bluuebunny/crossref_metadata_2025 huggingface dataset:
Common Effluent Treatment Plants Monitoring and Process Augmentation Options to Conform Non-potable Reuse
Authors: Ali Muntjeer , Almohana Abdulaziz Ibrahim , Alali Abdulrhman Fahmi , Kamal Mohab Amin , Khursheed Abbas , Khursheed Anwar , Kazmi A. A.
Published: December 2021

The stringency in effluent discharge and reuse standards has made it extremely expensive to discharge the effluents safely or reuse them. Therefore, existing wastewater treatment plants should be evaluated and improved or augmented. With this aim, five existing common effluent treatment plants (CETPs) in North India were evaluated, including: the State infrastructure Development Corporation Uttrakhand Limited (SIDCUL) Haridwar, which processes 4.5 Million Liters per day (MLD); the Industrial Model Township (IMT) Manesar Gurgaon, 55 MLD (comprising two streams of 25 and 30 MLD each); the Lawrence Road Industrial Area (LRIA), Delhi, 12MLD (12MLD LRIA); Mayapuri Industrial Area (MIA), Delhi, 12MLD; and the Integrated Industrial Estate (IIE) SIDCUL Pantnagar, 4.0 MLD. These plants were designed to produce treated effluent for non-potable reuse. Results showed that the integrated efficiency (IEa) of all CETPs was 10–20% larger than standard integrated efficiency (IEs), indicating the suitability of the technology, except for 12MLD at MIA CETP where the IEa was 20% lower than IEs, due to the absence of any biological unit in the process. Combined post-treatment of secondary effluent by coagulation, Ultrafiltration (UF), followed by ozonation for CETP SIDCUL Haridwar, was also conducted for its non-potable water reuse. This process was able to reduce Biochemical Oxygen Demand (BOD) by 77%, Chemical Oxygen Demand (COD) by 76%, turbidity by 96%, and Total Suspended Solids (TSS) by 100%. All these parameters confirmed the effluent standards for non-potable reuse. The color was reduced to 4.0 from 42.0 Pt-Co units by the exposure ozone concentration of 8.3 mg/L for up to 4.0 min on the treated water from SIDCUL CETP, which reduced the color by 90% and complied with reuse standards. Hence Combined post treatment by coagulation, UF followed Ozonation of secondary treated effluent could be a better option for the potable reuse of treated water in various domestic and industrial applications.
First Record of Fungal Diversity in the Tropical and Warm-Temperate Middle Miocene Climate Optimum Forests of Eurasia
Authors: Romero Ingrid C. , Nuñez Otaño Noelia B. , Gibson Martha E. , Spears Tyler M. , Fairchild C. Jolene , Tarlton Laikin , Jones Savannah , Belkin Harvey E. , Warny Sophie , Pound Matthew J. , O’Keefe Jennifer M. K.
Published: December 2021

The middle Miocene Climate Optimum (MMCO) was the warmest interval of the last 23 million years and is one of the best analogs for proposed future climate change scenarios. Fungi play a key role in the terrestrial carbon cycle as dominant decomposers of plant debris, and through their interactions with plants and other organisms as symbionts, parasites, and endobionts. Thus, their study in the fossil record, especially during the MMCO, is essential to better understand biodiversity changes and terrestrial carbon cycle dynamics in past analogous environments, as well as to model future ecological and climatic scenarios. The fossil record also offers a unique long-term, large-scale dataset to evaluate fungal assemblage dynamics across long temporal and spatial scales, providing a better understanding of how ecological factors influenced assemblage development through time. In this study, we assessed the fungal diversity and community composition recorded in two geological sections from the middle Miocene from the coal mines of Thailand and Slovakia. We used presence-absence data to quantify the fungal diversity of each locality. Spores and other fungal remains were identified to modern taxa whenever possible; laboratory codes and fossil names were used when this correlation was not possible. This study represents the first of its kind for Thailand, and it expands existing work from Slovakia. Our results indicate a total of 281 morphotaxa. This work will allow us to use modern ecological data to make inferences about ecosystem characteristics and community dynamics for the studied regions. It opens new horizons for the study of past fungal diversity based on modern fungal ecological analyses. It also sheds light on how global variations in fungal species richness and community composition were affected by different climatic conditions and under rapid increases of temperature in the past to make inferences for the near climatic future.
Screening and Functional Analysis of TEK Mutations in Chinese Children With Primary Congenital Glaucoma
Authors: Qiao Yunsheng , Chen Yuhong , Tan Chen , Sun Xinghuai , Chen Xueli , Chen Junyi
Published: December 2021

Purposes: Recent studies have suggested that loss-of-function mutations of the tunica intima endothelial receptor tyrosine kinase (TEK) are responsible for approximately 5% of primary congenital glaucoma (PCG) cases in diverse populations. However, the causative role of TEK mutations has not been studied in Chinese PCG patients. Here, we report the mutation spectrum of TEK after screening a large cohort of PCG patients of Chinese Han origin and analyze the identified variants in functional assays.

Methods: TEK-targeted next-generation sequencing (NGS) was performed in 200 PCG patients. Candidate variants were prioritized by mutation type and allele frequency in public datasets. Plasmids containing wild type and identified variants of TEK were constructed and used to assess protein expression, solubility, receptor auto-phosphorylation, and response to ligand stimulation in cell-based assays.

Results: Ten missense and one nonsense heterozygous variants were detected by NGS in 11 families. The clinical features of TEK variants carriers were comparable to that of TEK-mutated patients identified in other populations and CYP1B1-mutated individuals from in-house database. Functional analysis confirmed four variants involving evolutionarily conserved residues to be loss-of-function, while one variant (p.R1003H) located in tyrosine kinase domain seemed to be an activating mutation. However, our results did not support the pathogenicity of the other five variants (p.H52R, p.M131I, p.M228V, p.H494Y, and p.L888P).

Conclusion: We provide evidence for TEK variants to be causative in Chinese PCG patients for the first time. Attention needs to be paid to TEK mutations in future genetic testing.
Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells
Authors: Malmberg Henna-Riikka , Hanel Andrea , Taipale Mari , Heikkinen Sami , Carlberg Carsten
Published: December 2021

Microbe-associated molecular patterns, such as lipopolysaccharide (LPS) and β-glucan (BG), are surrogates of immune challenges like bacterial and fungal infections, respectively. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), supports the immune system in its fight against infections. This study investigated significant and prominent changes of the transcriptome of human peripheral blood mononuclear cells that immediately after isolation are exposed to 1,25(OH)2D3-modulated immune challenges over a time frame of 24-48 h. In this in vitro study design, most LPS and BG responsive genes are downregulated and their counts are drastically reduced when cells are treated 24 h after, 24 h before or in parallel with 1,25(OH)2D3. Interestingly, only a 1,25(OH)2D3 pre-treatment of the LPS challenge results in a majority of upregulated genes. Based on transcriptome-wide data both immune challenges display characteristic differences in responsive genes and their associated pathways, to which the actions of 1,25(OH)2D3 often oppose. The joined BG/1,25(OH)2D3 response is less sensitive to treatment sequence than that of LPS/1,25(OH)2D3. In conclusion, the functional consequences of immune challenges are significantly modulated by 1,25(OH)2D3 but largely depend on treatment sequence. This may suggest that a sufficient vitamin D status before an infection is more important than vitamin D supplementation afterwards.
Structure and Inter-Annual Variability of the Freshened Surface Layer in the Laptev and East-Siberian Seas During Ice-Free Periods
Authors: Osadchiev Alexander , Frey Dmitry , Spivak Eduard , Shchuka Sergey , Tilinina Natalia , Semiletov Igor
Published: December 2021

This work is focused on the structure and inter-annual variability of the freshened surface layer (FSL) in the Laptev and East-Siberian seas during ice-free periods. This layer is formed mainly by deltaic rivers among which the Lena River contributes about two thirds of the inflowing freshwater volume. Based on in situ measurements, we show that the area of this FSL during certain years is much greater than the area of FSL in the neighboring Kara Sea, while the total annual freshwater discharge to the Laptev and East-Siberian seas is 1.5 times less than to the Kara Sea (mainly from the estuaries of the Ob and Yenisei rivers). This feature is caused by differences in morphology of the estuaries and deltas. Shallow and narrow channels of the Lena Delta are limitedly affected by sea water. As a result, undiluted Lena discharge inflows to sea from multiple channels and forms relatively shallow plume, as compared to the Ob-Yenisei plume, which mixes with subjacent saline sea water in deep and wide estuaries. Due to small vertical extents of FSL in the Laptev and East-Siberian seas, wind conditions strongly affect its spreading and determine its significant inter-annual variability, as compared to relatively stable FSL in the Kara Sea. During years with prevailing western and northern winds, FSL is localized in the southern parts of the Laptev and East-Siberian seas due to southward Ekman transport, meridional extent (<250 km) and area (∼250,000 km2) of FSL are relatively small. During years with strong eastern winds FSL spreads northward over large area (up to 500,000 km2), its meridional extent increases up to 500–700 km. At the same time, area and position of FSL do not show any dependence on significant variability of the annual river discharge volume and ice coverage during warm season.
Kilometer-Scale Larval Dispersal Processes Predict Metapopulation Connectivity Pathways for Paramuricea biscaya in the Northern Gulf of Mexico
Authors: Liu Guangpeng , Bracco Annalisa , Quattrini Andrea M. , Herrera Santiago
Published: December 2021

Fine-scale larval dispersal and connectivity processes are key to species survival, growth, recovery and adaptation under rapidly changing disturbances. Quantifying both are required to develop any effective management strategy. In the present work, we examine the dispersal pattern and potential connectivity of a common deep-water coral, Paramuricea biscaya, found in the northern Gulf of Mexico by evaluating predictions of physical models with estimates of genetic connectivity. While genetic approaches provide estimates of realized connectivity, they do not provide information on the dispersal process. Physical circulation models can now achieve kilometer-scale resolution sufficient to provide detailed insight into the pathways and scales of larval dispersal. A high-resolution regional ocean circulation model is integrated for 2015 and its advective pathways are compared with the outcome of the genetic connectivity estimates of corals collected at six locations over the continental slope at depths comprised between 1,000 and 3,000 m. Furthermore, the likely interannual variability is extrapolated using ocean hindcasts available for this basin. The general connectivity pattern exhibits a dispersal trend from east to west following 1,000 to 2,000-m isobaths, corresponding to the overall westward near-bottom circulation. The connectivity networks predicted by our model were mostly congruent with the estimated genetic connectivity patterns. Our results show that although dispersal distances of 100 km or less are common, depth differences between tens to a few hundred meters can effectively limit larval dispersal. A probabilistic graphic model suggests that stepping-stone dispersal mediated by intermediate sites provides a likely mechanism for long-distance connectivity between the populations separated by distances of 300 km or greater, such as those found in the DeSoto and Keathley canyons.
Global Public Interest and Seasonal Variations in Alzheimer's Disease: Evidence From Google Trends
Authors: Mao Yan-Mei , Wang Peng , Wang Xiao-Yu , Ye Dong-Qing
Published: December 2021

Background: As the world's population ages, Alzheimer's disease (AD), a common neurodegenerative disease, is a major challenge to human health in the future. Understanding the information needs on AD of the global public can contribute to the prevention and control of AD. The purpose of this study was to explore global public interest and seasonal variations in AD using Google Trends (GT).

Methods: GT was used to obtain relative search volume (RSV) of the keyword “Alzheimer's disease” in six English-speaking countries (Australia, New Zealand, the USA, the UK, Canada, and Ireland) and the world from January 2004 to December 2020. Cosinor analysis was applied to detect the seasonality of AD-related RSV. Time series plot was used to observe the trend of annual mean AD-related RSV. Globally, hot topics and top rising topics related to AD were also analyzed. In addition, we also explored the geographical distribution characteristics of AD-related RSV.

Results: AD-related RSV declined steadily from January 2004 to December 2013 and rose steadily from January 2014 to December 2020. Search popularity of AD is low in the southern hemisphere, compared to the northern hemisphere. Cosinor analysis showed that there were significant seasonal variations in AD-related RSV in six English-speaking countries (all P < 0.05). Interestingly, regardless of the hemisphere, peaks were observed in the winter months and trough in the summer months. Topics related to the characteristics and etiology of AD, early onset AD, AD-related associations, care of AD patients, and diseases that can easily be confused with AD had received special attention.

Conclusions: There is increasing global public interest for AD and a significant seasonal variation in AD. A better understanding of the seasonal variations and public interest of AD by governments, health workers and patients can contribute to the prevention, management, and treatment of AD.
Extracts of Amazonian Fungi With Larvicidal Activities Against Aedes aegypti
Authors: de Oliveira Marta Rodrigues , Katak Ricardo de Melo , da Silva Gilvan Ferreira , Marinotti Osvaldo , Terenius Olle , Tadei Wanderli Pedro , de Souza Afonso Duarte Leão , de Souza Antonia Queiroz Lima
Published: December 2021

The global increase in diseases transmitted by the vector Aedes aegypti, new and re-emerging, underscores the need for alternative and more effective methods of controlling mosquitoes. Our aim was to identify fungal strains from the Amazon rain forest that produce metabolites with larvicidal activity against Aedes aegypti. Thirty-six fungal strains belonging to 23 different genera of fungi, isolated from water samples collected in the state of Amazonas, Brazil were cultivated. The liquid medium was separated from the mycelium by filtration. Medium fractions were extracted with ethyl acetate and isopropanol 9:1 volume:volume, and the mycelia with ethyl acetate and methanol 1:1. The extracts were vacuum dried and the larvicidal activity was evaluated in selective bioassays containing 500 μg/ml of the dried fungal extracts. Larval mortality was evaluated up to 72 h. None of the mycelium extracts showed larvicidal activity greater than 50% at 72 h. In contrast, 15 culture medium extracts had larvicidal activity equal to or greater than 50% and eight killed more than 90% of the larvae within 72 h. These eight extracts from fungi belonging to seven different genera (Aspergillus, Cladosporium, Trichoderma, Diaporthe, Albifimbria, Emmia, and Sarocladium) were selected for the determination of LC50 and LC90. Albifimbria lateralis (1160) medium extracts presented the lowest LC50 value (0.268 μg/ml) after 24 h exposure. Diaporthe ueckerae (1203) medium extracts presented the lowest value of LC90 (2.928 μg/ml) at 24 h, the lowest values of LC50 (0.108 μg/ml) and LC90 (0.894 μg/ml) at 48 h and also at 72 h (LC50 = 0.062 μg/ml and LC90 = 0.476 μg/ml). Extracts from Al. lateralis (1160) and D. ueckerae (1203) showed potential for developing new, naturally derived products, to be applied in integrated vector management programs against Ae. aegypti.
A New Way of Airline Traffic Prediction Based on GCN-LSTM
Authors: Yu Jiangni
Published: December 2021

With the development of society and the improvement of people's material level, more and more people like to travel by airplane. If we can predict the passenger flow of an airline in advance, it can be used as an important decision-making basis for its flight route planning, crew scheduling planning and ticket price formulation in the process of management and operation. However, due to the high complexity of aviation network, the existing traffic prediction methods generally have the problem of low prediction accuracy. In order to overcome this problem, this paper makes full use of graph convolutional neural network and long—short memory network to construct a prediction system with short—term prediction ability. Specifically, this paper uses the graph convolutional neural network as a feature extraction tool to extract the key features of air traffic data, and solves the problem of long term and short term dependence between data through the long term memory network, then we build a high-precision air traffic prediction system based on it. Finally, we design a comparison experiment to compare the algorithm with the traditional algorithms. The results show that the algorithm we proposed in this paper has a higher accuracy in air flow prediction according to the lower loss function value.
Association Between Epilepsy and Leigh Syndrome With MT-ND3 Mutation, Particularly the m.10191T>C Point Mutation
Authors: Na Ji-Hoon , Lee Min Jung , Lee Chul Ho , Lee Young-Mock
Published: December 2021

Background and Purpose: Recent advances in molecular genetic testing have led to a rapid increase in the understanding of the genetics of Leigh syndrome. Several studies have suggested that Leigh syndrome with MT-ND3 mutation is strongly associated with epilepsy. This study focused on the epilepsy-related characteristics of Leigh syndrome with MT-ND3 mutation identified in a single tertiary hospital in South Korea.

Methods: We selected 31 patients with mitochondrial DNA (mtDNA) mutations who were genetically diagnosed with mtDNA-associated Leigh syndrome. Among them, seven patients with MT-ND3 mutations were detected. We reviewed various clinical findings such as laboratory findings, brain images, electroencephalography data, seizure types, seizure frequency, antiepileptic drug use history, and current seizure status.

Results: The nucleotide changes in the seven patients with the Leigh syndrome with MT-ND3 mutation were divided into two groups: m.10191T>C and m.10158T>C. Six of the seven patients were found to have the m.10191T>C mutations. The median value of the mutant load was 82.5%, ranging from 57.9 to 93.6%. No particular tendency was observed for the first symptom or seizure onset or mutant load. The six patients with the m.10191T>C mutation were diagnosed with epilepsy. Three of these patients were diagnosed with Lennox–Gastaut syndrome (LGS).

Conclusion: We reported a very strong association between epilepsy and MT-ND3 mutation in Leigh syndrome, particularly the m.10191T>C mutation. The possibility of an association between the epilepsy phenotype of the m.10191T>C mutation and LGS was noted.
Methodology for Low-Field, Portable Magnetic Resonance Neuroimaging at the Bedside
Authors: Prabhat Anjali M. , Crawford Anna L. , Mazurek Mercy H. , Yuen Matthew M. , Chavva Isha R. , Ward Adrienne , Hofmann William V. , Timario Nona , Qualls Stephanie R. , Helland Juliana , Wira Charles , Sze Gordon , Rosen Matthew S. , Kimberly William Taylor , Sheth Kevin N.
Published: December 2021

Neuroimaging is a critical component of triage and treatment for patients who present with neuropathology. Magnetic resonance imaging and non-contrast computed tomography are the gold standard for diagnosis and prognostication of patients with acute brain injuries. However, these modalities require intra-hospital transport to strict, access-controlled environments, which puts critically ill patients at risk for complications and secondary injuries. A novel, portable MRI (pMRI) device that can be deployed at the patient's bedside provides a needed solution. In a dual-center investigation, Yale New Haven Hospital has obtained regular neuroimaging on patients using the pMRI as part of routine clinical care in the Emergency Department and Intensive Care Unit (ICU) since August of 2020. Massachusetts General Hospital has begun using pMRI in the Neuroscience Intensive Care Unit since January 2021. This technology has expanded the population of patients who can receive MRI imaging by increasing accessibility and timeliness for scan completion by eliminating the need for transport and increasing the potential for serial monitoring. Here we describe our methods for screening, coordinating, and executing pMRI exams and provide further detail on how to scan specific patient populations.
Efficacy of Virtual Reality and Exergaming in Improving Balance in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis
Authors: Calafiore Dario , Invernizzi Marco , Ammendolia Antonio , Marotta Nicola , Fortunato Francesco , Paolucci Teresa , Ferraro Francesco , Curci Claudio , Cwirlej-Sozanska Agnieszka , de Sire Alessandro
Published: December 2021

Multiple sclerosis (MS) is one of the most common causes of neurological progressive disease and can lead to loss of mobility, walk impairment, and balance disturbance. Among several rehabilitative approaches proposed, exergaming and virtual reality (VR) have been studied in the recent years. Active video game therapy could reduce the boredom of the rehabilitation process, increasing patient motivation, providing direct feedback, and enabling dual-task training. Aim of this systematic review was to assess the efficacy of exergaming and VR for balance recovery in patients with MS. PubMed, Scopus, and Web of Science were systematically searched from the inception until May 14, 2021 to identify randomized controlled trials (RCTs) presenting: patients with MS as participants, exergaming and VR as intervention, conventional rehabilitation as comparator, and balance assessment [Berg Balance Scale (BBS)] as outcome measure. We also performed a meta-analysis of the mean difference in the BBS via the random-effects method. Out of 93 records, this systematic review included and analyzed 7 RCTs, involving a total of 209 patients affected by MS, of which 97 patients performed exergaming or VR and 112 patients underwent conventional rehabilitation. The meta-analysis reported a significant overall ES of 4.25 (p < 0.0001), showing in the subgroup analysis a non-significant ES of 1.85 (p = 0.39) for the VR and a significant ES of 4.49 (p < 0.0001) for the exergames in terms of the BBS improvement. Taken together, these findings suggested that balance rehabilitation using exergames appears to be more effective than conventional rehabilitation in patients affected by MS.
Deep Brain Stimulation and Treatment Outcomes of Young- and Late-Onset (≤55 Years) Parkinson's Disease: A Population-Based Study
Authors: Camerucci Emanuele , Stang Cole D. , Turcano Pierpaolo , Tipton Philip W. , Bower James H. , Hassan Anhar , Klassen Bryan T. , Savica Rodolfo
Published: December 2021

Background: No studies have reported the rate of motor complications (MC) and response to medical and surgical treatment in a population-based cohort of young-onset Parkinson's Disease (YOPD) patients and a cohort of sex-matched late-onset Parkinson's Disease (LOPD).

Objective: To assess the outcomes of dopaminergic treatment in YOPD and LOPD, explore treatment-induced MC, medical adjustment, and rate of deep brain stimulation (DBS).

Methods: We used the expanded Rochester Epidemiology Project (eREP) to investigate a population-based cohort of YOPD between 2010 and 2015 in 7 counties in Minnesota. Cases with onset ≤55 years of age were included as YOPD. An additional sex-matched cohort of LOPD (onset at ≥56 years of age) was included for comparison. All medical records were reviewed to confirm the diagnoses.

Results: In the seven counties 2010–15, there were 28 YOPD patients, which were matched with a LOPD cohort. Sixteen (57%) YOPD had MC, as compared to 9 (32%) LOPD. In YOPD, 9 had motor fluctuations (MF) and Levodopa-induced dyskinesia (LID) together, whereas 3 had LID only and 4 MF only. In LOPD, 3 had MF and LID, 3 MF only, and 3 LID only. Following medical treatment for MC, 6/16 YOPD (38%) and 3/9 (33%) LOPD had symptoms resolution. In YOPD, 11/16 (69%) were considered for DBS implantation, in LOPD they were 2/9 (22%), but only 7 (6 YOPD and 1 LOPD) underwent the procedure. YOPD had significantly higher rates in both DBS candidacy and DBS surgery (respectively, p = 0.03 and p = 0.04). Among DBS-YOPD, 5/6 (83%) had positive motor response to the surgery; the LOPD case had a poor response. We report the population-based incidence of both YOPD with motor complications and YOPD undergoing DBS, which were 1.17 and 0.44 cases per 100,000 person-years, respectively.

Conclusion: Fifty-seven percent of our YOPD patients and 32% of the LOPD had motor complications. Roughly half of both YOPD and LOPD were treatment resistant. YOPD had higher rates of DBS candidacy and surgery. Six YOPD and 1 LOPD underwent DBS implantation and most of them had a positive motor response after the surgery.
Identification of Symptomatic Carotid Artery Plaque: A Three-Item Scale Combined Angiography With Optical Coherence Tomography
Authors: Yang Qingwen , Guo Hongquan , Shi Xuan , Xu Xiaohui , Zha Mingming , Cai Haodi , Yang Dahong , Huang Feihong , Zhang Xiaohao , Lv Qiushi , Liu Rui , Liu Xinfeng
Published: December 2021

Introduction: Symptomatic carotid disease conveys a high risk of recurrent stroke. Plaque morphology and specific plaque characteristics are associated with the risk of stroke. This study aimed to evaluate the detailed plaque features by optical coherence tomography (OCT) and develop a simple scale combining clinical indicators, digital subtraction angiography (DSA), and OCT imaging markers to identify symptomatic carotid plaque.

Methods: Carotid plaques from consecutive patients who underwent carotid OCT imaging between June 2017 and June 2021 were evaluated. Clinical characteristics, DSA, and OCT data were compared between the symptomatic and asymptomatic groups. Logistic regression was performed to identify the factors associated with symptomatic carotid plaque and to develop a scale. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the scale.

Results: A total of 90 carotid plaques from 90 patients were included (symptomatic 35.6%, asymptomatic 64.4%). Three main factors were found to be associated with symptomatic carotid plaque: high-density lipoprotein cholesterol (HDL-C) <0.925 mmol/L (OR, 4.708; 95% CI, 1.640 to 13.517; P = 0.004), irregular plaque (OR, 4.017; 95% CI, 1.250 to 12.910; P = 0.020), and white thrombus (OR, 4.594; 95% CI, 1.141 to 18.487; P = 0.032). The corresponding score of three items produced a scale with good discrimination (AUC, 0.768; 95% CI, 0.665 to 0.871). The optimal cutoff value of the scale was 1.5 points with 59.4% sensitivity and 84.5% specificity.

Conclusion: The three-item scale comprising HDL-C <0.925 mmol/L, angiographical irregular plaque, and white thrombus detected by OCT may provide information to identify symptomatic carotid plaque. Further large-scale studies are required to validate whether the symptomatic carotid plaque scale is clinically valuable in recognizing carotid atherosclerosis in the early stages.
Muscle Status Response to Oral Nutritional Supplementation in Hemodialysis Patients With Protein Energy Wasting: A Multi-Center Randomized, Open Label-Controlled Trial
Authors: Sahathevan Sharmela , Karupaiah Tilakavati , Khor Ban-Hock , Sadu Singh Birinder Kaur , Mat Daud Zulfitri Azuan , Fiaccadori Enrico , Sabatino Alice , Chinna Karuthan , Abdul Gafor Abdul Halim , Bavanandan Sunita , Visvanathan Ravindran , Yahya Rosnawati , Wahab Zaimi , Goh Bak-Leong , Morad Zaki , Bee Boon Cheak , Wong Hin Seng
Published: December 2021

Background: Muscle wasting, observed in patients with end-stage kidney disease and protein energy wasting (PEW), is associated with increased mortality for those on hemodialysis (HD). Oral nutritional supplementation (ONS) and nutrition counseling (NC) are treatment options for PEW but research targeting muscle status, as an outcome metric, is limited.

Aim: We compared the effects of combined treatment (ONS + NC) vs. NC alone on muscle status and nutritional parameters in HD patients with PEW.

Methods: This multi-center randomized, open label-controlled trial, registered under ClinicalTrials.gov (Identifier no. NCT04789031), recruited 56 HD patients identified with PEW using the International Society of Renal Nutrition and Metabolism criteria. Patients were randomly allocated to intervention (ONS + NC, n = 29) and control (NC, n = 27) groups. The ONS + NC received commercial renal-specific ONS providing 475 kcal and 21.7 g of protein daily for 6 months. Both groups also received standard NC during the study period. Differences in quadriceps muscle status assessed using ultrasound (US) imaging, arm muscle area and circumference, bio-impedance spectroscopy (BIS), and handgrip strength (HGS) methods were analyzed using the generalized linear model for repeated measures.

Results: Muscle indices as per US metrics indicated significance (p < 0.001) for group × time interaction only in the ONS + NC group, with increases by 8.3 and 7.7% for quadriceps muscle thickness and 4.5% for cross-sectional area (all p < 0.05). This effect was not observed for arm muscle area and circumference, BIS metrics and HGS in both the groups. ONS + NC compared to NC demonstrated increased dry weight (p = 0.039), mid-thigh girth (p = 0.004), serum prealbumin (p = 0.005), normalized protein catabolic rate (p = 0.025), and dietary intakes (p < 0.001), along with lower malnutrition–inflammation score (MIS) (p = 0.041). At the end of the study, lesser patients in the ONS + NC group were diagnosed with PEW (24.1%, p = 0.008) as they had achieved dietary adequacy with ONS provision.

Conclusion: Combination of ONS with NC was effective in treating PEW and contributed to a gain in the muscle status as assessed by the US, suggesting that the treatment for PEW requires nutritional optimization via ONS.
COVID-19 Outcome Relates With Circulating BDNF, According to Patient Adiposity and Age
Authors: Minuzzi Luciele Guerra , Seelaender Marília , Silva Bruna Spolador De Alencar , Cunha Eduardo del Bosco Brunetti , Deus Marina De Castro , Vasconcellos Franciane Thais Falcão , Marqueze Luis Felipe Beltrão , Gadotti Ana Carolina , Baena Cristina Pellegrino , Pereira Telmo , Krüger Karsten , Amaral Andréa Novais Moreno , Pinho Ricardo Aurino , Lira Fábio Santos
Published: December 2021

Background and Aims:We evaluated adipose tissue-derived hormones, body composition, serum metabolic profile, levels of brain-derived neurotrophic factor (BDNF), and the association of these parameters with the clinical outcome in patients with COVID-19. We sought to examine whether obesity, sex, and age influence the adipose tissue endocrine response to the disease.

Methods:This prospective study investigated 145 hospitalized patients with COVID-19. Patients were categorized based on their body mass index (BMI), sex and age, and were also classified regarding their outcome after hospitalization as: (a) Non-ICU: patients hospitalized who did not receive intensive care; (b) ICU-survivor: patients admitted to the intensive care unit and discharged; (c) ICU-death: patients who died. Blood samples were collected by the hospital staff between the first and third day of hospitalization. Serum leptin, adiponectin and BDNF concentrations, triglycerides, total cholesterol and cholesterol fractions were performed following the manufacturer's guidelines.

Results:We demonstrate that BDNF levels predict intensive care (IC) need (p< 0.01). This association was found to be stronger in patients >60y (p= 0.026). Neither leptin nor adiponectin concentration was associated with IC requirement or with patient's outcome, while the BDNF/adiponectin ratio was closely associated with worsened outcomes (p< 0.01). BDNF concentration was similar between sexes, however tended to be lower in male patients (p= 0.023). In older patients, BDNF concentration was lower than that of younger patients (p= 0.020). These age and sex-specific differences should be considered when employing these potential markers for prognosis assessment. While appetite and body composition regulating hormones secreted by the white adipose tissue are not reliable predictors of disease severity, the ratio BDNF/adiponectin was indicative of patient status.

Conclusion:Thus, we propose that serum BDNF content and BDNF/adiponectin ratio may serve as tools predicting worsened prognosis in COVID-19, especially for male patients.
Umbilical Cord Procalcitonin to Detect Early-Onset Sepsis in Newborns: A Promising Biomarker
Authors: Dongen O. R. E. , van Leeuwen L. M. , de Groot P. K. , Vollebregt K. , Schiering I. , Wevers B. A. , Euser S. M. , van Houten M. A.
Published: December 2021

Background: Up to 7% of neonates born in high-income countries receive antibiotics for suspected early-onset sepsis (EOS). Culture-proven neonatal sepsis has a prevalence of 0.2%, suggesting considerable overtreatment. We studied the diagnostic accuracy of umbilical cord blood and infant blood procalcitonin (PCT) in diagnosing EOS to improve antibiotic stewardship.

Methods: Umbilical cord blood PCT was tested in newborns ≥ 32 weeks of gestation. Groups were defined as following: A) culture-proven or probable EOS (n = 25); B) Possible EOS, based on risk factors for which antibiotics were administered for <72 h (n = 49); C) Risk factor(s) for EOS without need for antibiotic treatment (n = 181); D) Healthy controls (n = 74). Additionally, venous or capillary blood PCT and C-reactive protein (CRP) were tested if blood drawing was necessary for standard care.

Results: Between June 2019 and March 2021, 329 newborns were included. Umbilical cord blood PCT was significantly higher in group A than in group C and D. No difference between venous or arterial samples was found. Sensitivity and specificity for cord blood procalcitonin were 83 and 62%, respectively (cut-off 0.1 ng/mL). Antepartum maternal antibiotic administration was associated with decreased PCT levels in both cord blood and infant blood directly postpartum in all groups combined.

Conclusion: Umbilical cord blood PCT levels are increased in newborns ≥32 weeks with a proven or probable EOS and low in newborns with risk factors for infection, but PCT seems not a reliable marker after maternal antibiotic treatment. PCT could be useful to distinguish infected from healthy newborns with or without EOS risk factors.
Effects of Probiotic Supplementation on Inflammatory Markers and Glucose Homeostasis in Adults With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Ding Li-Na , Ding Wen-Yu , Ning Jie , Wang Yao , Yan Yan , Wang Zhi-Bin
Published: December 2021

Background: Several studies have revealed the effect of probiotic supplementation in patients with type 2 diabetes (T2DM) on the amelioration of low-grade inflammation, which plays an important role in the pathogenesis of T2DM. However, the effects of the clinical application of probiotics on inflammation in individuals with T2DM remain inconsistent. This study aims to investigate the comprehensive effects of probiotics on inflammatory markers in adults with T2DM.

Methods: PubMed, Embase, Cochrane Library, and the Web of Science were searched to identify randomized controlled trials (RCTs) exploring the effect of probiotic supplementation on inflammatory markers in individuals with T2DM through March 11, 2021. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. We used a random-effects model to calculate the standardized mean difference (SMD) between the probiotic supplementation and control groups.

Results: Seventeen eligible studies were selected with a total of 836 participants, including 423 participants in probiotic supplementation groups and 413 participants in control groups. Our study demonstrated that compared with the control condition, probiotic intake produced a beneficial effect in reducing the levels of plasma inflammation markers, including tumour necrosis factor-α (TNF-α) (SMD [95% CI]; −0.37 [−0.56, −0.19], p < 0.0001) and C-reactive protein (CRP) (SMD [95% CI]; −0.21 [−0.42, −0.01], p = 0.040), while it had no effect on the plasma interleukin-6 (IL-6) level (SMD [95% CI]; −0.07 [−0.27, 0.13], p = 0.520). In addition, our results support the notion that probiotic supplementation improves glycaemic control, as evidenced by a significant reduction in fasting blood glucose (FPG), HbA1c and HOMA-IR (SMD [95% CI]: −0.24 [−0.42, −0.05], p = 0.010; −0.19 [−0.37, −0.00], p = 0.040; −0.36 [−0.62, −0.10], p = 0.006, respectively).

Conclusion: Our study revealed some beneficial effects of probiotic supplementation on improving inflammatory markers and glucose homeostasis in individuals with T2DM. Probiotics might be a potential adjuvant therapeutic approach for T2DM.
The Art of War: Ferroptosis and Pancreatic Cancer
Authors: Liu Jiao , Kang Rui , Tang Daolin
Published: December 2021

Pancreatic cancer is a devastating gastrointestinal cancer, characterized by late diagnosis, low treatment success rate, and poor survival prognosis. The most common pathological type of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which is mainly driven by the K-Ras oncogene. Ferroptosis was originally described as Ras-dependent cell death, but is now defined as lipid peroxidation-mediated regulated necrosis, accompanied by excessive activation of the autophagy degradation pathway and limited membrane repair capacity. The impaired ferroptotic pathway is involved in many types of cancer, including PDAC. On the one hand, the chronic inflammation caused by ferroptotic damage contributes to the formation of K-Ras-driven PDAC. On the other hand, drug-induced ferroptosis is an emerging strategy to suppress tumor growth in established PDAC. In this mini-review, we outline the core process of ferroptosis, discuss the regulatory mechanism of ferroptosis in PDAC, and highlight some of the challenges of targeting ferroptosis in PDAC therapy.
Overactive Bladder Symptoms Within Nervous System: A Focus on Etiology
Authors: Qin Chuying , Wang Yinhuai , Gao Yunliang
Published: December 2021

Overactive bladder (OAB) is a common debilitating condition characterized by urgency symptoms with detrimental effects on the quality of life and survival. The exact etiology of OAB is still enigmatic, and none of therapeutic approaches seems curative. OAB is generally regarded as a separate syndrome, whereas in clinic, OAB symptoms could be found in numerous diseases of other non-urogenital systems, particularly nervous system. The OAB symptoms in neurological diseases are often poorly recognized and inadequately treated. This review provided a comprehensive overview of recent findings related to the neurogenic OAB symptoms. Relevant neurological diseases could be mainly divided into seven kinds as follows: multiple sclerosis and related neuroinflammatory disorders, Parkinson’s diseases, multiple system atrophy, spinal cord injury, dementia, peripheral neuropathy, and others. Concurrently, we also summarized the hypothetical reasonings and available animal models to elucidate the underlying mechanism of neurogenic OAB symptoms. This review highlighted the close association between OAB symptoms and neurological diseases and expanded the current knowledge of pathophysiological basis of OAB. This may increase the awareness of urological complaints in neurological disorders and inspire robust therapies with better outcomes.
Plasma Exosomal Mir-423-5p Is Involved in the Occurrence and Development of Bicuspid Aortopathy via TGF-β/SMAD2 Pathway
Authors: Zhang Hongqiang , Liu Dingqian , Zhu Shichao , Wang Fanshun , Sun Xiaoning , Yang Shouguo , Wang Chunsheng
Published: December 2021

Objectives: Patients with bicuspid aortic valve (BAV) are at increased risk for ascending aortic dilation (AAD). Our study was aimed at systemically analyzing the expression profile and mechanism of circulating plasma exosomal microRNAs (miRNAs) related to BAV and AAD.

Methods: We isolated plasma exosomes from BAV patients (n=19), BAV patients with AAD (BAVAD, n=26), and healthy tricuspid aortic valve individuals with low cardiovascular risk (TAVnon, n=16). We applied a small RNA sequencing approach to identify the specific plasma exosomal miRNAs associated with BAV (n=8) and BAVAD (n=10) patients compared with healthy TAVnon (n=6) individuals. The candidate differentially expressed (DE) miRNAs were selected and validated by RT-qPCR in the remaining samples. GO and KEGG pathway enrichment analyses were performed to illustrate the functions of target genes. Western blot analysis and luciferase reporter assay were conducted in human aortic vascular smooth muscle cells (VSMCs) to verify the results of target gene prediction in vitro.

Results: The expression levels of three up-regulated (miR-151a-3p, miR-423-5p, and miR-361-3p) and two down-regulated (miR-16-5p and miR-15a-5p) exosomal miRNAs were significantly altered in BAV disease. Additionally, miR-423-5p could be functionally involved in the occurrence and development of BAV and its complication BAVAD by regulating TGF-β signaling. miR-423-5p could target to SMAD2 and decreased the protein levels of SMAD2 and P-SMAD2.

Conclusion: Plasma exosomal miR-423-5p regulated TGF-β signaling by targeting SMAD2, thus exerting functions in the occurrence and development of BAV disease and its complication bicuspid aortopathy.
Identifying Traits Associated With Terminal Drought Tolerance in Sesame (Sesamum indicum L.) Genotypes
Authors: Pandey Brij Bihari , Ratnakumar P. , Usha Kiran B. , Dudhe Mangesh Y. , Lakshmi G. Sowjanya , Ramesh Kulasekaran , Guhey Arti
Published: December 2021

Sesame is predominantly cultivated in rainfed and low fertile lands and is frequently exposed to terminal drought.Sesamumspecies inhabiting dryland ecosystems adaptively diverge from those inhabiting rainfed habitats, and drought-specific traits have a genetic basis. In sesame, traits associated with drought conditions have not been explored to date, yet studies of these traits are needed given that drought is predicted to become more frequent and severe in many parts of the world because of climate change. Here, 76 accessions from the available Indian core set were used to quantify variation in several traits under irrigated (WW) and terminal drought stress (WS) conditions as well as their association with seed yield over two consecutive years. The range of trait variation among the studied genotypes under WW and WS was significant. Furthermore, the traits associated with seed yield under WW and WS differed. Theper seperformance of the accessions indicated that the expression of most traits was reduced under WS. The correlation analysis revealed that the number of branches, leaf area (LA), leaves dry weight (LDW), number of capsules plant–1, and harvest index (HI) were positively correlated with seed yield under WW and WS, and total dry matter (TDM), plant stem weight, and canopy temperature (CT) were negatively correlated with seed yield under WW and WS, indicating that smaller and cooler canopy genotypes had higher yields. The genotypes IC-131936, IC-204045, IC-204861, IC-205363, IC-205311, and IC-73576 with the highest seed yields were characterized by low canopy temperature, high relative water content, and high harvest index under WS. Phenotypic and molecular diversity analysis was conducted on genotypes along with checks. Phenotypic diversity was assessed using multivariate analysis, whereas molecular diversity was estimated using simple sequence repeat (SSR) loci to facilitate the use of sesame in breeding and genetic mapping. SSRs showed low allelic variation, as indicated by a low average number of alleles (2.31) per locus, gene diversity (0.25), and polymorphism information content (0.22). Cluster analysis (CA) [neighbor-joining (NJ) tree] revealed three major genotypic groups and structure analysis showed 4 populations. The diverse genotypes identified with promising morpho-physiological traits can be used in breeding programs to develop new varieties.
Manipulation of Cannabinoid Biosynthesis via Transient RNAi Expression
Authors: Matchett-Oates Lennon , Spangenberg German C. , Cogan Noel O. I.
Published: December 2021

Cannabis sativa L. produces unique phytocannabinoids, which are used for their pharmaceutical benefits. To date, there are no reports of in vivo engineering targeting the cannabinoid biosynthesis genes to greater elucidate the role each of these genes play in synthesis of these medically important compounds. Reported here is the first modulation of cannabinoid biosynthesis genes using RNAi via agroinfiltration. Vacuum infiltrated leaf segments of the Cannbio-2 C. sativa strain, transfected with different RNAi constructs corresponding to THCAS, CBDAS, and CBCAS gene sequences, showed significant downregulation of all cannabinoid biosynthesis genes using real-time quantitative PCR. Using RNAi, significant off-targeting occurs resulting in the downregulation of highly homologous transcripts. Significant (p < 0.05) downregulation was observed for THCAS (92%), CBDAS (97%), and CBCAS (70%) using pRNAi-GG-CBDAS-UNIVERSAL. Significant (p < 0.05) upregulation of CBCAS (76%) and non-significant upregulation of THCAS (13%) were observed when transfected with pRNAi-GG-CBCAS, suggesting the related gene’s ability to synthesize multiple cannabinoids. Using this approach, increased understanding of the relationship between cannabinoid biosynthesis genes can be further elucidated. This RNAi approach enables functional genomics screens for further reverse genetic studies as well as the development of designer cannabis strains with over-expression and/or downregulation of targeted cannabinoid biosynthesis genes. Functional genomics screens, such as these, will further provide insights into gene regulation of cannabinoid biosynthesis in Cannabis.