bluuebunny/crossref_metadata_2025 huggingface dataset:
The WHOQOL-BREF instrument: Psychometric evaluation of the Greek version in patients with advanced cancer and pain and associations with psychological distress
Authors: Siafaka Vassiliki , Mavridis Dimitris , Tsonis Orestis , Tzamakou Eleftheria , Christogiannis Christos , Tefa Louiza , Arnaoutoglou Eleni , Tzimas Petros , Pentheroudakis George
Published: August 2022

Objectives

Assessment of the psychometric characteristics of the Greek version of the brief World Health Organization Quality of Life Instrument (WHOQOL-BREF) in patients with advanced cancer and pain, and exploration of the association between psychological distress and quality of life (QoL).

Method

The sample consisted of 145 patients with advanced cancer and pain who completed the WHOQOL-BREF, the Symptom Checklist-90 (SCL-90), and the Pain Visual Analogue Scale (VAS). In analysis, the following methods were used: Cronbach's alpha, Item Response Theory (IRT), polychoric, Pearson and polyserial correlation, t-test, and Linear regression.

Results

The internal consistency was high for all domains of the WHOQOL-BREF (Cronbach's α ≥ 0.731). Similarly, with the exception of three items, the WHOQOL-BREF items has large discrimination parameters suggesting that they have a high ability in differentiating subjects. On SCL-90, the three dimensions with the highest scores were Depression, Somatization, and Anxiety. The overall score for psychological distress, the Global Severity Index (GSI), showed significant negative association with all the WHOQOL-BREF factor scores (Physical Health: B = −1.488, p < 0.001, Psychological Health: B = −1.688, p < 0.001, Social Relationships: B = −0.910, p < 0.001, Environment: B = −1.064, p < 0.001). Male gender was associated with lower scores for Social Relationships (B = −0.358, p = 0.007) and Environment (B = −0.293, p = 0.026).

Significance of results

The Greek version of the WHOQOL-BREF showed good psychometric properties in patients with advanced cancer and can be used as a reliable instrument in clinical practice. The level of psychological distress can be considered a determinant of QoL in patients with advanced cancer and pain, independently of pain intensity or other clinical characteristics. In cancer, the disease process can activate multiple physiological and psychological mechanisms that lead to a wide range of symptoms of psychological distress. To improve their QoL, psychological intervention focused on the identification and alleviation of psychological distress in patients with advanced cancer, and help in finding meaning in their experience, should be provided.
Clinical wisdom in the age of computer apps: a systematic review of four functions that may complement clinical treatment
Authors: Pacheco Catalina R. , Scheeringa Michael S.
Published: August 2022

Mental health clinicians perform complex tasks with patients that potentially could be improved by the massive computing power available through mobile apps. This study aimed to analyse commercially available mobile and computer applications (apps) focused on treating psychiatric disorders. Apps were analysed by two independent raters for whether they took advantage of computer power to process data in a fashion that augments four main elements of clinical treatment including (1) assessment/diagnosis, (2) treatment planning, (3) treatment fidelity monitoring, and (4) outcome tracking. The evidence base for each of these apps was also explored via PsychINFO, Research Gate and Google Scholar. Searches of the Google Play Store, the Apple App Store, and the One Mind PsyberGuide found 722 apps labelled for mental health use, of which 163 apps were judged relevant to clinical work with patients with psychiatric disorders. Fifty-nine of these were determined to contain a computer-driven function for at least one of the four main elements of clinical treatment. The most common element was assessment/diagnosis (55/59 apps), followed by outcome tracking (34/59 apps). Six apps updated treatment plans using user input. Only one app tracked treatment fidelity. None of the apps contained computer-driven functions for all four elements. Twelve apps were supported in randomized clinical trials to show greater efficacy compared with either wait-list or other active treatments. Results showed that these four clinical elements can be meaningfully augmented, but the full potential of computer processing appears unreached in mental health-related apps.

Key learning aims

(1)

To understand what apps are currently available to treat clinical-level psychiatric problems.

(2)

To understand how many of the commercially available mental health-focused apps can be used for the treatment of clinical populations.

(3)

To understand how mental health services can be complemented by utilizing computer processing power within apps.
Sprunggelenksinstabilität
Authors: Gaber Sonja , Knupp Markus
Published: August 2022

Zusammenfassung. Bandverletzungen des Sprunggelenkes zählen zu den häufigsten Verletzungen des Bewegungsapparates und werden auf der Notfallstation oder in der hausärztlichen Praxis oft behandelt. In den überwiegenden Fällen sind die lateralen Kollateralbänder betroffen. Korrekt behandelt haben Sprunggelenksdistorsionen eine gute Prognose, in ca. 80% der Fälle kann eine vollständige Rehabilitation erreicht werden. Risikofaktoren für die Entwicklung einer chronischen Sprunggelenksinstabilität sind eine ungenügende Nachbehandlung nach der akuten Bandverletzung, Verletzungen des Ligamentum deltoideum, eine Hyperlaxität oder Rückfussfehlstellungen (z.B. Pes cavovarus). Die adäquate Diagnostik und Behandlung einer Sprunggelenksdistorsion können das Risiko von langwierigen Verläufen und Spätschäden minimieren. Zur Abklärung nach einem akutem Distorsionsereignis gehören neben der Anamnese und klinischen Untersuchung auch bildgebende Verfahren, welche unter anderem Begleitverletzungen wie Frakturen, Knorpelläsionen oder Sehnenverletzungen ausschliessen sollen. Die Therapie der akuten Sprunggelenksdistorsion ist meist konservativ. In Abhängigkeit vom Schweregrad erfolgen eine Stabilisierung des Sprunggelenkes mit einer Bandage, einer Orthese für das obere Sprunggelenk (OSG), einem Stabilschuh oder die Ruhigstellung in einem Walker oder Gips. Eine chronische Instabilität stellt potenziell eine Präarthrose dar und kann bei Versagen der konservativen Therapie eine operative Stabilisierung des Sprunggelenkes notwendig machen.
Evaluation of the CMIP6 Precipitation Simulations Over Global Land
Authors: Li Zhengyang , Liu Tie , Huang Yue , Peng Jiabin , Ling Yunan
Published: August 2022

Precipitation's temporal and spatial patterns under climate change significantly impact global terrestrial ecology and human social activities. Climate models are essential tools for assessing the impacts of climate change and formulating policies to address climate change. The evaluation results of historical climate model simulations can represent the reliability of their future simulations. This study evaluated the simulation capabilities of 41 historical All‐Forcing monthly precipitation simulations and three integrated models over global land in the Coupled Model Comparison Project Phase 6 (CMIP6). The results show that the simulation capability of global climate models (GCMs) in CMIP6 is highly variable overland around the world. This variability is manifested in two aspects: the spatial variability of the comprehensive simulation ability of each model in different geographical regions and climatic zones of the world and the significant difference in the simulation ability of different models in each region. These GCMs generally overestimate global monthly precipitation over land, with the exception of southeast Asia and tropical rainforest climate (Af), where all models underestimate monthly precipitation. Some GCMS can perform well regionally but poorly on the global scale. One example shows that EC‐Earth3's best capability at Cwc climatic zone, surpassing the integrated model, but failed to rank in the top 10 in 22 of the 29 climate zones. Our results highlight the need to select appropriate models for integration when conducting climate change studies at global and regional scales as a critical factor in studying climate change predictions.
Vertical Structure in Phytoplankton Growth and Productivity Inferred From Biogeochemical‐Argo Floats and the Carbon‐Based Productivity Model
Authors: Arteaga Lionel A. , Behrenfeld Michael J. , Boss Emmanuel , Westberry Toby K.
Published: August 2022

Estimates of marine net primary production (NPP) commonly rely on limited in situ 14C incubations or satellite‐based algorithms mainly constrained to the surface ocean. Here we combine data from biogeochemical Argo floats with a carbon‐based productivity model (CbPM) to compute vertically resolved estimates of NPP. Inferred NPP profiles derived by informing the CbPM with float‐based, depth‐resolved, bio‐optical data are able to qualitatively reproduce the vertical structure in NPP inferred from in situ 14C incubations at various ocean regions. At station ALOHA, float‐based estimates agree within uncertainty with productivity observations at depth, but underestimate surface NPP. We test the ability of the CbPM to infer the depth‐resolved structure in NPP from bio‐optical properties in the mixed layer, in similar fashion as how remote sensing algorithms of ocean productivity operate. In Southern Ocean waters, the depth‐reconstructing implementation of the CbPM overestimates phytoplankton division rates and Chl:C below the mixed layer, resulting in artificially high subsurface NPP when compared with the fully float‐informed implementation of the model. The CbPM subsurface extrapolation of phytoplankton Chl, Chl:C, division rates, and NPP improves by accounting for deep nutrient (iron) stress impacts on photoacclimation in the Southern Ocean. This improvement is also observed in vertically integrated NPP, where the mean bias between model implementations in depth‐integrated productivity south of 30°S is reduced by 62% when account for deep iron limitation. Our results demonstrate that profiling data from biogeochemical Argo floats can serve to inform regional adjustments that lead to the improvement of marine productivity algorithms.
Separating Annual, Interannual and Regional Change in Sea Surface Temperature in the Northeastern Atlantic and Nordic Seas
Authors: Saes Mischa J. M. , Gjelstrup Caroline V. B. , Visser Andre W. , Stedmon Colin A.
Published: August 2022

Sea surface temperature (SST) in the Northeastern North Atlantic and Nordic Seas exhibits pronounced variability across seasonal to decadal time scales. These changes can be expected to be driven by a combination of altered local conditions, shifts in seasonality and large‐scale regional oceanographic change. Separating the contribution from each of these offers insight into how the region is changing. Here, we present the result of an analysis of weekly satellite‐derived SST data from 1979 to 2020. An empirical orthogonal function (EOF) analysis allows us to separate observed changes in SST into independent underlying timeseries. Each timeseries explains part of the variability in SST. EOF1 can be allocated with changes in seasonality and a long‐term warming trend, with summer maxima warming with twice the rate (0.043°C year−1) compared to winter minima (0.023°C year−1). EOF2 is associated with the North Atlantic subpolar gyre and the North Atlantic Oscillation, affecting the Atlantic Water flow across the Greenland‐Scotland Ridge, imposing a dipole cooling/warming pattern. Local sea‐ice melt along the southeast Greenland shelf is represented by EOF3, and finally the influx of warmer water with the North Icelandic Irminger Current is captured by EOF4. Each of these disaggregated signals differ considerably in their contribution to driving temporal and spatial trends in SST. The isolated signals offer a high‐resolution long‐time series of valuable indicators of oceanographic change which will likely be reflected in biogeochemistry, plankton, fish, mammals, and seabirds in the region.
The Importance of Storm Surge for Sediment Delivery to Microtidal Marshes
Authors: Zhu Qingguang , Wiberg Patricia L.
Published: August 2022

Storm surge has the potential to significantly increase suspended sediment flux to microtidal marshes. However, the overall effects of storm surge on microtidal marsh deposition have not been well quantified, with most modeling studies focusing on regular (astronomical) tidal flooding. Here we applied the Delft3D model to a microtidal bay‐marsh complex in Hog Bay, Virginia to quantify the contributions of storm surge to marsh deposition. We validated the model using spatially distributed hydrodynamic and suspended sediment data collected from the site and ran model simulations under different storm surge conditions with/without storm‐driven water level changes. Our results show that episodic storm surge events occurred 5% of the time at our study site, but contributed 40% of marsh deposition during 2009–2020. Our simulations illustrate that while wind‐driven waves control sediment resuspension on tidal flats, marsh deposition during storms was largely determined by tidal inundation associated with storm‐driven water levels. A moderate storm surge event can double sediment flux to most marshes around the bay and deliver more sediment to the marsh interior compared to simulations that include wind waves but not storm surge variations in water levels. Simulations of bay and marsh response to different storm surge events with varying magnitude of storm surge intensity reveal that total marsh deposition around the bay increased linearly with storm surge intensity, suggesting that future changes to storm magnitude and/or frequency would have significant implications for sediment supply to marshes at our study site.
Cerebrospinal fluid proteomic study of two bipolar disorder cohorts
Authors: Isgren Anniella , Göteson Andreas , Holmén-Larsson Jessica , Pelanis Aurimantas , Sellgren Carl , Joas Erik , Sparding Timea , Zetterberg Henrik , Smedler Erik , Jakobsson Joel , Landén Mikael
Published: August 2022

The pathophysiology of bipolar disorder remains to be elucidated and there are no diagnostic or prognostic biomarkers for the condition. In this explorative proteomic study, we analyzed 201 proteins in cerebrospinal fluid (CSF) from mood stable bipolar disorder patients and control subjects sampled from two independent cohorts, amounting to a total of 204 patients and 144 controls. We used three Olink Multiplex panels, whereof one specifically targets immune biomarkers, to assess a broad set of CSF protein concentrations. After quality control and removal of proteins with a low detection rate, 105 proteins remained for analyses in relation to case–control status and clinical variables. Only case–control differences that replicated across cohorts were considered. Results adjusted for potential confounders showed that CSF concentrations of growth hormone were lower in bipolar disorder compared with controls in both cohorts. The effect size was larger when the analysis was restricted to bipolar disorder type 1 and controls. We found no indications of immune activation or other aberrations. Growth hormone exerts many effects in the central nervous system and our findings suggest that growth hormone might be implicated in the pathophysiology of bipolar disorder.
Genomic insights into the phylogeny and biomass-degrading enzymes of rumen ciliates
Authors: Li Zongjun , Wang Xiangnan , Zhang Yu , Yu Zhongtang , Zhang Tingting , Dai Xuelei , Pan Xiangyu , Jing Ruoxi , Yan Yueyang , Liu Yangfan , Gao Shan , Li Fei , Huang Youqin , Tian Jian , Yao Junhu , Xing XvPeng , Shi Tao , Ning Jifeng , Yao Bin , Huang Huoqing , Jiang Yu
Published: August 2022

Understanding the biodiversity and genetics of gut microbiomes has important implications for host physiology and industrial enzymes, whereas most studies have been focused on bacteria and archaea, and to a lesser extent on fungi and viruses. One group, still underexplored and elusive, is ciliated protozoa, despite its importance in shaping microbiota populations. Integrating single-cell sequencing and an assembly-and-identification pipeline, we acquired 52 high-quality ciliate genomes of 22 rumen morphospecies from 11 abundant morphogenera. With these genomes, we resolved the taxonomic and phylogenetic framework that revised the 22 morphospecies into 19 species spanning 13 genera and reassigned the genus Dasytricha from Isotrichidae to a new family Dasytrichidae. Comparative genomic analyses revealed that extensive horizontal gene transfers and gene family expansion provided rumen ciliate species with a broad array of carbohydrate-active enzymes (CAZymes) to degrade all major kinds of plant and microbial carbohydrates. In particular, the genomes of Diplodiniinae and Ophryoscolecinae species encode as many CAZymes as gut fungi, and ~80% of their degradative CAZymes act on plant cell-wall. The activities of horizontally transferred cellulase and xylanase of ciliates were experimentally verified and were 2–9 folds higher than those of the inferred corresponding bacterial donors. Additionally, the new ciliate dataset greatly facilitated rumen metagenomic analyses by allowing ~12% of the metagenomic sequencing reads to be classified as ciliate sequences.
Confidence bands in survival analysis
Authors: Sachs Michael C. , Brand Adam , Gabriel Erin E.
Published: August 2022

Background

Providing estimates of uncertainty for statistical quantities is important for statistical inference. When the statistical quantity of interest is a survival curve, which is a function over time, the appropriate type of uncertainty estimate is a confidence band constructed to account for the correlation between points on the curve, we will call this a simultaneous confidence band. This, however, is not the type of confidence band provided in standard software, which is constructed by joining the confidence intervals at given time points.

Methods

We show that this type of band does not have desirable joint/simultaneous coverage properties in comparison to simultaneous bands.

Results

There are different ways of constructing simultaneous confidence bands, and we find that bands based on the likelihood ratio appear to have the most desirable properties. Although there is no standard software available in the three major statistical packages to compute likelihood-based simultaneous bands, we summarise and give code to use available statistical software to construct other simultaneous forms of bands, which we illustrate using a study of colon cancer.

Conclusions

There is a need for more user-friendly statistical software to compute simultaneous confidence bands using the available methods.
ESE3-positive PSCs drive pancreatic cancer fibrosis, chemoresistance and poor prognosis via tumour–stromal IL-1β/NF–κB/ESE3 signalling axis
Authors: Zhao Tiansuo , Xiao Di , Jin Fanjie , Sun Xugang , Yu Jie , Wang Hongwei , Liu Jing , Cai Wenrun , Huang Chongbiao , Wang Xiuchao , Gao Song , Liu Zhe , Yang Shengyu , Gao Chuntao , Hao Jihui
Published: August 2022

Background

Desmoplastic stroma, a feature of pancreatic ductal adenocarcinoma (PDAC), contains abundant activated pancreatic stellate cells (PSCs). How PSCs promote PDAC progression remains incompletely understood.

Methods

Effect of epithelium-specific E-twenty six factor 3 (ESE3)-positive PSCs on PDAC fibrosis and chemoresistance was examined by western blot, RT-PCR, immunofluorescence, flow cytometry assay, chromatin immunoprecipitation, luciferase assay, immunohistochemistry and subcutaneous pancreatic cancer mouse model.

Results

ESE3 expression increased in PSCs in PDAC tissues compared with those in normal PSCs. Clinical data showed that ESE3 upregulation in PSCs was positively correlated with tumour size, pTNM stage, CA19-9, carcinoembryonic antigen and serum CA242 level. ESE3 overexpression in PSCs was an independent negative prognostic factor for disease-free survival and overall survival amongst patients with PDAC. Mechanistically, the conditional medium from the loss and gain of ESE3-expressing PSCs influenced PDAC chemoresistance and tumour growth. ESE3 directly induced the transcription of α-SMA, collagen-I and IL-1β by binding to ESE3-binding sites on their promoters to activate PSCs. IL-1β upregulated ESE3 in PSCs through NF-κB activation, and ESE3 was required for PSC activation by tumour cell-derived IL-1β.

Conclusion

Inhibiting the IL-1β/ESE3 (PSCs)/IL-1β-positive feedback loop is a promising therapeutic strategy to reduce tumour fibrosis and increase chemotherapeutic efficacy in PDAC.
Accelerated prediction of atomically precise cluster structures using on-the-fly machine learning
Authors: Wang Yunzhe , Liu Shanping , Lile Peter , Norwood Sam , Hernandez Alberto , Manna Sukriti , Mueller Tim
Published: August 2022

The chemical and structural properties of atomically precise nanoclusters are of great interest in numerous applications, but predicting the stable structures of clusters can be computationally expensive. In this work, we present a procedure for rapidly predicting low-energy structures of nanoclusters by combining a genetic algorithm with interatomic potentials actively learned on-the-fly. Applying this approach to aluminum clusters with 21 to 55 atoms, we have identified structures with lower energy than any reported in the literature for 25 out of the 35 sizes. Our benchmarks indicate that the active learning procedure accelerated the average search speed by about an order of magnitude relative to genetic algorithm searches using only density functional calculations. This work demonstrates a feasible way to systematically discover stable structures for large nanoclusters and provides insights into the transferability of machine-learned interatomic potentials for nanoclusters.
Performance of glass fiber reinforced polyamide composites exposed to bioethanol fuel at high temperature
Authors: Wei Xin-Feng , Kallio Kai J. , Olsson Richard T. , Hedenqvist Mikael S.
Published: August 2022

The increasing use of bioethanol fuel, as a promising carbon-neutral alternative to petroleum-based gasoline, has raised concerns on compatibility issues between bioethanol and the polymer components used in the automotive fuel system. Here, the performance of two commercial glass-fiber reinforced polyamide composites (polyamide 12 (PA12) and an aromatic highly-biobased polyamide (polyphthalamide, PPA)) exposed to a mixture of ethanol and gasoline (E25 fuel), was investigated at high temperature (120 °C). The polyamide matrices showed a fast and remarkably high fuel uptake. The sorbed fuel had a strong plasticizing effect on both materials, as revealed by the large decrease in the glass transition temperature and a 60% decrease in stiffness and strength. The PPA, however, sustained degradation better than the PA12, which experienced swelling-induced surface cracking and oxidation-induced embrittlement. The results suggest that care should be taken when using polyamide composites in ethanol-based fuel applications at this high temperature level.
Plastic injection molding dies using hybrid additively manufactured 420/CX stainless steels: electrochemical considerations
Authors: Shahriari Ayda , Samei Javad , Sanjari Mehdi , Jahanbakht Mohammad , Amirkhiz Babak Shalchi , Mohammadi Mohsen
Published: August 2022

This research focused on the corrosion resistance and microstructure of hybrid additively manufactured (HAM) samples of AISI 420/CX (420/CX SS) stainless steels. Potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and Mott–Schottky analyses as well as the electrochemical noise (EN) technique were used to evaluate the electrochemical behavior of the as-built and heat-treated HAM parts in NaCl solution. The results showed a more protective passive layer formed on the CX SS side. The distribution of Cr-rich M23C6carbides in matrix of 420 SS side resulted in a lower corrosion resistance compared to the CX SS side. The noise data analysis confirmed an increase in the galvanic currents of the HAM parts after heat treatment. The stochastic analysis revealed the interface in the heat-treated condition increases pit growth more than the as-built one due to the evolution of nano-sized intermetallic compounds of Al-N/ (Cr, Nb) (N, C) at the heat-treated interface area.
An online survey of primary care physicians’ knowledge of common respiratory diseases in China
Authors: Pan Zihan , Yang Ting , Chi Chunhua , Chen Yahong , Liao Jiping , Huang Kewu , Williams Siân , Wang Chen
Published: August 2022

China has a huge population with respiratory diseases, these diseases should be managed well in primary care, however, primary care physicians’ knowledge level of these diseases were unknown. The aim of the study was to assess primary care physicians’ knowledge of asthma, CAP, COPD, and influenza in China. An e-questionnaire was distributed to attendees of respiratory diseases academic conferences in China from July, 2017 to December, 2018. 7391 questionnaires were returned and 4815 valid questionnaires were analyzed, 3802 (79.0%) from community health service centers and 1013 (21.0%) from township hospitals. The average score of the questionnaire was 83.3 (±20.397) and 72.1 (±20.898) in township and community hospitals, respectively (P < 0.05). 61.4%, 48.7%, and 42.5% of the primary care physicians were aware of clinical manifestations of COPD, asthma, and simple influenza. 85.7%, 8.1%, 16.1%, and 1.0% knew how to diagnose COPD, asthma, CAP and influenza, respectively. 94.4% of the physicians lacked the knowledge of treating COPD with bronchodilators; 53.7% knew non-pharmacological treatments for COPD. 73.6% were unable to deal with asthma attacks. 65.1% did not know what the most essential and important treatment for influenza was. 92% of physicians did not know the management for stable COPD; 3.0% knew all prevention and management measures for asthma. 37.9% knew all the preventive measures for CAP. 44.9% did not know the important role of influenza vaccine in preventing influenza and its complications. Primary care physicians in China had a poor knowledge of CAP, asthma, Influenza, COPD. There is a need for improved training of common respiratory diseases.
Vasculogenesis in kidney organoids upon transplantation
Authors: Koning Marije , Dumas Sébastien J. , Avramut M. Cristina , Koning Roman I. , Meta Elda , Lievers Ellen , Wiersma Loes E. , Borri Mila , Liang Xue , Xie Lin , Liu Ping , Chen Fang , Lin Lin , Luo Yonglun , Mulder Jaap , Spijker H. Siebe , Jaffredo Thierry , van den Berg Bernard M. , Carmeliet Peter , van den Berg Cathelijne W. , Rabelink Ton J.
Published: August 2022

Human induced pluripotent stem cell-derived kidney organoids have potential for disease modeling and to be developed into clinically transplantable auxiliary tissue. However, they lack a functional vasculature, and the sparse endogenous endothelial cells (ECs) are lost upon prolonged culture in vitro, limiting maturation and applicability. Here, we use intracoelomic transplantation in chicken embryos followed by single-cell RNA sequencing and advanced imaging platforms to induce and study vasculogenesis in kidney organoids. We show expansion of human organoid-derived ECs that reorganize into perfused capillaries and form a chimeric vascular network with host-derived blood vessels. Ligand-receptor analysis infers extensive potential interactions of human ECs with perivascular cells upon transplantation, enabling vessel wall stabilization. Perfused glomeruli display maturation and morphogenesis to capillary loop stage. Our findings demonstrate the beneficial effect of vascularization on not only epithelial cell types, but also the mesenchymal compartment, inducing the expansion of ´on target´ perivascular stromal cells, which in turn are required for further maturation and stabilization of the neo-vasculature. The here described vasculogenic capacity of kidney organoids will have to be deployed to achieve meaningful glomerular maturation and kidney morphogenesis in vitro.
Diagnosis of paediatric tuberculosis by optically detecting two virulence factors on extracellular vesicles in blood samples
Authors: Zheng Wenshu , LaCourse Sylvia M. , Song Bofan , Singh Dhiraj Kumar , Khanna Mayank , Olivo Juan , Stern Joshua , Escudero Jaclyn N. , Vergara Carlos , Zhang Fangfang , Li Shaobai , Wang Shu , Cranmer Lisa M. , Huang Zhen , Bojanowski Christine M. , Bao Duran , Njuguna Irene , Xiao Yating , Wamalwa Dalton C. , Nguyen Duc T. , Yang Li , Maleche-Obimbo Elizabeth , Nguyen Nhung , Zhang Lili , Phan Ha , Fan Jia , Ning Bo , Li Chenzhong , Lyon Christopher J. , Graviss Edward A. , John-Stewart Grace , Mitchell Charles D. , Ramsay Alistair J. , Kaushal Deepak , Liang Rongguang , Pérez-Then Eddy , Hu Tony Y.
Published: August 2022

Sensitive and specific blood-based assays for the detection of pulmonary and extrapulmonary tuberculosis would reduce mortality associated with missed diagnoses, particularly in children. Here we report a nanoparticle-enhanced immunoassay read by dark-field microscopy that detects twoMycobacterium tuberculosisvirulence factors (the glycolipid lipoarabinomannan and its carrier protein) on the surface of circulating extracellular vesicles. In a cohort study of 147 hospitalized and severely immunosuppressed children living with HIV, the assay detected 58 of the 78 (74%) cases of paediatric tuberculosis, 48 of the 66 (73%) cases that were missed by microbiological assays, and 8 out of 10 (80%) cases undiagnosed during the study. It also distinguished tuberculosis from latent-tuberculosis infections in non-human primates. We adapted the assay to make it portable and operable by a smartphone. With further development, the assay may facilitate the detection of tuberculosis at the point of care, particularly in resource-limited settings.
Fluorescent molecularly imprinted polymer particles for glyphosate detection using phase transfer agents
Authors: Kimani Martha , Kislenko Evgeniia , Gawlitza Kornelia , Rurack Knut
Published: August 2022

In this work, molecular imprinting was combined with direct fluorescence detection of the pesticide Glyphosate (GPS). Firstly, the solubility of highly polar GPS in organic solvents was improved by using lipophilic tetrabutylammonium (TBA+) and tetrahexylammonium (THA+) counterions. Secondly, to achieve fluorescence detection, a fluorescent crosslinker containing urea-binding motifs was used as a probe for GPS-TBA and GPS-THA salts in chloroform, generating stable complexes through hydrogen bond formation. The GPS/fluorescent dye complexes were imprinted into 2–3 nm fluorescent molecularly imprinted polymer (MIP) shells on the surface of sub-micron silica particles using chloroform as porogen. Thus, the MIP binding behavior could be easily evaluated by fluorescence titrations in suspension to monitor the spectral changes upon addition of the GPS analytes. While MIPs prepared with GPS-TBA and GPS-THA both displayed satisfactory imprinting following titration with the corresponding analytes in chloroform, GPS-THA MIPs displayed better selectivity against competing molecules. Moreover, the THA+ counterion was found to be a more powerful phase transfer agent than TBA+ in a biphasic assay, enabling the direct fluorescence detection and quantification of GPS in water. A limit of detection of 1.45 µM and a linear range of 5–55 µM were obtained, which match well with WHO guidelines for the acceptable daily intake of GPS in water (5.32 µM).
Catalytic synthesis of new pyrazolo [3,4-b] pyridine via a cooperative vinylogous anomeric-based oxidation
Authors: Sepehrmansourie Hassan , Zarei Mahmoud , Zolfigol Mohammad Ali , Babaee Saeed , Azizian Saeid , Rostamnia Sadegh
Published: August 2022

In this study, a novel nano-magnetic metal–organic frameworks based on Fe3O4 namely Fe3O4@MIL-101(Cr)-N(CH2PO3)2 was synthesized and fully characterized. The prepared sample was used as catalyst in the synthesis of pyrazolo [3,4-b] pyridines as convenient medicine by condensation reaction of aldehydes, 5-(1H-Indol-3-yl)- 2H-pyrazol-3-ylamine and 3-(cyanoacetyl)indole via a CVABO. The products were obtained with high yields at 100 °C and under solvent-free conditions.
Cannabinoid CB1 receptors regulate salivation
Authors: Andreis Kelsey , Billingsley Jenna , Naimi Shirazi Kian , Wager-Miller Jim , Johnson Clare , Bradshaw Heather , Straiker Alex
Published: August 2022

Saliva serves multiple important functions within the body that we typically take for granted, such as helping prepare food for swallowing and defense against oral pathogens. Dry mouth is a primary symptom of Sjӧgren’s syndrome and is a side effect of many drug treatments. Cannabis users frequently report dry mouth, but the basis for this is still unknown. If the effects occur via the endogenous cannabinoid signaling system, then this may represent a novel mechanism for the regulation of salivation. We examined expression of cannabinoid CB1 receptors in submandibular salivary gland using immunohistochemistry and tested regulation of salivation by THC and cannabinoid-related ligands. We now report that CB1 receptors are expressed in the axons of cholinergic neurons innervating the submandibular gland. No staining is seen in submandibular gland epithelial cells (acinar and ductal), or myoepithelial cells (MECs). Treatment with THC (4 mg/kg, IP) or the cannabinoid receptor agonist CP55940 (0.5 mg/kg) reduced salivation in both male and female mice 1 h after treatment. CBD had no effect on its own but reversed the effect of THC in a concentration-dependent manner. Neither the CB1 receptor antagonist SR141716 (4 mg/kg) nor the CB2-selective agonist JWH133 (4 mg/kg) had an effect on salivation. We also found that fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide and related lipids, regulates salivation. Salivation was reduced in FAAH knockout mice as well as mice treated with the FAAH blocker URB597 (4 mg/kg). URB597 had no effect in CB1 knockout mice. FAAH protein is detected intracellularly in acinar but not ductal epithelial cells. In lipidomics experiments, we found that FAAH knockout mice chiefly had elevated levels of acylethanolamines, including anandamide, and reduced levels of acyglycines. Our results are consistent with a model wherein endocannabinoids activate CB1 receptors on cholinergic axons innervating the submandibular gland. THC likely acts by plugging into this system, activating CB1 receptors to reduce salivation, thus offering a mechanism underlying the dry mouth reported by cannabis users.
Internal relocation as a relevant and feasible adaptation strategy in Rangiroa Atoll, French Polynesia
Authors: Duvat Virginie K. E. , Magnan Alexandre K. , Goeldner-Gianella Lydie , Grancher Delphine , Costa Stéphane , Maquaire Olivier , Le Cozannet Gonéri , Stahl Lucile , Volto Natacha , Pignon-Mussaud Cécilia
Published: August 2022

Atoll islands face increasing coastal risks (coastal erosion and marine flooding) due to climate change, especially sea-level rise. To face increasing coastal risks, various adaptation options are considered by atoll countries and territories, including in particular hard protection (preferred option to date), Nature-based Solutions (increasingly used) and island raising (considered a longer-term solution and a potential alternative to international migration, e.g. in the Maldives). Internal relocation within the same atoll island or atoll, which refers to long-term community movement from one threatened island area or island to a safer island area or island, has previously been disregarded by scholars as a potentially relevant climate adaptation strategy. However, in low-lying coastal areas, it offers real potential to address the dual context of increasing climate risks and the shrinking of the solution space. This paper assesses the potential of internal relocation for atolls by applying to Rangiroa Atoll, French Polynesia, Central Pacific, a two-fold assessment framework questioning its physical relevance (are some islands high enough to host settlements in the future?) and its societal feasibility (are the political-institutional and socio-economic conditions in place? Are people willing to relocate?). The findings show that internal relocation is both relevant and feasible on Rangiroa Atoll and should therefore serve as a pillar to develop robust in situ adaptation pathways in this atoll.
Stroke survivor perceptions of using an exoskeleton during acute gait rehabilitation
Authors: McDonald Caitlin , Fingleton Caitriona , Murphy Sean , Lennon Olive
Published: August 2022

Robotic-assisted gait training (RAGT) devices allow intensive high repetition of the gait cycle in individuals with locomotor disability, with reduced therapist effort. In addition to usual rehabilitation, RAGT post-stroke improves the likelihood of regaining independent walking, with maximum efficacy identified in the acute and subacute phases of stroke. This study explores the usability and acceptance of RAGT among persons with stroke in an acute hospital setting and examines users’ perceptions of two different modes of robotic assistance provided during rehabilitation. A mixed-methods approach comprised semi-structed interviews of end-user perspectives of RAGT in an acute hospital setting following stroke and two 10-point Likert scales rating how comfortable and how natural robotic gait felt using different assistance modes. Content analysis of qualitative data was undertaken with results synthesised by common meaning units. Quantitative data were reported using summary statistics, with Spearmann’s correlation co-efficient examining the relationship between Likert scale ratings and measures of participants’ stroke related disability. Ten individuals (6 men; 4 women; mean age of 64.5. ± 13 years) were recruited in an acute hospital setting following admission with a stroke diagnosis. Content analysis of interview transcripts identified discussion units centring around positive aspects of how helpful the device was, negative aspects related to set-up time, weight of the device and multiple instructions delivered during use. Initially participants identified that the device could look intimidating, and they feared falling in the device but they subsequently identified the correct mindset for using the device is to trust the technology and not be afraid. Mean ratings for device comfort (7.94 ± 1.4) and how natural walking felt (7.05 ± 1.9) were favourable. Interestingly, a strong relationship was identified, whereby the higher the level of disability, the more natural participants rated walking in the device during maximal assistance mode (rho = 0.62; p = 0.138). This study suggests individuals in the early phases of stroke perceive RAGT to be acceptable and helpful in the main, with some associated negative aspects. Walking in the device was rated as comfortable and natural. Those with greater disability rated the assisted walking as more natural.
Effect of valproate and lithium on dementia onset risk in bipolar disorder patients
Authors: Moon Woori , Ji Eunjeong , Shin Juyoung , Kwon Jun Soo , Kim Ki Woong
Published: August 2022

Although valproate and lithium are most commonly prescribed for bipolar disorder patients, studies comparing their effects on the risk of dementia are limited. Choosing a safer mood stabilizer is clinically crucial as elderly bipolar disorder patients are at high risk of dementia onset. Therefore, we aim to evaluate and compare the effects of valproate and lithium on the risk of dementia in elderly bipolar disorder patients. This study involved 4784 bipolar disorder patients aged 50 years or older from the Korean Health Insurance Review and Assessment Service database. We estimated the risk of dementia in valproate-only users, lithium-only users, and both users compared to both medication non-users using multivariable Cox proportional hazard models. Compared to non-users, valproate-only users and both users showed a higher risk of dementia (59% and 62%, respectively). In sub-group analysis, valproate increased the dementia risk when prescribed for at least 59 days or 23 cumulative defined daily doses. However, the dementia risk associated with lithium is unclear. Therefore, we concluded that lithium has the potential to be the safer choice as a mood stabilizer over valproate for elderly bipolar disorder patients considering the risk of dementia.
Offshore wind resource assessment off the coast of Daejeong, Jeju Island using 30-year wind estimates
Authors: Kim Byeongtaek , Lee Keonwoo , Ko Kyungnam , Choi Jungchul
Published: August 2022

Long-term offshore wind resource assessment was performed for the offshore site off the Daejeong coast on Jeju Island of South Korea. A jacket type offshore met mast was installed at the site to measure wind and meteorological conditions for 1 year from 1 July 2015 to 30 June 2016. The wind conditions were measured at 32.5 m, 72.5 m and 100.5 m above mean sea level (AMSL). Fundamental wind characteristics such as average wind speed, wind direction frequency, turbulence intensity and so on were analyzed utilizing 1-year wind measurements. In order to correct the limited period of 1-year measurements to long-term conditions, the Measure-Correlate-Predict (MCP) method was applied to estimate 30-year wind conditions using nearby Modern-Era Retrospective Analysis for Research and Applications, Version 2 (MERRA-2) reanalysis data. Also, wind turbine classes suitable for the offshore site were determined based on extreme wind speed estimations and the measured ambient turbulence intensity. Five commercial wind turbines were chosen for estimation of the 30-year annual energy productions (AEPs) and capacity factors (CFs). As a result, it was estimated that the 30-year average wind speed was 7.86 m/s at 100.5 m AMSL. The wind turbine class II rating was estimated to be suitable for enduring extreme wind speed for a return period of 50 years. For the 30-year results, the minimum CF of 30.48% was estimated, while the maximum nearly reached 45%.
Cross-platform validation of a mouse blood gene signature for quantitative reconstruction of radiation dose
Authors: Ghandhi Shanaz A. , Shuryak Igor , Ponnaiya Brian , Wu Xuefeng , Garty Guy , Morton Shad R. , Kaur Salan P. , Amundson Sally A.
Published: August 2022

In the search for biological markers after a large-scale exposure of the human population to radiation, gene expression is a sensitive endpoint easily translatable to in-field high throughput applications. Primarily, the ex-vivo irradiated healthy human blood model has been used to generate available gene expression datasets. This model has limitations i.e., lack of signaling from other irradiated tissues and deterioration of blood cells cultures over time. In vivo models are needed; therefore, we present our novel approach to define a gene signature in mouse blood cells that quantitatively correlates with radiation dose (at 1 Gy/min). Starting with available microarray datasets, we selected 30 radiation-responsive genes and performed cross-validation/training–testing data splits to downselect 16 radiation-responsive genes. We then tested these genes in an independent cohort of irradiated adult C57BL/6 mice (50:50 both sexes) and measured mRNA by quantitative RT-PCR in whole blood at 24 h. Dose reconstruction using net signal (difference between geometric means of top 3 positively correlated and top 4 negatively correlated genes with dose), was highly improved over the microarrays, with a root mean square error of ± 1.1 Gy in male and female mice combined. There were no significant sex-specific differences in mRNA or cell counts after irradiation.
Alterations in the kallikrein-kinin system predict death after heart transplant
Authors: Giangreco Nicholas P. , Lebreton Guillaume , Restaino Susan , Farr Maryjane , Zorn Emmanuel , Colombo Paolo C. , Patel Jignesh , Soni Rajesh Kumar , Leprince Pascal , Kobashigawa Jon , Tatonetti Nicholas P. , Fine Barry M.
Published: August 2022

Heart transplantation remains the definitive treatment for end stage heart failure. Because availability is limited, risk stratification of candidates is crucial for optimizing both organ allocations and transplant outcomes. Here we utilize proteomics prior to transplant to identify new biomarkers that predict post-transplant survival in a multi-institutional cohort. Microvesicles were isolated from serum samples and underwent proteomic analysis using mass spectrometry. Monte Carlo cross-validation (MCCV) was used to predict survival after transplant incorporating select recipient pre-transplant clinical characteristics and serum microvesicle proteomic data. We identified six protein markers with prediction performance above AUROC of 0.6, including Prothrombin (F2), anti-plasmin (SERPINF2), Factor IX, carboxypeptidase 2 (CPB2), HGF activator (HGFAC) and low molecular weight kininogen (LK). No clinical characteristics demonstrated an AUROC > 0.6. Putative biological functions and pathways were assessed using gene set enrichment analysis (GSEA). Differential expression analysis identified enriched pathways prior to transplant that were associated with post-transplant survival including activation of platelets and the coagulation pathway prior to transplant. Specifically, upregulation of coagulation cascade components of the kallikrein-kinin system (KKS) and downregulation of kininogen prior to transplant were associated with survival after transplant. Further prospective studies are warranted to determine if alterations in the KKS contributes to overall post-transplant survival.
Early-stage COVID-19 pandemic observations on pulmonary embolism using nationwide multi-institutional data harvesting
Authors: Wismüller Axel , DSouza Adora M. , Abidin Anas Z. , Ali Vosoughi M. , Gange Christopher , Cortopassi Isabel O. , Bozovic Gracijela , Bankier Alexander A. , Batra Kiran , Chodakiewitz Yosef , Xi Yin , Whitlow Christopher T. , Ponnatapura Janardhana , Wendt Gary J. , Weinberg Eric P. , Stockmaster Larry , Shrier David A. , Shin Min Chul , Modi Roshan , Lo Hao Steven , Kligerman Seth , Hamid Aws , Hahn Lewis D. , Garcia Glenn M. , Chung Jonathan H. , Altes Talissa , Abbara Suhny , Bader Anna S.
Published: August 2022

We introduce a multi-institutional data harvesting (MIDH) method for longitudinal observation of medical imaging utilization and reporting. By trackingbothlarge-scale utilizationandclinical imaging results data, the MIDH approach is targeted at measuring surrogates for important disease-related observational quantities over time. To quantitatively investigate its clinical applicability, we performed a retrospective multi-institutional study encompassing 13 healthcare systems throughout the United States before and after the 2020 COVID-19 pandemic. Using repurposed software infrastructure of a commercial AI-based image analysis service, we harvested data on medical imaging service requests and radiology reports for 40,037 computed tomography pulmonary angiograms (CTPA) to evaluate for pulmonary embolism (PE). Specifically, we compared two 70-day observational periods, namely (i) a pre-pandemic control period from 11/25/2019 through 2/2/2020, and (ii) a period during the early COVID-19 pandemic from 3/8/2020 through 5/16/2020. Natural language processing (NLP) on final radiology reports served as the ground truth for identifying positive PE cases, where we found an NLP accuracy of 98% for classifying radiology reports as positive or negative for PE based on a manual review of 2,400 radiology reports. Fewer CTPA exams were performed during the early COVID-19 pandemic than during the pre-pandemic period (9806 vs. 12,106). However, the PE positivity rate was significantly higher (11.6 vs. 9.9%,p < 10−4) with an excess of 92 PE cases during the early COVID-19 outbreak, i.e., ~1.3 daily PE cases more than statistically expected. Our results suggest that MIDH can contribute value as an exploratory tool, aiming at a better understanding of pandemic-related effects on healthcare.