bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTBackgroundFluoropyrimidine-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.MethodsWe 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.ResultsWe 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.ConclusionsThe 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

AbstractAggression 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

AbstractIn 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

AbstractRespiratory 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

AbstractMotivationClassification 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.ResultsHere, 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.AvailabilitypredatoR tool is available as an open-source R package at GitHub (https://github.com/berkgurdamar/predatoR).Contactberkgurdamar@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

AbstractFluorescence 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

AbstractCircadian 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 summaryThere 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

AbstractThe 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

ABSTRACTBackgroundThe 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.MethodsThe 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,ResultsA 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.ConclusionsRandom 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

AbstractImportant 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

AbstractIdiopathic 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

AbstractPlatelets 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

ABSTRACTOrganisms 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 statementCosts 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.