bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining of transcriptome and metabolome analyses for understanding the utilization and metabolic pathways of Xylo‐oligosaccharide in Bifidobacterium adolescentis ATCC 15703
Authors: Yang Jian , Tang Qilong , Xu Lei , Li Zhijiang , Ma Yongqiang , Yao Di
Published: October 2019

A combination of transcriptome and metabolome analyses was applied to understand the utilization and metabolism of Xylo‐oligosaccharide (XOS) in Bifidobacterium adolescentis 15703 as well as identifying the key regulatory‐related genes and metabolites. Samples of cultures grown on either XOS or xylose were collected. The transcript and metabolite profiles were obtained from high‐throughput RNA‐sequencing data analysis and UHPLC system. Compared with xylose, XOS highly promoted the growth of B. adolescentis 15703 and resulted in a growth yield about 1.5‐fold greater than xylose. The transcriptome analysis showed that XOS could enhance genes, including ABC transporters, galactosidase, xylosidase, glucosidase, and amylase, which were involved in transport and metabolism of carbohydrate compared with xylose. Furthermore, the expression profile of 16 candidate genes using qRT‐PCR has validated the accuracy of the RNA‐seq data. Also, the metabolomic analyses, particularly those related to metabolic biomarkers of fatty acids, amino acids, and sugars showed a similar trend of result and approved the advantages of XOS as growth medium for B. adolescentis 15703 compared with xylose. The expression and abundance of specific genes and metabolites highlighted the complex regulatory mechanisms involved in utilization of XOS by B. adolescentis 15703. These results are useful in the understanding of the metabolic pathway of XOS in B. adolescentis 15703 and contribute to the optimization of XOS probiotic effects as a food additive.
Functional characteristics and microbiological viability of foam‐mat dried Bambara groundnut (Vigna subterranea) yogurt from reconstituted Bambara groundnut milk powder
Authors: Hardy Zolelwa , Jideani Victoria A.
Published: October 2019

The functional, nutritional, and physical characteristics of foam‐mat dried Bambara groundnut (Vigna subterranea) yogurt were investigated. Bambara groundnut powdered yogurt (BGNPY) was produced using Bambara groundnut milk powder (BGNMP) and Bambara groundnut milk (BGNM). BGNMP was reconstituted with water (1:5). The reconstituted BGN milk (BGNM‐R) and original nonreconstituted BGNM (BGNM‐NR) were inoculated with normal yogurt culture while held at a temperature of 45°C and incubated for 24 hr at 35°C. The BGN yogurts were dried employing the foam‐mat drying process with gum arabic (6%) and methylcellulose (0.5%) as foaming agents and dried at 50°C for 24 hr. The BGN powdered yogurt from reconstituted milk (BGNPY‐RM) and BGN powdered yogurt from nonreconstituted milk (BGNPY‐NRM) were evaluated for functional, nutritional, thermal, and physical characteristics. Water absorption (1.27 and 1.31 g/g) and water solubility (73.3. and 71.22 100/g) index of the powdered yogurts did not differ significantly, while a significant (p < 0.05) difference was observed for the Tg of BGNPY‐R and BGNPY‐NR. Nutrient composition of BGNPY‐R and BGNPY‐NR had no significant (p > 0.05) difference, while ash differed significantly (p < 0.05). Particle size and particle size distribution of BGNPY‐R and BGNPY‐NR had no significant (p > 0.05) difference. Probiotic viability of BGNPY‐R (7.2 log cfu/ml) remained above the minimum recommended dosage (6 log cfu/ml).
Functional–structural relationship in large‐scale brain networks of patients with end stage renal disease after kidney transplantation: A longitudinal study
Authors: Chen Hui J. , Wang Yun F. , Wen Jiqiu , Xu Qiang , Lu Guang M. , Zhang Long J.
Published: October 2019

It is unclear how the brain network changed after kidney transplantation (KT). We explored the patterns of large‐scale complex network after KT in end‐stage renal disease (ESRD) patients with resting‐state functional MRI (rs‐fMRI) and diffusion tensor imaging (DTI). Twenty‐one ESRD patients (14 men; mean age, 31.5 ± 9.9 years) scheduled for KT and 17 age‐ and gender‐matched healthy controls (HC) (8 men; mean age, 28.9 ± 7.2 years) were enrolled in this study. Each participant underwent rs‐fMRI and DTI scans in three time points (pre‐KT, 1 and 6 months after KT [for ESRD]). Graph theory analysis was used to characterize the topological properties by using functional and structural network connectivities intergroup correlation analysis was performed between functional/structural MR indexes and clinical markers. Compared with HC, pre‐KT ESRD patients showed an altered topological organization in both functional and structural networks. Compared with pre‐KT, increased node degree and node efficiency were observed for both functional and structural networks at 1 month after KT (all p < .05), which were further increased at 6 months after KT (p < .05). Both functional and structural networks did not recover completely at 6 months after KT (all p < .05). The patients showed an increased functional–structural connectivity coupling at 1 month after KT compared with HC (p = .041). A trend of progressive recovery of functional and structural connectivity networks was observed in ERSD patients after KT, which did not recover to the normal levels even in 6 months after KT. The study results underlie cognitive function recovery in ESRD patients following KT in the neuropathophysiological perspective.
Rapid head and neck tissue identification in thyroid and parathyroid surgery using optical coherence tomography
Authors: Yang Nathan , Boudoux Caroline , De Montigny Etienne , Maniakas Anastasios , Gologan Olga , Madore Wendy‐Julie , Khullar Sharmila , Guertin Louis , Christopoulos Apostolos , Bissada Eric , Ayad Tareck
Published: October 2019

Background

Optical coherence tomography (OCT) is a noninvasive imaging modality that may reproduce the microarchitecture of tissues in real‐time. This study examines whether OCT can render distinct images of thyroid, parathyroid glands, adipose tissue, and lymph nodes in both healthy and pathological states.

Methods

Twenty‐seven patients undergoing thyroidectomy, parathyroidectomy, and/or neck dissection for thyroid cancer were recruited prospectively for imaging prior to histopathological analysis.

Results

Based on 122 imaged specimens, qualitative OCT descriptions were derived for healthy thyroid, parathyroid gland, adipose tissue, and lymph node. The frequencies at which distinguishing features were present for each tissue type were 88%, 83%, 100%, and 82%. OCT appearance of pathological specimens were also described.

Conclusions

Healthy neck tissues have distinct OCT appearances, which could facilitate parathyroid identification during thyroidectomies. However, images of parathyroid adenomas could be confused with those of lymph nodes, and benign and malignant thyroid nodules could not be differentiated.
Is hippocampal remapping the physiological basis for context?
Authors: Kubie John L. , Levy Eliott R. J. , Fenton André A.
Published: October 2019

In 1980, Nadel and Wilner extended Richard Hirsh's notion that the hippocampus creates environmental representations, called “contexts,” suggesting that the fundamental structure of context was the spatial representation proposed by O'Keefe and Nadel's landmark book, The Hippocampus as a Cognitive Map (1978). This book, in turn, derives from the discovery that individual hippocampal neurons act as place cells, with the complete set of place cells tiling an enclosure, forming a type of spatial map. It was found that unique environments had unique place cell representations. That is, if one takes the hippocampal map of a specific environment, this representation scrambles, or “remaps” when the animal is placed in a different environment. Several authors have speculated that “maps” and “remapping” form the physiological substrates for context and context shifting. One difficulty with this definition is that it is exclusively spatial; it can only be inferred when an animal locomotes in an enclosure. There are five aims for this article. The first is to give an historical overview of context as a variable that controls behavior. The second aim is to give an historical overview of concepts of place cell maps and remapping. The third aim is to propose an updated definition of a place cell map, based on temporal rather than spatial overlaps, which adds flexibility. The fourth aim is to address the issue of whether the biological phenomenon of hippocampal remapping, is, in fact, the substrate for shifts in the psychological phenomenon of context. The final aim is speculation of how contextual representations may contribute to effective behavior.
Event conjunction: How the hippocampus integrates episodic memories across event boundaries
Authors: Griffiths Benjamin J. , Fuentemilla Lluís
Published: October 2019

Our lives are a continuous stream of experience. Our episodic memories on the other hand have a definitive beginning, middle, and end. Theories of event segmentation suggest that salient changes in our environment produce event boundaries which partition the past from the present and, as a result, produce discretized memories. However, event boundaries cannot completely discretize two memories; any shared conceptual link will lead to the rapid integration of these memories. Here, we present a new framework inspired by electrophysiological research that resolves this apparent contradiction. At its heart, the framework proposes that hippocampal theta‐gamma coupling maintains a highly abstract model of an ongoing event and serves to encode this model as an episodic memory. When a second but related event begins, this theta‐gamma model is rapidly reconstructed within the hippocampus where new details of the second event can be appended to the existing event model. The event conjunction framework is the first electrophysiological explanation of how event memories can be formed at, and integrated across, event boundaries.
Association of dengue virus‐specific polyfunctional T‐cell responses with clinical disease severity in acute dengue infection
Authors: Wijeratne Dulharie T. , Fernando Samitha , Gomes Laksiri , Jeewandara Chandima , Jayarathna Geethal , Perera Yashoda , Wickramanayake Samurdhi , Wijewickrama Ananda , Ogg Graham S. , Malavige Gathsaurie N.
Published: October 2019

Introduction

Although the role of dengue virus (DENV)‐specific T cells in the pathogenesis of acute dengue infection is emerging, the functionality of virus‐specific T cells associated with milder clinical disease has not been well studied. We sought to investigate how the functionality of DENV–NS3 and DENV–NS5 protein‐specific T cells differ in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF).

Methods

Using intracellular cytokine assays, we assessed the production of interferon γ (IFNγ), tumor necrosis factor‐α (TNF‐α), macrophage inflammatory protein‐1β (MIP‐1β), and CD107a expression in adult patients with acute DF (n = 21) and DHF (n = 22).

Results

Quadruple cytokine‐producing, polyfunctional DENV–NS3‐ and DENV–NS5‐specific T cells were more frequent in those with DF when compared to those with DHF. While DENV–NS3‐ and DENV–NS5‐specific T cells in patients with DF expressed IFNγ > TNF‐α > MIP‐β > CD107a, T cells of those with DHF predominantly expressed CD107a > MIP‐1β > IFNγ > TNF‐α. Overall production of IFNγ or TNF‐α by DENV–NS3‐ and DENV–NS5‐specific T cells was significantly higher in patients with DF. The majority of NS3‐specific T cells in patients with DF (78.6%) and DHF (68.9%) were single‐cytokine producers; 76.6% of DENV–NS5‐specific T cells in those with DF and 77.1% of those with DHF, produced only a single cytokine. However, no significant association was found with polyfunctional T‐cell responses and the degree of viraemia.

Conclusions

Our results suggest that the functional phenotype of DENV‐specific T cells are likely to associate with clinical disease severity.
The FIGO Pregnancy Obesity and Nutrition Initiative (PONI)
Authors: Hanson Mark , Jacob Chandni Maria , Hod Moshe , Killeen Sarah Louise , McAuliffe Fionnuala M.
Published: October 2019

The activities of the FIGO Pregnancy Obesity and Nutrition Initiative are aimed at reducing all types of malnutrition in women before, during and after pregnancy.
Randomized controlled trial of gonadotropin‐releasing hormone agonist microdose flare‐up versus flare‐up among poor responders undergoing intracytoplasmic sperm injection
Authors: Ghaffari Firouzeh , Jahangiri Nadia , Madani Tahereh , Khodabakhshi Shabnam , Chehrazi Mohammad
Published: October 2019

Objective

To compare the effect of gonadotropin‐releasing hormone (GnRH) agonist microdose flare‐up and GnRH agonist flare‐up protocols among women with poor ovarian reserve undergoing intracytoplasmic sperm injection (ICSI) cycles.

Methods

Randomized controlled trial study among 131 women with poor ovarian reserve who underwent ICSI cycles at a single center in Tehran, Iran, between September 2008 and May 2014. Eligible women were randomly assigned to either the microdose flare‐up (n=66) or flare‐up (n=65) protocol. The primary outcome measure was live birth rate.

Results

Both groups were comparable in cycle cancellation, mean number of dominant follicles, retrieved oocytes, and metaphase II oocytes. Number of stimulation days (P=032) and endometrial thickness (P=0.001) were significantly higher, and gonadotropin dose was non‐significantly higher (P=0.075) in the microdose flare‐up group than in the flare‐up group. No difference in clinical pregnancy, implantation, or abortion rate was observed between the two protocols. Live birth was higher in the microdose flare‐up group than in the flare‐up group (P=0.036).

Conclusion

The microdose flare‐up protocol seemed to be superior to the flare‐up protocol, but it required a higher dose of gonadotropins and a longer duration of stimulation. Further prospective clinical trials of the microdose flare‐up protocol are recommended.

ClinicalTrials.gov

NCT01006954
Two‐ and three‐photon absorption cross‐section characterization for high‐brightness, cell‐specific multiphoton fluorescence brain imaging
Authors: Lanin Aleksandr A. , Chebotarev Artem S. , Pochechuev Matvei S. , Kelmanson Ilya V. , Kotova Daria A. , Bilan Dmitry S. , Ermakova Yulia G. , Fedotov Andrei B. , Ivanov Anatoly A. , Belousov Vsevolod V. , Zheltikov Aleksei M.
Published: October 2019

We demonstrate an accurate quantitative characterization of absolute two‐ and three‐photon absorption (2PA and 3PA) action cross sections of a genetically encodable fluorescent marker Sypher3s. Both 2PA and 3PA action cross sections of this marker are found to be remarkably high, enabling high‐brightness, cell‐specific two‐ and three‐photon fluorescence brain imaging. Brain imaging experiments on sliced samples of rat's cortical areas are presented to demonstrate these imaging modalities. The 2PA action cross section of Sypher3s is shown to be highly sensitive to the level of pH, enabling pH measurements via a ratiometric readout of the two‐photon fluorescence with two laser excitation wavelengths, thus paving the way toward fast optical pH sensing in deep‐tissue experiments.
Association of vitamin d with glycemic control in Saudi patients with type 2 diabetes: A retrospective chart review study in an emerging university hospital
Authors: Al Dossari Khaled K. , Ahmad Gulfam , Aljowair Abdulrahman , Alqahtani Naif , Shibrayn Mohammed Bin , Alshathri Mohammed , Alshehri Dahfer , Akhlaq Suhair , Hejab Faisal Bin , Alqahtani Abdulelah , Razzak Hira Abdul
Published: October 2019

Background

Vitamin D (mainly 25‐hydroxyvitamin D, 25[OH]D) has stimulated increasing interest in Saudi Arabia over the current years due to its association with several different chronic diseases such as diabetes. This study aims to ascertain whether the vitamin D level has any influence on glycemic control in Saudi patients with type 2 diabetes (T2DM).

Method

This retrospective study included 200 patients with T2DM who visited Prince Sattam Bin Abdulaziz University Hospital between January 2015 and December 2015. Venous blood was collected and examined for “serum/plasma levels of 25(OH)D” and related variables using kit methods. HbA1C levels <7% and ≥7% were taken as indicators of good and poor glycemic control, respectively. An association between vitamin D deficiency and poor glycemic control was determined using multinomial logistic regression analysis.

Results

Among the total of 200 patients with type 2 diabetes, 118 (59%) were female and 82 (41%) were males with the mean age 42.4 ± 14.8 years. Good glycemic control (HbA1c < 7) was observed in 127 (63.5%), and poor glycemic control (HbA1c > 7) was found in 73(36.5%). The mean serum 25(OH)vit D was 20.27 ± 8.66 ng/mL, with (52% vs 82%; P ≤ .001) of subjects identified to have vitamin D deficiency in good and poor glycemic control groups, respectively.

Conclusion

Taken together, our results demonstrated an association of vitamin D level with poor glycemic control in patients with type 2 diabetes. However, additional studies with larger sample size from local population are warranted in future to confirm and extend the findings of the present study.
LINC00205 modulates the expression of EPHX1 through the inhibition of miR‐184 in hepatocellular carcinoma as a ceRNA
Authors: Long Xi , Li Qian , Zhi Li‐Jun , Li Jin‐Mao , Wang Zheng‐Yu
Published: October 2019

Several studies have shown that low expression of epoxide hydrolase 1 (EPHX1) is closely associated with varying human cancers, including hepatocellular carcinoma (HCC). This study aims to explore the potential mechanism of EPHX1 silencing and revealed a novel regulatory pathway in the pathogenesis of HCC. In this study, micro ribonucleic acid (miR)‐184 was predicted and validated to be a regulator of EPHX1 through experiments, and its expression was negatively correlated with the messenger RNA (mRNA) levels of EPHX1 in primary tumors. Elevation of EPHX1 suppressed cell proliferation and migration as well as cell cycle progression, and induced apoptosis, while downregulation of miR‐184 exhibited the opposite effect on cellular processes. Moreover, LINC00205 interacted with miR‐184 and was markedly downregulated in tumors. The effects of the miR‐184 inhibitor on cell proliferation, apoptosis, and migration were reversed in part by the transfection with LINC00205 small interfering RNAs. In addition, LINC00205 acted as a molecular sponge to positively regulate the mRNA and protein levels of EPHX1 via regulating miR‐184. The tumorigenicity of HCC cells was enhanced by LINC00205 shRNA but diminished by overexpression of EPHX1 in vivo. Clinically, the EPHX1 expression in patients with HCC was markedly downregulated. Taken together, the results of this study suggest that as a competing endogenous RNA, LINC00205 may regulate EPHX1 by inhibiting miR‐184 in the progression of HCC and that targeting the LINC00205/miR‐184/EPHX1 axis may provide a treatment protocol for patients.
Upregulation of microRNA‐218 reduces cardiac microvascular endothelial cells injury induced by coronary artery disease through the inhibition of HMGB1
Authors: Gao Wenhui , Cui Hanbin , Li Qianjun , Zhong Hai , Yu Jingjing , Li Ping , He Xijie
Published: October 2019

This study is performed to examine the impacts of microRNA‐218 (miR‐218) on cardiac microvascular endothelial cells (CMECs) injury induced by coronary artery disease (CAD). Reverse‐transcription quantitative polymerase chain reaction (RT‐qPCR) was applied for detecting miR‐218 expression in serum of patients with CAD and healthy controls, and the correlation between miR‐218 expression and the clinical indexes such as creatine kinase, creatine kinase‐myocardial band, cardiac troponin I, and coronary Gensini score was analyzed. CMECs were coincubated with homocysteine for 24 hr for CMECs injury, and the cells were transfected with miR‐218 mimics or miR‐218 inhibitors. Besides, we used oxidized low density lipoprotein as an inducer to incubate with CMECs for 24 hr, and the model of CMECs injury was established to be transfected with miR‐218 mimics. RT‐qPCR and western blot analysis were used to detect miR‐218 and HMGB1 expression in CMECs. A series of experiments were used to determine cell proliferation, apoptosis, migration, and angiogenesis ability of CMECs. Vascular endothelial growth factor expression and inflammatory factor contents were measured. The obtained results suggested that miR‐218 expression in peripheral blood of patients with CAD descended substantially versus that of healthy controls. Low miR‐218 expression was found in CAD‐induced CMECs injury. Overexpressed miR‐218 promoted the proliferation, migration, angiogenesis ability, induced apoptosis, and alleviated the inflammatory injury of CAD‐induced CMECs. miR‐218 may negatively regulate the expression of HMGB1 in CAD. This study demonstrates that upregulation of miR‐218 reduces CMECs injury induced by CAD through the inhibition of HMGB1.
MiR‐20a‐containing exosomes from umbilical cord mesenchymal stem cells alleviates liver ischemia/reperfusion injury
Authors: Zhang Lin , Song Yaolin , Chen Lei , Li Donghang , Feng Haohao , Lu Zilong , Fan Tao , Chen Zubin , Livingston Man J. , Geng Qing
Published: October 2019

Mesenchymal stem cells (MSCs) have been proved to exert considerable therapeutic effects on ischemia‐reperfusion (I/R)‐induced injury, but the underlying mechanism remains unknown. In this study, we aimed to explore the potential molecular mechanism underlying the therapeutic effect of MSCs‐derived exosome reinforced with miR‐20a in reversing liver I/R injury. Quantitative real‐time polymerase chain reaction, Western blot, and IHC were carried out to compare the differential expressions of miR‐20a, Beclin‐I, FAS, Caspase‐3, mTOR and P62 in IR rats and normal rats. TUNEL was performed to assess IR‐induced apoptosis in IR rats, and luciferase assay was used to confirm the inhibitory effect of miR‐20a on Beclin‐I and FAS expression. Among the 12 candidate microRNAs (miRNAs), miR‐486, miR‐25, miR‐24, miR‐20a,miR‐466 and miR‐433‐3p were significantly downregulated in I/R. In particular, miR‐20a, a miRNA highly expressed in umbilical cord‐derived mesenchymal stem cells, was proved to bind to the 3ʹ UTR of Beclin‐I and FAS to exert an inhibitory effect on their expressions. Since Beclin‐I and FAS were aberrantly upregulated in IR, exosomes separated from UC‐MSCs showed therapeutic efficacy in reversing I/R induced apoptosis. In addition, exosomes reinforced with miR‐20a and separated from UC‐MSCs almost fully alleviated I/R injury. Furthermore, our results showed that miR‐20a could alleviate the abnormal expression of genes related to apoptosis and autophagy, such as active Caspase‐3, mTOR, P62, and LC3II. This study presented detailed evidence to clarify the mechanism underlying the therapeutic efficacy of UC‐MSCs in the treatment of I/R injury.
Thyroid‐stimulating hormone is an independent risk factor of non‐alcoholic fatty liver disease
Authors: Tahara Kazuki , Akahane Takemi , Namisaki Tadashi , Moriya Kei , Kawaratani Hideto , Kaji Kosuke , Takaya Hiroaki , Sawada Yasuhiko , Shimozato Naotaka , Sato Shinya , Saikawa Soichiro , Nakanishi Keisuke , Kubo Takuya , Fujinaga Yukihisa , Furukawa Masanori , Kitagawa Koh , Ozutsumi Takahiro , Tsuji Yuuki , Kaya Daisuke , Ogawa Hiroyuki , Takagi Hirotetsu , Ishida Koji , Mitoro Akira , Yoshiji Hitoshi
Published: October 2019

Background and Aim

Hypothyroidism might play a crucial role in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). The association of subclinical hypothyroidism with NAFLD has been inconsistent. The relationship of NAFLD with thyroid function parameters and subclinical hypothyroidism was determined.

Methods

This cross‐sectional study included 70 patients with subclinical hypothyroidism and 70 controls with euthyroidism matched according to gender, age, and body mass index (BMI). NAFLD was diagnosed via abdominal ultrasonography. The association between NAFLD and subclinical hypothyroidism was analyzed.

Results

The prevalence of NAFLD was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Multivariate analysis showed that subclinical hypothyroidism was an independent risk factor of NAFLD adjusted by metabolic‐related factors, such as BMI, triglyceride, high‐density lipoprotein‐cholesterol, hypertension, and diabetes. Thyroid‐stimulating hormone (TSH) was an independent risk factor of NAFLD adjusted by the same metabolic‐related factors, but free thyroxine (FT4) was not a risk factor. The FIB‐4 index, a noninvasive marker of liver fibrosis was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Compared with patients with euthyroidism, the proportion of the FIB‐4 index ≥2.67 was significantly higher, and the proportion of the FIB‐4 index <1.30 was lower in patients with subclinical hypothyroidism.

Conclusions

TSH elevation even within the euthyroid range is an independent risk factor of NAFLD and may influence the progression of liver fibrosis, even with a normal FT4 level.
Regional analysis of trend and non‐stationarity of hydro‐climatic time series in the Southern Alborz Region, Iran
Authors: Mirdashtvan Mahsa , Najafinejad Ali , Malekian Arash , Sa'doddin Amir
Published: October 2019

Analysis of the trend of climatic records is necessary for better climate modelling and subsequently adopting effective planning and management strategies. In this research, the Southern Alborz Range, Iran was selected to analyse the trends and stationarity of hydro‐climatic time series. The Mann–Kendall (M‐K) classic test was considered to identify the monotonic trend, while trend free pre‐whitening approach was applied for eliminating serial correlation from the time series. Meanwhile, time series stationarity was tested by Kwiatkowski–Phillips–Schmidt–Shin (KPSS) test. The results indicated both increasing and decreasing trends for precipitation, mean air temperature and pan evaporation in annual time‐scale which were insignificant in most of the stations. The western parts of the area illustrated the highest positive trend (2.018 mm⋅year–1) in annual precipitation; while the south of the study region showed the highest negative trend (−0.999 mm⋅year–1). The highest warming trend belongs to the northern parts of the region (0.035°C⋅year–1); while the western parts show the highest negative trend in temperature variable (–0.07°C⋅year–1); on the other hand, in the entire of the region, an insignificant decreasing trend is observed in most of the evaporation records. Non‐stationarity tested with the KPSS suggested annual time series to be significantly stationary after de‐trending and removing lag‐1 serial correlation. The findings of this investigation may provide important information about the climate of the region and consequently help to implement better management and planning strategies for scarce water resources of the region.
On the relationship between intensity changes and rainfall distribution in tropical cyclones over the North Indian Ocean
Authors: Ankur Kumar , Busireddy Nanda Kishore Reddy , Osuri Krishna K. , Niyogi Dev
Published: October 2019

Using Tropical Rainfall Measuring Mission rain estimates the relationship between rainfall and intensity changes in tropical cyclones (TCs) over the North Indian Ocean (NIO) based on 71 TCs during 1997–2017 is investigated. The axisymmetric analyses revealed that climatologically the Bay of Bengal (BoB) TCs produce extremely heavy rainfall (~9–10 mm⋅hr−1) and Arabian Sea TCs produce very heavy rainfall (~7–8 mm⋅hr−1) in the storm inner core region (0–100 km). The inner‐core region receives three times higher rainfall than the outer region (100–300 km). The left‐forward sector experiences the maximum rainfall for any TC intensity over the NIO basin. A significant increase (decrease) in the rain rate is seen during normal to rapid intensification (weakening) phase. A notable decrease in rainfall of ~4.3 mm⋅hr−1 is observed for the rapidly weakening TCs. Slow‐moving TCs are generally stronger and produce heavy rainfall (2–4 mm⋅hr−1) up to ~300 km storm radius. As the translation speed increases, rainfall gradually shifts from rear to the forward sector of the TC. The asymmetry (wavenumber‐1) in TC rainfall structures revealed that rainfall maximum is located in the left‐forward sector for almost all intensity stages. The amplitude of wave number‐1 asymmetry in TC rainfall shows cyclonic shift as the TC intensity increases and is particularly prevalent in the BoB region. These analyses would be helpful as a baseline for evaluating the performance of numerical models and to identify the vulnerable areas for TC heavy rainfall.
Niemann‐Pick C1‐like 1 Promotes Intestinal Absorption of Siphonaxanthin
Authors: Manabe Yuki , Ichihara Misato , Fukuda Kyoko , Tomonaga Nami , Li Zhuo‐Si , Yamanashi Yoshihide , Suzuki Hiroshi , Takada Tappei , Matsuo Michinori , Sugawara Tatsuya
Published: October 2019

Siphonaxanthin is a carotenoid found in certain green algae, and its promising beneficial properties, such as its anti‐obesity effect, have recently been demonstrated. However, there is little information about the molecular mechanisms underlying intestinal absorption of siphonaxanthin. In this study, we aimed to elucidate how siphonaxanthin is transported across the intestinal epithelium using differentiated Caco‐2 cells (dCaco‐2 cells), recombinant proteins, and an animal model. Siphonaxanthin was taken up by dCaco‐2 cells, a model of intestinal epithelial cells, and its uptake linearly increased up to at least 6 h. Pharmacological inhibition of Nieman‐Pick C1‐like 1 (NPC1L1), but not that of scavenger receptor class B type 1 (SR‐B1), significantly suppressed siphonaxanthin uptake by dCaco‐2 cells. Results from an in vitro binding assay suggested that the N‐terminal domain of NPC1L1, which is an extracellular domain of NPC1L1, binds with siphonaxanthin. Moreover, pretreatment with ezetimibe, an inhibitor of NPC1L1, significantly decreased the plasma level of siphonaxanthin following oral administration in mice. Considered together, we concluded that NPC1L1 promotes siphonaxanthin transport across the intestinal epithelium.
[Gly14]‐Humanin Prevents Lipid Deposition and Endothelial Cell Apoptosis in a Lectin‐like Oxidized Low‐density Lipoprotein Receptor‐1‐Dependent Manner
Authors: Ding Yu , Feng Yue , Zhu Wawa , Zou Yutian , Xie Ying , Wang Fen , Liu Chun‐Feng , Zhang Yanlin , Liu Huihui
Published: October 2019

Oxidized low‐density lipoprotein (Ox‐LDL) may induce apoptosis and dysfunction of vascular endothelial cells, contributing to the initiation and development of atherosclerosis and lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1) plays a central role in Ox‐LDL uptake in the course of atherogenesis. Humanin (HN), a mitochondrial‐derived peptide, was recently demonstrated to exert a protective role against endothelial dysfunction and Ox‐LDL‐induced progression of atherosclerosis. The HN analog HNGF6A (HNG) modulates cholesterol metabolism in macrophage RAW 264.7 cells. However, whether HNG affects Ox‐LDL metabolism in endothelial cells is unknown. In this study, we investigated the effect of HNG on Ox‐LDL accumulation in human umbilical vein endothelial cell (HUVEC) and its underlying mechanisms. HUVEC were preincubated with HNG for 1 h before addition of Ox‐LDL. Total cholesterol content was measured by using a tissue total cholesterol assay kit and flow cytometry. Cell viability was measured by CCK8 assay. Protein content was examined by Western blot assays. Flow cytometry was used to identify apoptotic cells. Flow cytometry and tissue total cholesterol assays showed that HNG reduced Ox‐LDL accumulation in HUVEC. In addition, HNG inhibited Ox‐LDL‐induced apoptosis of HUVEC. Western blot results showed that HNG reduced LOX‐1 protein content. However, when LOX‐1 was knocked down or inhibited, the effect of HNG in reducing Ox‐LDL aggregation and apoptosis in HUVEC disappeared. Our study demonstrated that HNG reduces lipid aggregation and apoptosis in HUVEC in a LOX‐1‐dependent manner.
Plastic particles adsorb to the roots of freshwater vascular plant Spirodela polyrhiza but do not impair growth
Authors: Dovidat Lena C. , Brinkmann Bregje W. , Vijver Martina G. , Bosker Thijs
Published: October 2019

We investigated the effect of nano‐ and microplastics on the freshwater duckweed species Spirodela polyrhiza, a vascular plant. S. polyrhiza was exposed for 120 h to concentrations ranging from 102 to 106 particles·mL−1. We assessed effects on growth and chlorophyll production, and explored adsorption and absorption by way of confocal microscopy. For both nano‐ and microsized particles, no concentration‐dependent effects on growth were found (expressed as fresh weight, frond, and root sizes). In addition, chlorophyll concentrations were not significantly affected. Confocal microscopy indicated that nanosized plastic particles adsorbed externally to the duckweed, especially to the roots. Internalized plastic particles could not be detected. Nevertheless, given their important role in ecosystems as a food source for a range of organisms, the adsorption of plastic particles to S. polyrhiza roots as detected in this study can result in the transfer of plastic particles to diverse herbivorous species within the ecosystem.
Ablative fractional resurfacing with laser‐facilitated steroid delivery for burn scar management: Does the depth of laser penetration matter?
Authors: Issler‐Fisher Andrea C. , Fisher Oliver M. , Haertsch Peter , Li Zhe , Maitz Peter K.M.
Published: October 2019

Background and Objective

To investigate whether the depth of ablative fractional CO2 laser (CO2‐AFL) penetration of pathological burn scars influences clinical outcomes.

Study Design/Materials and Methods

All patients presenting to the Concord Repatriation General Hospital (CRGH) Scar Clinic received ultrasound measurement at the thickest point of their burn scars. Subsequently, the effect of various CO2‐AFL settings (energy which correlates to penetration depths) on different outcome parameters was analysed. Patients were divided into five groups depending on minimal scar penetration depth.

Results

Seventy‐eight patients (158 scars) had complete data allowing for analysis. Median scar thickness was 3,400 μm and median laser scar penetration depth was 900 μm. Scar penetration categories were as follows: 0–25% (n = 40), 25–50% (n = 67), 50–75% (n = 31), 75–100% (n = 8), >100% (n = 3) of scar thickness. The median reduction in maximum scar thickness was 800 μm following one treatment (P < 0.001). However, this effect depended on scar penetration depth, whereby scars that were penetrated ≥75% showed no significant improvement in scar thickness and those penetrated >100% indicated a tendency to become worse. Other assessed outcome parameters included: the Vancouver Scar Scale, the Patient and Observer Scar Assessment Scale, a neuropathic pain score (DN4 Pain Questionnaire), and a pruritus score (modified D4 Pruritus Score). All these factors showed significant improvement in the categories up to 75% scar penetration depth.

Conclusions

CO2‐AFL scar penetration depth significantly influences subjective and objective pathologic burn scar modulation. The penetration depth of 51–75% achieves the greatest reduction in scar thickness. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Łoś's theorem and the axiom of choice
Authors: Tachtsis Eleftherios
Published: October 2019

In set theory without the Axiom of Choice (), we investigate the problem of the placement of Łoś's Theorem () in the hierarchy of weak choice principles, and answer several open questions from the book Consequences of the Axiom of Choice by Howard and Rubin, as well as an open question by Brunner. We prove a number of results summarised in § 3.
An examination of data from the American Gut Project reveals that the dominance of the genus Bifidobacterium is associated with the diversity and robustness of the gut microbiota
Authors: Feng Yuqing , Duan Yunfeng , Xu Zhenjiang , Lyu Na , Liu Fei , Liang Shihao , Zhu Baoli
Published: October 2019

Bifidobacterium and Lactobacillus are beneficial for human health, and many strains of these two genera are widely used as probiotics. We used two large datasets published by the American Gut Project (AGP) and a gut metagenomic dataset (NBT) to analyze the relationship between these two genera and the community structure of the gut microbiota. The meta‐analysis showed that Bifidobacterium, but not Lactobacillus, is among the dominant genera in the human gut microbiota. The relative abundance of Bifidobacterium was elevated when Lactobacillus was present. Moreover, these two genera showed a positive correlation with some butyrate producers among the dominant genera, and both were associated with alpha diversity, beta diversity, and the robustness of the gut microbiota. Additionally, samples harboring Bifidobacterium present but no Lactobacillus showed higher alpha diversity and were more robust than those only carrying Lactobacillus. Further comparisons with other genera validated the important role of Bifidobacterium in the gut microbiota robustness. Multivariate analysis of 11,744 samples from the AGP dataset suggested Bifidobacterium to be associated with demographic features, lifestyle, and disease. In summary, Bifidobacterium members, which are promoted by dairy and whole‐grain consumption, are more important than Lactobacillus in maintaining the diversity and robustness of the gut microbiota.
The role of polo‐like kinase 3 in the response of BRAF‐mutant cells to targeted anticancer therapies
Authors: Babagana Mahamat , Kichina Julia V. , Slabodkin Hannah , Johnson Sydney , Maslov Alexei , Brown Lorin , Attwood Kristopher , Nikiforov Mikhail A. , Kandel Eugene S.
Published: October 2019

The activation of oncogenic mitogen‐activated protein kinase cascade via mutations in BRAF is often observed in human melanomas. Targeted inhibitors of BRAF (BRAFi), alone or as a part of a combination therapy, offer a significant benefit to such patients. Unfortunately, some cases are initially nonresponsive to these drugs, while others become refractory in the course of treatment, underscoring the need to understand and mitigate the underlying resistance mechanisms. We report that interference with polo‐like kinase 3 (PLK3) reduces the tolerance of BRAF‐mutant melanoma cells to BRAFi, while increased PLK3 expression has the opposite effect. Accordingly, PLK3 expression correlates with tolerance to BRAFi in a panel of BRAF‐mutant cell lines and is elevated in a subset of recurring BRAFi‐resistant melanomas. In PLK3‐expressing cells, R406, a kinase inhibitor whose targets include PLK3, recapitulates the sensitizing effects of genetic PLK3 inhibitors. The findings support a role for PLK3 as a predictor of BRAFi efficacy and suggest suppression of PLK3 as a way to improve the efficacy of targeted therapy.
Successful Management of Anti‐mGluR1 Encephalitis with Immunosuppressive Treatment: Dengue Virus as a Trigger?
Authors: Chaumont Hugo , Petit Aimée , Mameri Tanicia , Schollhammer Romain , Honnorat Jérome , Lannuzel Annie
Published: October 2019

View Supplementary Video 1
The Movement Disorder Society Nonmotor Rating Scale: Initial Validation Study
Authors: Chaudhuri K. Ray , Schrag Anette , Weintraub Daniel , Rizos Alexandra , Rodriguez‐Blazquez Carmen , Mamikonyan Eugenia , Martinez‐Martin Pablo
Published: October 2019

Background

The Movement Disorder Society–sponsored Nonmotor Rating Scale is an update of the existing Parkinson's disease Nonmotor Symptoms Scale modified to address some limitations in Nonmotor Symptoms Scale scoring, structure, and symptom coverage.

Methods

PD patients were recruited from movement disorder centers in an international, multicenter study. The Movement Disorder Society Nonmotor Rating Scale, consisting of 13 domains plus a subscale for nonmotor fluctuations, was rater administered, along with the Nonmotor Symptoms Scale and other clinical assessments. Standard reliability and validity testing were conducted.

Results

Four hundred and two PD patients were recruited (mean age ± standard deviation, 67.42 ± 9.96 years; mean age at PD onset ± standard deviation, 59.27 ± 10.67 years; median Hoehn and Yahr stage 2 (interquartile range 2–3). Data quality was satisfactory for all Movement Disorder Society Nonmotor Rating Scale domains except sexual (6.7% missing data). There were no floor or ceiling effects for the Movement Disorder Society Nonmotor Rating Scale and nonmotor fluctuations total score; domains had no ceiling effects, but some floor effects (13.5%–83.5%). The Movement Disorder Society Nonmotor Rating Scale and nonmotor fluctuations total score internal consistency were acceptable (average Cronbach's alpha, 0.66 and 0.84, respectively); interrater reliability was excellent (intraclass correlation coefficient, >0.95); for test‐retest reliability, the intraclass correlation coefficient was 0.84 for the Movement Disorder Society Nonmotor Rating Scale and 0.70 for Movement Disorder Society nonmotor fluctuations total score, and precision was excellent for the Movement Disorder Society Nonmotor Rating Scale (standard error of measurement, 25.30) and fair for nonmotor fluctuations (standard error of measurement, 7.06). Correlations between Movement Disorder Society Nonmotor Rating Scale score and the corresponding Nonmotor Symptoms Scale and Movement Disorder Society UPDRS scores were high. There were no significant sex or age effects. The Movement Disorder Society Nonmotor Rating Scale score increased with increasing PD duration, disease severity, and PD medication dose (all P < 0.001).

Conclusions

The Movement Disorder Society Nonmotor Rating Scale is a valid measure for measuring the burden of a wide range of Nonmotor Rating Scale scores, including nonmotor fluctuations, in PD patients. © 2019 International Parkinson and Movement Disorder Society
Validation of the Movement Disorder Society Criteria for the Diagnosis of 4‐Repeat Tauopathies
Authors: Respondek Gesine , Grimm Max‐Joseph , Piot Ines , Arzberger Thomas , Compta Yaroslau , Englund Elisabet , Ferguson Leslie W. , Gelpi Ellen , Roeber Sigrun , Giese Armin , Grossman Murray , Irwin David J. , Meissner Wassilios G. , Nilsson Christer , Pantelyat Alexander , Rajput Alex , van Swieten John C. , Troakes Claire , Höglinger Günter U. ,   for the Movement Disorder Society–Endorsed Progressive Supranuclear Palsy Study Group
Published: October 2019

Background

The Movement Disorder Society criteria for progressive supranuclear palsy introduced the category “probable 4‐repeat (4R)‐tauopathy” for joint clinical diagnosis of progressive supranuclear palsy and corticobasal degeneration.

Objectives

To validate the accuracy of these clinical criteria for “probable 4R‐tauopathy” to predict underlying 4R‐tauopathy pathology.

Methods

Diagnostic accuracy for 4R‐tauopathies according to the established criteria was estimated retrospectively in autopsy‐confirmed patients with progressive supranuclear palsy and corticobasal degeneration (grouped as 4R‐tauopathies), and Parkinson's disease, multiple system atrophy, and frontotemporal lobar degeneration (grouped as non‐4R‐tauopathies).

Results

We identified 250 cases with progressive supranuclear palsy (N = 195) and corticobasal degeneration (N = 55) and with and non‐4R‐tauopathies (N = 161). Sensitivity and specificity of “probable 4R‐tauopathy” was 10% and 99% in the first year and 59% and 88% at final record.

Conclusions

The new diagnostic category “probable 4R‐tauopathy” showed high specificity and may be suitable for the recruitment of patients with progressive supranuclear palsy and corticobasal degeneration into therapeutic trials targeting 4R‐tauopathy. The low sensitivity underpins the need for diagnostic biomarkers. © 2019 International Parkinson and Movement Disorder Society
New insights into genetic variant spectrum and genotype–phenotype correlations of Rubinstein‐Taybi syndrome in 39 CREBBP‐positive patients
Authors: Pérez‐Grijalba Virginia , García‐Oguiza Alberto , López María , Armstrong Judith , García‐Miñaur Sixto , Mesa‐Latorre Jose María , O'Callaghan Mar , Pineda Marfa Mercé , Ramos‐Arroyo Maria Antonia , Santos‐Simarro Fernando , Seidel Verónica , Domínguez‐Garrido Elena
Published: October 2019

Background

Rubinstein‐Taybi syndrome (RSTS) is a rare congenital disorder characterized by broad thumbs and halluces, intellectual disability, distinctive facial features, and growth retardation. Clinical manifestations of RSTS are varied and overlap with other syndromes’ phenotype, which makes clinical diagnosis challenging. CREBBP is the major causative gene (55%–60% of the cases), whereas pathogenic variants found in EP300 represent the molecular cause in 8% of RSTS patients. A wide range of CREBBP pathogenic variants have been reported so far, including point mutations (30%–50%) and large deletions (10%).

Methods

The aim of this study was to characterize the CREBBP genetic variant spectrum in 39 RSTS patients using Multiplex Ligation‐dependent Probe Amplification and DNA sequencing techniques (Sanger and Trio‐based whole‐exome sequencing).

Results

We identified 15 intragenic deletions/duplications, ranging from one exon to the entire gene. As a whole, 25 de novo point variants were detected: 4 missense, 12 nonsense, 5 frameshift, and 4 splicing pathogenic variants. Three of them were classified as of uncertain significance and one of the patients carried two different variants.

Conclusion

Seventeen of the 40 genetic variants detected were reported for the first time in this work contributing, thus, to expand the molecular knowledge of this complex disorder.
Characterization of the renal phenotype in RMND1‐related mitochondrial disease
Authors: Shayota Brian J. , Le Nhon T. , Bekheirnia Nasim , Rosenfeld Jill A. , Goldstein Amy C. , Moritz Michael , Bartholomew Dennis W. , Pastore Matthew T. , Xia Fan , Eng Christine , Yang Yaping , Lamb Dolores J. , Scaglia Fernando , Braun Michael C. , Bekheirnia Mir Reza
Published: October 2019

Background

The nuclear encoded gene RMND1 (Required for Meiotic Nuclear Division 1 homolog) has recently been linked to RMND1‐related mitochondrial disease (RRMD). This autosomal recessive condition characteristically presents with an infantile‐onset multisystem disease characterized by severe hypotonia, global developmental delay, failure to thrive, sensorineural hearing loss, and lactic acidosis. Renal disease, however, appears to be one of the more prominent features of RRMD, affecting patients at significantly higher numbers compared to other mitochondrial diseases. We report the clinical, histological, and molecular findings of four RRMD patients across three academic institutions with a focus on the renal manifestations.

Methods

Four patients were identified for the purpose of this study, all of whom had molecular confirmation at the time of inclusion, which included the common pathogenic variant c.713A>G (p.N238S) as well as the three rare variants: c.485delC (p.P162fs), c.533C>T (p.T178M), and c.1317 + 1G>C splice donor variant. Medical history and laboratory findings were collected from the medical records and medical providers.

Results

In this study, all four patients developed renal disease characterized as tubulopathy (3/4), renal tubular acidosis (2/4), interstitial nephritis (1/4), and/or end‐stage renal disease (4/4) necessitating renal transplantation (2/4). Histological evaluation of renal biopsy specimens revealed generalized tubular atrophy and on electron microscopy, abundant mitochondria with pleomorphism and abnormal cristae.

Conclusion

Our experience with RRMD demonstrates a specific pattern of renal disease manifestations and clinical course. Patients are unlikely to respond to traditional chronic kidney disease (CKD) treatments, making early diagnosis and consideration of renal transplantation paramount to the management of RRMD.