bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental demonstration of novel beam characterization using a polarizable X-band transverse deflection structure
Authors: Marchetti B. , Grudiev A. , Craievich P. , Assmann R. , Braun H.-H. , Catalan Lasheras N. , Christie F. , D’Arcy R. , Fortunati R. , Ganter R. , González Caminal P. , Hoffmann M. , Huening M. , Jaster-Merz S. M. , Jonas R. , Marcellini F. , Marx D. , McMonagle G. , Osterhoff J. , Pedrozzi M. , Prat Costa E. , Reiche S. , Reukauff M. , Schreiber S. , Tews G. , Vogt M. , Wesch S. , Wuensch W.
Published: February 2021

The PolariX TDS (Polarizable X-Band Transverse Deflection Structure) is an innovative TDS-design operating in the X-band frequency-range. The design gives full control of the streaking plane, which can be tuned in order to characterize the projections of the beam distribution onto arbitrary transverse axes. This novel feature opens up new opportunities for detailed characterization of the electron beam. In this paper we present first measurements of the Polarix TDS at the FLASHForward beamline at DESY, including three-dimensional reconstruction of the charge-density distribution of the bunch and slice emittance measurements in both transverse directions. The experimental results open the path toward novel and more extensive beam characterization in the direction of multi-dimensional-beam-phase-space reconstruction.
Evaluation of the number of undiagnosed infected in an outbreak using source of infection measurements
Authors: Melka Akiva Bruno , Louzoun Yoram
Published: February 2021

In times of outbreaks, an essential requirement for better monitoring is the evaluation of the number of undiagnosed infected individuals. An accurate estimate of this fraction is crucial for the assessment of the situation and the establishment of protective measures. In most current studies using epidemics models, the total number of infected is either approximated by the number of diagnosed individuals or is dependent on the model parameters and assumptions, which are often debated. We here study the relationship between the fraction of diagnosed infected out of all infected, and the fraction of infected with known contaminator out of all diagnosed infected. We show that those two are approximately the same in exponential models and across most models currently used in the study of epidemics, independently of the model parameters. As an application, we compute an estimate of the effective number of infected by the SARS-CoV-2 virus in various countries.
Silver nanowires as plasmonic compensators of luminescence quenching in single up-converting nanocrystals deposited on graphene
Authors: Prymaczek A. , Cwierzona M. , Antoniak M. A. , Nyk M. , Mackowski S. , Piatkowski D.
Published: February 2021

Single nanocrystal spectroscopy is employed to demonstrate metal-enhanced optical response of Er3+/Yb3+ doped up-conversion nanocrystals deposited on graphene upon coupling with silver nanowires. Direct interaction between nanocrystals and graphene results in quenching of up-conversion emission and shortening of luminescence decay times, due to the energy transfer to graphene. The amount of the energy absorbed by graphene can be enhanced by coupling Er3+/Yb3+ doped up-conversion nanocrystals with silver nanowires. Microscopy studies with high spatial resolution together with time-resolved analysis of nanocrystal luminescence show increase of the emission rates with fourfold enhancement of the intensity for nanocrystals placed in the vicinity of silver nanowires. This strong enhancement emerges despite simultaneous interaction with graphene. The hybrid nanostructure provides thus a way to combine optical activity of up-conversion nanocrystals and enhancement provided by metallic nanowires with excellent electrical and mechanical properties of graphene.
Hydrodynamic assisted multiparametric particle spectrometry
Authors: Martín-Pérez Alberto , Ramos Daniel , Yubero Marina L. , García-López Sergio , Kosaka Priscila M. , Tamayo Javier , Calleja Montserrat
Published: February 2021

The real-time analysis of single analytes in flow is becoming increasingly relevant in cell biology. In this work, we theoretically predict and experimentally demonstrate hydrodynamic focusing with hollow nanomechanical resonators by using an interferometric system which allows the optical probing of flowing particles and tracking of the fundamental mechanical mode of the resonator. We have characterized the hydrodynamic forces acting on the particles, which will determine their velocity depending on their diameter. By using the parameters simultaneously acquired: frequency shift, velocity and reflectivity, we can unambiguously classify flowing particles in real-time, allowing the measurement of the mass density: 1.35 ± 0.07 g·mL-1 for PMMA and 1.7 ± 0.2 g·mL-1 for silica particles, which perfectly agrees with the nominal values. Once we have tested our technique, MCF-7 human breast adenocarcinoma cells are characterized (1.11 ± 0.08 g·mL-1) with high throughput (300 cells/minute) observing a dependency with their size, opening the door for individual cell cycle studies.
Exposure to perfluoroalkyl substances in early pregnancy and risk of sporadic first trimester miscarriage
Authors: Wikström Sverre , Hussein Ghada , Lingroth Karlsson Annika , Lindh Christian H. , Bornehag Carl-Gustaf
Published: February 2021

Many first trimester sporadic miscarriages are unexplained and the role of environmental exposures is unknown. The present aim was to study if levels of Perfluoroalkyl substances (PFASs) in early pregnancy are associated with unexplained, sporadic first trimester miscarriage. The study was performed within the Swedish SELMA pregnancy cohort. Seventy-eight women with non-recurrent first trimester miscarriage were included and 1449 women were available as live birth controls. Eight PFASs were measured in first trimester serum. A doubling of perfluorooctanoic acid (PFOA) exposure, corresponding to an inter-quartile increase, was associated with an odds ratio (95%CI) for miscarriage of 1.48 (1.09–2.01) when adjusting for parity, age and smoking. Analyses per quartiles of PFOA exposure indicated a monotonic dose response association with miscarriage. A similar, but not significant, pattern was observed for perfluorononanoic acid (PFNA). For other PFAS, there were no associations with miscarriage. We have previously shown associations between early pregnancy PFAS exposures and preeclampsia, as well as lower birth weight. Now we report an association between PFOA and miscarriage within the same cohort, which may suggest shared but unknown mechanisms. The study can only represent a period of early placentation and clinical pregnancy loss during the second half of the first trimester.
Visual working memory and sensory processing in autistic children
Authors: Stevenson Ryan A. , Ruppel Justin , Sun Sol Z. , Segers Magali , Zapparoli Busisiwe L. , Bebko James M. , Barense Morgan D. , Ferber Susanne
Published: February 2021

While atypical sensory processing is one of the more ubiquitous symptoms in autism spectrum disorder, the exact nature of these sensory issues remains unclear, with different studies showing either enhanced or deficient sensory processing. Using a well-established continuous cued-recall task that assesses visual working memory, the current study provides novel evidence reconciling these apparently discrepant findings. Autistic children exhibited perceptual advantages in both likelihood of recall and recall precision relative to their typically-developed peers. When autistic children did make errors, however, they showed a higher probability of erroneously binding a given colour with the incorrect spatial location. These data align with neural-architecture models for feature binding in visual working memory, suggesting that atypical population-level neural noise in the report dimension (colour) and cue dimension (spatial location) may drive both the increase in probability of recall and precision of colour recall as well as the increase in proportion of binding errors when making an error, respectively. These changes are likely to impact core symptomatology associated with autism, as perceptual binding and working memory play significant roles in higher-order tasks, such as communication.
Development of event-specific detection method for identification of insect resistant NIBGE-1601 cotton harboring double gene Cry1Ac-Cry2Ab construct
Authors: Asif Muhammad , Siddiqui Hamid Anees , Naqvi Rubab Zahra , Amin Imran , Asad Shaheen , Mukhtar Zahid , Bashir Aftab , Mansoor Shahid
Published: February 2021

Bt cotton expressing Cry1Ac is being cultivated in Pakistan. It has been observed that pink bollworm may have developed resistance against single Bt gene (Cry1Ac). For durable resistance, insect resistant NIBGE-1601 cotton harboring double gene Cry1Ac-Cry2Ab construct was developed. There was a need to characterize NIBGE-1601 event for intellectual property rights protection. The Presence of NIBGE Cry1Ac and NIBGE Cry2Ab genes was checked in NIBGE-1601 cotton plants through PCR, while there was no amplification using primers specific for Monsanto events (MON531, MON15985, MON1445). Using genome walking technology, NIBGE-601 event has been characterized. Event-specific primers of NIBGE-1601 were designed and evaluated to differentiate it from other cotton events mentioned above. NIBGE-1601 event detection primers are highly specific, therefore, can detect NIBGE 1601 event at different conditions using single or multiplex PCR. In the qualitative PCR, using NIBGE-1601 event specific primers, 0.05 ng was the limit of detection for NIBGE-1601double gene cotton genomic DNA. Thus event characterization and development of event-specific diagnostics will help in breeding new cotton varieties resistant to cotton bollworms.
Morpho-molecular identification and first report of Fusarium equiseti in causing chilli wilt from Kashmir (Northern Himalayas)
Authors: Hami Ammarah , Rasool Rovidha S. , Khan Nisar A. , Mansoor Sheikh , Mir Mudasir A. , Ahmed Nazeer , Masoodi Khalid Z.
Published: February 2021

Chilli (Capsicum annuum L.) is one of the most significant vegetable and spice crop. Wilt caused by Fusarium Sp. has emerged as a serious problem in chilli production. Internal transcribed spacer (ITS) region is widely used as a DNA barcoding marker to characterize the diversity and composition of Fusarium communities. ITS regions are heavily used in both molecular methods and ecological studies of fungi, because of its high degree of interspecific variability, conserved primer sites and multiple copy nature in the genome. In the present study we focused on morphological and molecular characterization of pathogen causing chilli wilt. Chilli plants were collected from four districts of Kashmir valley of Himalayan region. Pathogens were isolated from infected root and stem of the plants. Isolated pathogens were subjected to DNA extraction and PCR amplification. The amplified product was sequenced and three different wilt causing fungal isolates were obtained which are reported in the current investigation. In addition to Fusarium oxysporum and Fusarium solani, a new fungal species was found in association with the chilli wilt in Kashmir valley viz., Fusarium equiseti that has never been reported before from this region. The studies were confirmed by pathogenicity test and re-confirmation by DNA barcoding.
Generation of Werner-like states via a two-qubit system plunged in a thermal reservoir and their application in solving binary classification problems
Authors: Ghasemian E. , Tavassoly M. K.
Published: February 2021

We present a theoretical scheme for the generation of stationary entangled states. To achieve the purpose we consider an open quantum system consisting of a two-qubit plunged in a thermal bath, as the source of dissipation, and then analytically solve the corresponding quantum master equation. We generate two classes of stationary entangled states including the Werner-like and maximally entangled mixed states. In this regard, since the solution of the system depends on its initial state, we can manipulate it and construct robust Bell-like state. In the continuation, we analytically obtain the population and coherence of the considered two-qubit system and show that the residual coherence can be maintained even in the equilibrium condition. Finally, we successfully encode our two-qubit system to solve a binary classification problem. We demonstrate that, the introduced classifiers present high accuracy without requiring any iterative method. In addition, we show that the quantum based classifiers beat the classical ones.
Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2
Authors: Boshans Linda L. , Soh Heun , Wood William M. , Nolan Timothy M. , Mandoiu Ion I. , Yanagawa Yuchio , Tzingounis Anastasios V. , Nishiyama Akiko
Published: February 2021

Oligodendrocyte precursor cells (NG2 glia) are uniformly distributed proliferative cells in the mammalian central nervous system and generate myelinating oligodendrocytes throughout life. A subpopulation of OPCs in the neocortex arises from progenitor cells in the embryonic ganglionic eminences that also produce inhibitory neurons. The neuronal fate of some progenitor cells is sealed before birth as they become committed to the oligodendrocyte lineage, marked by sustained expression of the oligodendrocyte transcription factor Olig2, which represses the interneuron transcription factor Dlx2. Here we show that misexpression of Dlx2 alone in postnatal mouse OPCs caused them to switch their fate to GABAergic neurons within 2 days by downregulating Olig2 and upregulating a network of inhibitory neuron transcripts. After two weeks, some OPC-derived neurons generated trains of action potentials and formed clusters of GABAergic synaptic proteins. Our study revealed that the developmental molecular logic can be applied to promote neuronal reprogramming from OPCs.
Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation
Authors: Hu Wenyu , Dong Anqi , Karasaki Kohei , Sogabe Shota , Okamoto Daiki , Saigo Masato , Ishida Mari , Yoshizumi Masao , Kokubo Hiroki
Published: February 2021

Bmp plays an important role in cardiomyocyte differentiation, but the function of Smad4 in Bmp signaling remains elusive. Here, we show that disruption of the Smad4 gene in cardiac progenitors expressing Sfrp5 led to embryonic lethality with hypoplastic heart formation. Although the expression of Nkx2-5 is regulated by Bmp signaling, expression of Nkx2-5 was weakly detected in the mutant heart. However, the nuclear translocation of Nkx2-5 was impaired. Expression of CK2 or PP1, which could alter the phosphorylation status of the NLS of Nkx2-5, was not affected, but Nkx2-5 was found to bind to Smad4 by co-immunoprecipitation experiments. Introduction of Smad4 into cells derived from Smad4 conditional knockout embryonic hearts restored the nuclear localization of Nkx2-5, and exogenous Nkx2-5 failed to translocate into the nucleus of Smad4-depleted fibroblasts. These results suggest that Smad4 plays an essential role in cardiomyocyte differentiation by controlling not only transcription but also the nuclear localization of Nkx2-5.
Grading system utilising the total score of Oxford classification for predicting renal prognosis in IgA nephropathy
Authors: Miyabe Yoei , Karasawa Kazunori , Akiyama Kenichi , Ogura Shota , Takabe Tomo , Sugiura Naoko , Seki Momoko , Iwabuchi Yuko , Hanafusa Norio , Uchida Keiko , Nitta Kosaku , Moriyama Takahito
Published: February 2021

The Oxford classification of IgA nephropathy (IgAN) can evaluate each MEST-C score individually. We analysed a new grading system that utilised the total MEST-C score in predicting renal prognosis. Altogether, 871 IgAN patients were classified into three groups using the new Oxford classification system (O-grade) that utilised the total MEST-C score (O-grade I: 0–1, II: 2–4, and III: 5–7 points), and the 10-year renal prognosis was analysed. The clinical findings became significantly severer with increasing O-grades, and the renal survival rate by the Kaplan–Meier method was 94.1%, 86.9%, and 74.1% for O-grades I, II, and III, respectively. The hazard ratios (HRs) for O-grades II and III with reference to O-grade I were 2.8 (95% confidence interval [CI] 1.3–6.0) and 6.3 (95% CI 2.7–14.5), respectively. In the multivariate analysis, mean arterial pressure and eGFR, proteinuria at the time of biopsy, treatment of corticosteroids/immunosuppressors, and O-grade (HR 1.63; 95% CI 1.11–2.38) were the independent factors predicting renal prognosis. Among the nine groups classified using the O-grade and Japanese clinical-grade, the renal prognosis had an HR of 15.2 (95% CI 3.5–67) in the severest group. The O-grade classified by the total score of the Oxford classification was associated with renal prognosis.
Semantic segmentation of reflectance confocal microscopy mosaics of pigmented lesions using weak labels
Authors: D’Alonzo Marissa , Bozkurt Alican , Alessi-Fox Christi , Gill Melissa , Brooks Dana H. , Rajadhyaksha Milind , Kose Kivanc , Dy Jennifer G.
Published: February 2021

Reflectance confocal microscopy (RCM) is a non-invasive imaging tool that reduces the need for invasive histopathology for skin cancer diagnoses by providing high-resolution mosaics showing the architectural patterns of skin, which are used to identify malignancies in-vivo. RCM mosaics are similar to dermatopathology sections, both requiring extensive training to interpret. However, these modalities differ in orientation, as RCM mosaics are horizontal (parallel to the skin surface) while histopathology sections are vertical, and contrast mechanism, RCM with a single (reflectance) mechanism resulting in grayscale images and histopathology with multi-factor color-stained contrast. Image analysis and machine learning methods can potentially provide a diagnostic aid to clinicians to interpret RCM mosaics, eventually helping to ease the adoption and more efficiently utilizing RCM in routine clinical practice. However standard supervised machine learning may require a prohibitive volume of hand-labeled training data. In this paper, we present a weakly supervised machine learning model to perform semantic segmentation of architectural patterns encountered in RCM mosaics. Unlike more widely used fully supervised segmentation models that require pixel-level annotations, which are very labor-demanding and error-prone to obtain, here we focus on training models using only patch-level labels (e.g. a single field of view within an entire mosaic). We segment RCM mosaics into “benign” and “aspecific (nonspecific)” regions, where aspecific regions represent the loss of regular architecture due to injury and/or inflammation, pre-malignancy, or malignancy. We adopt Efficientnet, a deep neural network (DNN) proven to accurately accomplish classification tasks, to generate class activation maps, and use a Gaussian weighting kernel to stitch smaller images back into larger fields of view. The trained DNN achieved an average area under the curve of 0.969, and Dice coefficient of 0.778 showing the feasibility of spatial localization of aspecific regions in RCM images, and making the diagnostics decision model more interpretable to the clinicians.
Transcriptome analysis of arterial and venous circulating miRNAs during hypertension
Authors: Jin Ling , Li Min , Wang Hao , Yin Zhongnan , Chen Li , Zhou Yang , Han Yongzheng , Cui Qinghua , Zhou Yuan , Xue Lixiang
Published: February 2021

Most current circulating miRNA biomarkers are derived from peripheral venous blood, whereas miRNA deregulation in arterial blood in disease conditions has been largely ignored. To explore whether peripheral venous blood miRNAs could represent a bona fide specific miRNA deregulation pattern, we selected hypertension, a disease that is particularly associated with vessels, as the model. Circulating miRNA profiles of arterial and venous blood from spontaneously hypertensive (SHR) rats and their corresponding controls (i.e., WKY rats) were investigated by next-generation miRNA sequencing. Little miRNAs were observed between arterial and venous circulating miRNAs in WKY rats. Interestingly, this number was enhanced in SHR hypertensive rats. Bioinformatical analysis of disease association, enriched target genes and the regulatory transcription factors of these differentially expressed miRNAs implied a potential functional link with cardiovascular disease-related functions. Comparisons between arterial and venous miRNAs in hypertension-versus-control conditions also revealed prominent disease association of circulating miRNAs and their target genes in arteries but not in veins. Moreover, a young non-hypertensive animal model in SHR background (i.e. JSHR) was used as a second control for SHR. Additional transcriptomic analysis and droplet digital PCR validation of arterial and venous deregulated miRNAs among SHR and its two controls (WKY, JSHR) revealed a noticeable consensus of artery-deregulated miRNAs in hypertension and two novel arterial circulating signatures (miR-455-3p and miR-140-3p) of hypertension. These results suggest the necessity of re-evaluating the efficacy of certain venous miRNAs identified in previous studies as potential biomarkers in cardiovascular diseases or a wider disease spectrum.
Changes in the large carnivore community structure of the Judean Desert in connection to Holocene human settlement dynamics
Authors: Lazagabaster Ignacio A. , Ullman Micka , Porat Roi , Halevi Romi , Porat Naomi , Davidovich Uri , Marom Nimrod
Published: February 2021

Investigating historical anthropogenic impacts on faunal communities is key to understanding present patterns of biodiversity and holds important implications for conservation biology. While several studies have demonstrated the human role in the extinction of large herbivores, effective methods to study human interference on large carnivores in the past are limited by the small number of carnivoran remains in the paleozoological record. Here, we integrate a systematic paleozoological survey of biogenic cave assemblages with the archaeological and paleoenvironmental records of the Judean Desert, to reveal historical changes in the large carnivore community. Our results show a late Holocene (~ 3400 years ago) faunal reassembly characterized by the diminishment of the dominant large carnivoran, the Arabian leopard (Panthera pardus sbsp. nimr), and the spread of the Syrian striped hyena (Hyaena hyaena sbsp. syriaca). We suggest that increased hunting pressure in combination with regional aridification were responsible for the decrease in the number of leopards, while the introduction of domestic animals and settlement refuse brought new scavenging opportunities for hyenas. The recent extirpation of leopards from the region has been a final note to the Holocene human impact on the ecosystem.
Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration
Authors: Au K. S. , Hebert L. , Hillman P. , Baker C. , Brown M. R. , Kim D.-K. , Soldano K. , Garrett M. , Ashley-Koch A. , Lee S. , Gleeson J. , Hixson J. E. , Morrison A. C. , Northrup H.
Published: February 2021

Myelomeningocele (MMC) affects one in 1000 newborns annually worldwide and each surviving child faces tremendous lifetime medical and caregiving burdens. Both genetic and environmental factors contribute to disease risk but the mechanism is unclear. This study examined 506 MMC subjects for ultra-rare deleterious variants (URDVs, absent in gnomAD v2.1.1 controls that have Combined Annotation Dependent Depletion score ≥ 20) in candidate genes either known to cause abnormal neural tube closure in animals or previously associated with human MMC in the current study cohort. Approximately 70% of the study subjects carried one to nine URDVs among 302 candidate genes. Half of the study subjects carried heterozygous URDVs in multiple genes involved in the structure and/or function of cilium, cytoskeleton, extracellular matrix, WNT signaling, and/or cell migration. Another 20% of the study subjects carried heterozygous URDVs in candidate genes associated with gene transcription regulation, folate metabolism, or glucose metabolism. Presence of URDVs in the candidate genes involving these biological function groups may elevate the risk of developing myelomeningocele in the study cohort.
Development of an immune-related gene pairs signature for predicting clinical outcome in lung adenocarcinoma
Authors: Wu Chunlei , Hu Quanteng , Ma Dehua
Published: February 2021

Lung adenocarcinoma (LUAD) is the main pathological subtype of Non-small cell lung cancer. We downloaded the gene expression profile and immune-related gene set from the TCGA and ImmPort database, respectively, to establish immune-related gene pairs (IRGPs). Then, IRGPs were subjected to univariate Cox regression analysis, LASSO regression analysis, and multivariable Cox regression analysis to screen and develop an IRGPs signature. The receiver operating characteristic curve (ROC) was applied for evaluating the predicting accuracy of this signature by calculating the area under ROC (AUC) and data from the GEO set was used to validate this signature. The relationship of 22 tumor-infiltrating immune cells (TIICs) to the immune risk score was also investigated. An IRGPs signature with 8 IRGPs was constructed. The AUC for 1- and 3-year overall survival in the TCGA set was 0.867 and 0.870, respectively. Similar results were observed in the AUCs of GEO set 1, 2 and 3 (GEO set 1 [1-year: 0.819; 3-year: 0.803]; GEO set 2 [1-year: 0.834; 3-year: 0.870]; GEO set 3 [1-year: 0.955; 3-year: 0.827]). Survival analysis demonstrated high-risk LUAD patients exhibited poorer prognosis. The multivariable Cox regression indicated that the risk score was an independent prognostic factor. The immune risk score was highly associated with several TIICs (Plasma cells, memory B cells, resting memory CD4 T cells, and activated NK cells). We developed a novel IRGPs signature for predicting 1- and 3- year overall survival in LUAD, which would be helpful for prognosis assessment of LUAD.
Targeting the DNA replication stress phenotype of KRAS mutant cancer cells
Authors: Al Zubaidi Tara , Gehrisch O. H. Fiete , Genois Marie-Michelle , Liu Qi , Lu Shan , Kung Jong , Xie Yunhe , Schuemann Jan , Lu Hsiao-Ming , Hata Aaron N. , Zou Lee , Borgmann Kerstin , Willers Henning
Published: February 2021

Mutant KRAS is a common tumor driver and frequently confers resistance to anti-cancer treatments such as radiation. DNA replication stress in these tumors may constitute a therapeutic liability but is poorly understood. Here, using single-molecule DNA fiber analysis, we first characterized baseline replication stress in a panel of unperturbed isogenic and non-isogenic cancer cell lines. Correlating with the observed enhanced replication stress we found increased levels of cytosolic double-stranded DNA in KRAS mutant compared to wild-type cells. Yet, despite this phenotype replication stress-inducing agents failed to selectively impact KRAS mutant cells, which were protected by CHK1. Similarly, most exogenous stressors studied did not differentially augment cytosolic DNA accumulation in KRAS mutant compared to wild-type cells. However, we found that proton radiation was able to slow fork progression and preferentially induce fork stalling in KRAS mutant cells. Proton treatment also partly reversed the radioresistance associated with mutant KRAS. The cellular effects of protons in the presence of KRAS mutation clearly contrasted that of other drugs affecting replication, highlighting the unique nature of the underlying DNA damage caused by protons. Taken together, our findings provide insight into the replication stress response associated with mutated KRAS, which may ultimately yield novel therapeutic opportunities.
Urodynamic evaluation of patients with localized prostate cancer before and 4 months after robotic radical prostatectomy
Authors: Lee Dong Sup , Lee Seung-ju
Published: February 2021

Radical prostatectomy can alter the anatomy of the urinary bladder. We aimed to evaluate bladder function before and 4 months after radical prostatectomy using the urodynamic test and overactive bladder (OAB) symptom score. Among 70 prospectively enrolled patients, 61 patients completed the study. In the urodynamic test, bladder capacity and compliance did not change, the frequency of involuntary detrusor contraction decreased, the maximum flow rate and bladder outlet obstruction index improved, and the maximum urethral closure pressure (MUCP) deteriorated. Further evaluation of urodynamic parameters according to changes in symptoms was made. Although change in bladder compliance was correlated with changes in OAB symptoms, not the relative change of bladder compliance but the relative change in the MUCP was reliable factor when OAB symptoms were deteriorated. In general, prostatectomy did not deteriorate the condition of the detrusor; rather, change in the MUCP could be responsible for postprostatectomy OAB.
Effects of silicon doping on low-friction and high-hardness diamond-like carbon coating via filtered cathodic vacuum arc deposition
Authors: Kim Jae-Il , Jang Young-Jun , Kim Jisoo , Kim Jongkuk
Published: February 2021

In this study, silicon (Si) was doped on a tetrahedral amorphous carbon (ta-C) coating and the tribological characteristics of the resulting Si-doped diamond-like carbon (DLC; a-C:Si:H) were investigated against a SUJ2 ball. The Si fraction in the coating was varied from 0 to ~ 20 at.% by increasing the trimethylsilane gas flow rate during filtered cathodic vacuum arc deposition. The coefficient of friction (CoF) showed no obvious change when the Si fraction was less than ~ 7 at.%. However, after Si doping, it significantly decreased when the Si fraction was greater than ~ 8 at.%. The running-in period also decreased to less than 1000 cycles after Si doping. The rapid formation of Si-rich debris and transfer layer led to the fabrication of a low-friction tribofilm, which was induced by the tribochemical reaction with moisture under ambient conditions. When the Si fraction was ~ 17 at.%, the lowest CoF of less than 0.05 was obtained. Further Si doping beyond the critical point led to the destruction of the film because of reduced hardness.
Correlation between toxicity and dosimetric parameters for adjuvant intensity modulated radiation therapy of breast cancer: a prospective study
Authors: Pasquier David , Bataille Benoit , Le Tinier Florence , Bennadji Raoudha , Langin Hélène , Escande Alexandre , Tresch Emmanuelle , Darloy Franck , Carlier Damien , Crop Frederik , Lartigau Eric
Published: February 2021

ORCID: 0000–0001-6019–7309. In the treatment of breast cancer, intensity-modulated radiation therapy (IMRT) reportedly reduces the high-dose irradiation of at-risk organs and decreases the frequency of adverse events (AEs). Comparisons with conventional radiotherapy have shown that IMRT is associated with lower frequencies of acute and late-onset AEs. Here, we extended a prospective, observational, single-center study of the safety of IMRT to a second investigating center. Patients scheduled for adjuvant IMRT after partial or total mastectomy were given a dose of 50 Gy (25 fractions of 2 Gy over 5 weeks), with a simultaneous integrated boost in patients having undergone conservative surgery. 300 patients were included in the study, and 288 were analyzed. The median follow-up period was 2.1 years. The 2-year disease-free survival rate [95% CI] was 93.4% [89.2–96.0%]. Most AEs were mild. The most common AEs were skin-related—mainly radiodermatitis [in 266 patients (92.4%)] and hyperpigmentation (in 178 (61.8%)). 35% and 6% of the patients presented with grade 2 acute skin and esophageal toxicity, respectively. Only 4 patients presented with a grade 3 event (radiodermatitis). Smoking (odds ratio) [95% CI] = 2.10 [1.14–3.87]; p = 0.017), no prior chemotherapy (0.52 [0.27–0.98]; p = 0.044), and D98% for subclavicular skin (1.030 [1.001–1.061]; p = 0.045) were associated with grade ≥ 2 acute AEs. In a univariate analysis, the mean dose, (p < 0.0001), D2% (p < 0.0001), D50% (p = 0.037), D95% (p = 0.0005), D98% (p = 0.0007), V30Gy (p < 0.0001), and V45Gy (p = 0.0001) were significantly associated with grade ≥ 1 acute esophageal AEs. In a multivariate analysis, D95% for the skin (p < 0.001), D98% for the subclavicular skin and low D95% for the internal mammary lymph nodes were associated with grade ≥ 1 medium-term AEs. The safety profile of adjuvant IMRT after partial or total mastectomy is influenced by dosimetric parameters.

Trial registration: ClinicalTrials.gov NCT02281149.
Quality of life of HIV-negative, previously healthy individuals following cryptococcal meningoencephalitis
Authors: Dean Owen , Anjum Seher , Scott Terri , Ham Lillian , Traino Katherine , Wang Jing , Hunsberger Sally , Powers John H. , Marr Kieren A. , Snow Joseph , Williamson Peter R.
Published: February 2021

The morbidity and mortality of cryptococcal meningoencephalitis (CM) in previously healthy, HIV-negative individuals is increasingly recognized. We administered a healthcare associated quality of life (QOL) survey to the largest longitudinally followed cohort of these patients in the United States. We identified moderate or severe self-reported impairment in at least one QOL domain in 61% of subjects at least one year following diagnosis. Self-reported cognitive impairment was noted in 52% and sleep disturbance was noted in 55%. This is the first comprehensive study of cross-sectional long-term QOL in previously healthy patients following cryptococcal infection.
Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer
Authors: Fujita Shiro , Masago Katsuhiro
Published: February 2021

Both non-small-cell lung cancer cases in never-smokers and nonmedullary thyroid cancer cases have been increasing in developed countries. Some studies have shown an excess of co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer. We aimed to clarify the underlying genetic factors that contribute to the occurrence of these two malignancies. We performed germline exome sequencing in a cohort of 9 patients with the two malignancies. In terms of candidate genes, we performed target resequencing, immunohistochemistry, and microsatellite instability testing on another cohort. Two rare missense heterozygous variants in MSH6 were identified and verified by Sanger sequencing. One available tumour specimen showed heterogeneous MSH6 status in immunohistochemistry. Further exploration with different cohorts (a total of 8 patients with the two malignancies) demonstrated that 2 out of 8 patients had a germline missense or promotor variant of MLH1 and four out of 10 tumour specimens revealed heterogeneous immunohistochemistry staining in any of the four mismatch repair proteins: MLH1, PMS2, MSH2 and MSH6. Although our cohort showed a different disease profile than Lynch syndrome, this study suggests causal roles of impaired DNA mismatch repair capacity in non-small-cell lung cancer and nonmedullary thyroid cancer.
NIR self-powered photodetection and gate tunable rectification behavior in 2D GeSe/MoSe2 heterojunction diode
Authors: Hussain Muhammad , Jaffery Syed Hassan Abbas , Ali Asif , Nguyen Cong Dinh , Aftab Sikandar , Riaz Muhammad , Abbas Sohail , Hussain Sajjad , Seo Yongho , Jung Jongwan
Published: February 2021

Two-dimensional (2D) heterostructure with atomically sharp interface holds promise for future electronics and optoelectronics because of their multi-functionalities. Here we demonstrate gate-tunable rectifying behavior and self-powered photovoltaic characteristics of novel p-GeSe/n-MoSe2 van der waal heterojunction (vdW HJ). A substantial increase in rectification behavior was observed when the devices were subjected to gate bias. The highest rectification of ~ 1 × 104 was obtained at Vg = − 40 V. Remarkable rectification behavior of the p-n diode is solely attributed to the sharp interface between metal and GeSe/MoSe2. The device exhibits a high photoresponse towards NIR (850 nm). A high photoresponsivity of 465 mAW−1, an excellent EQE of 670%, a fast rise time of 180 ms, and a decay time of 360 ms were obtained. Furthermore, the diode exhibits detectivity (D) of 7.3 × 109 Jones, the normalized photocurrent to the dark current ratio (NPDR) of 1.9 × 1010 W−1, and the noise equivalent power (NEP) of 1.22 × 10–13 WHz−1/2. The strong light-matter interaction stipulates that the GeSe/MoSe2 diode may open new realms in multi-functional electronics and optoelectronics applications.
Continuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation
Authors: Gao Huashan , Zhao Qian , Tang Shanshan , Li Kaiying , Qin Fujian , Song Ziwei , Pan Yi , Jin Liang , Zhang Yanfeng
Published: February 2021

Multiple animal and human studies have shown that administration of GLP-1RA can enhance β-cell recovery, reduce insulin dosage, reduce HbA1c content in the blood, reduce the risk of hypoglycemia and reduce inflammation. In the NOD mouse model, peptide VP treatment can prevent and treat type 1 diabetes through immunomodulation. Therefore, we designed a new dual-functional PGLP-1-VP, which is expected to combine the anti-inflammatory effect of PGLP-1 and the immunomodulatory effect of VP peptide. In streptozotocin-induced hyperglycemic mice model, we demonstrated that PGLP-1-VP can act as a GLP-1R agonist to improve hyperglycemia and increase insulin sensitivity. In the NOD mouse model, PGLP-1-VP treatment reduced morbidity, mortality, and pancreatic inflammation, and showed superior effect to PGLP-1 or VP treatment alone, confirming that PGLP-1-VP may act as a dual-function peptide. PGLP-1-VP provided immunomodulatory effect through increasing Th2 cell percentage and balancing the ratio of Th2/Th1 in spleen and PLN, similar to P277 and VP. Additionally, PGLP-1-VP and PGLP-1 act the anti-inflammation by increasing Treg cells and TGF-β1 content like DPP-IV inhibitor. Taken together, our data shows that the dual-functional PGLP-1-VP reduces morbidity and mortality in the NOD model, suggesting a potential role in preventing and treating type 1 diabetes.
Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2
Authors: Weglarz-Tomczak Ewelina , Tomczak Jakub M. , Talma Michał , Burda-Grabowska Małgorzata , Giurg Mirosław , Brul Stanley
Published: February 2021

An efficient treatment against a COVID-19 disease, caused by the novel coronavirus SARS-CoV-2 (CoV2), remains a challenge. The papain-like protease (PLpro) from the human coronavirus is a protease that plays a critical role in virus replication. Moreover, CoV2 uses this enzyme to modulate the host’s immune system to its own benefit. Therefore, it represents a highly promising target for the development of antiviral drugs. We used Approximate Bayesian Computation tools, molecular modelling and enzyme activity studies to identify highly active inhibitors of the PLpro. We discovered organoselenium compounds, ebselen and its structural analogues, as a novel approach for inhibiting the activity of PLproCoV2. Furthermore, we identified, for the first time, inhibitors of PLproCoV2 showing potency in the nanomolar range. Moreover, we found a difference between PLpro from SARS and CoV2 that can be correlated with the diverse dynamics of their replication, and, putatively to disease progression.
Selective loss of microvesicles is a major issue of the differential centrifugation isolation protocols
Authors: Nigro Annamaria , Finardi Annamaria , Ferraro Marzia M. , Manno Daniela E. , Quattrini Angelo , Furlan Roberto , Romano Alessandro
Published: February 2021

Microvesicles (MVs) are large extracellular vesicles differing in size, cargo and composition that share a common mechanism of release from the cells through the direct outward budding of the plasma membrane. They are involved in a variety of physiological and pathological conditions and represent promising biomarkers for diseases. MV heterogeneity together with the lack of specific markers had strongly hampered the development of effective methods for MV isolation and differential centrifugation remains the most used method to purify MVs. In this study, we analysed the capacity of the differential centrifugation method to isolate MVs from cell-conditioned medium using flow cytometry and TEM/AFM microscopy. We found that the loss of MVs (general population and/or specific subpopulations) represents a major and underestimate drawback of the differential centrifugation protocol. We demonstrate that the choice of the appropriate rotor type (fixed-angle vs swinging-bucket) and the implementation of an additional washing procedure to the first low-speed centrifugation step of the protocol allow to overcome this problem increasing the total amount of isolated vesicles and avoiding the selective loss of MV subpopulations. These parameters/procedures should be routinely employed into optimized differential centrifugation protocols to ensure isolation of the high-quantity/quality MVs for the downstream analysis/applications.
Supercritical carbon dioxide decellularization of plant material to generate 3D biocompatible scaffolds
Authors: Harris Ashlee F. , Lacombe Jerome , Liyanage Sumedha , Han Margaret Y. , Wallace Emily , Karsunky Sophia , Abidi Noureddine , Zenhausern Frederic
Published: February 2021

The use of plant-based biomaterials for tissue engineering has recently generated interest as plant decellularization produces biocompatible scaffolds which can be repopulated with human cells. The predominant approach for vegetal decellularization remains serial chemical processing. However, this technique is time-consuming and requires harsh compounds which damage the resulting scaffolds. The current study presents an alternative solution using supercritical carbon dioxide (scCO2). Protocols testing various solvents were assessed and results found that scCO2 in combination with 2% peracetic acid decellularized plant material in less than 4 h, while preserving plant microarchitecture and branching vascular network. The biophysical and biochemical cues of the scCO2 decellularized spinach leaf scaffolds were then compared to chemically generated scaffolds. Data showed that the scaffolds had a similar Young’s modulus, suggesting identical stiffness, and revealed that they contained the same elements, yet displayed disparate biochemical signatures as assessed by Fourier-transform infrared spectroscopy (FTIR). Finally, human fibroblast cells seeded on the spinach leaf surface were attached and alive after 14 days, demonstrating the biocompatibility of the scCO2 decellularized scaffolds. Thus, scCO2 was found to be an efficient method for plant material decellularization, scaffold structure preservation and recellularization with human cells, while performed in less time (36 h) than the standard chemical approach (170 h).
Load-sharing biomechanics of lumbar fixation and fusion with pedicle subtraction osteotomy
Authors: La Barbera Luigi , Wilke Hans-Joachim , Ruspi Maria Luisa , Palanca Marco , Liebsch Christian , Luca Andrea , Brayda-Bruno Marco , Galbusera Fabio , Cristofolini Luca
Published: February 2021

Pedicle subtraction osteotomy (PSO) is an invasive surgical technique allowing the restoration of a well-balanced sagittal profile, however, the risks of pseudarthrosis and instrumentation breakage are still high. Literature studied primary stability and posterior instrumentation loads, neglecting the load shared by the anterior column, which is fundamental to promote fusion early after surgery. The study aimed at quantifying the load-sharing occurring after PSO procedure across the ventral spinal structures and the posterior instrumentation, as affected by simple bilateral fixation alone, with interbody cages adjacent to PSO level and supplementary accessory rods. Lumbar spine segments were loaded in vitro under flexion–extension, lateral bending, and torsion using an established spine tester. Digital image correlation (DIC) and strain-gauge (SG) analyses measured, respectively, the full-field strain distribution on the ventral surface of the spine and the local strain on posterior primary rods. Ventral strains considerably decreased following PSO and instrumentation, confirming the effectiveness of posterior load-sharing. Supplemental accessory rods considerably reduced the posterior rod strains only with interbody cages, but the ventral strains were unaffected: this indicates that the load transfer across the osteotomy could be promoted, thus explaining the higher fusion rate with decreased rod fracture risk reported in clinical literature.
Double-layered fiber for lightweight flexible clothing providing shielding from low-dose natural radiation
Authors: Kim Seon-Chil , Son Jun Sik
Published: February 2021

Natural and medical radiation are the most frequent sources of daily low-dose radiation exposure for the general public, but these radiation levels are generally acceptable. Among various occupations, aviation crew members and medical workers are exposed to high levels of radiation from scattered rays. This study focused on developing clothing for shielding aviation crew members from natural radiation during air travel. Materials were selected considering their radiation-shielding properties. A tungsten double-layered composite yarn and a polyethylene terephthalate (PET) fiber fabric containing BaSO4 were manufactured. The characteristics and shielding performances of the products were analyzed. Prototypes of a protective scarf (for shielding the thyroid gland) and apron (for shielding the torso) for flight attendants were produced. A lightweight fabric was produced that neither restricts the movement of the wearer nor causes them skin discomfort. The shielding performances of the tungsten composite and PET fiber fabrics containing BaSO4 were 0.018 mmPb and 0.03 mmPb, respectively, demonstrating low-dose shielding that may be useful for protecting aviation crew members from scattered rays. The characteristics of the developed fibers are comparable to those of materials used in clothing production; therefore, low-dose radiation-shielding clothing could be manufactured for use in aviation, medical, and other industries.
Diffuse reflectance spectroscopy reveals heat stress-induced changes in hemoglobin concentration in chicken breast
Authors: Dadgar Sina , Greene Elizabeth , Dhamad Ahmed , Mallmann Barbara , Dridi Sami , Rajaram Narasimhan
Published: February 2021

Heat stress (HS) is devastating to the poultry industry due to its adverse effects on animal well-being and performance. The effects of heat stress are typically measured using a portable i-STAT blood analyzer that quantifies circulatory hemoglobin concentration and other blood chemistry parameters. Here, we used diffuse reflectance spectroscopy (DRS) as a novel non-invasive method to directly determine changes in hematological parameters in the breast tissues of live heat-stressed broilers. Three-week-old male broilers were randomly subjected to two environmental conditions (thermoneutral, TN, 24 °C vs. cyclic heat stress, HS, 35 °C, 12 h/day). Optical spectra were acquired using DRS to monitor breast hemoglobin (Hb) concentration and vascular oxygen saturation (sO2) at three time points: at baseline prior to heat stress, 2 days, and 21 days after initiation of HS. While i-STAT did not demonstrate a discernible change due to HS in circulatory hemoglobin, DRS found a significant decrease in breast Hb and sO2 after exposure to chronic HS. The decrease in sO2 was found to be due to a decrease in oxygenated hemoglobin concentration, indicating a large increase in oxygen consumption in heat-stressed broilers. Our results demonstrate that DRS could potentially be used to study the effects of HS directly in specific organs of interest, such as the breast and thigh, to improve meat quality.