bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping potential implications of temporary COVID‐19 export bans for the food supply in importing countries using precrisis trade flows
Authors: Koppenberg Maximilian , Bozzola Martina , Dalhaus Tobias , Hirsch Stefan
Published: December 2020

Despite pleas from international organizations, governments and trade economists to refrain from imposing trade‐distorting measures, over 20 countries have implemented bans on the export of agri‐food products since the onset of the COVID‐19 crisis. These export prohibitions might adversely impact food security and disrupt well‐established global supply chains. We identify importing countries that could potentially be affected by the imposed export bans using a measure of their import dependency during the pre‐pandemic period to illustrate our results on global trade maps. We find that many importers rely on just one country for a significant share of the overall domestic supply of a particular commodity. [EconLit Citations: F10, F13, Q17, Q18]
Circulating microRNAs Associated With Reversible Cerebral Vasoconstriction Syndrome
Authors: Chen Shih‐Pin , Chang Yi‐An , Chou Chih‐Hung , Juan Chi‐Chang , Lee Hsin‐Chen , Chen Luen‐Kui , Wu Pei‐Chun , Wang Yen‐Feng , Fuh Jong‐Ling , Lirng Jiing‐Feng , Ducros Anne , Huang Hsien‐Da , Wang Shuu‐Jiun
Published: December 2020

Objective

The purpose of this study was to investigate the significance of circulating micro RNAs (miRNAs) in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS).

Methods

We prospectively recruited 3 independent cohorts of patients with RCVS and age‐matched and sex‐matched controls in a single medical center. Next‐generation small RNA sequencing followed by quantitative polymerase chain reaction (PCR) was used to identify and validate differentially expressed miRNAs, which was cross‐validated in migraine patients in ictal stage or interictal stage. Computational analysis was used to predict the target genes of miRNAs, followed by in vitro functional analysis.

Results

We identified a panel of miRNAs including miR‐130a‐3p, miR‐130b‐3p, let‐7a‐5p, let‐7b‐5p, and let‐7f‐5p that well differentiated patients with RCVS from controls (area under the receiver operating characteristics curve [AUC] was 0.906, 0.890, and 0.867 in the 3 cohorts, respectively). The abundance of let‐7a‐5p, let‐7b‐5p, and let‐7f‐5p, but not miR‐130a‐3p nor miR‐130b‐3p, was significantly higher in patients with ictal migraine compared with that of controls and patients with interictal migraine. Target prediction and pathway enrichment analysis suggested that the transforming growth factor‐β signaling pathway and endothelin‐1 responsible for vasomotor control might link these miRNAs to RCVS pathogenesis, which was confirmed in vitro by transfecting miRNAs mimics or incubating the patients’ cerebrospinal fluid (CSF) in 3 different vascular endothelial cells. Moreover, miR‐130a‐3p was associated with imaging‐proven disruption of the blood‐brain barrier (BBB) in patients with RCVS and its overexpression led to reduced transendothelial electrical resistance (ie, increased permeability) in in vitro human BBB model.

Interpretation

We identified the circulating miRNA signatures associated with RCVS, which may be functionally linked to its headache, BBB integrity, and vasomotor function. ANN NEUROL 2021;89:459–473
Greater Somatosensory Afference With Acupuncture Increases Primary Somatosensory Connectivity and Alleviates Fibromyalgia Pain via Insular γ‐Aminobutyric Acid: A Randomized Neuroimaging Trial
Authors: Mawla Ishtiaq , Ichesco Eric , Zöllner Helge J. , Edden Richard A. E. , Chenevert Thomas , Buchtel Henry , Bretz Meagan D. , Sloan Heather , Kaplan Chelsea M. , Harte Steven E. , Mashour George A. , Clauw Daniel J. , Napadow Vitaly , Harris Richard E.
Published: December 2020

Objective

Acupuncture is a complex multicomponent treatment that has shown promise in the treatment of fibromyalgia (FM). However, clinical trials have shown mixed results, possibly due to heterogeneous methodology and lack of understanding of the underlying mechanism of action. The present study was undertaken to understand the specific contribution of somatosensory afference to improvements in clinical pain, and the specific brain circuits involved.

Methods

Seventy‐six patients with FM were randomized to receive either electroacupuncture (EA), with somatosensory afference, or mock laser acupuncture (ML), with no somatosensory afference, twice a week over 8 treatments. Patients with FM in each treatment group were assessed for pain severity levels, measured using Brief Pain Inventory (BPI) scores, and for levels of functional brain network connectivity, assessed using resting state functional magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy in the right anterior insula, before and after treatment.

Results

Fibromyalgia patients who received EA therapy experienced a greater reduction in pain severity, as measured by the BPI, compared to patients who received ML therapy (mean difference in BPI from pre‐ to posttreatment was −1.14 in the EA group versus −0.46 in the ML group; P for group × time interaction = 0.036). Participants receiving EA treatment, as compared to ML treatment, also exhibited resting functional connectivity between the primary somatosensory cortical representation of the leg (S1leg; i.e. primary somatosensory subregion activated by EA) and the anterior insula. Increased S1leg–anterior insula connectivity was associated with both reduced levels of pain severity as measured by the BPI (r = −0.44, P = 0.01) and increased levels of γ‐aminobutyric acid (GABA+) in the anterior insula (r = 0.48, P = 0.046) following EA therapy. Moreover, increased levels of GABA+ in the anterior insula were associated with reduced levels of pain severity as measured by the BPI (r = −0.59, P = 0.01). Finally, post–EA treatment changes in levels of GABA+ in the anterior insula mediated the relationship between changes in S1leg–anterior insula connectivity and pain severity on the BPI (bootstrap confidence interval −0.533, −0.037).

Conclusion

The somatosensory component of acupuncture modulates primary somatosensory functional connectivity associated with insular neurochemistry to reduce pain severity in FM.
The Pretreatment Gut Microbiome Is Associated With Lack of Response to Methotrexate in New‐Onset Rheumatoid Arthritis
Authors: Artacho Alejandro , Isaac Sandrine , Nayak Renuka , Flor‐Duro Alejandra , Alexander Margaret , Koo Imhoi , Manasson Julia , Smith Philip B. , Rosenthal Pamela , Homsi Yamen , Gulko Percio , Pons Javier , Puchades‐Carrasco Leonor , Izmirly Peter , Patterson Andrew , Abramson Steven B. , Pineda‐Lucena Antonio , Turnbaugh Peter J. , Ubeda Carles , Scher Jose U.
Published: December 2020

Objective

Although oral methotrexate (MTX) remains the anchor drug for rheumatoid arthritis (RA), up to 50% of patients do not achieve a clinically adequate outcome. In addition, there is a lack of prognostic tools for treatment response prior to drug initiation. This study was undertaken to investigate whether interindividual differences in the human gut microbiome can aid in the prediction of MTX efficacy in new‐onset RA.

Methods

We performed 16S ribosomal RNA gene and shotgun metagenomic sequencing on the baseline gut microbiomes of drug‐naive patients with new‐onset RA (n = 26). Results were validated in an additional independent cohort (n = 21). To gain insight into potential microbial mechanisms, we conducted ex vivo experiments coupled with metabolomics analysis to evaluate the association between microbiome‐driven MTX depletion and clinical response.

Results

Our analysis revealed significant associations of the abundance of gut bacterial taxa and their genes with future clinical response (q < 0.05), including orthologs related to purine and MTX metabolism. Machine learning techniques were applied to the metagenomic data, resulting in a microbiome‐based model that predicted lack of response to MTX in an independent group of patients. Finally, MTX levels remaining after ex vivo incubation with distal gut samples from pretreatment RA patients significantly correlated with the magnitude of future clinical response, suggesting a possible direct effect of the gut microbiome on MTX metabolism and treatment outcomes.

Conclusion

Taken together, these findings are the first step toward predicting lack of response to oral MTX in patients with new‐onset RA and support the value of the gut microbiome as a possible prognostic tool and as a potential target in RA therapeutics.
Association of image‐defined risk factors with clinical features, histopathology, and outcomes in neuroblastoma
Authors: Temple William C. , Vo Kieuhoa T. , Matthay Katherine K. , Balliu Brunilda , Coleman Christina , Michlitsch Jennifer , Phelps Andrew , Behr Spencer , Zapala Matthew A.
Published: December 2020

Background

Clinical, molecular, and histopathologic features guide treatment for neuroblastoma, but obtaining tumor tissue may cause complications and is subject to sampling error due to tumor heterogeneity. We hypothesized that image‐defined risk factors (IDRFs) would reflect molecular features, histopathology, and clinical outcomes in neuroblastoma.

Methods

We performed a retrospective cohort study of 76 patients with neuroblastoma or ganglioneuroblastoma. Diagnostic CT scans were reviewed for 20 IDRFs, which were consolidated into five IDRF groups (involvement of multiple body compartments, vascular encasement, tumor infiltration of adjacent organs/structures, airway compression, or intraspinal extension). IDRF groups were analyzed for association with clinical, molecular, and histopathologic features of neuroblastoma.

Results

Patients with more IDRF groups had a higher risk of surgical complications (OR = 3.1, p = 0.001). Tumor vascular encasement was associated with increased risk of surgical complications (OR = 5.40, p = 0.009) and increased risk of undifferentiated/poorly differentiated histologic grade (OR = 11.11, p = 0.013). Tumor infiltration of adjacent organs and structures was associated with decreased survival (HR = 8.90, p = 0.007), MYCN amplification (OR = 9.91, p = 0.001), high MKI (OR = 6.20, p = 0.003), and increased risk of International Neuroblastoma Staging System stage 4 disease (OR = 8.96, p < 0.001).

Conclusions

The presence of IDRFs at diagnosis was associated with high‐risk clinical, molecular, and histopathologic features of neuroblastoma. The IDRF group tumor infiltration into adjacent organs and structures was associated with decreased survival. Collectively, these findings may assist surgical planning and medical management for neuroblastoma patients.
High fidelity modeling of aerosol pathogen propagation in built environments with moving pedestrians
Authors: Löhner Rainald , Antil Harbir
Published: December 2020

A high fidelity model for the propagation of pathogens via aerosols in the presence of moving pedestrians is proposed. The key idea is the tight coupling of computational fluid dynamics and computational crowd dynamics in order to capture the emission, transport and inhalation of pathogen loads in space and time. An example simulating pathogen propagation in a narrow corridor with moving pedestrians clearly shows the considerable effect that pedestrian motion has on airflow, and hence on pathogen propagation and potential infectivity.
Cyst formation in the subchondral bone following cartilage repair
Authors: Gao Liang , Cucchiarini Magali , Madry Henning
Published: December 2020

Subchondral bone cysts represent an early postoperative sign associated with many articular cartilage repair procedures. They may be defined as an abnormal cavity within the subchondral bone in close proximity of a treated cartilage defect with a possible communication to the joint cavity in the absence of osteoarthritis. Two synergistic mechanisms of subchondral cyst formation, the theory of internal upregulation of local proinflammatory factors, and the external hydraulic theory, are proposed to explain their occurrence. This review describes subchondral bone cysts in the context of articular cartilage repair to improve investigations of these pathological changes. It summarizes their epidemiology in both preclinical and clinical settings with a focus on individual cartilage repair procedures, examines an algorithm for subchondral bone analysis, elaborates on the underlying mechanism of subchondral cyst formation, and condenses the clinical implications and perspectives on subchondral bone cyst formation in cartilage repair.
RETRACTED: Effect of adding Aloe vera jell on the quality and sensory properties of yogurt
Authors: Ikram Ali , Qasim Raza Syed , Saeed Farhan , Afzaal Muhammad , Munir Haroon , Ahmed Aftab , Babar Bin Zahid Muhammad , Muhammad Anjum Faqir
Published: December 2020

This study was planned to investigate the effect of replacing milk fat with aloe vera gel addition on yogurt quality. Purposely, yogurt was prepared with different concentration of aloe vera gel and coded as AGY0, = Control (3.5% fat and no AG), AGY1 = (1% fat and 1% AG), AGY2 = (1% fat and 2% AG), AGY3 = (1% fat and 3% AG), AGY4 = (2% fat and 1% AG), AGY5 = (2% fat and 2% AG), and AGY6 = (2% fat and 3% AG). Aloe vera gel yogurt was analyzed for physicochemical, microbial, and sensory characteristics with defined interval (0, 7th, 14th, and 21st) days. All attributes of the yogurt were significantly (0.05) affected by the addition of aloe vera gel. Results showed that the pH (4.6–4.05), viscosity (46.4–4.3), WHC (32.8%–26.1%), fat (0.9%–3.48%), protein (3.14%–3.36%), lactose (4.07%–4.23%), ash (0.48%–0.63%), total solids (11.08%–17.18%), SNF (7.69‐l5.21%), and TPC (2.36 × 107 to 1.02 × 107 CFU/ml) values of yogurt samples decreased with storage time. However, acidity and syneresis of yogurt increased with the passage of time ranging from 1.12%–1.67% and 0.9–5 ml, respectively. In conclusion, aloe vera improved the texture of the yogurt which leads to higher consumer acceptability. Addition of 3% aloe vera to 1% fat (AGY3) containing buffalo milk yogurt was found to best for physicochemical as well as organoleptic characteristics as well as organoleptic characteristics.
Fermented‐Rhus verniciflua extract ameliorate Helicobacter pylori eradication rate and gastritis
Authors: Kim Seungwoo , Shin Suk Pyo , Kim Seul Ki , Ham Young Lim , Choi Han Seok , Kim Myong Jo , Han Sang Hak , Suk Ki Tae
Published: December 2020

An antibacterial effect of fermented‐Rhus verniciflua extract (FRVE), an urushiol‐free extract fermented by Fomitella fraxinea, on Helicobacter pylori was evaluated in mice. Minimal inhibitory concentration of FRVE against H. pylori eradication was checked with serial dilution method in vitro. H. pylori infection‐induced mice were utilized to determine the effect of oral administration of FRVE with/without standard triple therapy (STT: metronidazole, omeprazole, and clarithromycin) on H. pylori colonization and gastric inflammation. H. pylori was clearly eradicated by FRVE at a concentration of ≥2 mg/ml in vitro. In animal study, FRVE at a concentration of ≥6 mg/ml significantly reduced colonized H. pylori grading (0.2 vs. 2.2, p < .01) and improved gastric inflammation (0.4 vs. 1.6, p < .01) compared to control. STT with FRVE (3 mg/ml) exerted synergistic effect on both H. pylori colonization grade (STT, 0.6 ± 0.9; FRVE, 1.4 ± 0.5; STT + FRVE, 0.8 ± 0.4) and gastric inflammation (STT, 0.4 ± 0.5; FRVE, 1.4 ± 0.5; STT + FRVE,1.0 ± 0.1) compared with single therapy (p < .01). H. pylori eradication rate of FRVE (6 mg/ml) was higher than that of STT (60% vs. 20%). FRVE has potential antibacterial activity against H. pylori infection and can be used as an additional therapy on STT.
RETRACTED: Exploring the amino acid profile and microbial properties of locally sweet preserved kachra hareer (Terminalia chebula)
Authors: Ikram Ali , Saeed Farhan , Munir Haroon , Sultan Muhammad Tauseef , Afzaal Muhammad , Ahmed Aftab , Anjum Faqir Muhammad
Published: December 2020

The current research was designed to determine the amino acid profile and microbial properties of kachra hareer. For the purpose, kachra hareer was purchased with their brand names coded as S1, S2, S3, and S4 from five towns named as L1, L2, L3, L4, and L5. The samples were analyzed for their amino acid profile and microbial properties, while the water and alcohol extractive values were analyzed to obtain the different levels of purity during processing. The results explained that physicochemical analyses, that is, pH, moisture, acidity, and vitamin C, ranged from 4.67% to 9.44%, 22% to 40%, 0.054% to 1.44%, and 7.67% to 19.36%, respectively. However, essential amino acids histidine, isoleucine, leucine, methionine, phenylalanine, proline, threonine, and valine ranged from 470.3 to 484.5, 516.1 to 527.5, 805.5 to 817.4, 910.1 to 922.5, 240.2 to 250.5, 508.2 to 518.2, 1,160.5 to 1,172.6, 466.9 to 476.3, and 502.5 to 513.4 mg/kg, respectively, whereas nonessential amino acids alanine, arginine, aspartic acid cysteine, glutamic acid, serine, tyrosine, and glycine ranged from 612.7 to 628.2, 1,212.3 to 1,225.9, 7,254.2 to 7,258.8, ND, 1,561.2 to 1,575.2, 634.8 to 648.9, 618.4 to 630.4, and 712.8 to 723.7 mg/kg, respectively. Conclusively, sample S2 showed the maximum nutritional content and minimum microbial load.
Critical concepts and management recommendations for cutaneous T‐cell lymphoma: A consensus‐based position paper from the Italian Group of Cutaneous Lymphoma
Authors: Zinzani Pier Luigi , Quaglino Pietro , Violetti Silvia Alberti , Cantonetti Maria , Goteri Gaia , Onida Francesco , Paulli Marco , Rupoli Serena , Barosi Giovanni , Pimpinelli Nicola
Published: December 2020

In this paper, we present a review of critical concepts, and produce recommendations on management issues in cutaneous T‐cell lymphomas (CTCLs) of adults. A panel of nine experts was selected for their expertise in research and clinical practice of CTCLs. During an initial meeting, the areas of major concern in the management of CTCLs were selected by generating and rank‐ordering clinical key questions using the criterion of clinical relevance, through group discussion. Recommendations were achieved by multiple‐step formalized procedures to reach a consensus after a comprehensive analysis of the scientific literature. The panel produced recommendations on how to facilitate the clinical suspicion of CTCL; indication of cutaneous biopsy; optimal histological diagnosis, immunohistochemistry and genetic markers; and staging pathway and up‐to‐date therapeutics (with particular focus on new treatments). The critical concept of integration of the different medical expertise in the management of the patients with CTCL was thoroughly examined. These recommendations are intended for use not only by expert centers but above all by "not experienced" dermatologists and hematologists as well as general practitioners.
Woody buffer effects on water temperature: The role of spatial configuration and daily temperature fluctuations
Authors: Kail Jochem , Palt Martin , Lorenz Armin , Hering Daniel
Published: December 2020

Water temperature is a key driver for riverine biota and strongly depends on shading by woody riparian vegetation in summer. While the general effects of shading on daily maximum water temperature Tmax are well understood, knowledge gaps on the role of the spatial configuration still exist. In this study, the effect of riparian buffer length, width, and canopy cover (percentage of buffer area covered by woody vegetation) on Tmax was investigated during summer baseflow using data measured in seven small lowland streams in western Germany (wetted width 0.8–3.7 m). The effect of buffer length on Tmax differed between downstream cooling and heating: Tmax approached cooler equilibrium conditions after a distance of 0.4 km (~45 min travel‐time) downstream of a sharp increase in canopy cover. In contrast, Tmax continued to rise downstream of a sharp decrease in canopy cover along the whole 1.6 km stream length investigated. The effect of woody vegetation on Tmax depended on buffer width, with changes in canopy cover in a 10 m wide buffer being a better predictor for changes in Tmax compared to a 30 m buffer. The effect of woody vegetation on Tmax was linearly related to canopy cover but also depended on daily temperature range Trange, which itself was governed by cloudiness, upstream canopy cover, and season. The derived empirical relationship indicated that Tmax was reduced by −4.6°C and increased by +2.7°C downstream of a change from unshaded to fully shaded conditions and vice versa. This maximum effect was predicted for a 10 m wide buffer at sunny days in early summer, in streams with large diel fluctuations (large Trange). Therefore, even narrow woody riparian buffers may substantially reduce the increase in Tmax due to climate change, especially in small shallow headwater streams with low baseflow discharge and large daily temperature fluctuations.
Effects of low‐molecular‐weight heparin and aspirin in recurrent pre‐eclampsia: A stratified cohort study
Authors: Zhang Yi , Shen Fangrong , Yang Weiwen , Wang Juan , Zhou Jinhua , Chen Youguo
Published: December 2020

Objective

To evaluate the effects of low‐molecular‐weight heparin (LMWH) combined with low‐dose aspirin (LDA) in pregnant women with a history of pregnancy‐related hypertensive disorders.

Methods

In the current retrospective stratified cohort study, 33 women with previous hypertensive disorders of pregnancy treated with LMWH and LDA were compared with 37 control women who did not undergo LMWH or LDA treatment. Rates of pre‐eclampsia recurrence, placental abruption, and other adverse outcomes for the fetuses and pregnant women were compared in the two groups.

Results

The pre‐eclampsia recurrence rates were 12/33 (36.4%) in the LMWH + LDA group and 28/37 (75.7%) in the control group (P < 0.01). In stratified cohort analysis, pregnant women with a history of early‐onset pre‐eclampsia, a body mass index of at least 24 (calculated as weight in kilograms divided by the square of height in meters), and aged less than 35 years benefited from LMWH + LDA treatment. In women with chronic hypertension or a history of placental abruption there was no protective effect. There were no significant differences in other adverse outcomes such as placental abruption and small size for gestational age in fetuses or pregnant women in the two groups.

Conclusion

Administration of LMWH + LDA only lowered the risk of pre‐eclampsia recurrence in subgroups of pregnant women with a history of pregnancy‐associated hypertensive disorders.
Characterizing thrombus with multiple red blood cell compositions by optical coherence tomography attenuation coefficient
Authors: Liu Hsiao‐Chuan , Abbasi Mehdi , Ding Yong Hong , Polley Eric C. , Fitzgerald Seán , Kadirvel Ramanathan , Kallmes David F. , Brinjikji Waleed , Urban Matthew W.
Published: December 2020

Embolectomy is one of the emergency procedures performed to remove emboli. Assessing the composition of human blood clots is an important diagnostic factor and could provide guidance for an appropriate treatment strategy for interventional physicians. Immunostaining has been used to identity compositions of clots as a gold‐standard procedure, but it is time‐consuming and cannot be performed in situ. Here, we proposed that the optical attenuation coefficient of optical coherence tomography (OCT) can be a reliable indicator as a new imaging modality to differentiate clot compositions. Fifteen human blood clots with multiple red blood cell (RBC) compositions from 21% to 95% were prepared using healthy human whole blood. A homogeneous gelatin phantom experiment and numerical simulation based on the Lambert–Beer's law were examined to verify the validity of the attenuation coefficient estimation. The results displayed that optical attenuation coefficients were strongly correlated with RBC compositions. We reported that attenuation coefficients could be a promising biomarker to guide the choice of an appropriate interventional device in a clinical setting and assist in characterizing blood clots.
Improving the image quality in STED nanoscopy using frequency spectrum modulation
Authors: Wang Jialin , Wang Luwei , Zhang Jia , Yang Zhigang , Yan Wei , Qu Junle
Published: December 2020

Since stimulated emission depletion (STED) nanoscopy was invented in 1994, this technique has been widely used in the fields of biomedicine and materials science. According to the imaging principle of STED technology, increasing the power of the depletion laser within a certain threshold can improve the resolution. However, it will cause not only severe photo‐damage to the samples and photo‐bleaching to the fluorophores but also serious background noise, leading to the degeneration of the quality of STED images. Here we propose a new processing method based on frequency spectrum modulation to improve the quality of STED images, abbreviated as FM‐STED. We have demonstrated the performance of FM‐STED in improving the signal‐to‐noise ratio and the resolution using fluorescent beads and biological cells as samples.
PyVisA: Visualization and Analysis of path sampling trajectories
Authors: Aarøen Ola , Kiær Henrik , Riccardi Enrico
Published: December 2020

Rare event methods applied to molecular simulations are growing in popularity, accessible and customizable software solutions have thus been developed and released. One of the most recent is PyRETIS, an open Python library for performing path sampling simulations. Here, we introduce PyVisA, a postprocessing package for path sampling simulations, which includes visualization and analysis tools for interpreting path sampling outputs. PyVisA integrates PyRETIS functionalities and aims to facilitate the determination of: (a) the correlation of the order parameter with other descriptors; (b) the presence of latent variables; and (c) intermediate meta‐stable states. To illustrate some of the main PyVisA features, we investigate the proton transfer reaction in a protonated water trimer simulated via a simple polarizable model (Stillinger−David).
The relationship between plasma serglycin levels and the diagnosis of diabetic retinopathy
Authors: Wang Layi , Han Yin , Wang Xiajun
Published: December 2020

Background

Diabetic retinopathy (DR), a microvascular complication which is closely related to diabetes, remains the leading cause of vision loss around the world among older adults. Serglycin (SRGN) was known as a hematopoietic cell granule proteoglycan, exerting its function in the formation of mast cell secretory granules and mediates the storage of various compounds in secretory vesicles. The present study illustrates the potential clinical value and experimental mechanisms of SRGN in the DR.

Methods

Firstly, the mRNA expression and protein expression of SRGN in plasma samples from NPDR, PDR patients, type 2 diabetes mellitus (T2Dm) cases, and healthy controls were measured by qPCR and Western blotting assays, respectively. Then, the potentials of SRGN functioning as a diagnostic indicator in DR were verified by the receiver operating characteristic (ROC) analysis. We established in vitro DR model of human retinal endothelial cells through high‐glucose treatment. The expression of SRGN and its mechanisms of regulating cellular processes were illustrated subsequently.

Results

Our data revealed that SRGN was dramatically upregulated in NPDR and PDR cases compared with healthy controls and T2DM patients; meanwhile, the expression of SRGN was further increased in the PDR group with regard to the NPDR group. Furthermore, the ROC analysis demonstrated that SRGN could distinguish the DR cases from type 2 diabetes mellitus (T2DM) patients and healthy controls with the area under the curve (AUC) of 0.7680 (95% CI = 0.6780 ~ 0.8576, sensitivity = 47.27%, specificity = 100%, cutoff value = 1.4727) and 0.8753 (95% CI = 0.8261 ~ 0.9244, sensitivity = 69.23%, specificity = 100%, cutoff value = 1.6923), respectively. In vitro high‐glucose treatment showed that the SRGN expressions were dramatically increased. The loss of SRGN could partially counteract the inhibition of HREC proliferation caused by high‐glucose stimulation. Meanwhile, SRGN knockdown could reverse the promotion of HREC apoptosis induced by high glucose as well.

Conclusions

Consequently, our study implied that SRGN might serve as a promising biomarker with high specificity and sensitivity in the DR diagnosis and progression.
Effect of Body Fat on Population Pharmacokinetics of High‐Dose Methotrexate in Pediatric Patients With Acute Lymphoblastic Leukemia
Authors: Orgel Etan , Nabais Teresa , Douglas Christopher , Mittelman Steven D. , Neely Michael
Published: December 2020

Nearly all international regimens for pediatric acute lymphoblastic leukemia (ALL) incorporate intravenous “high‐dose” methotrexate (HDMTX, ≥1 g/m2) to penetrate the central nervous system. Dosing is routinely adjusted for body surface area (BSA), but limited data describe the pharmacokinetics of HDMTX, particularly in obese and/or large patients. To understand the impact of body size (BSA) and body fat percentage (BFP) on HDMTX pharmacokinetics, we performed a secondary analysis of 36 children and adolescents 10‐21 years old treated for newly diagnosed ALL and who were enrolled in a prospective study examining body composition. All patients received 5 g/m2 of HDMTX infused over 24 hours. Plasma methotrexate concentrations were measured at 24, 42, and 48 hours. At 48 hours, ≥0.4 μmol/L was defined as “delayed elimination,” necessitating prolonged supportive care. BFP was measured using dual‐energy x‐ray absorptiometry. A nonparametric population pharmacokinetic model was constructed with subsequent simulations to explore effects of BSA and BFP extremes. Despite standard BSA‐adjusted dosing, we found significant intrapatient variability in mean MTX concentration (38%; range, 1.2%‐86%). BSA and BFP were not linearly associated with increased area under the curve (AUC, P = 0.74 and P = 0.12), but both larger size (BSA) and greater obesity (BFP) were associated with an approximately 2‐fold higher risk for delayed elimination at 48 hours. HDMTX AUC was not associated with toxicity. MTX pharmacokinetics vary among and even within patients despite BSA‐adjusted dosing. Obesity and large size are identified as new risk factors for delayed elimination, requiring further investigation.
Prostatic Pharmacokinetic/Pharmacodynamic Evaluation of Ampicillin‐Sulbactam for Bacterial Prostatitis and Preoperative Prophylaxis
Authors: Onita Tetsushu , Ikawa Kazuro , Nakamura Kogenta , Nishikawa Genya , Kobayashi Ikuo , Ishihara Noriyuki , Tamaki Hiroki , Yano Takahisa , Naora Kohji , Morikawa Norifumi
Published: December 2020

This study aims to define the penetration of ampicillin and sulbactam into prostate tissue, develop a prostatic pharmacokinetic model of each drug, and assess the appropriateness of ampicillin‐sulbactam regimens for the treatment of prostatitis and the prophylaxis of postoperative infection, based on a pharmacokinetic and pharmacodynamic simulation. Subjects were prostatic hyperplasia patients prophylactically receiving a 0.5‐hour infusion of 1.5 g (1:0.5 g) or 3 g (2:1 g) ampicillin‐sulbactam before transurethral resection of the prostate. Ampicillin and sulbactam concentrations in plasma and prostate tissue were measured. The prostate tissue/plasma ratios of both ampicillin and sulbactam were approximately 0.37 (area under the drug concentration‐time curve), and penetration was similar. The prostatic population pharmacokinetic model, which included a covariate analysis, adequately predicted prostate tissue concentrations in our patient population. For therapeutic use, aiming for a bactericidal target of 50% of time above minimum inhibitory concentration (T > MIC) in prostate tissue, 3 g ampicillin‐sulbactam 4 times daily achieved ≥90% expected probability against only Enterococcus faecalis in typical patients with a creatinine clearance (CLcr) of 30 mL/min. For prophylactic use, aiming for a bacteriostatic target of 30% T > MIC, 3 g ampicillin‐sulbactam 4 times daily achieved ≥90% expected probability of attaining the bacteriostatic target against E. faecalis and Proteus species when CLcr was 30 mL/min. Based on prostatic simulations, the present study provides helpful recommendations for the treatment of bacterial prostatitis and preoperative prophylaxis in prostatectomy.
Effectiveness of a psychological intervention delivered by general nurses for alcohol use disorders in people living with HIV in Zimbabwe: a cluster randomized controlled trial
Authors: Madhombiro Munyaradzi , Kidd Martin , Dube Bazondlile , Dube Michelle , Mutsvuke Wilson , Muronzie Thabani , Zhou Danai Tavonga , Derveeuw Sarah , Chibanda Dixon , Chingono Alfred , Rusakaniko Simbarashe , Hutson Alan , Morse Gene D , Abas Melanie A , Seedat Soraya
Published: December 2020

Introduction

There have been very few randomized clinical trials of interventions for alcohol use disorders (AUD) in people living with HIV (PLWH) in African countries. This is despite the fact that alcohol use is one of the modifiable risk factors for poor virological control in PLWH on antiretroviral therapy.

Methods

Sixteen clinic clusters in Zimbabwe were selected through stratified randomization and randomized 1: 1 to Intervention and Control arms. Inclusion criteria for individual participants were being adult, living with HIV and a probable alcohol use disorder as defined by a score of 6 (women) or 7 (men) on the Alcohol Use Disorders Identification Test (AUDIT). In the Intervention clusters, participants received 8 to 10 sessions of Motivational Interviewing blended with brief Cognitive Behavioural Therapy (MI‐CBT). In the control clusters, participants received four Enhanced Usual Care (EUC) sessions based on the alcohol treatment module from the World Health Organisation mhGAP intervention guide. General Nurses from the clinics were trained to deliver both treatments. The primary outcome was a change in AUDIT score at six‐month post‐randomization. Viral load, functioning and quality of life were secondary outcomes. A random‐effects analysis‐of‐covariance model was used to account for the cluster design.

Results

Two hundred and thirty‐four participants (n = 108 intervention and n = 126 control) were enrolled across 16 clinics. Participants were recruited from November 2016 to November 2017 and followed through to May 2018. Their mean age was 43.3 years (SD = 9.1) and 78.6% (n = 184) were male. At six months, the mean AUDIT score fell by −6.15 (95% CI −6.32; −6.00) in the MI‐CBT arm, compared to a fall of − 3.09 95 % CI − 3.21; −2.93) in the EUC arm (mean difference −3.09 (95% CI −4.53 to −1.23) (p = 0.05). Viral load reduced and quality of life and functioning improved in both arms but the difference between arms was non‐significant.

Conclusions

Interventions for hazardous drinking and AUD comprising brief, multiple alcohol treatment sessions delivered by nurses in public HIV facilities in low‐income African countries can reduce problematic drinking among PLWH. Such interventions should be integrated into the primary care management of AUD and HIV and delivered by non‐specialist providers. Research is needed on cost‐effectiveness and implementation of such interventions, and on validation of cut‐points for alcohol use scales in low resource settings, in partnership with those with lived experience of HIV and AUD.
Impacts of convectively coupled equatorial waves on rainfall extremes in Java, Indonesia
Authors: Lubis Sandro W. , Respati Muhamad R.
Published: December 2020

Rainfall extremes cause significant socioeconomic impacts in Indonesia, as they are often followed by disastrous events, such as floods and landslides. Of particular interest is Java Island, the most populated region in Indonesia, which is prone to damaging flooding as a result of heavy rainfall. The prediction of rainfall extremes in this region has mainly been focused on the effects of seasonal and intraseasonal variability, such as monsoons and the Madden–Julian Oscillation. Here, using an extensive station database from 1987 to 2017 and the gridded Asian Precipitation‐Highly Resolved Observational Data Integration Toward Evaluation of Water Resources (APHRODITE) product from 1980 to 2007, we show that severe weather conditions associated with rainfall extremes in Java during the rainy season (November to April) can also be attributed to convectively coupled equatorial waves (CCEWs) that occur on a shorter time scale.

Evidence is presented that CCEWs, including Kelvin, equatorial Rossby (ER), and mixed Rossby‐gravity (MRG) waves, significantly modulate daily rainfall extremes over Java Island. Of these three types, the Kelvin waves have the greatest influence on heavy rainfall over Java Island. The convectively active (suppressed) phases of Kelvin waves increase (decrease) the probability of extreme rain events over land regions by up to 60% (50%) of the baseline probability. On the other hand, the convectively active phases of ER (MRG) waves increase the probability by up to 45% (40%), while the suppressed phases decrease this by up to 40% (30%). In terms of the mechanism of rainfall extremes, CCEWs modulate moisture flux convergence, leading to the enhancement of local convection over the region. In addition, the analysis of multiple wave events indicates that positive (negative) interferences of the CCEWs lead to an amplification (suppression) of extreme rainfall probability. Overall, the results suggest that equatorial waves provide an important source of the predictability for daily extreme rainfall events over Java Island.
Interdecadal change in the relationship of Indochina Peninsula May precipitation to ENSO
Authors: Wu Renguang , Zhu Peijun
Published: December 2020

The present study detected an obvious interdecadal change in the relationship of Indochina Peninsula (ICP) May precipitation to El Niño‐Southern Oscillation (ENSO). During the 1950s through the late‐1970s, more (less) ICP precipitation tends to occur in May of La Niña (El Niño) developing years, whereas after the late‐1990s, more (less) ICP precipitation tends to appear in May of La Niña (El Niño) decaying years. During the late‐1970s through the late‐1990s, more (less) ICP precipitation occurs in May of La Niña (El Niño) persisting years. The interdecadal change in the ICP May precipitation‐ENSO relationship is related to two factors. One factor is the developing time of ENSO events. During the 1950s through the late‐1970s, ENSO events develop earlier with larger equatorial central‐eastern Pacific sea surface temperature (SST) anomalies in May. SST‐induced lower‐level wind anomalies extend northwestward from the equatorial central Pacific to the ICP. After the late‐1990s, ENSO events develop later with smaller equatorial central‐eastern Pacific SST anomalies in May. SST‐induced lower‐level wind anomalies are confined to the Pacific region. The other factor is the tropical Indo‐Pacific SST anomaly pattern. During the ENSO decaying years after the late‐1990s, opposite SST anomalies in the North Indian Ocean and central North Pacific work together to induce stronger wind anomalies over the ICP in May. In contrast, during the ENSO decaying years during the 1950s through the late‐1970s, wind anomalies are weaker over the ICP in May under the sole influence of the North Indian Ocean SST anomalies.
Phrenic nerve conduction study to diagnose unilateral diaphragmatic paralysis
Authors: Reynaud Vivien , Prigent Hélène , Mulliez Aurélien , Durand Marie‐Christine , Lofaso Frédéric
Published: December 2020

Background

Unilateral diaphragmatic paralysis (UDP) has major clinical and etiological implications and, therefore, is important to diagnose. Lung function tests and invasive transdiaphragmatic pressure (Pdi) measurements are widely used to this end but, contrary to phrenic nerve conduction study (NCS), they require volitional maneuvers and/or may be poorly tolerated by patients. The purpose of this study was to compare the diagnostic accuracy of Pdi and phrenic NCS for UDP.

Methods

We retrospectively reviewed 28 patients with suspected UDP. The diagnosis established during a multidisciplinary meeting was the reference standard.

Results

Phrenic NCS correlated well with Pdi (r = 0.82, P < .005), and the two tests showed good agreement (κ = 0.82, P < .005). Phrenic NCS and Pdi measurements both had 95% sensitivity, 87.5% specificity, 95% positive predictive, and 87.5% negative predictive values.

Conclusions

Both tests were highly sensitive and specific. Phrenic NCS measurement is a simple, reproducible, noninvasive method whose results correlate well with Pdi and provide insight into the UDP mechanism. In the most difficult cases, combining lung function tests, respiratory muscle assessments, and phrenic NCS can help to establish the diagnosis.
Quantifying Consumption of Native Fishes by Nonnative Channel Catfish in a Desert River
Authors: Hedden S. C. , Gido K. B. , Hedden C. K. , Pennock C. A. , Duran B. R. , Hines B. A. , Gilbert E. I. , McKinstry M. C. , Durst S. L. , Franssen N. R.
Published: December 2020

The establishment of nonnative predators can have devastating consequences for native fish communities, but predation rates are often difficult to quantify due to spatial and temporal variation in predator foraging behavior. Predation by Channel Catfish Ictalurus punctatus throughout the Colorado River basin potentially threatens the recovery of native fishes. Because Channel Catfish are highly opportunistic feeders, an understanding of how piscivory by this species impacts prey populations should help to guide management in invaded systems. We used laboratory observations to model temperature-dependent stomach evacuation rates and combined those estimates with field-collected diet data to derive annual consumption across a 152-km reach of the San Juan River (New Mexico, Colorado, and Utah). In the field, stomach fullness increased with water temperature while the probability of observing fish prey in the diet increased with TL of Channel Catfish and water turbidity. Based on estimates of daily ration, diet composition, and Channel Catfish population demographics, we estimated the San Juan River population’s fish consumption to be 4.9 kg·ha−1·year−1 (95% CI = 4.0–6.1 kg·ha−1·year−1) in 2018 and 2.3 kg·ha−1·year−1 (95% CI = 1.8–2.8 kg·ha−1·year−1) in 2019. Native fishes accounted for 54% of the fish biomass consumed, which included two incidents of endangered Colorado Pikeminnow Ptychocheilus lucius consumption. Although these estimates should help managers to assess the predatory threat of Channel Catfish, additional information, such as the efficacy of nonnative control and prey population compensatory responses, will likely be necessary to develop robust management strategies aimed at reducing the predatory impacts of this nonnative species on native fish assemblages.
Cluster sampling for Morris method made easy
Authors: Shi Wen , Chen Xi
Published: December 2020

In this paper we provide a thorough investigation of the cluster sampling scheme for Morris' elementary effects method (MM), a popular model‐free factor screening method originated in the setting of design and analysis of computational experiments. We first study the sampling mechanism underpinning the two sampling schemes of MM (i.e., cluster sampling and noncluster sampling) and unveil its nature as a two‐level nested sampling process. This in‐depth understanding sets up a foundation for tackling two important aspects of cluster sampling: budget allocation and sampling plan. On the one hand, we study the budget allocation problem for cluster sampling under the analysis of variance framework and derive optimal budget allocations for efficient estimation of the importance measures. On the other hand, we devise an efficient cluster sampling algorithm with two variants to achieve enhanced statistical properties. The numerical evaluations demonstrate the superiority of the proposed cluster sampling algorithm and the budget allocations derived (when used both separately and in conjunction) to existing cluster and noncluster sampling schemes.
Quality of life among frail older persons (65+ years) in nursing homes: A cross‐sectional study
Authors: Sandgren Anna , Arnoldsson Lisa , Lagerholm Annika , Bökberg Christina
Published: December 2020

Aim

To assess the quality of life in frail older persons (65+ years) living in nursing homes and to examine differences between quality of life perceptions among different gender and age groups.

Design

Cross‐sectional.

Methods

Data were collected during 2015‐2017 based on two questionnaires (WHOQOL‐OLD and WHOQOL‐BREF). Seventy‐eight older persons living in nursing homes in southern Sweden answered the questionnaires in structured interviews. Descriptive and comparative statistics were used to analyse the data. The study was guided by Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) guidelines.

Results

The frail older persons reported low autonomy related to few opportunities to engage in everyday activities and were unable to do the things they liked to do and not feeling in control of their future. Another important result was that frail older persons seemed to have no or little fear of death and dying. No significant differences between gender or age on quality of life were revealed.
Simultaneous phase change energy storage and thermoresponsive shape memory properties of porous poly(vinyl alcohol)/phase change microcapsule composites
Authors: Ma Chao‐Qun , Shi Wen‐Zhao , Liu Jin‐Shu , Xing Jian‐Wei , Li Su‐Song , Huang Ya‐Yi
Published: December 2020

Porous poly(vinyl alcohol) (PVA)/phase change microcapsule composites with shape memory properties were prepared by physical foaming, cycles of freezing–thawing and freeze drying. The effects of phase change microcapsules on pore structure, phase change energy storage capacity, thermal stability, crystallinity, mechanical properties, shape memory properties and water absorption and retention of the porous composites were investigated. With an increase of the proportion of phase change microcapsules, the pore density, pore size and water absorption and retention of the porous composite materials were decreased, while the phase change energy storage performance was improved and ΔHm was up to 31.22 J g−1. The phase change energy storage of the porous composites was stable even after 50 phase transition cycles. Meanwhile, the thermal stability of the porous composites was also not affected by the addition of phase change microcapsules. The entanglement of PVA molecular chains in the porous composites was affected by the microcapsules embedded in the matrix of PVA during freezing–thawing cycles, resulting in a change of crystallinity and mechanical properties of the porous composites. The porous composites with phase change energy storage capacity also showed good shape memory performance with shape recovery rate of 100% even after multiple deformation, which was expected to expand the multi‐field application of dual‐functional materials. © 2020 Society of Chemical Industry