bluuebunny/crossref_metadata_2025 huggingface dataset:
Strain and crystallographic identification of the helically concaved gap surfaces of chiral nanoparticles
Authors: Choi Sungwook , Im Sang Won , Huh Ji-Hyeok , Kim Sungwon , Kim Jaeseung , Lim Yae-Chan , Kim Ryeong Myeong , Han Jeong Hyun , Kim Hyeohn , Sprung Michael , Lee Su Yong , Cha Wonsuk , Harder Ross , Lee Seungwoo , Nam Ki Tae , Kim Hyunjung
Published: June 2023

Identifying the three-dimensional (3D) crystal plane and strain-field distributions of nanocrystals is essential for optical, catalytic, and electronic applications. However, it remains a challenge to image concave surfaces of nanoparticles. Here, we develop a methodology for visualizing the 3D information of chiral gold nanoparticles ≈ 200 nm in size with concave gap structures by Bragg coherent X-ray diffraction imaging. The distribution of the high-Miller-index planes constituting the concave chiral gap is precisely determined. The highly strained region adjacent to the chiral gaps is resolved, which was correlated to the 432-symmetric morphology of the nanoparticles and its corresponding plasmonic properties are numerically predicted from the atomically defined structures. This approach can serve as a comprehensive characterization platform for visualizing the 3D crystallographic and strain distributions of nanoparticles with a few hundred nanometers, especially for applications where structural complexity and local heterogeneity are major determinants, as exemplified in plasmonics.
Examining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration
Authors: Follmann Dean , O’Brien Meagan P. , Fintzi Jonathan , Fay Michael P. , Montefiori David , Mateja Allyson , Herman Gary A. , Hooper Andrea T. , Turner Kenneth C. , Chan Kuo- Chen , Forleo-Neto Eduardo , Isa Flonza , Baden Lindsey R. , El Sahly Hana M. , Janes Holly , Doria-Rose Nicole , Miller Jacqueline , Zhou Honghong , Dang Weiping , Benkeser David , Fong Youyi , Gilbert Peter B. , Marovich Mary , Cohen Myron S.
Published: June 2023

While new vaccines for SARS-CoV-2 are authorized based on neutralizing antibody (nAb) titer against emerging variants of concern, an analogous pathway does not exist for preventative monoclonal antibodies. In this work, nAb titers were assessed as correlates of protection against COVID-19 in the casirivimab + imdevimab monoclonal antibody (mAb) prevention trial (ClinicalTrials.gov #NCT4452318) and in the mRNA-1273 vaccine trial (ClinicalTrials.gov #NCT04470427). In the mAb trial, protective efficacy of 92% (95% confidence interval (CI): 84%, 98%) is associated with a nAb titer of 1000 IU50/ml, with lower efficacy at lower nAb titers. In the vaccine trial, protective efficacies of 93% [95% CI: 91%, 95%] and 97% (95% CI: 95%, 98%) are associated with nAb titers of 100 and 1000 IU50/ml, respectively. These data quantitate a nAb titer correlate of protection for mAbs benchmarked alongside vaccine induced nAb titers and support nAb titer as a surrogate endpoint for authorizing new mAbs.
Morphogenesis of starfish polymersomes
Authors: Sun Jiawei , Kleuskens Sandra , Luan Jiabin , Wang Danni , Zhang Shaohua , Li Wei , Uysal Gizem , Wilson Daniela A.
Published: June 2023

The enhanced membrane stability and chemical versatility of polymeric vesicles have made them promising tools in micro/nanoreactors, drug delivery, cell mimicking, etc. However, shape control over polymersomes remains a challenge and has restricted their full potential. Here we show that local curvature formation on the polymeric membrane can be controlled by applying poly(N-isopropylacrylamide) as a responsive hydrophobic unit, while adding salt ions to modulate the properties of poly(N-isopropylacrylamide) and its interaction with the polymeric membrane. Polymersomes with multiple arms are fabricated, and the number of arms could be tuned by salt concentration. Furthermore, the salt ions are shown to have a thermodynamic effect on the insertion of poly(N-isopropylacrylamide) into the polymeric membrane. This controlled shape transformation can provide evidence for studying the role of salt ions in curvature formation on polymeric membranes and biomembranes. Moreover, potential stimuli-responsive non-spherical polymersomes can be good candidates for various applications, especially in nanomedicine.
Predicting frictional aging from bulk relaxation measurements
Authors: Farain Kasra , Bonn Daniel
Published: June 2023

The coefficient of static friction between solids normally increases with the time they have remained in static contact before the measurement. This phenomenon, known as frictional aging, is at the origin of the difference between static and dynamic friction coefficients but has remained difficult to understand. It is usually attributed to a slow expansion of the area of atomic contact as the interface changes under pressure. This is however challenging to quantify as surfaces have roughness at all length scales. In addition, friction is not always proportional to the contact area. Here we show that the normalized stress relaxation of the surface asperities during frictional contact with a hard substrate is the same as that of the bulk material, regardless of the asperities’ size or degree of compression. This result enables us to predict the frictional aging of rough interfaces based on the bulk material properties of two typical polymers: polypropylene and polytetrafluoroethylene.
The inhibition mechanism of the SUR2A-containing KATP channel by a regulatory helix
Authors: Ding Dian , Hou Tianyi , Wei Miao , Wu Jing-Xiang , Chen Lei
Published: June 2023

KATP channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing KATP channels differ from other subtypes in their sensitivity to Mg-ADP activation. However, the underlying structural mechanism remains poorly understood. Here we present a series of cryo-EM structures of SUR2A in the presence of different combinations of Mg-nucleotides and the allosteric inhibitor repaglinide. These structures uncover regulatory helix (R helix) on the NBD1-TMD2 linker, which wedges between NBD1 and NBD2. R helix stabilizes SUR2A in the NBD-separated conformation to inhibit channel activation. The competitive binding of Mg-ADP with Mg-ATP to NBD2 mobilizes the R helix to relieve such inhibition, allowing channel activation. The structures of SUR2B in similar conditions suggest that the C-terminal 42 residues of SUR2B enhance the structural dynamics of NBD2 and facilitate the dissociation of the R helix and the binding of Mg-ADP to NBD2, promoting NBD dimerization and subsequent channel activation.
A corrosion-resistant RuMoNi catalyst for efficient and long-lasting seawater oxidation and anion exchange membrane electrolyzer
Authors: Kang Xin , Yang Fengning , Zhang Zhiyuan , Liu Heming , Ge Shiyu , Hu Shuqi , Li Shaohai , Luo Yuting , Yu Qiangmin , Liu Zhibo , Wang Qiang , Ren Wencai , Sun Chenghua , Cheng Hui-Ming , Liu Bilu
Published: June 2023

Direct seawater electrolysis is promising for sustainable hydrogen gas (H2) production. However, the chloride ions in seawater lead to side reactions and corrosion, which result in a low efficiency and poor stability of the electrocatalyst and hinder the use of seawater electrolysis technology. Here we report a corrosion-resistant RuMoNi electrocatalyst, in which the in situ-formed molybdate ions on its surface repel chloride ions. The electrocatalyst works stably for over 3000 h at a high current density of 500 mA cm−2 in alkaline seawater electrolytes. Using the RuMoNi catalyst in an anion exchange membrane electrolyzer, we report an energy conversion efficiency of 77.9% and a current density of 1000 mA cm−2 at 1.72 V. The calculated price per gallon of gasoline equivalent (GGE) of the H2 produced is $ 0.85, which is lower than the 2026 technical target of $ 2.0/GGE set by the United Stated Department of Energy, thus, suggesting practicability of the technology.
The NAD salvage pathway in mesenchymal cells is indispensable for skeletal development in mice
Authors: Warren Aaron , Porter Ryan M. , Reyes-Castro Olivia , Ali Md Mohsin , Marques-Carvalho Adriana , Kim Ha-Neui , Gatrell Landon B. , Schipani Ernestina , Nookaew Intawat , O’Brien Charles A. , Morello Roy , Almeida Maria
Published: June 2023

NAD is an essential co-factor for cellular energy metabolism and multiple other processes. Systemic NAD+ deficiency has been implicated in skeletal deformities during development in both humans and mice. NAD levels are maintained by multiple synthetic pathways but which ones are important in bone forming cells is unknown. Here, we generate mice with deletion of Nicotinamide Phosphoribosyltransferase (Nampt), a critical enzyme in the NAD salvage pathway, in all mesenchymal lineage cells of the limbs. At birth, NamptΔPrx1 exhibit dramatic limb shortening due to death of growth plate chondrocytes. Administration of the NAD precursor nicotinamide riboside during pregnancy prevents the majority of in utero defects. Depletion of NAD post-birth also promotes chondrocyte death, preventing further endochondral ossification and joint development. In contrast, osteoblast formation still occurs in knockout mice, in line with distinctly different microenvironments and reliance on redox reactions between chondrocytes and osteoblasts. These findings define a critical role for cell-autonomous NAD homeostasis during endochondral bone formation.
Psychosocial stress, interpersonal sensitivity, and social withdrawal in clinical high risk for psychosis: a systematic review
Authors: Georgiades A. , Almuqrin A. , Rubinic P. , Mouhitzadeh K. , Tognin S. , Mechelli A.
Published: June 2023

Stress has repeatedly been implicated in the onset and exacerbation of positive symptoms of psychosis. Increasing interest is growing for the role of psychosocial stress in the development of psychosis symptoms in individuals at Clinical High Risk (CHR) for psychosis. A systematic review was therefore conducted to summarize the existing evidence base regarding psychosocial stress, interpersonal sensitivity, and social withdrawal in individuals at CHR for psychosis. An electronic search of Ovid (PsychINFO, EMBASE, MEDLINE, and GLOBAL HEALTH) was conducted until February 2022. Studies that examined psychosocial stress in CHR were included. Twenty-nine studies were eligible for inclusion. Psychosocial stress, interpersonal sensitivity, and social withdrawal were higher in CHR individuals compared to healthy controls and there was some evidence of their association with positive symptoms of psychosis. Two types of psychosocial stressors were found to occur more frequently with CHR status, namely daily stressors, and early and recent trauma, while significant life events did not appear to be significant. Greater exposure to psychosocial stress, emotional abuse, and perceived discrimination significantly increased risk of transition to psychosis in CHR. No studies examined the role of interpersonal sensitivity on transition to psychosis in CHR. This systematic review provides evidence for the association of trauma, daily stressors, social withdrawal, and interpersonal sensitivity with CHR status. Further studies investigating the impact of psychosocial stress on psychosis symptom expression in individuals at CHR and its effects on transition to psychosis are therefore warranted.
Ramularia leaf spot: PCR-based methods reveal widespread distribution of Ramulariopsis pseudoglycines and limited presence of R. gossypii in Brazil
Authors: da Silva Aline Suelen , Rennó Marcelo Henrique Lisboa , Quitania Ana Clara Ribeiro , Café-Filho Adalberto Corrêa , Miller Robert Neil Gerard , de Araújo Alderi Emidio , Pinho Danilo Batista
Published: June 2023

Whilst Brazil is the fourth largest cotton producer globally, incidence of ramularia leaf spot (RLS) has decreased yield. In 2017–18 and 2018–19, ca. 300 fungal samples were collected throughout Brazil. Hyphal tip cultures were obtained for amplification of the RNA polymerase II (RPB2), 28S rRNA, the ribosomal DNA internal transcribed spacers (ITS), actin (ACT), elongation factor (EF1-α) and histone H3 (HIS3) genomic regions. Additionally, sequences of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were obtained by nanopore sequencing and the EF1-α region was selected as a marker for rapid recognition of Ramulariopsis species. Clade assignments based on the concatenated-sequence tree were identical to those in tree generated by RPB2-sequences, as well as in an RPB2 haplotype network and an ISSR (TGTC)4 dendrogram, in identification with species-specific primers and based on morphological comparisons. Out of 267 examined isolates, 252 were identified as Ramulariopsis pseudoglycines, indicating this species as the most widespread causal agent of cotton RLS in the Brazilian growing regions. Species-specific primers developed in the study that target the EF1-α gene provide an opportunity for extensive RLS sampling worldwide to study the distribution of Ramulariopsis species. Such data will aid breeders and plant pathologists in cotton disease resistance development and fungicide resistance avoidance.
The QuantuMDx Q-POC SARS-CoV-2 RT-PCR assay for rapid detection of COVID-19 at point-of-care: preliminary evaluation of a novel technology
Authors: Caffry Jessica , Selby Matthew , Barr Katie , Morgan George , McGurk David , Scully Philip , Park Catherine , Caridis Anna-Maria , Southworth Emily , Morrison Jack , Clark David J. , Davies Benedict M. O. , Eckersley Nicholas M. , Groppelli Elisabetta , Kirwan Daniela E. , Monahan Irene , Augustin Yolanda , Toombs Colin , Planche Tim , Staines Henry M. , Krishna Sanjeev
Published: June 2023

Accurate and rapid point-of-care (PoC) diagnostics are critical to the control of the COVID-19 pandemic. The current standard for accurate diagnosis of SARS-CoV-2 is laboratory-based reverse transcription polymerase chain reaction (RT-PCR) assays. Here, a preliminary prospective performance evaluation of the QuantuMDx Q-POC SARS-CoV-2 RT-PCR assay is reported. Between November 2020 and March 2021, 49 longitudinal combined nose/throat (NT) swabs from 29 individuals hospitalised with RT-PCR confirmed COVID-19 were obtained at St George’s Hospital, London. In addition, 101 mid-nasal (MN) swabs were obtained from healthy volunteers in June 2021. These samples were used to evaluate the Q-POC SARS-CoV-2 RT-PCR assay. The primary analysis was to compare the sensitivity and specificity of the Q-POC test against a reference laboratory-based RT-PCR assay. The overall sensitivity of the Q-POC test compared with the reference test was 96.88% (83.78– 99.92% CI) for a cycle threshold (Ct) cut-off value for the reference test of 35 and 80.00% (64.35–90.95% CI) without altering the reference test’s Ct cut-off value of 40. The Q-POC test is a sensitive, specific and rapid PoC test for SARS-CoV-2 at a reference Ct cut-off value of 35. The Q-POC test provides an accurate option for RT-PCR at PoC without the need for sample pre-processing and laboratory handling, enabling rapid diagnosis and clinical triage in acute care and other settings.
Research on psychological attributions and intervention strategies of new energy hybrid vehicle purchase behavior
Authors: Guo Qing , You Wenlan
Published: June 2023

Based on the questionnaire survey, this paper developed a theoretical model of the factors influencing consumers' purchase behavior for new energy hybrid vehicles using the theory of planned behavior and structural equation modeling techniques. It then used SPSS and AMOS to perform factor analysis, model fitness, and path analysis to reach the following conclusions: perceived behavioral control, behavioral attitude, and subjective norm have a significant positive influence on behavioral intention, and behavioral intention has a significant influence on actual behavior. However, there is no significant effect of perceived behavioral control on actual purchase behavior, but rather an indirect effect on actual behavior through the mediating variable of behavioral intention. The analysis of the multi-group model based on the individual characteristics of consumers showed that the coefficient of subjective norm on behavioral intention was higher for extroverted consumers than for introverted consumers; the influence of behavioral attitude on behavioral intention was significantly higher for introverted consumers than for subjective norm on behavioral intention.
Stacked ensemble machine learning for porosity and absolute permeability prediction of carbonate rock plugs
Authors: Kalule Ramanzani , Abderrahmane Hamid Ait , Alameri Waleed , Sassi Mohamed
Published: June 2023

This study employs a stacked ensemble machine learning approach to predict carbonate rocks' porosity and absolute permeability with various pore-throat distributions and heterogeneity. Our dataset consists of 2D slices from 3D micro-CT images of four carbonate core samples. The stacking ensemble learning approach integrates predictions from several machine learning-based models into a single meta-learner model to accelerate the prediction and improve the model's generalizability. We used the randomized search algorithm to attain optimal hyperparameters for each model by scanning over a vast hyperparameter space. To extract features from the 2D image slices, we applied the watershed-scikit-image technique. We showed that the stacked model algorithm effectively predicts the rock's porosity and absolute permeability.
Evolving relationship of Nares Strait ice arches on sea ice along the Strait and the North Water, the Arctic’s most productive polynya
Authors: Moore G. W. K. , Howell S. E. L. , Brady M.
Published: June 2023

Nares Strait, the waterway that separates northwest Greenland from Ellesmere Island, is a major pathway along which sea ice leaves the Arctic, including the planet’s oldest and thickest sea ice that is experiencing an accelerated loss. Ice arches that develop during the winter at the Strait’s northern or southern terminus can remain stable for months at a time during which the transport of sea ice ceases. The Arctic’s most productive polynya, the North Water (NOW) orPikialasorsuaq(West Greenlandic for ‘great upwelling’) forms at the Strait’s southern end. There is evidence that a warming climate and the concomitant thinning of Arctic sea ice is weakening the arches and it has been proposed that this may impact the stability of NOW and the complex ecosystem that it sustains. Here we employ a categorization of recent winters with respect to the presence or absence of ice arches to explore their impact on sea ice along the Strait and over the NOW. We find that winters during which a southern ice arch is absent are associated with a reduced and thinner ice cover along the Strait with ice conditions over the NOW similar to that during winters with a southern arch. In winters, without a southern arch, there is also an acceleration of the winds along the Strait that contributes to the presence of reduced ice cover. Ocean color remote sensing data suggests that current levels of primary productivity over the NOW are independent of the presence or absence of an ice arch. The results suggest more research is needed to assess the stability of the NOW, with respect to reduced ice cover and primary productivity, in a future where ice arches cease to form along Nares Strait.
Interplay between uncertainty intolerance, emotion regulation, cognitive flexibility, and psychopathology during the COVID-19 pandemic: a multi-wave study
Authors: Godara Malvika , Everaert Jonas , Sanchez-Lopez Alvaro , Joormann Jutta , De Raedt Rudi
Published: June 2023

The COVID-19 pandemic has created a significant mental health burden on the global population. Studies during the pandemic have shown that risk factors such as intolerance of uncertainty and maladaptive emotion regulation are associated with increased psychopathology. Meanwhile, protective factors such as cognitive control and cognitive flexibility have been shown to protect mental health during the pandemic. However, the potential pathways through which these risk and protective factors function to impact mental health during the pandemic remain unclear. In the present multi-wave study, 304 individuals (18 years or older, 191 Males), residing in the USA during data collection, completed weekly online assessments of validated questionnaires across a period of five weeks (27th March 2020–1st May 2020). Mediation analyses revealed that longitudinal changes in emotion regulation difficulties mediated the effect of increases in intolerance of uncertainty on increases in stress, depression, and anxiety during the COVID-19 pandemic. Further, individual differences in cognitive control and flexibility moderated the relationship between intolerance of uncertainty and emotion regulation difficulties. While intolerance of uncertainty and emotion regulation difficulties emerged as risk factors for mental health, cognitive control and flexibility seems to protect against the negative effects of the pandemic and promote stress resilience. Interventions aimed at enhancing cognitive control and flexibility might promote the protection of mental health in similar global crises in the future.
Screening macroalgae for mitigation of enteric methane in vitro
Authors: Wasson D. E. , Stefenoni H. , Cueva S. F. , Lage C. , Räisänen S. E. , Melgar A. , Fetter M. , Hennessy M. , Narayan K. , Indugu N. , Pitta D. , Yarish C. , Hristov A. N.
Published: June 2023

This study investigated the effects of 67 species of macroalgae on methanogenesis and rumen fermentation in vitro. Specimens were analyzed for their effect on ruminal fermentation and microbial community profiles. Incubations were carried out in an automated gas production system for 24-h and macroalgae were tested at 2% (feed dry matter basis) inclusion rate. Methane yield was decreased 99% byAsparagopsis taxiformis(AT) when compared with the control.Colpomenia peregrinaalso decreased methane yield 14% compared with control; no other species influenced methane yield. Total gas production was decreased 14 and 10% by AT andSargassum hornericompared with control, respectively. Total volatile fatty acid (VFA) concentration was decreased between 5 and 8% by 3 macroalgae, whereas AT reduced it by 10%. Molar proportion of acetate was decreased 9% by AT, along with an increase in propionate by 14%.Asparagopsis taxiformisalso increased butyrate and valerate molar proportions by 7 and 24%, respectively, whereas 3 macroalgae species decreased molar proportion of butyrate 3 to 5%.Vertebrata lanosaincreased ammonia concentration, whereas 3 other species decreased it. Inclusion of AT decreased relative abundance ofPrevotella, Bacteroidales, Firmicutes and Methanobacteriaceae,whereasClostridium, AnaerovibrioandMethanobrevibacterwere increased. Specific gene activities forMethanosphaera stadtmaneandMethanobrevibacter ruminantiumwere decreased by AT inclusion. In this in vitro study,Asparagopsis taxiformiswas most effective in decreasing methane concentration and yield, but also decreased total gas production and VFA concentration which indicates overall inhibition of ruminal fermentation. No other macroalgae were identified as potential mitigants of enteric methane.
miRNAs signature as potential biomarkers for cervical precancerous lesions in human papillomavirus positive women
Authors: González-Ramírez Martha I. , Cardona Yurley T. , Agudelo María C. , López Carolina , Florez-Acosta Juan J. , Agudelo-Gamboa Samuel , Garai Jone , Li Li , Orozco-Castaño Carlos A. , Zabaleta Jovanny , Sánchez Gloria I.
Published: June 2023

Biomarkers to identify women at risk of cervical cancer among those with high-risk HPV infection (hrHPV+) are needed. Deregulated expression of microRNAs (miRNAs) contributes to hrHPV-induced cervical carcinogenesis. We aimed at identifying miRNAs with the capacity to distinguish high (CIN2+) and low (≤ CIN1) grade cervical lesions. We sequenced miRNA libraries from Formalin-Fixed Paraffin-Embedded (FFPE) tissues from women with CIN2+ (n = 10) and age-matched women with ≤ CIN1 (n = 10), randomly and retrospectively selected from a trial that followed women for 24 months after a hrHPV+ test at the screening visit. Five miRNAs differentially expressed were validated by RT-qPCR in an independent set of FFPE tissues with a reviewed diagnosis of CIN2+ (n = 105) and ≤ CIN1 (n = 105). The Ingenuity Pathway Analysis (IPA) was conducted to identify mRNAs inversely correlated with the top 25 differentially expressed miRNAs. Inverse correlations with 401 unique mRNA targets were identified for fourteen of the top 25 differentially expressed miRNAs. Eleven of these miRNAs targeted 26 proteins of pathways deregulated by HPV E6 and E7 oncoproteins and two of them, miR-143-5p and miR-29a-3p, predicted CIN2+ and CIN3+ in the independent validation by RT-qPCR of FFPE tissues from hrHPV-positive women.
Diagnostic performance of calf circumference, SARC-F, and SARC-CalF for possible sarcopenia screening in Indonesia
Authors: Kandinata Stefanus G. , Widajanti Novira , Ichwani Jusri , Firdausi Hadiq , Aryana I. G. P. S. , Alkaff Firas F.
Published: June 2023

Asian working group for sarcopenia (AWGS) recently introduced “possible sarcopenia” diagnosis for early identification of sarcopenia in the primary healthcare. For initial screening, 3 modalities, i.e. calf circumference (CC) measurement, strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) questionnaire, and a combination of both (SARC-CalF), are recommended. However, no validation study has been done until now. Therefore, this study aims to evaluate the diagnostic performance of the recommended screening modalities using data from Indonesia. This cross-sectional study included subjects aged ≥ 60 years old who visited primary healthcare in Surabaya, Indonesia. The diagnosis of possible sarcopenia was confirmed with hand-grip strength and repeated chair stand test. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. Among 266 subjects, 186 (70%) were diagnosed with possible sarcopenia. Using the recommended cut-off, the area under the curve, sensitivity, and specificity were 0.511, 48.39% and 53.75% for CC, 0.543, 8.60% and 100% for SARC-F, and 0.572, 19.35% and 95% for SACRC-CalF. Our findings indicate that the diagnostic performance of the recommended screening modalities is poor. Multicenter studies from different areas in Indonesia should be done to confirm these findings.
Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce inflammation and epithelial dysfunction
Authors: England Elizabeth , Rees D. Gareth , Scott Ian Christopher , Carmen Sara , Chan Denice T. Y. , Chaillan Huntington Catherine E. , Houslay Kirsty F. , Erngren Teodor , Penney Mark , Majithiya Jayesh B. , Rapley Laura , Sims Dorothy A. , Hollins Claire , Hinchy Elizabeth C. , Strain Martin D. , Kemp Benjamin P. , Corkill Dominic J. , May Richard D. , Vousden Katherine A. , Butler Robin J. , Mustelin Tomas , Vaughan Tristan J. , Lowe David C. , Colley Caroline , Cohen E. Suzanne
Published: June 2023

Interleukin (IL)-33 is a broad-acting alarmin cytokine that can drive inflammatory responses following tissue damage or infection and is a promising target for treatment of inflammatory disease. Here, we describe the identification of tozorakimab (MEDI3506), a potent, human anti-IL-33 monoclonal antibody, which can inhibit reduced IL-33 (IL-33red) and oxidized IL-33 (IL-33ox) activities through distinct serum-stimulated 2 (ST2) and receptor for advanced glycation end products/epidermal growth factor receptor (RAGE/EGFR complex) signalling pathways. We hypothesized that a therapeutic antibody would require an affinity higher than that of ST2 for IL-33, with an association rate greater than 107 M−1 s−1, to effectively neutralize IL-33 following rapid release from damaged tissue. An innovative antibody generation campaign identified tozorakimab, an antibody with a femtomolar affinity for IL-33red and a fast association rate (8.5 × 107 M−1 s−1), which was comparable to soluble ST2. Tozorakimab potently inhibited ST2-dependent inflammatory responses driven by IL-33 in primary human cells and in a murine model of lung epithelial injury. Additionally, tozorakimab prevented the oxidation of IL-33 and its activity via the RAGE/EGFR signalling pathway, thus increasing in vitro epithelial cell migration and repair. Tozorakimab is a novel therapeutic agent with a dual mechanism of action that blocks IL-33red and IL-33ox signalling, offering potential to reduce inflammation and epithelial dysfunction in human disease.
Association between interatrial septum adiposity and atrial fibrillation: transesophageal echocardiography imaging and autopsy study
Authors: Miyoshi Miho , Abe Ichitaro , Kodama Nozomi , Zhan Yinge , Kira Shintaro , Ishii Yumi , Harada Taisuke , Takano Masayuki , Takahashi Masaki , Sato Hiroki , Tawara Katsunori , Kondo Hidekazu , Fukui Akira , Fukuda Tomoko , Akioka Hidefumi , Shinohara Tetsuji , Teshima Yasushi , Yufu Kunio , Nakagawa Mikiko , Daa Tsutomu , Shimada Tatsuo , Takahashi Naohiko
Published: June 2023

Recent clinical evidence has suggested that interatrial septal (IAS) adiposity contributes to atrial fibrillation (AF). The present study aimed to confirm the usefulness of transesophageal echocardiography (TEE) to estimate IAS adiposity in patients with AF. The histological IAS analysis based on autopsy samples sought to clarify characteristics that underlie the contribution of IAS adiposity to AF. The imaging study analyzed the TEE results in patients with AF (n = 184) in comparison with transthoracic echocardiography (TTE) and computed tomography (CT) results. The autopsy study histologically analyzed IAS in subjects with (n = 5) and without (n = 5) history of AF. In the imaging study, the ratio of interatrial septum adipose tissue (IAS-AT) volume per epicardial adipose tissue (EpAT) volume was greater in patients with persistent AF compared (PerAF) to those with paroxysmal AF (PAF). Multivariable analysis revealed that both TEE-assessed IAS thickness and TTE-assessed left atrial dimension were predicted by CT-assessed IAS-AT volume. In the autopsy study, the histologically-assessed IAS section thickness was greater in the AF group than that in the non-AF group and was positively correlated with the IAS-AT area percentage. In addition, the size of adipocytes in IAS-AT was smaller, compared to EpAT and subcutaneous adipose tissue (SAT). IAS-AT infiltrated into the IAS myocardium, as if adipose tissue split the myocardium (designated as myocardial splitting by IAS-AT). The number of island-like myocardium pieces as a result of myocardial splitting by IAS-AT was greater in the AF group than in the non-AF group and was positively correlated with the IAS-AT area percentage. The present imaging study confirmed the usefulness of TEE to estimate IAS adiposity in patients with AF without radiation exposure. The autopsy study suggested that the myocardial splitting by IAS-AT may contribute to atrial cardiomyopathy leading to AF.
Fatty acid fingerprints in bronchoalveolar lavage fluid and its extracellular vesicles reflect equine asthma severity
Authors: Höglund Nina , Nieminen Petteri , Mustonen Anne-Mari , Käkelä Reijo , Tollis Sylvain , Koho Ninna , Holopainen Minna , Ruhanen Hanna , Mykkänen Anna
Published: June 2023

Equine asthma (EA) is an inflammatory disease of the lower airways driven by mediators released from cells. Extracellular vesicles (EVs) are vehicles for lipid mediators, which possess either pro-inflammatory or dual anti-inflammatory and pro-resolving functions. In this study, we investigated how the respiratory fatty acid (FA) profile reflects airway inflammatory status. The FA composition of bronchoalveolar lavage fluid (BALF), BALF supernatant, and bronchoalveolar EVs of healthy horses (n = 15) and horses with mild/moderate EA (n = 10) or severe EA (SEA, n = 5) was determined with gas chromatography and mass spectrometry. The FA profiles distinguished samples with different diagnoses in all sample types, yet they were insufficient to predict the health status of uncategorized samples. Different individual FAs were responsible for the discrimination of the diagnoses in different sample types. Particularly, in the EVs of SEA horses the proportions of palmitic acid (16:0) decreased and those of eicosapentaenoic acid (20:5n-3) increased, and all sample types of asthmatic horses had elevated dihomo-γ-linolenic acid (20:3n-6) proportions. The results suggest simultaneous pro-inflammatory and resolving actions of FAs and a potential role for EVs as vehicles for lipid mediators in asthma pathogenesis. EV lipid manifestations of EA can offer translational targets to study asthma pathophysiology and treatment options.
Revisiting and updating molecular epidemiology of α-thalassemia mutations in Thailand using MLPA and new multiplex gap-PCR for nine α-thalassemia deletion
Authors: Jomoui Wittaya , Panyasai Sitthichai , Sripornsawan Pornpun , Tepakhan Wanicha
Published: June 2023

α-thalassemia is an inherited blood disorder that is most frequently found in Southeast Asian populations. In Thailand, molecular characterization can diagnose most patients with α-thalassemia; however, several atypical patients are also observed in routine analyses. Here, we characterized α-thalassemia mutations among 137 Hemoglobin H (Hb H) disease patients and three fetuses of Hb Bart’s hydrops, a fatal clinical phenotype of α-thalassemia. Specifically, we performed multiplex ligation-dependent probe amplification (MLPA) followed by direct DNA sequencing. We noticed common genotypes in 129 patients and eight patients had rare Hb H disease caused by compound heterozygous α0-thalassemia (--CR or --SA deletion) with α+-thalassemia (-α3.7/-α4.2/αConstant Springα). Furthermore, two affected fetuses had the --SA/--SEA and one had the --CR/--SEA genotypes. Next, we developed and validated a new multiplex gap-PCR and applied this method to 844 subjects with microcytic red blood cells (RBCs) from various parts of Thailand. The frequency of heterozygous α0-thalassemia was dominated by --SEA 363/844 (43%), followed by --THAI 3/844 (0.4%), --SA 2/844 (0.2%), and --CR 2/844 (0.2%) mutations. These findings suggest that aforementioned four mutations should be routinely applied to increase the effectiveness of diagnosis and genetic counseling in this region.
Investigating the role of Kinesin family in lung adenocarcinoma via integrated bioinformatics approach
Authors: Tabassum Gulnaz , Singh Prithvi , Gurung Rishabh , Hakami Mohammed Ageeli , Alkhorayef Nada , Alsaiari Ahad Amer , Alqahtani Leena S. , Hasan Mohammad Raghibul , Rashid Summya , Kumar Atul , Dev Kapil , Dohare Ravins
Published: June 2023

Lung cancer is the leading cause of mortality from cancer worldwide. Lung adenocarcinoma (LUAD) is a type of non-small cell lung cancer (NSCLC) with highest prevalence. Kinesins a class of motor proteins are shown to be involved in carcinogenesis. We conducted expression, stage plot and survival analyses on kinesin superfamily (KIF) and scrutinized the key prognostic kinesins. Genomic alterations of these kinesins were studied thereafter via cBioPortal. A protein–protein interaction network (PPIN) of selected kinesins and 50 closest altering genes was constructed followed by gene ontology (GO) term and pathway enrichment analyses. Multivariate survival analysis based on CpG methylation of selected kinesins was performed. Lastly, we conducted tumor immune infiltration analysis. Our results found KIF11/15/18B/20A/2C/4A/C1 to be significantly upregulated and correlated with poor survival in LUAD patients. These genes also showed to be highly associated with cell cycle. Out of our seven selected kinesins, KIFC1 showed the highest genomic alteration with highest number of CpG methylation. Also, CpG island (CGI) cg24827036 was discovered to be linked to LUAD prognosis. Therefore, we deduced that reducing the expression of KIFC1 could be a feasible treatment strategy and that it can be a wonderful individual prognostic biomarker. CGI cg24827036 can also be used as a therapy site in addition to being a great prognostic biomarker.
Taxonomic and functional diversity of land snails reflects habitat complexity in riparian forests
Authors: Gheoca Voichița , Benedek Ana Maria , Schneider Erika
Published: June 2023

Habitat complexity affects the structure and dynamics of ecological communities, more often with increased complexity leading to greater species diversity and abundance. Among the terrestrial invertebrate groups, the low vagility of land snails makes them susceptible to react to small-scale habitat alteration. In the current paper we aimed to assess the relationship between taxonomic and functional composition and diversity of land snail communities and habitat structure in the riparian forest habitat. We found that both snail abundance and species richness responded positively to the increase in habitat complexity. The complexity of the riparian forest affected also the snail trait composition. Forest species, species living in woody debris, leaf litter, and root zone and those feeding on detritus were more abundant in complex habitats, while large snails with more offspring, snails having the ability to survive longer periods of dryness, as well as species that prefer arid habitats, were more abundant in less complex habitats. We concluded that habitat complexity promoted functional diversity, with the amount of woody debris as main positive driver, and the adjacent agricultural fields as negative driver of functional diversity.
Method comparison and estimation of causal effects of insomnia on health outcomes in a survey sampled population
Authors: Shahu Anja , Chung Joon , Tarraf Wassim , Ramos Alberto R. , González Hector M. , Redline Susan , Cai Jianwen , Sofer Tamar
Published: June 2023

Applying causal inference methods, such as weighting and matching methods, to a survey sampled population requires properly incorporating the survey weights and design to obtain effect estimates that are representative of the target population and correct standard errors (SEs). With a simulation study, we compared various approaches for incorporating the survey weights and design into weighting and matching-based causal inference methods. When the models were correctly specified, most approaches performed well. However, when a variable was treated as an unmeasured confounder and the survey weights were constructed to depend on this variable, only the matching methods that used the survey weights in causal estimation and as a covariate in matching continued to perform well. If unmeasured confounders are potentially associated with the survey sample design, we recommend that investigators include the survey weights as a covariate in matching, in addition to incorporating them in causal effect estimation. Finally, we applied the various approaches to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and found that insomnia has a causal association with both mild cognitive impairment (MCI) and incident hypertension 6–7 years later in the US Hispanic/Latino population.
Complete genomes and comparative analyses of Streptomyces phages that influence secondary metabolism and sporulation
Authors: Kronheim Sarah , Solomon Ethan , Ho Louis , Glossop Michelle , Davidson Alan R. , Maxwell Karen L.
Published: June 2023

Bacteria in the genus Streptomyces are found ubiquitously in nature and are known for the number and diversity of specialized metabolites they produce, as well as their complex developmental lifecycle. Studies of the viruses that prey on Streptomyces, known as phages, have aided the development of tools for genetic manipulation of these bacteria, as well as contributing to a deeper understanding of Streptomyces and their behaviours in the environment. Here, we present the genomic and biological characterization of twelve Streptomyces phages. Genome analyses reveal that these phages are closely related genetically, while experimental approaches show that they have broad overlapping host ranges, infect early in the Streptomyces lifecycle, and induce secondary metabolite production and sporulation in some Streptomyces species. This work expands the group of characterized Streptomyces phages and improves our understanding of Streptomyces phage-host dynamics.
Machine-learning-based diagnosis of thyroid fine-needle aspiration biopsy synergistically by Papanicolaou staining and refractive index distribution
Authors: Lee Young Ki , Ryu Dongmin , Kim Seungwoo , Park Juyeon , Park Seog Yun , Ryu Donghun , Lee Hayoung , Lim Sungbin , Min Hyun-Seok , Park YongKeun , Lee Eun Kyung
Published: June 2023

We developed a machine learning algorithm (MLA) that can classify human thyroid cell clusters by exploiting both Papanicolaou staining and intrinsic refractive index (RI) as correlative imaging contrasts and evaluated the effects of this combination on diagnostic performance. Thyroid fine-needle aspiration biopsy (FNAB) specimens were analyzed using correlative optical diffraction tomography, which can simultaneously measure both, the color brightfield of Papanicolaou staining and three-dimensional RI distribution. The MLA was designed to classify benign and malignant cell clusters using color images, RI images, or both. We included 1535 thyroid cell clusters (benign: malignancy = 1128:407) from 124 patients. Accuracies of MLA classifiers using color images, RI images, and both were 98.0%, 98.0%, and 100%, respectively. As information for classification, the nucleus size was mainly used in the color image; however, detailed morphological information of the nucleus was also used in the RI image. We demonstrate that the present MLA and correlative FNAB imaging approach has the potential for diagnosing thyroid cancer, and complementary information from color and RI images can improve the performance of the MLA.
Correlation between standardized uptake value of 18F-FDG PET/CT and conductivity with pathologic prognostic factors in breast cancer
Authors: Shin Dong-Joo , Choi Hongyoon , Oh Dong Kyu , Sung Hyun Pil , Kim Jun-Hyeong , Kim Dong-Hyun , Kim Soo-Yeon
Published: June 2023

We investigated the correlation between standardized uptake value (SUV) of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and conductivity parameters in breast cancer and explored the feasibility of conductivity as an imaging biomarker. Both SUV and conductivity have the potential to reflect the tumors’ heterogeneous characteristics, but their correlations have not been investigated until now. Forty four women diagnosed with breast cancer who underwent breast MRI and 18F-FDG PET/CT at the time of diagnosis were included. Among them, 17 women received neoadjuvant chemotherapy followed by surgery and 27 women underwent upfront surgery. For conductivity parameters, maximum and mean values of the tumor region-of-interests were examined. For SUV parameters, SUVmax, SUVmean, and SUVpeak of the tumor region-of-interests were examined. Correlations between conductivity and SUV were evaluated, and among them, the highest correlation was observed between mean conductivity and SUVpeak (Spearman’s correlation coefficient = 0.381). In a subgroup analysis for 27 women with upfront surgery, tumors with lymphovascular invasion (LVI) showed higher mean conductivity than those without LVI (median: 0.49 S/m vs 0.06 S/m, p < 0.001). In conclusion, our study shows a low positive correlation between SUVpeak and mean conductivity in breast cancer. Furthermore, conductivity showed a potential to noninvasively predict LVI status.
Tracking volcanic explosions using Shannon entropy at Volcán de Colima
Authors: Rey-Devesa Pablo , Prudencio Janire , Benítez Carmen , Bretón Mauricio , Plasencia Imelda , León Zoraida , Ortigosa Félix , Gutiérrez Ligdamis , Arámbula-Mendoza Raúl , Ibáñez Jesús M.
Published: June 2023

The main objective of this work is to show that Shannon Entropy (SE) calculated on continuous seismic signals can be used in a volcanic eruption monitoring system. We analysed three years of volcanic activity of Volcán de Colima, México, recorded between January 2015 and May 2017. This period includes two large explosions, with pyroclastic and lava flows, and intense activity of less energetic explosion, culminating with a period of quiescence. In order to confirm the success of our results, we used images of the Visual Monitoring system of Colima Volcano Observatory. Another of the objectives of this work is to show how the decrease in SE values can be used to track minor explosive activity, helping Machine Learning algorithms to work more efficiently in the complex problem of distinguishing the explosion signals in the seismograms. We show that the two big eruptions selected were forecasted successfully (6 and 2 days respectively) using the decay of SE. We conclude that SE could be used as a complementary tool in seismic volcano monitoring, showing its successful behaviour prior to energetic eruptions, giving time enough to alert the population and prepare for the consequences of an imminent and well predicted moment of the eruption.
Cannabis sativa-based oils against aluminum-induced neurotoxicity
Authors: Alves Carla , Tamagno Wagner Antonio , Vanin Ana Paula , Pompermaier Aline , Barcellos Leonardo José Gil
Published: June 2023

The use of terpenoid compounds in different neural-related conditions is becoming useful for several illnesses. Another possible activity of these compounds is the reduction of nervous impairment. Cannabis sativa plants are known for their concentration of two important terpenoids, the delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD and THC have central peripheral activities already described and their usage in different brain diseases, such as Alzheimer's and multiple sclerosis. Aluminum (Al) is known as an important neurotoxic compound, the physiological action of Al is not known already, and in high concentrations can lead to intoxication and cause neurotoxicity. Here we evaluated the potential effect of two different doses of CBD- and THC-rich based oils against Al-induced toxicity, in the zebrafish model. We evaluated behavioral biomarkers of the novel tank test (NTT) and social preference test (SPT), and biochemical markers: the activity of the enzyme acetylcholinesterase (AChE) and the antioxidant enzymes—catalase, superoxide dismutase, and glutathione-S-transferase. CBD- and THC-based oils were able to increase the AChE activity helping the cholinergic nervous system actuate against Al toxicity which was reflected by the behavioral biomarkers changes. We concluded that the oils have a protective effect and might be used with proposals for neurological and antioxidant impairment avoidance caused by Al intoxications.