or endovascular techniques. Case presentation: In this article, seven interesting cases of splenic artery aneurysms in different size and parts of artery and various interventions (open, endovascular and hybrid surgery) are discussed. Six of the patients were male. Five of them had giant SAAs (≥5 cm). Two patients underwent hybrid surgery. Coil embolization was carried out for one patient. All seven patients discharged with no procedure-related complications. Endovascular procedures considered as a first choice of treatment for splenic artery aneurysm. Open surgery is reserved mostly for the treatment of complications or if the endovascular techniques fail, lack of availability of endovascular procedures or allergy to contrast medium.
OGLE-2018-BLG-1428Lb: a Jupiter-mass planet beyond the snow line of a dwarf star
Authors: Kim Yun Hak , Chung Sun-Ju , Udalski Andrej , Gould Andrew , Albrow Michael D , Jung Youn Kil , Hwang Kyu-Ha , Han Cheongho , Ryu Yoon-Hyun , Shin In-Gu , Shvartzvald Yossi , Yee Jennifer C , Zang Weicheng , Cha Sang-Mok , Kim Dong-Jin , Kim Hyoun-Woo , Kim Seung-Lee , Lee Chung-Uk , Lee Dong-Joo , Lee Yongseok , Park Byeong-Gon , Pogge Richard W ,   (KMTNet Collaboration), Mróz Przemek , Poleski Radek , Wrona Marcin , Iwanek Patryk , Szymański Michał K , Skowron Jan , Soszyński Igor , Kozłowski Szymon , Pietrukowicz Paweł , Ulaczyk Krzysztof , Rybicki Krzysztof ,   (The OGLE collaboration), Kim Y H , Chung S-J
Published: February 2021

We present the analysis of the microlensing event OGLE-2018-BLG-1428, which has a short-duration (∼1 d) caustic-crossing anomaly. The event was caused by a planetary lens system with planet/host mass ratio q = 1.7 × 10−3. Because of the detection of the caustic-crossing anomaly, the finite source effect was well measured, but the microlens parallax was not constrained due to the relatively short time-scale (tE = 24 d). From a Bayesian analysis, we find that the host star is a dwarf star $M_{\rm host}=0.43^{+0.33}_{-0.22} \ \mathrm{M}_{\odot }$ at a distance $D_{\rm L}=6.22^{+1.03}_{-1.51}\ {\rm kpc}$ and the planet is a Jovian-mass planet $M_{\rm p}=0.77^{+0.77}_{-0.53} \ M_{\rm J}$ with a projected separation $a_{\perp }=3.30^{+0.59}_{-0.83}\ {\rm au}$. The planet orbits beyond the snow line of the host star. Considering the relative lens-source proper motion of $\mu _{\rm rel} = 5.58 \pm 0.38\ \rm mas\ yr^{-1}$, the lens can be resolved by adaptive optics with a 30 m telescope in the future.
Globular cluster systems of relic galaxies
Authors: Alamo-Martínez Karla A , Chies-Santos Ana L , Beasley Michael A , Flores-Freitas Rodrigo , Furlanetto Cristina , Trevisan Marina , Schnorr-Müller Allan , Leaman Ryan , Bonatto Charles J
Published: February 2021

We analyse the globular cluster (GC) systems of a sample of 15 massive, compact early-type galaxies (ETGs), 13 of which have already been identified as good relic galaxy candidates on the basis of their compact morphologies, old stellar populations and stellar kinematics. These relic galaxy candidates are likely the nearby counterparts of high-redshift red nugget galaxies. Using F814W (≈I) and F160W (≈H) data from the WFC3 camara onboard the Hubble Space Telescope, we determine the total number, luminosity function, specific frequency, colour, and spatial distribution of the GC systems (GCSs). We find lower specific frequencies (SN < 2.5 with a median of SN = 1) than ETGs of comparable mass. This is consistent with a scenario of rapid, early dissipative formation, with relatively low levels of accretion of low-mass, high-SN satellites. The GC half-number radii are compact, but follow the relations found in normal ETGs. We identify an anticorrelation between the specific angular momentum (λR) of the host galaxy and the (I − H) colour distribution width of their GCSs. Assuming that λR provides a measure of the degree of dissipation in massive ETGs, we suggest that the (I − H) colour distribution width can be used as a proxy for the degree of complexity of the accretion histories in these systems.
Gravitational redshifting of galaxies in the SPIDERS cluster catalogue
Authors: Mpetha C T , Collins C A , Clerc N , Finoguenov A , Peacock J A , Comparat J , Schneider D , Capasso R , Damsted S , Furnell K , Merloni A , Padilla N D , Saro A
Published: February 2021

Data from the SPectroscopic IDentification of ERosita Sources (SPIDERS) are searched for a detection of the gravitational redshifting of light from ${\sim}20\, 000$ galaxies in ∼2500 galaxy clusters using three definitions of the cluster centre: its Brightest Cluster Galaxy (BCG), the redMaPPer identified Central Galaxy (CG), or the peak of X-ray emission. Distributions of velocity offsets between galaxies and their host cluster’s centre, found using observed redshifts, are created. The quantity $\hat{\Delta }$, the average of the radial velocity difference between the cluster members and the cluster systemic velocity, reveals information on the size of a combination of effects on the observed redshift, dominated by gravitational redshifting. The change of $\hat{\Delta }$ with radial distance is predicted for SPIDERS galaxies in General Relativity (GR), and f(R) gravity, and compared to the observations. The values of $\hat{\Delta }=-13.5\pm 4.7$ km s−1, $\hat{\Delta }=-12.5\pm 5.1$ km s−1, and $\hat{\Delta }=-18.6\pm 4.8$ km s−1 for the BCG, X-ray, and CG cases, respectively, broadly agree with the literature. There is no significant preference of one gravity theory over another, but all cases give a clear detection (>2.5σ) of $\hat{\Delta }$. The BCG centroid is deemed to be the most robust method in this analysis, due to no well-defined central redshift when using an X-ray centroid, and CGs identified by redMaPPer with no associated spectroscopic redshift. For future gravitational redshift studies, an order-of-magnitude more galaxies, ${\sim}500\, 000$, will be required – a possible feat with the forthcoming Vera C. Rubin Observatory, Euclid and eROSITA.
X-raying the galaxy pair Arp 41: no collision in NGC 1232 and three ultraluminous sources in NGC 1232A
Authors: Soria Roberto , Pakull Manfred W
Published: February 2021

We studied the apparent galaxy pair NGC 1232/NGC 1232A with Chandra, looking for evidence of interactions and collisions. We report that there is no cloud of diffuse emission in NGC 1232, contrary to previous claims in the literature. Instead, we find that the small ‘companion’ galaxy NGC 1232A contains three ultraluminous X-ray sources with peak 0.3–10 keV luminosities above 1040 erg s−1 (assuming a cosmological distance of ≈93 Mpc for this galaxy). For its mass, morphology, metal abundance, and bright ULX population, NGC 1232A is analogous to the more nearby late-type spiral NGC 1313.
Probing ultradiffuse galaxies out to the virial radius of the Coma cluster with XMM–Newton
Authors: Mirakhor M S , Walker S A
Published: February 2021

We probe the formation scenarios and the active galactic nucleus (AGN) occupation fraction of ultradiffuse galaxies (UDGs) in the nearby Coma cluster by utilizing XMM–Newton observations of 779 out of 854 UDG candidates identified by the Subaru survey. Their origin is probed by measuring the dark matter halo mass of the stacked sample of UDGs and the population of low-mass X-ray binaries residing in globular clusters. Our measurements suggest that the average UDG population does not have a substantial amount of hot gas or a large number of globular clusters. This supports the formation scenario, in which UDGs are puffed-up dwarf galaxies, agreeing with that obtained for 404 Coma cluster UDGs using Chandra. We also determine AGN occupation fraction of UDGs by cross-correlating the position of UDGs with the detected point sources in Coma. We detect three X-ray sources with detection significance σ ≥ 5 that could be off-centre AGNs within 5 arcsec from the centre of the UDG 317, UDG 432, and UDG 535. We identify an optical counterpart for the X-ray source associated with the UDG 317, suggesting that this source is more likely an off-centre AGN. Based on the current data, however, we cannot conclusively constrain whether the detected AGN is residing in the Coma cluster or not.
Angiopoietin 2 stimulates trophoblast invasion via a mechanism associated with JNK signaling
Authors: Hou Huomei , Ning Fen , Zhang Joy Yue , Lu Qinsheng , Zhang Min , Wu Peihuang , Chen Miaojuan , Lash Gendie E
Published: February 2021

Extravillous trophoblast cell (EVT) invasion is tightly controlled, and its dysregulation can lead to altered spiral artery remodeling and contribute to a number of different pregnancy complications. Angiopoietin-2 (Ang-2) is expressed by trophoblast cells and various cells in the decidua, and trophoblast cells express its receptor, Tie2. Ang-2 has been shown to play roles in tumor progression and metastasis but it is not known if it also regulates EVT invasion. Here, we show that both the HTR-8/SVneo cell line and primary isolates of human EVT expressed various integrins and the Tie2 receptor, and Ang-2 stimulated their migration and/or invasion. Ang-2 increased expression of matrix metalloproteinase (MMP)2 and MMP9, altered the cytoskeleton of HTR-8/SVneo cells and also induced phosphorylation of Tie2, JNK and c-Jun. Inhibition of p-JNK (using SP600125) blocked the Ang-2 induced invasion of HTR-8/SVneo cells. In addition, inhibition of Tie2 (pexmetinib) and integrin signaling (RGDS and ATN-161) also blocked Ang-2-induced invasion. In conclusion, we demonstrate that Ang-2 can stimulate EVT invasion via a mechanism associated with activation of both the Tie2 receptor and integrins, which appear to work through different pathways; Tie2 through the JNK/c-JUN pathway and integrins through an as yet unidentified pathway(s). We therefore propose that any alterations in Ang-2 expression in the decidua would lead to an imbalance in pro- and anti-invasive factors, disrupting regulation of EVT invasion and spiral artery remodeling and thereby contribute to the etiology of several complications of pregnancy.
Ultraviolet-induced RNA:DNA hybrids interfere with chromosomal DNA synthesis
Authors: Kouzminova Elena A , Kuzminov Andrei
Published: February 2021

Ultraviolet (UV) induces pyrimidine dimers (PDs) in DNA and replication-dependent fragmentation in chromosomes. The rnhAB mutants in Escherichia coli, accumulating R-loops and single DNA-rNs, are generally resistant to DNA damage, but are surprisingly UV-sensitive, even though they remove PDs normally, suggesting irreparable chromosome lesions. We show here that the RNase H defect does not cause additional chromosome fragmentation after UV, but inhibits DNA synthesis after replication restart. Genetic analysis implies formation of R-loop-anchored transcription elongation complexes (R-loop-aTECs) in UV-irradiated rnhAB mutants, predicting that their chromosomal DNA will accumulate: (i) RNA:DNA hybrids; (ii) a few slow-to-remove PDs. We confirm both features and also find that both, surprisingly, depend on replication restart. Finally, enriching for the UV-induced RNA:DNA hybrids in the rnhAB uvrA mutants also co-enriches for PDs, showing their co-residence in the same structures. We propose that PD-triggered R-loop-aTECs block head-on replication in RNase H-deficient mutants.
Binding site profiles and N-terminal minor groove interactions of the master quorum-sensing regulator LuxR enable flexible control of gene activation and repression
Authors: Zhang Jun , Liu Bing , Gu Dan , Hao Yuan , Chen Mo , Ma Yue , Zhou Xiaohui , Reverter David , Zhang Yuanxing , Wang Qiyao
Published: February 2021

LuxR is a TetR family master quorum sensing (QS) regulator activating or repressing expression of hundreds of genes that control collective behaviors in Vibrios with underlying mechanism unknown. To illuminate how this regulator controls expression of various target genes, we applied ChIP-seq and DNase I-seq technologies. Vibrio alginolyticus LuxR controls expression of ∼280 genes that contain either symmetric palindrome (repDNA) or asymmetric (actDNA) binding motifs with different binding profiles. The median number of LuxR binding sites for activated genes are nearly double for that of repressed genes. Crystal structures of LuxR in complex with the respective repDNA and actDNA motifs revealed a new mode of LuxR DNA binding that involves contacts of its N-terminal extension to the minor groove. The N-terminal contacts mediated by Arginine-9 and Arginine-11 differ when LuxR binds to repDNA vs actDNA, leading to higher binding affinity at repressed targets. Moreover, modification of LuxR binding sites, binding profiles, and N-terminal extension have important consequences on QS-regulated phenotypes. These results facilitate fundamental understanding of the high flexibility of mechanisms of LuxR control of gene activation and repression in Vibrio QS, which may facilitate to design QS inhibiting chemicals that interfere with LuxR regulation to effectively control pathogens.
Somatic CAG expansion in Huntington's disease is dependent on the MLH3 endonuclease domain, which can be excluded via splice redirection
Authors: Roy Jennie C L , Vitalo Antonia , Andrew Marissa A , Mota-Silva Eduarda , Kovalenko Marina , Burch Zoe , Nhu Anh M , Cohen Paula E , Grabczyk Ed , Wheeler Vanessa C , Mouro Pinto Ricardo
Published: February 2021

Somatic expansion of the CAG repeat tract that causes Huntington's disease (HD) is thought to contribute to the rate of disease pathogenesis. Therefore, factors influencing repeat expansion are potential therapeutic targets. Genes in the DNA mismatch repair pathway are critical drivers of somatic expansion in HD mouse models. Here, we have tested, using genetic and pharmacological approaches, the role of the endonuclease domain of the mismatch repair protein MLH3 in somatic CAG expansion in HD mice and patient cells. A point mutation in the MLH3 endonuclease domain completely eliminated CAG expansion in the brain and peripheral tissues of a HD knock-in mouse model (HttQ111). To test whether the MLH3 endonuclease could be manipulated pharmacologically, we delivered splice switching oligonucleotides in mice to redirect Mlh3 splicing to exclude the endonuclease domain. Splice redirection to an isoform lacking the endonuclease domain was associated with reduced CAG expansion. Finally, CAG expansion in HD patient-derived primary fibroblasts was also significantly reduced by redirecting MLH3 splicing to the endogenous endonuclease domain-lacking isoform. These data indicate the potential of targeting the MLH3 endonuclease domain to slow somatic CAG repeat expansion in HD, a therapeutic strategy that may be applicable across multiple repeat expansion disorders.
How Does the Use of Flavored Nicotine Vaping Products Relate to Progression Toward Quitting Smoking? Findings From the 2016 and 2018 ITC 4CV Surveys
Authors: Li Lin , Borland Ron , Cummings Kenneth Michael , Fong Geoffrey T , Gravely Shannon , Smith Danielle M , Goniewicz Maciej L , O’Connor Richard J , Thompson Mary E , McNeill Ann
Published: February 2021

Introduction

There is limited research on the role of flavors in nicotine vaping products (NVPs) in relation to smoking. We examined patterns of flavor use in NVPs in relation to progression toward quitting.

Aims and Methods

Data come from 886 concurrent users of NVPs (at least weekly) and cigarettes who were first surveyed in 2016 and then successfully recontacted in 2018 as part of the ITC 4CV Surveys conducted in Australia, Canada, England, and the United States. Participants were asked about their main vaping flavor categorized as: (1) tobacco or unflavored, (2) menthol or mint flavored, and (3) “sweet” flavors (eg, fruit or candy). We examined whether flavor was associated with progression toward quitting smoking between survey years.

Results

Overall, 11.1% of baseline concurrent users quit smoking by 2018. Compared with users of tobacco flavors, those vaping “sweet” flavors were more likely to quit smoking between surveys (13.8% vs. 9.6%; adjusted odds ratio [aOR] = 1.61, 95% confidence interval [CI] 1.01–2.58, p < .05), but those using menthol flavors were no more likely to quit smoking (8.3% vs. 9.6%, aOR = 0.87, 95% CI 0.43–1.47, p = .69). Among those who had quit smoking in 2018, 52.0% were still vaping, which was lower than the 65.8% among continuing smokers (aOR = 0.60, 95% CI 0.39–0.92, p = .02). Sweet flavor users were no more likely to continue vaping compared with tobacco flavor users, either for those continuing smoking or those having quit smoking by 2018. There was a net shift away from tobacco flavor among those who continued to vape at follow-up.

Conclusions

Use of fruit and other sweet flavored e-liquids is positively related to smokers’ transition away from cigarettes.

Implications

With multiple jurisdictions considering limiting or banning the sale of flavored NVPs, it is important to consider how such policies may impact smokers using NVPs to transition away from cigarette smoking. Our results indicate that vapers who used sweet flavors were more likely to transition away from cigarette smoking and quit cigarette use, at least in the short term, compared with those who used tobacco or unflavored NVPs. Randomized clinical trials are needed to establish if the observed association between use of flavored e-liquids and smoking cessation is due to self-selection or is truly causal.
Cosmopolitanism
Authors: Maresh Moriah
Published: February 2021

Cosmopolitanism is the ideology that all people are “citizens of the world” (Cosmopolitanism: Ethics in a World of Strangers, under General Overviews) and can be traced back to ancient Greek and Roman philosophers, with the addition of the Egyptian pharaoh, Akhanoton (“The Greek Origins of the Idea of Cosmopolitanism,” cited under Influence and Origins). With increasing global interconnectedness thanks to technological advancements, the ideology of cosmopolitanism is perhaps now more relevant than ever before. Thanks to thinkers and writers such as Immanuel Kant, Francisco de Vitoria, Anthony Kwame Appiah, and Martha Nussbaum, to name a few, cosmopolitanism and its implications continue to influence theoretical visions of society, politics, economics, education, literature, and art.
Nazi Looting of Art
Authors: Petropoulos Jonathan , Sage Nicholas
Published: February 2021

Adolf Hitler and the Nazis were not only the most systematic mass murderers in history, they were also history’s greatest thieves. Beginning with the duress sales of Jewish property starting in 1933 and escalating to expropriation as part of emigration in Austria to outright seizure in conquered nations during World War II, the Nazis carried out a plundering program that extended to millions of cultural objects. The Allied response began during the war: after concerned academics (such as the Harvard Defense Group) alerted military and civilian leaders to the dangers to Europe’s cultural patrimony, the United States created the Roberts Commission to study the issue, which in turn led to the creation of Monuments, Fine Arts, and Archives section, where officers accompanied the invading armies and tried to mitigate the damage from combat, as well as track the looted works. The Monuments officers undertook a massive, international restitution effort, but could not complete the task: there is still much “unfinished business” from this era. The literature on Nazi plundering and Allied restitution is rich and varied: from the vivid accounts of the Monuments officers to the technical and occasionally arcane scholarly interventions (e.g., how to interpret labels on the backs of paintings). The opening of archives and the continued discovery of Nazi-looted works in museums and private collections has served as an impetus for continued research, and an international effort promises to yield further discoveries. This article is divided into twenty-two sections, with the entries in chronological order. It bears mentioning that there are four sections where the historiography is particularly rich: (1) plunder and restitution in France, (2) the literature on “degenerate art,” (3) Nazi-looted art and the law, and (4) anthologies. The first is likely due to the cultural riches of France, as well as the accessibility of archives. The scholarship on “degenerate art” took off in the late 1980s, with the observance of the fifty-year anniversary of the Aktion in 1987, and the public revelation of the Gurlitt cache in 2013 contributed to this impetus (Hildebrand Gurlitt had been one of the four official dealers of the purged art). Due to the emergence of myriad restitution cases starting in the early 2000s, the legal aspects of looting and recovery have attracted intense scholarly interest. And the international nature of the research, which has involved scholars from both North America and Europe, has led to many conferences, which in turn yielded a rich array of anthologies.