bluuebunny/crossref_metadata_2025 huggingface dataset:
What can we learn from talented General Practitioners and Elderly Care Medicine Specialists? A protocol for a qualitative interview study
Authors: Khawar Abdullah , Visser Mechteld , Mak Marianne , Smalbrugge Martin , Slootweg Irene , van Dijk Nynke
Published: November 2022

1.

Background

Some postgraduate medical trainees in the General Practice (GP) and Elderly Care Medicine (ECM) training program, are considered being talented trainees (TTs) by their peers, teachers (at the institute), trainers (in clinical practice), and/or patients. We are currently unaware if these TTs are trained to meet their maximal potential or whether they are not fully stimulated during their learning process in the postgraduate training program. It is important to acknowledge them, because if we fail to acknowledge and suitably challenge TTs, it may lower their work ethos and satisfaction or cause loss of our TTs. As a first step, we will explore the way TTs make use of the learning possibilities provided during the postgraduate training program and what stimulates and hinders their learning in the clinical workplace.

Knowledge on this subject is important for two reasons. First, knowing how TTs learn, can provide insights for improving learning in the workplace for all trainees. Secondly, with this knowledge, we can enrich the development of TTs. Thirdly, enhancement of workplace-based learning might lead to higher quality of learning, resulting in health care professionals trained to their full potential.

Methods and analysis

We will address these questions in an open approach, conducting explorative qualitative semi-structured interview study with GPs and ECM specialists, who during their postgraduate training were seen as talented by their third year supervisors and completed their postgraduate medical training two or less than two years ago. We will perform the interviews in Dutch. We expect that the interview will not take longer than 45-60 minutes per interview. We plan to start at the beginning of 2023 and will continue until data sufficiency is reached. All interviews will be audio-recorded and transcribed verbatim. We will use thematic analysis to analyse the transcripts of the interviews. This is an iterative process of familiarizing yourself with the data, generating initial codes, searching for themes, reviewing themes, defining and naming themes. We will use MAXQDA 2022 software.

Ethical considerations

The Ethics committee of the Dutch Association of Medical Education (NVMO) gave ethical approval for this work (NERB dossier number: 2022.7.3).

Data availability statement

All data produced in the present study are available upon reasonable request to the authors.

Funding statement

This study is funded by ZonMw (project number 839130008).
A lightweight, automated neural network-based stage-specific malaria detection software using dimension reduction: The malaria stage classifier
Authors: Katharina Preißinger , István Kézsmárki , János Török
Published: November 2022

Due to climate change and the COVID-19 pandemic, the number of malaria cases and deaths increased between 2019 and 2020 [1]. Reversing this trend and eliminating malaria worldwide requires improvements in malaria diagnosis, in which artificial intelligence (AI) has recently been demonstrated to have a great potential. Here, we describe an AI-based approach that boosts the performance of light (LM), atomic force (AFM) and fluorescence microscopy (FM)-based malaria diagnosis. As the main challenge, the stage-specific recognition of infected red blood cells (RBCs) usually requires large sets of microscopy images for training a neural network, which is difficult to obtain. Our tool, the Malaria Stage Classifier, provides a fast, high-accuracy recognition that works even with limited training sets due to a smart reduction of data dimension. Individual RBCs are extracted from an image, reduced to characteristic one-dimensional cross-sections, and classified. We show that our method is applicable to images recorded by various microscopy techniques. It is available as a software package athttps://github.com/KatharinaPreissinger/Malaria_stage_classifierand can be used within a python environment. Technical support is provided by the corresponding author (katharina.preissinger@physik.uni-augsburg.de).

Author summary

The Malaria Stage Classifier is a software helping the user to detect and stage RBCs infected with malaria. Accurate recognition of malaria infected RBCs still imposes a challenge in endemic regions, as it is time-consuming and subjective. These deficiencies can be overcome by autonomous computer assisted recognition using neural networks (NNs). The Malaria Stage Classifier offers a user-friendly interface for the stage-specific classification of malaria infected RBCs into four categories—healthy ones and three classes of infected ones according to the parasite age. The use of data reduction, which forms the central element of the Malaria Stage Classifier, allows for a fast and accurate classification of RBCs. It is applicable for light, atomic force, and fluorescence microscopy images and allows for retraining the implemented NN with new images. Our simple concept further has the potential to be generalised for the classification of other cells or objects.
Adverse events connected to breast cancer treatment and their associated decrease in quality of life scores
Authors: Diernberger Katharina , Gray Ewan , Atter Marek , Bullen Alistair , Hall Peter
Published: November 2022

Background

Breast cancer is the most commonly diagnosed form of cancer in the UK, with over 55,000 newly diagnosed cases annually. Fortunately, many patients are cured, with a five-year survival rate of about 80%. Adjuvant chemotherapy in early breast cancer is common and has been shown to increase survival but frequently comes with several adverse events. These can impact patients’ quality of life (QoL) and influence health care costs. Relatively little is known about the magnitude of effects on the QoL of specific toxicities and toxicity profiles.

Methods

Adverse event and QoL data (using EQ-VAS and EQ5D) from sub-studies embedded in two different randomized controlled trials (RCTs) of standard adjuvant chemotherapy regimens were used in the analysis. Adverse events were grouped into 20 main toxicity categories. QoL data were reported at baseline and following phases of chemotherapy treatment. Correlations between toxicity groups were explored. Univariate and multivariate analyses investigated the association between individual adverse events and reported QoL. To predict the impact of specific adverse events, a regression model specification was developed based on data from one trial using a backwards selection procedure and assessed for validity using data from the other trial.

Results

The most frequently reported toxicities in both trials were Alopecia, Lethargy-Depression-Anxiety, Nausea-Vomiting and Stomatitis. The univariate analysis showed a clear decrease in patients’ QoL measured through the visual analogue scale (EQ-VAS). Results based on EQ5D measurements did not show a clear direction of toxicities’ influence on patients’ QoL. Multivariate results demonstrated a significant change in QoL for Lethargy-Depression-Anxiety, Diarrhoea, Skin-disorders, Infection, Dyspnoea-Respiratory and specified pain.

Conclusions

Only a small part of the change in patients’ QoL is induced by the different adverse events the patients faced. Results based on VAS showed a much bigger influence of certain adverse events on patients’ QoL than those derived from EQ5D, leading to the question of whether EQ5D’s domains are capturing what is of importance to patients during chemotherapy treatment.
Wearable devices can identify Parkinson’s disease up to 7 years before clinical diagnosis
Authors: Schalkamp Ann-Kathrin , Peall Kathryn J , Harrison Neil A , Sandor Cynthia
Published: November 2022

Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder with a latent phase and no currently existing disease-modifying treatments. Reliable predictive biomarkers that could transform efforts to develop neuroprotective treatments remain to be identified. Using UK Biobank, we investigated the predictive value of accelerometry in identifying prodromal PD in the general population and compared this digital biomarker to models based on genetics, lifestyle, blood biochemistry, and prodromal symptoms data. Machine learning models trained using accelerometry data achieved better test performance in distinguishing both clinically diagnosed PD (N = 153) (area under precision recall curve (AUPRC): 0.14+ 0.04) and prodromal PD (N = 113) up to seven years pre-diagnosis (AUPRC: 0.07+ 0.03) from the general population (N = 33009) than all other modalities tested. Accelerometry is a potentially important, low-cost screening tool for determining people at risk of developing PD and identifying subjects for clinical trials of neuroprotective treatments.
Characterization of secretory phospholipase A2 inhibitory activity inTragia hispidaas potential therapeutic agent for treatment of dengue
Authors: Hemalika D. V. Dayangi , Chandrika U.G. , Abeysekera Ajith M. , Samarakoon Sameera , Wijewickrama Ananda , Malavige Gathsaurie Neelika
Published: November 2022

Background

As secretory phospholipase A2 (sPLA2) was shown to be elevated in patients who progress to severe dengue, it would be important to evaluate the usefulness of therapeutics that inhibit sPLA2 enzymes to prevent progression to severe dengue.

Objectives

To explore the presence of sPLA2 inhibitors in plant extracts used in traditional medicine for treatment of fever in Sri Lanka.

Study design

Aqueous and butanol extracts ofTragia hispida, Justicia adathodaand tubers ofCyperus rotunduswere screened for the presence of potential sPLA2 inhibitors using a commercial assay measuring sPLA2 activity.

Results

Both the aqueous (THA) and butanol extracts (THB) ofTragia hispidahad sPLA2 inhibition levels comparable to the levels seen with the commercial sPLA2 inhibitor CAY10590. THB at concentrations of 0.1 µg/µL and 0.2 µg/µL, significantly reduced the sPLA2 activity (p<0.0001) in the sera of dengue patients and the inhibitory activity was significantly higher (p<0.0001) than of CAY10590. Thin layer chromatography of THB showed that it was likely to contain a mixture of flavonoid and phenolic compounds. HPLC displayed peaks at 3.207 min (λmax 222 nm, 272 nm) and 7.972 min (λmax 224 nm, 272 nm) were most likely to represent phenolics and that the peaks at 11.883 min (λmax 276 nm, 366 nm) and 16.898 min (λmax 254 nm, 370 nm) most likely to represent flavonoids.

Conclusions

T. hispidaaqueous and butanol soluble fraction had potent sPLA2 inhibitory activities, which should be further explored for their potential to be used for treatment of dengue.
ethoscopy & ethoscope-lab: a framework for behavioural analysis to lower entrance barrier and aid reproducibility
Authors: Blackhurst Laurence , Gilestro Giorgio F.
Published: November 2022

High-throughput analysis of behaviour is a pivotal instrument in modern neuroscience, allowing researchers to combine modern genetics breakthrough to unbiased, objective, reproducible experimental approaches. To this extent, we recently created an open-source hardware platform (ethoscope (Geissmannet al., 2017)) that allows for inexpensive, accessible, high-throughput analysis of behaviour inDrosophilaor other animal models. Here we equip ethoscopes with a Python framework for data analysis, ethoscopy, designed to be a user-friendly yet powerful platform, meeting the requirements of researchers with limited coding expertise as well as experienced data scientists. Ethoscopy is best consumed in a prebaked Jupyter-based docker container, ethoscope-lab, to improve accessibility and to encourage the use of notebooks as a natural platform to share post-publication data analysis.

Availability and implementation

Ethoscopy is a Python package available on GitHub and PyPi. Ethoscope-lab is a docker container available on DockerHub. A landing page aggregating all the code and documentation is available athttps://lab.gilest.ro/ethoscopy.
Performance modulations phase-locked to action depend on internal state
Authors: Tosato Tommaso , Rohenkohl Gustavo , Fries Pascal
Published: November 2022

Several studies have probed perceptual performance at different times after a self-paced motor action and found frequency-specific modulations of perceptual performance phase-locked to the action. Such action-related modulation has been reported for various frequencies and modulation strengths. In an attempt to establish a basic effect at the population level, we had a relatively large number of participants (n=50) perform a self-paced button press followed by a detection task at threshold, and we applied both fixed- and random-effects tests. The combined data of all trials and participants surprisingly did not show any significant action-related modulation. However, based on previous studies, we explored the possibility that such modulation depends on the participant’s internal state. Indeed, when we split trials based on performance in neighboring trials, then trials in periods of low performance showed an action-related modulation at ≈17 Hz. When we split trials based on the performance in the preceding trial, we found that trials following a “miss” showed an action-related modulation at ≈17 Hz. Finally, when we split participants based on their false-alarm rate, we found that participants with no false alarms showed an action-related modulation at ≈17 Hz. All these effects were significant in random-effects tests, supporting an inference on the population. Together, these findings indicate that action-related modulations are not always detectable. However, the results suggest that specific internal states such as lower attentional engagement and/or higher decision criterion are characterized by a modulation in the beta-frequency range.
PTEN-induced kinase 1 gene single-nucleotide variants as biomarkers in adjuvant chemotherapy for colorectal cancer
Authors: Mihara Yoshiaki , Hirasaki Masataka , Horita Yosuke , Fujino Takashi , Fukushima Hisayo , Kamakura Yasuo , Uranishi Kousuke , Hirano Yasumitsu , Ryozawa Shomei , Yasuda Masanori , Makino Yoshinori , Shibasaki Satomi , Hamaguchi Tetsuya
Published: November 2022

Background

Fluoropyrimidine-based adjuvant chemotherapy is globally recommended for postoperative stage III colon cancer and high-risk stage II patients. However, adjuvant chemotherapy is often associated with severe adverse events and is not highly effective in preventing recurrence. Therefore, a recurrence-prevention biomarker of adjuvant chemotherapy for colorectal cancer is necessary for providing such treatments to appropriate patients.

Autophagy (including mitophagy) is activated under chemotherapy-induced stress and contributes to chemotherapy resistance. Expression of autophagy-related genes and their single-nucleotide polymorphisms are reported to be effective predictors of chemotherapy response in some cancers.

Our goal was to evaluate the relationship between the single-nucleotide variants of autophagy-related genes and recurrence rates to identify the recurrence-prevention biomarkers of adjuvant chemotherapy in colorectal cancer.

Methods

We analyzed surgical or biopsy specimens from 84 patients who underwent radical surgery followed by fluoropyrimidine-based adjuvant chemotherapy at Saitama Medical University International Medical Center between January and December 2016. Using targeted enrichment sequencing, we identified single-nucleotide variants and insertions/deletions in 50 genes, including autophagy-related genes, and examined their association with colorectal cancer patient relapse rates.

Results

We detected 560 single-nucleotide variants or insertions/deletions in the target region. The results of Fisher’s exact test indicated that the recurrence rate of colorectal cancer after adjuvant chemotherapy was significantly lower in patients with the single- nucleotide variants (c.1018G>A [p< 0.005] or c.1562A>C [p< 0.01]) of the mitophagy-related gene PTEN-induced kinase 1.

Conclusions

The two single-nucleotide variants of this mitophagy-related gene may be biomarkers of non-recurrence in colorectal cancer patients who received postoperative adjuvant chemotherapy.
Proopiomelanocortin (POMC) is a negative regulator of tadpole aggression through opioid receptor signaling
Authors: McKinney Jordan E. , Ludington Sarah C. , Butler Julie M. , O’Connell Lauren A.
Published: November 2022

Aggression is a common behavioral response to limited environmental resources. Most research on the neural basis of aggression in vertebrates focuses on adult males, where sex steroid hormones and the ventromedial hypothalamus are important regulators of aggressive behavior. However, the young of many species also display aggression, although the neural basis of juvenile aggression is not well understood. Here we examine juvenile aggression in Mimic poison frog (Ranitomeya imitator) tadpoles, who live in small isolated pools with limited resources and display aggressive behaviors towards intruder tadpoles. We first conducted a longitudinal study of dyadic behavior and found aggressive behavior increases with tadpole age. We next evaluated which brain regions may be important for tadpole aggression by quantifying pS6-positive cells as a proxy for neural activity. We found more pS6-positive cells in the ventral hypothalamus of aggressive tadpoles compared to controls, similar to findings in adult mammals. We then quantified colocalization of pS6 with vasopressin and oxytocin cells and found no difference across behavior groups. Based on this information, we hypothesized that similar brain regions, but different neuromodulators, may promote aggression in juvenile tadpoles compared to the literature in adult animals. We then used an untargeted approach to molecularly profile pS6-positive neurons and found enrichment of the proopiomelanocortin (POMC) gene in aggressive tadpoles. As POMC is cleaved into several signaling peptides, we used pharmacology to target each pathway and discovered that blocking opioid receptors increases aggressive behavior. Together, this work suggests that POMC-derived B-endorphin is a negative regulator of juvenile aggression through the opioid receptor signaling. More broadly, this work suggests that similar brain regions, but different signaling molecules may be used to regulate aggression in adult and juvenile animals.
Opinions of Former Jail Residents about Self-collection of SARS-CoV-2 Specimens, Paired with Wastewater Surveillance: A Qualitative Study Rapidly Examining Acceptability of COVID-19 Mitigation Measures
Authors: González-Montalvo Myrna del Mar , Dickson Peter F. , Saber Lindsay B. , Boehm Rachel A. , Phillips Victoria L. , Akiyama Matthew J. , Spaulding Anne C.
Published: November 2022

In year one of the COVID-19 epidemic, the incidence of infection for US carceral populations was 5.5-fold higher than that in the community. Prior to the rapid roll out of a comprehensive jail surveillance program of Wastewater-Based Surveillance (WBS) and individual testing for SARS-CoV-2, we sought the perspectives of formerly incarcerated individuals regarding mitigation strategies against COVID-19 to inform acceptability of the new program. In focus groups, participants discussed barriers to their receiving COVID-19 testing and vaccination. We introduced WBS and individual nasal self-testing, then queried if wastewater testing to improve surveillance of emerging outbreaks before case numbers surged, and specimen self-collection, would be valued. The participants’ input gives insight into ways to improve the delivery of COVID-19 interventions. Hearing the voices of those with lived experiences of incarceration is critical to understanding their views on infection control strategies and supports including justice-involved individuals in decision-making processes regarding jail-based interventions.
Disruption in seasonality, patient characteristics and disparities of respiratory syncytial virus infection among young children in the US during and before the COVID-19 pandemic: 2010-2022
Authors: Wang Lindsey , Davis Pamela B. , Berger Nathan A. , Kaelber David C. , Volkow Nora D. , Xu Rong
Published: November 2022

Respiratory syncytial virus (RSV) infections and hospitalization have surged sharply among young children. Here we test how the seasonal patterns of RSV infections in 2022 compared with those from other COVID-19 pandemic and pre-pandemic years. For this purpose, we analyzed a nation-wide and real-time database of electronic health records of 56 million patients across 50 states in the US. The monthly incidence rate of first-time RSV infection in young children (<5 years of age) and very young children (<1 year of age) followed a seasonal pattern from 2010 to 2019 with increases during the autumn, peaking in winter, subsiding in spring and summer. This seasonal pattern was significantly disrupted during the COVID-19 pandemic. In 2020, the incidence rate of RSV infections was remarkably low throughout the year. In 2021, the RSV season expanded to 9 months starting in the early summer and peaking in October. In 2022, RSV infections started to rise in May and were significantly higher than in previous years reaching a historically highest incidence rate in November 2022. There were significant racial and ethnic disparities in the peak RSV infection rate during 2010-2021 and the disparities further exacerbated in 2022 with peak incidence rate in black and Hispanic children 2-3 times that in white children. Among RSV-infected children in 2022, 19.2% had prior documented COVID-19 infection, significantly higher than the 9.7% among uninfected children, suggesting that prior COVID-19 could be a risk factor for RSV infection or that there are common risk factors for both viral infections. Our study calls for continuous monitoring of RSV infection in young children alongside its clinical outcomes and for future work to assess potential COVID-19 related risk factors.
predatoR: an R package for network-based mutation impact prediction
Authors: Gurdamar Berk , Sezerman Osman Ugur
Published: November 2022

Motivation

Classification of a mutation is important for variant prioritization and diagnostics. However, it is still a challenging task that many mutations are classified as variant of unknown significance. Therefore, in silico tools are required for classifying variants with unknown significance. Over the past decades, several computational methods have been developed but they usually have limited accuracy and high false-positive rates. To address these needs, we developed a new machine learning-based method for calculating the impact of a mutation by converting protein structures to networks and using network properties of the mutated site.

Results

Here, we propose a novel machine learning-based method, predatoR, for mutation impact prediction. The model was trained using both VariBench and ClinVar datasets and benchmarked against currently available methods using the Missense3D datasets. predatoR outperformed 32 different mutation impact prediction methods with an AUROC value of 0.941.

Availability

predatoR tool is available as an open-source R package at GitHub (https://github.com/berkgurdamar/predatoR).

Contact

berkgurdamar@gmail.com
Building Fluorescence Lifetime Maps Photon-by-photon by Leveraging Spatial Correlations
Authors: Fazel Mohamadreza , Jazani Sina , Scipioni Lorenzo , Vallmitjana Alexander , Zhu Songning , Gratton Enrico , Digman Michelle A. , Pressé Steve
Published: November 2022

Fluorescence lifetime imaging microscopy (FLIM) has become a standard tool in the quantitative analysis of sub-cellular environments. However, quantitative FLIM analyses face several challenges. First, spatial correlations between pixels are often ignored as signal from individual pixels is analyzed independently thereby limiting spatial resolution. Second, existing methods deduce photon ratios instead of absolute lifetime maps. Next, the number of lifetime components contributing to the signal is unknown, while excited state lifetimes with <1 ns difference are difficult to discriminate. Finally, existing analyses require high photon budgets, and often cannot rigorously propagate experimental uncertainty into values over lifetime maps and number of components involved. To overcome all of these challenges simultaneously and self-consistently at once, we propose the first doubly nonparametric framework. That is, we learn the number of fluorescent species (through beta-Bernoulli process priors) and absolute lifetime maps of these species (through Gaussian process priors) by leveraging information from pulses not leading to observed photon. We benchmark our algorithm using a broad range of synthetic and experimental data and demonstrate its robustness across a number of scenarios including cases where we recover lifetime differences between components as small as 0.3 ns with merely 1000 photons.
Genome-wide circadian gating of a cold temperature response in bread wheat
Authors: Graham Calum A. , Paajanen Pirita , Edwards Keith J. , Dodd Antony N.
Published: November 2022

Circadian rhythms coordinate the responses of organisms to their daily fluctuating environments, by establishing a temporal program of gene expression. This schedules aspects of metabolism, physiology, development and behaviour according to the time of day. Circadian regulation in plants is extremely pervasive, and is important because it underpins both productivity and seasonal reproduction. Circadian regulation extends to the control of environmental responses through a regulatory process known as circadian gating. Circadian gating is the process whereby the circadian clock regulates the response to an environmental cue, such that the magnitude of response to an identical cue varies according to the time of day of the cue. Here, we show that there is genome-wide circadian gating of responses to cold temperatures in plants. By using bread wheat as an experimental model, we establish that circadian gating is crucial to the programs of gene expression that underlie the environmental responses of a crop of major socioeconomic importance. Furthermore, we identify that circadian gating of cold temperature responses are distributed unevenly across the three wheat subgenomes, which might reflect the geographical origins of the ancestors of modern wheat.

One-sentence summary

There is genome-wide circadian gating of a response to low temperatures in a crop of major socioeconomic importance.
The Effect of Anesthesia Gases on the Oxygen Reduction Reaction
Authors: Gupta Anu , Sang Yutao , Fontanesi Claudio , Turin Luca , Naaman Ron
Published: November 2022

The oxygen reduction reaction (ORR) is of high importance, among others because of its role in cellular respiration and in the operation of fuel cells. Recently, a possible relation between respiration and general anesthesia has been found. This work aims to explore whether anesthesia related gases affect the ORR. In ORR, oxygen which is in its triplet ground state is reduced to form products that are all in the singlet state. While this process is “in principle” forbidden because of spin conservation, it is known that if the electrons transferred in the ORR are spin polarized, the reaction occurs efficiently. Here we show, in electrochemical experiments, that the efficiency of the oxygen reduction is reduced by the presence of general anesthetics in solution. We suggest that a spin-orbit coupling to the anesthetics depolarizes the spins. This causes both a reduction in reaction efficiency and a change in the reaction products. The findings may point to a possible relation between ORR efficiency and anesthetic action.

TOC
Role of pharmacists and community pharmacies in screening, knowledge and awareness investigation about diabetes mellitus type 2 of Jordanian people visiting community pharmacies
Authors: Khaleel Anas , Abu-Asal Mona , Zakariea Abdullah Bassam , Alejielat Rowan , Al-Nweiran Anas Z.
Published: November 2022

Background

The problem is that approximately half of people with diabetes are unaware that they have the disease. Because there are few signs or symptoms in the early stages of diabetes, unnoticed symptoms will persist until diabetic complications appear just before D.M. is diagnosed. Diabetes is increasing exponentially worldwide, particularly in Africa and the Middle East. This study aims to determine Jordanians’ awareness of type 2 diabetes among those who visit community pharmacies in Amman, Jordan, as well as clarify the role of community pharmacies in T2DM screening.

Methods

The design was based on participants who visited community pharmacies in Amman, Jordan, in 2021. The personal contact interview questionnaire collected demographic information, geographic location, educational attainment, and insurance status. In addition, we created 15 knowledge questions. The study included 305 participants. Descriptive and regression analyses were deployed by using SPSS,

Results

A significant relationship between the type of medical degree and knowledge of risk factors for type 2 diabetes mellitus was confirmed in this study (p <0.012). Some subjects scored slightly higher than others (n = 175; 57.4% of participants scored above 7, compared to n = 130; 42.6% scored below 7). Although 50.5% of the participants (n = 154) held a bachelor’s, master’s, or doctorate, these degrees did not improve the participants’ knowledge levels. The association was tested using chi-square analysis, but no significance was found.

Conclusions

Random visitors to Jordanian community pharmacies are expected to benefit from the current awareness and education campaign. These test results revealed a lack of knowledge, indicating the need for education to dispel myths and highlight the serious risks associated with type 2 diabetes mellitus. The study discovered that participants’ understanding of diabetes disease prevention through lifestyle and dietary changes was inadequate. A specialist-led educational program may increase knowledge among visitors who participate. In order to prevent the spread of diabetes, more campaigns and health-promoting prevention educational activities are required.
Study of Pinelliae Rhizoma hepatotoxicity based on complex network algorithm improvement
Authors: Zhang Aijun , Li Zhaohang , Qi Guanpeng , Xu Ze , Liu Xin , Ma Juman , Li Zuojing
Published: November 2022

Important protein identification methods based on centrality have reached a high level of accuracy. However, there is a need to improve centrality algorithms because they currently consider the nature of protein–protein interaction (PPI) network topology but not protein properties. To improve the centrality algorithm, we introduce the weighted PageRank algorithm, which represents node importance, and the protein interaction combined_score, which represents PPI network edge importance in the STRING database to construct a weighted PPI network. We constructed yeast protein networks for simulations to validate the improved algorithm. Finally, we studied the hepatotoxicity of Pinelliae Rhizoma by applying the PageRank and Edge Clustering (PEC) algorithm. Our study shows that the PageRank and Edge Clustering algorithm can pre-screen important targets and has superior accuracy, sensitivity, and specificity to other centrality algorithms.
Hippo signaling impairs alveolar epithelial regeneration in pulmonary fibrosis
Authors: Warren Rachel , Lyu Handeng , Gao Shan , Klinkhammer Kylie , De Langhe Stijn P.
Published: November 2022

Idiopathic pulmonary fibrosis (IPF) consists of fibrotic alveolar remodeling and progressive loss of pulmonary function. Genetic and experimental evidence indicate that chronic alveolar injury and failure to properly repair the respiratory epithelium are intrinsic to IPF pathogenesis. Loss of alveolar type 2 (AT2) stem cells or mutations that either impair their self-renewal and/or impair their differentiation into AT1 cells can serve as a trigger of pulmonary fibrosis. Recent reports indicate increased YAP activity in respiratory epithelial cells in IPF lungs. Individual IPF epithelial cells with aberrant Yap activation in bronchiolized regions frequently co-express AT1, AT2, conducting airway selective markers and even mesenchymal or EMT markers, demonstrating “indeterminate” states of differentiation and suggesting that aberrant Yap signaling might promote pulmonary fibrosis. Yet, Yap and Taz have recently also been shown to be important for AT1 cell maintenance and alveolar epithelial regeneration afterStreptococcus pneumoniaeinduced injury. To investigate how epithelial Yap/Taz might promote pulmonary fibrosis or drive alveolar epithelial regeneration, we inactivated the Hippo pathway in AT2 stem cells resulting in increased nuclear Yap/Taz and found that this promotes their alveolar regenerative capacity and reduces pulmonary fibrosis following bleomycin injury by pushing them along the AT1 cell lineage. Vice versa, inactivation of bothYapandTazorTazalone in AT2 cells stem cells impaired alveolar epithelial regeneration and resulted in increased pulmonary fibrosis upon bleomycin injury. Interestingly, inactivation of onlyYapin AT2 stem cells promoted alveolar epithelial regeneration and reduced pulmonary fibrosis. Together, these data suggest that epithelial Yap promotes, and epithelial Taz reduces pulmonary fibrosis suggesting that targeting Yap but not Taz mediated transcription might help promote AT1 cell regeneration and treat pulmonary fibrosis.
Changes of platelet morphology, ultrastructure and function in patients with acute ischemic stroke based on super-resolution microscopy
Authors: Yang Bingxin , Wang Xifeng , Hu Xiaoyu , Xiao Yao , Xu Xueyu , Yu Xiaomei , Wang Min , Luo Honglian , Li Jun , Ma Yan , Shen Wei
Published: November 2022

Platelets are important in acute ischemic stroke (AIS) thrombosis. The observation and evaluation of platelet ultrastructure and efficacy of antiplatelet drug in AIS patients is difficult due to microscopic limitations and sensitivity of platelet. The new super-resolution microscope (SIM) can accurately, quickly analyze the platelet ultrastructure and antiplatelet drug in AIS patients. We applied SIM to observe the morphology and ultrastructure of platelets with AIS patients in different state. SIM images were analyzed to specify the dense granules and α granules change of platelets in AIS patients. Testing platelet factor 4 (PF4) to reflect platelet releasing function. We observed that platelet activation in AIS patients was greater after stimulation, with α granule showing a pattern of parenchymatous masses. SIM images analyzing showed diameter of platelets, average size of granules, area% of granules per field and mean area of granules per platelet in AIS patient were lower than healthy people. Platelet releasing function was suppressed at rest stage and more efficacy release after stimulation. 2MeSamp inhibited parenchymatous masses of α granules and reduced PF4 release of platelets after stimulation. According to the results, the structure and function of platelets in AIS patients are indeed altered. Additionally, SIM could be used as a new method to indicates the onset of AIS and assess antiplatelet drugs.
Host genetic variation in feeding rate mediates a fecundity cost of parasite resistance in aDaphnia-parasite system
Authors: Auld Stuart K.J.R. , Raidma Kätlin
Published: November 2022

Organisms face numerous challenges over their lifetimes, including from competitors and parasites, and experience selection to maximise their fitness in the face of these various pressures. However, selection can rarely maximise individual ability to cope with all challenges, and trade-offs therefore emerge. One such trade-off is the cost of resisting parasitic infection, whereby hosts that have a high intrinsic capacity to resist parasitic infection have comparatively low fitness in the absence of the parasite, and spatio-temporal variation in the relative strength of parasite- and non parasite-mediated selection is thought to maintain diversity in host resistance. Here, we test for, and find, a simple cost of resistance in the freshwater hostDaphnia magnaand its sterilising bacterial parasite,Pasteuria ramosathat is shaped by ecology as opposed to immunity. We uncovered significant genetic variation inDaphniafeeding rate, and show that rapid-feedingDaphniagenotypes have high fecundity in the absence of the parasite, but are more likely to go on to suffer sterilising infection when exposed to the parasite. This feeding rate-mediated cost of resistance can explain the persistence of parasite-susceptible genotypes. Further, we found evidence of infection induced anorexia inPasteuria-infected hosts. It follows that reduced feeding in infected hosts means that high parasite prevalence could result in greater host food availability; this could reduce intra-specific competition and mask the cost of resistance in nature.

Summary statement

Costs ofDaphniaimmunity to a sterilising bacterial parasite are mediated by feeding ecology and not immunity, and infection-induced anorexia can further alter the relative strength of parasitism and host-host competition.
Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression
Authors: Grotehans Nils , McGarry Lynn , Nolte Hendrik , Kroker Moritz , Narbona-Pérez Álvaro Jesús , Deshwal Soni , Giavalisco Patrick , Langer Thomas , MacVicar Thomas
Published: November 2022

Replication and expression of the mitochondrial genome depend on the sufficient supply of nucleotide building blocks to mitochondria. Dysregulated nucleotide metabolism is detrimental to mitochondrial genomes and can result in instability of mitochondrial DNA and inflammation. Here, we report that a mitochondrial nucleoside diphosphate kinase, NME6, supplies mitochondria with ribonucleotides to drive the transcription of mitochondrial genes. Moreover, NME6 supports the maintenance of mitochondrial DNA when the access to cytosolic deoxyribonucleotides is limited. Perturbation of NME6 leads to the depletion of mitochondrial transcripts, destabilisation of the electron transport chain and impaired oxidative phosphorylation; deficiencies which are suppressed upon supplementation with pyrimidine ribonucleotides. Our work proposes NME6 and mitochondrial nucleotide metabolism to be untapped therapeutic targets in diseases associated with aberrant mitochondrial gene expression including cancer and autoimmune disorders.
AMPK activation restores salivary function following radiation treatment
Authors: Meyer Rachel , Gilman Kristy , Rheinheimer Brenna A. , Meeks Lauren , Limesand Kirsten H.
Published: November 2022

Head and neck cancers represent a significant portion of cancer diagnoses, with head and neck cancer incidence increasing in some parts of the world. Typical treatment of early-stage head and neck cancers includes either surgery or radiotherapy; however, advanced cases often require surgery followed by radiation and chemotherapy. Salivary gland damage following radiotherapy leads to severe and chronic hypofunction with decreased salivary output, xerostomia, impaired ability to chew and swallow, increased risk of developing oral mucositis, and malnutrition. There is currently no standard of care for radiation-induced salivary gland dysfunction and treatment is often limited to palliative treatment that provides only temporary relief. AMP-activated protein kinase (AMPK) is an enzyme that activates catabolic processes and has been shown to influence the cell cycle, proliferation, and autophagy. In the present study, we found that radiation (IR) treatment decreases tissue levels of phosphorylated AMPK following radiation and decreases intracellular NAD+ and AMP while increasing intracellular ATP. Further, expression of Sirtuin-1 (SIRT1) and nicotinamide phosphoribosyl transferase (NAMPT) were lower five days following IR. Treatment with AMPK activators, AICAR and metformin, attenuated compensatory proliferation (days 6, 7 and 30) following IR, and reversed chronic (day 30) salivary gland dysfunction post-IR. Additionally, treatment with metformin or AICAR increased markers of apical/basolateral polarity (phosphorylated aPKCζT560 positive area) and differentiation (amylase positive area) within irradiated parotid glands to levels similar to untreated controls. Taken together, these data suggest that AMPK may be a novel therapeutic target for treatment of radiation-induced salivary damage.
Virus-like particle displaying SARS-CoV-2 receptor binding domain elicits neutralizing antibodies and is protective in a challenge model
Authors: McKechnie Julia L. , Fiala Brooke , Wolf Clancey , Ellis Daniel , Holtzman Douglas , Feldhaus Andrew
Published: November 2022

While the effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has largely been successful, particularly in the developed world, the rise of new variants as well as waning immunity illustrate the need for a new generation of vaccines that provide broader and/or more durable protection against infection and severe disease. Here we describe the generation and characterization of IVX-411, a computationally designed, two-component virus-like particle (VLP) displaying the ancestral SARS-CoV-2 receptor binding domain (RBD) on its surface. Immunization of mice with IVX-411 generates neutralizing antibodies against the ancestral strain as well as three variants of concern. Neutralizing antibody titers elicited by IVX-411 are durable and significantly higher than those elicited by immunization with soluble RBD and spike antigens. Furthermore, immunization with IVX-411 is shown to be protective in a Syrian Golden hamster challenge model using two different strains of SARS-CoV-2. Overall, these studies demonstrate that IVX-411 is highly immunogenic and capable of eliciting broad, protective immunity.
IFNγ and acute prenatal infection withToxoplasma gondiiactivate fetal hematopoietic stem cells
Authors: López Diego A. , Otsuka Kelly S. , Apostol April C. , Posada Jasmine , Sánchez-Arcila Juan C. , Jensen Kirk D.C. , Beaudin Anna E.
Published: November 2022

Infection directly influences adult hematopoietic stem cell (HSC) function and differentiation, but much less is known about the fetal hematopoietic response to infection during pregnancy. Here, we investigated the fetal hematopoietic response to maternal infection withToxoplasma gondii(T. gondii), an intracellular parasite that elicits Type II IFNγ-mediated maternal immunity. The effects of maternal IFNγ on developing HSCs and the signals that mediate these interactions have not been investigated. Our investigation reveals that the fetal HSCs respond toT. gondiiinfection with virulence-dependent changes in proliferation, self-renewal potential, and lineage output. We demonstrate that maternal IFNγ crosses the fetal-maternal interface and is perceived by fetal HSCs. By comparing the effects of maternal IFNγ injection with maternalT. gondiiinfection, our observations reveal that IFNγ mimics aspects of the fetal HSC response to infection. Moreover, our data disentangle the role of infection-induced inflammatory cytokines in driving the expansion of downstream hematopoietic progenitors. Our findings illuminate that the fetal HSC response to prenatal infection is distinct from the adult HSC response to IFNγ-induced inflammation.
In silico study on evaluation of corosolic acid of Lagerstroemia speciosa against Alzheimer’s disease
Authors: Venkateswarulu T.C , Vajiha  , Krupanidhi S. , Mikkili Indira , Angelina Jacinth , John Babu D. , Peele K. Abraham
Published: November 2022

Purpose

Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative disorder caused by the aggregation of amyloid-beta (Aβ) at outside of neuron cells and also due to tau aggregation inside the cell. Corosolic acid is aimed to be selected as a main active constituent of Lagerstroemia speciosa for the study.

Design/methodology/approach

In the present study, molecular docking of corosolic acid and tau protein was examined using PyRx-v.0.8 software. Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties were described and a molecular dynamics study of the bound complex was performed using Desmond.

Findings

The docking score and interactions suggested that the corosolic acid (CID:6918774) could bind to tau protein to prevent the fibrillar network, to prevent AD. During simulation corosolic acid-bound protein root mean square deviation (RMSD) values showed more stability when compared to the Apo form of protein. Molecular dynamics study of tau protein and corosolic acid complex gave the insights to develop a drug-like candidate against AD.

Originality/value

The use of corosolic acid of Lagerstroemia speciosa to prevent AD is supported by preliminary analysis on a computational basis. This compound should explore in terms of experimental strategies for the further drug development process. However, in vitro and in vivo evaluation studies are required to suggest the use of corosolic acid against AD.
Nonadditive tourism forecast combination using grey relational analysis
Authors: Hu Yi-Chung
Published: November 2022

Purpose

Forecasting tourism demand accurately can help private and public sector formulate strategic planning. Combining forecasting is feasible to improving the forecasting accuracy. This paper aims to apply multiple attribute decision-making (MADM) methods to develop new combination forecasting methods.

Design/methodology/approach

Grey relational analysis (GRA) is applied to assess weights for individual constituents, and the Choquet fuzzy integral is employed to nonlinearly synthesize individual forecasts from single grey models, which are not required to follow any statistical property, into a composite forecast.

Findings

The empirical results indicate that the proposed method shows the superiority in mean accuracy over the other combination methods considered.

Practical implications

For tourism practitioners who have no experience of using grey prediction, the proposed methods can help them avoid the risk of forecasting failure arising from wrong selection of one single grey model. The experimental results demonstrated the high applicability of the proposed nonadditive combination method for tourism demand forecasting.

Originality/value

By treating both weight assessment and forecast combination as MADM problems in the tourism context, this research investigates the incorporation of MADM methods into combination forecasting by developing weighting schemes with GRA and nonadditive forecast combination with the fuzzy integral.