bluuebunny/crossref_metadata_2025 huggingface dataset:
Untargeted metabolite profiling of liver in mice exposed to 2‐methylfuran
Authors: Hu Chuanqin , Li Ren , Wang Jiahui , Liu Yingli , Wang Jing , Sun Baoguo
Published: December 2020

Furan, a significant food contaminant, was found in many cooked foods. In most cooked foods, furan has been found to be coexisted with some alkylated derivatives such as 2‐methylfuran. 2‐methylfuran was found to be potent hepatotoxins. Little toxicological data is available for 2‐methylfuran. The objective of this study was to investigate metabolite changes in the liver samples from mice fed with 2‐methylfuran by untargeted metabolomic approach. Metabolomic analysis was conducted by using gas chromatography coupled with mass spectrometry (GC‐MS). Twenty‐four metabolites were identified as differential metabolites. The important metabolic pathway was linoleic acid metabolism, glycine, serine, and threonine metabolism, methane metabolism, ascorbate, and aldarate metabolism, valine, leucine, and isoleucine biosynthesis, arachidonic acid metabolism, alanine, aspartate, and glutamate metabolism, aminoacyl‐tRNA biosynthesis, cysteine, and methionine metabolism, inositol phosphate metabolism, and pyruvate metabolism. These newly identified pathways provide evidence for investigating toxic mechanism of 2‐methylfuran.

Practical Application

Furan in foods has caused public health concern for its hepatotoxicity and hepatic carcinogenicity in rodents. The metabolomics method was constructed to find more biomarkers to study underlying hepatotoxic mechanisms of 2‐methylfuran. It will offer important information for official limits of 2‐methylfuran in foods.
Regional collaboration to improve quality of radiation therapy in Asia
Authors: Gondhowiardjo Soehartati A , Handoko  , Tham Ivan , Giselvania Angela , Bilimagga Ramesh S , Octavianus Steven , Hiraoka Masahiro , Jayalie Vito Filbert , Tamaki Tomoaki , Calaguas Miriam , Nakano Takashi
Published: December 2020

In Asia, several challenges hinder the delivery of high‐quality cancer treatment, especially radiation therapy (RT). Many Asian countries face large‐scale shortage of RT centres and treatment machines. Additionally, there is also a significant technological gap, with many RT centres in Asia still using outdated technology. There is an urgent need to improve radiation treatment quality in Asia. The Federation of Asian Organizations for Radiation Oncology (FARO) was set up to foster regional collaboration, which we believe can help to identify and solve some of these issues collectively. This report describes the background and rationale of starting FARO, and puts forth some of the early achievements of the group, including fact‐finding and educational activities. Finally, we discuss future possibilities, including strategic proposals that may benefit the RT community and our patients in Asia.
Pore Characteristics and Factors Controlling Lacustrine Shales from the Upper Cretaceous Qingshankou Formation of the Songliao Basin, Northeast China: A Study Combining SEM, Low‐temperature Gas Adsorption and MICP Experiments
Authors: HAN Hui , DAI Jie , GUO Chen , ZHONG Ningning , PANG Peng , DING Zhengang , CHEN Jianping , HUANG Zhenkai , GAO Yuan , LUO Jinyu , LI Qirui , ZHANG Zhaokun
Published: December 2020

To investigate pore characteristics and the factors controlling lacustrine shales, geochemical, mineralogical and petrophysical experiments were performed on 23 shale samples from the Qingshankou Formation of the Songliao Basin, China. A comparison of mercury injection capillary pressure (MICP) and low‐temperature N2 adsorption pore‐size distribution showed that MICP has a higher pore‐size distribution (PSD) line in its overlapping pore diameter range, which may be elevated by the higher pressure of MICP. Therefore, in the overlapping range, low‐temperature N2 adsorption data were preferred in pore characterization. Negative correlations were observed between pore volumes and TOC content, indicating organic matter pores are not well‐developed in the studied samples. This may be related to their low grade of maturity and type I kerogens. There existed negative relationships between pore volumes and S1, which illustrated that liquid hydrocarbons occupied some pore space. Micropore volume had a better correlation with S1 than mesopore and macropore volumes, which suggests that liquid hydrocarbons preferentially occur in micropores. No obvious relationships between pore volumes and quartz or feldspar were observed, while pore volumes increased with the increasing clay mineral content. These relationships indicate that intraparticle pores in clay minerals represent the principal pore type.
Targeted Geoengineering: Local Interventions with Global Implications
Authors: Moore John C. , Mettiäinen Ilona , Wolovick Michael , Zhao Liyun , Gladstone Rupert , Chen Ying , Kirchner Stefan , Koivurova Timo
Published: December 2020

Targeted geoengineering aims to tackle a global scale impact of climate warming by addressing local or regional systemic interventions. We consider three examples: conserving the West Antarctic ice sheet by limiting rates of ice discharge or increasing snow accumulation, thereby reducing global sea level rise; transforming the Arctic permafrost zone into steppe grassland; raising the albedo of Arctic sea ice. There are important differences between targeted interventions and archetypal solar geoengineering, which ideally would have global governance structures, while some targeted interventions may be done entirely under the accepted purview of small numbers of nation states. For example, the West Antarctic ice sheet is governed by the consultative members of the Antarctic Treaty. Of the interventions we look at, only ice sheet conservation seems viable and efficient relative to solar geoengineering. Many important treaties and conventions rely on the precautionary approach. While at first glance this principle seems to argue against targeted interventions, we argue that it may in fact do the opposite. Given the existence of irreversible thresholds in many natural systems, the precautionary approach may be better upheld by a targeted intervention that prevents a system from changing in ways that cannot be undone.
Functional inhibition of heat shock protein 70 by VER‐155008 suppresses pleural mesothelioma cell proliferation via an autophagy mechanism
Authors: Sakai Kosuke , Inoue Maya , Mikami Shintaro , Nishimura Hiroaki , Kuwabara Yoshiki , Kojima Akitoshi , Toda Maiko , Ogawa‐Kobayashi Yumiko , Kikuchi Satoshi , Hirata Yusuke , Mikami‐Saito Yuriko , Kyoyama Hiroyuki , Moriyama Gaku , Shiibashi Michio , Seike Masahiro , Gemma Akihiko , Uematsu Kazutsugu
Published: December 2020

Background: Pleural mesothelioma, a devastating asbestos‐associated malignancy, urgently requires a novel effective therapy. Heat shock protein 70 (HSP70), which is synthesized in the cell response to protein damage, is expected to be a new target for antitumor treatment. In addition to its well‐known protein refolding function, HSP70 regulates cell proliferation through different pathways, including PI3K/AKT/mTOR, and autophagy in malignant cells. In this study, we attempted to clarify the effects of VER‐155008, an HSP70 inhibitor, on pleural mesothelioma.

Methods: Human pleural mesothelioma cell lines 211H, H2452 and H28 were cultured with VER‐155008, and protein expression, cell proliferation, colony formation, cell cycle, synergistic effect with cisplatin, and autophagy induction were analyzed.

Results: In mesothelioma cell lines, VER‐155008 (5.0 μM or more) inhibited cell growth and colony formation, accompanied by G1 cell cycle arrest. According to western blot analysis, VER‐155008 reduced p‐AKT expression. However, VER‐155008 failed to show a synergistic effect with cisplatin on cell growth. Mesothelioma cells transfected with the novel plasmid pMRX‐IP‐GFP‐LC3‐RFP‐LC3ΔG, which was developed for the quantitative and statistical estimation of macroautophagy, showed enhanced macroautophagy upon treatment with VER‐155008 and gefitinib which is an EGFR‐tyrosine kinase inhibitor. In addition, fetal bovine serum deprivation induced macroautophagy was further enhanced by VER‐155008.

Conclusions: On the basis of these results, functional HSP70 inhibition by VER‐155008 suppressed cell growth in pleural mesothelioma cells, accompanied by enhanced macroautophagy. HSP70 inhibition is thus expected to become a new strategy for treating mesothelioma.

Key points

Significant findings of the study

In pleural mesothelioma cells, inhibition of HSP70 function by VER‐155008 suppressed cell proliferation accompanied by induction of autophagy which was synergistically enhanced under the starvation condition, whereas gefitinib, an EGFR‐TKI, did not show the same synergistic effect in autophagy.

What this study adds

The inhibition of HSP70 induced autophagy and suppressed cell proliferation in mesothelioma cells.
Postwar wildlife recovery in an African savanna: evaluating patterns and drivers of species occupancy and richness
Authors: Gaynor K. M. , Daskin J. H. , Rich L. N. , Brashares J. S.
Published: December 2020

As local and global disturbances reshape African savannas, an understanding of how animal communities recover and respond to landscape features can inform conservation and restoration. Here, we explored the spatial ecology of a wildlife community in Gorongosa National Park, Mozambique, where conservation efforts have fostered the recovery of large mammal populations after their near‐extirpation during Mozambique’s civil war. We deployed a grid of 60 camera traps and used a hierarchical, multi‐species occupancy modeling approach to examine patterns of occupancy and its environmental and anthropogenic correlates for different functional groups and species. Our survey provides strong evidence that wildlife in Gorongosa is recovering. Throughout the study area, modeled species richness was comparable to richness in less‐disturbed savanna systems in Tanzania and Botswana, and exceeded estimates of richness from a mixed‐use landscape outside the park and from postwar (1997–2002) aerial surveys. However, the mammal community in Gorongosa differs from prewar conditions and from those of more intact systems, with few large carnivores, low occupancy probabilities for large ungulate species that were dominant prior to the war, and high occupancy for other ungulates that are now ubiquitous. Associations with tree cover varied among species and guilds. Contrary to our expectation, there was no effect of lake proximity on community and group‐level occupancy, and previously dominant floodplain ungulate species now occupy more wooded areas. Mammals were more likely to occupy areas that burned frequently, as post‐fire vegetation regrowth provides high‐quality forage, highlighting the importance of Gorongosa’s fire regime. Occupancy was lower in areas with more illegal hunting, and higher closer to roads, potentially because roads were established in areas of high wildlife density and facilitate animal movement. Continued multi‐species monitoring in Gorongosa can shed light on the different recovery trajectories of ungulate species and the consequences of ongoing large carnivore restoration, guiding conservation interventions.
Have Confidence in the Sea: Maritime Maroons and Fugitive Geographies
Authors: Dunnavant Justin P.
Published: December 2020

Since the birth of the Transatlantic slave trade, enslaved Africans have exploited their geographic circumstances to obtain liberation, effectively transforming them into maroons. However, geographies of marronage have disproportionately investigated terrestrial landscapes to understand how self‐liberated Africans made life in the Atlantic world. Turning our attention to the sea, I use geospatial analyses to map ocean currents and explore routes of passage for maritime maroons from the island of St. Croix (Ay Ay). Mapping this oceanic cartography of Black fugitivity provides renewed insight into the ways in which maroons used oceanic literacy to actualise their quest for freedom and their experiences in their new homes.
Building a high‐resolution chronology of a medieval urban site through Bayesian modelling*
Authors: Haase K. , Olsen J.
Published: December 2020

This paper shows that combining stratigraphic information with dendrochronological and radiocarbon dating in a Bayesian model is a powerful tool in producing a high‐resolution chronology for a medieval urban site. By using all available archaeological information, it is possible to construct a chronology of higher accuracy, transparency and reproducibility than that created through informal interpretation and ceramics chronologies. The example shows how a modelling process is also a valuable tool in validating and reassessing the stratigraphic interpretations. The model is used on two levels: (1) to establish the overall site chronology; and (2) to investigate the age and duration of individual events and structures. Finally, since the model is constructed independently of ceramics chronologies, it is suggested that the current local ceramics chronology could be revised.
Giant circumferential esophageal leiomyoma successfully treated by thoracoscopic enucleation with the patient in a prone position: A case report
Authors: Higuchi Tadashi , Koyanagi Kazuo , Ozawa Soji , Ninomiya Yamato , Yatabe Kentaro , Yamamoto Miho
Published: December 2020

Esophageal leiomyomas are common benign tumors. Although surgical resection is warranted in symptomatic patients, the procedure used to enucleate a giant, circumferential tumor is complicated. A 38‐year‐old man was referred to our institution with a diagnosis of submucosal esophageal tumor. An endoscopic examination revealed a protruding submucosal mass in the lower third of the esophagus. Computed tomography scans demonstrated a circumferential mass measuring 90 × 40 mm. Examination of the biopsy specimens resulted in a diagnosis of leiomyoma of the esophagus, and thoracoscopic enucleation of the tumor via the right thorax with the patient in the prone position was planned. Histopathological and immunohistochemical staining of the surgical specimen confirmed the preoperative diagnosis of benign leiomyoma. The patient was discharged on postoperative day 7 without any complications.
Distinct JNK/VEGFR signaling on angiogenesis of breast cancer‐associated pleural fluid based on hormone receptor status
Authors: Changchien Chih‐Ying , Chang Hsin‐Han , Dai Ming‐Shen , Tsai Wen‐Chiuan , Tsai Hao‐Chung , Wang Chieh‐Yung , Shen Ming‐Sheng , Cheng Li‐Ting , Lee Herng‐Sheng , Chen Ying , Tsai Chen‐Liang
Published: December 2020

Malignant pleural effusion is a common complication in metastatic breast cancer (MBC); however, changes in the pleural microenvironment are poorly characterized, especially with respect to estrogen receptor status. Histologically, MBC presents with increased microvessels beneath the parietal and visceral pleura, indicating generalized angiogenic activity. Breast cancer‐associated pleural fluid (BAPF) was collected and cultured with HUVECs to recapitulate the molecular changes in subpleural endothelial cells. The clinical progression of triple‐negative breast cancer (TNBC) is much more aggressive than that of hormone receptor‐positive breast cancer (HPBC). However, BAPF from HPBC (BAPF‐HP) and TNBC (BAPF‐TN) homogeneously induced endothelial proliferation, migration, and angiogenesis. In addition, BAPF elicited negligible changes in the protein marker of endothelial‐mesenchymal transition. Both BAPF‐HP and BAPF‐TN exclusively upregulated JNK signaling among all MAPKs in HUVECs. By contrast, the response to the JNK inhibitor was insignificant in Transwell and tube formation assays of the HUVECs cultured with BAPF‐TN. The distinct contribution of p‐JNK to endothelial angiogenesis was consequently thought to be induced by BAPF‐HP and BAPF‐TN. Due to increased angiogenic factors in HUVECs cultured with BAPF, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor was applied accordingly. Responses to VEGFR2 blockade were observed in both BAPF‐HP and BAPF‐TN concerning endothelial migration and angiogenesis. In conclusion, the above results revealed microvessel formation in the pleura of MBC and the underlying activation of p‐JNK/VEGFR2 signaling. Distinct responses to blocking p‐JNK and VEGFR2 in HUVECs cultured with BAPF‐HP or BAPF‐TN could lay the groundwork for future investigations in treating MBC based on hormone receptor status.
Immunological basis of early clearance ofMycobacterium tuberculosisinfection: the role of natural killer cells
Authors: Abebe F
Published: December 2020

Tuberculosis (TB) kills more people than any other single infectious disease globally. Despite decades of research, there is no vaccine to prevent TB transmission. Bacille Calmette–Guérin (BCG) vaccine, developed a century ago, is effective against childhood (disseminated and miliary) TB. However, its protective efficacy against pulmonary TB varies from 0 to 80% in different populations. One of the main reasons for the lack of an effective vaccine against TB is the lack of complete understanding about correlates of protective immunity on which to base vaccine design and development. However, some household contacts who are extensively exposed to Mtb infection remain persistently negative to tuberculin skin test and interferon-gamma assay. These individuals, called ‘resisters’, clear Mtb infection early before the development of acquired immunity. The immunological basis of early Mtb clearance is yet to be established; however, innate lymphocytes such as monocytes/macrophages, dendritic cells, neutrophils and natural killer cells, and innate-like T cells such as mucosal-associated invariant T cells, invariant natural killer (NK) T cells and gamma-delta (γδ) T cells, have been implicated in this early protection. In recent years, NK cells have attracted increasing attention because of their role in controlling Mtb infection. Emerging data from animal and epidemiological studies indicate that NK cells play a significant role in the fight against Mtb. NK cells express various surface markers to recognize and kill both Mtb and Mtb-infected cells. This review presents recent advances in our understanding of NK cells in the fight against Mtb early during infection, with emphasis on cohort studies.
Global effects of extreme temperatures on wild bumblebees
Authors: Martinet Baptiste , Dellicour Simon , Ghisbain Guillaume , Przybyla Kimberly , Zambra Ella , Lecocq Thomas , Boustani Mira , Baghirov Ruslan , Michez Denis , Rasmont Pierre
Published: December 2020

Climate plays a key role in shaping population trends and determining the geographic distribution of species because of limits in species’ thermal tolerance. An evaluation of species tolerance to temperature change can therefore help predict their potential spatial shifts and population trends triggered by ongoing global warming. We assessed inter‐ and intraspecific variations in heat resistance in relation to body mass, local mean temperatures, and evolutionary relationships in 39 bumblebee species, a major group of pollinators in temperate and cold ecosystems, across 3 continents, 6 biomes, and 20 regions (2386 male specimens). Based on experimental bioassays, we measured the time before heat stupor of bumblebee males at a heatwave temperature of 40 °C. Interspecific variability was significant, in contrast to interpopulational variability, which was consistent with heat resistance being a species‐specific trait. Moreover, cold‐adapted species are much more sensitive to heat stress than temperate and Mediterranean species. Relative to their sensitivity to extreme temperatures, our results help explain recent population declines and range shifts in bumblebees following climate change.
Colour appearance in immersive three‐dimensional virtual environments
Authors: Díaz‐Barrancas Francisco , Cwierz Halina Carmen , Pardo Pedro J. , Perez Angel L. , Suero María Isabel
Published: December 2020

Technology is constantly evolving and, consequently, all the technological advances taking place are regularly integrated into the daily life of society. During recent years, there has been a trend towards virtual resources such as teleworking, telemedicine and e‐commerce. In many countries, this virtualisation process has been accelerated by the changing circumstances caused by the COVID‐19 pandemic. In any case, there is a growing demand for virtual systems, and virtual reality is a suitable field for the application of a multitude of solutions. However, advances in virtual reality occur without any regard to colour science, and there are several challenges to be overcome to improve the visual appearance and fidelity of colour reproduction in all types of related devices. This paper discusses three open issues related to the visual appearance and visual fidelity of virtual reality systems. We believe it is necessary to direct future research efforts in each of these directions to secure improvements in the visual fidelity of virtual reality systems.
Stem‐cell‐based therapies for retinal degenerative diseases: Current challenges in the establishment of new treatment strategies
Authors: Uyama Hirofumi , Mandai Michiko , Takahashi Masayo
Published: December 2020

Various advances have been made in the treatment of retinal diseases, including new treatment strategies and innovations in surgical devices. However, the treatment of degenerative retinal diseases, such as retinitis pigmentosa (RP) and age‐related macular degeneration (AMD), continues to pose a significant challenge. In this review, we focus on the use of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to treat retinal diseases by harnessing the ability of stem cells to differentiate into different body tissues. The retina is a tissue specialized for light sensing, and its degradation leads to vision loss. As part of the central nervous system, the retina has very low regenerative capability, and therefore, treatment options are limited once it degenerates. Nevertheless, innovations in methods to induce the generation of retinal cells and tissues from ESCs/iPSCs enable the development of novel approaches for these irreversible diseases. Here we review some historical background and current clinical trials involving the use of stem‐cell‐derived retinal pigment epithelial cells for AMD treatment and stem cell‐derived retinal cells/tissues for RP therapy. Finally, we discuss our future vision of regenerative treatment for retinal diseases with a partial focus on our studies and introduce other interesting approaches for restoring vision.
Physical therapy interventions to improve sitting ability in children with or at‐risk for cerebral palsy: a systematic review and meta‐analysis
Authors: Inamdar Ketaki , Molinini Rebecca M , Panibatla Siva Tejaa , Chow Jason C , Dusing Stacey C
Published: December 2020

Aim

To conduct a systematic review and meta‐analysis on the effectiveness of physical therapy interventions to improve sitting ability in young children with or at risk for cerebral palsy (CP).

Method

A systematic literature search was performed using five databases. Study selection criteria were randomized controlled trials published in English on physical therapy interventions targeting sitting, reporting developmental or functional sitting outcomes, and focused on young children with or at risk for CP (mean age ≤5y). Risk of bias (ROB) was assessed using the Cochrane ROB 2.0 tool.

Results

Twelve unique studies met the inclusion criteria and were categorized into one of two categories: (1) comparison of two physical therapy interventions or (2) physical therapy plus adjunct versus physical therapy alone. The combined pooled effect size (g) for the 10 studies included in meta‐analysis was large (g=0.78) but non‐significant. Pooled effect for category 1 was small (g=–0.06) and non‐significant. Interventions in category 2 showed a large and significant effect (g=1.90, p=0.022).

Interpretation

There is a lack of strong evidence for physical therapy interventions targeting sitting in young children with or at‐risk for CP due to limitations in methodological rigor and sample sizes. Components of impairment remediation combined with functional balance training should be explored to improve sitting in children diagnosed with CP. Given the benefits of early achievement of sitting, strong evidence‐based research is needed.

What this paper adds

Strong evidence is lacking for physical therapy interventions to improve sitting ability in young children with/at risk for cerebral palsy (CP).

Kinesio‐taping may be an effective adjunct to conventional physical therapy in improving sitting ability in children with spastic bilateral CP.

Task‐specific, intensive, and child‐initiated intervention components show promise for improving sitting in young infants at risk for CP.
Change in glucose‐lowering medication regimens in individuals with type 2 diabetes mellitus during the COVID‐19 pandemic in Germany
Authors: Jacob Louis , Rickwood Sarah , Rathmann Wolfgang , Kostev Karel
Published: December 2020

Aim

To estimate the proportion of individuals with type 2 diabetes mellitus (T2DM) undergoing changes in glucose‐lowering therapy in 2019 and 2020.

Method

Individuals with T2DM who had at least one consultation in one of 940 general (including diabetologist) practices in Germany between January and July 2019 (N = 79 268) and between January and July 2020 (N = 85 046) were included. Therapy changes were defined as the prescription of new glucose‐lowering drugs, with or without the discontinuation of previous treatments (therapy switch and add‐on therapy, respectively). The number of T2DM patients with at least one medication regimen change was calculated for the periods 1 January to 14 March in 2019 and 2020, and for the periods 15 March to 31 July in 2019 and 2020. March 2020 corresponded to the beginning of the lockdown in Germany.

Results

Overall, there was a decrease in the number of patients with at least one medication regimen change in the period 15 March to 31 July 2019 compared with 15 March to 31 July 2020 (dipeptidyl peptidase‐4 inhibitors: −15%; sodium‐glucose co‐transporter‐2 inhibitors: −3%; glucagon‐like peptide‐1 receptor agonists: 0%; other oral glucose‐lowering drugs: −6%; and insulin: −21%).

Conclusions

The coronavirus disease‐2019 (COVID‐2019) pandemic had a strong impact on glucose‐lowering drug use in T2DM patients in Germany. More research is warranted to further investigate the treatment and management of T2DM individuals during the COVID‐19 era in Germany and elsewhere.
A retrospective observational population‐based study to assess the prevalence and burden of illness of type 2 diabetes with an estimated glomerular filtration rate < 90 mL/min/1.73 m2 in Ontario, Canada
Authors: Rapattoni Wally , Zante David , Tomas Marko , Myageri Varun , Golden Shane , Grover Prerna , Tehrani Ali , Millson Brad , Tobe Sheldon W. , Rose Jennifer B.
Published: December 2020

Aim

To better understand the healthcare burden of people with type 2 diabetes (T2D) and estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 in Ontario, Canada.

Materials and Methods

We used administrative data to evaluate the prevalence of T2D, eGFR < 90 mL/min/1.73 m2 and adverse cardiovascular co‐morbidities in individuals aged ≥ 30 years living in Ontario, Canada. We also examined incremental healthcare costs and healthcare resource utilization (HCRU) for these patients with specific incident cardiovascular and renal outcomes, in comparison with controls without these outcomes.

Results

While the prevalence of T2D in the general population aged ≥ 30 years in Ontario increased by 1.8% over a 5‐year period (2011‐2012 to 2015‐2016), the prevalence of eGFR < 90 mL/min/1.73 m2 among people with T2D increased by 35%. In comparison with corresponding controls without these outcomes, the per patient average total costs (Canadian dollars) over a 2‐year analysis period were higher for patients with cardiovascular disease/chronic kidney disease related death ($69 827; n = 32 407), doubling of serum creatinine ($52 260; n = 22 825), those who started dialysis ($150 627; n = 3499) or received a kidney transplant ($50 664; n = 651). Similarly, HCRU was significantly greater for patients with these incident outcomes.

Conclusions

This real‐world retrospective study highlights an increasing prevalence of T2D, eGFR < 90 mL/min/1.73 m2, and the substantially higher healthcare costs and HCRU when these patients have adverse cardiovascular and renal outcomes. The existence of such a large economic burden underpins the importance of preventing these diabetes‐related complications.
Effectiveness of premixed insulin to achieve glycaemic control in type 2 diabetes: A retrospective UK cohort study
Authors: Jude Edward B. , Trescoli Carlos , Emral Rifat , Ali Amar , Lubwama Robert , Palmer Karen , Shaunik Alka , Nanda Nithya , Raskin Philip , Gomez‐Peralta Fernando
Published: December 2020

Aim

To investigate the effectiveness of premixed insulin for achieving glycaemic outcomes in clinical practice in the UK.

Materials and Methods

Electronic medical record data from The Health Improvement Network database were captured for adults with type 2 diabetes (T2D) uncontrolled (HbA1c ≥9%) on two or more oral antihyperglycaemic drugs (OADs) initiating premixed insulin. Effectiveness of premixed insulin was assessed by the probability and incidence of achieving glycaemic outcomes (target HbA1c <7.5% [<58 mmol/mol] and a ≥1% or ≥2% HbA1c reduction) over 24 months.

Results

Data from 974 participants (mean age 62 years; 56% male; 52% obese or extremely obese; mean HbA1c 11.3% [100 mmol/mol]; hypertension 64%, dyslipidaemia 23% and nephropathy 21%) were analysed. The probability of achieving HbA1c  <7.5% was highest during months 3‐6 (18.2%), while the cumulative probability of achieving this target plateaued between months 15‐24 (15.7%‐16.0%). Incidence of achieving all glycaemic outcomes plateaued after 12 months and differed by baseline HbA1c, but not OAD use. Factors affecting some glycaemic outcomes included a body mass index >40 kg/m2 and co‐morbidities including nephropathy and stroke.

Conclusions

In people with uncontrolled T2D (HbA1c ≥9%), glycaemic outcome achievement on premixed insulin was low at 6 months with little additional clinical benefit beyond 12 months, suggesting a high unmet need for early, timely treatment changes with more effective, simpler therapies.
Diverging functional strategies but high sensitivity to an extreme drought in tropical dry forests
Authors: González‐M. Roy , Posada Juan M. , Carmona Carlos P. , Garzón Fabián , Salinas Viviana , Idárraga‐Piedrahita Álvaro , Pizano Camila , Avella Andrés , López‐Camacho René , Norden Natalia , Nieto Jhon , Medina Sandra P. , Rodríguez‐M. Gina M. , Franke‐Ante Rebeca , Torres Alba M. , Jurado Rubén , Cuadros Hermes , Castaño‐Naranjo Alejandro , García Hernando , Salgado‐Negret Beatriz
Published: December 2020

Extreme drought events have negative effects on forest diversity and functioning. At the species level, however, these effects are still unclear, as species vary in their response to drought through specific functional trait combinations. We used long‐term demographic records of 21,821 trees and extensive databases of traits to understand the responses of 338 tropical dry forests tree species to ENSO2015, the driest event in decades in Northern South America. Functional differences between species were related to the hydraulic safety‐efficiency trade‐off, but unexpectedly, dominant species were characterised by high investment in leaf and wood tissues regardless of their leaf phenological habit. Despite broad functional trait combinations, tree mortality was more widespread in the functional space than tree growth, where less adapted species showed more negative net biomass balances. Our results suggest that if dry conditions increase in this ecosystem, ecological functionality and biomass gain would be reduced.
Inflammation, ictogenesis, and epileptogenesis: An exploration through human disease
Authors: Tan Tracie Huey‐Lin , Perucca Piero , O’Brien Terence J. , Kwan Patrick , Monif Mastura
Published: December 2020

Epilepsy is seen historically as a disease of aberrant neuronal signaling manifesting as seizures. With the discovery of numerous auto‐antibodies and the subsequent growth in understanding of autoimmune encephalitis, there has been an increasing emphasis on the contribution of the innate and adaptive immune system to ictogenesis and epileptogenesis. Pathogenic antibodies, complement activation, CD8+ cytotoxic T cells, and microglial activation are seen, to various degrees, in different seizure‐associated neuroinflammatory and autoimmune conditions. These aberrant immune responses are thought to cause disruptions in neuronal signaling, generation of acute symptomatic seizures, and, in some cases, the development of long‐term autoimmune epilepsy. Although early treatment with immunomodulatory therapies improves outcomes in autoimmune encephalitides and autoimmune epilepsies, patient identification and treatment selection are not always clear‐cut. This review examines the role of the different components of the immune system in various forms of seizure disorders including autoimmune encephalitis, autoimmune epilepsy, Rasmussen encephalitis, febrile infection–related epilepsy syndrome (FIRES), and new‐onset refractory status epilepticus (NORSE). In particular, the pathophysiology and unique cytokine profiles seen in these disorders and their links with diagnosis, prognosis, and treatment decision‐making are discussed.
A histological evaluation of facial suture lines in six horses aged 1 day to 9 years
Authors: Geitzenauer L. , Geyer H. , Fürst A. E. , Klein L. , Jackson M. A.
Published: December 2020

Craniofacial sutures are fibrous connections between the flat bones in the skull, allowing a small amount of movement to absorb strain and load as long as they are patent. In the present study, we examined the histological appearance of facial suture lines in horses of different ages. The internasal, nasofrontal and maxillolacrimal sutures were macroscopically identified and extracted from the skulls of six horses aged 1 day (two horses), 5 days, 2, 6 and 9 years and prepared into histological samples. The suture lines were then examined for width, form, cell density and morphology, vascularisation and morphology of the surrounding tissue and compared based on the age of the horse. Although macroscopically the sutures became difficult to identify in the 6‐ and 9‐year‐old horses, histologically they were clearly visible in all samples, indicating that the sutures were patent and consisted of connective tissue in all analysed horses. The sutures became subjectively narrower with lower cell density in older horses as compared to young horses, and there was a noticeable maturation from woven to cancellous bone surrounding the sutures. Vascular structures were present in all sutures regardless of age or location. In conclusion, this study raises awareness of the histological suture conformation in neonatal and adult horses and their persistence into adulthood. A better understanding of the histological structure of facial sutures and their continued patency into adulthood can aide in the interpretation of radiographs and computed tomography images of the head and in improving treatment methods and outcomes for horses affected with suture exostosis. In addition, if biopsies are taken, clinicians will have a basis on which to determine which cells are related to the disease process and which are normally occurring.
What can the hair tell us about COVID‐19?
Authors: Trüeb Ralph M. , Dutra Rezende Hudson , Gavazzoni Dias Maria Fernanda Reis
Published: December 2020

The novel viral pandemic coronavirus disease 2019 (COVID‐19) has sparked uncertainties as to its origin, epidemiology and natural course. The study of the cutaneous manifestations of COVID‐19 has evolved with the hope that they may be useful as markers for the disease, prognostication and pathogenic insights into the disease. With regard to the hair, clinicopathological correlations have remained elusive. More recently, androgenetic alopecia and grey hair have been proposed as cutaneous markers for elevated severity risk. So far, we have only observed postinfectious effluvium in a causal association with COVID‐19. The onset and acuity of hair shedding depended on the clinical severity of disease. There was complete recovery of hair.
Culture and vision in virtual reality narratives
Authors: Mills Nicole , Courtney Matthew , Dede Christopher , Dressen Arnaud , Gant Rus
Published: December 2020

Hansen states that “FL studies must learn to conceive of culture as an open, multi‐voiced and dialogical interaction full of contradictions.” One advocated approach to teach transcultural understanding is through the analysis of cultural narratives. Kearney defines cultural narratives as “the multiple (sometimes competing), conventional storylines that cultural groups produce and use to make sense of and attribute meaning to their shared experiences.” This article will showcase a project in a beginning French course in which four different Parisians from the same quarter were asked to document and share the stories of their lives with a virtual reality (VR) camera. Findings reveal that the VR narratives allowed students to envision, experience, and understand diverse facets of Parisian culture and more vividly imagine their future role as participants in Parisian communities.
Wheat and barley cultivars show plant traits acclimation and increase grain yield under simulated shade in Mediterranean conditions
Authors: Arenas‐Corraliza M. Guadalupe , López‐Díaz M. Lourdes , Rolo Víctor , Moreno Gerardo
Published: December 2020

Agroforestry systems are reported as climate‐resilient productive systems, but it is yet unclear how tree shade affects crops performance. The aim of this work was to assess how the phenology, plant traits and grain yield of wheat and barley were affected by shade. In an open greenhouse experiment, we cultivated in pots nine cultivars differing in precocity for each species and imposed three artificial shading levels (S0 ~ 0%, S1 ~ 25%, S2 ~ 50%) at the start of cereal booting. Our results showed that shade speeded up first growth stages in both species, until the starting of milk development. Barley showed consistent phenological responses to the three irradiance levels among cultivars, but not wheat that showed larger phenological differences among cultivars at moderate shade. Deep shade prolonged the time needed for wheat grain ripening. Both species increased grain yield by 15%–20% with shade, driven by shade‐acclimations of plant traits that differed among species. For wheat, grain yield was determined by the assemblage of traits that contribute to yield, such as grain weight, precocity and non‐photochemical quenching, while, for barley, SPAD value, precocity to reach phenological stages, grains per spike and plant height had the strongest influence. These traits varied widely among cultivars and seem of interest to identify best suited cultivars for shading conditions of Mediterranean agroforestry systems.
How should we measure blood pressure? Implications of the fourth blood pressure measurement in office blood pressure
Authors: Vischer Annina S. , Socrates Thenral , Winterhalder Clemens , Eckstein Jens , Mayr Michael , Burkard Thilo
Published: December 2020

According to the European Hypertension Guidelines regarding office blood pressure measurements (OBPMs), the mean between second/third or third/fourth OBPM should be taken if the first two readings differ by ≤10 or >10 mmHg, respectively. Our aim was to explore the value of the fourth OBPM and determine whether a simplified OBPM procedure is feasible without loss of quality. In this cross‐sectional study, four standard OBPMs were taken. The mean of the second/third OBPM (S2S3/D2D3) and third/fourth OBPM (S3S4/D3D4) for systolic/diastolic values was calculated. Correlation, agreement, and differences regarding BP classification were explored for the entire cohort and subsets with a difference between the first/second OBPM (S1S2/D1D2) ≤10 and >10 mmHg. Overall (n = 802) and for the subsets with an S1S2 (n = 596) and D1D2 (n = 742) difference ≤10 mmHg, S3S4/D3D4 was in median 0.5 mmHg lower than S2S3/D2D3, respectively (p < .0005 for all). In participants with an S1S2 (n = 206) and D1D2 (n = 60) difference >10 mmHg, S3S4/D3D4 differed numerically from S2S3/D2D3, respectively (p > .1 for all). Overall and for all subsets with an S1S2/D1D2 difference ≤10/>10 mmHg, less subjects were numerically classified as hypertensive with S3S4/D3D4 than with S2S3/D2D3 (p > .04), but BP reclassification occurred in both directions in 1.0%‐10.0%, depending on the cohort. In conclusion, the third/fourth OBPM results in lower BP values than the second/third measurement, regardless of the difference between first/second OBPM, whereby BP reclassifications occurred in both directions. Therefore, the cutoff of >10 versus ≤10mmHg difference between first/second OBPM to implement a fourth BPM harbors the risk of distorted results. We therefore recommend using the second/third BPM for standardized OBPM.

Trial registration: Registered on clinicaltrials.gov (NCT02552030).
Preoperative fundus examination in patients with diabetes scheduled for surgery
Authors: Watanabe Hirotaka , Takahara Mitsuyoshi , Katakami Naoto , Matsuoka Taka‐aki , Shimomura Iichiro
Published: December 2020

This study aimed to show the proportion of fundus examinations in patients with diabetes who were scheduled for surgery. We retrospectively analyzed 455 consecutive patients with diabetes admitted for surgery. Just 49% had fundus examinations before hospitalization. The decision tree analysis showed that the type of family doctor was the first split associated with fundus examination; patients treated by a diabetes specialist were more likely to receive the examination. In this subgroup, glycated hemoglobin levels ≥8.0% and age ≥71 years were associated with a lower proportion of receiving the examination. In patients whose family doctor was not a diabetes specialist, glycated hemoglobin levels <7.2% and body mass index <27.4 kg/m2 without severe comorbidities were associated with a higher proportion of receiving the examination. In conclusion, half of patients scheduled for surgery did not receive fundus examinations. A high‐risk population for not receiving the examination varied with the consultation setting.
Phosphatidylinositol‐3 kinase mediates the sweet suppressive effect of leptin in mouse taste cells
Authors: Yoshida Ryusuke , Margolskee Robert F. , Ninomiya Yuzo
Published: December 2020

Leptin is known to selectively suppress neural and taste cell responses to sweet compounds. The sweet suppressive effect of leptin is mediated by the leptin receptor Ob‐Rb, and the ATP‐gated K+ (KATP) channel expressed in some sweet‐sensitive, taste receptor family 1 member 3 (T1R3)‐positive taste cells. However, the intracellular transduction pathway connecting Ob‐Rb to KATP channel remains unknown. Here we report that phosphoinositide 3‐kinase (PI3K) mediates leptin's suppression of sweet responses in T1R3‐positive taste cells. In in situ taste cell recording, systemically administrated leptin suppressed taste cell responses to sucrose in T1R3‐positive taste cells. Such leptin's suppression of sucrose responses was impaired by co‐administration of PI3K inhibitors (wortmannin or LY294002). In contrast, co‐administration of signal transducer and activator of transcription 3 inhibitor (Stattic) or Src homology region 2 domain‐containing phosphatase‐2 inhibitor (SHP099) had no effect on leptin's suppression of sucrose responses, although signal transducer and activator of transcription 3 and Src homology region 2 domain‐containing phosphatase‐2 were expressed in T1R3‐positive taste cells. In peeled tongue epithelium, phosphatidylinositol (3,4,5)‐trisphosphate production and phosphorylation of AKT by leptin were immunohistochemically detected in some T1R3‐positive taste cells but not in glutamate decarboxylase 67‐positive taste cells. Leptin‐induced phosphatidylinositol (3,4,5)‐trisphosphate production was suppressed by LY294002. Thus, leptin suppresses sweet responses of T1R3‐positive taste cells by activation of Ob‐Rb–PI3K–KATP channel pathway.

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A new de novo SYT2 mutation presenting as distal weakness. Neuropathy or neuromuscular junction dysfunction?
Authors: Fionda Laura , Turon‐Sans Janina , Fuentes Prior Pablo , Bernal Noguera Sara , Cortés‐Vicente Elena , López‐Pérez Maria Angeles , Gallardo Eduard , Rojas‐García Ricard
Published: December 2020

We report the case of a patient with a clinical phenotype characterized by distal lower limb weakness and pes cavus. The electrophysiological study showed slightly reduced or normal amplitude of motor potentials, a decremental response to repetitive nerve stimulation and post‐exercise facilitation. Muscle biopsy showed only mild neurogenic features. Genetic analysis included a clinical exome sequencing, followed by Sanger analysis. Three‐dimensional (3D) models were generated with a SwissModel (https://swissmodel.expasy.org/) to explain the clinical observations and reinforce the pathogenic nature of the genetic variant identified. Genetic analysis demonstrated a new de novo heterozygous in frame deletion of the SYT2 gene (NM_177402.4: c.1082_1096del), confirmed by Sanger sequencing, which removes five aminoacids in the C2B domain of synaptotagmin‐2 protein, that cause a profound effect on the structure and function of this synaptic vesicle protein. We identified a de novo genetic variant in the SYT2 gene, further supporting its association with a highly stereotyped clinical and electrophysiological phenotype. Our case showed electrophysiological features consistent with a presynaptic dysfunction in the neuromuscular junction with normal post‐exercise amplitudes, not supporting the presence of predominant axonal damage. Although the analysis of SYT2 gene should be included in genetic analysis of patients presenting with this clinical phenotype that mimics motor neuropathy, clinicians have to consider the study of neuromuscular transmission to early identify this potentially treatable condition.
Motivations for Family Members’ Visits to Nursing Home Residents With Dementia in Taiwan: A Qualitative Study
Authors: Tsai Hsiu‐Hsin , Cheng Ching‐Yu , Weng Li‐Chueh , Shieh Wann‐Yun , Liu Chia‐Yih
Published: December 2020

Purpose

The purpose of this study was to explore what motivates family members to visit a relative with dementia who has been transferred to a nursing home in Taiwan.

Design and Methods

Data were collected for this qualitative descriptive study using audiotaped, semi‐structured, in‐depth, face‐to‐face interviews. A total of 20 family members of elderly nursing home residents participated in the study. Nursing home residents were from four nursing homes in Taiwan and had been diagnosed with probable or possible dementia by a psychiatrist or neurologist. Transcribed audiotaped interviews were analyzed using thematic analysis.

Findings

Most family members were the children of the residents (n =17, 85%). The theme describing the core motivation for family members’ visits to nursing home residents was “to maintain the unforgotten family affection.” This motivation comprised four relevant categories: hoping to slow degeneration, providing a congruous environment, honoring filial and karmic duty, and ensuring the quality of care.

Conclusions

Motivations for Taiwanese family members’ visits to nursing home residents with dementia were similar to those in Western cultures. However, “hoping to slow degeneration” and “providing a congruous environment” were unique categories.

Clinical Relevance

Nurses and policymakers could use these findings to design interventions that might increase holistic care for both family members and nursing home residents with dementia. Providing programming focused on family members’ unique priorities could address swallowing difficulties, management of dementia symptoms, nutritional needs, and selection of residents’ roommates. These programs could improve the quality of family members’ visits as well as the quality of staff–family relationships.