bluuebunny/crossref_metadata_2025 huggingface dataset:
Residential exposure to electromagnetic fields and risk of amyotrophic lateral sclerosis: a dose–response meta-analysis
Authors: Filippini Tommaso , Hatch Elizabeth E. , Vinceti Marco
Published: June 2021

Amyotrophic lateral sclerosis (ALS) is neurodegenerative disease characterized by a fatal prognosis and still unknown etiology. Some environmental risk factors have been suggested, including exposure to magnetic fields. Studies have suggested positive associations in occupationally-exposed populations, but the link with residential exposure is still debated as is the shape of such relation. Due to recent availability of advanced biostatistical tools for dose–response meta-analysis, we carried out a systematic review in order to assess the dose–response association between ALS and residential exposure to magnetic fields. We performed an online literature searching through April 30, 2021. Studies were included if they assessed residential exposure to electromagnetic fields, based either on distance from overhead power lines or on magnetic field modelling techniques, and if they reported risk estimates for ALS. We identified six eligible studies, four using distance-based and one modelling-based exposure assessment, and one both methods. Both distance-based and particularly modelling-based exposure estimates appeared to be associated with a decreased ALS risk in the highest exposure category, although estimates were very imprecise (summary RRs 0.87, 95% CI 0.63–1.20, and 0.27, 95% CI 0.05–1.36). Dose–response meta-analysis also showed little association between distance from power lines and ALS, with no evidence of any threshold. Overall, we found scant evidence of a positive association between residential magnetic fields exposure and ALS, although the available data were too limited to conduct a dose–response analysis for the modelled magnetic field estimates or to perform stratified analyses.
Aspartate aminotransferase to alanine aminotransferase ratio is associated with frailty and mortality in older patients with heart failure
Authors: Maeda Daichi , Kagiyama Nobuyuki , Jujo Kentaro , Saito Kazuya , Kamiya Kentaro , Saito Hiroshi , Ogasahara Yuki , Maekawa Emi , Konishi Masaaki , Kitai Takeshi , Iwata Kentaro , Wada Hiroshi , Hiki Masaru , Dotare Taishi , Sunayama Tsutomu , Kasai Takatoshi , Nagamatsu Hirofumi , Ozawa Tetsuya , Izawa Katsuya , Yamamoto Shuhei , Aizawa Naoki , Yonezawa Ryusuke , Oka Kazuhiro , Momomura Shin-ichi , Matsue Yuya
Published: June 2021

Frailty is a common comorbidity associated with adverse events in patients with heart failure, and early recognition is key to improving its management. We hypothesized that the AST to ALT ratio (AAR) could be a marker of frailty in patients with heart failure. Data from the FRAGILE-HF study were analyzed. A total of 1327 patients aged ≥ 65 years hospitalized with heart failure were categorized into three groups based on their AAR at discharge: low AAR (AAR < 1.16, n = 434); middle AAR (1.16 ≤ AAR < 1.70, n = 487); high AAR (AAR ≥ 1.70, n = 406). The primary endpoint was one-year mortality. The association between AAR and physical function was also assessed. High AAR was associated with lower short physical performance battery and shorter 6-min walk distance, and these associations were independent of age and sex. Logistic regression analysis revealed that high AAR was an independent marker of physical frailty after adjustment for age, sex and body mass index. During follow-up, all-cause death occurred in 161 patients. After adjusting for confounding factors, high AAR was associated with all-cause death (low AAR vs. high AAR, hazard ratio: 1.57, 95% confidence interval, 1.02–2.42; P = 0.040). In conclusion, AAR is a marker of frailty and prognostic for all-cause mortality in older patients with heart failure.
Hyperlipidemic hypersensitivity to lethal microbial inflammation and its reversal by selective targeting of nuclear transport shuttles
Authors: Liu Yan , Zienkiewicz Jozef , Boyd Kelli L. , Smith Taylor E. , Xu Zhi-Qi , Hawiger Jacek
Published: June 2021

Hyperlipidemia, the hallmark of Metabolic Syndrome that afflicts millions of people worldwide, exacerbates life-threatening infections. We present a new evidence for the mechanism of hyperlipidemic hypersensitivity to microbial inflammation caused by pathogen-derived inducer, LPS. We demonstrate that hyperlipidemic animals succumbed to a non-lethal dose of LPS whereas normolipidemic controls survived. Strikingly, survival of hyperlipidemic animals was restored when the nuclear import of stress-responsive transcription factors (SRTFs), Sterol Regulatory Element-Binding Proteins (SREBPs), and Carbohydrate-Responsive Element-Binding Proteins (ChREBPs) was impeded by targeting the nuclear transport checkpoint with cell-penetrating, biselective nuclear transport modifier (NTM) peptide. Furthermore, the burst of proinflammatory cytokines and chemokines, microvascular endothelial injury in the liver, lungs, heart, and kidneys, and trafficking of inflammatory cells were also suppressed. To dissect the role of nuclear transport signaling pathways we designed and developed importin-selective NTM peptides. Selective targeting of the importin α5, ferrying SRTFs and ChREBPs, protected 70–100% hyperlipidemic animals. Targeting importin β1, that transports SREBPs, was only effective after 3-week treatment that lowered blood triglycerides, cholesterol, glucose, and averted fatty liver. Thus, the mechanism of hyperlipidemic hypersensitivity to lethal microbial inflammation depends on metabolic and proinflammatory transcription factors mobilization, which can be counteracted by targeting the nuclear transport checkpoint.
Highly efficient reusable superhydrophobic sponge prepared by a facile, simple and cost effective biomimetic bonding method for oil absorption
Authors: Wang Jiaqi , Chen Yan , Xu Qinyao , Cai Miaomiao , Shi Qian , Gao Junkai
Published: June 2021

Superhydrophobic sponges have considerable potential for oil/water separation. Most of the methods used for superhydrophobic modification of sponges require toxic or harmful solvents, which have the drawbacks of hazardous to environment, expensive, and complex to utilize. Moreover, the hydrophobic layer on the surface of sponge is often easily destroyed. In this paper, a highly efficient superhydrophobic sponge with excellent reusability was developed by using a facile, simple and environmentally friendly dopamine biomimetic bonding method. Different types of sponges, such as melamine, polyethylene or polyurethane sponge wastes, were used as raw materials to prepare superhydrophobic sponges, which possess the advantages of inexpensive and abundant. The effects of different dopamine polymerization time and different hydrophobic agent dosage on the hydrophobicity and oil absorption capacity of melamine sponges were optimized. The study results showed that the water contact angle of the superhydrophobic sponge could reach 153° with excellent organic solvent absorption capacity of 165.9 g/g. Furthermore, the superhydrophobic sponge retained approximately 92.1% of its initial absorption capacity after 35 reutilization cycles. More importantly, the dopamine biomimetic bonding superhydrophobic modification method can be used for different types of sponges. Therefore, a universally applicable, facile, simple and environmentally friendly superhydrophobic modification method for sponges was developed.
Clinical significance of subclinical atherosclerosis in retinal vein occlusion
Authors: Lyu Minhyung , Lee Yonggu , Kim Byung Sik , Kim Hyun-Jin , Hong Rimkyung , Shin Yong Un , Cho Heeyoon , Shin Jeong-Hun
Published: June 2021

Retinal vein occlusion (RVO) is associated with atherosclerotic cardiovascular risk factors; however, its association with the specific markers of subclinical atherosclerosis has not yet been established. To investigate this association, we compared 70 patients with RVO to 70 age- and sex-matched patients without RVO. Low-density lipoprotein cholesterol (LDL-C) levels and brachial-ankle pulse wave velocity (baPWV) were significantly higher in the RVO group than in the control group. Carotid plaques (54.3% vs. 28.6%, p = 0.004) were more frequent in the RVO group. Multivariate logistic regression analysis showed that the presence of carotid plaques (odds ratio [OR]: 3.15, 95% confidence interval [CI] 1.38–7.16, p = 0.006), as well as smoking, LDL-C level, and baPWV were associated with RVO. Additionally, a multinomial logistic regression model showed that the presence of carotid plaques (OR: 3.94, 95% CI 1.65–9.41, p = 0.002) and LDL-C level were associated with branch RVO, whereas smoking and baPWV were associated with central RVO. In conclusion, RVO was associated with subclinical atherosclerosis markers, including carotid plaques and baPWV. These results support the hypothesis that atherosclerosis contributes to the etiology of RVO and suggest the evaluation of subclinical atherosclerosis in patients with RVO.
SNP rs10420324 in the AMPA receptor auxiliary subunit TARP γ-8 regulates the susceptibility to antisocial personality disorder
Authors: Peng Shi-Xiao , Wang Yue-Ying , Zhang Min , Zang Yan-Yu , Wu Dan , Pei Jingwen , Li Yansong , Dai Jiapei , Guo Xiaoyun , Luo Xingguang , Zhang Ning , Yang Jian-Jun , Zhang Chen , Gao Xiang , Liu Na , Shi Yun Stone
Published: June 2021

In the brain, AMPA receptors mediate fast excitatory neurotransmission, the dysfunction of which leads to neuropsychiatric disorders. Synaptic function of AMPA receptors is tightly controlled by a protein group called transmembrane AMPAR regulatory proteins (TARPs). TARP γ-8 (also known as CACNG8) preferentially expresses in the hippocampus, cortex and subcortical regions that are critical for emotion generation indicating its association with psychiatric disorders. Here, we identified rs10420324 (T/G), a SNP located in the human CACNG8 gene, regulated reporter gene expression in vitro and TARP γ-8 expression in the human brain. A guanine at the locus (rs10420324G) suppressed transcription likely through modulation of a local G-quadruplex DNA structure. Consistent with these observations, the frequency of rs10420324G was higher in patients with anti-social personality disorder (ASPD) than in controls, indicating that rs10420324G in CACNG8 is more voluntary for ASPD. We then characterized the behavior of TARP γ-8 knockout and heterozygous mice and found that consistent with ASPD patients who often exhibit impulsivity, aggression, risk taking, irresponsibility and callousness, a decreased γ-8 expression in mice displayed similar behaviors. Furthermore, we found that a decrease in TARP γ-8 expression impaired synaptic AMPAR functions in layer 2–3 pyramidal neurons of the prefrontal cortex, a brain region that inhibition leads to aggression, thus explaining, at least partially, the neuronal basis for the behavioral abnormality. Taken together, our study indicates that TARP γ-8 expression level is associated with ASPD, and that the TARP γ-8 knockout mouse is a valuable animal model for studying this psychiatric disease.
A modelling analysis of the effectiveness of second wave COVID-19 response strategies in Australia
Authors: Milne George J. , Xie Simon , Poklepovich Dana , O’Halloran Dan , Yap Matthew , Whyatt David
Published: June 2021

There is a significant challenge in responding to second waves of COVID-19 cases, with governments being hesitant in introducing hard lockdown measures given the resulting economic impact. In addition, rising case numbers reflect an increase in coronavirus transmission some time previously, so timing of response measures is highly important. Australia experienced a second wave from June 2020 onwards, confined to greater Melbourne, with initial social distancing measures failing to reduce rapidly increasing case numbers. We conducted a detailed analysis of this outbreak, together with an evaluation of the effectiveness of alternative response strategies, to provide guidance to countries experiencing second waves of SARS-Cov-2 transmission. An individual-based transmission model was used to (1) describe a second-wave COVID-19 epidemic in Australia; (2) evaluate the impact of lockdown strategies used; and (3) evaluate effectiveness of alternative mitigation strategies. The model was calibrated using daily diagnosed case data prior to lockdown. Specific social distancing interventions were modelled by adjusting person-to-person contacts in mixing locations. Modelling earlier activation of lockdown measures are predicted to reduce total case numbers by more than 50%. Epidemic peaks and duration of the second wave were also shown to reduce. Our results suggest that activating lockdown measures when second-wave case numbers first indicated exponential growth, would have been highly effective in reducing COVID-19 cases. The model was shown to realistically predict the epidemic growth rate under the social distancing measures applied, validating the methods applied. The timing of social distancing activation is shown to be critical to their effectiveness. Data showing exponential rise in cases, doubling every 7–10 days, can be used to trigger early lockdown measures. Such measures are shown to be necessary to reduce daily and total case numbers, and the consequential health burden, so preventing health care facilities being overwhelmed. Early control of second wave resurgence potentially permits strict lockdown measures to be eased earlier.
High seebeck coefficient in middle-temperature thermocell with deep eutectic solvent
Authors: Antariksa Naura Fakhira , Yamada Teppei , Kimizuka Nobuo
Published: June 2021

Deep eutectic solvent (DES) was applied to the solvent of thermocell and high Seebeck coefficient (Se) of the thermocell was achieved at high-temperatures operation. The Se of a redox couple of ferricyanide and ferrocyanide ([Fe(CN)6]3−/4−) reaches − 1.67 mV/K in a DES consisting of ethylene glycol and choline chloride. Spectroscopic analysis reveals that this is due to the strong interactions between the redox couple and the DES. Furthermore, the cell can operate over a wide temperature range of 135–165 °C. This result is a desired feature for waste-heat recovery applications.
Chicken-eaters and pork-eaters have different gut microbiota and tryptophan metabolites
Authors: Shi Jie , Zhao Di , Zhao Fan , Wang Chong , Zamaratskaia Galia , Li Chunbao
Published: June 2021

This study was aimed to evaluate the differences in the composition of gut microbiota, tryptophan metabolites and short-chain fatty acids in feces between volunteers who frequently ate chicken and who frequently ate pork. Twenty male chicken-eaters and 20 male pork-eaters of 18 and 30 years old were recruited to collect feces samples for analyses of gut microbiota composition, short-chain fatty acids and tryptophan metabolites. Chicken-eaters had more diverse gut microbiota and higher abundance of Prevotella 9, Dialister, Faecalibacterium, Megamonas, and Prevotella 2. However, pork-eaters had higher relative abundance of Bacteroides, Faecalibacterium, Roseburia, Dialister, and Ruminococcus 2. In addition, chicken-eaters had high contents of skatole and indole in feces than pork-eaters, as well as higher contents of total short chain fatty acids, in particular for acetic acid, propionic acid, and branched chain fatty acids. The Spearman’s correlation analysis revealed that the abundance of Prevotella 2 and Prevotella 9 was positively correlated with levels of fecal skatole, indole and short-chain fatty acids. Thus, intake of chicken diet may increase the risk of skatole- and indole-induced diseases by altering gut microbiota.
A novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids
Authors: Lee Hanil , Choi Eun-Jeong , Kim Eun Jung , Son Eui Dong , Kim Hyoung-June , Park Won-Seok , Kang Young-Gyu , Shin Kyong-Oh , Park Kyungho , Kim Jin-Chul , Kim Su-Nam , Choi Eung Ho
Published: June 2021

Excess glucocorticoids (GCs) with either endogenous or exogenous origins deteriorate skin barrier function. GCs bind to mineralocorticoid and GC receptors (MRs and GRs) in normal human epidermal keratinocytes (NHEKs). Inappropriate MR activation by GCs mediates various GC-induced cutaneous adverse events. We examined whether MR antagonists can ameliorate GC-mediated skin barrier dysfunction in NHEKs, reconstructed human epidermis (RHE), and subjects under psychological stress (PS). In a preliminary clinical investigation, topical MR antagonists improved skin barrier function in topical GC-treated subjects. In NHEKs, cortisol induced nuclear translocation of GR and MR, and GR and MR antagonists inhibited cortisol-induced reductions of keratinocyte differentiation. We identified 7,3’,4’-trihydroxyisoflavone (7,3’,4’-THIF) as a novel compound that inhibits MR transcriptional activity by screening 30 cosmetic compounds. 7,3’,4’-THIF ameliorated the cortisol effect which decreases keratinocyte differentiation in NHEKs and RHE. In a clinical study on PS subjects, 7,3',4'-THIF (0.1%)-containing cream improved skin barrier function, including skin surface pH, barrier recovery rate, and stratum corneum lipids. In conclusion, skin barrier dysfunction owing to excess GC is mediated by MR and GR; thus, it could be prevented by treatment with MR antagonists. Therefore, topical MR antagonists are a promising therapeutic option for skin barrier dysfunction after topical GC treatment or PS.
Introduction and reproducibility of an updated practical grading system for lumbar foraminal stenosis based on high-resolution MR imaging
Authors: Sartoretti Elisabeth , Wyss Michael , Alfieri Alex , Binkert Christoph A. , Erne Cyril , Sartoretti-Schefer Sabine , Sartoretti Thomas
Published: June 2021

In this paper we sought to develop and assess the reproducibility of an updated 6-point grading system for lumbar foraminal stenosis based on the widely used Lee classification that more accurately describes lumbar foraminal stenosis as seen on high-resolution MRI. Grade A indicates absence of foraminal stenosis. Grades B, C, D and E indicate presence of foraminal stenosis with contact of the nerve root with surrounding anatomical structures (on one, two, three or four sides for B, C, D and E respectively) yet without morphological change of the nerve root. To each grade, a number code indicating the location of contact between the nerve root and surrounding anatomical structure(s) is appended. 1, 2, 3 and 4 indicate contact of the nerve root at superior, posterior, inferior and anterior position of the borders of the lumbar foramen. Grade F indicates presence of foraminal stenosis with morphological change of the nerve root. Three readers graded the lumbar foramina of 101 consecutive patients using high-resolution T2w (and T1w) MR images with a spatial resolution of beyond 0.5 mm3. Interreader agreement was excellent (Cohen’s Kappa = 0.866–1). Importantly, 30.6%/31.6%/32.2% (reader 1/reader 2/ reader 3) of foramina were assigned grades that did not appear in the original Lee grading system (grades B and D). The readers found no foramen that could not be described accurately with the updated grading system. Thus, an updated 6-point grading system for lumbar foraminal stenosis is reproducible and comprehensively describes lumbar foraminal stenosis as seen on high-resolution MRI.
Contribution of genetic ancestry and polygenic risk score in meeting vitamin B12 needs in healthy Brazilian children and adolescents
Authors: Fuzo Carlos Alessandro , da Veiga Ued Fábio , Moco Sofia , Cominetti Ornella , Métairon Sylviane , Pruvost Solenn , Charpagne Aline , Carayol Jerome , Torrieri Raul , Silva Wilson Araujo , Descombes Patrick , Kaput Jim , Monteiro Jacqueline Pontes
Published: June 2021

Polymorphisms in genes related to the metabolism of vitamin B12 haven’t been examined in a Brazilian population. To (a) determine the correlation between the local genetic ancestry components and vitamin B12 levels using ninety B12-related genes; (b) determine associations between these genes and their SNPs with vitamin B12 levels; (c) determine a polygenic risk score (PRS) using significant variants. This cross-sectional study included 168 children and adolescents, aged 9–13 years old. Total cobalamin was measured in plasma. Genotyping arrays and whole exome data were combined to yield ~ 7000 SNPs in 90 genes related to vitamin B12. The Efficient Local Ancestry Inference was used to estimate local ancestry for African (AFR), Native American, and European (EUR). The association between the genotypes and vitamin B12 levels were determined with generalized estimating equation. Vitamin B12 levels were driven by positive (EUR) and negative (AFR, AMR) correlations with genetic ancestry. A set of 36 variants were used to create a PRS that explained 42% of vitamin level variation. Vitamin B12 levels are influenced by genetic ancestry and a PRS explained almost 50% of the variation in plasma cobalamin in Brazilian children and adolescents.
Urine NMR-based TB metabolic fingerprinting for the diagnosis of TB in children
Authors: Comella-del-Barrio Patricia , Izquierdo-Garcia José Luis , Gautier Jacqueline , Doresca Mariette Jean Coute , Campos-Olivas Ramón , Santiveri Clara M. , Muriel-Moreno Beatriz , Prat-Aymerich Cristina , Abellana Rosa , Pérez-Porcuna Tomas M. , Cuevas Luis E. , Ruiz-Cabello Jesús , Domínguez José
Published: June 2021

Tuberculosis (TB) is a major cause of morbidity and mortality in children, and early diagnosis and treatment are crucial to reduce long-term morbidity and mortality. In this study, we explore whether urine nuclear magnetic resonance (NMR)-based metabolomics could be used to identify differences in the metabolic response of children with different diagnostic certainty of TB. We included 62 children with signs and symptoms of TB and 55 apparently healthy children. Six of the children with presumptive TB had bacteriologically confirmed TB, 52 children with unconfirmed TB, and 4 children with unlikely TB. Urine metabolic fingerprints were identified using high- and low-field proton NMR platforms and assessed with pattern recognition techniques such as principal components analysis and partial least squares discriminant analysis. We observed differences in the metabolic fingerprint of children with bacteriologically confirmed and unconfirmed TB compared to children with unlikely TB (p = 0.041 and p = 0.013, respectively). Moreover, children with unconfirmed TB with X-rays compatible with TB showed differences in the metabolic fingerprint compared to children with non-pathological X-rays (p = 0.009). Differences in the metabolic fingerprint in children with different diagnostic certainty of TB could contribute to a more accurate characterisation of TB in the paediatric population. The use of metabolomics could be useful to improve the prediction of TB progression and diagnosis in children.
Aortic valve function post-replacement of severe aortic stenosis by transcatheter procedure versus surgery: a systematic review and metanalysis
Authors: Abi Khalil Charbel , Ignatiuk Barbara , Erdem Guliz , Chemaitelly Hiam , Barilli Fabio , El-Shazly Mohamed , Al Suwaidi Jassim , Aboulsoud Samar , Kofler Markus , Stastny Lukas , Jneid Hani , Bonaros Nikolaos
Published: June 2021

Transcatheter aortic valve replacement (TAVR) has shown to reduce mortality compared to surgical aortic valve replacement (sAVR). However, it is unknown which procedure is associated with better post-procedural valvular function. We conducted a meta-analysis of randomized clinical trials that compared TAVR to sAVR for at least 2 years. The primary outcome was post-procedural patient-prosthesis-mismatch (PPM). Secondary outcomes were post-procedural and 2-year: effective orifice area (EOA), paravalvular gradient (PVG) and moderate/severe paravalvular leak (PVL). We identified 6 trials with a total of 7022 participants with severe aortic stenosis. TAVR was associated with 37% (95% CI [0.51–0.78) mean RR reduction of post-procedural PPM, a decrease that was not affected by the surgical risk at inclusion, neither by the transcatheter heart valve system. Postprocedural changes in gradient and EOA were also in favor of TAVR as there was a pooled mean difference decrease of 0.56 (95% CI [0.73–0.38]) in gradient and an increase of 0.47 (95% CI [0.38–0.56]) in EOA. Additionally, self-expandable valves were associated with a higher decrease in gradient than balloon ones (beta = 0.38; 95% CI [0.12–0.64]). However, TAVR was associated with a higher risk of moderate/severe PVL (pooled RR: 9.54, 95% CI [5.53–16.46]). All results were sustainable at 2 years.
Skin biopsies in acute myeloid leukemia patients undergoing intensive chemotherapy are safe and effect patient management
Authors: Berger Tamar , Sherman Shany , Hayman Lucille , Wolach Ofir , Shacham-Abulafia Adi , Raanani Pia , Pasvolsky Oren
Published: June 2021

There is paucity of data regarding the diagnostic yield and safety of skin biopsies in patients with acute myeloid leukemia (AML), though skin eruptions are common in these patients. We evaluated 216 patients treated in our hemato-oncology unit at a tertiary medical center between 2007 and 2018 and identified 35 patients who underwent 37 skin biopsies. The majority of biopsies were performed during induction treatment for AML (n = 26, 70%), whereas the remainder of biopsies were done prior to induction initiation (n = 8, 22%) or during consolidation chemotherapy (n = 3, 8%). Pathology findings were inconclusive in 13 cases (35%), while diagnostic biopsies were positive for drug eruptions (24%), leukemia cutis (16%), infections (11%), reactive processes (8%) and Sweet syndrome (5.5%). In almost half of cases (16/37) tissue cultures were performed. Of those, only a quarter (4/16) were positive. Histopathology and tissue culture results altered immediate patient care in 3 cases (8%), yet information obtained from biopsies had potential to affect long term patient care in 8 additional cases (21.6%). Although most skin biopsies were performed while patients had severe thrombocytopenia and neutropenia, only one patient had a complication due to the biopsy (fever and local bleeding). With the limitation of a retrospective analysis, our study suggests that skin biopsies in patients treated for AML are relatively safe. Although biopsy results infrequently alter immediate patient management, long term effect on patient care expand the potential diagnostic yield of skin biopsies.
Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders
Authors: Rajewska-Rager Aleksandra , Dmitrzak-Weglarz Monika , Kapelski Pawel , Lepczynska Natalia , Pawlak Joanna , Twarowska-Hauser Joanna , Skibinska Maria
Published: June 2021

Mood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14–24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.
Publisher Correction: Diabetic vascular hyperpermeability: optical coherence tomography angiography and functional loss assessments of relationships among retinal vasculature changes
Authors: Arima Mitsuru , Nakao Shintaro , Kaizu Yoshihiro , Wada Iori , Yamaguchi Muneo , Fujiwara Kohta , Akiyama Masato , Stitt Alan W. , Sonoda Koh‑Hei
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
REG3A/REG3B promotes acinar to ductal metaplasia through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway
Authors: Zhang Huairong , Corredor Andrea Liliam Gomez , Messina-Pacheco Julia , Li Qing , Zogopoulos George , Kaddour Nancy , Wang Yifan , Shi Bing-yin , Gregorieff Alex , Liu Jun-li , Gao Zu-hua
Published: June 2021

Persistent acinar to ductal metaplasia (ADM) is a recently recognized precursor of pancreatic ductal adenocarcinoma (PDAC). Here we show that the ADM area of human pancreas tissue adjacent to PDAC expresses significantly higher levels of regenerating protein 3A (REG3A). Exogenous REG3A and its mouse homolog REG3B induce ADM in the 3D culture of primary human and murine acinar cells, respectively. Both Reg3b transgenic mice and REG3B-treated mice with caerulein-induced pancreatitis develop and sustain ADM. Two out of five Reg3b transgenic mice with caerulein-induced pancreatitis show progression from ADM to pancreatic intraepithelial neoplasia (PanIN). Both in vitro and in vivo ADM models demonstrate activation of the RAS-RAF-MEK-ERK signaling pathway. Exostosin-like glycosyltransferase 3 (EXTL3) functions as the receptor for REG3B and mediates the activation of downstream signaling proteins. Our data indicates that REG3A/REG3B promotes persistent ADM through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway. Targeting REG3A/REG3B, its receptor EXTL3, or other downstream molecules could interrupt the ADM process and prevent early PDAC carcinogenesis.
The therapeutic potential of multiclonal tumoricidal T cells derived from tumor infiltrating lymphocyte-derived iPS cells
Authors: Ito Takeshi , Kawai Yohei , Yasui Yutaka , Iriguchi Shoichi , Minagawa Atsutaka , Ishii Tomoko , Miyoshi Hiroyuki , Taketo M. Mark , Kawada Kenji , Obama Kazutaka , Sakai Yoshiharu , Kaneko Shin
Published: June 2021

Tumor-infiltrating lymphocytes (TIL), which include tumor-specific T lymphocytes with frequency, are used for adoptive cell transfer therapy (ACT) in clinical practice. The optimization of TIL preparation has been investigated to reduce the senescence and increase the abundance of TIL, as both the quality and quantity of the transferred cells have great influence on the outcome of TIL-based ACT (TIL-ACT). Considering the effects of cell reprogramming on senescence, we expected that the anti-tumor effect could be enhanced by TIL regeneration. To confirm this hypothesis, we established tumor-specific TIL-derived iPS cells (TIL-iPSC) with human colorectal cancer specimens. T cells differentiated from TIL-iPSC (TIL-iPS-T) retained not only intrinsic T cell functions and tumor specificity, but also exhibited improved proliferation capacity and additional killing activity. Moreover, less differentiated profiles and prolonged persistency were seen in TIL-iPS-T compared with primary cells. Our findings imply that iPSC technology has great potential for TIL-ACT.
Single-cell RNA sequencing of human nail unit defines RSPO4 onychofibroblasts and SPINK6 nail epithelium
Authors: Kim Hyun Je , Shim Joon Ho , Park Ji-Hye , Shin Hyun Tae , Shim Jong Sup , Jang Kee-Taek , Park Woong-Yang , Lee Kyung-Hoon , Kwon Eun Ji , Jang Hyung-Suk , Yang Hanseul , Lee Jong Hee , Yang Jun-Mo , Lee Dongyoun
Published: June 2021

Research on human nail tissue has been limited by the restricted access to fresh specimen. Here, we studied transcriptome profiles of human nail units using polydactyly specimens. Single-cell RNAseq with 11,541 cells from 4 extra digits revealed nail-specific mesenchymal and epithelial cell populations, characterized by RSPO4 (major gene in congenital anonychia) and SPINK6, respectively. In situ RNA hybridization demonstrated the localization of RSPO4, MSX1 and WIF1 in onychofibroblasts suggesting the activation of WNT signaling. BMP-5 was also expressed in onychofibroblasts implicating the contribution of BMP signaling. SPINK6 expression distinguished the nail-specific keratinocytes from epidermal keratinocytes. RSPO4+ onychofibroblasts were distributed at close proximity with LGR6+ nail matrix, leading to WNT/β-catenin activation. In addition, we demonstrated RSPO4 was overexpressed in the fibroblasts of onychomatricoma and LGR6 was highly expressed at the basal layer of the overlying epithelial component, suggesting that onychofibroblasts may play an important role in the pathogenesis of onychomatricoma.
Higher-order simplicial synchronization of coupled topological signals
Authors: Ghorbanchian Reza , Restrepo Juan G. , Torres Joaquín J. , Bianconi Ginestra
Published: June 2021

Simplicial complexes capture the underlying network topology and geometry of complex systems ranging from the brain to social networks. Here we show that algebraic topology is a fundamental tool to capture the higher-order dynamics of simplicial complexes. In particular we consider topological signals, i.e., dynamical signals defined on simplices of different dimension, here taken to be nodes and links for simplicity. We show that coupling between signals defined on nodes and links leads to explosive topological synchronization in which phases defined on nodes synchronize simultaneously to phases defined on links at a discontinuous phase transition. We study the model on real connectomes and on simplicial complexes and network models. Finally, we provide a comprehensive theoretical approach that captures this transition on fully connected networks and on random networks treated within the annealed approximation, establishing the conditions for observing a closed hysteresis loop in the large network limit.
Magnetic and f-electron effects in LaNiO2 and NdNiO2 nickelates with cuprate-like $$3{d}_{{x}^{2}-{y}^{2}}$$ band
Authors: Zhang Ruiqi , Lane Christopher , Singh Bahadur , Nokelainen Johannes , Barbiellini Bernardo , Markiewicz Robert S. , Bansil Arun , Sun Jianwei
Published: June 2021

Recent discovery of superconductivity in the doped infinite-layer nickelates has renewed interest in understanding the nature of high-temperature superconductivity more generally. The low-energy electronic structure of the parent compound NdNiO2, the role of electronic correlations in driving superconductivity, and the possible relationship between the cuprates and the nickelates are still open questions. Here, by comparing LaNiO2 and NdNiO2 systematically within a parameter-free, all-electron first-principles density-functional theory framework, we reveal the role of Nd 4f electrons in shaping the ground state of pristine NdNiO2. Strong similarities are found between the electronic structures of LaNiO2 and NdNiO2, except for the effects of the 4f electrons. Hybridization between the Nd 4f and Ni 3d orbitals is shown to significantly modify the Fermi surfaces of various magnetic states. In contrast, the competition between the magnetically ordered phases depends mainly on the gaps in the Ni $$3{d}_{{x}^{2}-{y}^{2}}$$
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band. Our estimated value of the on-site Hubbard U in the nickelates is similar to that in the cuprates, but the value of the Hund’s coupling JH is found to be sensitive to the Nd magnetic moment. In contrast with the cuprates, NdNiO2 presents 3D magnetism with competing antiferromagnetic and (interlayer) ferromagnetic exchange, which may explain why the Tc is lower in the nickelates.
Confinement of long-lived interlayer excitons in WS2/WSe2 heterostructures
Authors: Montblanch Alejandro R.-P. , Kara Dhiren M. , Paradisanos Ioannis , Purser Carola M. , Feuer Matthew S. G. , Alexeev Evgeny M. , Stefan Lucio , Qin Ying , Blei Mark , Wang Gang , Cadore Alisson R. , Latawiec Pawel , Lončar Marko , Tongay Sefaattin , Ferrari Andrea C. , Atatüre Mete
Published: June 2021

Interlayer excitons in layered materials constitute a novel platform to study many-body phenomena arising from long-range interactions between quantum particles. Long-lived excitons are required to achieve high particle densities, to mediate thermalisation, and to allow for spatially and temporally correlated phases. Additionally, the ability to confine them in periodic arrays is key to building a solid-state analogue to atoms in optical lattices. Here, we demonstrate interlayer excitons with lifetime approaching 0.2 ms in a layered-material heterostructure made from WS2 and WSe2 monolayers. We show that interlayer excitons can be localised in an array using a nano-patterned substrate. These confined excitons exhibit microsecond-lifetime, enhanced emission rate, and optical selection rules inherited from the host material. The combination of a permanent dipole, deterministic spatial confinement and long lifetime places interlayer excitons in a regime that satisfies one of the requirements for simulating quantum Ising models in optically resolvable lattices.
Maternal milk microbiota and oligosaccharides contribute to the infant gut microbiota assembly
Authors: Laursen Martin Frederik , Pekmez Ceyda T , Larsson Melanie Wange , Lind Mads Vendelbo , Yonemitsu Chloe , Larnkjær Anni , Mølgaard Christian , Bode Lars , Dragsted Lars Ove , Michaelsen Kim F , Licht Tine Rask , Bahl Martin Iain
Published: June 2021

Breastfeeding protects against diseases, with potential mechanisms driving this being human milk oligosaccharides (HMOs) and the seeding of milk-associated bacteria in the infant gut. In a cohort of 34 mother–infant dyads we analyzed the microbiota and HMO profiles in breast milk samples and infant’s feces. The microbiota in foremilk and hindmilk samples of breast milk was compositionally similar, however hindmilk had higher bacterial load and absolute abundance of oral-associated bacteria, but a lower absolute abundance of skin-associated Staphylococcus spp. The microbial communities within both milk and infant’s feces changed significantly over the lactation period. On average 33% and 23% of the bacterial taxa detected in infant’s feces were shared with the corresponding mother’s milk at 5 and 9 months of age, respectively, with Streptococcus, Veillonella and Bifidobacterium spp. among the most frequently shared. The predominant HMOs in feces associated with the infant’s fecal microbiota, and the dominating infant species B. longum ssp. infantis and B. bifidum correlated inversely with HMOs. Our results show that breast milk microbiota changes over time and within a feeding session, likely due to transfer of infant oral bacteria during breastfeeding and suggest that milk-associated bacteria and HMOs direct the assembly of the infant gut microbiota.
Aquatic reservoir of Vibrio cholerae in an African Great Lake assessed by large scale plankton sampling and ultrasensitive molecular methods
Authors: Vezzulli Luigi , Oliveri Caterina , Borello Alessio , Gregory Lance , Kimirei Ismael , Brunetta Martina , Stern Rowena , Coco Simona , Longo Luca , Taviani Elisa , Santos Andrès , Martinez-Urtaza Jaime , Wilson William H , Colwell Rita R , Pruzzo Carla , Plisnier Pierre-Denis
Published: June 2021

The significance of large tropical lakes as environmental reservoirs of Vibrio cholerae in cholera endemic countries has yet to be established. By combining large scale plankton sampling, microbial culture and ultrasensitive molecular methods, namely Droplet Digital PCR (ddPCR) and targeted genomics, the presence of Vibrio cholerae was investigated in a 96,600 L volume of surface water collected on a 322 nautical mile (596 km) transect in Lake Tanganyika. V. cholerae was detected and identified in a large area of the lake. In contrast, toxigenic strains of V. cholerae O1 or O139 were not detected in plankton samples possibly in relation to environmental conditions of the lake ecosystem, namely very low salinity compared to marine brackish and coastal environments. This represents to our knowledge, the largest environmental study to determine the role of tropical lakes as a reservoir of V. cholerae.
Levan Polysaccharide for Biomedical Applications
Authors: Kırtel O. , Öner E. T.
Published: June 2021

Levan is a homopolysaccharide of fructose units containing β-2,6 linkages between the fructosyl moieties on its backbone with occasional β-2,1 branches, and it is synthesized by a diverse genera of both Gram-positive and Gram-negative bacteria, fungi, some flowering plants, and some halophilic Archaea. With the discovery of its unique physiochemical features such as exceptionally low intrinsic viscosity and high adhesive strength, and bioactive characteristics as an anti-oxidant, anti-carcinogenic, prebiotic, hypoglycemic, and cell-proliferating agent, growing attention toward this polysaccharide has been seen especially in recent years. As a result, levan and its chemically modified derivatives have been the subject of several biomedical applications via development of novel levan-based biomaterials like films, electrospun and 3D-printed scaffolds, and hydrogels. This chapter summarizes the most recent findings from studies that focus on biomedical aspects of levan polysaccharide.
Minimalistic Peptide Self-assembly into Supramolecular Biomaterials
Authors: Cringoli M. C. , Fornasiero P. , Marchesan S.
Published: June 2021

Short peptides are attractive building blocks for supramolecular biomaterials for their low-cost, scalability of production and purification, possibility to encode biological messages, and to be processed by enzymes to fine-tune their lifetime toward controlled biodegradation. Over the last few decades, great progress has been made in the understanding of these building blocks for their tailored design to a variety of biological applications. This chapter reviews the design strategies to achieve hydrogels that have been applied to address a variety of biomedical needs. As more knowledge has been gathered in the field, a higher complexity could be achieved, for instance to target subcellular organelles, specific cells, and even to stimulate the immune response. Overall, self-assembling short peptides are reaching their full potential and have opened the gates to new paradigms in therapy to realize futuristic medicine.
Stimuli-responsive Nanocomposite Hydrogels Incorporating Soft Nanoparticles for Biomedical Applications
Authors: Lavrador P. , Borges J. , Gaspar V. M. , Mano J. F.
Published: June 2021

Soft nanoparticles represent a unique class of nanomaterials that can be engineered to react and adapt distinctly in different biological milieus while modulating the presentation of biochemical and biophysical cues to neighbouring receptive cells. This flexibility has fuelled the development of soft nanoparticle-laden nanocomposite hydrogels that are increasingly sophisticated in stimuli-responsiveness and promising for satisfying a plethora of biomedical applications. Such hybrid platforms can be encoded with intelligent disease-discerning tools, smart adaptability under external triggers for bioactive cargo delivery or be engineered for manipulating biomechanical properties in different tissue microenvironments. In addition, they can be interfaced with biological components(i.e. enzymes, cell membranes) or specific substrates recognisable by biological machinery, yielding biomolecule-responsive systems that perceive changes in their surroundings and alter their therapeutic outputs accordingly. In essence, this chapter highlights the unique opportunities of soft nanoparticles to function as versatile building blocks for programming and modulating a large array of features in hydrogel-based platforms, thus extending their biofunctionality and applicability in tissue engineering and regenerative medicine practices.
Decellularized Matrix Hydrogels for In Vitro Disease Modeling
Authors: Ferreira L. P. , Monteiro M. V. , Gaspar V. M. , Mano J. F.
Published: June 2021

The extracellular matrix (ECM) operates as a complex network of cell-supporting macromolecules in tissue homeostasis and disease scenarios. Given ECM structural and bio-signaling roles, understanding and modeling matrix components and their dysfunction in disease is crucial for the development of novel therapeutic approaches for numerous pathologies including pulmonary, renal and intestinal fibrosis, osteoarthritis or cancer. The discovery and preclinical in vitro screening of candidate therapeutics for tackling such conditions remains challenging owing to the lack of in vitro models capable of recapitulating ECM biochemical/biophysical cues and its complex tri-dimensional bioarchitecture in a laboratory setting. Advances in the decellularization, processing and modification of naturally available ECM into cell-free extracellular matrices (dECM) obtained from human or animal tissues, and its processing into designer hydrogels with tunable mechanical/structural features, open opportunities for bioengineering a new generation of more organotypic 3D testing platforms. Herein, we provide an overview of state-of-the-art methodologies employed for the development of dECM-hydrogels showcasing their key applications for generating tumor and fibrotic disease models. Standard and advanced processing technologies for dECM hydrogels such as 3D bioprinting and organ-on-a-chip platforms are also presented and discussed in light of future opportunities and improvements. By taking advantage of the capacity of dECM-hydrogels to closely recapitulate key matrix components, it is foreseeable that in vitro generating organotypic 3D microtissues will better capture key aspects of human diseases and contribute with predictive data on candidate therapeutics bioperformance prior to clinical trials.
A structure map for AB2 type 2D materials using high-throughput DFT calculations
Authors: Fukuda Masahiro , Zhang Jingning , Lee Yung-Ting , Ozaki Taisuke
Published: June 2021

A structure map for AB2 type monolayers of 3844 compounds is constructed by high-throughput DFT calculations with the symmetry-unconstrained geometry optimizations starting from ferromagnetic 1T, 1H and planar structures as initial states.
Tuneable manganese oxide nanoparticle based theranostic agents for potential diagnosis and drug delivery
Authors: Poon Kingsley , Lu Zufu , De Deene Yves , Ramaswamy Yogambha , Zreiqat Hala , Singh Gurvinder
Published: June 2021

Here, we demonstrate the design of l-dopamine coated manganese oxide nanoparticle based theranostics for MRI imaging and drug delivery. The release of drug molecules can be controlled by altering the size and chemical composition of nanoparticles.
Blood platelet quantification by light scattering: from morphology to activation
Authors: Litvinenko Alena L. , Nekrasov Vyacheslav M. , Strokotov Dmitry I. , Moskalensky Alexander E. , Chernyshev Andrey V. , Shilova Anna N. , Karpenko Andrey A. , Maltsev Valeri P.
Published: June 2021

Analysis of blood platelets encounters a number of different preanalytical issues, which greatly decrease the reliability and accuracy of routine clinical analysis.
Using a 3-hydroxyflavone derivative as a fluorescent probe for the indirect determination of aminothiols separated by ion-pair HPLC
Authors: Mikaliunaite Lina , Green David B.
Published: June 2021

Homocysteine, cysteine, cysteinyl-glycine, and glutathione are aminothiols (ATs) that are marker-molecules in Down syndrome, Alzheimer's disease, or are implicated in a number of vascular diseases, thus rapid determination of these ATs is desirable.
In situ construction of a direct Z-scheme CdIn2S4/TiO2 heterojunction for improving photocatalytic properties
Authors: Chen Yanyan , Hu Qi , Yu Minghui , Gong Xiaoyu , Li Shenjie , Wang Shuang , Yu Hao , Li Zhiqiang
Published: June 2021

Direct Z-scheme photocatalytic systems driven by visible light to eliminate organic pollutants in wastewater have become important scientific tools in the field of photocatalysis.