bluuebunny/crossref_metadata_2025 huggingface dataset:
Echocardiography in adult patients with PDA: A simplified approach
Authors: Rajesh Vinutha , Kheiwa Ahmed , Varadarajan Padmini
Published: December 2020

Patent ductus arteriosus is a common congenital heart anomaly in the newborn and children. It is often diagnosed and treated in childhood; however, there are a subset of patients who survive to adulthood undiagnosed, and it is present in adulthood with various clinical presentations. The clinical presentation, hemodynamics, and management of PDA presentation in adults depend on various factors, primarily the size of PDA, magnitude of shunting, and status of pulmonary vasculature. Echocardiography is often the primary imaging modality in the evaluation of adult patients with PDA and is an important tool that provides diagnostic and hemodynamic assessment for the initial evaluation and routine follow‐up after PDA closure. In this review, we present a simplified approach of basic echocardiographic assessment of various types of PDA presentations in adults.
Plasma soluble suppression of tumorigenicity 2 and depression after acute ischemic stroke
Authors: Lu Yaling , Qian Sifan , Chen Haichang , Yuan Pengcheng , Zhang Rui , Wang Aili , Zhang Jintao , Ju Zhong , Zhang Yonghong , Xu Tan , Zhong Chongke
Published: December 2020

Background and purpose

Soluble suppression of tumorigenicity 2 (sST2) might be related to stroke and depression, but the association of sST2 with poststroke depression (PSD) is unclear. The study aimed to prospectively assess the association between plasma sST2 levels and PSD.

Methods

A total of 635 acute ischemic stroke patients with sST2 measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this analysis. We used the 24‐item Hamilton Rating Scale for Depression to assess depression at 3 months, and PSD was defined as a score of ≥8. Logistic regression analysis was performed to estimate the risk of PSD associated with sST2, and net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to assess the predictive value of sST2.

Results

Two hundred fifty (39.4%) patients developed depression at 3 months after ischemic stroke. Patients with PSD had higher sST2 levels than patients without PSD (172.7 vs. 153.8 pg/ml; p = 0.003). After adjustment for age, sex, education, National Institutes of Health Stroke Scale score, and other covariates, the odds ratio for the highest quartile of sST2 compared with the lowest quartile was 1.84 (95% confidence interval, 1.10–3.08) for PSD. Adding sST2 to a conventional model notably improved risk prediction for PSD (category‐free NRI = 19.34%, 95% confidence interval = 4.39%–34.28%, p = 0.017; IDI = 1.20%, 95% confidence interval = 0.25%–2.15%, p = 0.014).

Conclusions

Increased plasma sST2 levels in the acute phase of ischemic stroke were significantly associated with the increased risk of PSD, independently of conventional risk factors.
Embodiment, Empathic Perception, and Spiritual Ontologies in Q'eqchi’ Maya Healing: An Ethnographic Exploration
Authors: Hatala Andrew R. , Caal Thomas
Published: December 2020

Social science research and theory suggests that perception can be viewed as an embodied process of social and cultural mediation. This embodied view of perception involves deep connections between the mind and body, as well as the larger social context. Previous research with Maya communities has outlined how aspects of subject and object, or self and other, can be bridged through forms of social connectedness with the family or community. This ethnographic work with Q'eqchi’ Maya healers in southern Belize details embodied and sensual aspects of therapeutic encounters, including aspects of healers embodied modes of perception or “signs” during pulse reading, manual manipulation, dreams, and prayer that mesh together and span across worlds of flesh and spirit. These embodied forms of somatic knowledge further allow us to reflect on the notions of “empathy” in Q'eqchi’ clinical encounters, challenging cognitive biases and boundaries of patients, healers, and spiritual worlds. Exploring an ontological shift away from mere material bodies and social actors opens new directions for embodiment literature and a query of spiritual ontologies. Methodological and theoretical tools to critique a spiritual/material dualism and re‐vision embodiment practices of therapeutic engagement, including their clinical significations, representations, and cultural meanings, are also explored.
Right atrial‐related structures in horses of interest during electrophysiological studies
Authors: Vernemmen Ingrid , Vera Lisse , Van Steenkiste Glenn , Deserranno Bram , Muylle Sofie , Decloedt Annelies , van Loon Gunther
Published: December 2020

Background

Arrhythmias are common in horses, but catheter‐based minimally invasive electrophysiological studies and therapeutic interventions have been poorly explored in equine medicine, partly due to the lack of detailed anatomical knowledge of the equine heart.

Objectives

To describe the dimensions and anatomical features of some electrophysiologically important landmarks of the right atrium in detail and assess their correlation with bodyweight and aortic diameter.

Study design

Ex vivo cadaveric study.

Methods

Twenty‐one hearts of Warmblood horses, subjected to euthanasia for noncardiovascular reasons, were examined post‐mortem. The dimensions and anatomical features of the coronary sinus, the great cardiac vein and the oval fossa were recorded. Spearman's Rho correlation coefficients were calculated for correlations between the quantitative parameters and bodyweight and aortic diameter.

Results

Median dimensions for coronary sinus, great cardiac vein and oval fossa were obtained. A Thebesian valve, partially covering the ostium of the coronary sinus, was present in 9 of the 21 hearts. A median of 6.5 (range 4‐9) valves were present in the great cardiac vein. Several parameters, among which the dimensions of the oval fossa and the length of the great cardiac vein, were significantly positively correlated with bodyweight and aortic diameter.

Main limitations

Measurements do not consider the dynamic changes during the cardiac cycle as measurements were performed ex vivo. All specimens were retrieved from Warmblood horses, therefore measurements might not apply to other breeds.

Conclusions

This study delivers a detailed description of important right atrial‐related structures, necessary for the development of minimally invasive intracardiac procedures in horses. Adequate imaging techniques will have to be explored in order to guide these procedures.
Validation of standing cone beam computed tomography for diagnosing subchondral fetlock pathology in the Thoroughbred racehorse
Authors: Curtiss Alexandra L. , Ortved Kyla F. , Dallap‐Schaer Barbara , Gouzeev Sergei , Stefanovski Darko , Richardson Dean W. , Wulster Kathryn B.
Published: December 2020

Background

Subchondral bone pathology is common in Thoroughbred racehorses and believed to precede more serious injury. Early identification of pathology is critical to allow for intervention.

Objectives

To determine interobserver variability of fetlock subchondral bone lesions using cone beam and fan beam computed tomography (CBCT, FBCT) and to validate a robotics‐controlled CBCT to identify fetlock subchondral bone pathology in the Thoroughbred racehorse.

Study design

Prospective cohort study.

Methods

FBCT and CBCT images were acquired of 25 metacarpo‐/metatarsophalangeal joints of Thoroughbred racehorses. Images were analysed for subchondral bone lesions commonly identified in Thoroughbred fetlocks by an imaging specialist and surgery specialist. Interobserver and intermodality equivalence were determined with a Pearson correlation analysis and Bland‐Altman equivalence test.

Results

Interobserver FBCT correlation was significant (P < .05) for 19 of 25 variables (Pearson R mean 0.77). Concordance was significant for all 25 variables (Bland Altman average difference 0.28 ± 0.21 mm). Interobserver CBCT correlation was significant for 21 of 25 variables (Pearson R mean 0.73). Concordance was significant for all variables (Bland Altman average difference 0.07 ± 1.90 mm). Intermodality (FBCT vs CBCT) correlation and concordance was significant for all variables as interpreted by the radiologist (Pearson R mean of 0.72, Bland Altman average difference 0.21 ± 0.47 mm). Intermodality correlation was significant for 19 of 25 variables as interpreted by the surgeon (Pearson R mean of 0.72). Concordance was significant for all variables (Bland Altman average difference 0.49 ± 0.52 mm).

Main limitations

Neither FBCT nor CBCT images were compared with other imaging modalities/histopathology; limited number of cases included; inconsistent agreement of small lesions in specific categories.

Conclusions

Standing CBCT is a valid diagnostic modality to identify subchondral bone lesions in Thoroughbred fetlocks. This technology may provide valuable information regarding the development and progression of fetlock pathology and yield insight into predisposing factors leading to more severe pathology.
Parental lifespan and the likelihood of reaching the age of 90 years in the Netherlands Cohort Study
Authors: Brandts Lloyd , van Poppel Frans WA , van den Brandt Piet A
Published: December 2020

Aim

Growing evidence suggests an association between parental longevity and lifespan of subsequent generations. We aimed to reproduce earlier findings, showing a positive association between parental longevity and offspring's longevity. Additionally, we investigated whether this is mainly driven by the maternal or paternal germline in male and female offspring.

Methods

For these analyses, data from the oldest birth cohort (1916–17) of the Netherlands Cohort Study was used. Participants filled in a baseline questionnaire in 1986 (at age 68–70 years). Follow up for vital status information until the age of 90 years (2006–07) was >99.9% complete. Multivariable‐adjusted Cox regression analyses with a fixed follow‐up time were based on 2368 men and 2657 women with complete parental survival data and relevant confounders to calculate risk ratios (RR) of reaching longevity.

Results

In age‐adjusted models, paternal and maternal age at death were significantly positively associated with reaching 90 years in both male and female offspring. In male offspring, paternal age at death (≥90 yearsvs<80 years) showed the strongest association with survival to 90 years (RR 1.42, 95% CI 1.07–1.89), after confounder correction. In female offspring, maternal age at death (≥90 yearsvs<80 years) showed the strongest association with survival to 90 years (RR 1.20, 95% CI 1.04–1.40).

Discussion

After confounder adjustment, stronger and significant associations were observed between paternal lifespan and male offspring longevity, and maternal lifespan and female offspring longevity. Future research should investigate through which pathways a longer lifespan of parents is transmitted to their offspring.Geriatr Gerontol Int 2021; 21: 215–221.
Incidence of recently acquired hepatitis C virus infection among HIV‐infected patients in southern Spain
Authors: Gonzalez‐Serna A , Macias J , Palacios R , Gómez‐Ayerbe C , Tellez F , Rivero‐Juárez A , Fernandez M , Santos J , Real LM , Gonzalez‐Domenech CM , Gomez‐Mateos J , Pineda JA ,   the HEPAVIR study group
Published: December 2020

Objectives

Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV.

Methods

Primary RAHC infection was diagnosed when anti‐HCV antibody seroconversion was documented. In anti‐HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected.

Results

All 350 patients tested negative for anti‐HCV at baseline and had at least one follow‐up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person‐years were 3.77 (0.5–12.9) in 2016, 1.85 (0.6–4.3) in 2017, 1.49 (0.4–3.8) in 2018 and 1.98 (0.6–4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93–172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38–54.15; P = 0.026) and sharing chem‐sex drugs (IRR: 4.93, 95% CI: 1.17–20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected.

Conclusions

The incidence of RAHC among HIV‐infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem‐sex drugs among MSM.
Ultrasound imaging for the differential diagnosis of periapical lesions of endodontic origin in comparison with histopathology – a systematic review and meta‐analysis
Authors: Natanasabapathy V. , Arul B. , Mishra A. , Varghese A. , Padmanaban S. , Elango S. , Arockiam S.
Published: December 2020

Background

Differentiating periapical lesions is important for treatment planning and subsequent treatment outcome.

Objective

To assess the diagnostic accuracy of ultrasound imaging for the differentiation of periapical lesions in comparison with histopathology.

Methods

PubMed, Scopus, Embase, Web of Science and ProQuest databases were searched for clinical studies published until June 2020 that evaluated the use of ultrasound (US) imaging for differential diagnosis of periapical lesions and used histopathology as the reference standard. Animal studies, laboratory‐based studies, reviews and clinical studies not using a reference standard were excluded. Risk of bias (RoB) assessment was performed using a modified Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool. The random effects model was used for quantitative analysis of the data, and the Deeks test was used for calculating publication bias. Quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results

Twelve articles were included in the systematic review, out of which ten articles were quantitatively assessed. All the articles had a high RoB and concerns regarding applicability in the patient selection domain. For the index test domain, seven articles had low and the remaining five had unclear RoB and concerns regarding applicability. In the reference standard domain, low RoB and concerns regarding applicability were observed for all the articles. The RoB was low in flow and timing domains in all the articles except for one, where it was high. Summary estimates of sensitivity and specificity of US to diagnose periapical granulomas were 0.94 and 0.98, whereas for periapical cysts it was 0.98 and 0.99, respectively. Area under the curve for diagnosis of both periapical granulomas and periapical cysts was 0.99. All the included articles had inherent publication bias. Quality of evidence using GRADE, for sensitivity, was moderate for periapical granulomas and high for periapical cysts, whereas for specificity, it was high for periapical granulomas and low for periapical cysts.

Discussion

The available evidence is considered to be of low quality due to the observational nature of the studies and inherent publication bias.

Conclusion

Although the sensitivity and specificity for differentiating periapical cysts and periapical granulomas using US were high, taking the quality of evidence into consideration, it can serve as an additional tool in differential diagnosis of periapical lesions.
Caregivers’ report of HIV‐associated oral manifestations among HIV‐unexposed, exposed, and infected Kenyan children
Authors: Seminario Ana Lucia , Kemoli Arthur , Benki‐Nugent Sarah , Chebet Daisy , Gomez Lauren , Wamalwa Dalton , John‐Stewart Grace , Slyker Jennifer A.
Published: December 2020

Background

Few oral health studies have been conducted in HIV‐exposed uninfected children, who, like their HIV‐infected peers, have altered immunity and perinatal drug exposures.

Aim

To compare caregiver’ self‐report of oral diseases, hygiene practices and utilization of routine dental care, between HIV‐infected (HIV), HIV‐exposed uninfected (HEU), and HIV‐unexposed uninfected (HUU) children in Kenya.

Design

This nested cross‐sectional study was conducted at the Kenyatta National Hospital, Nairobi, Kenya. Caregivers of 196 children (104 HIV‐infected, 55 HEU, and 37 HUU) participated in this study. Using a validated questionnaire from the WHO and photographs of HIV‐related oral lesions, we collected data on oral diseases and oral health practices.

Results

Caregivers of HIV‐infected children reported at least one oral disease in their children (42%; HEU [27%]; HUU [17%; P = .008]). Oral candidiasis was the most common disease reported (HIV‐infected [24%], HEU [5.5%], and HUU [2.8%; P < .05]). Baseline CD4% was associated with oral candidiasis (OR = 0.93, 95% CI: 0.88‐0.98). Only 16% of children had ever visited a dentist, and most initiated brushing after 3 years of age (83%). Nearly all (98%) caregivers desired a follow‐up oral examination.

Conclusions

HIV infection/exposure and low CD4% were associated with increased odds of oral diseases. Most caregivers desired a follow‐up oral examination for their children.
Decision support for the selection of optimal tower site locations for early‐warning wildfire detection systems in South Africa
Authors: Heyns Andries M. , du Plessis Warren , Curtin Kevin M. , Kosch Michael , Hough Gavin
Published: December 2020

Effective early detection of forest fires can be achieved by specialised systems of tower‐mounted cameras. Foresters and locals with intimate knowledge of the terrain traditionally plan the tower site locations – without the aid of computational optimisation tools. However, such knowledge and expertise may not be available to system planners when entering vast new territories. The process of selecting multiple tower sites from a large number of potential site locations with the aim of maximising system visibility of smoke above a prescribed region is a complex combinatorial optimisation problem. We present two recent applications of novel site‐selection frameworks for tower‐mountedcamera‐based wildfire detection systems(CWDS), which have been under development with guidance from experts from the South African developedForestWatchwildfire detection system. A novel single‐site search framework determined alternatives for 13 proposed sites in South Africa's Mpumalanga province, of which 6 alternatives were chosen over the initially proposed sites. The system site selection framework was showcased in determining a four‐camera CWDS layout in South Africa's Southern Cape – significantly improving on the detection capability of the layout initially proposed by technical experts.
An integrative review: Women’s psychosocial vulnerability in relation to paid work after a breast cancer diagnosis
Authors: Melnyk Halia , Djukic Maja , Merriman John , Vaughan Dickson Victoria
Published: December 2020

Aim

The aim of this integrative review was to explore psychosocial vulnerabilities in women after a breast cancer diagnosis that are related to their paid work.

Design

The review methodology was guided by Whittemore and Knafl. The Mehnert Cancer Survivorship and Work Model provided a lens through which to view vulnerability in working women with a focus on facilitating interventions to improve both recovery and work outcomes.

Data Sources

PUBMED, CINAHL, Web of Science, and PsycNET databases were searched for English language papers published between January 2014–June 2020.

Review Methods

Titles and abstracts were screened. Inclusion/exclusion criteria were then applied to full text screen of the remaining articles following PRISMA guidelines. Thirteen studies meeting the inclusion criteria were critically appraised using the Critical Appraisal Skills Programme (CASP) checklist. A constant comparison approach was used to systematically distil findings into categories and assess their fit within the Mehnert Model subdomains.

Results

Vulnerabilities coalesced predominantly within the following subdomains: (a) changes in identity and role functioning; (b) social reintegration; (c) coping strategies; and (d) social supports. Patterns and themes within these subdomains were related both positively and negatively to form the contours of a survivor's satisfaction/dissatisfaction with quality of life related to work and breast cancer recovery.

Conclusion

Overall, findings highlight the importance of employment and work environments in bolstering women's psychosocial health after a breast cancer diagnosis.

Impact

Findings from this review support adapting psychosocial distress screening to include vulnerabilities relating to work life. Nurses are ideally positioned to facilitate this screening and engage clinicians in a dialogue surrounding patient's support needs due to nursing's central role on the interdisciplinary team. Nurses may also foster collective accountability for implementing ongoing multidisciplinary survivorship care plans that include a return to work component.
Who Should Bear the Risk When Self‐Driving Vehicles Crash?
Authors: Kauppinen Antti
Published: December 2020

The moral importance of liability to harm has so far been ignored in the lively debate about what self‐driving vehicles should be programmed to do when an accident is inevitable. But as discussions in the context of self‐defense have highlighted, liability matters a great deal to just distribution of risk of harm. While it is sometimes morally required simply to minimize the risk of relevant harms, this is not so when one party is responsible for creating the risky situation, which is common in real‐world traffic scenarios. In particular, insofar as possible, those who have voluntarily engaged in activity that foreseeably poses the risk of harm should be the ones who bear it, other things being equal. This should not be controversial when someone intentionally or recklessly creates a risky situation. But I argue that on plausible assumptions, merely choosing to use a self‐driving vehicle typically gives rise to a degree of liability, so that such vehicles should be programmed to shift the larger share of the risk from innocent outsiders to users by default. Insofar as automated vehicles cannot be programmed to take all the factors affecting liability into account, there is a pro tanto moral reason to restrict their use.
The anti‐angiogenesis role of FBXW7 in diabetic retinopathy by facilitating the ubiquitination degradation of c‐Myc to orchestrate the HDAC2
Authors: Hu Lihua , Lv Xiangyun , Li Dai , Zhang Wanping , Ran Guangyao , Li Qingchun , Hu Jun
Published: December 2020

Diabetic retinopathy (DR) is the most prevalently occurring microvascular complication in diabetic patients that triggers severe visual impairments. The anti‐angiogenesis role of FBXW7 has been identified in breast cancer. Therefore, this study intends to decipher the mechanism of FBXW7 in angiogenesis of DR. DR model was induced on mice using high‐glucose (HG) and high‐fat diet, and retinal microvascular endothelial cells (RMECs) isolated from normal mice were induced with HG, followed by evaluation of FBXW7, Ki67, HIF‐1α and VEGF expression by immunofluorescence, immunohistochemistry or Western blot analysis. After gain‐ and loss‐of‐function assays in normal and DR mice, angiogenesis was assessed by CD31 fluorescence staining and Western blot analysis. After ectopic expression and silencing experiments in HG‐induced RMECs, RMEC proliferation, migration and angiogenesis were, respectively, determined by EdU, Transwell and in vitro angiogenesis assays. The impact of FBXW7 on the ubiquitination of c‐Myc was studied by cycloheximide chase assay and proteasome inhibition, and the binding of c‐Myc to HDAC2 promoter by dual‐luciferase reporter gene experiment. DR mice and HG‐induced RMECs possessed down‐regulated FBXW7 and up‐regulated Ki67, HIF‐1α and VEGF. Silencing FBXW7 enhanced angiogenesis in normal mouse retinal tissue, but overexpressing FBXW7 or silencing c‐Myc diminished angiogenesis in DR mouse retinal tissue. Overexpressing FBXW7 or silencing c‐Myc depressed proliferation, migration and angiogenesis in HG‐induced RMECs. FBXW7 induced c‐Myc ubiquitination degradation, and c‐Myc augmented HDAC2 expression by binding to HDAC2 promoter. Conclusively, our data provided a novel sight of anti‐angiogenesis role of FBXW7 in DR by modulating the c‐Myc/HDAC2 axis.
Melatonin inhibiting the survival of human gastric cancer cells under ER stress involving autophagy and Ras‐Raf‐MAPK signalling
Authors: Huang Yongye , Yuan Kexun , Tang Meifang , Yue Jiaming , Bao Lijun , Wu Shuang , Zhang Yanxin , Li Yin , Wang Yihang , Ou Xu , Gou Jiaxin , Zhao Qi , Yuan Lin
Published: December 2020

Melatonin exhibits antitumour activities in the treatment of many human cancers. In the present study, we aimed to improve the therapeutic potential of melatonin in gastric cancer. Our results confirmed that melatonin dose‐dependently suppressed the proliferation and necrosis, and increased G0/G1 phase arrest, apoptosis, autophagy and endoplasmic reticulum (ER) stress. The Ras‐Raf‐MAPK signalling pathway was activated in cells after melatonin treatment. RNA‐seq was performed and GSEA analysis further confirmed that many down‐regulated genes in melatonin‐treated cells were associated with proliferation. However, GSEA analysis also indicated that many pathways related to metastasis were increased after melatonin treatment. Subsequently, combinatorial treatment was conducted to further investigate the therapeutic outcomes of melatonin. A combination of melatonin and thapsigargin increased the apoptotic rate and G0/G1 cell cycle arrest when compared to treatment with melatonin alone. Melatonin in combination with thapsigargin triggered the increased expression of Bip, LC3‐II, phospho‐Erk1/2 and phospho‐p38 MAPK. In addition, STF‐083010, an IRE1a inhibitor, further exacerbated the decrease in survival rate induced by combinatorial treatment with melatonin and thapsigargin. Collectively, melatonin was effective in gastric cancer treatment by modifying ER stress.
Impact of glucagon response on early postprandial glucose excursions irrespective of residual β‐cell function in type 1 diabetes: A cross‐sectional study using a mixed meal tolerance test
Authors: Ito Ayako , Horie Ichiro , Miwa Masaki , Sako Ayaka , Niri Tetsuro , Nakashima Yomi , Shigeno Riyoko , Haraguchi Ai , Natsuda Shoko , Akazawa Satoru , Kamada Akie , Kawakami Atsushi , Abiru Norio
Published: December 2020

Aims/Introduction

Controlling postprandial glucose levels in patients with type 1 diabetes is challenging even under the adequate treatment of insulin injection. Recent studies showed that dysregulated glucagon secretion exacerbates hyperglycemia in type 2 diabetes patients, but little is known in type 1 diabetes patients. We investigated whether the glucagon response to a meal ingestion could influence the postprandial glucose excursion in patients with type 1 diabetes.

Materials and Methods

We enrolled 34 patients with type 1 diabetes and 23 patients with type 2 diabetes as controls. All patients underwent a liquid mixed meal tolerance test. We measured levels of plasma glucose, C‐peptide and glucagon at fasting (0 min), and 30, 60 and 120 min after meal ingestion. All type 1 diabetes patients received their usual basal insulin and two‐thirds of the necessary dose of the premeal bolus insulin.

Results

The levels of plasma glucagon were elevated and peaked 30 min after the mixed meal ingestion in both type 1 diabetes and type 2 diabetes patients. The glucagon increments from fasting to each time point (30, 60 and 120 min) in type 1 diabetes patients were comparable to those in type 2 diabetes patients. Among the type 1 diabetes patients, the glucagon response showed no differences between the subgroups based on diabetes duration (<5 vs ≥5 years) and fasting C‐peptide levels (<0.10 vs ≥0.10 nmol/L). The changes in plasma glucose from fasting to 30 min were positively correlated with those in glucagon, but not C‐peptide, irrespective of diabetes duration and fasting C‐peptide levels in patients with type 1 diabetes.

Conclusions

The dysregulated glucagon likely contributes to postprandial hyperglycemia independent of the residual β‐cell functions during the progression of type 1 diabetes.
Drying of sliced tomato (Lycopersicon esculentumL.) by a novel halogen dryer: Effects of drying temperature on physical properties, drying kinetics, and energy consumption
Authors: Al‐Hilphy Asaad Rehman , Gavahian Mohsen , Barba Francisco J. , Lorenzo José M. , Al‐Shalah Zainab Musaddaq , Verma Deepak Kumar
Published: December 2020

This study aimed to explore the impact of halogen drying temperature (60, 70, and 80°C) on drying kinetics and some sensory and physical properties of tomato slices. Also, the suitability of previously proposed models for predicting the drying process of tomato slices was assessed and compared with that of a newly proposed model using root mean square error, reduced chi‐square, and determination of coefficient. According to the results, increasing the drying temperature from 60 to 80°C reduced the drying time from 150 to 106 min but increased energy consumption. Experimental drying curves indicated only one falling drying rate period for the drying temperatures of 60 and 70°C, while two consecutive falling rate periods were observed for drying temperatures of 80°C due to the case‐hardening phenomenon. The highest sensory score was obtained for samples dried at 60°C. Also, the effective moisture diffusion varied between 7.96 × 10−9and 1.07 × 10−8m2/s. The color parameters (L*,a*,b*,a*/b*, and ∆E) of samples were significantly affected by drying temperature. The browning index and mass transfer coefficient increased significantly (p< .05) with the increase of the drying temperature. The results introduced halogen drying as a promising processing technology for drying tomato slices.

Practical applications

Drying, such as tomato slices drying, is one of the common process in the food industry. A novel drying technique, that is, halogen drying, was explored in the present study. This innovative process showed a good potential for upscaling, considering its ability in saving energy consumption, reducing drying time, and producing high‐quality products. Also, the effects of important process parameters, such as drying temperature, on the quality of the product were explained which can help with future commercial applications. Furthermore, the new mathematical models proposed in this study can be used by the industry to predict the quality parameters of the product and to achieve process automation.
Metabolic engineering of oleaginous yeasts to enhance single cell oil production
Authors: Chawla Kirti , Kaur Sumandeep , Kaur Ranjeet , Bhunia Rupam Kumar
Published: December 2020

The perpetual increase in global population has led to a sharp hike in the per capita consumption of vegetable oils. To meet the demands for both edible and non‐edible oils, scientists have developed alternative sources of fuel that are sustainable yet eco‐friendly. Oleaginous yeasts are capable of producing lipids that form up to 20% of their total biomass and are mostly stored in the form of neutral lipids, also known as triacylglycerol (TAG). Yeast grows quickly and accumulates fatty acids that are very similar to vegetable oils. The production of single cell oil (SCO) from yeast can be easily enhanced genetically to meet the rising global demand for edible and renewable fuels as an alternative to traditional fossil fuels. Thus, SCO could serve as a promising platform for oil production, thereby preventing the current food‐fuel competition in land use. This review will focus on the recent understanding of TAG metabolic pathways and the subsequent metabolic engineering of the related genes involved in oleaginous yeasts that paved the platform for enhanced SCO production.

Practical applications

Oleaginous yeast single cell oil is a non‐plant‐based, renewable lipid source that can be used for the production of bio‐based oleochemicals.
Optimization of ohmic heating assisted hydrodistillation of cinnamon and bay leaf essential oil
Authors: Tunç Merve Tuğçe , Koca İlkay
Published: December 2020

In this work, optimum ohmic heating assisted hydrodistillation (OAHD) conditions for extraction of cinnamon (CEO) and bay leaf (BEO) essential oil were determined by response surface methodology (RSM). OAHD were compared with conventional hydrodistillation (HD). Hydrodistillation time (30–120 min), mass of sample (20–40 g) and voltage gradient (7.5–12.5 V/cm), were varied to maximize essential oil (EO) yield and minimize energy consumption. Optimized OAHD conditions were determined as 119.90 min, 8.83 V/cm and 40 g, and 120 min, 8.53 V/cm and 40 g for CEO and BEO, respectively. EO yields of cinnamon and bay leaves at optimum conditions were found 3.98 ± 0.25% and 1.36 ± 0.14%, respectively. Energy consumptions were found 0.42 ± 0.02 and 0.86 ± 0.09 kWh/g EO for CEO and BEO, respectively. EO yield of OAHD was found to be higher when compared with HD methods for both plant materials. Energy consumptions and emitted CO2 values of OAHD method were significantly (p < 0.05) lower than HD methods. Cinnamaldehyde (CEO) and eucalyptol (BEO) contents of essential oils extracted with OAHD were higher when compared with HD methods. Antioxidant activities of essential oils extracted with different methods were not significantly different. CEO and BEO formed inhibition zones against all tested microorganism strains.

Practical Applications

Essential oils of cinnamon bark and bay leaf are commonly used for food and pharmaceutical industries and, have important economic value. Conventional hydrodistillation method to extraction essential oils is time consuming, requires more energy and has more CO2 emission rates. Ohmic heating assisted hydrodistillation as a novel technology, is a promising method to extraction of essential oils from different plant materials with lower process times and energy consumption when compared with conventional hydrodistillation. Ohmic heating assisted hydrodistillation method can developed with regard to scale up as a green technology to essential oil production. This work provides a knowledge about the effects of different OAHD process variables on essential oil yield and energy consumption for cinnamon bark and bay leaf essential oils. It is expected that the outcomes of this study will be useful for the designing of large scale ohmic heating assisted hydrodistillation units.
Integration of catastrophe and entropy theories for flood risk mapping in peninsular Malaysia
Authors: Ziarh Ghaith Falah , Asaduzzaman Md , Dewan Ashraf , Nashwan Mohamed Salem , Shahid Shamsuddin
Published: December 2020

A major challenge in flood mapping using multi‐criteria decision analysis (MCDA) is the selection of the flood risk factors and the estimation of their relative importance. A novel MCDA method through the integration of two state‐of‐the‐art MCDA methods based on catastrophe and entropy theory is proposed for mapping flood risk in the Peninsular Malaysia, an area very susceptible to flooding events, is presented. A literature review was undertaken which identified the various socioeconomic, physical and environmental factors which can influence flood vulnerability and risk. A set of variables was selected using an importance index which was developed based on a questionnaire survey. Population density, percentage of vulnerable people, household income, local economy, percentage of foreign nationals, elevation and forest cover were all deemed highly relevant in mapping flood risk and determining the zones of maximum vulnerability. Spatial integration of factors using the proposed MCDA revealed that coastal regions are highly vulnerable to floods when compared to inland locations. Flood risk maps indicate that the northeastern coastal region of Malaysia is at greatest risk of flooding. The prediction capability of the integrated method was found to be 0.93, which suggests good accuracy of the proposed method in flood risk mapping.
The pressure–temperature–time–deformation history of the Beni Mzala unit (Upper Sebtides, Rif belt, Morocco): Refining the Alpine tectono‐metamorphic evolution of the Alboran Domain of the western Mediterranean
Authors: Marrone Sara , Monié Patrick , Rossetti Federico , Lucci Federico , Theye Thomas , Bouybaouene Mohamed L. , Zaghloul Mohamed Najib
Published: December 2020

The structural and thermal relaxation overprint associated with the Neogene Alboran rifting have obscured the early Alpine tectono‐metamorphic evolution of the Alboran Domain, representing the metamorphic core of the Betic–Rif orogen of the western Mediterranean region. This study focuses on the Beni Mzala unit, forming the lower and deeper structural level of the Alpine metamorphic nappe stack (Upper Sebtides) in the Moroccan Rif. Meso‐ and micro‐scale structural investigations are carried out on high‐P aluminum silicate (Ky‐bearing)‐quartz segregations that occur as boudins within the main retrogressive syn‐greenschist foliation (S2/D2) and assumed to preserve the early M1 HP metamorphism associated with the Alpine orogenic construction in the Alboran Domain. These boudins host an early crenulated high‐P foliation (S1, D1/M1) made of quartz–kyanite–white mica–rutile. A large spread in white mica composition is documented, with the highest Si content per formula unit (up to 3.18 apfu) preserved along the S1 foliation and the lower Si content observed in the white mica marking the S2 retrogressive foliation (D2/M2) and the rim of S1 mica. Microtextural evidence documents post‐tectonic andalusite growth and static recrystallization of the quartz microlithons. Inverse (Zr‐in‐Rt thermometry) and forward modelling thermobarometry are integrated with Ar–Ar white mica geochronology to define the peak and exhumation pressure–temperature–time (P–T–t) path of the Beni Mzala unit. Minimum thermo‐baric estimates for the M1 event are ~1.4 GPa and 600°C, corresponding to a metamorphic gradient of ~11°/km, consistent with subduction zone metamorphism. Exhumation is constrained by re‐equilibration of the white mica composition (from high to low celadonite) between c. 29 and 22 Ma, during a nearly isothermal retrogressive path, with final equilibration at high‐T/low‐P conditions within the andalusite stability field (~0.2–0.3 GPa and 500°C). A minimum late Oligocene age is proposed for the Alpine D1 tectono‐metamorphic stage in the Rif, suggesting as feasible the previously proposed Eocene timing for the subduction‐zone metamorphism of the Alboran Domain. Conclusive evidence is provided to link the early Miocene tectono‐metamorphic event to a late thermal perturbation that affected the Alboran Domain at shallow crustal conditions, post‐dating the almost complete exhumation of the deep roots of the Alpine belt in the western Mediterranean.
fISHing with immunohistochemistry for housekeeping gene changes in Alzheimer’s disease using an automated quantitative analysis workflow
Authors: Highet Blake , Vikas Anekal Praju , Ryan Brigid , Murray Helen , Coppieters Natacha , Victor Dieriks Birger , Singh‐Bains Malvindar K. , Mehrabi Nasim F. , Faull Richard L. M. , Dragunow Michael , Curtis Maurice A.
Published: December 2020

In situ hybridization (ISH) is a powerful tool that can be used to localize mRNA expression in tissue samples. Combining ISH with immunohistochemistry (IHC) to determine cell type provides cellular context of mRNA expression, which cannot be achieved with gene microarray or polymerase chain reaction. To study mRNA and protein expression on the same section we investigated the use of RNAscope® ISH in combination with fluorescent IHC on paraffin‐embedded human brain tissue. We first developed a high‐throughput, automated image analysis workflow for quantifying RNA puncta across the total cell population and within neurons identified by NeuN+ immunoreactivity. We then applied this automated analysis to tissue microarray (TMA) sections of middle temporal gyrus tissue (MTG) from neurologically normal and Alzheimer's Disease (AD) cases to determine the suitability of three commonly used housekeeping genes: ubiquitin C (UBC), peptidyl‐prolyl cis‐trans isomerase B (PPIB) and DNA‐directed RNA polymerase II subunit RPB1 (POLR2A). Overall, we saw a significant decrease in total and neuronal UBC expression in AD cases compared to normal cases. Total expression results were validated with RT‐qPCR using fresh frozen tissue from 5 normal and 5 AD cases. We conclude that this technique combined with our novel automated analysis pipeline provides a suitable platform to study changes in gene expression in diseased human brain tissue with cellular and anatomical context. Furthermore, our results suggest that UBC is not a suitable housekeeping gene in the study of post‐mortem AD brain tissue.

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Microbiota‐gut‐brain axis as a regulator of reward processes
Authors: García‐Cabrerizo Rubén , Carbia Carina , O´Riordan Kenneth J. , Schellekens Harriet , Cryan John F.
Published: December 2020

Our gut harbours trillions of microorganisms essential for the maintenance of homeostasis and host physiology in health and disease. In the last decade, there has been a growing interest in understanding the bidirectional pathway of communication between our microbiota and the central nervous system. With regard to reward processes there is accumulating evidence from both animal and human studies that this axis may be a key factor in gating reward valence. Focusing on the mesocorticolimbic pathway, we will discuss how the intestinal microbiota is involved in regulating brain reward functions, both in natural (i.e. eating, social or sexual behaviours) and non‐natural reinforcers (drug addiction behaviours including those relevant to alcohol, psychostimulants, opioids and cannabinoids). We will integrate preclinical and clinical evidence suggesting that the microbiota‐gut‐brain axis could be implicated in the development of disorders associated with alterations in the reward system and how it may be targeted as a promising therapeutic strategy.

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Cover Image for this issue: https://doi.org/10.1111/jnc.15065.
An altered secretome is an early marker of the pathogenesis of CLN6 Batten disease
Authors: Best Hannah L. , Clare Alison J. , McDonald Kirstin O. , Wicky Hollie E. , Hughes Stephanie M.
Published: December 2020

Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited childhood neurodegenerative disorders. In addition to the accumulation of auto‐fluorescent storage material in lysosomes, NCLs are largely characterised by region‐specific neuroinflammation that can predict neuron loss. These phenotypes suggest alterations in the extracellular environment—making the secretome an area of significant interest. This study investigated the secretome in the CLN6 (ceroid‐lipofuscinosis neuronal protein 6) variant of NCL. To investigate the CLN6 secretome, we co‐cultured neurons and glia isolated from Cln6nclf or Cln6± mice, and utilised mass spectrometry to compare protein constituents of conditioned media. The significant changes noted in cathepsin enzymes, were investigated further via western blotting and enzyme activity assays. Viral‐mediated gene therapy was used to try and rescue the wild‐type phenotype and restore the secretome—both in vitro in co‐cultures and in vivo in mouse plasma. In Cln6nclf cells, proteomics revealed a marked increase in catabolic and cytoskeletal‐associated proteins—revealing new similarities between the pathogenic signatures of NCLs with other neurodegenerative disorders. These changes were, in part, corrected by gene therapy intervention, suggesting these proteins as candidate in vitro biomarkers. Importantly, these in vitro changes show promise for in vivo translation, with Cathepsin L (CTSL) activity reduced in both co‐cultures and Cln6nclf plasma samples post gene‐therapy. This work suggests the secretome plays a role in CLN6 pathogenesis and highlights its potential use as an in vitro model. Proteomic changes present a list of candidate biomarkers for monitoring disease and assessing potential therapeutics in future studies.

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Multimodal MRI Response to Fingolimod in Multiple Sclerosis: A Nonrandomized, Single Arm, Observational Study
Authors: Bernitsas Evanthia , Kopinsky Hannah , Lichtman‐Mikol Samuel , Razmjou Sarah , Santiago‐Martinez Carla , Yarraguntla Kalyan , Bao Fen
Published: December 2020

BACKGROUND AND PURPOSE

Fingolimod has a favorable effect on conventional MRI measures; however, its neuroprotective effect is not clear. We aim to investigate changes of conventional and advanced MRI measures in lesions and normal‐appearing white matter (NAWM) over 2 years in fingolimod‐treated patients.

METHODS

Fifty relapsing‐remitting multiple sclerosis patients and 27 healthy controls were enrolled in the study and underwent baseline, 1‐year, and 2‐year 3T MRI scans. T2 lesion volume, whole brain volume, cortical gray matter volume, white matter volume, corpus callosum area, percentage brain volume change (PBVC), Expanded Disability Status Scale, gadolinium‐enhancing lesions, PBVC, magnetization transfer ratio (MTR), and diffusion tensor imaging metrics (fractional anisotropy [FA] and median diffusivity [MD]) in lesions and NAWM were calculated. Longitudinal changes were examined using one‐way repeated measures ANOVA. Bonferroni correction for multiple testing was used when appropriate.

RESULTS

Conventional MRI measures were unchanged in both groups. Lesion MTR increased significantly (P < .001), but NAWM‐MTR remained unchanged. Lesion FA improved significantly in year 1 (P = .003) and over the study duration (P = .05). Lesion MD changed significantly from baseline to year 1 (P < .001) and remained stable over 2 years. NAWM‐FA was significant from baseline to year 1 (P = .002) and from baseline to year 2 (P < .001). NAWM‐MD was significant only from baseline to year 1 (P = .001).

CONCLUSIONS

These findings suggest a possible neuroreparative effect of fingolimod on the MS lesions and NAWM. Larger and longer randomized studies are required to confirm these results.
Imaging Transcriptomics in Neurodegenerative Diseases
Authors: Mroczek Magdalena , Desouky Ahmed , Sirry Wadid
Published: December 2020

Imaging transcriptomics investigates the relationship between neuroanatomical/neuroimaging features and gene expression. The spatial and temporal distribution of the expressed genes and their pattern of spreading over time can contribute to elucidating cellular and molecular processes involved in neurodegeneration. In this study, we review recent findings regarding the correlation between neuroimaging and expression data in neurodegenerative diseases with a focus on Alzheimer's disease and Parkinson's disease. An association between gene expression data and different neuroimaging neurodegeneration features, such as R2 relaxation time and volumetric cortical atrophy, was established. Several positive and negative expression correlations were identified, and they confirmed the focal nature of neurodegeneration. Positively correlated genes were associated with cell motility, immune system activity, neuroinflammation, and microglia. Data from connectome studies support the hypothesis of selective network vulnerability and a temporal spreading pattern in neurodegenerative pathologies. Genes related to cellular mobility and transport are overexpressed in the neuroimaging‐defined delineated areas of degeneration. In addition, expression enrichment of genes involved in immunological processes in vulnerable regions—such as the Toll‐like receptor, a receptor involved in innate immunity—plays a major role in neuroinflammation in neurodegenerative diseases. However, substantial limitations must be overcome in future studies: the lack of high‐quality resolution expression data, the lack of standardized study protocols, and insufficient sensitive early stage neuroimaging markers of degeneration. Identifying neuroimaging and expression prodromal biomarkers and investigating their causal relation in the preclinical disease stage may enable early targeted therapy before the onset of irreversible brain changes.