bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspirin overcomes cisplatin resistance in lung cancer by inhibiting cancer cell stemness
Authors: Zhao Maoyuan , Wang Ting , Hui Zhouguang
Published: September 2020

Background

Lung cancer is the leading cause of cancer death and is commonly treated by cisplatin. Although cisplatin treatment may initially be successful, its effectiveness usually reduces significantly in disease‐recurrent patients. Aspirin, a nonselective COX inhibitor, has been shown to help reverse the status of cisplatin sensitivity in recurrent human ovarian cancer cells. This study aimed to explore the effect of aspirin on cisplatin resistance through the perspective of cancer cell stemness.

Methods

We used clustering analysis to predict the H460 cisplatin resistance from the GSE21656 dataset. The increased lung cancer cell stemness may contribute to enhanced tolerance. In this study, we used aspirin, a nonselective COX inhibitor, with cisplatin for several hours in cells and days in vivo, and studied the inhibition against human cisplatin‐resistant H460 cells. H460 cisplatin‐sensitive and H460 cisplatin‐resistant cells were treated with 16 μM aspirin or/and 0.3 μg/mL cisplatin for 72 hours.

Results

H460 cisplatin‐resistant cells showed stronger resistance, stemness, and invasiveness than H460 cisplatin‐sensitive, and cisplatin significantly reduced the survival of cisplatin‐sensitive cells, while cisplatin with aspirin dramatically reduced the surviving fractions of cisplatin‐resistant cells.

Conclusions

This study revealed that stemness is a latent inhibitor of the resistance of lung cancer cisplatin‐resistant cells and might be effectively inhibited by aspirin.
Effect of ventilator modes on neonatal cerebral and peripheral oxygenation using near‐infrared spectroscopy
Authors: Ericksen Kristina , Alpan Gad , La Gamma Edmund F.
Published: September 2020

Aim

The effect of ventilator modes on regional tissue oxygenation in premature neonates with respiratory distress syndrome (RDS) has yet to be delineated. Previous studies have looked at global oxygen delivery and have not assessed the effects on regional tissue oxygenation. Our aim in this study was to assess such tissue oxygenation in premature babies with RDS in relation to differing modes of ventilation using near‐infrared spectroscopy (NIRS).

Methods

In 24 stable preterm infants with RDS, undergoing elective wean in ventilator mode, cerebral and muscle tissue oxygenation were assessed using NIRS. Infants were weaned from high‐frequency oscillator or jet ventilator to conventional invasive ventilation (CV) or extubated from CV to non‐invasive mechanical ventilation. Data at 30 minutes prior and at one hour after change in ventilator mode were compared (paired t test).

Results

In babies changed from high‐frequency oscillation to CV, jet to CV and CV to non‐invasive ventilation, the differences in cerebral NIRS (mean ± SD) were 1.7 ± 9.9%, 2.3 ± 5.7% and 2.1 ± 8.4%, respectively. The concomitant changes in muscle NIRS were −2.9 ± 8.5%, 8.1 ± 9.7% and 3.6 ± 22.4%, respectively. No changes were statistically significant.

Conclusion

Our data suggest that there is no alteration in regional tissue oxygenation related to ventilator mode in stable preterm infants with improving RDS.
Making sense of young people’s digital practices in informal contexts: The Digital Practice Framework
Authors: Twining Peter
Published: September 2020

There is a growing body of research looking at young people’s use of digital technology in informal contexts. However, there is a gap in the literature about how to describe and categorise young people’s digital practices in such contexts. This gap is important because in order to be able to understand the differences between young people’s digital practices in informal contexts and how these differences arise, you first need to be able to describe and categorise those differences in meaningful ways. You need to be able to answer the question “How do young people use digital technology in informal contexts?” in order to be able to answer questions such as “How do children’s digital practices in informal contexts vary?” and “Why do children’s digital practices vary?”. This paper is significant because it introduces The Digital Practice Framework, an original, theoretically informed, tool to fill this critical gap in the literature. It goes on to indicate how this framework has been used to analyse the factors that facilitate or hinder the development of young people’s digital practices in informal contexts.
COVID‐19 and Venous Thromboembolism in Intensive Care or Medical Ward
Authors: Avruscio Giampiero , Camporese Giuseppe , Campello Elena , Bernardi Enrico , Persona Paolo , Passarella Christian , Noventa Franco , Cola Marco , Navalesi Paolo , Cattelan Annamaria , Tiberio Ivo , Boscolo Annalisa , Spiezia Luca , Simioni Paolo ,   for the COVID‐VTE Study Group
Published: September 2020

Despite thromboprophylaxis, patients with coronavirus disease 2019 (COVID‐19) exhibit hypercoagulability and higher venous thromboembolic risk, although its real incidence is still unknown. The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) in patients with COVID‐19 admitted to both intensive care units (ICUs) and medical wards (MWs). Consecutive patients admitted for COVID‐19 to the MW and the ICU at Padua University Hospital, all receiving thromboprophylaxis, underwent systematic ultrasonography of the internal jugular, and the upper and lower limbs veins every 7 days (± 1 day) after the admission; and, if negative, once‐weekly until discharge or death. In case of suspected pulmonary embolism, a multidetector computed tomographic angiography was performed. The primary outcome was the proportion of any deep‐vein thrombosis (DVT) and symptomatic pulmonary embolism in both groups. An extended blood coagulative test was performed as well. From March 4 to April 30, 2020, a total of 85 patients were investigated, 44 (52%) in MWs and 41 (48%) in the ICU. Despite thromboprophylaxis, VTE occurred in 12 patients in the MWs (27.3%) and 31 patients in the ICU (75.6%) with an odds ratio of 9.3 (95% confidence interval (CI) 3.5–24.5; P < 0.001). Multiple‐site DVT occurred in 55.6% of patients (95% CI 39.6–70.5). Increased D‐dimer levels significantly correlated with VTE (P = 0.001) and death (P = 0.015). Summarizing, patients with COVID‐19 admitted to the MW or ICU showed a high frequency of venous thromboembolism, despite standard‐dose or high‐dose thromboprophylaxis. Whether thrombosis, particularly asymptomatic events, may play a role in the morbidity and mortality of patients with COVID‐19 remain to be clarified.
Hypersensitivity reactions to non‐steroidal anti‐inflammatory drugs (NSAIDs) – a retrospective study
Authors: Angeletti Flavia , Meier Franziska , Zöller Nadja , Meissner Markus , Kaufmann Roland , Valesky Eva Maria
Published: September 2020

Background

The aim of this study was to verify the validity of clinical history and oral provocation challenges of patients with NSAID hypersensitivity and to identify safe alternatives. The COX‐2 inhibitor etoricoxib, in particular, was studied.

Patients and methods

In all, 104 patients with confirmed diagnoses of NSAID hypersensitivity treated at the Department of Dermatology, Frankfurt University Hospital, Germany between 2004 and 2012 were retrospectively studied.

Results

The medical history and hypersensitivity symptoms during oral provocation testing (OPT) largely coincided and were mostly mild to moderate. Acetylsalicylic acid (ASA) was the most frequent trigger both anamnestically (27.9 %) and during OPT (47.8 %). Etoricoxib caused the fewest reactions during OPT (4.2 %). Acetaminophen led to reactions in only 6.7 % of the cases studied although it was named more often in clinical histories (14 %).

Conclusions

OPT should be the aim whenever possible as most symptoms are mild to moderate. To distinguish between selective and cross‐hypersensitivity reactions, ASA should be part of the test protocol. Furthermore, the findings of this study indicate that etoricoxib and acetaminophen are safe treatment alternatives in case of NSAID hypersensitivity. However, these drugs should not be administered without prior OPT in an inpatient setting, as severe symptoms can occur.
The use of contrast‐enhanced transthoracic echocardiography for spiral‐variant hypertrophic cardiomyopathy
Authors: Begg Andrew , Dahiya Garima , Kyvernitakis Andreas , Biederman Robert W. W.
Published: September 2020

Hypertrophic cardiomyopathy is a common heritable cardiomyopathy with various clinical phenotypes. A rare spiral variant has been recently reported that has been associated with adverse outcomes and has traditionally been diagnosed using cardiac magnetic resonance. We report a case of the rare variant spiral hypertrophic cardiomyopathy where we used transthoracic echocardiography with an ultrasound enhancing agent to demonstrate the geometry of spiral hypertrophic cardiomyopathy and compared to simultaneous cardiac MRI images. The use of echocardiography with ultrasound enhancing agents may prove to be a valuable tool in identifying the geometry of hypertrophic cardiomyopathy variants in selected patients.
Phenological and isotopic evidence for migration as a life history strategy in Aeshna canadensis (family: Aeshnidae) dragonflies
Authors: Schilling Emily Gaenzle , Kardynal Kevin J. , Kundel Holly , Crews‐Erjaveck Zephyr , Zobitz John M. , Hobson Keith A.
Published: September 2020

1. Investigating dragonfly migration is important for understanding species' life history strategies, migratory connectivity, terrestrial‐aquatic linkages, and for successful species conservation. While migration patterns are well‐documented for some species (e.g., Anax junius), questions remain about potential migratory behaviour of others.

2. We investigated the potential for migration of Aeshna canadensis (Walker, 1908; Canada darner) using phenological observations in three study ponds in central Minnesota, 2017–2019. We also conducted probabilistic assignment to natal origins by measuring stable hydrogen isotope values of wing tissue (δ2Hw) of dragonflies collected in Minnesota and acquired through Canadian museum collections.

3. This species emerged May–June from study ponds in central Minnesota, with a 10–15 week lag after onset of emergence before mature adults were observed flying and ovipositing in late summer. The probabilistic assignment depictions of emerging tenerals overlapped with the sampling location, confirming accuracy of isotopic assignments of natal origin.

4. Late‐flying mature adults collected at our study ponds likely originated from southern Manitoba, suggesting a north–south migration pathway. We found further evidence for migration by analysing δ2Hw of adult dragonflies collected in northern Minnesota and south‐central Canada. Their likely origins were farther north in central Canada (Manitoba/Quebec) or the northeastern reaches of this species' range in eastern Canada.

5. We provide the first conclusive evidence of Aeshna migration in North America and demonstrate a robust approach, combining field observations with probabilistic assignment to origin using stable isotope analysis, which can test for migration in other dragonfly populations.
Long‐term coexistence of a hybridization‐derived population of Drosophila parapallidosa with closely related Drosophila ananassae (Diptera: Drosophilidae)
Authors: Hama Yosuke , Lee Chow‐Yang , Matsuda Muneo , Kamimura Yoshitaka , Sawamura Kyoichi
Published: September 2020

A 2012–13 survey on Penang Island, Malaysia, revealed the existence of both Drosophila ananassae and Drosophila parapallidosa, the latter of which carries chromosomes Y and 4 from D. ananassae and thus is of hybrid origin. We collected the flies again from the same location in 2018. The hybrid population remained present, which suggests that the D. parapallidosa of hybrid origin does not represent a mere transient population but is stable. Why do these two species coexist irrespective of gene flow? We realized that body size is generally larger in D. ananassae than in D. parapallidosa, which constitutes a new character with which to discriminate these species; previously the number of sex comb teeth was the only diagnostic trait. Character displacement was not detected, however, for those traits. We crossed these two species, which resulted in offspring that had an altered genomic constitution. The body size of D. ananassae was dominant, and the presence of chromosomes Y and 4 did not have a significant effect on body size. By contrast, the presence of chromosome 4 from D. ananassae significantly affected the number of sex comb teeth. Even flies having a genomic constitution similar to that of the Penang D. parapallidosa exhibited a number of sex comb teeth that was intermediate between the two species. We propose that the D. parapallidosa sex comb character underwent selection during evolution of the Penang Island population. Reproductive interference between the species, presumably caused by signal jamming, was detected.
Biofilm removal from a simulated isthmus and lateral canal during syringe irrigation at various flow rates: a combined experimental and Computational Fluid Dynamics approach
Authors: Pereira T. C. , Boutsioukis C. , Dijkstra R. J. B. , Petridis X. , Versluis M. , de Andrade F. B. , van de Meer W. J. , Sharma P. K. , van der Sluis L. W. M. , So M. V. R.
Published: September 2020

Aim

(i) To quantify biofilm removal from a simulated isthmus and a lateral canal in an artificial root canal system during syringe irrigation with NaOCl at different concentrations and delivered at various flow rates (ii) to examine whether biofilm removal is further improved by a final high‐flow‐rate rinse with an inert irrigant following irrigation with NaOCl. (iii) to simulate the irrigant flow in these areas using a computer model (iv) to examine whether the irrigant velocity calculated by the computer model is correlated to biofilm removal.

Methodology

Ninety‐six artificial root canals with either a simulated isthmus or lateral canal were used. A dual‐species in vitro biofilm was formed in these areas using a Constant Depth Film Fermenter. NaOCl at various concentrations (2, 5 and 10%) or adhesion buffer (control) was delivered for 30 s by a syringe and an open‐ended needle at 0.033, 0.083, or 0.166 mL s−1 or passively deposited in the main root canal (phase 1). All specimens were subsequently rinsed for 30 s with adhesion buffer at 0.166 mL s−1 (phase 2). The biofilm was scanned by Optical Coherence Tomography to determine the percentage of the remaining biofilm. Results were analysed by two 3‐way mixed‐design ANOVAs (α = 0.05). A Computational Fluid Dynamics model was used to simulate the irrigant flow inside the artificial root canal system.

Results

The flow rate during phase 1 and additional irrigation during phase 2 had a significant effect on the percentage of the remaining biofilm in the isthmus (P = 0.004 and P < 0.001). Additional irrigation during phase 2 also affected the remaining biofilm in the lateral canal significantly (P ≤ 0.007) but only when preceded by irrigation at medium or high flow rate during phase 1. The effect of NaOCl concentration was not significant (P > 0.05). Irrigant velocity in the isthmus and lateral canal increased with increasing flow rate and it was substantially correlated to biofilm removal from those areas.

Conclusions

The irrigant flow rate affected biofilm removal in vitro more than NaOCl concentration. Irrigant velocity predicted by the computer model corresponded with the pattern of biofilm removal from the simulated isthmus and lateral canal.
Comparison of efficacy of noncultured hair follicle cell suspension and noncultured epidermal cell suspension in repigmentation of leukotrichia and skin patch in vitiligo: a randomized trial
Authors: Gunaabalaji D. R. , Pangti Rashi , Challa Apoorva , Chauhan Suman , Sahni Kanika , Arava Sudheer Kumar , Sethuraman Gomathy , Vishnubhatla Sreenivas , Sharma Vinod Kumar , Gupta Somesh
Published: September 2020

Background

Vitiligo manifests as hypo‐ to de‐pigmented macules, which are sometimes associated with leukotrichia. For complete cosmetic improvement, the repigmentation of leukotrichia is an important component.

Methods

This randomized controlled trial included patients with stable vitiligo with leukotrichia. Two vitiligo patches in each patient were randomized to receive either of the two procedures. The patients were followed up for 9 months posttransplantation. The efficacy of hair follicle cell suspension (HFCS) with epidermal cell suspension (ECS) in repigmentation of leukotrichia and skin in vitiligo was compared.

Results

A total of 20 patients underwent the procedure, and 19 completed the follow‐up. The area of the vitiligo patch and the number of leukotrichia in the patches were comparable between the two groups. There was a significant difference in the mean ± S.D. number of cells transplanted between the two groups (5.06 × 105 in HFCS vs. 39.8 × 105 in ECS, P < 0.0001). The percentage viability of cells and proportion of melanocytes were comparable between the two groups. A total of 10 patients in HFCS and eight patients in ECS had repigmentation of leukotrichia. The mean ± S.D. percentages of depigmented hair showing repigmentation at nine months were 7.42 ± 11.62% in HFCS and 11.42 ± 17.90% in ECS (P = 0.4195), whereas the mean ± S.D. percentage repigmentation of vitiligo patches was 61.58 ± 42.68% in HFCS and 78.68 ± 30.03% in ECS (P = 0.1618).

Conclusions

The mean number of cells transplanted in the HFCS group was about eight times less than those in ECS. ECS was better than HFCS in repigmentation of leukotrichia and vitiligo, although the difference was not statistically significant.
ndufa7 plays a critical role in cardiac hypertrophy
Authors: Shi Xingjuan , Zhang Yu , Chen Ru , Gong Yijie , Zhang Mingming , Guan Rui , Rotstein Ori D. , Liu Xiangdong , Wen Xiao‐Yan
Published: September 2020

Cardiac hypertrophy is a common pathological change in patients with progressive cardiac function failure, which can be caused by hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) or arterial hypertension. Despite years of study, there is still limited knowledge about the underlying molecular mechanisms for cardiac hypertrophy. NDUFA7, a subunit of NADH:ubiquinone oxidoreductase (complex I), has been reported to be a novel HCM associated gene. However, the biological role of NDUFA7 in heart remains unknown. In this study, we found that NDUFA7 exhibited high expression in the heart, and its level was significantly decreased in mice model of cardiac hypertrophy. Moreover, we demonstrated that ndufa7 knockdown in developing zebrafish embryos resulted in cardiac development and functional defects, associated with increased expression of pathological hypertrophy biomarkers nppa (ANP) and nppb (BNP). Mechanistic study demonstrated that ndufa7 depletion promoted ROS production and calcineurin signalling activation. Moreover, NDUFA7 depletion contributed to cardiac cell hypertrophy. Together, these results report for the first time that ndufa7 is implicated in pathological cardiac hypertrophy.
Formation and regeneration of a Wnt‐responsive junctional epithelium
Authors: Yuan Xue , Chen Jinlong , Van Brunt Lauren A. , Grauer Joseph , Xu Quanchen , Pei Xibo , Wang Liao , Zhao Yuan , Helms Jill A.
Published: September 2020

Aim

To identify the molecular mechanisms mediating the persistent defensive functions of the self‐renewing junctional epithelium (JE).

Materials and methods

Two strains of Wnt reporter mice, Axin2CreErt2/+;R26RmTmG/+ and Axin2LacZ/+, were employed, along with three clinically relevant experimental scenarios where the function of the JE is disrupted: after tooth extraction, after a partial gingivectomy, and after a complete circumferential gingivectomy.

Results

Using transgenic Wnt reporter strains of mice, we established the JE is a Wnt‐responsive epithelium beginning at the time of its formation and that it maintains this status into adulthood. After tooth extraction, progeny of the initial Wnt‐responsive JE population directly contributed to healing and ultimately adopted an oral epithelium (OE) phenotype. In the traditional partial gingivectomy model, the JE completely regenerated and did so via progeny of the original Wnt‐responsive population. However, following circumferential gingivectomy, the OE was incapable of re‐establishing a functional JE.

Conclusions

A Wnt‐responsive niche at the interface between tooth and oral epithelia is required for a functional JE.
Comparison of non‐contrast‐enhanced dental magnetic resonance imaging and cone‐beam computed tomography in assessing the horizontal and vertical components of furcation defects in maxillary molars: An in vivo feasibility study
Authors: Juerchott Alexander , Sohani Meysam , Schwindling Franz Sebastian , Jende Johann M. E. , Kurz Felix T. , Rammelsberg Peter , Heiland Sabine , Bendszus Martin , Hilgenfeld Tim
Published: September 2020

Aim

To compare non‐contrast‐enhanced dental magnetic resonance imaging (NCE‐dMRI) and cone‐beam computed tomography (CBCT) in assessing horizontal and vertical furcation defects in maxillary molars in vivo.

Materials and methods

(NCE‐dMRI) and CBCT were performed in 23 patients with severe periodontitis. Sixty‐five first/second maxillary molars (195 furcation entrances) were analysed by two independent observers on both modalities to assess the horizontal and vertical components of furcation defects. Reliability of defect classification was evaluated using weighted kappa (κ) statistics. Agreement between NCE‐dMRI and CBCT was determined by the Bland–Altman analysis. Sensitivity and specificity of NCE‐dMRI were calculated using CBCT as the reference.

Results

Inter‐radicular bone loss was observed in 94 furcation entrances. Intra‐ and inter‐rater κ‐values were ≥0.9 for both NCE‐dMRI and CBCT. The Bland–Altman analysis showed mean differences (95% limits of agreement) of 0.12 mm (−0.67 to 0.90) for horizontal and 0.12 mm (−1.27 to 1.50) for vertical measurements. For the detection of furcation defects, sensitivity/specificity of NCE‐dMRI was 98%/100% for horizontal and 99%/99% for vertical components. For defect classification, sensitivity values of NCE‐dMRI were 88%/89%/100% (horizontal degree I/II/III) and 95%/91%/80% (vertical subclass A/B/C), respectively.

Conclusions

Non‐contrast‐enhanced dental magnetic resonance imaging demonstrated high reliability and high agreement with CBCT for the assessment of furcation defects in maxillary molars.
The impact of periodontitis exposure misclassification bias from partial‐mouth measurements on association with diabetes and cardiovascular disease
Authors: Alshihayb Talal S. , Kaye Elizabeth A. , Zhao Yihong , Leone Cataldo W. , Heaton Brenda
Published: September 2020

Aim

To quantify exposure misclassification bias arising from use of partial‐mouth protocols in studies of periodontitis–systemic disease associations.

Materials and Methods

Using data from 10,134 adults participating in the National Health and Nutrition Examination Survey, we classified periodontal status based on full‐mouth clinical examinations and three commonly used partial‐mouth protocols. Associations between periodontitis and self‐reported diabetes and cardiovascular disease were evaluated under each protocol using adjusted logistic regression. Percent relative bias was calculated to evaluate magnitude and direction of bias.

Results

Misclassification primarily resulted in underestimation of associations, the extent of which depended on both the outcome under study and exposure severity. Bias due to misclassification of severe periodontitis was negligible for cardiovascular disease (0%–4.1%) compared to diabetes (177.7%–234.1%). In contrast, bias in moderate periodontitis associations was comparable across each outcome—diabetes (28.4%–39.5%) and cardiovascular disease (8.9%–46.7%). Results did not meaningfully change based on the partial‐mouth protocol implemented. Stratified analyses showed increased bias among those with ≤15 teeth. Use of mean attachment loss as a continuous exposure resulted in minimal‐to‐no bias.

Conclusions

Exposure misclassification bias due to use of partial‐mouth protocols can yield inaccurate conclusions about periodontitis–systemic disease associations, the extent of which may depend on periodontitis classification and the association under study.
The developmental origins of genetic factors influencing language and literacy: Associations with early‐childhood vocabulary
Authors: Verhoef Ellen , Shapland Chin Yang , Fisher Simon E. , Dale Philip S. , St Pourcain Beate
Published: September 2020

Background

The heritability of language and literacy skills increases from early‐childhood to adolescence. The underlying mechanisms are little understood and may involve (a) the amplification of genetic influences contributing to early language abilities, and/or (b) the emergence of novel genetic factors (innovation). Here, we investigate the developmental origins of genetic factors influencing mid‐childhood/early‐adolescent language and literacy. We evaluate evidence for the amplification of early‐childhood genetic factors for vocabulary, in addition to genetic innovation processes.

Methods

Expressive and receptive vocabulary scores at 38 months, thirteen language‐ and literacy‐related abilities and nonverbal cognition (7–13 years) were assessed in unrelated children from the Avon Longitudinal Study of Parents and Children (ALSPAC, Nindividuals ≤ 6,092). We investigated the multivariate genetic architecture underlying early‐childhood expressive and receptive vocabulary, and each of 14 mid‐childhood/early‐adolescent language, literacy or cognitive skills with trivariate structural equation (Cholesky) models as captured by genome‐wide genetic relationship matrices. The individual path coefficients of the resulting structural models were finally meta‐analysed to evaluate evidence for overarching patterns.

Results

We observed little support for the emergence of novel genetic sources for language, literacy or cognitive abilities during mid‐childhood or early adolescence. Instead, genetic factors of early‐childhood vocabulary, especially those unique to receptive skills, were amplified and represented the majority of genetic variance underlying many of these later complex skills (≤99%). The most predictive early genetic factor accounted for 29.4%(SE = 12.9%) to 45.1%(SE = 7.6%) of the phenotypic variation in verbal intelligence and literacy skills, but also for 25.7%(SE = 6.4%) in performance intelligence, while explaining only a fraction of the phenotypic variation in receptive vocabulary (3.9%(SE = 1.8%)).

Conclusions

Genetic factors contributing to many complex skills during mid‐childhood and early adolescence, including literacy, verbal cognition and nonverbal cognition, originate developmentally in early‐childhood and are captured by receptive vocabulary. This suggests developmental genetic stability and overarching aetiological mechanisms.
Adolescents and Sexual Violations Online
Authors: Sivan Holst Nicolaj , Adolphsen Caroline
Published: September 2020

The article describes and discusses sexual violations online using the recent Danish case law and legislation as an example and drawing upon the United Nation Convention on the Rights of the Child. It is argued that the legislation does not provide a sufficient solution to the problems connected to digital violations of the physical integrity of the victim.
Factors affecting the recovery of hepatic reserve after sustained virologic response by direct‐acting antiviral agents in chronic hepatitis C virus‐infected patients
Authors: Nakajima Tomoaki , Karino Yoshiyasu , Hige Shuhei , Suii Hirokazu , Tatsumi Ryoji , Yamaguchi Masakatsu , Arakawa Tomohiro , Kuwata Ysuaki , Hasegawa Takashi , Toyota Joji
Published: September 2020

Background and Aim

Since the advent of direct‐acting antiviral (DAA) therapy, the total eradication of hepatitis C virus has been achievable with the recovery of hepatic reserve after achievement of sustained virologic response (SVR). Hence, here, we examined the factors affecting the recovery of hepatic reserve.

Methods

We followed up 403 patients (male: 164, female: 239; genotype 1: 299, genotype 2: 104; median age: 69 years) for at least 3 years after they achieved SVR to DAA therapy. Of these patients, 75 (18.6%) had a history of hepatocellular carcinoma (HCC). Biochemical tests were periodically performed, and the hepatic reserve was evaluated based on the albumin–bilirubin grade. We examined background factors such as age, biochemical test results, HCC occurrence and portosystemic shunt by computed tomography.

Results

At the start of treatment, the albumin–bilirubin grades were grades 1, 2, and 3 in 241, 157, and 5 patients, respectively, and 3 years later, 117 of 162 (72%) patients with grade 2 or 3 improved to grade 1. Multivariate analysis identified the HCC occurrence after achievement of SVR (hazard ratio [HR]: 3.08, P < 0.0138), male sex (HR: 3.45, P = 0.0143), hemoglobin level of <11.5 g/dL (HR: 4.19, P = 0.0157), the presence of a portosystemic shunt (HR: 3.07, P = 0.0349), and alanine aminotransferase levels <45 U/L (HR: 2.67, P = 0.0425) as factors inhibiting improvement to grade 1. However, old age was not an inhibitory factor.

Conclusion

Our results demonstrate that hepatic reserve could be improved even in elderly patients over a long course of time.
Geriatric Syndromes and Atrial Fibrillation: Prevalence and Association with Anticoagulant Use in a National Cohort of Older Americans
Authors: Shah Sachin J. , Fang Margaret C. , Jeon Sun Y. , Gregorich Steven E. , Covinsky Kenneth E.
Published: September 2020

BACKGROUND

Although guidelines recommend focusing primarily on stroke risk to recommend anticoagulants in atrial fibrillation (AF), physicians report that geriatric syndromes (e.g., falls and disability) are important when considering anticoagulants. Little is known about the prevalence of geriatric syndromes in older adults with AF or the association with anticoagulant use.

METHODS

We performed a cross‐sectional analysis of the 2014 Health and Retirement Study, a nationally representative study of older Americans. Participants were asked questions to assess domains of aging, including function, cognition, and medical conditions. We included participants 65 years and older with 2 years of continuous Medicare enrollment who met AF diagnosis criteria by claims codes. We examined five geriatric syndromes: one or more falls within the last 2 years, receiving help with activities of daily living (ADLs) or instrumental ADLs (IADL), experienced incontinence, and cognitive impairment. We determined the prevalence of geriatric syndromes and their association with anticoagulant use, adjusting for ischemic stroke risk (i.e., CHA2DS2‐VASc score [congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, and sex]).

RESULTS

In this study of 779 participants with AF (median age = 80 years; median CHA2DS2‐VASc score = 4), 82% had one or more geriatric syndromes. Geriatric syndromes were common: 49% reported falls, 38% had ADL impairments, 42% had IADL impairments, 37% had cognitive impairments, and 43% reported incontinence. Overall, 65% reported anticoagulant use; guidelines recommend anticoagulant use for 97% of participants. Anticoagulant use rate decreased for each additional geriatric syndrome (average marginal effect = −3.7%; 95% confidence interval = −1.4% to −5.9%). Lower rates of anticoagulant use were reported in participants with ADL dependency, IADL dependency, and dementia.

CONCLUSION

Most older adults with AF had at least one geriatric syndrome, and geriatric syndromes were associated with reduced anticoagulant use. The high prevalence of geriatric syndromes may explain the lower than expected anticoagulant use in older adults.
Manganese sulfide nanospheres as mycocidal material and priming agent for fungi‐infested rice seeds
Authors: Ahuja Radha , Sidhu Anjali , Bala Anju
Published: September 2020

Manganese sulfide nanospheres (MnS‐NSs) prepared in situ via sonochemical process were characterized to investigate the effect of nanoscale MnS on antifungal potential against mycopathogens of rice viz. Fusarium verticillioides, Drechslera oryzae and Curvularia lunata. MnS‐NSs dispersed in aqueous medium resulted in significant inhibition of growth of all the test fungi (ED50 ≤ 18 μg/ml) at concentration much lower than standard commercial fungicides (captan and carbendazim with ED50 ≥ 230 μg/ml) against respective fungi. The maximum per cent inhibition (98 ± 1.4) was recorded against C. lunata with a minimum ED50 value of 14 μg/ml, followed by D. oryzae and F. verticillioides with ED50 values of 17 and 18 μg/ml, respectively. Nanopriming of rice seeds with MnS‐NSs at 35 μg/ml for 8 hr resulted in significant reduction in seed rot (76%) and seedling blight (89.13%) along with enhancement in percent germination, root length, shoot length, dry weight and vigour index of seedlings by 33.7%, 55%, 66.3%, 85.3% and 89.3%, respectively, compared with control. Hydropriming of seeds was found to control the seed health parameters less effectively than nanopriming.
Evaluation of signal detection algorithms within the Elanco Animal Health Pharmacovigilance database
Authors: Novotny Mark J. , Rhodes Austin , Shields Jacob , Wilson Andrea , Giraldo Camilo , O’Gorman Michael , Real Theresa , Sarsadskikh Alexandra , Wiseman Scott
Published: September 2020

Statistical algorithms for detecting safety signals are beginning to be applied to Animal Health Pharmacovigilance (PV) databases. How these signal detection algorithms (SDAs) perform in an animal health PV database is the subject of this report. Statistical methods and SDAs were assessed against a set of known signals in order to identify which SDAs were most appropriate for signal detection using the Elanco Animal Health PV database. A reference set of adverse events that should signal was created for 31 products across four species. Nine SDAs based on five disproportionality statistical methods were evaluated against the reference set. The performance metrics were sensitivity, precision, specificity, accuracy, and F score. For bovine and porcine products, the Observed‐to‐Expected (O/E) SDA was the closest in terms of geometric distance to 100% sensitivity and 100% precision. For canine and feline products, the Information Component (IC) SDA was geometrically closest to 100% sensitivity and 100% precision. Principal Component Analysis confirmed that the O/E and IC SDAs were unique performers with respect to one another and other SDAs. The performance of the SDAs was dependent on the choice of the statistical method with differences seen between animal species.
An evaluation of a mindfulness‐based stress reduction intervention for critical care nursing staff: A quality improvement project
Authors: Anderson Neil
Published: September 2020

Background

Critical care is a stressful workplace for nursing staff. Mindfulness‐based stress reduction programmes are an emerging concept to manage stress in nursing, but little is known about the impact of such interventions, especially in critical care settings.

Aims and objectives

A quality improvement initiative was introduced to explore the effects of a mindfulness‐based stress reduction intervention on a cohort of critical care nurses in terms of quality of life, perceived stress, mindfulness awareness, and sickness and absence rates.

Methods

A pre‐/post‐interventional design recruited nurses (n = 25) working within a critical care unit to undertake the intervention. Participants were asked to complete psychometric questionnaires at three time points, pre‐course (0 months), immediately post‐course (8 weeks), and at a follow‐up point at month 4. Sickness and absence rates were analysed to detect differences pre‐ and post‐course. Retention rates were ascertained by numbers of participants completing the psychometric tests.

Findings

Overall, positive correlations were found when comparing pre‐course vs 8‐week mean scores of satisfaction with life (P < .001), reduced perceived stress (P < .001), and mindfulness awareness (P = .002). Bootstrap analysis of the data confirmed that positive outcome measures were more significant at the 4‐month mark in reduced perceived stress and mindfulness awareness (P < .001) compared with the satisfaction with life scale (P = .41). There was no significant change in sickness rates pre‐ and post‐intervention (P = .69). The retention rate was 70% at month 4.

Conclusions and recommendations

Mindfulness training is a feasible and accepted intervention that critical care nurses may benefit from in terms of quality of life, perceived stress, and mindfulness awareness. This has positive outcomes for staff and patients.
Seated anorectal manometry during simulated evacuation: A physiologic exercise or a new clinically useful diagnostic test?
Authors: Basilisco Guido , Corsetti Maura
Published: September 2020

Symptoms such as a feeling of incomplete evacuation, straining, absence of the call to stool, anal blockage, or digitation suggest the presence a functional defecation disorder. As symptoms do not distinguish between patients with and without functional defecation disorder, Rome IV criteria recommend that this disorder is diagnosed when two of three tests are positive: balloon expulsion test (BET), anorectal manometry (ARM), and defecography. However, previous studies have demonstrated that the agreement among these tests is limited. In this issue of Neurogastroenterology and Motility, Sharma et al tested the hypothesis that conducting the ARM in a seated position would increase the diagnostic accuracy of the test in discriminating between patients with normal and prolonged BET. This minireview discusses the current knowledge on the role of the techniques to diagnose defecation disorder and the potential role of the ARM in a seated position.
The triangular space of abiotic stress tolerance in woody species: a unified trade‐off model
Authors: Puglielli Giacomo , Hutchings Michael J. , Laanisto Lauri
Published: September 2020

Tolerance of abiotic stress in woody plants is known to be constrained by biological trade‐offs between different forms of stress, especially shade and drought. However, there is still considerable uncertainty on the relationship between tolerances and the limits on tolerance combinations.

Using the most extensive database available on shade, drought, waterlogging and cold tolerance for 799 northern hemisphere woody species, we determined the number of dimensions needed to summarise their tolerance combinations, and the best trade‐off model among those currently available, for description of the interdependence between tolerances.

Two principal component analysis (PCA) dimensions summarised stress tolerance combinations. They defined a triangular stress tolerance space (STS). The first STS dimension reflected segregation between drought‐tolerant and waterlogging‐tolerant species. The second reflected shade tolerance, which is independent of the other tolerances. Cold tolerance scaled weakly with both dimensions. Tolerance combinations across the species in the database were limited by boundary‐line trade‐offs.

The STS reconciles all major theories about trade‐offs between abiotic stress tolerances, providing a unified trade‐off model and a set of coordinates that can be used to examine how other aspects of plant biology, such as plant functional traits, change within the limits of abiotic stress tolerance.
Mapping sites of gibberellin biosynthesis in the Arabidopsis root tip
Authors: Barker Richard , Fernandez Garcia Maria Nieves , Powers Stephen J. , Vaughan Simon , Bennett Malcolm J. , Phillips Andrew L. , Thomas Stephen G. , Hedden Peter
Published: September 2020

Root elongation depends on the action of the gibberellin (GA) growth hormones, which promote cell production in the root meristem and cell expansion in the elongation zone. Sites of GA biosynthesis in the roots of 7‐d‐old Arabidopsis thaliana seedlings were investigated using tissue‐specific GA inactivation in wild‐type (Col‐0) or rescue of GA‐deficient dwarf mutants.

Tissue‐specific GA depletion was achieved by ectopic expression of the GA‐inactivating enzyme AtGA2ox2, which is specific for C19‐GAs, and AtGA2ox7, which acts on C20‐GA precursors. In addition, tissue‐specific rescue of ga20ox triple and ga3ox double mutants was shown. Furthermore, GUS reporter lines for major GA20ox, GA3ox and GA2ox genes were used to observe their expression domains in the root.

The effects of expressing these constructs on the lengths of the root apical meristem and cortical cells in the elongation zone confirmed that roots are autonomous for GA biosynthesis, which occurs in multiple tissues, with the endodermis a major site of synthesis.

The results are consistent with the early stages of GA biosynthesis within the root occurring in the meristematic region and indicate that the penultimate step of GA biosynthesis, GA 20‐oxidation, is required in both the meristem and elongation zone.
Repurposing disulfiram to induce OSCC cell death by cristae dysfunction promoted autophagy
Authors: Wang Zhen , Jiang Han , Cai Lu‐Yao , Ji Ning , Zeng Xin , Zhou Yu , Shen Ying‐Qiang , Chen Qian‐Ming
Published: September 2020

Objective

Disulfiram has been repurposed as a potential candidate to suppress various cancers. However, its anti‐tumor effects and molecular mechanisms of oral squamous cell carcinoma remain unclear. In this study, we aimed to assess the anti‐cancer activity and underlying mechanisms of disulfiram in the context of oral squamous cell carcinoma.

Materials and Methods

We tested the cytotoxicity of disulfiram in oral squamous cell carcinoma using a 3D culture model and a PDX model. Cell proliferation, cell death, and related signaling pathways were evaluated. Mitochondrial DNA copy number, mitochondrial respiration, mitochondrial mass, and mitochondrial complexes were analyzed.

Results

Disulfiram can induce excessive autophagy in oral squamous cell carcinoma cells as a result of OXPHOS deficiency. Disulfiram‐induced OPA1 degradation can impair the functional cristae structure, which results in a dramatic reduction in mitochondrial respiration capability as well as ATP production. Subsequently, energy deprivation leads to excessive autophagy through AMPK activation. In addition, exogenous ATP blocked the activation of AMPK and rescued disulfiram‐induced cell death.

Conclusion

DSF targets mitochondrial inner membrane protein OPA1 to disturb the energy supply, triggering excessive autophagy, and cell death in OSCC. Our study suggests OPA1‐dependent ATP generation is pharmacologically targetable in OSCC treatment.
Psychological distance and imitation
Authors: Hansen Jochim , Genschow Oliver
Published: September 2020

Imitation is a ubiquitous part of everybody's life. When imitating other people, a certain psychological distance is always involved—for instance, the imitator may be near to or distant from observed behavior in space (e.g., when one is learning a task face‐to‐face vs. by watching a video) or time (e.g., the behavior appears in a new vs. an old video). In this article, we review recent research that investigated the influence of psychological distance on imitation. In doing so, we differentiate between imitation of movements and imitation of goals. The reviewed research suggests that movement‐based (vs. goal‐based) imitation is stronger when the observed behavior is near than when it is distant. Additionally, the influence of psychological distance on imitation appears to happen already on an input level. That is, the level of construal guides observers' attention either to the observed movement or its goal, facilitating the imitation of the respective action feature. In addition, we review research demonstrating that psychological distance reduces goal contagion—a finding that seems to be at odds with studies showing that distance increases goal‐based imitation. We identify differences between the two lines of research (goal contagion vs. goal imitation) and discuss open questions and future directions that result from the reviewed findings.
Nocardia prophylaxis, treatment, and outcomes of infection in lung transplant recipients: A matched case‐control study
Authors: Goodlet Kellie J. , Tokman Sofya , Nasar Aasya , Cherrier Lauren , Walia Rajat , Nailor Michael D.
Published: September 2020

Background

Lung transplant recipients are at heightened risk for nocardiosis compared to other solid organ transplant recipients, with incidence rates as high as 9% and up to 30% associated mortality. No controlled studies assessing risk factors for nocardiosis in this high‐risk population have been reported.

Methods

Patients undergoing lung transplantation at a single center between 2012 and 2018 and diagnosed with nocardiosis post‐transplant were matched 1:2 to uninfected control subjects on the basis of age, transplant date, and sex.

Results

The incidence of nocardiosis in this lung transplant population was 3.4% (20/586), occurring a median of 9.4 months (range 4.4‐55.2) post‐transplant. In multivariable analysis, consistent use of trimethoprim/sulfamethoxazole (TMP/SMX) in the 12 weeks prior to diagnosis was independently associated with protection against nocardiosis (OR 0.038; 95% CI 0.01‐0.29; P = .002). Augmented immunosuppression in the 6 months prior to diagnosis was independently associated with the development of nocardiosis (OR 9.94; 95% CI 1.62‐ 61.00; P = .013). Six case patients (30%) had disseminated disease; all‐cause 6‐month mortality was 25%. The most common species was Nocardia farcinica (7/17 isolates), which was associated with dissemination and mortality. The most active antibiotics were TMP/SMX (100%), linezolid (100%), and amikacin (76%). Imipenem was only active against 4/17 isolates (24% susceptibility), with two isolates becoming non‐susceptible later in therapy.

Conclusions

Trimethoprim/sulfamethoxazole prophylaxis was shown to be protective against nocardiosis in lung transplant recipients, while augmented immunosuppression conferred increased risk. Institutional epidemiologic data are needed to best guide empiric therapy for Nocardia, as historical in vitro data may not predict local susceptibilities.
Presumptive herpesvirus‐associated erythema multiforme in a cat
Authors: De Lucia Michela , Cabré Maria , Denti Daria , Mezzalira Giorgia , Rondena Marco , Furlanello Tommaso
Published: September 2020

L’érythème polymorphe (EM), est une dermatose à médiation immune rare chez le chat, théoriquement déclenché par une infection FHV‐1 (feline herpesvirus type‐1), de la même façon que chez l’homme avec HAEM (human herpesvirus‐associated EM). Cet article décrit un chat croisé Persan de 10 ans avec un diagnostic présumé de HAEM.