bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth differentiation factor 1-induced tumour plasticity provides a therapeutic window for immunotherapy in hepatocellular carcinoma
Authors: Cheng Wei , Li Hao-Long , Xi Shao-Yan , Zhang Xiao-Feng , Zhu Yun , Le Xing  , Mo Yan-Xuan , Li Mei-Mei , Kong Fan-En , Zhu Wen-Jie , Chen Xiao-Gang , Cui Hui-Qing , Cao Zhi-Ming , Gong Yuan-Feng , Tang Yun-Qiang , Zhang Yan , Guan Xin-Yuan , Ma Ning-Fang , Liu Ming
Published: December 2021

Tumour lineage plasticity is an emerging hallmark of aggressive tumours. Tumour cells usually hijack developmental signalling pathways to gain cellular plasticity and evade therapeutic targeting. In the present study, the secreted protein growth and differentiation factor 1 (GDF1) is found to be closely associated with poor tumour differentiation. Overexpression of GDF1 suppresses cell proliferation but strongly enhances tumour dissemination and metastasis. Ectopic expression of GDF1 can induce the dedifferentiation of hepatocellular carcinoma (HCC) cells into their ancestral lineages and reactivate a broad panel of cancer testis antigens (CTAs), which further stimulate the immunogenicity of HCC cells to immune-based therapies. Mechanistic studies reveal that GDF1 functions through the Activin receptor-like kinase 7 (ALK7)-Mothers against decapentaplegic homolog 2/3 (SMAD2/3) signalling cascade and suppresses the epigenetic regulator Lysine specific demethylase 1 (LSD1) to boost CTA expression. GDF1-induced tumour lineage plasticity might be an Achilles heel for HCC immunotherapy. Inhibition of LSD1 based on GDF1 biomarker prescreening might widen the therapeutic window for immune checkpoint inhibitors in the clinic.
The salivary metatranscriptome as an accurate diagnostic indicator of oral cancer
Authors: Banavar Guruduth , Ogundijo Oyetunji , Toma Ryan , Rajagopal Sathyapriya , Lim Yen Kai , Tang Kai , Camacho Francine , Torres Pedro J. , Gline Stephanie , Parks Matthew , Kenny Liz , Perlina Ally , Tily Hal , Dimitrova Nevenka , Amar Salomon , Vuyisich Momchilo , Punyadeera Chamindie
Published: December 2021

Despite advances in cancer treatment, the 5-year mortality rate for oral cancers (OC) is 40%, mainly due to the lack of early diagnostics. To advance early diagnostics for high-risk and average-risk populations, we developed and evaluated machine-learning (ML) classifiers using metatranscriptomic data from saliva samples (n = 433) collected from oral premalignant disorders (OPMD), OC patients (n = 71) and normal controls (n = 171). Our diagnostic classifiers yielded a receiver operating characteristics (ROC) area under the curve (AUC) up to 0.9, sensitivity up to 83% (92.3% for stage 1 cancer) and specificity up to 97.9%. Our metatranscriptomic signature incorporates both taxonomic and functional microbiome features, and reveals a number of taxa and functional pathways associated with OC. We demonstrate the potential clinical utility of an AI/ML model for diagnosing OC early, opening a new era of non-invasive diagnostics, enabling early intervention and improved patient outcomes.
Deep nasal sinus cavity microbiota dysbiosis in Parkinson’s disease
Authors: Pal Gian , Ramirez Vivian , Engen Phillip A. , Naqib Ankur , Forsyth Christopher B. , Green Stefan J. , Mahdavinia Mahboobeh , Batra Pete S. , Tajudeen Bobby A. , Keshavarzian Ali
Published: December 2021

Olfactory dysfunction is a pre-motor symptom of Parkinson’s disease (PD) that appears years prior to diagnosis and can affect quality of life in PD. Changes in microbiota community in deep nasal cavity near the olfactory bulb may trigger the olfactory bulb-mediated neuroinflammatory cascade and eventual dopamine loss in PD. To determine if the deep nasal cavity microbiota of PD is significantly altered in comparison to healthy controls, we characterized the microbiota of the deep nasal cavity using 16S rRNA gene amplicon sequencing in PD subjects and compared it to that of spousal and non-spousal healthy controls. Correlations between microbial taxa and PD symptom severity were also explored. Olfactory microbial communities of PD individuals were more similar to those of their spousal controls than to non-household controls. In direct comparison of PD and spousal controls and of PD and non-spousal controls, significantly differently abundant taxa were identified, and this included increased relative abundance of putative opportunistic-pathobiont species such as Moraxella catarrhalis. M. catarrhalis was also significantly correlated with more severe motor scores in PD subjects. This proof-of-concept study provides evidence that potential pathobionts are detected in the olfactory bulb and that a subset of changes in the PD microbiota community could be a consequence of unique environmental factors associated with PD living. We hypothesize that an altered deep nasal microbiota, characterized by a putative pro-inflammatory microbial community, could trigger neuroinflammation in PD.
Hotspots for mutations in the SARS-CoV-2 spike glycoprotein: a correspondence analysis
Authors: Rahbar Mohammad Reza , Jahangiri Abolfazl , Khalili Saeed , Zarei Mahboubeh , Mehrabani-Zeinabad Kamran , Khalesi Bahman , Pourzardosht Navid , Hessami Anahita , Nezafat Navid , Sadraei Saman , Negahdaripour Manica
Published: December 2021

Spike glycoprotein (Sgp) is liable for binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the host receptors. Since Sgp is the main target for vaccine and drug designing, elucidating its mutation pattern could help in this regard. This study is aimed at investigating the correspondence of specific residues to the SgpSARS-CoV-2 functionality by explorative interpretation of sequence alignments. Centrality analysis of the Sgp dissects the importance of these residues in the interaction network of the RBD-ACE2 (receptor-binding domain) complex and furin cleavage site. Correspondence of RBD to threonine500 and asparagine501 and furin cleavage site to glutamine675, glutamine677, threonine678, and alanine684 was observed; all residues are exactly located at the interaction interfaces. The harmonious location of residues dictates the RBD binding property and the flexibility, hydrophobicity, and accessibility of the furin cleavage site. These species-specific residues can be assumed as real targets of evolution, while other substitutions tend to support them. Moreover, all these residues are parts of experimentally identified epitopes. Therefore, their substitution may affect vaccine efficacy. Higher rate of RBD maintenance than furin cleavage site was predicted. The accumulation of substitutions reinforces the probability of the multi-host circulation of the virus and emphasizes the enduring evolutionary events.
Opisthenar microvessel area as a sensitive predictive index of arterial stiffness in hypertensive patients
Authors: Guo Zhen Yi , Chen Chen , Jin Xin , Zhao Zai Hao , Cui Lan , Zhang Yin Hua
Published: December 2021

We aimed to analyze whether opisthenar microvessel area (OMA, measured with Optical Coherence Tomography (OCT) angiography) was associated with blood pressure (BP), arterial stiffness and whether OMA can predict arterial stiffness in hypertensive (HTN) patients. Results from 90 participants showed that BP, brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI) were significantly higher but OMA (in control, with cold- and warm-stimulation, NT, CST, HST and the differences, CSD, HSD) were significantly reduced in HTN group (n = 36) compared to non-HTN (n = 54). NT, CST, HST and HSD showed negative correlations with baPWV and ABI in all participants, female (n = 47) and male group (n = 43), but the correlation was absent when the participants were divided into HTN and non-HTN. Logistic Regression analysis showed that only baPWV was a significant risk factor for HSD (OR 19.7, 95%CI 4.959–78.733, p < 0.0001) but not the age, BMI, smoking, drinking or exercise status (p > 0.05). Receiver Operating Characteristics analysis for HSD was 0.781, 0.804, 0.770, respectively. HSD < 9439.5 μm2 predicted high BP and arterial stiffness (95% CI in all participants: baPWV, 0.681–0.881, SBP, 0.709–0.900, DBP, 0.672–0.867, p < 0.001). These results suggest that OMA is a sensitive index to predict arterial stiffness in HTN population.
An altered microbiome in a Parkinson’s disease model Drosophila melanogaster has a negative effect on development
Authors: Parker-Character Jade , Hager David R. , Call Tanner B. , Pickup Zachary S. , Turnbull Scott A. , Marshman Evan M. , Korch Shaleen B. , Chaston John M. , Call Gerald B.
Published: December 2021

Parkinson’s disease (PD) is the second most common neurodegenerative disease, besides Alzheimer’s Disease, characterized by multiple symptoms, including the well-known motor dysfunctions. It is well-established that there are differences in the fecal microbiota composition between Parkinson’s disease (PD) patients and control populations, but the mechanisms underlying these differences are not yet fully understood. To begin to close the gap between description and mechanism we studied the relationship between the microbiota and PD in a model organism, Drosophila melanogaster. First, fecal transfers were performed with a D. melanogaster model of PD that had a mutation in the parkin (park25) gene. Results indicate that the PD model feces had a negative effect on both pupation and eclosion in both control and park25 flies, with a greater effect in PD model flies. Analysis of the microbiota composition revealed differences between the control and park25 flies, consistent with many human studies. Conversely, gnotobiotic treatment of axenic embryos with feces-derived bacterial cultures did not affect eclosure. We speculate this result might be due to similarities in bacterial prevalence between mutant and control feces. Further, we confirmed a bacteria-potentiated impact on mutant and control fly phenotypes by measuring eclosure rate in park25 flies that were mono-associated with members of the fly microbiota. Both the fecal transfer and the mono-association results indicate a host genotype-microbiota interaction. Overall, this study concludes functional effects of the fly microbiota on PD model flies, providing support to the developing body of knowledge regarding the influence of the microbiota on PD.
Comparing data driven and physics inspired models for hopping transport in organic field effect transistors
Authors: Lakshminarayanan Madhavkrishnan , Dutta Rajdeep , Repaka D. V. Maheswar , Jayavelu Senthilnath , Leong Wei Lin , Hippalgaonkar Kedar
Published: December 2021

The past few decades have seen an uptick in the scope and range of device applications of organic semiconductors, such as organic field-effect transistors, organic photovoltaics and light-emitting diodes. Several researchers have studied electrical transport in these materials and proposed physical models to describe charge transport with different material parameters, with most disordered semiconductors exhibiting hopping transport. However, there exists a lack of a consensus among the different models to describe hopping transport accurately and uniformly. In this work, we first evaluate the efficacy of using a purely data-driven approach, i.e., symbolic regression, in unravelling the relationship between the measured field-effect mobility and the controllable inputs of temperature and gate voltage. While the regressor is able to capture the scaled mobility well with mean absolute error (MAE) ~ O(10–2), better than the traditionally used hopping transport model, it is unable to derive physically interpretable input–output relationships. We then examine a physics-inspired renormalization approach to describe the scaled mobility with respect to a scale-invariant reference temperature. We observe that the renormalization approach offers more generality and interpretability with a MAE of the ~ O(10–1), still better than the traditionally used hopping model, but less accurate as compared to the symbolic regression approach. Our work shows that physics-based approaches are powerful compared to purely data-driven modelling, providing an intuitive understanding of data with extrapolative ability.
Closely related gull species show contrasting foraging strategies in an urban environment
Authors: Lato K. A. , Madigan D. J. , Veit R. R. , Thorne L. H.
Published: December 2021

The expansion of urban landscapes has both negative and positive effects on wildlife. Understanding how different species respond to urbanization is key to assessing how urban landscapes influence regional wildlife behavior and ecosystem structure. Gulls are often described as strong urban adapters, but few studies have explored species-specific differences in habitat use. Here, we use GPS tracking in conjunction with stable isotope analysis (SIA) to quantify the habitat use and trophic ecology of great black-backed gulls (Larus marinus) and herring gulls (L. argentatus) in an urbanized area. Non-Metric Multidimensional Scaling (NMDS) of foraging locations revealed significant differences in the habitat use between species. Great black-backed gulls foraged primarily in marine habitats and herring gulls foraged primarily in specific urban habitats (e.g., landfills, dumpsters) and showed higher site fidelity in terms of the proportion of foraging sites revisited. Further, great black-backed gulls had significantly higher δ15N and δ13C than herring gulls, reflecting the use of marine, rather than urban, food sources. This study highlights the variability in urban habitat utilization among closely related species, assesses stable isotope signatures of urban diets in wild birds, and discusses ecological implications of the relative contribution of urban and marine foraging.
Response triggering by an acoustic stimulus increases with stimulus intensity and is best predicted by startle reflex activation
Authors: Maslovat Dana , Sadler Christin M. , Smith Victoria , Bui Allison , Carlsen Anthony N.
Published: December 2021

In a simple reaction time task, the presentation of a startling acoustic stimulus has been shown to trigger the prepared response at short latency, known as the StartReact effect. However, it is unclear under what conditions it can be assumed that the loud stimulus results in response triggering. The purpose of the present study was to examine how auditory stimulus intensity and preparation level affect the probability of involuntary response triggering and the incidence of activation in the startle reflex indicator of sternocleidomastoid (SCM). In two reaction time experiments, participants were presented with an irrelevant auditory stimulus of varying intensities at various time points prior to the visual go-signal. Responses were independently categorized as responding to either the auditory or visual stimulus and those with or without SCM activation (i.e., SCM+/−). Both the incidence of response triggering and proportion of SCM+ trials increased with stimulus intensity and presentation closer to the go-signal. Data also showed that participants reacted to the auditory stimulus at a much higher rate on trials where the auditory stimulus elicited SCM activity versus those that did not, and a logistic regression analysis confirmed that SCM activation is a reliable predictor of response triggering for all conditions.
Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans
Authors: Suarez-Pajes Eva , Díaz-García Claudio , Rodríguez-Pérez Héctor , Lorenzo-Salazar Jose M. , Marcelino-Rodríguez Itahisa , Corrales Almudena , Zheng Xiuwen , Callero Ariel , Perez-Rodriguez Eva , Garcia-Robaina Jose C. , González-Montelongo Rafaela , Flores Carlos , Guillen-Guio Beatriz
Published: December 2021

Despite asthma has a considerable genetic component, an important proportion of genetic risks remain unknown, especially for non-European populations. Canary Islanders have the largest African genetic ancestry observed among Southwestern Europeans and the highest asthma prevalence in Spain. Here we examined broad chromosomal regions previously associated with an excess of African genetic ancestry in Canary Islanders, with the aim of identifying novel risk variants associated with asthma susceptibility. In a two-stage cases-control study, we revealed a variant within HLA-DQB1 significantly associated with asthma risk (rs1049213, meta-analysis p = 1.30 × 10–7, OR [95% CI] = 1.74 [1.41–2.13]) previously associated with asthma and broad allergic phenotype. Subsequent fine-mapping analyses of classical HLA alleles revealed a novel allele significantly associated with asthma protection (HLA-DQA1*01:02, meta-analysis p = 3.98 × 10–4, OR [95% CI] = 0.64 [0.50–0.82]) that had been linked to infectious and autoimmune diseases, and peanut allergy. HLA haplotype analyses revealed a novel haplotype DQA1*01:02-DQB1*06:04 conferring asthma protection (meta-analysis p = 4.71 × 10–4, OR [95% CI] = 0.47 [0.29– 0.73]).
Hole doping effect of MoS2 via electron capture of He+ ion irradiation
Authors: Han Sang Wook , Yun Won Seok , Kim Hyesun , Kim Yanghee , Kim D.-H. , Ahn Chang Won , Ryu Sunmin
Published: December 2021

Beyond the general purpose of noble gas ion sputtering, which is to achieve functional defect engineering of two-dimensional (2D) materials, we herein report another positive effect of low-energy (100 eV) He+ ion irradiation: converting n-type MoS2 to p-type by electron capture through the migration of the topmost S atoms. The electron capture ability via He+ ion irradiation is valid for supported bilayer MoS2; however, it is limited at supported monolayer MoS2 because the charges on the underlying substrates transfer into the monolayer under the current condition for He+ ion irradiation. Our technique provides a stable and universal method for converting n-type 2D transition metal dichalcogenides (TMDs) into p-type semiconductors in a controlled fashion using low-energy He+ ion irradiation.
The structure of the superior and inferior parietal lobes predicts inter-individual suitability for virtual reality
Authors: Hosoda Chihiro , Futami Kyosuke , Hosokawa Kenchi , Isogaya Yuko , Terada Tsutomu , Maruya Kazushi , Okanoya Kazuo
Published: December 2021

The global virtual reality (VR) market is significantly expanding and being challenged with an increased demand owing to COVID-19. Unfortunately, VR is not useful for everyone due to large interindividual variability existing in VR suitability. To understand the neurobiological basis of this variability, we obtained neural structural and functional data from the participants using 3T magnetic resonance imaging. The participants completed one of two tasks (sports training or cognitive task) using VR, which differed in the time scale (months/minutes) and domain (motor learning/attention task). Behavioral results showed that some participants improved their motor skills in the real world after 1-month training in the virtual space or obtained high scores in the 3D attention task (high suitability for VR), whereas others did not (low suitability for VR). Brain structure analysis revealed that the structural properties of the superior and inferior parietal lobes contain information that can predict an individual’s suitability for VR.
Dengue NS1 antigen kit shows high sensitivity for detection of recombinant dengue virus-2 NS1 antigen spiked with Aedes aegypti mosquitoes
Authors: Abraham Philip Raj , R Bharathy , N Pradeep Kumar , Kumar Ashwani
Published: December 2021

Dengue, caused by the dengue virus (DENV) is a significant vector-borne disease. In absence of a specific treatment and vaccine, dengue is becoming a rising threat to public health. Currently, control of dengue mainly focuses on the surveillance of the mosquito vectors. Improved surveillance methods for DENV in mosquito populations would be highly beneficial to the public health. However, current methods of DENV detection in mosquitoes requires specialized equipment and expensive reagents and highly trained personnel. As an alternative, commercially available dengue NS1 antigen ELISA kits could be used for detection of DENV infection inAedes aegyptimosquitoes. In this study, we explored the utility of commercially available Dengue NS1 antigen kit (J. Mitra & Co. Pvt. Ltd) for the detection of recombinant dengue virus-2 (rDENV-2) NS1 protein and serum of dengue infected patient spiked withAe. aegyptimosquito pools. The kit was found to be highly sensitive and specific towards detection of all serotypes of DENV. Further, it could detect as low as 750 femto gram rDENV-2 NS1 protein. It was also observed that rDENV-2 NS1 antigen spiked with blood-fed and unfed mosquito pools could be detected. In addition, the kit also detected dengue infected patient serum spiked withAe. aegyptimosquito pools. Overall, the Dengue NS1 antigen kit displayed high sensitivity towards detection of recombinant as well as serum NS1 protein spiked withAe. aegyptimosquito pools and could be considered for the dengue virus surveillance after a field evaluation inAe. aegyptimosquitoes.
Machine learning of native T1 mapping radiomics for classification of hypertrophic cardiomyopathy phenotypes
Authors: Antonopoulos Alexios S. , Boutsikou Maria , Simantiris Spyridon , Angelopoulos Andreas , Lazaros George , Panagiotopoulos Ioannis , Oikonomou Evangelos , Kanoupaki Mikela , Tousoulis Dimitris , Mohiaddin Raad H. , Tsioufis Konstantinos , Vlachopoulos Charalambos
Published: December 2021

We explored whether radiomic features from T1 maps by cardiac magnetic resonance (CMR) could enhance the diagnostic value of T1 mapping in distinguishing health from disease and classifying cardiac disease phenotypes. A total of 149 patients (n = 30 with no heart disease, n = 30 with LVH, n = 61 with hypertrophic cardiomyopathy (HCM) and n = 28 with cardiac amyloidosis) undergoing a CMR scan were included in this study. We extracted a total of 850 radiomic features and explored their value in disease classification. We applied principal component analysis and unsupervised clustering in exploratory analysis, and then machine learning for feature selection of the best radiomic features that maximized the diagnostic value for cardiac disease classification. The first three principal components of the T1 radiomics were distinctively correlated with cardiac disease type. Unsupervised hierarchical clustering of the population by myocardial T1 radiomics was significantly associated with myocardial disease type (chi2 = 55.98, p < 0.0001). After feature selection, internal validation and external testing, a model of T1 radiomics had good diagnostic performance (AUC 0.753) for multinomial classification of disease phenotype (normal vs. LVH vs. HCM vs. cardiac amyloid). A subset of six radiomic features outperformed mean native T1 values for classification between myocardial health vs. disease and HCM phenocopies (AUC of T1 vs. radiomics model, for normal: 0.549 vs. 0.888; for LVH: 0.645 vs. 0.790; for HCM 0.541 vs. 0.638; and for cardiac amyloid 0.769 vs. 0.840). We show that myocardial texture assessed by native T1 maps is linked to features of cardiac disease. Myocardial radiomic phenotyping could enhance the diagnostic yield of T1 mapping for myocardial disease detection and classification.
Switching costs in stochastic environments drive the emergence of matching behaviour in animal decision-making through the promotion of reward learning strategies
Authors: Lyu Nan , Hu Yunbiao , Zhang Jiahua , Lloyd Huw , Sun Yue-Hua , Tao Yi
Published: December 2021

A principle of choice in animal decision-making named probability matching (PM) has long been detected in animals, and can arise from different decision-making strategies. Little is known about how environmental stochasticity may influence the switching time of these different decision-making strategies. Here we address this problem using a combination of behavioral and theoretical approaches, and show, that although a simple Win-Stay-Loss-Shift (WSLS) strategy can generate PM in binary-choice tasks theoretically, budgerigars (Melopsittacus undulates) actually apply a range of sub-tactics more often when they are expected to make more accurate decisions. Surprisingly, budgerigars did not get more rewards than would be predicted when adopting a WSLS strategy, and their decisions also exhibited PM. Instead, budgerigars followed a learning strategy based on reward history, which potentially benefits individuals indirectly from paying lower switching costs. Furthermore, our data suggest that more stochastic environments may promote reward learning through significantly less switching. We suggest that switching costs driven by the stochasticity of an environmental niche can potentially represent an important selection pressure associated with decision-making that may play a key role in driving the evolution of complex cognition in animals.
A proteomics study identifying interactors of the FSHD2 gene product SMCHD1 reveals RUVBL1-dependent DUX4 repression
Authors: Goossens Remko , Tihaya Mara S. , van den Heuvel Anita , Tabot-Ndip Klorane , Willemsen Iris M. , Tapscott Stephen J. , González-Prieto Román , Chang Jer-Gung , Vertegaal Alfred C. O. , Balog Judit , van der Maarel Silvère M.
Published: December 2021

Structural Maintenance of Chromosomes Hinge Domain Containing 1 (SMCHD1) is a chromatin repressor, which is mutated in > 95% of Facioscapulohumeral dystrophy (FSHD) type 2 cases. In FSHD2, SMCHD1 mutations ultimately result in the presence of the cleavage stage transcription factor DUX4 in muscle cells due to a failure in epigenetic repression of the D4Z4 macrosatellite repeat on chromosome 4q, which contains the DUX4 locus. While binding of SMCHD1 to D4Z4 and its necessity to maintain a repressive D4Z4 chromatin structure in somatic cells are well documented, it is unclear how SMCHD1 is recruited to D4Z4, and how it exerts its repressive properties on chromatin. Here, we employ a quantitative proteomics approach to identify and characterize novel SMCHD1 interacting proteins, and assess their functionality in D4Z4 repression. We identify 28 robust SMCHD1 nuclear interactors, of which 12 are present in D4Z4 chromatin of myocytes. We demonstrate that loss of one of these SMCHD1 interacting proteins, RuvB-like 1 (RUVBL1), further derepresses DUX4 in FSHD myocytes. We also confirm the interaction of SMCHD1 with EZH inhibitory protein (EZHIP), a protein which prevents global H3K27me3 deposition by the Polycomb repressive complex PRC2, providing novel insights into the potential function of SMCHD1 in the repression of DUX4 in the early stages of embryogenesis. The SMCHD1 interactome outlined herein can thus provide further direction into research on the potential function of SMCHD1 at genomic loci where SMCHD1 is known to act, such as D4Z4 repeats, the inactive X chromosome, autosomal gene clusters, imprinted loci and telomeres.
The enlargement of the maxillary ostium after balloon sinuplasty evaluated by a novel measuring technique from 3D CBCT images
Authors: Kalliomäki Eerika , Bizaki-Vallaskangas Argyro J. , Valtonen Olli , Rautiainen Markus
Published: December 2021

Our aim was to evaluate the effects of balloon sinuplasty on the size of the ostium in the maxillary sinuses in patients with chronic rhinosinusitis from cone beam computer tomography (CBCT) scans of the sinus. This is a blinded retrospective trial in patients who had undergone balloon sinuplasty of the maxillary sinus. CBCT scans were taken and SNOT-22 Quality of Life questionnaire completed before and 12 months after the operation. The size of the maxillary ostium was measured from the CBCT scans three-dimensionally. The association of changes in the SNOT-22 scores of the ostium was analysed. We discovered that the balloon sinuplasty increased the size of the maxillary ostium in all dimensions. The changes were statistically significant (p<0.05) in the axial diameter and the ostium area. The number of patent ostia increased after the intervention. The association between SNOT-22 score and ostium patency were statistically significant before the operation. Our conclusion is that the threedimensional measuring technique provides a reliable method to evaluate ostium dimensions. Balloon sinuplasty increased the size of the maxillary ostium and the result was maintained for 12 months after the operation.
Essential role of a Plasmodium berghei heat shock protein (PBANKA_0938300) in gametocyte development
Authors: Kashif Mohammad , Quadiri Afshana , Singh Agam Prasad
Published: December 2021

The continued existence of Plasmodium parasites in physiologically distinct environments during their transmission in mosquitoes and vertebrate hosts requires effector proteins encoded by parasite genes to provide adaptability. Parasites utilize their robust stress response system involving heat shock proteins for their survival. Molecular chaperones are involved in maintaining protein homeostasis within a cell during stress, protein biogenesis and the formation of protein complexes. Due to their critical role in parasite virulence, they are considered targets for therapeutic interventions. Our results identified a putative P. berghei heat shock protein (HSP) belonging to the HSP40 family (HspJ62), which is abundantly induced upon heat stress and expressed during all parasite stages. To determine the role HspJ62, a gene-disrupted P. berghei transgenic line was developed (ΔHspJ62), which resulted in disruption of gametocyte formation. Such parasites were unable to form subsequent sexual stages because of disrupted gametogenesis, indicating the essential role of HspJ62 in gametocyte formation. Transcriptomic analysis of the transgenic line showed downregulation of a number of genes, most of which were specific to male or female gametocytes. The transcription factor ApiAP2 was also downregulated in ΔHspJ62 parasites. Our findings suggest that the downregulation of ApiAP2 likely disrupts the transcriptional regulation of sexual stage genes, leading to impaired gametogenesis. This finding also highlights the critical role that HspJ62 indirectly plays in the development of P. berghei sexual stages and in facilitating the conversion from the asexual blood stage to the sexual stage. This study characterizes the HspJ62 protein as a fertility factor because parasites lacking it are unable to transmit to mosquitoes. This study adds an important contribution to ongoing research aimed at understanding gametocyte differentiation and formation in parasites. The molecule adds to the list of potential drug targets that can be targeted to inhibit parasite sexual development and consequently parasite transmission.
An ultrasensitive planar array p24 Gag ELISA to detect HIV-1 in diverse biological matrixes
Authors: Levinger Callie , Howard J. Natalie , Cheng Jie , Tang Pingtao , Joshi Amit , Catalfamo Marta , Bosque Alberto
Published: December 2021

Human immunodeficiency virus-1 (HIV-1) persistence in the presence of antiretroviral therapy (ART) has halted the development of curative strategies. Measuring HIV persistence is complex due to the low frequency of cells containing virus in vivo. Most of the commercially available assays to date measure nucleic acid. These assays have the advantage of being highly sensitive and allow for the analysis of sequence diversity, intactness of the HIV genome or evaluation of diverse RNA species. However, these assays are limited in evaluating translational competent viral reservoirs. In here, we developed an ultrasensitive p24 ELISA that uses the Simoa planar array technology that can detect HIV-1 virions and HIV-1 infected cells with limit of detection similar to nucleic acid assays. Furthermore, the assay is optimized to measure very low levels of p24 in different biological fluids without a major loss of sensitivity or reproducibility. Our results demonstrate that the ‘homebrew’ planar p24 ELISA immunoassay is a broadly applicable new tool to evaluate HIV persistence in diverse biological fluids and cells.
A calculation method of gas emission zone in a coal mine considering main controlling factors
Authors: Chen Yong , Liu Ronghua , Xuan Pushi
Published: December 2021

The gas emission zone is an important parameter for the space–time effect of coal excavation and gas emission. In this paper, according to the effect of roadway excavation, a numerical model of gas emission zone based on the evolution of stress and permeability was established to obtain the width of gas emission zone with different pressure and permeability coefficient. Then the numerical simulation results were verified by measuring the gas content at different depths. Through numerical simulation and field measured data, the theoretical calculation formula is established on the basis of comprehensive consideration of the influencing factors of gas emission zone. The results showed that the gas emission zone increases with the increase of coal seam gas pressure and permeability coefficient when the roadway section and exposure time are the same. The measured gas emission zone, when taking gas content as the index with the same logistic function growth curve, matches the measured results with a relative error of 1.3 to 6%. The validity of the model is also verified by field experiments. The results can provide guidance for mine gas emission and gas drainage design.
Effects of exercise training on behavior and brain function after high dose isoproterenol-induced cardiac damage
Authors: Tóth Kata , Oroszi Tamás , van der Zee Eddy A. , Nyakas Csaba , Schoemaker Regien G.
Published: December 2021

Acute sympathetic stress can result in cardiac fibrosis, but may also lead to mental dysfunction. Exercise training after isoproterenol (ISO)-induced acute sympathetic stress was investigated regarding cardiac damage, neuroinflammation, brain function and behavior. Male Wistar rats (12 months) received ISO or saline. One week later, treadmill running or control handling (sedentary) started. After 4 weeks, cognitive- and exploratory behavior were evaluated, and heart and brain tissues were analyzed regarding cardiac damage, hippocampal neuroinflammation and neuronal function. ISO did not affect cognitive performance nor hippocampal function. However, ISO reduced anxiety, coinciding with locally reduced microglia (processes) size in the hippocampus. Exercise in ISO rats reversed anxiety, did not affect microglia morphology, but increased brain function. Thus, exercise after ISO did not affect cardiac damage, cognition or hippocampal neuroinflammation, but normalized anxiety. Increased localized BDNF expression may indicate improved brain function.
Overcooling of offices reveals gender inequity in thermal comfort
Authors: Parkinson Thomas , Schiavon Stefano , de Dear Richard , Brager Gail
Published: December 2021

Growth in energy use for indoor cooling tripled between 1990 and 2016 to outpace any other end use in buildings. Part of this energy demand is wasted on excessive cooling of offices, a practice known as overcooling. Overcooling has been attributed to poorly designed or managed air-conditioning systems with thermostats that are often set below recommended comfort temperatures. Prior research has reported lower thermal comfort for women in office buildings, but there is insufficient evidence to explain the reasons for this disparity. We use two large and independent datasets from US buildings to show that office temperatures are less comfortable for women largely due to overcooling. Survey responses show that uncomfortable temperatures are more likely to be cold than hot regardless of season. Crowdsourced data suggests that overcooling is a common problem in warm weather in offices across the US. The associated impacts of this pervasive overcooling on well-being and performance are borne predominantly by women. The problem is likely to increase in the future due to growing demand for cooling in increasingly extreme climates. There is a need to rethink the approach to air-conditioning office buildings in light of this gender inequity caused by overcooling.
Characteristics of the disastrous debris flow of Chediguan gully in Yinxing town, Sichuan Province, on August 20, 2019
Authors: Li Ning , Tang Chuan , Zhang Xianzheng , Chang Ming , Shu Zhile , Bu Xianghang
Published: December 2021

On August 20, 2019, at 2 a.m., a disastrous debris flow occurred in Chediguan gully in Yinxing town, China. The debris flow destroyed the drainage groove and the bridge at the exit of the gully. In addition, the debris flow temporarily blocked the Minjiang River during the flood peak, flooding the Taipingyi hydropower station 200 m upstream and leaving two plant workers missing. To further understand the activity of the debris flow after the Wenchuan earthquake, the characteristics of this debris flow event were studied. Eleven years after the Wenchuan earthquake, a disastrous debris flow still occurred in the Chediguan catchment, causing more severe losses than those of earlier debris flows. In this paper, the formation mechanism and dynamic characteristics of this debris flow event are analysed based on a drone survey, high-definition remote sensing interpretations and other means. The catastrophic debris flow event indicates that debris flows in the Wenchuan earthquake area are still active. A large amount of dredging work in the main gully could effectively reduce the debris flow risk in the gully. In addition, it is also important to repair or rebuild damaged mitigation measures and to establish a real-time monitoring and early warning system for the high-risk gully.
Ectomycorrhizal fungus supports endogenous rhythmic growth and corresponding resource allocation in oak during various below- and aboveground biotic interactions
Authors: Tarkka Mika T. , Grams Thorsten E. E. , Angay Oguzhan , Kurth Florence , Maboreke Hazel R. , Mailänder Sarah , Bönn Markus , Feldhahn Lasse , Fleischmann Frank , Ruess Liliane , Schädler Martin , Scheu Stefan , Schrey Silvia D. , Buscot Francois , Herrmann Sylvie
Published: December 2021

Endogenous rhythmic growth (ERG) is displayed by many tropical and some major temperate tree species and characterized by alternating root and shoot flushes (RF and SF). These flushes occur parallel to changes in biomass partitioning and in allocation of recently assimilated carbon and nitrogen. To address how biotic interactions interplay with ERG, we cross-compared the RF/SF shifts in oak microcuttings in the presence of pathogens, consumers and a mycorrhiza helper bacterium, without and with an ectomycorrhizal fungus (EMF), and present a synthesis of the observations. The typical increase in carbon allocation to sink leaves during SF did not occur in the presence of root or leaf pathogens, and the increase in nitrogen allocation to lateral roots during RF did not occur with the pathogens. The RF/SF shifts in resource allocation were mostly restored upon additional interaction with the EMF. Its presence led to increased resource allocation to principal roots during RF, also when the oaks were inoculated additionally with other interactors. The interactors affected the alternating, rhythmic growth and resource allocation shifts between shoots and roots. The restoring role of the EMF on RF/SF changes in parallel to the corresponding enhanced carbon and nitrogen allocation to sink tissues suggests that the EMF is supporting plants in maintaining the ERG.
Inference of tissue relative proportions of the breast epithelial cell types luminal progenitor, basal, and luminal mature
Authors: Bartlett Thomas E. , Jia Peiwen , Chandna Swati , Roy Sandipan
Published: December 2021

Single-cell analysis has revolutionised genomic science in recent years. However, due to cost and other practical considerations, single-cell analyses are impossible for studies based on medium or large patient cohorts. For example, a single-cell analysis usually costs thousands of euros for one tissue sample from one volunteer, meaning that typical studies using single-cell analyses are based on very few individuals. While single-cell genomic data can be used to examine the phenotype of individual cells, cell-type deconvolution methods are required to track the quantities of these cells in bulk-tissue genomic data. Hormone receptor negative breast cancers are highly aggressive, and are thought to originate from a subtype of epithelial cells called the luminal progenitor. In this paper, we show how to quantify the number of luminal progenitor cells as well as other epithelial subtypes in breast tissue samples using DNA and RNA based measurements. We find elevated levels of cells which resemble these hormone receptor negative luminal progenitor cells in breast tumour biopsies of hormone receptor negative cancers, as well as in healthy breast tissue samples from BRCA1 (FANCS) mutation carriers. We also find that breast tumours from carriers of heterozygous mutations in non-BRCA Fanconi Anaemia pathway genes are much more likely to be hormone receptor negative. These findings have implications for understanding hormone receptor negative breast cancers, and for breast cancer screening in carriers of heterozygous mutations of Fanconi Anaemia pathway genes.
Clinical characteristics and outcomes of Korean patients with sarcoidosis
Authors: Kim Ho Jeong , Kim Hyeong Min , Song Jin Woo
Published: December 2021

Sarcoidosis is a systemic granulomatous disorder of unknown cause involving multiple organs. Its clinical presentation and prognosis vary among races. We identified the clinical characteristics and outcomes of Korean patients with sarcoidosis. Clinical data of 367 Korean patients with biopsy-proven sarcoidosis diagnosed in 2001–2017 were retrospectively analyzed. Treatment responses included improvement, stability, or progression based on changes in pulmonary sarcoidosis on chest images. The mean age was 47.4 years, and 67.3% of patients were women. The median follow-up period was 80 months. The highest prevalence was observed in individuals aged 50–59 years (30–39 years in men, 50–59 years in women), and the number of diagnoses showed an increasing trend. Lung involvement was the most common (93.5%), followed by the skin, eyes, and extrathoracic lymph nodes. Among patients with lung involvement and a follow-up period of ≥ 3 months, 66.8%, 31.0%, and 2.2% showed improvement, stability, and progression, respectively. Eleven patients (2.9%) died, and the 5-year survival rate was 99%. The number of diagnosed cases showed an increasing trend, and the mean age at diagnosis was increased compared with that in previous reports. Organ involvement was similar to that of Westerners, although the prognosis appeared better.
Quantitative assessment of dry mouth in scrub typhus using salivary scintigraphy
Authors: Hwang Joo-Hee , Han Yeon-Hee , Rahman MD Tazikur , Lee Chang-Seop
Published: December 2021

Scrub typhus is an acute febrile illness caused by the intracellular pathogen Orientia tsutsugamushi. The clinical features include fever, myalgia, lymphadenopathy, and dry mouth. However, no studies have assessed the symptom of dry mouth in patients with scrub typhus. We investigated the pattern of salivary scintigraphy during the acute febrile state and compared it with any changes after treatment. Fourteen patients underwent both pre- and post-treatment salivary scintigraphy. Imaging analysis was conducted using radioactivity in the oral cavity, parotid glands, and submandibular glands. During the acute phase, the radioactivity in the oral cavity markedly decreased, while that in the parotid and submandibular glands was preserved. After treatment, radioactivity in the oral cavity showed a significant increase at 20-min, 40-min, and after wash-out. The ejection fraction (%) of the parotid glands also increased after treatment. In contrast, the radioactivity levels of the parotid and submandibular glands were not statistically different after treatment. Salivary scintigraphy indicated that insufficient saliva excretion from the salivary glands into the oral cavity was one reason for the dry mouth reported by patients with scrub typhus. In the future, salivary scintigraphy imaging could contribute to the evaluation of dry mouth in patients with scrub typhus.
High resolution proteomics of Aedes aegypti salivary glands infected with either dengue, Zika or chikungunya viruses identify new virus specific and broad antiviral factors
Authors: Chowdhury Avisha , Modahl Cassandra M. , Missé Dorothée , Kini R. Manjunatha , Pompon Julien
Published: December 2021

Arboviruses such as dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses infect close to half a billion people per year, and are primarily transmitted throughAedes aegyptibites. Infection-induced changes in mosquito salivary glands (SG) influence transmission by inducing antiviral immunity, which restricts virus replication in the vector, and by altering saliva composition, which influences skin infection. Here, we profiled SG proteome responses to DENV serotype 2 (DENV2), ZIKV and CHIKV infections by using high-resolution isobaric-tagged quantitative proteomics. We identified 218 proteins with putative functions in immunity, blood-feeding or related to the cellular machinery. We observed that 58, 27 and 29 proteins were regulated by DENV2, ZIKV and CHIKV infections, respectively. While the regulation patterns were mostly virus-specific, we separately depleted four uncharacterized proteins that were upregulated by all three viral infections to determine their effects on these viral infections. Our study suggests that gamma-interferon responsive lysosomal thiol-like (GILT-like) has an anti-ZIKV effect, adenosine deaminase (ADA) has an anti-CHIKV effect, salivary gland surface protein 1 (SGS1) has a pro-ZIKV effect and salivary gland broad-spectrum antiviral protein (SGBAP) has an antiviral effect against all three viruses. The comprehensive description of SG responses to three global pathogenic viruses and the identification of new restriction factors improves our understanding of the molecular mechanisms influencing transmission.
Identification of an epithelial-mesenchymal transition-related lncRNA prognostic signature for patients with glioblastoma
Authors: Yang XinJie , Niu Sha , Liu JiaQiang , Fang Jincheng , Wu ZeYu , Ling Shizhang , Di GuangFu , Jiang XiaoChun
Published: December 2021

Glioblastoma (GBM) is a strikingly heterogeneous and lethal brain tumor with very poor prognosis. LncRNAs play critical roles in the tumorigenesis of GBM through regulation of various cancer-related genes and signaling pathways. Here, we focused on the essential role of EMT and identified 78 upregulated EMT-related genes in GBM through differential expression analysis and Gene set enrichment analysis (GSEA). A total of 301 EMT-related lncRNAs were confirmed in GBM through Spearman correlation analysis and a prognostic signature consisting of seven EMT-related lncRNAs (AC012615.1, H19, LINC00609, LINC00634, POM121L9P, SNHG11, and USP32P3) was established by univariate and multivariate Cox regression analyses. Significantly, Kaplan–Meier analysis and receiver-operating-characteristic (ROC) curve validated the accuracy and efficiency of the signature to be satisfactory. Quantitative real-time (qRT)-PCR assay demonstrated the expression alterations of the seven lncRNAs between normal glial and glioma cell lines. Functional enrichment analysis revealed multiple EMT and metastasis-related pathways were associated with the EMT-related lncRNA prognostic signature. In addition, we observed the degree of immune cell infiltration and immune responses were significantly increased in high-risk subgroup compared with low-risk subgroup. In conclusion, we established an effective and robust EMT-related lncRNA signature which was expected to predict the prognosis and immunotherapy response for GBM patients.