bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-time batch processing at a GPU-based edge with a passive optical network
Authors: Onodera Yukito , Inoue Yoshiaki , Hisano Daisuke , Yoshimoto Naoto , Nakayama Yu
Published: May 2023

In recent years, advances in deep learning technology have significantly improved the research and services relating to artificial intelligence. Real-time object recognition is an important technique in smart cities, in which low-cost network deployment and low-latency data transfer are key technologies. In this study, we focus on time- and wavelength-division multiplexed passive optical network (TWDM-PON)-based inference systems to deploy cost-efficient networks that accommodate several network cameras. A significant issue for a graphics processing unit (GPU)-based inference system via a TWDM-PON is the optimal allocation of the upstream wavelength and bandwidth to enable real-time inference. However, an increase in the batch size of the arrival data at the edge servers, thereby ensuring low-latency transmission, has not been considered previously. Therefore, this study proposes the concept of an inference system in which a large number of cameras periodically upload image data to a GPU-based server via the TWDM-PON. Moreover, we propose a cooperative wavelength and bandwidth allocation algorithm to ensure low-latency and time-synchronized data arrivals at the edge. The performance of the proposed scheme is verified through a computer simulation.
Silicon-thulium hybrid microdisk lasers with low threshold and wide emission wavelength range
Authors: Kiani Khadijeh Miarabbas , Frankis Henry C. , Knights Andrew P. , Bradley Jonathan D. B.
Published: May 2023

We demonstrate low-threshold and wide emission wavelength range hybrid-integrated silicon-thulium microdisk lasers based on a pulley-coupled design. The resonators are fabricated on a silicon-on-insulator platform using a standard foundry process and the gain medium is deposited using a straightforward, low-temperature post-processing step. We show lasing in 40- and 60-µm diameter microdisks with up to 2.6 mW double-sided output power and bidirectional slope efficiencies of up to 13.4% with respect to 1620 nm pump power launched to the bus waveguides. We observe thresholds less than 1 mW versus on-chip pump power and both single-mode and multimode laser emission spanning across wavelengths from 1825 to 1939nm. These low threshold lasers with emissions over a > 100 nm range open the door to monolithic silicon photonic integrated circuits with broadband optical gain and highly compact and efficient light sources in the emerging ∼1.8–2.0 µm wavelength band.
Robust dynamic spectroscopic imaging ellipsometer based on a monolithic polarizing Linnik interferometer
Authors: Hwang Gukhyeon , Choi Inho , Choi Sukhyun , Kheiryzadehkhanghah Saeid , Chegal Won , Kim Sungtae , Kim Sangjun , Magnusson Robert , Kim Daesuk
Published: May 2023

We describe a robust dynamic spectroscopic imaging ellipsometer (DSIE) based on a monolithic Linnik-type polarizing interferometer. The Linnik-type monolithic scheme combined with an additional compensation channel solves the long-term stability problem of previous single-channel DSIE. The importance of a global mapping phase error compensation method is also addressed for accurate 3-D cubic spectroscopic ellipsometric mapping in large-scale applications. To evaluate the effectiveness of the proposed compensation method for enhancing system robustness and reliability, a whole thin film wafer mapping is conducted in a general environment where various external disturbances affect the system.
Underwater image restoration based on adaptive parameter optimization of the physical model
Authors: Ning Yu , Jin Yong-ping , Peng You-duo , Yan Jian
Published: May 2023

Underwater images have the advantage of carrying high information density and are widely used for marine information acquisition. Due to the complex underwater environment, the captured images are often unsatisfactory and often suffer from color distortion, low contrast, and blurred details. Physical model-based methods are often used in relevant studies to obtain clear underwater images; however, water selectively absorbs light, making the use of a priori knowledge-based methods no longer applicable and thus rendering the restoration of underwater images ineffective. Therefore, this paper proposes an underwater image restoration method based on adaptive parameter optimization of the physical model. Firstly, an adaptive color constancy algorithm is designed to estimate the background light value of underwater image, which effectively guarantees the color and brightness of underwater image. Secondly, aiming at the problem of halo and edge blur in underwater images, a smoothness and uniformity transmittance estimation algorithm is proposed to make the estimated transmittance smooth and uniform, and eliminate the halo and blur of the image. Then, in order to further smooth the edge and texture details of the underwater image, a transmittance optimization algorithm for smoothing edge and texture details is proposed to make the obtained scene transmittance more natural. Finally, combined with the underwater image imaging model and histogram equalization algorithm, the image blurring is eliminated and more image details are retained. The qualitative and quantitative evaluation on the underwater image dataset (UIEBD) shows that the proposed method has obvious advantages in color restoration, contrast and comprehensive effect, and has achieved remarkable results in application testing. It shows that the proposed method can effectively restore underwater degraded images and provide a theoretical basis for the construction of underwater imaging models.
High-entropy-rate broadband chaos generation by using short-resonant-cavity DFB semiconductor laser with optical feedback
Authors: Jia Zhiwei , Zhao Aizhong , Li Qingtian , Chen Wenchao , Wang Longsheng , Zhao Tong , Guo Yuanyuan , Chang Pengfa , Sun Yuehui , Wang Yuncai , Wang Anbang
Published: May 2023

Semiconductor lasers with delayed optical feedback are a promising source of optical chaos for practical applications, owing to simple configurations that are easy to integrate and synchronize. However, for traditional semiconductor lasers, the chaos bandwidth is limited by the relaxation frequency to several gigahertz. Here, we propose and experimentally demonstrate that a short-resonant-cavity distributed-feedback (SC-DFB) laser can generate broadband chaos only with simple feedback from an external mirror. The short distributed-feedback resonant cavity not only enhances laser relaxation frequency but also makes the laser mode more susceptible to external feedback. Experiments obtained a laser chaos with 33.6 GHz bandwidth and a spectral flatness of 4.5 dB. The corresponding entropy rate is estimated as more than 33.3 Gbit/s. It is believed that the SC-DFB lasers will promote development of chaos-based secure communication and physical key distribution.
Modified Mach–Zehnder interferometer for spatial coherence measurement
Authors: Torcal-Milla F. J. , Lobera J. , Roche E. M. , Lopez A. M. , Palero V. , Andres N. , Arroyo M. P.
Published: May 2023

Spatial coherence of light sources is usually obtained by using the classical Young’s interferometer. Although the original experiment was improved upon in successive works, some drawbacks still remain. For example, several pairs of points must be used to obtain the complex coherence degree (normalized first-order correlation function) of the source. In this work, a modified Mach–Zehnder interferometer which includes a pair of lenses and is able to measure the spatial coherence degree is presented. With this modified Mach–Zehnder interferometer, it is possible to measure the full 4D spatial coherence function by displacing the incoming beam laterally. To test it, we have measured only a 2D projection (zero shear) of the 4D spatial coherence, which is enough to characterize some types of sources. The setup has no movable parts, making it robust and portable. To test it, the two-dimensional spatial coherence of a high-speed laser with two cavities was measured for different pulse energy values. We observe from the experimental measurements that the complex degree of coherence changes with the selected output energy. Both laser cavities seem to have similar complex coherence degrees for the maximum energy, although it is not symmetrical. Thus, this analysis will allow us to determine the best configuration of the double-cavity laser for interferometric applications. Furthermore, the proposed approach can be applied to any other light sources.
Soliton control in fiber lasers with a semiconductor optical amplifier by off-set filtering
Authors: Turitsyn Sergei K.
Published: May 2023

The path-averaged model is applied to described soliton characteristics in the anomalous cavity dispersion fiber laser with semiconductor optical amplifier. It is shown that, by off-setting the optical filter relative to the gain spectral maximum, it is possible to control velocity and frequency of both the fundamental optical soliton and chirped dissipative solitons.
Multimode Experimental Band Dynamics of Resonant Nanophotonic Lattices with Tunable Waveguides
Authors: Razmjooei Nasrin , Magnusson Robert
Published: May 2023

Subwavelength resonant lattices provide a host of interesting spectral expressions on broadside illumination. The resonance mechanism is based on generation of lateral Bloch modes phase matched to evanescent diffraction orders. The leaky mode structure and mode count determine the spectra and the number of resonance states. Here, we study band flips and bound-state transitions in guided-mode resonant structures supporting multiple resonant modes. We present theoretical simulations and experimental results for a subwavelength silicon-nitride lattice integrated with a liquid film with adjustable boundary. The relatively thick liquid waveguiding region supports additional modes such that the first four transverse-electric (TE) leaky modes are present and generate observable resonance signatures. By varying the duty cycle of the basic lattice in experiment, the 4 bands undergo band transitions and band closures as quantified herein. The experimental results taken in the 1400-1600 nm spectral region agree reasonably well with numerical analysis.
Evaluating the validity of depression-related stigma measurement among diabetes and hypertension patients receiving depression care in Malawi: A mixed-methods analysis
Authors: Dussault Josée M. , Akiba Christopher , Zimba Chifundo , Malava Jullita , Akello Harriet , Stockton Melissa , Mbota MacDonald , Matewere Maureen , Masiye Jones , Udedi Michael , Gaynes Bradley N. , Go Vivian F. , Hosseinipour Mina C. , Pence Brian W.
Published: May 2023

Mental illness stigma research is sparse in Malawi. Our team previously analyzed the reliability and statistical validity of a quantitative tool to measure depression-related stigma among participants with depressive symptoms using quantitative psychometric methods. This analysis aims to further evaluate the content validity of the stigma tool by comparing participants’ quantitative responses with qualitative data. The SHARP project conducted depression screening and treatment at 10 noncommunicable disease clinics across Malawi from April 2019 through December 2021. Eligible participants were 18–65 years with depressive symptoms indicated by a PHQ-9 score ≥5. Questionnaires at each study timepoint included a vignette-based quantitative stigma instrument with three thematic domains: disclosure carryover (i.e., concerns about disclosure), treatment carryover (i.e., concerns about external stigma because of receiving depression treatment), and negative affect (i.e., negative attitudes about people having depression). Sub-scores were aggregated for each domain, with higher scores indicating greater stigma. To better understand participants’ interpretation of this quantitative stigma questionnaire, we asked a subset of six participants a parallel set of questions in semi-structured qualitative interviews in a method similar to cognitive interviewing. Qualitative responses were linked with participants’ most recent quantitative follow-up interviews using Stata 16 and NVivo software. Participants with lower quantitative stigma disclosure sub-scores had qualitative responses that indicated less stigma around disclosure, while participants with higher quantitative stigma sub-scores had qualitative responses indicating greater stigma. Similarly, in the negative affect and treatment carryover domains, participants had parallel quantitative and qualitative responses. Further, participants identified with the vignette character in their qualitative interviews, and participants spoke about the character’s projected feelings and experiences based on their own lived experiences. The stigma tool was interpreted appropriately by participants, providing strong evidence for the content validity of the quantitative tool to measure these stigma domains.
Spatial variation and attributable risk factors of anaemia among young children in Uganda: Evidence from a nationally representative survey
Authors: Wasswa Ronald , Kananura Rornald Muhumuza , Muhanguzi Hillary , Waiswa Peter
Published: May 2023

Anaemia continues to be a burden especially in developing countries that not only affects the physical growth and cognitive development of children but also increases their risk to death. Over the past decade, the prevalence of anaemia among Ugandan children has been unacceptably high. Despite this, spatial variation and attributable risk factors of anaemia are not well explored at national level. The study utilized the 2016 Uganda Demographic and Health Survey (UDHS) data with a weighted sample of 3805 children aged 6–59 months. Spatial analysis was performed using ArcGIS version 10.7 and SaTScan version 9.6. This was followed by a multilevel mixed-effects generalized linear model for the analysis of the risk factors. Estimates for population attributable risks (PAR) and fractions (PAF) were also provided using STATA version 17. In the results, intra-cluster correlation coefficient (ICC) indicates that 18% of the total variability of anaemia was due to communities within the different regions. Moran’s index further confirmed this clustering (Global Moran’s index = 0.17; p-value<0.001). The main hot spot areas of anaemia were Acholi, Teso, Busoga, West Nile, Lango and Karamoja sub-regions. Anaemia prevalence was highest among boy-child, the poor, mothers with no education as well as children who had fever. Results also showed that if all children were born to mothers with higher education or were staying in rich household, the prevalence would be reduced by 14% and 8% respectively. Also having no fever reduces anaemia by 8%. In conclusion, anaemia among young children is significantly clustered in the country with disparities noted across communities within different sub-regions. Policies targeting poverty alleviation, climate change or environment adaptation, food security as well interventions on malaria prevention will help to bridge a gap in the sub regional inequalities of anaemia prevalence.
School-based preventive chemotherapy program for schistosomiasis and soil-transmitted helminth control in Angola: 6-year impact assessment
Authors: Bartlett Adam W. , Mendes Elsa P. , Dahmash Latifeh , Palmeirim Marta S. , de Almeida Maria C. , Peliganga Luis B. , Lufunda Luis M. M. , Direito Ana , Ramirez Julio , Mwinzi Pauline N. , Lopes Sergio , Vaz Nery Susana
Published: May 2023

Background

A school preventive chemotherapy (PC) program for soil-transmitted helminths (STHs) and schistosomiasis has operated in Huambo, Uige and Zaire provinces, Angola, since 2013 and 2014, respectively; complemented by a school water, sanitation and hygiene (WASH) program in a subset of schools from 2016. Conducted in 2021, this is the first impact assessment of the school program for the control of schistosomiasis and STHs.

Methodology/Principal findings

A two-stage cluster design was used to select schools and schoolchildren for parasitological and WASH surveys. The rapid diagnostic tests (RDTs), point of care circulating cathodic antigen (POC-CCA) and Hemastix, were used to estimate Schistosoma mansoni and Schistosoma haematobium prevalence, respectively. Kato Katz was used to detect STHs, and quantify STH and S. mansoni infections. Urine filtration was used to quantify S. haematobium infections. Prevalence, infection intensity, relative prevalence reduction and egg reduction rates were calculated for schistosomiasis and STHs. Cohen’s Kappa co-efficient was used to assess agreement between RDTs and microscopy. Chi-square or Fisher’s exact test was used to compare WASH indicators in WASH-supported and WASH-unsupported schools.

Overall, 17,880 schoolchildren (599 schools) and 6,461 schoolchildren (214 schools) participated in the schistosomiasis and STH surveys, respectively. Prevalence of any schistosomiasis in Huambo was 29.6%, Uige 35.4%, and Zaire 28.2%. Relative reduction in schistosomiasis prevalence from 2014 for Huambo was 18.8% (95% confidence interval (CI) 8.6, 29.0), Uige -92.3% (95%CI -162.2, -58.3), and Zaire -14.0% (95%CI -48.6, 20.6). Prevalence of any STH in Huambo was 16.3%, Uige 65.1%, and Zaire 28.2%. Relative reduction in STH prevalence for Huambo was -28.4% (95%CI -92.1, 35.2), Uige -10.7% (95%CI -30.2, 8.8), and Zaire -20.9% (95%CI -79.5, 37.8). A higher proportion of WASH-supported schools had improved water sources, and toilet and handwashing facilities compared to WASH-unsupported schools.

Conclusions/Significance

The limited impact this school program has had in controlling schistosomiasis and STHs identifies the need for a comprehensive understanding of individual, community, and environmental factors associated with transmission, and consideration for a community-wide control program.
Extravascular optical coherence tomography of cerebral vessel walls in vivo
Authors: Hartmann Karl , Neyazi Belal , Dumitru Claudia A. , Haghikia Aiden , Sandalcioglu I. Erol , Stein Klaus-Peter
Published: May 2023

Purpose

Evaluation of extravascular, microscope integrated OCT (iOCT) as an in vivo imaging modality of cerebral blood vessels and as an intraoperative imaging method.

Methods

Microscope integrated optical coherence tomography of major cerebral arteries (n = 13) and superficial sylvian veins (n = 5) and one incidental cerebral vasospasm (n = 1) in (n = 10) patients. Post procedural analysis of OCT volume scans, microscopic images and videos during the time of scan as well as measurements of the diameter of vessel walls and its layers with an accuracy of 7.5 μm.

Results

iOCT was feasible during vascular microsurgical procedures. In all scanned arteries a clear delineation of the physiological three layered vessel wall composition could be achieved. Pathological arteriosclerotic alterations of cerebral artery walls could precisely be demonstrated. Major superficial cortical veins conversely presented a mono layered composition. First in vivo measurements of vascular mean diameters were possible. Cerebral artery walls showed a diameter of 296 μm, tunica externa 78 μm, media 134 μm and interna 84 μm.

Conclusion

For the first time the microstructural composition of cerebral blood vessels could be illustrated in vivo. Due to an outstanding spatial resolution a clear definition of physiological and pathological characteristics was possible. Therefore, microscope integrated optical coherence tomography holds promise for basic research in the field of cerebrovascular arteriosclerotic diseases and for intraoperative guidance during microvascular surgery.
Impact of valganciclovir therapy on severe IRIS-Kaposi Sarcoma mortality: An open-label, parallel, randomized controlled trial
Authors: Volkow Patricia , Chavez Galan Leslie , Ramon-Luing Lucero , Cruz-Velazquez Judith , Cornejo-Juarez Patricia , Sada-Ovalle Isabel , Perez-Padilla Rogelio , Islas-Muñoz Beda ,   on behalf of the Kaposi Sarcoma Study Group
Published: May 2023

Introduction

High HHV-8 viral load (VL) in Kaposi Sarcoma (KS) has been associated with Severe Immune Reconstitution Inflammatory Syndrome (Severe-IRIS-KS), which can occur after initiating cART, and leads to high mortality, particularly in patients with pulmonary involvement. We investigate if valganciclovir (as an anti-HHV-8 agent) initiated before cART reduces the mortality associated with Severe-IRIS-KS and the incidence of Severe-IRIS-KS.

Methods

Open-label parallel-group randomized clinical trial in AIDS cART naïve patients with disseminated KS (DKS) as defined by at least two of the following: pulmonary, lymph-node, or gastrointestinal involvement, lymphedema, or ≥30 skin lesions. In the experimental group (EG), patients received valganciclovir 900 mg BID four weeks before cART and continued until week 48; in the control group (CG), cART was initiated on week 0. Non-severe-IRIS-KS was defined as: an increase in the number of lesions plus a decrease of ≥one log10 HIV-VL, or an increase of ≥50cells/mm3 or ≥2-fold in baseline CD4+cells. Severe-IRIS-KS was defined as abrupt clinical worsening of KS lesions and/or fever after ruling out another infection following cART initiation, and at least three of the following: thrombocytopenia, anemia, hyponatremia, or hypoalbuminemia.

Results

40 patients were randomized and 37 completed the study. In the ITT analysis, at 48 weeks, total mortality was the same in both groups (3/20), severe-IRIS-KS attributable mortality was 0/20 in the EG, compared with 3/20 in the CG (p = 0.09), similar to the per-protocol analysis: 0/18 in the EG, and 3/19 in the control group (p = 0.09). The crude incidence rate of severe-IRIS-KS was four patients developed a total of 12 episodes of Severe-IRIS-KS in the CG and two patients developed one episode each in the EG. Mortality in patients with pulmonary KS was nil in the EG (0/5) compared with 3/4 in the CG (P = 0.048). No difference was found between groups in the number of non-S-IRIS-KS events. Among survivors at week 48, 82% achieved >80% remission.

Conclusions

Although mortality attributable to KS was lower in the EG the difference was not statistically significant.
Transfer of learning: Analysis of dose-response functions from a large-scale, online, cognitive training dataset
Authors: Osman Allen M. , Jaffe Paul I. , Ng Nicole F. , Kerlan Kelsey R. , Schafer Robert J.
Published: May 2023

Fundamental to the efficacy of cognitive training (CT) is its dose. Here we used the power and breadth afforded by a large dataset to measure precisely dose-response (D-R) functions for CT and to examine the generality of their magnitude and form. The present observational study involved 107,000 users of Lumosity, a commercial program comprising computer games designed to provide CT over the internet. In addition to training with Lumosity games, these users took an online battery of cognitive assessments (NeuroCognitive Performance Test, NCPT) on two or more occasions separated by at least 10 weeks. Changes in performance on the NCPT between the first and second assessments were examined as a function of the amount of intervening gameplay. The resulting D-R functions were obtained both for overall performance on the NCPT and performance on its eight subtests. Also examined were differences between D-R functions from demographic groups defined by age, gender, and education. Monotonically increasing D-R functions, well fit by an exponential approach to an asymptote, were found consistently for overall performance on the NCPT, performance on seven of the eight subtests, and at each level of age, education, and gender. By examining how individual parameters of the D-R functions varied across subtests and groups, it was possible to measure separately changes in the effects on NCPT performance of 1) transfer from CT and 2) direct practice due to repeated testing. The impact of both transfer and direct practice varied across subtests. In contrast, while the effects of direct practice diminished with age, those of transfer remained constant. Besides its implications for CT by older adults, this latter finding suggests that direct practice and transfer do not involve identical learning processes, with transfer being limited to learning processes that remain constant across the adult lifespan.
Effect of environmental NGOs on human health in China: An empirical analysis
Authors: Wang Wenxin , Hafeez Muhammad , Guo Ziyu , Zia Muhammad Yasin , Salahodjaev Raufhon , Ali Iftikhar
Published: May 2023

The emergence of environmental nongovernmental organizations (ENGOs) has proved beneficial in improving environmental quality and related health issues. Therefore, this study attempts to investigate the impact of ENGO on human health in China from 1995 to 2020. To investigate the relationship between the variables, we have employed the ARDL model. The ARDL model results demonstrate that the long-run impact of ENGO is negative on infant mortality and death rate, meaning that an increase in the proportion of ENGOs in China considerably decreases infant mortality and death rate. On the other hand, ENGOs have a favorable influence on life expectancy in China, demonstrating ENGOs’ supporting role in raising birth life expectancy. In the short run, estimates of ENGOs have no substantial influence on newborn mortality and death rates in China, whereas ENGOs have a positive and significant impact on life expectancy. These results imply that ENGOs help improves people’s health status in China, which is also supported by the rise in GDP, technology, and health expenditures. The causal analysis confirms the bi-directional causal link between ENGO and IMR and ENGO and LE, while the unidirectional causal link runs from ENGO to DR. The results of the study provide insights into the impact of environmental NGOs on human health in China and may help guide policies aimed at improving public health outcomes through environmental protection efforts.
High acceptability and viral suppression rate for first-Line patients on a dolutegravir-based regimen: An early adopter study in Nigeria
Authors: Abudiore Opeyemi , Amamilo Ikechukwu , Campbell Jennifer , Eigege Williams , Harwell Joseph , Conroy James , Jiboye Justus , Lufadeju Folu , Amole Carolyn , Wiwa Owens , Anweh Damien , Agbaji Oche Ochai , Akanmu Alani Sulaimon
Published: May 2023

Nigeria adopted dolutegravir (DTG) as part of first line (1L) antiretroviral therapy (ART) in 2017. However, there is limited documented experience using DTG in sub-Saharan Africa. Our study assessed DTG acceptability from the patient’s perspective as well as treatment outcomes at 3 high-volume facilities in Nigeria. This is a mixed method prospective cohort study with 12 months of follow-up between July 2017 and January 2019. Patients who had intolerance or contraindications to non-nucleoside reverse-transcriptase inhibitors were included. Patient acceptability was assessed through one-on-one interviews at 2, 6, and 12 months following DTG initiation. ART-experienced participants were asked about side effects and regimen preference compared to their previous regimen. Viral load (VL) and CD4+ cell count tests were assessed according to the national schedule. Data were analysed in MS Excel and SAS 9.4. A total of 271 participants were enrolled on the study, the median age of participants was 45 years, 62% were female. 229 (206 ART-experienced, 23 ART-naive) of enrolled participants were interviewed at 12 months. 99.5% of ART-experienced study participants preferred DTG to their previous regimen. 32% of particpants reported at least one side effect. “Increase in appetite” was most frequently reported (15%), followed by insomnia (10%) and bad dreams (10%). Average adherence as measured by drug pick-up was 99% and 3% reported a missed dose in the 3 days preceding their interview. Among participants with VL results (n = 199), 99% were virally suppressed (<1000 copies/ml), and 94% had VL <50 copies/ml at 12 months. This study is among the first to document self-reported patient experiences with DTG in sub-Saharan Africa and demonstrated high acceptability of DTG-based regimens among patients. The viral suppression rate was higher than the national average of 82%. Our findings support the recommendation of DTG-based regimen as the preferred 1L ART.
Biologic targets of prescription medications and risk of neurodegenerative disease in United States Medicare beneficiaries
Authors: Song Yizhe , Racette Brad A. , Camacho-Soto Alejandra , Searles Nielsen Susan
Published: May 2023

Objective

To identify prescription medications associated with a lower risk of three neurodegenerative diseases: Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis.

Methods

We conducted a population-based, case-control study of U.S. Medicare beneficiaries in 2009 (42,885 incident neurodegenerative disease cases, 334,387 randomly selected controls). Using medication data from 2006–2007, we categorized all filled medications according to their biological targets and mechanisms of action on those targets. We used multinomial logistic regression models, while accounting for demographics, indicators of smoking, and health care utilization, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 141 target-action pairs and each neurodegenerative disease. For target-action pairs inversely associated with all three diseases, we attempted replication in a cohort study that included an active comparator group. We constructed the cohort by following controls forward for incident neurodegenerative disease from the beginning of 2010 until death or end of 2014, i.e., up to five years after the two-year exposure lag. We used Cox proportional hazards regression while accounting for the same covariates.

Results

The most consistent inverse association across both studies and all three neurodegenerative diseases was for xanthine dehydrogenase/oxidase blockers, represented by the gout medication, allopurinol. Allopurinol was associated with a 13–34% lower risk for each neurodegenerative disease group in multinomial regression, and a mean reduction of 23% overall, as compared to individuals who did not use allopurinol. In the replication cohort we observed a significant 23% reduction for neurodegenerative disease in the fifth year of follow-up, when comparing allopurinol users to non-users, and more marked associations with an active comparator group. We observed parallel associations for a related target-action pair unique to carvedilol.

Discussion/Conclusion

Xanthine dehydrogenase/oxidase blockade might reduce risk of neurodegenerative disease. However, further research will be necessary to confirm that the associations related to this pathway are causal or to examine whether this mechanism slows progression.
NAV-001, a high-efficacy antibody-drug conjugate targeting mesothelin with improved delivery of a potent payload by counteracting MUC16/CA125 inhibitory effects
Authors: Nicolaides Nicholas C. , Kline J. Bradford , Grasso Luigi
Published: May 2023

Subsets of tumor-produced cell surface and secreted proteins can bind to IgG1 type antibodies and suppress their immune-effector activities. As they affect antibody and complement-mediated immunity, we call these proteins humoral immuno-oncology (HIO) factors. Antibody-drug conjugates (ADCs) use antibody targeting to bind cell surface antigens, internalize into the cell, then kill target cells upon liberation of the cytotoxic payload. Binding of the ADC antibody component by a HIO factor may potentially hamper ADC efficacy due to reduced internalization. To determine the potential effects of HIO factor ADC suppression, we evaluated the efficacy of a HIO-refractory, mesothelin-directed ADC (NAV-001) and a HIO-bound, mesothelin-directed ADC (SS1). The HIO factor MUC16/CA125 binding to SS1 ADC was shown to have a negative effect on internalization and tumor cell killing. The MUC16/CA125 refractory NAV-001 ADC was shown to have robust killing of MUC16/CA125 expressing and non-expressing tumor cells in vitro and in vivo at single, sub-mg/kg dosing. Moreover, NAV-001-PNU, which contains the PNU-159682 topoisomerase II inhibitor, demonstrated good stability in vitro and in vivo as well as robust bystander activity of resident cells while maintaining a tolerable safety profile in vivo. Single-dose NAV-001-PNU demonstrated robust tumor regression of a number of patient-derived xenografts from different tumor types regardless of MUC16/CA125 expression. These findings suggest that identification of HIO-refractory antibodies to be used in ADC format may improve therapeutic efficacy as observed by NAV-001 and warrants NAV-001-PNU’s advancement to human clinical trials as a monotherapy to treat mesothelin-positive cancers.
A cohort study on the association between changing occupational stress, hair cortisol concentration, and hypertension
Authors: Wang Jin , Zhu Lejia , Song Lin , Zhou Ziqi , Chan Weiling , Li Geyang , Zhou Li , Xiao Jing , Lian Yulong
Published: May 2023

Objective

To explore the relationship between changing occupational stress levels, hair cortisol concentration (HCC), and hypertension.

Methods

Baseline blood pressure of 2520 workers was measured in 2015. The Occupational Stress Inventory—Revised Edition (OSI-R) was used to assess changes in occupational stress. Occupational stress and blood pressure were followed up annually from January 2016 to December 2017. The final cohort numbered 1784 workers. The mean age of the cohort was 37.77±7.53 years and the percentage male was 46.52%. At baseline, 423 eligible subjects were randomly selected for hair sample collection to determine cortisol levels.

Results

Increased occupational stress was a risk factor for hypertension [risk ratio (RR) = 4.200, 95% confidence interval (CI): 1.734–10.172]. The HCC of workers with elevated occupational stress was higher than that of workers with constant occupational stress [(ORQ score ≥70: geometric mean±geometric standard deviation = 5.25±3.59 ng/g hair; 60–90: 5.02±4.00; 40–59: 3.45±3.41; <40: 2.73±3.40) x2 = 5.261]. High HCC increased the risk of hypertension (RR = 5.270, 95% CI: 2.375–11.692) and high HCC was associated with higher rates of elevated diastolic and systolic blood pressure. The mediating effect of HCC was 0.51[(95% CI: 0.23–0.79, odds ratio(OR) = 1.67] and accounted for 36.83% of the total effect.

Conclusions

Increased occupational stress could lead to an increase in hypertension incidence. High HCC could increase the risk of hypertension. HCC acts as a mediator between occupational stress and hypertension.
Vancomycin prescribing and therapeutic drug monitoring: Challenges of real clinical practice
Authors: Abdel Jalil Mariam Hantash , Ηijazeen Rima , Khaled Abu-Mahfouz Farah , Abu Hammour Khawla , Hasan Matalqah Maria , Saleh Khaleel Albadaineh Jwan , Khaled AlOmoush Shrouq , Al-Iede Montaha
Published: May 2023

Background

Vancomycin prescription and monitoring guidelines have been reported to be poorly followed by various centers.

Aims

Identifying barriers to compliance with vancomycin dosing and therapeutic drug monitoring guidelines (TDM) and possible ways to enhance compliance based on the healthcare providers’ (HCPs) perspective.

Methods

A qualitative study based on semi-structured interviews with HCP (physicians, pharmacists, and nurses) was conducted at two Jordanian Teaching Hospitals. Interviews were audio-recorded and analyzed through thematic analysis. The COREQ criteria for qualitative research were utilized to report the study findings.

Results

A total of 34 HCPs were interviewed. HCP perceived several factors as barriers to guideline recommendation compliance. Such factors included negative perception towards prescription guidelines, lack of knowledge regarding TDM guidelines, the hierarchy of medication management, work pressure, and ineffective communication among healthcare providers. Potential strategies to optimize guidelines adaptation included providing HCPs with more training and decision support tools in addition to activating the role of clinical pharmacists.

Conclusions

The main barriers to guideline recommendations uptake were identified. Interventions should address those barriers related to the clinical environment, including enhancing interprofessional communication related to vancomycin prescription and TDM, reducing workload and providing support systems, promoting educational and training programs, in addition to adopting guidelines suitable for the local environment.
The diversity of energy consumption structure, energy efficiency and carbon emissions: Evidence from Shaanxi, China
Authors: Yin Tengfei
Published: May 2023

As a major energy sources province in China, Shaanxi Province ranks top three in terms of raw coal production in China and undertakes the important task of ensuring national energy supply and security. Affected by the endowment of energy resources, fossil energy accounts for a large proportion of the energy consumption structure in Shaanxi Province, and it will face huge challenges under the severe carbon emission situation in future. In order to analyze the relationship between energy consumption structure, energy efficiency and carbon emissions, the paper introduces the concept of biodiversity into the energy industry. Taking Shaanxi Province as an example, the paper calculates the energy consumption structure diversity index and analyzes the impact of energy consumption structure diversity on energy efficiency and carbon emissions in Shaanxi Province. The results shows that the diversity index and equilibrium index of energy consumption structure in Shaanxi exhibits a slow upward trend in general. In most years, energy consumption structure diversity index in Shaanxi is higher than 0.8, and the equilibrium index is higher than 0.6. The carbon emissions of energy consumption in Shaanxi generally show increasing trend, and the carbon emissions have increased from 5,064.6 tons to 21899.67 tons from 2000 to 2020. The paper also shows that Shaanxi H index is negatively correlated with total factor energy utilization efficiency in Shaanxi, and positively correlated with carbon emissions in Shaanxi. The main reason is the internal substitution of fossil energy, and the proportion of primary electricity and other energy sources is still relatively low, which leads to a higher level of carbon emissions.
How does framing influence preference for multiple solutions to societal problems?
Authors: Wu James Shyan-Tau , Kremen Claire , Zhao Jiaying
Published: May 2023

Solutions to environmental and social problems are often framed in dichotomous ways, which can be counterproductive. Instead, multiple solutions are often needed to fully address these problems. Here we examine how framing influences people’s preference for multiple solutions. In a pre-registered experiment, participants (N = 1,432) were randomly assigned to one of four framing conditions. In the first three conditions, participants were presented with a series of eight problems, each framed with multiple causes, multiple impacts, or multiple solutions to the problem. The control condition did not present any framing information. Participants indicated their preferred solution, perceived severity and urgency of the problem, and their dichotomous thinking tendency. Pre-registered analyses showed that none of the three frames had a significant impact on preference for multiple solutions, perceived severity, perceived urgency, or dichotomous thinking. However, exploratory analyses showed that perceived severity and urgency of the problem were positively correlated with people’s preference for multiple solutions, while dichotomous thinking was negatively correlated. These findings showed no demonstrable impact of framing on multi-solution preference. Future interventions should focus on addressing perceived severity and urgency, or decreasing dichotomous thinking to encourage people to adopt multiple solutions to address complex environmental and social problems.
Interspecies evaluation of a physiologically based pharmacokinetic model to predict the biodistribution dynamics of dendritic nanoparticles
Authors: Vasalou Christina , Harding Joanna , Jones Rhys D. O. , Hariparsad Niresh , McGinnity Dermot F.
Published: May 2023

The exposure of a dendritic nanoparticle and its conjugated active pharmaceutical ingredient (API) was determined in mouse, rat and dog, with the aim of investigating interspecies differences facilitating clinical translation. Plasma area under the curves (AUCs) were found to be dose proportional across species, while dose normalized concentration time course profiles in plasma, liver and spleen were superimposable in mouse, rat and dog. A physiologically based pharmacokinetic (PBPK) model, previously developed for mouse, was evaluated as a suitable framework to prospectively capture concentration dynamics in rat and dog. The PBPK model, parameterized either by considering species-specific physiology or using alternate scaling methods such as allometry, was shown to capture exposure profiles across species. A sensitivity analysis highlighted API systemic clearance as a key parameter influencing released API levels. The PBPK model was utilized to simulate human exposure profiles, which overlaid dose-normalized data from mouse, rat and dog. The consistency in measured interspecies exposures as well as the capability of the PBPK model to simulate observed dynamics support its use as a powerful translational tool.
Purification of recombinant bacterial collagens containing structural perturbations
Authors: Gahlawat Sonal , Nanda Vikas , Shreiber David I.
Published: May 2023

Streptococcus pyogenes-derived recombinant bacterial collagen-like proteins (CLPs) are emerging as a potential biomaterial for biomedical research and applications. Bacterial CLPs form stable triple helices and lack specific interactions with human cell surface receptors, thus enabling the design of novel biomaterials with specific functional attributes. Bacterial collagens have been instrumental in understanding collagen structure and function in normal and pathological conditions. These proteins can be readily produced in E. coli, purified using affinity chromatography, and subsequently isolated after cleavage of the affinity tag. Trypsin is a widely used protease during this purification step since the triple helix structure is resistant to trypsin digestion. However, the introduction of Gly→X mutations or natural interruptions within CLPs can perturb the triple helix structure, making them susceptible to trypsin digestion. Consequently, removing the affinity tag and isolating collagen-like (CL) domains containing mutations is impossible without degradation of the product. We present an alternative method to isolate CL domains containing Gly→X mutations utilizing a TEV protease cleavage site. Protein expression and purification conditions were optimized for designed protein constructs to achieve high yield and purity. Enzymatic digestion assays demonstrated that CL domains from wild-type CLPs could be isolated by digestion with either trypsin or TEV protease. In contrast, CLPs containing Gly→Arg mutations are readily digested by trypsin while digestion with TEV protease cleaved the His6-tag, enabling the isolation of mutant CL domains. The developed method can be adapted to CLPs containing various new biological sequences to develop multifunctional biomaterials for tissue engineering applications.
Far-right virtual communities: Exploring users and uses of far-right pages on social media
Authors: Gagnon Audrey
Published: May 2023

The role of social media in facilitating far-right networks and propagating far-right narratives is increasingly documented. However, research tends to focus on far-right pages on social media, thus leaving the users of these pages understudied. Relying on interviews with users of the Facebook page of the radical right organization La Meute in Canada, this study investigates individuals’ motivations and practices when using far-right pages on social media, as well as the interplay between their use of these pages and their view of themselves and society. It shows that users of La Meute’s Facebook page perceive (to varying degrees) that mainstream media are biased and do not represent their views nor address their concerns about immigration issues. As such, they seek meaning by using far-right pages on social media, either as their main source of information or to complement mainstream media. On these pages, they encounter a virtual community of like-minded people, which is conceived in opposition to the rest of society who would not be critical enough of mainstream media and immigration. Boundaries delineating the virtual community tend to be particularly pronounced among individuals who use far-right pages on social media as their main source of information.
Local media in transitional fragile states: The cases of Iraq and Libya
Authors: Richter Carola , Wollenberg Anja , Fhelboom Reda
Published: May 2023

Local media that cater to their local communities are still rare in Arab countries due to government control and centralization of media production. In some transitional states, however, we observe a mushrooming of new local small media initiatives after regulation modes have changed. Yet, these media operate in often fragile states in which a sustainable development of autonomous media is difficult to achieve. In this study, we investigate how local media in Iraq and Libya unfolded and developed over the past decade(s) after regime change. We map the status quo and compare the proliferation of small local media in both countries against the backdrop of media capture and flawed media regulation – patterns that are typical for transitional states.
OBTAINING AND RHEOLOGICAL PROPERTIES OF PECTIN ISOLATED USING MICROWAVE RADIATION
Authors: Azimova Luiza Bakhtiyarovna , Filatova Al'bina Vasil'yevna , Mukhamedzhanova Muyassarhon Yusufdzhanovna , Turaev Abbaskhan Sabirkhanovich
Published: May 2023

А method has been developed for extracting modified pectin from plant raw materials by using microwave radiation at the stage of washing. The rheological properties of 5.0% aqueous solutions of apple PV obtained by exposure to microwave radiation of various powers: 300, 450 and 600 W, as well as PV obtained by the traditional method at temperatures of 25, 40, 55, 70 °C were investigated. It is shown that the use of microwave radiation makes it possible to improve the method of obtaining pectins with the possibility of increasing the yield of pectin substances and regulating their structure and properties. The rheological properties of concentrated aqueous solutions of pectins obtained by exposure to microwave radiation of various powers have been studied. It is shown, that all the studied systems of PV solutions are non-Newtonian fluids with a pseudoplastic type of viscous flow anomaly, determined by the values of the microwave energy. The values of the apparent activation energies of the viscous flow of solutions, which are an indirect characteristic of the strength of the structures of the system, have been estimated. Information was obtained on the structure and changes in the structure of their concentrated solutions under the action of external forces and temperature in the course of a viscous flow. It is shown that the power values оf microwave radiation are the main factor determining the structure of molecular matrices of pectin substances and the structure of their concentrated aqueous solutions.