bluuebunny/crossref_metadata_2025 huggingface dataset:
Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands
Authors: Shpakov Alexander
Published: February 2023

A separate group consists of compounds that are able to simultaneously interact with both orthosteric and allosteric sites, which are classified as bitopic GPCR ligands [74, 76-81]. They have two pharmacophores, one of which binds with high affinity to the orthosteric site, while the other, with lower affinity, binds to the allosteric site. If these sites are spatially separated in the receptor, then the pharmacophores in the bitopic ligand must be connected with a flexible linker, the length of which exactly corresponds to the distance between the orthosteric and allosteric sites. At the same time, it is important that the linker does not significantly affect the conformational rearrangements in the receptor caused by its activation by orthosteric and (or) allosteric agonists [74, 79].
Machine Learning for Healthcare: A Bibliometric Study of Contributions from Africa
Authors: Turki Houcemeddine , Pouris Anastassios , Ifeanyichukwu Francis-Alfred Michaelangelo , Namayega Catherine , Hadj Taieb Mohamed Ali , Adedayo Sadiq Adewale , Fourie Chris , Currin Christopher Brian , Asiedu Mercy Nyamewaa , Tonja Atnafu Lambebo , Owodunni Abraham Toluwase , Dere Abdulhameed , Emezue Chris Chinenye , Muhammad Shamsuddeen Hassan , Isa Muhammad Musa , Ben Aouicha Mohamed
Published: February 2023

Machine learning has seen enormous growth in the last decade, with healthcare being a prime application for advanced diagnostics and improved patient care. The application of machine learning for healthcare is particularly pertinent in Africa, where many countries are resource-scarce. However, it is unclear how much research on this topic is arising from African institutes themselves, which is a crucial aspect for applications of machine learning to unique contexts and challenges on the continent. Here, we conduct a bibliometric study of African contributions to research publications related to machine learning for healthcare, as indexed in Scopus, between 1993 and 2022. We identified 3,772 research outputs, with most of these published since 2020. North African countries currently lead the way with 64.5% of publications for the reported period, yet Sub-Saharan Africa is rapidly increasing its output. We found that international support in the form of funding and collaborations is correlated with research output generally for the continent, with local support garnering less attention. Understanding African research contributions to machine learning for healthcare is a crucial first step in surveying the broader academic landscape, forming stronger research communities, and providing advanced and contextually aware biomedical access to Africa.
Clinical Utility of the FilmArray® Blood Culture Identification (BCID) Panel for the Diagnosis of Neonatal Sepsis
Authors: Caunedo-Jiménez María , Fernández-Colomer Belén , Fernández-Suárez Jonathan , Arias-Llorente Rosa Patricia , Lareu-Vidal Sonia , Mantecón-Fernandez Laura , Solís-Sánchez Gonzalo , Suárez-Rodríguez Marta
Published: February 2023

This prospective single-center study was designed to assess the clinical utility of the FilmArray® blood culture identification (BCID) panel for improving the diagnostic accuracy in neonatal sepsis. Results obtained using the FilmArray® BCID panel were correlated with results of blood culture in all consecutive neonates with suspicion of early-onset (EOS) and late-onset sepsis (LOS) attended in our service over a 2-year period. A total of 102 blood cultures from 92 neonates were included, 69 (67.5%) in cases of EOS and 33 (32.3%) in LOS. The FilmArray® BCID panel was performed in negative culture bottles at a median of 10 hours of blood culture incubation (range 7.5-20 hours), without differences by the type of sepsis. The FilmArray® BCID panel showed a 66.7% sensitivity, 100% specificity, 100% positive predictive value, and 95.7% negative predictive value. There were four false-negative cases, three of which of Streptococcus epidermidis in neonates with LOS and one case of Granulicatella adiacens in one neonate with EOS. We conclude that the use of the FilmArray® BCID panel in negative blood cultures from neonates with clinical suspicion of sepsis is useful in decision-making of starting or early withdrawal of empirical antimicrobials because of the high specificity and negative predictive values of this assay.
Digital Mental Health Service Engagement Changes during Covid-19 in Children and Young People across the UK: Presenting Concerns, Service Activity, and Access by Gender, Ethnicity, and Deprivation
Authors: Knipe Duleeka , De Ossorno Garcia Santiago , Salhi Louisa , Mainstone-Cotton Lily , Sefi Aaron , John Ann
Published: February 2023

The adoption of digital health technologies accelerated during Covid-19, with concerns over the equity of access due to digital exclusion. Using data from a text-based online mental health service for children and young people we explore the impact of the pandemic on service access and presenting concerns and whether differences were observed by sociodemographic characteristics in terms of access (gender, ethnicity and deprivation). We used interrupted time-series models to assess whether there was a change in the level and rate of service use during the Covid-19 pandemic (April 2020-April 2021) compared to pre-pandemic trends (June 2019-March 2020). Routinely collected data from 61221 service users were extracted for observation, those represented half of the service population as only those with consent to share their data were used. The majority of users identified as female (74%) and White (80%), with an age range between 13 and 20 years of age,. There was evidence of a sudden increase (13%) in service access at the start of the pandemic (RR 1.13 95% CI 1.02, 1.25), followed by a reduced rate (from 25% to 21%) of engagement during the pandemic compared to pre-pandemic trends (RR 0.97 95% CI 0.95,0.98). There was a sudden increase in almost all presenting issues apart from physical complaints. There was evidence of a step increase in the number of contacts for Black/African/Caribbean/Black British (38% increase; 95% CI: 1%-90%) and White ethnic groups (14% increase; 95% CI: 2%-27%) ), the sudden increase in service use at the start of the pandemic for the most (58% increase; 95% CI: 1%-247%) and least (47% increase; 95% CI: 6%-204%) deprived areas. During the pandemic, contact rates decreased, and referral sources change at the start. Findings on access and service activity align with other studies observing reduced service utilisation. The lack of differences in deprivation levels and ethnicity at lockdown suggests exploring equity of access to the anonymous service. The study provides unique insights into changes in digital mental health use during Covid-19 in the UK.
Nearest Neighbours Graph Variational AutoEncoder
Authors: Arsini Lorenzo , Caccia Barbara , Ciardiello Andrea , Giagu Stefano , Mancini Terracciano Carlo
Published: February 2023

We present a Deep Learning generative model specialized to work with graphs with a regular geometry. It is build on a Variational Autoencoder framework and employs Graph convolutional layers in both encoding and decoding phases. We also introduce a pooling technique (ReNN-Pool), used in the encoder, that allows to downsample graph nodes in a spatially uniform and highly interpretable way. In the decoder, a symmetrical un-pooling technique is used to retrieve the original dimensionality of graphs. Performance of the model are tested on the standard Sprite benchmark dataset, a set of 2D images of video game characters, adequately transforming images data into graphs, and on the more realistic use-case of a dataset of cylindrical-shaped graph data that describe the distributions of the energy deposited by a particle beam in a medium.
Long Covid and Neurodegenerative Disease
Authors: Chambers Patrick
Published: February 2023

Brain fog with compromised ability to concentrate has been the most frequent Long Covid (LC) complaint. This is due to an increased TGF beta/IFN gamma with consequently increased bradykinin (BKN), especially in Caucasian females. Brain and lung blood vessels “leak.” This same ratio is increased in Alzheimer’s disease (AD), but decreased in Parkinson’s disease (PD), because CD4+ and CD8+ T cells are differentially affected by the invading associated viruses, e.g., SARS CoV2, HIV, …. In Covid-19 CD147 receptors on immune cells are critical in generating the increased TGF beta/IFN gamma and those on endothelial cells, platelets, and erythrocytes are critical to the abnormal microvascular blood flow. ACE2 receptors on pneumocytes and enterocytes enable pulmonary and GI entry, initiating gut dysbiosis. Epigenetics, methylation, magnesium, vitamin D, the B vitamins, and antioxidants suggest that these issues can be surmounted. Biochemical, physiologic, and epidemiologic data are analyzed to answer these questions. An LC model is presented and discussed in the context of the most recent research. Suggestions to avoid these and other worrisome concerns are included. Other topics discussed include estrogen, the gut microbiome, type 2 diabetes (T2D), and homocysteine.
Analysis of Efficacy/Safety Ratio of Angiogenesis-inhibitors based Therapies in Ovarian Cancer: A Comprehensive Meta-analysis
Authors: Simion Laurentiu , Rotaru Vlad , Cirimbei Ciprian , Ştefan Daniela-Cristina , Gherghe Mirela , Ionescu Sinziana , Tănase Bogdan Cosmin , Luca Dan Cristian , Gales Laurentia Nicoleta , Chitoran Elena
Published: February 2023

(1)Background: Among new anti-angiogenetic agents being developed and everchanging guidelines indications, the question of benefits/safety ratio remains unclear. (2)Methods: we have conducted a systematic review and meta-analysis of 25 randomized controlled trials (15487 patients), evaluating overall survival – OS, progression free survival– PFS and toxicity (grade ≥3 adverse effects, type and number of all adverse effects. (3)Results: analysis showed improvement of pooled-PFS (HR 0.72, 95%CI 0.66–0.78, I2 = 77%, P<0.00001) regardless of treatment settings (first-line - HR 0.83, 95%CI 0.77-0.90, P<0.00001, recurrent cancer – HR 0.61, 95%CI 0.54-0.68, P<0.00001 or maintenance – HR 0.82, 95%CI 0.67-1.00, P=0.04) and type of anti-angiogenetic drug used (VEGF inhibitors, VEGF-R inhibitors or angiopoietin inhibitors). Improved OS was also observed (HR 0.95, 95%CI 0.91–0.99, P=0.02). OS benefits were only observed in recurrent platinum-sensitive or platinum-resistant cancers. Grade≥3 adverse effects were increased across all trials. Anti-angiogenetic therapy increased the risk of hypertension, infection, thromboembolic/ hemorrhagic events, gastro-intestinal perforations but not the risk of wound related issues, anemia or posterior leukoencephalopathy syndrome. (4)Conclusions: Although angiogenesis inhibitors improve PFS, there is little to no OS benefits. Given the high risk of severe adverse reactions a careful selection of patients is required for obtaining the best results possible.
Numerical modeling of spatial problems of hydrodynamics taking into account elastic processes
Authors: Poveschenko Yuri Andreevich , Krukovskiy Alexander Yur’evich , Podryga Victoria Olegovna , Rahimly Parvin Ilgar gizi , Boykov Dmitri Sergeevich
Published: February 2023

In the present work, the support operator method for spatial problems of elasticity theory is used to construct a finite-difference approximation of elastic forces on staggered Lagrangian meshes. For displacement vectors on irregular meshes, as applied to difference schemes, for problems of elasticity theory, the corresponding discrete operations have been developed. Taking into account the energy balance of the medium, the presented families of integrally consistent approximations of vector analysis operations are sufficient for numerical modeling of these processes. The resulting forces acting on the nodal domains of the medium are obtained explicitly in two-dimensional and three-dimensional geometry. Calculations are given for the propagation of sound waves in an aluminum three-dimensional orthogonal plate due to an end impact. On the example of numerical calculations, the invariance of the elastic force and energy characteristics of the medium during solid-state rotations is confirmed.
Message from the Winner
Authors: Karaki Hideaki ,   Professor Emeritus, The University of Tokyo, Tokyo, Japan
Published: January 2023

I would like to express my sincere gratitude for the MURAKAMI Suminao Award for Disaster Research 2022 and the JDR Award for the Most Contributory Reviewer 2022. It has been a great pleasure to serve on the editorial board for many years, and I have had the opportunity to talk with distinguished members of the editorial board who specialize in natural disasters such as earthquakes, volcanoes, and floods, which are completely outside my field of expertise, biology and medicine, and who have greatly broadened my perspective.

The saying goes that disasters come just when you forget about them, but we have been in a situation recently where disasters come before we forget about them. There have been so many disasters: the panic that began with the discovery of cattle infected with bovine spongiform encephalopathy in Japan in 2001, the simultaneous terrorist attacks in the U.S. and the U.S. military invasion of Afghanistan around the same time, the poisoning of frozen dumplings made in China in 2007, the Tohoku Earthquake and Fukushima Daiichi Nuclear Power Plant accident in 2011, the COVID-19 problem that has continued from 2019 to the present, the invasion of Ukraine by Russia in 2022 and the resulting energy crisis and food shortages, as well as earthquakes, torrential rains, landslides, and typhoons that have occurred every year.

The purpose of JDR, I believe, would be to stimulate research on these disasters, thereby providing a basis for the development of technologies for disaster prevention and control. In this regard, I have been concerned about the distance between science and technology: in the case of COVID-19, research on the causative virus, combined with messenger RNA vaccine technology, led to the fastest vaccine ever developed. On the other hand, the development of a cure has been slow, and the only treatment for pneumonia has been the old-fashioned one. Recently, antiviral drugs have been developed, but their efficacy has yet to be determined.

There are many reasons for the distance between science and technology, and I hope that the research results published in JDR will play a role in reducing that distance.
Message from the Winner
Authors: Liu Wen ,   Assistant Professor, Graduate School of Engineering, Chiba University, Chiba, Japan
Published: January 2023

It is my honor to receive the JDR Award for the Most Cited Paper 2022. I would sincerely like to thank the JDR editorial office, reviewers, and my co-author, Professor Yamazaki, for their support.

The paper that received this honor was “Extraction of Collapsed Buildings in the 2016 Kumamoto Earthquake Using Multi-Temporal PALSAR-2 Data.” In this work, we proposed three change indices for evaluating the damage to buildings in Mashiki Town, Kumamoto Prefecture that were severely affected by the 2016 Kumamoto Earthquake. The indices were calculated from two pre- and one co-event ALOS-2 PALSAR-2 images. The most valid factor was adopted by comparing the extracted results with the reference data from field surveys. The factor was then applied to larger affected areas of Kumamoto City and its surroundings. In this work, the ALOS-2 proved to very effective in recognizing damages caused by nature disasters.

This work has been cited by 21 journal papers as of December 2022. I am grateful to the editorial board of the JDR for affording us the opportunity to have this work published. We hope our results in this paper will help even more scientific works. Encouraged by this award, we will continue to conduct future investigations to further disaster prevention and management.
Co-Evolution Framework Between Humans and Simulations: Planning Post-Disaster Restoration of a Water Distribution Network
Authors: Tada Shunichi , Wakayama Kento , Kanno Taro , Kawase Yuji , Furuta Kazuo
Published: January 2023

This paper developed a new framework for better knowledge management through computational simulations, enabling both human knowledge creation and updating simulation models. The framework was developed based on the concepts of the socialization, externalization, combination, and internalization (SECI) model, and it contains a structured workshop that includes the four types of Ba the model requires. To evaluate this framework, the planning of post-disaster restoration of water distribution networks was employed as a case study. In addition, a new optimization method was developed using empirical heuristics obtained from practitioners, aiming for meaningful feedback from the practitioners working in a water management company. Based on our simulation, three workshops were conducted to create new knowledge, and new features were added to the simulation. In these workshops, practitioners performed simulation-based training in planning the restoration and then discussed their decisions. Afterward, it was concluded that the proposed framework was sufficient for updating the simulation. However, it required additional methods to provide practitioners with opportunities to obtain new insights.
Modeling and Simulation of In-Hospital Disaster Medicine in a Mass Casualty Event for the Resilience Evaluation of BCPs
Authors: Umemoto Mizuki , Kadono Shunsuke , Kanno Taro , Kajiyama Kazumi , Sharikura Sachika , Ikari Ryoko , Yoneyama Masashi , Chuang Sheuwen
Published: January 2023

In this study, we developed a simulation model of detailed in-hospital disaster response to a mass casualty incident based on the analysis of related documents and actual in-hospital disaster response training, aiming to assess the hospital’s response capacity under various disaster situations. This simulation model includes detailed models of patients, floor configurations, resources, and response tasks, which consider resource requirements for the treatment of different patients with various injuries and physical conditions. The model covers patients’ arrivals to hospitalization or discharge. We conducted simulations of the target hospital to test two resource allocation strategies under two patient scenarios. By comparing the results under different resource allocation strategies, we found that the X-ray photography examination capacity could become a fundamental bottleneck in responding to mass casualty incidents. Also, we found that the appropriate resource allocations and quick replenishment could alleviate the negative effect of resource shortages and maintain a higher performance. Furthermore, the results show that the length of stay can be heavily affected by the patients’ configuration. As a result, by monitoring and anticipating the situation, a resilient and responsive resource allocation strategy must be prepared to handle such uncertain disaster situations.
Childfree Practices in Indonesia
Authors: Meidina Ahmadrezy , Puspita Mega
Published: January 2023

This article discusses child-free practices in Indonesia. Childfree means an agreement made by husband and wife not to have children during the marriage period. Practices in society are still taboo when you hear the term childfree itself. There is also a small portion of society that is no longer a taboo and has even practiced it, especially among the upper elite. This research is interesting to study because childfree itself is contrary to the purpose of marriage, namely having children and reproductive rights in Islam to enjoy biological relations. This article aims to explore the views and responses of several Islamic organizations in Kebumen regarding childfree.

This research uses qualitative methods (field research). The main object of this research is child-free practices and the views and responses of Islamic organizations in Kebumen. Data collection techniques were carried out by interviewing several Islamic organizations in Kebumen. Then the data analysis technique is descriptive analysis. The results of the study identified: (1) childfree as a phenomenon of current issues that reap various opinions, some support it and some don’t (2) childfree as a radical feminism. (3) childfree in the opinion of Islamic organizations in Kebumen regency such as (Nahdlatul Ulama, Muhamadiyah, Indonesian Islamic Da'wah Institute, and Hidayatullah) is that childfree has gone against nature, because it has deviated from the Qur’an, Hadis and the purpose of marriage.
Conversion to Arthroplasty After Internal Fixation of Nondisplaced Femoral Neck Fractures
Authors: Lagergren Johan , Mukka Sebastian , Wolf Olof , Nauclér Emma , Möller Michael , Rogmark Cecilia
Published: February 2023

Background:

Although most nondisplaced or minimally displaced femoral neck fractures are routinely treated with internal fixation, high rates of secondary surgical procedures are common, especially in the elderly population. Primary arthroplasty in elderly patients has been proposed as an alternative treatment to reduce the need for a secondary surgical procedure. The objective of this study was to describe the rate of conversion to arthroplasty within 5 years after internal fixation of nondisplaced femoral neck fractures in patients ≥60 years of age.

Methods:

In this observational cohort study of prospectively collected data from the Swedish Fracture Register (SFR) between 2012 and 2018, cross-matched with the Swedish Arthroplasty Register (SAR), 5,428 nondisplaced femoral neck fractures in patients ≥60 years of age were included. Competing risk analysis was used to estimate conversion rates to arthroplasty and mortality in various age groups at 1, 2, and 5 years.

Results:

The cumulative incidence function (CIF) for conversion to arthroplasty was 6.3% at 1 year, 8.1% at 2 years, and 10.1% at 5 years. The conversion rates within 2 years were 6.5% in 60 to 69-year-olds, 9.6% in 70 to 79-year-olds, and 7.8% in ≥80-year-olds. Women had a higher risk of conversion; the hazard ratio (HR) was 1.49 (95% confidence interval [CI], 1.19 to 1.87). The cumulative mortality was 21.3% (95% CI, 20.3% to 22.5%) at 1 year, 31.3% (95% CI, 30.0% to 32.6%) at 2 years, and 54.9% (95% CI, 53.1% to 56.7%) at 5 years. Mortality was higher in men at all time points, and the adjusted 1-year HR was 1.79 (95% CI, 1.61 to 2.00).

Conclusions:

One in 10 patients ≥60 years of age treated with internal fixation for a nondisplaced femoral neck fracture underwent conversion to arthroplasty within 5 years, and more than one-half of the conversions occurred within the first year. The risk of conversion was highest in women and in patients 70 to 79 years of age. These data warrant further studies in this frail patient group to identify subgroups of patients who would benefit from primary arthroplasty for nondisplaced femoral neck fractures.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Drilling-System Optimization Leads to Expedited Wells Delivery
Authors: Carpenter Chris
Published: January 2023

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This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper SPE 202172, “Drilling System Optimization Leads to Expedited Wells Delivery,” by Efe M. Ovwigho, SPE, Saleh Al Marri, and Abdulaziz Al Hajri, Schlumberger. The paper has not been peer reviewed.

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The authors write in the complete paper that simple changes in drillstring design can lead to huge savings in a climate requiring a constant push for reduction in well times and well costs and in improved well delivery. The complete paper explains the process that was followed before implementation of this solution.

Introduction

To access hydrocarbon reserves in a deep gas field, directional drilling through highly interbedded and abrasive formations was necessary. Designing a fit-for-purpose drilling system for optimal performance was critical. The reservoir drainage strategy required that the development wells be drilled directionally to attain a horizontal displacement of 1,500–2,500 ft at the 7-in. liner point above the gas reservoir formation.

The well architecture was designed such that the well would be landed in the 8⅜-in. hole section. This required building inclination from vertical (0°) and landing the well at 80° inclination. Then, 4,000–5,000 ft of a 5⅞-in. hole lateral section would be drilled while holding 80° inclination or occasionally building to 90° inclination.

Several initiatives had been implemented with the aim of optimizing drilling performance but had not experienced meaningful success in tackling vibration issues.

Design Background

An analysis of more than 100 horizontal wells drilled on the project revealed that 35% of total well time was consumed in the 8⅜-in. hole section. The majority of this time was spent on slow drilling or remedial operations. It was imperative that the proposed engineered drillstring meet the following requirements:

- Able to drill through highly abrasive and interbedded formations

- Maintain stability to avoid or reduce stick/slip, shocks, and vibration

- Address surge and swab concerns

- Minimize exposure through reduced handling

- Optimize torque and drag

- Optimized based on available tubulars on the rigsite

- Reduce flat time

Finite element analysis (FEA) and bottomhole assembly (BHA) modeling was performed with these requirements taken into consideration in a bid to generate a fit-for-purpose BHA (Fig. 1).

In the deep gas field where the study was completed, the well had to be landed in the reservoir formation and maintain the 5⅞-in. lateral across the entire pay zone.

A critical analysis of the formation determined that compressive strength exceeded 30,000 psi and that the formation was highly abrasive. A complete review of the drilling system was completed to optimize the approach to be taken.
Formin-mediated nuclear actin assembly at androgen receptors
promotes transcriptional droplet formation
Authors: Knerr Julian , Werner Ralf , Schwan Carsten , Wang Hong , Gebhardt Peter , Grötsch Helga , Caliebe Almuth , Spielmann Malte , Holterhus Paul-Martin , Grosse Robert , Hornig Nadine
Published: January 2023

Steroid hormone receptors are ligand-binding transcription factors essential for mammalian physiology. The androgen receptor (AR) binds androgens mediating gene expression for sexual, somatic, and behavioral functions, and is involved in various conditions including androgen-insensitivity-syndrome (AIS) or prostate cancer. Here we identified functional AIS-patient mutations in the formin and actin nucleator DAAM2. DAAM2 localized to the nucleus and colocalized with the AR to form actin-dependent transcriptional droplets in response to dihydrotestosterone. DAAM2-AR-droplets ranged from 0.02 to 0.06 µm3 in size and associated with active RNA polymerase II. DAAM2 polymerizes actin directly at the AR to promote droplet fusion in a highly dynamic manner and actin polymerization is required for prostate-specific antigen expression in cancer cells. Our data uncover signal-regulated nuclear actin assembly at a steroid hormone receptor necessary for transcription.
N-butanol fraction of Olax subscorpioidea Oliv. (Olacaceae) attenuates lipopolysaccharide-induced depressive-like symptoms in mice.
Authors: Adeoluwa Olusegun Adebayo , Agboola Isaiah , Akinluyi Elizabeth , Eduviere Anthony , Adeoluwa Gladys , Ajayi Abayomi , Aderibigbe Adegbuyi
Published: February 2023

Background: The leaves of Olax subscorpioidea have become a mainstay in the management of inflammatory diseases and mental illness in folkloric medicine in Nigeria. Previous studies have shown its antidepressant and anti-inflammatory properties in experimental animals. Recently its antidepressant action was linked to the involvement of monoaminergic transmission. However, with accumulating evidences suggesting link between immuno-inflammatory signaling pathways and depression, there is dearth of information about its beneficial effect on inflammation associated depression. We thus evaluated the effect of n-butanol fraction of O. subscorpioidea leaves on lipopolysaccharide (LPS)-induced depressive-like behaviours and investigated its antidepressant effect with respect to its action on inflammatory and oxidative pathways.
Methods: Fifty Swiss male mice were randomly assigned into five groups (n= 10): group 1 (vehicle only), group 2 (nBFOS 5mg/kg), group 3 (nBFOS 10 mg/kg), group 4 (imipramine 10 mg/kg), group 5 (vehicle). Mice were treated with vehicle or nBFOS (5 & 10 mg/kg) or imipramine intraperitoneal for seven days. Thirty minutes after treatment on day seven, animals were injected with LPS (0.83 mg/kg, i.p.) except group 1 (vehicle only). Twenty-four hours following LPS injection, animals were assessed for depressive symptoms using sucrose preference test and immobility using tail suspension test (TST). Brain levels of pro-inflammatory mediators interleukin-1β (IL-1β) and tumor necrosis factor (TNF), oxidative stress biomarkers (malondialdehyde and reduced glutathione) and plasma level of corticosterone were measured by Enzyme Linked immunosorbent assay.
Results: LPS significantly (p < 0.05) increased immobility of mice in TST and decreased sucrose preference which is indicative of depressive-like behaviours. The depressive behaviours were significantly (p < 0.05) attenuated by nBFOS and imipramine compared to control. Furthermore, LPS-induced increase in malondialdehyde, corticosterone, TNF, IL-1β, and decrease in reduced glutathione, in the brain were significantly reversed by treatment with nBFOS and imipramine.
Conclusion: The findings suggest that attenuation of LPS-induced depressive-like behaviours by the fraction of O. subscorpioidea leaves may be related to suppression of oxidative stress and inhibitory effect on inflammatory mediators in the central nervous system.
Meta-analysis of the relationship between bullying and depressive symptoms in children and adolescents
Authors: Ye Zixiang , Wu Dongmei , He Xiaoyan , Ma Qin , Peng Jianyan , Mao Guoju , Feng Lanling , Tong Yuhao
Published: January 2023

Childhood and adolescence are critical periods for physical and mental development; thus, they are high-risk periods for the occurrence of mental disorders. The purpose of this study was to systematically evaluate the association between bullying and depressive symptoms in children and adolescents. We searched the PubMed, MEDLINE and other databases to identify studies related to bullying behavior and depressive symptoms in children and adolescents. A total of 31 studies were included, with a total sample size of 133,688 people. The results of the meta-analysis showed that the risk of depression in children and adolescents who were bullied was 2.77 times higher than that of those who were not bullied, that the risk of depression in bullying individuals was 1.73 times higher than that in nonbullying individuals, and that the risk of depression in individuals who bullied and experienced bullying was 3.19 times higher than that in nonbullying-bullied individuals. This study confirmed significant associations of being bullied, bullying, and bullying-bullied behavior with depression in children and adolescents. However, these findings are limited by the quantity and quality of the included studies and need to be confirmed by future studies.
Index of Financial Inclusion and its Relationship with Human Development: Comparative Study of Composite Index and Sarma Analysis
Authors: samputra palupi lindiasari
Published: January 2023

This study to find the dimensions and weights as the best measure of the financial inclusion index by comparing the Sarma analysis with the Composite Index, then analyzing its relationship to human development. The quantitative approach uses Factor Analysis followed by Fixed Effect Model. The data sample is 217 countries grouped by income level from 2011 to 2017. It was found that Access and Usage are two essential dimensions of the financial inclusion index, with the weight of Access (0.60) greater than usage (0.4). Human development acts as an intervening variable and has a significant effect on increasing financial inclusion.
FGFR blockade inhibits targeted therapy-tolerant persister cells in basal FGFR1 and FGF2 high expressing cancers with driver oncogenes
Authors: Yoshiura Shigeki , Furugaki Koh , Fujimura Takaaki , Yoshimura Yasushi , Yoshimoto Takuya , Asakawa Takashi
Published: January 2023

Cancer cell resistance arises when tyrosine kinase inhibitor (TKI)-targeted therapies induce a drug-tolerant persister (DTP) state with growth via genetic aberrations, making DTP cells potential therapeutic targets. We screened an anti-cancer compound library and identified fibroblast growth factor receptor 1 (FGFR1) promoting alectinib-induced ALK fusion-positive DTP cell's survival. FGFR1 signaling promoted DTP cell survival generated from basal FGFR1- and FGF2-high expressing cells, following alectinib treatment, which is blocked by FGFR inhibition. The hazard ratio for progression-free survival of ALK-TKIs tended to increase in ALK fusion-positive non-small cell lung cancer patients with FGFR1- and FGF2-high expression. Combination of FGFR and targeted TKIs enhanced cell growth inhibition in FGFR1- and FGF2-high expressing cells with ALK fusion, HER2 amplification, and EGFR or BRAF mutations. Initial dual blockade of FGFR and various driver oncogenes based on FGFR1 and FGF2 expression levels before starting treatment would be a potent treatment strategy to prevent intrinsic resistance to targeted TKIs through DTP cells.
Vendor Evaluation Platform for Acquisition of Medical Equipment based on Multi-Criteria Decision-Making Approach
Authors: Saleh Neven , Gaber Mohamed N. , Eldosoky Mohamed A. , Soliman Ahmed M.
Published: February 2023

Background The purchase of medical equipment is a critical issue that should be planned properly. The selection of the most appropriate vendor impacts time, effort, and expenses. Therefore, the challenge is to strike a balance between the available budget and the required equipment. The study aims to select the best vendor for supplying medical equipment based on Emergency Care Research Institute (ECRI) standards. Methods The multi-criteria decision-making approach has been adopted through three methods; Multi-Objective Optimization by Ratio Analysis (MOORA), Simple Additive Weighting (SAW), and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS). The criteria of selection are divided into general, technical, and financial. The criteria are weighted using three methods: CRITIC, entropy, and expert judgment. The Vendor Evaluation Program for Medical Equipment (VEPME) is designed to automatically select the best vendor. Results Medical imaging equipment is selected to test the program by four modalities: X-ray equipment, CT, MRI, and ultrasound. The best scenario was given by the entropy-TOPSIS. As a result, this methodology was adopted by the program. Conclusions The results demonstrate the robustness of the proposed methodology by comparing the VEPME output to expert judgment.
The global apparel industry: a significant, yet overlooked source of plastic leakage
Authors: Kounina Anna , Daystar Jesse , Chalumeau Sophie , Devine Jon , Geyer Roland , Pires Steven , Sonar Shreya , Venditti Richard , Boucher Julien
Published: January 2023

This study is the first comprehensive assessment of the global apparel industry’s contribution to plastic pollution. It includes leakage of packaging and end-of-life apparel waste in addition to fiber emissions during apparel production and use. We estimate that the apparel industry generated 9.2 [5.5 – 13] million tons (Mt) of plastic pollution in 2019, corresponding to 15% [6.3% – 31%] of the estimated 61 Mt from all sectors. The main source of plastic pollution from the apparel supply chain is synthetic clothing as mismanaged waste either in the country of its original use or in the countries receiving used apparel exports. A fundamental transformation of the apparel economy towards a circular framework along with decreased synthetic apparel consumption is needed to tackle apparel-related plastic pollution.
Association Between Breakfast Cereals and Risk of Cardiovascular Diseases and Type 2 Diabetes: A Mendelian Randomization Study
Authors: Cheng Tao , Shi Shuqing , Zhang Xuesong , Duan Chenglin , Yun Zhangjun , Hu Yuanhui
Published: February 2023

Background: Evidence suggests that cereals are associated with cardiovascular diseases and type 2 diabetes. However, the results from existing studies are inconsistent and the causality remains to be determined. In this study, we used Mendelian randomization analysis to evaluate the potential causal relationship between breakfast cereals and cardiovascular diseases and type 2 diabetes.
Methods: We accessed summary data of breakfast cereals from genome-wide association studies (GWAS) involving 299,898 people. Additionally, we accessed summary data on cardiovascular diseases from FinnGen R7. Mendelian randomization analysis using inverse variance-weighting (IVW) served as the main analytical method. Besides, multiple sensitivity analysis methods were performed to ensure that the results were robust.
Results: Among breakfast cereals, bran cereal, biscuit cereal, oat cereal, and other types of breakfast cereal were not linked to a risk of cardiovascular diseases and type 2 diabetes, according to gene prediction results. However, genetic liability to muesli was significantly associated with a reduced risk of hypertension (odds ratio (OR) = 0.090; 95% confidence interval (CI) = 0.012-0.660; P = 0.018), myocardial infarction (OR = 0.154; 95% CI = 0.030-0.787; P = 0.025), type 2 diabetes (OR = 0.078; 95% CI = 0.017-0.350; P = 0.00086), and stroke (OR = 0.189; 95% CI = 0.048-0.733; P = 0.016). Further analysis showed no evidence of pleiotropy.
Conclusions: Our research offers genetic support for a possible causal link between muesli and hypertension, myocardial infarction, type 2 diabetes, and stroke.
The episodic resurgence of highly pathogenic avian influenza H5 virus
Authors: Dhanasekaran Vijaykrishna , Xie Ruopeng , Edwards Kimberly , Wille Michelle , Wei Xiaoman , Wong Sook-san , Zanin Mark , El-Shesheny Rabeh , Ducatez Mariette , Poon Leo , Kayali Ghazi , Webby Richard
Published: January 2023

Highly pathogenic avian influenza (HPAI) H5N1 activity has intensified globally since 2021, replacing the dominant clade 2.3.4.4 H5N8 virus. H5N1 viruses have spread rapidly to four continents, causing increasing reports of mass mortality in wild birds and poultry. The ecological and virological properties required for future mitigation strategies are unclear. Using epidemiological, spatial and genomic approaches, we demonstrate changes in the source of resurgent H5 HPAI and reveal significant shifts in virus ecology and evolution. Outbreak data indicates key resurgent events in 2016/17 and 2020/21 that contributed to the panzootic spread of H5N1 in 2021/22, including an increase in virus diffusion velocity and persistence in wild birds. Genomic analysis reveals that the 2016/17 epizootics originated in Asia, where HPAI H5 reservoirs are documented as persistent. However, in 2020/21, 2.3.4.4b H5N8 viruses emerged in domestic poultry in Africa, featuring several novel mutations altering the HA structure, receptor binding, and antigenicity. The new H5N1 virus emerged from H5N8 through reassortment in wild birds along the Adriatic flyway around the Mediterranean Sea. It was characterized by extensive reassortment with low pathogenic avian influenza in domestic and wild birds as it spread globally. In contrast, earlier outbreaks of H5N8 were caused by a more stable genetic constellation, highlighting dynamic changes in HPAI H5 genomic evolution. These results suggest a shift in the epicenter of HPAI H5 beyond Asia to new regions in Africa, the Middle East, Europe, and North and South America. The persistence of HPAI H5 with resurgence potential in domestic birds indicates that elimination strategies remain a high priority.
Cardiac MRI to guide heart failure and atrial fibrillation drug discovery: a Mendelian randomization analysis
Authors: Schmidt Amand , Finan Chris , Bourfiss Mimount , Velthuis Birgitta , Puyol-Antón Esther , Alasiri Abdulrahman , Ruijsink Bram , Asselbergs Folkert , Riele Anneline ter , Setten Jessica van
Published: February 2023

Background
drug development and disease prevention of heart failure (HF) and atrial fibrillation (AF) are impeded by a lack of robust early-stage surrogates. We determined to what extent cardiac magnetic resonance (CMR) measurements act as surrogates for the development of HF or AF in healthy individuals.
Methods
Genetic data was sourced on the association with 22 atrial and ventricular CMR measurements. Mendelian randomization was used to determine CMR associations with atrial fibrillation (AF), heart failure (HF), non-ischemic cardiomyopathy (CMP), and dilated cardiomyopathy (DCM). Additionally, for the CMR surrogates of AF and HF, we explored their association with non-cardiac traits.
Results
In total we found that 9 CMR measures were associated with the development of HF, 7 with development of non-ischemic CMP, 6 with DCM, and 12 with AF. biventricular ejection fraction (EF), biventricular or end-systolic volumes (ESV) and left-ventricular (LV) end diastolic volume (EDV) were associated with all 4 cardiac outcomes. Increased LV-MVR (mass to volume ratio) affected HF (odds ratio (OR) 0.83, 95%CI 0.79; 0.88), and DCM (OR 0.26, 95%CI 0.20; 0.34. We were able to identify 9 CMR surrogates for HF and/or AF (including LV-MVR, biventricular EDV, ESV, and right-ventricular EF) which associated with non-cardiac traits such as blood pressure, lung function traits, BMI, cardioembolic stroke, and late-onset Alzheimer’s disease.
Conclusion
CMR measurements may act as surrogate endpoints for the development of HF (including non-ischemic CMP and DCM) or AF. Additionally, we show that changes in cardiac function and structure measured through CMR, may affect diseases of other organs leading to lung disease or late-onset Alzheimer’s disease.
Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism
Authors: Cohen Justin , Huang Shushu , Koczwara Katherine , Ho Vincent , Woodman Keryn , Lek Angela , Arbiser Jack , Lek Monkol , DeSimone Alec
Published: February 2023

Facioscapulohumeral muscular dystrophy (FSHD) is among the most common of the muscular dystrophies, affecting nearly 1 in 8000 individuals, and is a cause of profound disability. Genetically, FSHD is linked to the contraction and/or epigenetic de-repression of the D4Z4 repeat array on chromosome 4, thereby allowing expression of the DUX4 gene in skeletal muscle. If the DUX4 transcript incorporates a stabilizing polyadenylation site the myotoxic DUX4 protein will be synthesized, resulting in muscle wasting. The mechanism of toxicity remains unclear, as many DUX4-induced cytopathologies have been described, however cell death does primarily occur through caspase 3/7-dependent apoptosis. To date, most FSHD therapeutic development has focused on molecular methods targeting DUX4 expression or the DUX4 transcript, while therapies targeting processes downstream of DUX4 activity have received less attention. Several studies have demonstrated that inhibition of multiple signal transduction pathways can ameliorate DUX4-induced toxicity, and thus compounds targeting these pathways have the potential to be developed into FSHD therapeutics. To this end, we have screened a group of small molecules curated based on their reported activity in relevant pathways and/or structural relationships with known toxicity-modulating molecules. We have identified a panel of five compounds that function downstream of DUX4 activity to inhibit DUX4-induced toxicity. Unexpectedly, this effect was mediated through an mTor-independent mechanism that preserved expression of ULK1 and correlated with an increase in a marker of active cellular autophagy. This identifies these flavones as compounds of interest for therapeutic development, and potentially identifies the autophagy pathway as a target for therapeutics.
Efficient segmentation algorithm for estimation of revised reservoir capacities in Google Earth Engine
Authors: Jaiswal Rahul , Dhruw Gunja , Jain Sukant , Galkate Ravi V , Lohani Anil K , Verma Akhilesh
Published: February 2023

The periodic assessment of the revised capacity is essential and conventional techniques through bathymetric surveys and inflow-outflow techniques are time and resource intensive. The unsupervised classification of optical remote sensing data is practiced for a long time to reduce the cost of the survey but has the limitation of selecting threshold values and inefficacy of the method during the cloudy season. This research proposed the application of the Otsu segmentation technique in Google Earth Engine (GEE) to determine revised water spread using microwave data. The Otsu technique is efficient in classifying the image into two distinct classes using within and between-class variances (Bangare et al 2015). An application has been developed using Sentinel data in GEE, which has the capacity of cloud-based computing and applied to the four reservoirs of Mahanadi Reservoir Project (MRP) namely Ravishankar Sagar, Murumsilli, Dudhawa, and Sondur reservoir in the Chhattisgarh state of India. The original capacities of these reservoirs vary from 910.51 MCM of Ravishankar (RS) Sagar to 165.89 MCM of Murumsilli reservoir. The revised water spreads computed in the GEE were further used to compute revised volume and in turn the revised cumulative capacities at different levels. The analysis suggested that 17.65% of dead storage (118.26 MCM from 143.00 MCM) and 9.25% of gross storage (85.26 MCM from 910.52 MCM) of RS Sagar has been lost in 42 years (1978 to 2020). Similarly, 10.33% gross capacity of Murumsilli, 13.12% of Sondur, and 12.37% of Dudhawa reservoirs has been lost due to the deposit of sediments from the catchments, and results were found comparable with bathymetric survey results of three reservoirs. The proposed application has been developed in GEE so it can be used in any part of the world in cloudy weather with no human interference.