bluuebunny/crossref_metadata_2025 huggingface dataset:
Supravesical hernias: a systematic review of the literature
Authors: Katsaros Ioannis , Routsi Eleni , Papapanou Michail , Mastoraki Aikaterini , Kontogeorgi Evangelia , Tsapralis Dimitrios , Vlachos Konstantinos , Schizas Dimitrios
Published: August 2020

Background

A supravesical hernia (SH) is a rare abdominal wall hernia that is defined by the protrusion of abdominal viscera through the supravesical fossa. The objective of this study was to review current literature on SHs and elucidate their clinical manifestations and preferred therapeutic approach.

Methods

PubMed, Embase and Cochrane bibliographical databases were searched (last search: 30 March 2020) for articles reporting on SHs.

Results

Thirty‐four studies met our inclusion criteria and involved collectively 38 patients (94.7% males) with an age of 59.57 ± 14.84 (mean ± standard deviation) years. Abdominal pain (81.6%) and nausea and vomit (71.1%) were the most frequently encountered symptoms. The majority of patients (78.1%) had signs of bowel obstruction. Twenty‐nine patients (76.3%) suffered from an internal SH, while nine (23.7%) had an external one. An open hernia repair was conducted at 29 patients (76.3%), while eight (21.1%) had a laparoscopic approach and in one case (2.6%) the laparoscopic operation was converted to an open one. A mesh was applied at 14.3% of included cases. Eight patients (21.1%) underwent a bowel resection and hernia sac was resected at six (15.8%) cases. Four patients (11.8%) experienced postoperative complications and one patient (2.9%) died on first postoperative day.

Conclusion

SH is an extremely rare type of hernia occurring through the supravesical fossa between the remnants of urachus and foetal umbilical arteries. All clinicians should be aware of this entity and further studies are necessary in order to clarify their aetiology, true incidence and optimal therapeutic approach.
Aminoglycosides were associated with higher rates of surgical patent ductus arteriosus closure in preterm infants
Authors: Marissen Janina , Erdmann Harald , Böckenholt Kai , Hoppenz Marc , Rausch Tanja K. , Härtel Christoph , Herting Egbert , Göpel Wolfgang ,   the German Neonatal Network
Published: August 2020

Aim

In animal studies, aminoglycosides induced ductus arteriosus relaxation in a dose‐dependent fashion. We tested the hypothesis that antibiotic treatment of preterm infants with aminoglycosides is associated with higher rates of surgical patent ductus arteriosus (PDA) closure.

Methods

Preterm infants (birthweight <1000 grams or gestational age <29 weeks) enrolled in 62 German neonatal intensive care units (NICUs) were analysed. NICUs were stratified according to the use of aminoglycosides as first‐line antibiotics.

Results

Baseline data were not different when NICUs using aminoglycosides (n = 9965 infants) were compared to NICUs using other antibiotics (n = 1948 infants). Rates of surgical PDA closure were 5.9% for NICUs using aminoglycosides; 6.2% for units using gentamicin; and 5.0% for NICUs using tobramycin compared to 4.1% in NICUs using other antibiotics (P < .001, P < .001 and P = .140, respectively, Fisher's exact test). Indomethacin and ibuprofen use was more common in NICUs using aminoglycosides (41% vs 33%, P < .001, Fisher's exact test). Gentamicin trough levels were higher in NICUs with surgical closure rates above the mean (median 2.0 µg/mL, inter‐quartile range 0.8‐4.0 µg/mL vs 1.2 µg/mL, IQR 0.8‐1.7, P < .001, Mann‐Whitney U test).

Conclusion

First‐line antibiotic treatment of preterm infants with aminoglycosides was associated with higher rates of surgical PDA closure.
Nicotinamide adenine dinucleotide: Biosynthesis, consumption and therapeutic role in cardiac diseases
Authors: Tannous Cynthia , Booz George W. , Altara Raffaele , Muhieddine Dina H. , Mericskay Mathias , Refaat Marwan M. , Zouein Fouad A.
Published: August 2020

Nicotinamide adenine dinucleotide (NAD) is an abundant cofactor that plays crucial roles in several cellular processes. NAD can be synthesized de novo starting with tryptophan, or from salvage pathways starting with NAD precursors like nicotinic acid (NA), nicotinamide (NAM) or nicotinamide riboside (NR), referred to as niacin/B3 vitamins, arising from dietary supply or from cellular NAD catabolism. Given the interconversion between its oxidized (NAD+) and reduced form (NADH), NAD participates in a wide range of reactions: regulation of cellular redox status, energy metabolism and mitochondrial biogenesis. Plus, NAD acts as a signalling molecule, being a cosubstrate for several enzymes such as sirtuins, poly‐ADP‐ribose‐polymerases (PARPs) and some ectoenzymes like CD38, regulating critical biological processes like gene expression, DNA repair, calcium signalling and circadian rhythms. Given the large number of mitochondria present in cardiac tissue, the heart has the highest NAD levels and is one of the most metabolically demanding organs. In several models of heart failure, myocardial NAD levels are depressed and this depression is caused by mitochondrial dysfunction, metabolic remodelling and inflammation. Emerging evidence suggests that regulating NAD homeostasis by NAD precursor supplementation has therapeutic efficiency in improving myocardial bioenergetics and function. This review provides an overview of the latest understanding of the different NAD biosynthesis pathways, as well as its role as a signalling molecule particularly in cardiac tissue. We highlight the significance of preserving NAD equilibrium in various models of heart diseases and shed light on the potential pharmacological interventions aiming to use NAD boosters as therapeutic agents.
A systematic review of mental health literacy in Pakistan
Authors: Munawar Khadeeja , Abdul Khaiyom Jamilah Hanum , Bokharey Iram Zehra , Park Miriam Sang‐Ah , Choudhry Fahad Riaz
Published: August 2020

Individual mental health has become a primary global concern. In Pakistan, the prevalence of mental health issues is still unclear, as not many studies have assessed the level of mental health literacy (MHL) in the country. This systematic review aims to bridge this gap by encouraging the early detection of mental disorders, lessening stigma, and improving help‐seeking behavior. Nine electronic databases were searched to identify empirical literature in this area. Only studies that evaluated MHL efficacy and those published in English were selected. Non‐peer reviewed articles and gray literature were excluded. From 613 studies retrieved, 59 studies met the inclusion criteria and were reviewed. Forty‐three of the included studies mentioned mental health outcome measures (of which only four mentioned reliability indices), 13 discussed stigma, 18 examined help‐seeking approaches to mental illness treatments, and 47 discussed mental health knowledge. Additionally, the outcome of the MHL measures had considerable heterogeneity and limited validity. Meta‐analysis was not conducted due to a lack of MHL operationalization. Besides, the measurement tools in the studies lacked consistency and standardization. This review compiled the available studies on MHL to assist researchers currently studying the various dimensions of MHL, as well as those designing new studies or investigating effective methods to increase MHL. This review highlights the need for well‐designed controlled intervention studies. Further implications for researchers, practitioners, and policymakers are mentioned.
Inter‐relationships between burnout, personality and coping features in residents within an ACGME‐I Accredited Psychiatry Residency Program
Authors: Lee Yu Wei , Kudva Kundadak Ganesh , Soh Mark , Chew Qian Hui , Sim Kang
Published: August 2020

Background

Burnout during residency training is associated with various factors. Within the context of stress/coping transactional model in which one's personality can influence stress appraisal and coping, there is limited evidence examining the relationship between burnout and personality factors amongst psychiatry residents.

Objectives

We aim to evaluate the prevalence of burnout within a cohort of psychiatry residents and its relationship with personality factors, demographic, work‐related factors and coping features.

Methods

We conducted a cross‐sectional study involving 50 out of 77 eligible residents (response rate 64.9%) and administered the Oldenberg Burnout Inventory (OLBI), NEO‐Five Factor Inventory (NEO‐FFI) and Brief COPE Inventory. Burnout was defined as crossing the thresholds for exhaustion (≥2.25) and disengagement (≥2.1) scores. We compared the burnout vs nonburnout groups and examined the relationship between burnout, personality factors and coping strategies using correlational and mediational analyses.

Results

Overall, 78% of our cohort met criteria for burnout. Burnout was correlated with hours of work per week (rs = .409, P = .008), neuroticism (OR 1.2, 95% CI 1.01‐1.43, P = .041) and avoidance coping (OR 1.61, 95% CI 1.06‐2.46, P = .025). Neuroticism was significantly correlated (all P < .001) with all coping domains (Seeking Social Support, rs = 0.40; Problem Solving, rs = 0.52; Avoidance, rs = 0.55; Positive thinking, rs = 0.41) and was a partial mediator between avoidance coping and burnout (β of indirect path = 0.168, [SE = 0.066]; P = .011).

Conclusions

We found a considerable burnout rate amongst psychiatry residents which was associated with neuroticism and avoidance coping, and suggest ways to better tackle occupational burnout during residency training.
Effects of different sources and levels of dietary chromium supplementation on performance of broiler chicks
Authors: Safwat Assem Mohamed , Elnaggar Asmaa Shawkey , Elghalid Osama Ahmed , EL‐Tahawy Waleed Salah
Published: August 2020

The current experiment was carried out to evaluate the effect of different dietary chromium supplementation sources, chromium oxide (Cr2O3), chromium methionine (Cr‐Met), or chromium yeast (Cr‐yeast), at different levels each (500 or 1,000 ppb) on growth performance, physiological traits, and carcass characteristics of broiler chicks. A total of 490 seven‐day‐old Arbor Acres chicks were randomly distributed into 7 experimental groups each in 10 replicates of 7 birds each. The groups were control, 500 ppb Cr2O3, 1,000 ppb Cr2O3, 500 ppb Cr‐Met, 1,000 ppb Cr‐Met, 500 ppb Cr‐yeast, and 1,000 ppb Cr‐yeast. The results showed significant superiority of the organic chromium sources (Cr‐Met or Cr‐yeast) concerning body weight and weight gain, the group supplemented with 1,000 ppb Cr‐yeast consumed the lowest feed (3,185 g) and had the best feed conversion ratio (1.60) compared to the control (1.73). The chromium treatments recorded significantly better protein and lipid profile, antioxidant status, and immunological parameters than the control group. Similarly, dietary chromium supplementation increased carcass yield and decreased intestinal pathogenic bacteria. In conclusion, supplementing broiler diets with organic chromium sources at 1,000 ppb promotes growth performance, physiological traits, and carcass characteristics; such chromium treatments enhanced the antioxidant status and immunity levels of broilers.
Drug exposure of first‐line anti‐tuberculosis drugs in China: A prospective pharmacological cohort study
Authors: Gao Yazhou , Davies Forsman Lina , Ren Weihua , Zheng Xubin , Bao Ziwei , Hu Yi , Bruchfeld Judith , Alffenaar Jan‐Willem
Published: August 2020

Aim

Exploring the need for optimization of drug exposure to improve tuberculosis (TB) treatment outcome is of great importance. We aimed to describe drug exposure at steady state as well as the population pharmacokinetics (PK) of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) in Chinese TB patients.

Methods

A prospective multicentre PK study of RIF, INH and PZA was conducted in China between January 2015 and December 2017. Six blood samples were collected from each subject for drug concentration measurement. Nonlinear mixed effect analyses were used to develop population PK models.

Results

In total, 217 patients were included. Positive correlations between body weight, clearance and volume of distribution were identified for RIF and PZA, whereas body weight only influenced clearance for INH. In addition, males had higher RIF clearance and thus lower RIF exposure than women. Acetylator status was significantly associated with INH clearance as INH exposure in intermediate and fast acetylators was significantly lower than in slow acetylators, especially in low‐weight bands. Simulations also showed significantly lower drug exposures in low‐weight bands for all three drugs. Patients weighing <38 kg were respectively exposed to 30.4%, 45.9% and 18.0% lower area under the concentration‐time curve of RIF, INH and PZA than those weighing ≥70 kg. Higher doses by addition of one fixed‐dose combination tablet or 150 mg INH were simulated and found to be effective in improving INH drug exposures, especially in low‐weight bands.

Conclusion

PK variability of first‐line anti‐TB drugs is common in Chinese TB patients. The developed population PK models can be used to optimize drug exposures in Chinese patients. Moreover, standard dosing needs to be adjusted to increase target attainment.
Pharmacologic effects of oseltamivir in immunocompromised adult patients as assessed by population PK/PD analysis and drug‐disease modelling for dosing regimen optimization
Authors: Sturm Stefan , Lemenuel‐Diot Annabelle , Patel Kashyap , Gibiansky Leonid , Bhardwaj Rajinder , Smith Patrick F. , Dang Steve , Zwanziger Elke , Nasmyth‐Miller Clare , Ravva Patanjali
Published: August 2020

Aim

Pharmacologic effects were analysed to determine a dose recommendation for oseltamivir in immunocompromised (IC) adults with influenza.

Methods

Quantitative clinical pharmacology methods were applied to data from 160 adult IC patients (aged 18‐78 years) from two studies (NV20234, 150 patients; NV25118, 10 patients) who received oseltamivir 75‐200 mg twice daily for up to 10 days. An established population‐pharmacokinetic (PK) model with additional effects on oseltamivir and oseltamivir carboxylate (OC) clearance described the PK characteristics of oseltamivir in IC patients versus otherwise healthy (OwH) patients from previous clinical trials. Estimated PK parameters were used to evaluate exposure‐response relationships for virologic endpoints (time to cessation of viral shedding, viral load measures and treatment‐emergent resistance). A drug‐disease model characterized the viral kinetics of influenza accounting for the effect of OC on viral production.

Results

Oseltamivir clearance was 32.5% lower (95% confidence interval [CI], 26.1‐38.8) and OC clearance was 33.7% lower (95% CI, 23.2‐44.1) in IC versus OwH patients. No notable exposure‐response relationships were identified for exposures higher than those achieved after conventional dose oseltamivir 75 mg, which appeared to be close to the maximum effect of oseltamivir. Simulations of the drug‐disease model predicted that initiating treatment within 48 hours of symptom onset had maximum impact, and a treatment duration of 10 days was favourable over 3‐5 days to limit viral rebound.

Conclusions

Our findings support the use of conventional‐dose oseltamivir 75 mg twice daily for 10 days in the treatment of IC adult patients with influenza.
Bromodomain 4 is a potent prognostic marker associated with immune cell infiltration in breast cancer
Authors: Zhong Limei , Yang Zhiyong , Lei Da , Li Lijuan , Song Shaohua , Cao Donglin , Liu Yufeng
Published: August 2020

Bromodomain 4 (BRD4), a member of the bromodomain and extra‐terminal domain protein family, has become a promising epigenetic target in cancer and inflammatory diseases; however, the detailed biological role of BRD4 in breast cancer (BRCA) remains undetermined. We analysed the BRD4 expression levels using the Oncomine and TIMER databases and evaluated the clinical impact of BRD4 on BRCA prognosis using Kaplan‐Meier plot and PrognoScan. The correlation between BRD4 and tumour‐infiltrating immune cells was investigated using TIMER. Furthermore, the correlation between BRD4 expression levels was also analysed using TIMER in addition to the GEPIA database for immune cell gene markers. BRD4 expression was significantly higher in BRCA tissues than in normal tissues, which was significantly correlated with poor overall survival (OS). Specifically, high BRD4 expression was correlated with worse OS and progression‐free survival in patients with BRCA. In addition, BRD4 expression was correlated with levels of infiltrating monocytes (CSF1R, cor = 0.204, P = 9.19e−12), tumour‐associated macrophages (CD68, cor = 0.129, P = 1.81e−05), M1/M2 macrophages and different effector T cells (including Th1/Th2/Treg) in BRCA. These findings suggest that BRD4 could be used as a prognostic biomarker for determining prognosis and immune cell infiltration levels in BRCA.
Bayesian variable selection for non‐Gaussian responses: a marginally calibrated copula approach
Authors: Klein Nadja , Smith Michael Stanley
Published: August 2020

We propose a new highly flexible and tractable Bayesian approach to undertake variable selection in non‐Gaussian regression models. It uses a copula decomposition for the joint distribution of observations on the dependent variable. This allows the marginal distribution of the dependent variable to be calibrated accurately using a nonparametric or other estimator. The family of copulas employed are “implicit copulas” that are constructed from existing hierarchical Bayesian models widely used for variable selection, and we establish some of their properties. Even though the copulas are high dimensional, they can be estimated efficiently and quickly using Markov chain Monte Carlo. A simulation study shows that when the responses are non‐Gaussian, the approach selects variables more accurately than contemporary benchmarks. A real data example in the Web Appendix illustrates that accounting for even mild deviations from normality can lead to a substantial increase in accuracy. To illustrate the full potential of our approach, we extend it to spatial variable selection for fMRI. Using real data, we show our method allows for voxel‐specific marginal calibration of the magnetic resonance signal at over 6000 voxels, leading to an increase in the quality of the activation maps.
Can typical game features have unintended consequences? A study of players’ learning and reactions to challenge and failure in an educational programming game
Authors: Chase Catherine C. , Malkiewich Laura J. , Lee Alison , Slater Stefan , Choi Ahram , Xing Chenmu
Published: August 2020

It is difficult to motivate learners to seek out and persist at challenging learning tasks where failure is likely. However, in game environments, people seem highly motivated to engage with challenges and respond productively to failure. Many typical game features purportedly enhance intrinsic motivation and self‐efficacy, which should improve students’ reactions to challenge and failure, which should in turn enhance learning. An experimental study with early middle school students tested these assumptions by comparing a “Full” version of a typical, commercial programming game to a “Minimal” version of the same game where common game features such as narrative, performance metrics, high‐quality graphics, and sound were removed. In contrast to our hypotheses, players of the Full Game were less likely to choose coding challenges, were less tolerant of coding failures and gained less coding knowledge. Intrinsic motivation and self‐efficacy did not differ between conditions. Correlational analyses showed that failure tolerance and challenge seeking may critically affect learning from educational games. The current study offers an existence proof that some common game features can hinder players' failure tolerance, challenge‐seeking and learning, in certain game contexts. Future research should isolate the effects of individual game features, test generalizability and explore which contextual variables influence the findings.
Lacking socio‐economic status reduces subjective well‐being through perceptions of meta‐dehumanization
Authors: Sainz Mario , Martínez Rocío , Moya Miguel , Rodríguez‐Bailón Rosa , Vaes Jeroen
Published: August 2020

Previous research has identified that both low‐ and high‐socio‐economic groups tend to be dehumanized. However, groups that have a deprived position are more willing to interiorize the negative perceptions that others have about them compared with affluent groups. In this project, we address the role of meta‐(de)humanization (the perceived humanity one thinks is ascribed or denied to one’s group) based on socio‐economic status differences and its influence in the perceived psychological well‐being. We conducted two studies: In Study 1 (correlational,N = 990), we analysed the relationship between socio‐economic status, meta‐dehumanization, and well‐being. Results indicated that lower socio‐economic status positively predicted more meta‐dehumanization and worse well‐being. Moreover, meta‐dehumanization mediated the relationship between socio‐economic status and well‐being. In Study 2 (experimental,N = 354), we manipulated socio‐economic status (low‐, middle‐, and high‐socio‐economic status conditions) to evaluate its influence on meta‐dehumanization and well‐being. Results indicated that individuals of low (vs. higher)‐socio‐economic status perceived more meta‐dehumanization and reported worse well‐being. Finally, a multicategorical mediational analysis indicated that low (vs. middle or high)‐socio‐economic status led to worse well‐being through higher perceived meta‐dehumanization. We discuss differences in perceived meta‐(de)humanization based on groups’ socio‐economic status and implications on the population’s well‐being.
Identity enactment as collective accomplishment: Religious identity enactment at home and at a festival
Authors: Reicher Stephen , Hopkins Nick , Stevenson Clifford , Pandey Kavita , Shankar Shail , Tewari Shruti
Published: August 2020

Much research addresses the proposition that identifying with a group shapes individuals’ behaviour. Typically, such research employs experimental or survey methods, measuring or manipulating social identification and relating this to various outcome variables. Although shedding much light on the processes involved in the identity–behaviour relationship, such research tends to overlook the various constraints that limit individuals’ abilities to act in accordance with their identities. Using interview data gathered in north India, we explore the factors affecting the enactment of a religious identity. More specifically, using data gathered at a religious mass gathering, we compare and contrast participants’ reports of identity enactment when they are at the event and when they are in their home villages. These two contexts differ in terms of their social organization, especially the degree to which they are marked by the presence of a shared identity. Exploring participants’ accounts of such differences in social organization, we consider the social processes that constrain or facilitate identity enactment. In so doing, our analysis contributes to a richer analysis of the identity–behaviour relationship.
Targeting IL‐5 pathway against airway hyperresponsiveness: A comparison between benralizumab and mepolizumab
Authors: Calzetta Luigino , Ritondo Beatrice Ludovica , Matera Maria Gabriella , Facciolo Francesco , Rogliani Paola
Published: August 2020

Background and Purpose

Airway hyperresponsiveness (AHR) is a central abnormality in asthma. IL‐5 may modulate AHR in animal models of asthma, but the available data is inconsistent on the impact of targeting IL‐5 pathway against AHR. The difference between targeting IL‐5 or the IL‐5 receptor, α subunit (IL‐5Rα) in modulating AHR remains to be investigated in human airways. The aim of this study was to compare the role of the anti‐IL‐5Rα benralizumab and the anti‐IL‐5 mepolizumab against AHR and to assess whether these agents influence the levels of cAMP.

Experimental Approach

Passively sensitized human airways were treated with benralizumab and mepolizumab. The primary endpoint was the inhibition of AHR to histamine. The secondary endpoints were the protective effect against AHR to parasympathetic activation and mechanical stress, and the tissue modulation of cAMP.

Key Results

Benralizumab and mepolizumab significantly inhibited the AHR to histamine (maximal effect −134.14 ± 14.93% and −108.29 ± 32.16%, respectively), with benralizumab being 0.73 ± 0.10 logarithm significantly more potent than mepolizumab. Benralizumab and mepolizumab significantly inhibited the AHR to transmural stimulation and mechanical stress. Benralizumab was 0.45 ± 0.16 logarithm significantly more potent than mepolizumab against AHR to parasympathetic activation. The effect of these agents was significantly correlated with increased levels of cAMP.

Conclusion and Implications

Targeting the IL‐5/IL‐5Rα axis is an effective strategy to prevent the AHR. Benralizumab was more potent than the mepolizumab and the concentration‐dependent beneficial effects of both these monoclonal antibodies were related to improved levels of cAMP in hyperresponsive airways.
Assessing avian diversity and community composition along a successional gradient in traditional Lacandon Maya agroforests
Authors: Falkowski Tomasz B. , Vázquez‐Pérez José Raúl , Chankin Adolfo , Campos‐Beltrán Atzin Yetlanezi , Rangel‐Salazar José L. , Cohen Jonathan B. , Diemont Stewart A.W.
Published: August 2020

Abstract

Evidence regarding the ability of agroforests to conserve biological diversity has been mixed; they tend to maintain avian communities with species richness similar to that of undisturbed forest ecosystems but generally do not completely preserve community composition. Using a combination of occupancy modeling and non‐metric multidimensional scaling on point‐count data, we assessed changes in avian community diversity and composition along a successional gradient in traditional Lacandon Maya agroforests and compared them to protected areas in the region. Bird species richness and diversity in Lacandon agroforests peaked in early secondary forest stages. These agroforests' mean Shannon–Weiner diversity was 5% higher than that of nearby protected areas, but their species richness was similar. Community composition in Lacandon agroforests changed throughout succession, with earlier stages supporting communities distinctly characterized by generalist species, while subsequent, less‐intensively managed stages tended to support more forest‐dwellers. The bird community observed in even the most mature secondary forest stages in Lacandon agroforests differed from that of undisturbed rain forest ecosystems. These results demonstrate the potential of traditional Lacandon agroforestry management to conserve avian biodiversity while ensuring food sovereignty for farmers. However, because the community composition of early‐successional stages was different than later stages, shortening fallow cycles and reducing forest cover to increase agricultural production will limit the species this system can support. This study illustrates the value of incorporating traditional agroecosystems into conservation planning as well as maintaining protected areas, because the latter serve as refugia for species that require undisturbed forest habitat in an agroecological matrix.

Abstract in Spanish is available with online material.
Deficiency of pseudogene UPAT leads to hepatocellular carcinoma progression and forms a positive feedback loop with ZEB1
Authors: Xiang Leyang , Huang Xiaoting , Wang Siqi , Ou Huohui , Chen Zhanjun , Hu Zhigang , Huang Yu , Li Xianghong , Yuan Yawei , Yang Dinghua
Published: August 2020

Hepatocellular carcinoma (HCC) is a common disease worldwide. Accumulating reports have evidenced the internal connection between epithelial‐mesenchymal transition (EMT) and cancer stem cells (CSCs), as well as their significance in metastasis and post–operative recurrence. In this study, we investigated an interesting ubiquitin‐proteasome pathway associated pseudogene of AOC4, also known as UPAT, and showed that it was downregulated in 39.78% (37/93) of patients with hepatitis B virus (HBV)‐related HCC. Downregulation of UPAT was associated with multiple worse clinicopathological parameters, as well as decreased recurrence‐free survival (RFS). In vitro and in vivo assays found that overexpression of UPAT significantly suppressed cellular migration, invasion, EMT processes, and CSC properties. Mechanistic studies showed that UPAT promoted ZEB1 degradation via a ubiquitin‐proteasome pathway and, in contrast, ZEB1 transcriptionally suppressed UPAT by binding to multiple E‐box (CACCTG) elements in the promoter region. Moreover, UPAT was negatively correlated with ZEB1 protein in HCC tissues, their combined expression discriminated RFS outcomes for patients with HBV‐related HCC. These data on the UPAT‐ZEB1 circuit‐mediated pathway will further knowledge on EMT and CSCs, and may help to develop novel therapeutic approaches for the prevention of HCC metastasis.
A novel scoring method based on RNA‐Seq immunograms describing individual cancer‐immunity interactions
Authors: Kobayashi Yukari , Kushihara Yoshihiro , Saito Noriyuki , Yamaguchi Shigeo , Kakimi Kazuhiro
Published: August 2020

Because of the complexity of cancer‐immune system interactions, combinations of biomarkers will be required for predicting individual patient responses to treatment and for monitoring combination strategies to overcome treatment resistance. To this end, the “immunogram” has been proposed as a comprehensive framework to capture all relevant immunological variables. Here, we developed a method to convert transcriptomic data into immunogram scores (IGS). This immunogram includes 10 molecular profiles, consisting of innate immunity, priming and activation, T cell response, interferon γ (IFNG) response, inhibitory molecules, regulatory T cells, myeloid‐derived suppressor cells (MDSCs), recognition of tumor cells, proliferation, and glycolysis. Using genes related to these 10 parameters, we applied single‐sample gene set enrichment analysis (ssGSEA) to 9417 bulk RNA‐Seq data from 9362 cancer patients with 29 different solid cancers in The Cancer Genome Atlas (TCGA). Enrichment scores were z‐score normalized (Z) for each cancer type or the entire TCGA cohort. The IGS was defined by the formula IGS = 3 + 1.5 × Z so that patients would be well distributed over a range of scores from 1 to 5. The immunograms constructed in this way for all individual patients in the entire TCGA cohort can be accessed at “The RNA‐Seq based Cancer Immunogram Web” (https://yamashige33.shinyapps.io/immunogram/).
Emergence of the Link Between the Approximate Number System and Symbolic Math Ability
Authors: Wang Jinjing (Jenny) , Halberda Justin , Feigenson Lisa
Published: August 2020

Experimentally manipulating Approximate Number System (ANS) precision has been found to influence children’s subsequent symbolic math performance. Here in three experiments (N = 160; 81 girls; 3–5 year old) we replicated this effect and examined its duration and developmental trajectory. We found that modulation of 5‐year‐olds’ ANS precision continued to affect their symbolic math performance after a 30‐min delay. Furthermore, our cross‐sectional investigation revealed that children 4.5 years and older experienced a significant transfer effect of ANS manipulation on math performance, whereas younger children showed no such transfer, despite experiencing significant changes in ANS precision. These findings support the existence of a causal link between nonverbal numerical approximation and symbolic math performance that first emerges during the preschool years.
Cord blood androgen levels of females from same sex and opposite sex twins – A pilot study
Authors: Galiano Valentina , Solazzo Giulia , Rabinovici Jaron , Nahid Farzam , Rina Hemi , Baccarelli Andrea A. , Machtinger Ronit
Published: August 2020

Objective

Opposite‐sex twins have shown behavioural and reproductive differences between females and males. These differences may be determined by higher intrauterine levels of androgens among females that were exposed to a male co‐twin. The aim of this study was to compare cord blood androgen levels in females from same‐sex and opposite‐sex twins.

Design

A prospective study. In this pilot study, we compared cord blood androgens (DHEA‐S, Δ‐4 androstenedione, total testosterone—TT) and sex hormone‐binding globulin (SHBG) levels in 20 females from same sex and 20 females from opposite‐sex dichorionic diamniotic twins. We used generalized estimating equation (GEE) modelling to assess differences in cord blood androgens between females from same‐sex twin pregnancies and females from opposite‐sex twin pregnancies.

Patients

Twenty opposite‐sex twin pairs (female‐male twins) and 20 same‐sex twin pairs (female‐female).

Measurements

Cord blood total testosterone, Δ‐4 androstenedione, DHEA‐S and sex hormone‐binding globulin (SHBG) levels.

Results

No difference in the levels of androgens as Δ‐4 androstenedione, total testosterone and SHBG was identified between females that were exposed to a female co‐twin compared with females that were exposed to a male co‐twin. DHEA‐S levels were significantly lower among females from opposite‐sex twins compared with females from same‐sex twins.

Conclusions

Our preliminary data do not support the hypothesis that females exposed to male co‐twins are exposed to higher levels of androgens in utero compared with females exposed to female co‐twins. Further studies are needed to explain the reported behavioural and reproductive differences among opposite‐sex twins.
Anti‐striational antibodies: Expanding their clinical significance
Authors: Suzuki Shigeaki , Nagane Yuriko , Uzawa Akiyuki , Imai Tomihiro , Murai Hiroyuki , Nakahara Jin , Utsugisawa Kimiaki
Published: August 2020

Anti‐striational antibodies (StrAbs) have been described as serum immunoglobulins that react with cross‐striations of skeletal muscle in patients with myasthenia gravis (MG). StrAbs were expected to be useful biomarkers of MG; however, because of their low specificity, the diagnostic utility of StrAbs has been limited. The main autoantigens of StrAbs include titin, ryanodine receptor and Kv1.4. MG patients with StrAbs tend to suffer from bulbar symptoms and myasthenic crisis. The most remarkable finding regarding the clinical significance of StrAbs is their association with myositis concomitant with MG. Myocarditis is a lethal complication in MG patients, but it is treatable by immunotherapy. Patients with myocarditis usually show rapid deterioration, with serious arrhythmias and severe heart failure. As myocarditis often develops in patients with myositis accompanied by MG, MG with myositis and/or myocarditis is an important subset of patients. MG is one of the immune‐related adverse events associated with immune checkpoint inhibitors. MG with myositis and/or myocarditis is an infrequent subset of patients in the usual clinical settings; however, it is more common in patients with immune‐related adverse events. Anti‐titin and anti‐Kv1.4 antibodies were preferentially detected in patients with MG with myositis and/or myocarditis, and in patients with late‐onset and thymoma‐associated MG. The detection of StrAbs provides more specific and useful clinical information for the classification and management of MG patients, and identifies diagnostic biomarkers of serious immune‐related adverse events in cancer patients treated with immune checkpoint inhibitors.
Exosomal miR‐130a‐3p regulates osteogenic differentiation of Human Adipose‐Derived stem cells through mediating SIRT7/Wnt/β‐catenin axis
Authors: Yang Shude , Guo Shu , Tong Shuang , Sun Xu
Published: August 2020

Objectives

It is of profound significance for clinical bone regeneration to clarify the specific molecular mechanism from which we found that osteogenic differentiation of adipose‐derived stem cells (ADSCs) will be probably promoted by exosomes.

Materials and Methods

By means of lentiviral transfection, miR‐130a‐3p overexpression and knockdown ADSCs were constructed. Alizarin Red S was used to detect the calcium deposits, and qPCR was used to detect osteogenesis‐related genes, to verify the effect of miR‐130a‐3p on the osteogenic differentiation of ADSCs. CCK‐8 was used to detect the effect of miR‐130a‐3p on the proliferation of ADSCs. The target binding between miR‐130a‐3p and SIRT7 was verified by dual‐luciferase reporter gene assay. Furthermore, the role of Wnt signalling pathway in the regulation of ADSCs osteogenesis and differentiation by miR‐130a‐3p was further verified by detecting osteogenic‐related genes and proteins and alkaline phosphatase activity.

Results

(a) Overexpression of miR‐130a‐3p can enhance the osteogenic differentiation of ADSCs while reducing protein and mRNA levels of SIRT7, a target of miR‐130a‐3p. (b) Our study further found that overexpression of miR‐130a‐3p leads to down‐regulation of SIRT7 expression with up‐regulation of Wnt signalling pathway‐associated protein. (c) Overexpression of miR‐130a‐3p inhibited proliferation of ADSCs, while knockdown promoted it.

Conclusions

The obtained findings indicate that exosomal miR‐130a‐3p can promote osteogenic differentiation of ADSCs partly by mediating SIRT7/Wnt/β‐catenin axis, which will hence promote the application of exosomal microRNA in the field of bone regeneration.
Care of international living kidney donor candidates in the United States: A survey of contemporary experience, practice, and challenges
Authors: Lentine Krista L. , Motter Jennifer D. , Henderson Macey L. , Hays Rebecca E , Shukhman Ellen , Hunt Julia , Al Ammary Fawaz , Kumar Vineeta , LaPointe Rudow Dianne , Van Pilsum Rasmussen Sarah E. , Nishio‐Lucar Angie G. , Schaefer Heidi M. , Cooper Matthew , Mandelbrot Didier A.
Published: August 2020

The evaluation and care of non‐US citizen, non‐US residents who wish to come to the United States to serve as international living kidney donors (ILKDs) can pose unique challenges. We surveyed US transplant programs to better understand practices related to ILKD care. We distributed the survey by email and professional society list‐servs (Fall 2018, assessing 2017 experience). Eighty‐five programs responded (36.8% program response rate), of which 80 considered ILKD candidates. Only 18 programs had written protocols for ILKD evaluation. Programs had a median of 3 (range: 0,75) ILKD candidates who initiated contact during the year, from origin countries spanning 6 continents. Fewer (median: 1, range: 0,25) were approved for donation. Program‐reported reasons for not completing ILKD evaluations included visa barriers (58.6%), inability to complete evaluation (34.3%), concerns regarding follow‐up (31.4%) or other healthcare access (28.6%), and financial impacts (21.4%). Programs that did not evaluate ILKDs reported similar concerns. Staff time required to evaluate ILKDs was estimated as 1.5‐to‐3‐times (47.9%) or >3‐times (32.9%) that needed for domestic candidates. Among programs accepting ILKDs, on average 55% reported successful completion of 1‐year follow‐up. ILKD evaluation is a resource‐intensive process with variable outcomes. Planning and commitment are necessary to care for this unique candidate group.
Revisiting cytomorphology, including unusual features and clinical scenarios of 8 cases of alveolar soft part sarcoma with TFE3 immunohistochemical staining in 7 cases
Authors: Rekhi Bharat , Rao Vidya , Ramadwar Mukta
Published: August 2020

Objectives

To present a comprehensive analysis of cytomorphological features, including clinical scenarios, for 8 cases (4 males, 4 females, aged 17‐39 years, average = 28.5) of, retrospectively diagnosed alveolar soft part sarcoma (ASPS), with TFE3 immunostaining in 7 cases.

Methods

Conventional Papanicolaou and May Grunwald‐Giemsa (MGG) stained smears and corresponding tissue sections were critically reviewed. Fine needle aspiration cytology was performed for primary diagnosis in 6 cases and for metastatic lesions in 2 cases. TFE3 and other immunohistochemical stains were tested using polymer detection technique.

Results

Tumour sites were thigh (n = 6), shoulder (1) and neck (1). Tumour size (n = 6) varied from 5 to 14.5 cm (average = 7.2). Seven out of 8 cases were correctly diagnosed on cytosmears. The smears were mostly hypercellular (5), composed of cohesive clusters (8), including cell balls and pseudopapillae (3) and singly scattered cells (8). Tumour cells were round to oval, containing central to eccentric nuclei (8), abundant granular (8) to finely vacuolated (7) cytoplasm that was ill‐ to well‐defined, intracytoplasmic rod‐like or needle‐shaped crystals (3) and prominent nucleoli (8), Additionally, there were binucleated cells (7), multinucleation (2), intracytoplasmic inclusions (3), intranuclear inclusions (2), intercellular stroma (5) and bare nuclei (8). Immunohistochemically, 7/8 tumours were positive for TFE3.

Conclusions

This constitutes the largest series describing cytomorphological spectrum of ASPS with TFE3 immunostaining results. Frequently observed features and rod‐like/needle‐shaped crystals on MGG smears, can help to differentiate ASPS from its mimics. TFE3 immunostaining aids in substantiating diagnoses, in an appropriate clinicoradiological context.
Using modelled prey to predict the distribution of a highly mobile marine mammal
Authors: Pendleton Daniel E. , Holmes Elizabeth E. , Redfern Jessica , Zhang Jinlun
Published: August 2020

Aim

Species distribution models (SDMs) are a widely used tool to estimate and map habitat suitability for wildlife populations. Most studies that model marine mammal density or distributions use oceanographic proxies for marine mammal prey. However, proxies could be a problem for forecasting because the relationships between the proxies and prey may change in a changing climate. We examined the use of model‐derived prey estimates in SDMs using an iconic species, the western Arctic bowhead whale (Balaena mysticetus).

Location

Western Beaufort Sea, Alaska, USA.

Methods

We used Biology Ice Ocean Modeling and Assimilation System (BIOMAS) to simulate ocean conditions important to western Arctic bowhead whales, including important prey species. Using both static and dynamic predictors, we applied Maxent and boosted regression tree (BRT) SDMs to predict bowhead whale habitat suitability on an 8‐day timescale. We compared results from models that used bathymetry with those that used only BIOMAS simulated variables.

Results

The best model included bathymetry and BIOMAS variables. Inclusion of dynamic variables in SDMs produced predictions that reflected temporal dynamics evident from the survey data. Bathymetry was the most influential variable in models that included that variable. Zooplankton was the most important variable for models that did not include bathymetry. Models with bathymetry performed slightly better than models with only BIOMAS derived variables.

Main conclusions

Bathymetry and modelled zooplankton were the most important predictor variables in bowhead whale distribution models. Our predictions reflected within‐year variability in bowhead whale habitat suitability. Using modelled prey availability, rather than oceanographic proxies, could be important for forecasting species distributions. Predictor variables used in our study were derived from a biophysical ocean model with demonstrated ability to project future ocean conditions. A natural next step is to use output from our biophysical ocean model to understand the effects of Arctic climate change.
At multiple fronts: Diabetes stigma and weight stigma in adults with type 2 diabetes
Authors: Himmelstein M. S. , Puhl R. M.
Published: August 2020

Aim

The diabetes and obesity fields have called for attention to the harmful role of stigma in obesity and diabetes, especially given that little is known about the extent and nature of diabetes stigma facing adults with type 2 diabetes, or the experience of weight stigma in this population. This study addresses this research gap by examining the prevalence and demographic correlates of weight stigma and diabetes stigma in individuals with type 2 diabetes.

Methods

Adults (N = 1212, Mage = 52) with type 2 diabetes living in the USA were recruited by a healthcare‐oriented market research firm, and completed online questionnaires to assess their experiences with weight stigma and diabetes stigma, as well as their internalization of both forms of stigma. Rates of stigma and sociodemographic correlates (years with type 2 diabetes, age, education, income, gender, race and BMI) were examined.

Results

More than half of participants reported prior experiences of weight stigma, and 40–60% reported experiencing weight stigma in a healthcare context. Participants reported frequent experiences with diabetes‐related stigma including blame and judgement, self‐stigma and differential treatment. Women reported more weight stigma than men, and White women appeared particularly at risk for experiencing weight and diabetes related stigma relative to Black women.

Conclusions

Individuals with type 2 diabetes reported higher rates of weight stigma than the general population, experienced high rates of diabetes‐related stigma, and many internalized these forms of stigma. Increased attention to stigma reduction is essential to ensuring equitable care for individuals with type 2 diabetes.
Echocardiographic reference ranges for normal cardiac Doppler data in healthy Turkish population: ECHO‐DOP‐TR Trial
Authors: Şafak Özgen , Gürsoy Ozan , Emren Volkan , Demir Emre , Yıldırım Tarık , Argan Onur , Şimşek Ersin Çağrı , Aytemiz Fatih , Özdemir Emre , Bayar Nermin , Erkal Zehra , Çelik Oğuzhan , Akhan Onur , Dönmez Cevdet , Kemaloğlu Öz Tuğba , Akyel Serdar , Oktay Ergene Asim , Özkan Mehmet
Published: August 2020

Aim

Doppler echocardiography has become the standard imaging modality for diastolic function and provides pathophysiological insight into systolic and diastolic heart failure. In this study, we aimed to obtain normal echocardiographic Doppler parameters of healthy Turkish population.

Methods

Among 31 collaborating institutions from all regions of Turkey, 1154 healthy volunteers were enrolled in this study. Predefined protocols were used for all participants during echocardiographic examination and The American Society of Echocardiography and European Association of Cardiovascular Imaging recommendations were used for echocardiographic Doppler measurements.

Results

A total of 967 healthy participants were enrolled in this study after applying exclusion criteria. Echocardiographic examination was obtained from all subjects following predefined protocols. Mitral E wave velocity and E/A ratio were higher in females and decreased progressively in advancing ages. E wave deceleration time and A wave velocity were increased with aging. Assessment of tissue Doppler velocities showed that left ventricular lateral e′, septal e′, and septal s′ were higher in younger subjects and in females. E/e′ ratio was increased progressively with advancing decades. Right ventricular e′ and s′ were decreased but a′ was increased with increasing age. Septal e′ lower than 8 cm/s was 1.9% in the fifth decade and 13.7% in ages older than 50 years. The E/e′ ratio greater than 15 (and also 13) was not found.

Conclusion

This study, for the first time, provides echocardiographic reference ranges for normal cardiac Doppler data in healthy Turkish population which will be useful in routine clinical practice as well as in future clinical trials.