bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and safety of sodium‐glucose co‐transporter‐2 inhibitors compared with dipeptidyl peptidase‐4 inhibitors in older adults with type 2 diabetes: A nationwide population‐based study
Authors: Han Seung Jin , Ha Kyoung Hwa , Lee Nami , Kim Dae Jung
Published: November 2020

Aim

To examine the real‐world cardiovascular effectiveness and safety associated with sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor compared with dipeptidyl peptidase‐4 (DPP‐4) inhibitor treatment in older adults with type 2 diabetes.

Materials and Methods

In this retrospective cohort study, older adults with type 2 diabetes (aged ≥65 years) were identified in the Korean National Health Insurance Service database from September 2014 to December 2016. In total, 408 506 new users of an SGLT2 inhibitor or DPP‐4 inhibitor were propensity score matched. Cox regression was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for outcomes of interest: hospitalization for heart failure (HHF), all‐cause death, myocardial infarction, stroke, diabetic ketoacidosis (DKA), bone fracture, severe hypoglycaemia, genital infection and urinary tract infection (UTI).

Results

Compared with DPP‐4 inhibitors, new users of SGLT2 inhibitors had a lower risk of HHF (HR 0.86; 95% CI 0.76‐0.97), all‐cause death (HR 0.85; 95% CI 0.75‐0.98) and stroke (HR 0.86; 95% CI 0.77‐0.97), but a similar risk of myocardial infarction (HR 0.95; 95% CI 0.77‐1.19). The risks of DKA, bone fracture and severe hypoglycaemia were similar between both groups, although genital infection (HR 2.44; 95% CI 2.22‐2.67) and UTI (HR 1.05; 95% CI 1.00‐21.11) were more frequent among new users of SGLT2 inhibitors compared with DPP‐4 inhibitors.

Conclusion

Our findings suggest that initiation of SGLT2 inhibitors offers cardiovascular disease protection and can be used safely in older adults with type 2 diabetes.
Results from the Effects of MEtformin on cardiovasculaR function in AdoLescents with type 1 Diabetes (EMERALD) study: A brief report of kidney and inflammatory outcomes
Authors: Tommerdahl Kalie L. , Bjornstad Petter , Kendrick Jessica , Cree‐Green Melanie , Baumgartner Amy D. , Pyle Laura , Reusch Jane E. B. , Nadeau Kristen J.
Published: November 2020

Youth with type 1 diabetes (T1D) demonstrate insulin resistance, independently of glycaemia, when compared to normoglycaemic peers. Insulin resistance increases the risk of cardiovascular disease and diabetic kidney disease, factors also associated with systemic inflammation. We evaluated the effect of metformin on markers of inflammation and diabetic kidney disease in adolescents with T1D. EMERALD, a double‐blind, randomized, placebo‐controlled trial of 3 months of metformin in 48 participants aged 12–21 years with T1D, included baseline and follow‐up assessments of serum creatinine and cystatin C to estimate glomerular filtration rate (eGFR), aspartate aminotransferase, alanine aminotransferase, high‐sensitivity C‐reactive protein, white blood count, platelets, adiponectin, leptin, and urine albumin: creatinine ratio (UACR). Metformin was associated with a 13.9 mL/min/1.73 m2 (95% confidence interval 4.7–23.1 mL/min/1.73 m2) increase in estimated GFR by serum creatinine versus placebo (P ≤ 0.01), with a significant difference remaining after multivariable adjustments (P = 0.03). Whereas eGFR measured by serum creatinine increased significantly after metformin treatment, no differences were observed in cystatin C, UACR, or systemic inflammatory markers. Additional studies with directly measured GFR in response to metformin in T1D are needed.
Weight‐loss response to naltrexone/bupropion is modulated by the Taq1A genetic variant near DRD2 (rs1800497): A pilot study
Authors: Mullally Jamie A. , Chung Wendy K. , LeDuc Charles A. , Reid Tirissa J. , Febres Gerardo , Holleran Steven , Ramakrishnan Rajasekhar , Korner Judith
Published: November 2020

Naltrexone/bupropion (NB) is a US Food and Drug Administration‐approved antiobesity medication. Clinical trials have shown variable weight loss, with responders and non‐responders. NB is believed to act on central dopaminergic pathways to suppress appetite. The Taq1A polymorphism near DRD2 (rs1800497) is associated with the density of striatal dopamine D2 receptors, with individuals carrying the A allele (AA or AG; termed A1+) having 30%‐40% fewer dopamine binding sites than those who do not carry the A allele (GG; termed A1‐). We performed a pilot study to assess the association of the rs1800497 ANKK1 c.2137G > A (p.Glu713Lys) variant with weight loss with NB treatment in 33 subjects. Mean (SD) weight loss was 5.9% (3.2%) for the A1+ genotype group (n = 15) and 4.2% (4.2%) for the A1‐ genotype group (n = 18). The mean weight loss for the A1+ genotype group was significantly greater than the predefined clinically significant 4% weight‐loss target (one‐sample t‐test, P = .035), whereas the mean weight loss for the A1‐ genotype group was not (P = .85). Individuals with the A1+ genotype appear to respond better to NB than A1‐ individuals.
Inequalities in higher education in low‐ and middle‐income countries: A scoping review of the literature
Authors: Reinders Simone , Dekker Marleen , Falisse Jean‐Benoît
Published: November 2020

Motivation

Higher education is regarded as a key instrument to enhance socioeconomic mobility and reduce inequalities. Recent literature reviews have examined inequalities in the higher education systems of high‐income countries, but less is known about the situation in low‐ and middle‐income countries, where higher education is expanding fast.

Purpose

The article reviews the academic literature on higher education in low‐ and middle‐income countries using a research framework inspired by social justice and capability approaches. It considers the financial, sociocultural, human and political resource domains on which people draw, and how they relate to access, participation and outcomes in higher education.

Methods

A literature search for studies explicitly discussing in‐country inequalities in higher education revealed 22 publications. Substantial knowledge gaps remain, especially regarding the political (and decision‐making) side of inequalities; the ideologies and philosophies underpinning higher education systems; and the linkages between resource domains, both micro and macro.

Findings

The review highlights key elements for policy‐makers and researchers: (1) the financial lens alone is insufficient to understand and tackle inequalities, since these are also shaped by human and other non‐financial factors; (2) sociocultural constructs are central in explaining unequal outcomes; and (3) inequalities develop throughout one’s life and need to be considered during higher education, but also before and after. The scope of inequalities is wide, and the literature offers a few ideas for short‐term fixes, such as part‐time and online education.

Policy implications

Inclusive policy frameworks for higher education should include explicit goals related to (in)equality, which are best measured in terms of the extent to which certain actions or choices are feasible for all. Policies in these frameworks, we argue, should go beyond providing financial support, and also address sociocultural and human resource constraints and challenges in retention, performance and labour market outcomes. Finally, they should consider relevant contextual determinants of inequalities.
How does conversion from forest to pasture affect the taxonomic and functional structure of the fish assemblages in Amazonian streams?
Authors: Cantanhêde Lorrane Gabrielle , Luiza‐Andrade Ana , Leão Híngara , Montag Luciano Fogaça de Assis
Published: November 2020

Clearing land for the establishment of pasture is the principal cause of deforestation in the Amazon basin. We investigated how stream habitats and the taxonomic and functional structure of the fish fauna respond to the effects of the conversion of forest to pasture in the eastern Brazilian Amazon. We sampled 13 streams located in areas of forest and 13 streams within a pasture matrix. The structure of the stream habitats, and the taxonomic and functional structure of the fish assemblages were compared between forest and pasture, using univariate and multivariate analyses. Species richness did not vary between environments, although abundance was greater in forest streams. Functional divergence was lower in the pasture streams, indicating a reduced degree of niche differentiation. The pasture streams presented a higher percentage of artificial shelters, such as pipes and plastic containers, and riffles, while the forest streams had greater canopy cover formed by large trees, and a denser substrate formed by leaf litter. Environmental variables influenced the distribution of species based on their functional traits. The greater canopy cover in forest streams benefitted benthic species. The ongoing increase in the area of pasture in the Amazon region is causing changes in stream habitats, and in the taxonomic and functional structure of the local fish assemblages. The impacted streams did not favour the occurrence of species with parental care or piscivorous, invertivorous, and benthic habits. Overall, protecting forests and the stream margins will promote adequate conditions to maintain the equilibrium of Amazonian stream ecosystems.
Negative symptom dimensions in first episode psychosis: Is there a difference between schizophrenia and non‐schizophrenia spectrum disorders?
Authors: Pelizza Lorenzo , Azzali Silvia , Paterlini Federica , Garlassi Sara , Scazza Ilaria , Chiri Luigi Rocco , Poletti Michele , Pupo Simona , Raballo Andrea
Published: November 2020

Aim

Identifying discrete dimensions that underline negative symptoms in First Episode Psychosis (FEP) could improve the understanding and the treatment of such invalidating symptomatology. The aim of this study is to examine the negative symptom structure in FEP individuals and to compare the resulting factor configurations between FEP subjects with and without Schizophrenia Spectrum Disorders (SSD vs non‐SSD).

Methods

One hundred and seventy participants (88 SSD and 82 non‐SSD), aged 13–35 years, completed the Comprehensive Assessment of At‐Risk Mental States (CAARMS) and the Positive and Negative Syndrome Scale (PANSS). A principal component analysis was then performed to investigate PANSS negative symptom structure in both non‐SSD and SSD groups.

Results

Whereas in the SSD sample a 3‐factor model solution (i.e., “Socio‐Emotional Disengagement”, “Motor/Thought Poverty”, and “Avolition/Apathy” dimensions) was identified, a 2‐factor model solution (with a mixed alogia/avolition domain in addition to a mixed socio‐emotional disengagement/expressive deficits dimension) appeared more appropriate in the non‐SSD group.

Conclusions

Our results show a relevant difference in the negative symptom factor structure between SSD and non‐SSD individuals. In particular, a different specificity and significance of negative symptom models in FEP populations with diagnoses other than schizophrenia (compared to those with SSD) must be realistically considered. Notably, a “Motor/Thought Poverty” domain, which specifically includes alogia and motor retardation separately from the other PANSS negative items, appears to specifically characterize FEP young patients with the schizophrenia spectrum.
SCN2A‐Developmental and Epileptic Encephalopathies: Challenges to trial‐readiness for non‐seizure outcomes
Authors: Berg Anne T. , Palac Hannah , Wilkening Greta , Zelko Frank , Schust Meyer Leah
Published: November 2020

Objective

SCN2A‐associated developmental and epileptic encephalopathies (DEEs) present with seizures, developmental impairments, and often both. We sought to characterize the level and pattern of development in children with SCN2A variants, and to address the sensitivity of the Vineland Adaptive Behavior Scales (VABS) in measuring changes over time in children with SCN2A‐DEEs.

Methods

Clinical histories for participants with pathogenic SCN2A variants in the Simons SearchLight project were analyzed for descriptive purposes. VABS scores obtained at study entry and yearly thereafter were analyzed for floor and ceiling effects, change with age, and association with epilepsy through use of regression and longitudinal regression methods.

Results

Sixty‐four participants (50 with epilepsy, 30 [47%] female, median age 49 months, interquartile range [IQR] 28 to 101) were included. Histories of birth complications (N = 34, 54%), neonatal neurological signs (N = 45, 74%), and other neurological symptoms (N = 31, 48%) were common and similar in epilepsy and nonepilepsy subgroups. Mean standardized VABS scores (Composite 53.5; Motor, 55.8, Communication, 54.1, Socialization, 59.4, and Daily living skills, 55.1) reflected performance ~3 standard deviations below the normative test average. In longitudinal regression analyses, standardized scores decreased between 1.3 and 2.8 points per year, suggesting regression of abilities. Raw score analyses, however, revealed several subdomains with substantial floor effects (eg, community use); other raw scores increased with increasing age. Participants with epilepsy scored 0.6 to 1 SD lower than those without epilepsy (all P’s < .05).

Significance

The VABS, as standardly administered, has shortcomings for addressing growth or regression in individuals with SCN2A‐DEEs. Some subdomain raw scores reflected substantial floor effects. Raw scores increased so slowly over time that standardized scores declined. Alternative measures sensitive to incremental meaningful change are required if outcomes such as adaptive behavior are to be primary outcomes in short‐term clinical trials.
Single‐cell transcriptomic analysis of small and large wounds reveals the distinct spatial organization of regenerative fibroblasts
Authors: Phan Quan M. , Sinha Sarthak , Biernaskie Jeff , Driskell Ryan R.
Published: November 2020

Wound‐induced hair follicle neogenesis (WIHN) has been an important model to study hair follicle regeneration during wound repair. However, the cellular and molecular components of the dermis that make large wounds more regenerative are not fully understood. Here, we compare and contrast recently published scRNA‐seq data of small scarring wounds to wounds that regenerate in hope to elucidate the role of fibroblasts lineages in WIHN. Our analysis revealed an over‐representation of the newly identified upper wound fibroblasts in regenerative wound conditions, which express the retinoic acid binding protein Crabp1. This regenerative cell type shares a similar gene signature to the murine papillary fibroblast lineage, which are necessary to support hair follicle morphogenesis and homeostasis. RNA velocity analysis comparing scarring and regenerating wounds revealed the divergent trajectories towards upper and lower wound fibroblasts and that the upper populations were closely associated with the specialized dermal papilla. We also provide analyses and explanation reconciling the inconsistency between the histological lineage tracing and the scRNA‐seq data from recent reports investigating large wounds. Finally, we performed a computational test to map the spatial location of upper wound fibroblasts in large wounds which revealed that upper peripheral fibroblasts might harbour equivalent regenerative competence as those in the centre. Overall, our scRNA‐seq reanalysis combining multiple samples suggests that upper wound fibroblasts are required for hair follicle regeneration and that papillary fibroblasts may migrate from the wound periphery to the centre during wound re‐epithelialization. Moreover, data from this publication are made available on our searchable web resource: https://skinregeneration.org/.
Viruses join the circular RNA world
Authors: Tan Ke‐En , Lim Yat‐Yuen
Published: November 2020

Circular RNAs (circRNAs) are a recently discovered class of noncoding RNAs found in many species across the eukaryotic kingdom. These intriguing RNA species are formed through a unique mechanism that is known as back splicing in which the 5′ and 3′ termini are covalently joined. Recent research has revealed that viruses also encode a repertoire of circRNAs. Some of these viral circRNAs are abundantly expressed and are reported to play a role in disease pathogenesis. A growing number of studies also indicate that host circRNAs are involved in immune responses against virus infections with either an antiviral or proviral role. In this review, we briefly introduce circRNA, its biogenesis, and mechanism of action. We go on to summarize the latest research on the expression, regulation, and functions of viral and host‐encoded circRNAs during the host–virus interaction, with the aim of highlighting the potential of viral and host circRNAs as a suitable target for diagnostic biomarker development and therapeutic treatment of viral‐associated diseases. We conclude by discussing the current limitations in knowledge and significance of elucidating the roles of circRNAs in host–virus interactions, as well as future directions for this emerging field.
Bioinformatics analysis of autophagy‐lysosomal degradation in cardiac aging
Authors: Kamihara Takahiro , Murohara Toyoaki
Published: November 2020

Aim

Cardiac aging, which causes cardiac diastolic dysfunction, frequently occurs in older people. The role of autophagy in cardiac aging is the subject of intensive research. Autophagy comprises steps called the autophagosome formation and autophagosome–lysosome fusion. Caloric restriction (CR) is the gold standard used to induce autophagosome formation, and autophagosome–lysosome fusion is reduced by aging. However, few studies are available that survey and compare signaling during CR (autophagosome formation induced status) and old (potentially autophagosome–lysosome fusion‐reduced status). Here we aimed to identify the rate‐limiting step of autophagic disorders during cardiac aging.

Methods

We employed bioinformatics to analyze publicly available DNA microarray datasets. The first dataset compared the hearts of young and old C57BL6 mice (OLD). The second dataset compared the hearts of young C57BL6 mice fed a normal diet with those of young C57BL6 mice subjected to CR.

Results

We analyzed OLD‐upregulated genes that were significantly associated with the Gene Ontogeny term “Autophagy,” indicating that autophagic genes were upregulated in OLD mice. The autophagy‐related gene Atg5 and Atg5‐related genes were upregulated in OLD and CR mice. The identified hub and bottleneck genes are autophagic autophagosome formation suppressors such as Sirt2, Ilk and Islr, as well as the autophagosome–lysosome fusion inducer Snapin.

Conclusions

Autophagosome formation genes were upregulated in aging mice subjected to CR, indicating that an upregulated autophagosome formation is not a change specific to cardiac aging. However, autophagosome–lysosome fusion genes, particularly the lysosome transportation‐related gene Snapin, were downregulated in aging, indicating that autophagosome–lysosome fusion may cause autophagic disorders in cardiac aging. Geriatr Gerontol Int 2021; 21: 108–115.
African Hospital Libraries: How Shane Godbolt inspired and shaped a seedling
Authors: Blacklock Claire
Published: November 2020

The co‐founderof African Hospital Libraries (AHL) chronicles how this charity grew from a tiny pop‐up library set up by two VSO volunteers and the hospital management team, to establishing health care library services in three provincial government referral hospitals (Makeni, Bo, Kenema) in Sierra Leone, and supporting link‐ups with a shared maternity and paediatric hospital library service in Freetown and two libraries in healthcare training institutions. She reflects on the impact that Shane Godbolt had and continues to have on the work and growth of the organisation.
A comparison of the in vitro permeation of 3‐O‐ethyl‐l‐ascorbic acid in human skin and in a living skin equivalent (LabSkin™)
Authors: Iliopoulos Fotis , Chapman Alex , Lane Majella E.
Published: November 2020

OBJECTIVES

The safety assessment of personal care products often entails determining dermal absorption of their ingredients. Such experiments are typically performed in human or animal skin in vitro; however, ethical and safety considerations are associated with obtaining these tissues. Several human skin equivalent models (HSEs) have been developed as alternatives to human tissue. The barrier function of such models however, is normally less developed than human skin. Here, we examine the permeability of the HSE LabSkinTM to a model compound, 3‐O‐ethyl‐l‐ascorbic acid (EA) compared with human skin.

METHODS

Skin uptake and permeation of EA was investigated in vitro using heat‐separated human epidermis and LabSkinTM. Finite dose (5 μL cm‐2) Franz‐diffusion studies were conducted using 2 % (w/w) EA in a ternary solvent mixture comprising propylene glycol (PG), propylene glycol monolaurate (PGML), and isopropyl myristate (IPM). These excipients are commonly used in cosmetic products and they have been reported to promote permeation of EA in a different model, namely porcine skin.

RESULTS

Permeation of EA through LabSkinTM was evident from 2 h; however, EA permeation in human skin was not detected until 5 h. Similar amounts of EA permeated through the two membranes at time points 8, 10, 12 and 24 h (p > 0.05). The cumulative amounts of EA delivered through LabSkinTM at 24 h were 41.3 ± 2.0 µg cm−2, corresponding to 55.1 ± 1.8 % of the applied dose. Similar amounts permeated across human skin, 49.4 ± 4.1 µg cm−2, accounting for 58.0 ± 4.2 % of the dose applied (p > 0.05).

CONCLUSION

The permeation of EA in LabSkinTM compared well with results for human epidermis in terms of the permeation profiles and the cumulative amounts of EA that permeated. The data suggest that the skin barrier of the two models was similar with regard to their overall permeability to the hydrophilic active EA. The findings are promising for the use of LabSkinTM as a surrogate for human skin in permeability testing. Future studies will focus on exploring the reproducibility and robustness of LabSkinTM for delivery of other actives that span a range of physicochemical properties.
Evaluating Arabic textbooks: A corpus‐based lexical frequency study
Authors: Moser Janelle
Published: November 2020

Textbooks play an essential role in foreign language programs; however, it is unclear if their contents match the most salient linguistic forms championed by usage‐based approaches to second language acquisition (SLA). Through the lens of a corpus‐based approach via lexical frequency, this study evaluates five of the most popular Arabic textbooks. Vocabulary was vowelled and lemmatized using the MADAMIRA morphological analyzer and compared to the first 3,000 most frequent words from A frequency dictionary of Arabic using AntWordProfiler. Results show a relatively low number of items at each frequency band, and subsequent recommendations are made for filling lexical gaps in Arabic and L2 textbooks.
Neuromuscular stimulation of the common peroneal nerve increases arterial and venous velocity in patients with venous leg ulcers
Authors: Das Saroj K. , Dhoonmoon Luxmi , Chhabra Swati
Published: November 2020

Activation of the venous muscle pumps by neuromuscular stimulation of the common peroneal nerve has been previously shown to increase venous and arterial flow in the legs of healthy subjects. The aim of this study is to determine whether a similar effect is observed in patients with chronic venous leg ulcers. 1 Hz intermittent electrostimulation of the common peroneal nerve was applied to 14 patients with ulcers between 1 and 10 cm in diameter, eliciting a small, painless, regular, muscular twitch of the leg. Flow was measured using Duplex ultrasound in the popliteal vein and the popliteal artery. Peak arterial velocity increased from 57 to 78 cm/s (P = .001) in sitting position, and from 79 to 98 cm/s in recumbent position (P = .001). Peak venous velocity increased from 10 to 33 cm/s (P = .001) sitting, and from 14 to 47 cm/s (P = .001) recumbent. Significant increases were observed in both venous and arterial blood flow in the lower limb. This suggestsed that activation of the venous muscle pump and improvement of arterial flow assisted oxygen delivery at the wound site. Moreover this may be a worthwhile intervention to assist in the healing of venous leg ulcers, and may provide a mechanistic explanation for the increased healing rates previously reported with neuromuscular stimulation of the common peroneal nerve.
A relational database within the Leg Club Network: an audit
Authors: McIntyre Neil , Galazka Anna Milena , Lindsay Ellie , Bawden Robert , Renyi Roland
Published: November 2020

The growing prevalence of venous leg ulcers in an ageing population presents challenges for wound care and management. The Lindsay Leg Club model is an alternative approach to the management of leg health that can improve patient outcomes. This article reports on an audit of a relational database located within the Leg Club Network, containing records of more than 17 000 patients (known as members) who attended a Leg Club in a 5‐year period (2014‐2019). Overall, over 266 000 member leg assessments and treatments were entered into the database. The average nurse‐member attendance time was 28 min, with a skill mix of 23% senior nurses, 70% qualified and associate nurses, and 7% nurses in supervisory roles. Healing rates averaged 62% after 12 weeks. Recurrence rates were 20% after 12 weeks. Annual clinical and volunteer hours averaged 821 and 800 h, respectively. Staffing costs were £28 per wound treatment or leg assessment with a typical duration of 27 min; 71% of members were aged 70 to 94 years old, which indicates the need for a service that caters to the specific requirements of this age group. However, no data on psychosocial and well‐being outcomes were recorded. Their inclusion in further developments of this database is recommended.
PERIPHERAL CIRCULATION IN DIABETES MELLITUS—A STUDY WITH INFRARED THERMOGRAPHY
Authors: Langer L. , Fagerberg S.‐E. , Johnsén Ch.
Published: November 2020

A controlled study of the peripheral circulation in 47 diabetics has been performed with the aid of thermography. Infrared emission patterns over hands and feet revealed asymmetries and/or deviations of the normal skin temperature distribution in all diabetics. The thermographic findings of the diabetic patients were in most cases distinctive, with an asymmetric decrease in the emission levels over one or more toes or fingers. These thermographic abnormalities are interpreted as reflecting probable vascular disturbances, which are characteristic of diabetes mellitus.
VAGAL FUNCTION IN PATIENTS WITH DIABETIC NEUROPATHY
Authors: Dotevall G. , Fagerberg S.‐E. , Langer L. , Walan A.
Published: November 2020

The gastric secretory response to insulin administration has been investigated in eleven diabetic patients in order to study their vagal function. The mean duration of the disease was 16 years. One patient suffered from diarrhoea. The other diabetic patients were free of symptoms from the gastrointestinal tract. From the criteria in the literature for surgical vagotomy, some patients with long duration of the disease and with severe signs of vascular and neurological involvement exhibited impaired vagal function. This supports the theory that impaired vagal function is the cause of disturbances of the gastrointestinal tract in diabetes mellitus.
THE PERIPHERAL NERVE FUNCTION IN CHRONIC RENAL FAILURE
Authors: Nielsen V. Kamp
Published: November 2020

The vibratory perception threshold (VPT) has been determined in 85 normal persons and 97 patients with chronic renal failure. Innormal personsVPT was an exponential function of age. The rate of elevation was faster on the lower than on the upper extremity and faster in males than in females. In thepatient groupas a whole the average deviation from the normal mean VPT, adjusted for age and sex, was significantly elevated in the upper and lower extremities. Male patients were significantly more affected than female patients. In females no correlation was present with kidney function and/or age. In males the vibratory perception deteriorated significantly with advancing renal failure, and for comparable degree of renal failure the vibratory perception was more severely affected in old than in young patients. The vibratory perception was more affected on the lower than on the upper extremity and on distal than on proximal test spots. The degree of impairment was roughly correlated with the severity of clinical neuropathy. A significant correlation with the motor conduction velocity (Vm) in the peroneal nerve could be referred to a joint covariation with the kidney function. In the median nerve no correlation was present between VPT and electrophysiological data from sensory nerve conduction studies. Like other clinical components of peripheral neuropathy the diagnostic significance of VPT as an indicator of peripheral nerve dysfunction could be characterized by high specificity and low sensitivity. However, VPT is a quantitative measure and readily applicable for bedside examination, which may prove to be of particular value in longitudinal studies.
BLOOD PRESSURE IN SWEDISH BOYS OF 18
Authors: Ahlborg Björn , Linroth Klas , Nordgren Bengt , Nordesjö Lars‐Olof , Schéle Rickard
Published: November 2020

In 1965, in connection with enlistment for compulsory military service, 1 789 18‐year‐old men from practically the whole of Sweden have been examined in respect of different medical variables, e.g. blood pressure (BP), heart rate (HR), body weight (b.wt.). The subjects constituted a representative sample of about 3% of the whole population of 18‐year‐old males. The variation of the sample in systolic and diastolic BP is reported. Due to illness or other causes of decreased fitness for service 394 individuals have been excluded as not being suitable in a normal material. For another 80 individuals the examinations were not complete for all variables, and these 80 individuals were therefore also excluded. The remaining material consisted of 1315 men. Relationships between BP and other variables are presented. The difference in BP between the excluded 474 individuals and the remaining material is small. Multiple correlation and regression between BP (systolic and diastolic), on the one hand, and resting HR and b.wt., on the other, are presented.
HEART RATE DURING EXERCISE IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Åberg Hans , Ström Gunnar , Werner Ivar
Published: November 2020

A group of 195 patients with atrial fibrillation, mostly due to advanced valvular heart disease, have been examined by the graded work test and an orthostatic test when they were on maintenance digitalis therapy. The highest attained work load averaged 275 kpm/min, at an average heart (ventricular) rate of 134 beats/min. This corresponded to a load of 145 at heart rate 110. There was a wide range of work capacity. The individual relationships of heart rate increase to work load increase varied considerably from linearity, but were approximately linear in many cases and the average for groups of patients were also relatively linear. Alinearity was observed especially in patients with a very low work capacity. The increase in heart rate during an orthostatic test was 30 beats/min or more in 8% of the patients. A ‘steady state’ was obtained during the highest work load in 44% of the patients. Our experience is that, in atrial fibrillation, the graded work test must be evaluated with caution but often gives valid clinical information.
PENTAGASTRIN‐ AND INSULIN‐INDUCED SECRETION IN DIABETES MELLITUS
Authors: Langer L.
Published: November 2020

The insulin test has been accepted as the most reliable means of evaluating vagal function. A modified form of it—combined insulin/pentagastrin test—demonstrated in a controlled study that the vagal influence on gastric secretion is reduced, suggesting vagal dysfunction in 10 diabetics with an average duration of diabetes of 15 years without symptoms from the gastro‐intestinal tract. This agrees with the contention that delayed gastric emptying is another sign of vagal dysfunction.
Variability and selection among mutant families of wheat for biomass allocation, yield and yield‐related traits under drought‐stressed and non‐stressed conditions
Authors: OlaOlorun Boluwatife M. , Shimelis Hussein A. , Mathew Isack
Published: November 2020

Genetic variation is fundamental for plant breeding programmes. Exploiting the genetic variation of wheat for biomass allocation, yield and yield‐related traits enhances breeding for drought tolerance. The aim of this study was to evaluate genetic variation and to select best individuals among 180 M3 mutant families of wheat developed through EMS mutagenesis based on better biomass allocation to root systems, desirable agronomic traits and high yield potential under greenhouse and field environment evaluations with drought‐stressed and non‐stressed conditions. Experiments were conducted using a randomized complete block design with two replications. Days to 50% heading (DTH), days to 90% maturity (DTM), plant height (PH), number of productive tillers (PTN), shoot biomass (SB), root biomass (RB), total biomass (TB), root–shoot ratio (RSR), spike length (SL), spikelet per spike (SPS), one thousand seed weight (TSW) and grain yield (GY) were collected. Mutant families showed significant genotypic (p < .05) variation for yield and biomass traits, whereas genotype × environment × water regime interaction effects were significant (p < .05) for DTM, SB, TB, TSW and GY. Superior families designated as 52, 159, 103, 126 and 145 were selected for improved drought tolerance and high biomass allocation to roots.
G protein‐coupled oestrogen receptor promotes cell growth of non‐small cell lung cancer cells via YAP1/QKI/circNOTCH1/m6A methylated NOTCH1 signalling
Authors: Shen Yi , Li Chong , Zhou Lin , Huang Jian‐An
Published: November 2020

Results from various studies reveal that the role of G protein‐coupled oestrogen receptor (GPER) is cancer‐context dependent, and the function of GPER in non–small‐cell lung cancer (NSCLC) is still unclear. The present study demonstrated that neoplasm lung tissues expressed higher level of GPER compared with the normal lung tissues. The clinical data also showed that GPER expression level was positively correlated with the tumour stage of NSCLC. Our experimental data confirmed that GPER played an oncogenic role to promote cell growth of NSCLC cells. Mechanistic dissection revealed that GPER could modulate the NOTCH1 pathway to regulate cell growth in NSCLC cells. Further exploration of the mechanism demonstrated that GPER could up‐regulate circNOTCH1, which could compete with NOTCH1 mRNA for METTL14 binding. Because of the lack of m6A modification by METTL14 on the NOTCH1 mRNA, NOTCH1 mRNA was more stable and much easier to undergo protein translation. Subsequently, we found that GPER could prevent YAP1 phosphorylation and promote YAP1‐TEAD's transcriptional regulation on QKI, a transacting RNA‐binding factor involved in circRNA biogenesis, to facilitate circNOTCH1 generation. Supportively, data from preclinical mice model with implantation of H1299 cells also demonstrated that knock‐down of circNOTCH1 could block GPER‐induced NOTCH1 to suppress NSCLC tumour growth. Together, our data showed that GPER could promote NSCLC cell growth via regulating the YAP1/QKI/circNOTCH1/m6A methylated NOTCH1 pathway, and targeting our identified molecules may be a potentially therapeutic approach to suppress NSCLC development.
Long intergenic non‐coding RNA Linc00485 promotes lung cancer progression by modulating miR‐298/c‐Myc axis
Authors: Zhang Zhenyang , Lin Wenwei , Lin Yuhan , Kang Mingqiang , Zhu Jiafu , Tong Zhangwei , Wu Long , Sun Jianhai , Lin Jiangbo
Published: November 2020

Long non‐coding RNAs (lncRNAs), which are non‐protein‐coding transcripts, are emerging as novel biomarkers for cancer diagnosis. Their dysregulation is increasingly recognized to contribute to the development and progression of human cancers, including lung cancer. Linc00485 is a newly discovered cancer‐related lncRNA; however, little is known about its role in lung cancer progression. In this study, we found that the expression of Linc00485 was significantly increased in human lung cancer tissue and associated with malignant phenotypes, including tumour‐node‐metastasis (TNM) stage, metastasis and relapse. Furthermore, the proliferative, migratory and invasive abilities of lung cancer cells in vitro were significantly enhanced by overexpression of Linc00485 but inhibited by its silencing. Mechanistically, Linc00485 regulated the expression of c‐Myc by directly binding to miR‐298; the effects of Linc00485 overexpression could be significantly reversed by a c‐Myc inhibitor or small interfering RNA. Xenotransplantation experiments showed that Linc00485 silencing significantly weakened the proliferation potential of A549 cells in vivo. Overall, these findings indicate that Linc00485 overexpression down‐regulates miR‐298, resulting in the up‐regulation of c‐Myc and thereby promoting the development of lung cancer.
Responses to Liability Immunization: Evidence from Medical Devices
Authors: Gentry Elissa P. , McMichael Benjamin J.
Published: November 2020

The Supreme Court's decision in Riegel v. Medtronic immunized medical device manufacturers from certain types of state product liability claims. However, this immunization applies only when the devices underlying those claims have been approved through the Food and Drug Administration's most rigorous—and costly—review process, premarket approval (PMA). Exploiting this decision, we examine whether manufacturers strategically respond to this new immunity. We find evidence that, following Riegel, approvals for high‐risk product categories increase relative to the comparable change for low‐risk categories, suggesting that firms are sensitive to the newly immunized risk. We additionally find evidence that physician treatment patterns with respect to medical devices also change, consistent with Riegel shifting liability away from device manufacturers and toward physicians. The analysis provides evidence that sophisticated actors respond to changes in their expected legal liability and that technical legal decisions have important ramifications for the provision of healthcare.
Roles of DEMETER in regulating DNA methylation in vegetative tissues and pathogen resistance
Authors: Zeng Wenjie , Huang Huan , Lin Xueqiang , Zhu Chen , Kosami Ken‐ichi , Huang Chaofeng , Zhang Huiming , Duan Cheng‐Guo , Zhu Jian‐Kang , Miki Daisuke
Published: November 2020

DNA methylation is an epigenetic mark important for genome stability and gene expression. In Arabidopsis thaliana, the 5‐methylcytosine DNA glycosylase/demethylase DEMETER (DME) controls active DNA demethylation during the reproductive stage; however, the lethality of loss‐of‐function dme mutations has made it difficult to assess DME function in vegetative tissues. Here, we edited DME using clustered regularly interspaced short palindromic repeats (CRISPR) /CRISPR‐associated protein 9 and created three weak dme mutants that produced a few viable seeds. We also performed central cell‐specific complementation in a strong dme mutant and combined this line with mutations in the other three Arabidopsis demethylase genes to generate the dme ros1 dml2 dml3 (drdd) quadruple mutant. A DNA methylome analysis showed that DME is required for DNA demethylation at hundreds of genomic regions in vegetative tissues. A transcriptome analysis of the drdd mutant revealed that DME and the other three demethylases are important for plant responses to biotic and abiotic stresses in vegetative tissues. Despite the limited role of DME in regulating DNA methylation in vegetative tissues, the dme mutants showed increased susceptibility to bacterial and fungal pathogens. Our study highlights the important functions of DME in vegetative tissues and provides valuable genetic tools for future investigations of DNA demethylation in plants.
Necrostatin‐1, RIP1/RIP3 inhibitor, relieves transforming growth factor β‐induced wound‐healing process in formation of hypertrophic scars
Authors: Lin Pei‐Ting , Xue Xiao‐Dong , Zhao Zhong‐Dong , Lu Jun‐Yang , Xie Pei‐Lin
Published: November 2020

Background

Hypertrophic scars (HS) are common pathologic processes emerged during wound‐healing process. The receptor‐interacting protein kinase (RIP) might participate in keloid formation.

Aims

This study aimed to investigate Necrostatin‐1 (Nec‐1), a RIP1/RIP3 inhibitor, in the formation of hypertrophic scar.

Methods

Human hypertrophic scar fibroblasts (HSF) were extracted from patients with hypertrophic scar. Transforming growth factor‐β1 (TGF‐β1) was performed to induce wound‐healing process including cell proliferation (CCK‐8, Flow cytometry, and Western blot), migration (Transwell assay, Western blot), collagen production (Western blot), and extracellular matrix dysfunction (Western blotting and immunofluorescence).

Results

Our results reported that Nec‐1 inhibited TGF‐β1‐induced cell proliferation and promoted G0/G1 phase arrest in HSF. In addition, Nec‐1 attenuated TGF‐β1‐induced cell migration and inhibited the expression of MMP2 and MMP9 in TGF‐β1‐induced HSF. Besides, Nec‐1 also reduced TGF‐β1‐induced collagen production and α‐smooth muscle actin expression in HSF.

Conclusions

The present data in this study showed the potential role of Nec‐1 as a novel treatment for HS.
Modeling lipid layers of atopic skin and observation of changes in lipid layer properties with changes in ceramide content
Authors: Jung In‐Keun , Choi Joonho , Nam Jin , No Kyoung Tai
Published: November 2020

Background

Studies have shown that there is a high correlation between atopic dermatitis and decrease in ceramide content in the lipid bilayer of skin. Moreover, it has been shown that the reduction in ceramide content in the stratum corneum is unique to atopic dermatitis, indicating that there are particular structural differences between the lipid bilayers of normal and atopic skin.

Aim

This study aimed to compare the lipid bilayer of the atopic skin with that of the healthy skin and to establish a structural model of the lipid bilayer for atopy.

Methods

Molecular dynamics simulations were performed using NAMD 2.8. Models of lipid bilayers of normal skin and atopic skin, and a model of lipid bilayer containing only ceramide were built with CHARMM‐GUI. The thickness, area occupied per lipid, and alignment of lipids were compared among the three models. Potential mean force (PMF) of the sodium laureth sulfate (SLES) on lipid bilayers was calculated to predict the affinity between SLES and lipid bilayers.

Results

Potential mean force calculations showed that the lipid bilayer of atopic skin was able to absorb the surfactant more easily than that of normal skin.

Conclusions

When the ceramide ratio is low, the thickness of lipid bilayer is reduced and its structure is weakened. Other structural differences between the lipid layers of normal and atopic skin included increased area per lipid and poor alignment of lipids. Further, the atopy lipid bilayer model was found to absorb more SLES than the normal skin lipid bilayer model.
The use of biostatic human amnion and platelet‐rich plasma in topical treatment of toxic epidermal necrolysis—A case report
Authors: Klama‐Baryła Agnieszka , Strzelec Przemysław , Pawlik‐Knapik Danuta , Cholewa Zbigniew , Szapski Michał , Kitala Diana , Łabuś Wojciech , Kraut Małgorzata , Smętek Wojciech , Kucharzewski Marek
Published: November 2020

Background

Toxic epidermal necrolysis (TEN) (also known as Lyell syndrome) and Stevens‐Johnson syndrome (SJS) are life‐threatening mucocutaneous blistering diseases. They are characterized by generalized blisters and epidermal inflammation, most likely resulting from the administration or interaction of medicines.

Aims

To report potential new method in the treatment of TEN.

Patients/Methods

This article presents a case report of a 35‐year‐old man suffering from TEN covering about 95% of his body surface. Lesions occurred in the patient during antiepileptic therapy, after taking simultaneously amoxicillin (with clavulanic acid) and naproxen followed by lamotrigine treatment. Standard general treatment was performed. Intravenous feeding was necessary. Due to acute respiratory failure, the patient required mechanical ventilation. Two methods were combined in topical treatment: application of platelet‐rich plasma (PRP) and a simultaneous biostatic human amnion transplant.

Results

In the presented case, the combination of both methods contributed to a significant acceleration of wound healing. After the application of PRP and biostatic amnion transplantation, the healing of wounds on the back and posterior surfaces of the legs was completed after six days. The surgical treatment most probably contributed to a significant acceleration of wound healing.

Conclusion

The case report shows that topical TEN/SJS treatment with biostatic human amnion and PRP has a positive clinical effect and may be a new method of treatment of TEN.
Ethics, health disparities, and discourses in oncology nursing’s research: If we know the problems, why are we asking the wrong questions?
Authors: Rabelais Em , Walker Rachel K.
Published: November 2020

Aims and Objectives

To disrupt conflations between ‘health disparities research’ and critical engagement with racism, whiteness, other oppressions and our profession's ongoing roles in white supremacy.

Background

In Oncology Nursing Society's (ONS) 2019–2023 research agenda, health disparities are highlighted as a top priority for nursing knowledge generation and intervention. The document concludes needs for increased ‘minority and vulnerable population’ participation in cancer clinical trials, reduced financial toxicity, behavioural interventions for risk reduction, incorporation of social determinants of health and technology to promote rural access to high‐quality care.

Design

In this critical resistive, theoretical and ethical analysis on current discourses on health disparities research in oncology nursing, we ask: (a) What forces (stated and unstated) shape current oncology nursing discourses about health disparities?; (b) What assumptions about health and power are embedded in these discourses?; (c) Are we, as nurses and scientists, asking the right questions?

Methods

Line‐by‐line analysis of the ONS Research Agenda for 2019–2023 ‘Health Disparities’ section.

Results

The health disparities described in this report are not new to the literature, nor are many of the proposed solutions. As noted, disparities such as disproportionate cancer‐related morbidity and mortality across identities (gender, race and sexual orientation) have not improved and some have worsened over several decades.

Conclusions

That discourses on prioritising cancer‐related health disparities persist while disparity‐related outcomes remain largely unchanged presents challenges—both moral and pragmatic. We must ask, ‘Rather than the concept of “health disparities,” as presently understood in cancer nursing, what is the better approach to examine health equity and ethical nursing research practices?’

Relevance to Clinical Practice

This paper offers several starting places for nurses, especially with the following questions: ‘Who does this harm?’ Answer then revise: ‘Who might this harm now?’ Answer then revise: ‘Are these harms worth the activity?’ And repeat this process.