bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Argo Float Trajectories Under Ice
Authors: Oke Peter R. , Rykova Tatiana , Pilo Gabriela S. , Lovell Jennifer L.
Published: June 2022

Since the Argo program began, 568 floats returned almost 31,000 profiles, at high‐southern latitudes, with no measured position. These data are either disseminated with positions linearly interpolated between known positions, or with no geographic positions. Here, we present a simple method for estimating unknown Argo float trajectories. We try to identify trajectories that approximately follow contours along three different properties: potential vorticity (f/H), sea‐level, and density at 1,000 m. No single property‐constraint can be used to estimate trajectories for all position‐gaps. Each constraint fails for 9%–18% of gaps, where no continuous contour between the end‐points exists. But all constraints fail for the same position‐gap, for fewer than 1% of cases. For a given position‐gap, when a trajectory is identified using two or three different constraints, we select the shortest trajectory to be used to “fill the gap”. This selection process could be performed better by an Expert Operator, inspecting each estimated trajectory, and selecting the trajectory that is most consistent with a priori knowledge of the circulation in the vicinity of the position‐gap. Nonetheless, using the objective metric for selection, we find that 41.2% of position‐gaps use the f/H‐constraint, 32.1% use density, and 25.8% use sea‐level. We assess the estimated trajectories for consistency, by comparing bottom depths beneath trajectories to the deepest measurements in each profile. We find inconsistencies for 11.6% of position‐gaps using our method, compared to 28.0% using linearly‐interpolated trajectories. Adoption of the estimated trajectories for measurements under ice may yield benefits to many applications.
Combined Scattering of Concurrent Unusual High‐Frequency EMIC Waves and MS Waves on Radiation Belt Electrons
Authors: Zhou Ruoxian , Fu Song , Gu Xudong , Ma Xin , Ni Binbin , Yi Juan , Guo Yingjie , Guo Deyu , Jiao Luhuai , Yun Xiaotong , Wang Xiaoyu
Published: June 2022

We report a concurrent event of unusual high‐frequency Electromagnetic ion cyclotron (EMIC) and Magnetosonic (MS) waves in correspondence with butterfly distributions for sub‐MeV electrons and flux decay of MeV electrons, observed by Van Allen Probe A on 16 October 2017. The scattering effects are quantitatively investigated by test particle simulations. The results indicate that the unusual EMIC waves mainly scatter electrons from hundreds of keV to several MeV at pitch angles <60° while the MS waves mainly influence sub‐MeV and MeV electrons at pitch angles >60°. Their combined scattering effects are suitably analyzed to be justified as the linear superposition of the effect induced by each wave mode. The Fokker‐Planck simulations exhibit the formation of butterfly pitch angle distributions for sub‐MeV electrons and the obvious flux decay for electrons ∼1.8 MeV at all pitch angles, showing similar variation trends to the observations. Our study suggests that the occurrence of the two waves can significantly influence the electrons over the whole pitch angle range, which can help us better understand the radiation belt dynamics.
Catchment‐Scale Architecture of the Deep Critical Zone Revealed by Seismic Imaging
Authors: Pasquet Sylvain , Marçais Jean , Hayes Jorden L. , Sak Peter B. , Ma Lin , Gaillardet Jérôme
Published: June 2022

Weathering and erosion processes are crucial to Critical Zone (CZ) evolution, landscape formation and availability of natural resources. Although many of these processes take place in the deep CZ (∼10–100 m), direct information about its architecture remain scarce. Near‐surface geophysics offers a cost‐effective and minimally intrusive alternative to drilling that provides information about the physical properties of the CZ. We propose a novel workflow combining seismic measurements, petrophysical modelling and geostatistical analysis to characterize the architecture of the deep CZ at the catchment scale, on the volcanic tropical island of Basse‐Terre (Guadeloupe, France). With this original workflow, we are for the first time able to jointly produce maps of the water table and the weathering front across an entire catchment, by means of a single geophysical method. This integrated view of the CZ highlights complex weathering patterns that call for going beyond “simple” hillslope CZ models.
Heterogeneous Weathering Process of Lunar Regolith Revealed by Polarimetric Attributes Analysis of Chang’E‐4 Lunar Penetrating Radar Data Acquired During the Yutu‐2 Turnings
Authors: Zhou Haoqiu , Feng Xuan , Ding Chunyu , Dong Zejun , Liu Cai , Liang Wenjing
Published: June 2022

This paper provides analyses to quantify the maturity of regolith within 24 m depth using a novel polarimetric attributes analysis of lunar penetrating radar (LPR) data. The results demonstrate that LPR signals were mainly from subsurface rock fragments of different sizes and were rarely from strata interfaces. The averages and ranges of maturities for the near‐surface (0–2 m), the fine‐grained regolith (2–12 m), and the coarse‐grained ejecta (12–24 m) are 68.98% (0%–99.82%), 82.61% (41.52%–96.56%), and 72.33% (5.91%–96.66%), respectively. Local regions with anomalously low maturities on the lunar surface may be due to the dense materials formed by local impacts or the rock fragments from distal impacts; a newly discovered sandwich structure with low maturity at a depth between 12 and 18 m is formed by the heterogeneous weathering in a paleo‐crater. Based on these new insights, we infer a heterogeneous weathering process of the regolith.
Variability of Water Vapor in the Tropical Middle Atmosphere Observed From Satellites and Interpreted Using SD‐WACCM Simulations
Authors: Yu Wandi , Garcia Rolando , Yue Jia , Russell James , Mlynczak Martin
Published: June 2022

Water vapor in the middle atmosphere plays an essential role in global warming, ozone depletion, and the formation of polar stratospheric and mesospheric clouds. We show that tropical middle atmospheric water vapor simulated with the specified‐dynamics version of the Whole Atmosphere Community Climate Model (SD‐WACCM) is consistent with changes observed in a merged satellite data set, which encompasses the period 1993–2020. Consistent with previous work, we find no significant trend in the stratosphere in either the observations or the simulation; in the mesosphere, we find a long‐term trend of 0.1 ppmv per decade, but only in the observations. We also analyze an SD‐WACCM simulation for the longer period 1980–2019 to quantify the contribution of various factors to the decadal variation of middle atmospheric water vapor. Over 1980–1995, the simulated water vapor in the upper stratosphere and mesosphere, averaged zonally and over ±30° latitude, increases by 0.30 ppmv per decade due to increasing methane emissions. After 1995, a significant abrupt decrease of water vapor of 0.37 ppmv per decade and then a gradual increase of 0.33 ppmv per decade result from changes in stratospheric cold point temperature. The cold‐point temperature is strongly influenced by the strength of the Brewer‐Dobson circulation. The acceleration of the Brewer‐Dobson circulation before about 2003 leads to a cooler tropical tropopause and a decrease of water vapor, and the deceleration thereafter leads to corresponding warming of the tropopause and an increase in water vapor.
Targeting signaling pathways in prostate cancer: mechanisms and clinical trials
Authors: He Yundong , Xu Weidong , Xiao Yu-Tian , Huang Haojie , Gu Di , Ren Shancheng
Published: June 2022

Prostate cancer (PCa) affects millions of men globally. Due to advances in understanding genomic landscapes and biological functions, the treatment of PCa continues to improve. Recently, various new classes of agents, which include next-generation androgen receptor (AR) signaling inhibitors (abiraterone, enzalutamide, apalutamide, and darolutamide), bone-targeting agents (radium-223 chloride, zoledronic acid), and poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib, rucaparib, and talazoparib) have been developed to treat PCa. Agents targeting other signaling pathways, including cyclin-dependent kinase (CDK)4/6, Ak strain transforming (AKT), wingless-type protein (WNT), and epigenetic marks, have successively entered clinical trials. Furthermore, prostate-specific membrane antigen (PSMA) targeting agents such as177Lu-PSMA-617 are promising theranostics that could improve both diagnostic accuracy and therapeutic efficacy. Advanced clinical studies with immune checkpoint inhibitors (ICIs) have shown limited benefits in PCa, whereas subgroups of PCa with mismatch repair (MMR) or CDK12 inactivation may benefit from ICIs treatment. In this review, we summarized the targeted agents of PCa in clinical trials and their underlying mechanisms, and further discussed their limitations and future directions.
Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia
Authors: Zhang Cheng , He Jiaping , Liu Li , Wang Jishi , Wang Sanbin , Liu Ligen , Ge Jian , Gao Lei , Gao Li , Kong Peiyan , Liu Yao , Liu Jia , Han Yu , Zhang Yongliang , Sun Zhe , Ye Xun , Yin Wenjie , Sersch Martina , Shen Lianjun , Cao Wei William , Zhang Xi
Published: June 2022

Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL. A total of 21 patients over 14 years of age with CD19+  R/R B-ALL were screened, enrolled and infused with a single infusion of GC007F CAR-T at three different dose levels. The primary objective of the study was to assess safety, secondary objectives included pharmacokinetics of GC007F cells in patients with R/R B-ALL and preliminary efficacy. We were able to demonstrate in preclinical studies that GC007F cells exhibited better proliferation and tumor killing than conventional CAR-T (C-CAR-T) cells. In this investigator-initiated study all 18 efficacy-evaluable patients achieved a complete remission (CR) (18/18, 100.00%) by day 28, with 17 of the patients (94.4%) achieving CR with minimal residual disease (MRD) negative. Fifteen (83.3%) remained disease free at the 3-month assessment, 14 patients (77.8%) maintaining MRD negative at month 3. Among all 21 enrolled patients, the median peak of CAR-T cell was on day 10, with a median peak copy number of 104899.5/µg DNA and a median persistence period of 56 days (range: 7–327 days). The incidence of cytokine release syndrome (CRS) was 95.2% (n = 20), with severe CRS occurring in 52.4% (n = 11) of the patients. Six patients (28.6%) developed neurotoxicity of any grade. GC007F demonstrated superior expansion capacity and a less exhausted phenotype as compared to (C-CAR-T) cells. Moreover, this first-in-human clinical study showed that the novel, next-day manufacturing FasTCAR-T cells was feasible with a manageable toxicity profile in patients with R/R B-ALL.
Finely tunable dynamical coloration using bicontinuous micrometer-domains
Authors: Xi Yuyin , Zhang Fan , Ma Yuanchi , Prabhu Vivek M. , Liu Yun
Published: June 2022

Nanostructures similar to those found in the vividly blue wings of Morpho butterflies and colorful photonic crystals enable structural color through constructive interference of light waves. Different from commonly studied structure-colored materials using periodic structures to manipulate optical properties, we report a previously unrecognized approach to precisely control the structural color and light transmission via a novel photonic colloidal gel without long-range order. Nanoparticles in this gel form micrometer-sized bicontinuous domains driven by the microphase separation of binary solvents. This approach enables dynamic coloration with a precise wavelength selectivity over a broad range of wavelengths extended well beyond the visible light that is not achievable with traditional methods. The dynamic wavelength selectivity is thermally tunable, reversible, and the material fabrication is easily scalable.
The encephalomyocarditis virus Leader promotes the release of virions inside extracellular vesicles via the induction of secretory autophagy
Authors: van der Grein Susanne G. , Defourny Kyra A. Y. , Rabouw Huib H. , Goerdayal Soenita S. , van Herwijnen Martijn J. C. , Wubbolts Richard W. , Altelaar Maarten , van Kuppeveld Frank J. M. , Nolte-‘t Hoen Esther N. M.
Published: June 2022

Naked viruses can escape host cells before the induction of lysis via release in extracellular vesicles (EVs). These nanosized EVs cloak the secreted virus particles in a host-derived membrane, which alters virus-host interactions that affect infection efficiency and antiviral immunity. Currently, little is known about the viral and host factors regulating this form of virus release. Here, we assessed the role of the encephalomyocarditis virus (EMCV) Leader protein, a ‘viral security protein’ that subverts the host antiviral response. EV release upon infection with wildtype virus or a Leader-deficient mutant was characterized at the single particle level using high-resolution flow cytometry. Inactivation of the Leader abolished EV induction during infection and strongly reduced EV-enclosed virus release. We demonstrate that the Leader promotes the release of virions within EVs by stimulating a secretory arm of autophagy. This newly discovered role of the EMCV Leader adds to the variety of mechanisms via which this protein affects virus-host interactions. Moreover, these data provide first evidence for a crucial role of a non-structural viral protein in the non-lytic release of picornaviruses via packaging in EVs.
Spectroscopy and chromaticity characterization of yellow to light-blue iron-containing beryl
Authors: Shang Yanran , Guo Ying , Tang Jun
Published: June 2022

The chemical composition and influencing factors of the colour of 95 yellow to light blue iron-bearing beryl are studied through Electron Microprobe Analysis (EMPA), Energy-dispersive X-ray fluorescence (ED-XRF) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, ultraviolet–visible (UV–vis) spectroscopy and X-Rite SP62 spectrophotometer. The intensities of the three characteristic hydroxyl stretching bands of the beryl from 3500 cm−1 to 3800 cm−1 prove they are low to medium levels of alkali bearing natural beryl. The wide absorption edge of 320 ~ 465 nm caused by the ultra-violet charge transfer from O2− to Fe3+ and the 650 nm absorption band in E//c-polarization caused by the intervalence charge transfer between Fe2+ and Fe3+ are the main factors affecting the colour of beryl. By applying CIE D65 standard light source and N9 Munsell neutral background as testing conditions, the colour parameters of 82 gem-quality beryl are tested. According to the results, iron-containing beryl colours are classified into yellow, yellowish-green, bluish-green, greenish-blue, and blue by the K-means cluster analysis method. The blue tone has a greater influence on the hue of beryl, while the yellow tone has a greater influence on the chroma. Iron content is higher in yellow and blue beryl. With the increase of iron content, the lightness of beryl decreased and the chroma increased.
Evidence of geoelectrical resistivity values on groundwater conditions in Wadi El Natrun and its vicinities, West Delta, Egypt (cases studies)
Authors: Zarif Fardous M. , Elshenawy Ahmed M. , Barseem Mostafa S. M. , Al-Abaseiry Abdalla A. , Sayed Ahmed N. El
Published: June 2022

Recently, Wadi El Natrun and its surroundings have witnessed intensive investments in land reclamation, including the arbitrary drilling of hundreds of groundwater wells. Currently, serious hydrogeological and environmental problems have been addressed, such as groundwater quality degradation and water head drop. Electrical resistivity measurements were performed at six locations across the study area to assess its ability to reveal the heterogeneous subsurface stratigraphic and hydrogeological setting of groundwater aquifer(s). The geoelectrical results successfully reflect the current vulnerable hydrogeological setting of the study sites. The current study highlights the current practice in which farmers rely on isolated 1-dimensional vertical electrical sounding (1D VES), which is not the only exploration tool for such electrically conductive stratigraphic succession. One of the main findings is addressing the advantage of applying 2-dimensional electrical resistivity imaging (2D ERI), where it offers a more robust view of both vertical and lateral variation of the investigated subsurface section (Case 3). On the other hand, the Geographic Information System (GIS) could mirror the present groundwater potentiality status, where both GIS analysis and resistivity results coincide, and where the good potentiality zone is restricted to the west and southwest directions of the study area (area of interest (aoi)), where the resistivity values of water bearing are relatively high and lie on the main drainage (Cases 2, 5, and 6). On the contrary, poor potentiality zones are deemed because of their proximity to tiny attributers, and are characterized by low resistivity values (Cases 1, 3 & 4), Finally, the current research study demonstrates the significance of combining morphometrical analysis with geophysics techniques for such environmental problems, where groundwater is primarily controlled by geomorphological features and geological conditions, including lithology and geological structures.
Silver-doped phosphate coacervates to inhibit pathogenic bacteria associated with wound infections: an in vitro study
Authors: Nikolaou Athanasios , Felipe-Sotelo Monica , Dorey Robert , Gutierrez-Merino Jorge , Carta Daniela
Published: June 2022

There is a great demand from patients requiring skin repair, as a result of poorly healed acute wounds or chronic wounds. These patients are at high risk of constant inflammation that often leads to life-threatening infections. Therefore, there is an urgent need for new materials that could rapidly stimulate the healing process and simultaneously prevent infections. Phosphate-based coacervates (PC) have been the subject of increased interest due to their great potential in tissue regeneration and as controlled delivery systems. Being bioresorbable, they dissolve over time and simultaneously release therapeutic species in a continuous manner. Of particular interest is the controlled release of metallic antibacterial ions (e.g. Ag+), a promising alternative to conventional treatments based on antibiotics, often associated with antibacterial resistance (AMR). This study investigates a series of PC gels containing a range of concentrations of the antibacterial ion Ag+ (0.1, 0.3 and 0.75 mol%). Dissolution tests have demonstrated controlled release of Ag+ over time, resulting in a significant bacterial reduction (up to 7 log), against both non-AMR and AMR strains of both Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa). Dissolution tests have also shown controlled release of phosphates, Ca2+, Na+ and Ag+ with most of the release occurring in the first 24 h. Biocompatibility studies, assessed using dissolution products in contact with human keratinocyte cells (HaCaT) and bacterial strains, have shown a significant increase in cell viability (p ≤ 0.001) when gels are dissolved in cell medium compared to the control. These results suggest that gel-like silver doped PCs are promising multifunctional materials for smart wound dressings, being capable of simultaneously inhibit pathogenic bacteria and maintain good cell viability.
Lipocalin 15 in the olfactory mucus is a biomarker for Bowman’s gland activity
Authors: Ijichi Chiori , Kondo Kenji , Kobayashi Masayoshi , Shirasawa Ayaka , Shimbo Kazutaka , Nakata Kunio , Maruyama Yutaka , Ihara Yusuke , Kawato Yayoi , Mannen Teruhisa , Takeshita Rie , Kikuchi Yoshimi , Saito Yuki , Yamasoba Tatsuya
Published: June 2022

Olfactory mucus contributes to the specific functions of the olfactory mucosa, but the composition and source of mucus proteins have not been fully elucidated. In this study, we used comprehensive proteome analysis and identified lipocalin 15 (LCN15), a human-specific lipocalin family protein, as an abundant component of the olfactory mucus. Western blot analysis and enzyme-linked immunosorbent assay (ELISA) using a newly generated anti-LCN15 antibody showed that LCN15 was concentrated in olfactory mucus samples, but not in respiratory mucus samples. Immunohistochemical staining using anti-LCN15 antibody revealed that LCN15 localized to the cytokeratin 18-positive Bowman's glands of the olfactory cleft mucosa. Quantitative image analysis revealed that the area of LCN15 immunoreactivity along the olfactory cleft mucosa significantly correlated with the area of neuron-specific Protein-Gene Product 9.5 (PGP9.5) immunoreactivity, suggesting that LCN15 is produced in non-degenerated areas of the olfactory neuroepithelium. ELISA demonstrated that the concentration of LCN15 in the mucus was lower in participants with normal olfaction (≥ 50 years) and also tended to be lower in patients with idiopathic olfactory loss (≥ 50 years) than in participants with normal olfaction (< 50 years). Thus, LCN15 may serve as a biomarker for the activity of the Bowman’s glands.
Clinical risk, sociodemographic factors, and SARS-CoV-2 infection over time in Ontario, Canada
Authors: Udell Jacob A. , Behrouzi Bahar , Sivaswamy Atul , Chu Anna , Ferreira-Legere Laura E. , Fang Jiming , Goodman Shaun G. , Ezekowitz Justin A. , Bainey Kevin R. , van Diepen Sean , Kaul Padma , McAlister Finlay A. , Bogoch Isaac I. , Jackevicius Cynthia A. , Abdel-Qadir Husam , Wijeysundera Harindra C. , Ko Dennis T. , Austin Peter C. , Lee Douglas S.
Published: June 2022

We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction < 0.0001). Prior to the first-wave peak, SARS-CoV-2 infection increased with age whereas this association reversed thereafter. Risk factors that persisted included male sex, residing in lower income neighborhoods, residing in more racially/ethnically diverse communities, immigration to Canada, hypertension, and diabetes. While there was a reduction in infection rates after mid-April 2020, there was less impact in regions with higher racial/ethnic diversity. Immediately following the initial peak, individuals living in the most racially/ethnically diverse communities with 2, 3, or ≥ 4 risk factors had ORs of 1.89, 3.07, and 4.73-fold higher for SARS-CoV-2 infection compared to lower risk individuals in their community (all P < 0.0001). In the latter half of 2020, this disparity persisted with corresponding ORs of 1.66, 2.48, and 3.70-fold higher, respectively. In the least racially/ethnically diverse communities, there was little/no gradient in infection rates across risk strata. Further efforts are necessary to reduce the risk of SARS-CoV-2 infection among the highest risk individuals residing in the most racially/ethnically diverse communities.
Left atrial epicardial adipose tissue is closely associated with left atrial appendage flow velocity in patients with nonvalvular atrial fibrillation
Authors: Shao Yameng , Chen Lei , Xu Changjiang , Gao Beibei , Zhang Dongdong , Sang Chuanyi , Zhang Chaoqun
Published: June 2022

Epicardial adipose tissue (EAT) can play an important role in the occurrence and development of atrial fibrillation and stroke. In this study, we explored the relationship between left atrial epicardial adipose tissue (LA-EAT) and left atrial appendage flow velocity (LAA-FV) in patients with nonvalvular atrial fibrillation (NV-AF). A total of 145 patients with NV-AF who underwent their first radiofrequency ablation were enrolled. They underwent left aortopulmonary vein computed tomography angiography (CTA) and transesophageal echocardiography (TEE) before AF ablation. Left atrial (LA) electroanatomical mapping was performed intraoperatively to assess left atrial voltage. Univariate regression analysis showed that LAA-FV was lower in patients with a low voltage zone (LAA-FV; 35.02 ± 10.78 cm/s vs. 50.60 ± 12.17 cm/s, P < 0.001). A multiple linear regression model showed that the left atrial low voltage zone (β = − 0.311 P < 0.001), LA-EAT volume (β = − 0.256 P < 0.001), left atrial appendage shape (β = − 0.216 P = 0.041), LAVI (β = − 0.153 P = 0.041), and type of atrial fibrillation (paroxysmal vs. persistence) (β = − 0.146 P < 0.048) were independent predictors of LAA-FV. In NV-AF patients, the increase in LA-EAT volume is related to the decrease in LAA-FV.
Label-free flow cytometry of rare circulating tumor cell clusters in whole blood
Authors: Vora Nilay , Shekhar Prashant , Esmail Michael , Patra Abani , Georgakoudi Irene
Published: June 2022

Circulating tumor cell clusters (CTCCs) are rare cellular events found in the blood stream of metastatic tumor patients. Despite their scarcity, they represent an increased risk for metastasis. Label-free detection methods of these events remain primarily limited to in vitro microfluidic platforms. Here, we expand on the use of confocal backscatter and fluorescence flow cytometry (BSFC) for label-free detection of CTCCs in whole blood using machine learning for peak detection/classification. BSFC uses a custom-built flow cytometer with three excitation wavelengths (405 nm, 488 nm, and 633 nm) and five detectors to detect CTCCs in whole blood based on corresponding scattering and fluorescence signals. In this study, detection of CTCC-associated GFP fluorescence is used as the ground truth to assess the accuracy of endogenous back-scattered light-based CTCC detection in whole blood. Using a machine learning model for peak detection/classification, we demonstrated that the combined use of backscattered signals at the three wavelengths enable detection of ~ 93% of all CTCCs larger than two cells with a purity of > 82% and an overall accuracy of > 95%. The high level of performance established through BSFC and machine learning demonstrates the potential for label-free detection and monitoring of CTCCs in whole blood. Further developments of label-free BSFC to enhance throughput could lead to important applications in the isolation of CTCCs in whole blood with minimal disruption and ultimately their detection in vivo.
Neurofilament light chain plasma levels are associated with area of brain damage in experimental cerebral malaria
Authors: Wai Chi Ho , Jin Jessica , Cyrklaff Marek , Genoud Christel , Funaya Charlotta , Sattler Julia , Maceski Aleksandra , Meier Stephanie , Heiland Sabine , Lanzer Michael , Frischknecht Friedrich , Kuhle Jens , Bendszus Martin , Hoffmann Angelika
Published: June 2022

Neurofilament light chain (NfL), released during central nervous injury, has evolved as a powerful serum marker of disease severity in many neurological disorders, including infectious diseases. So far NfL has not been assessed in cerebral malaria in human or its rodent model experimental cerebral malaria (ECM), a disease that can lead to fatal brain edema or reversible brain edema. In this study we assessed if NfL serum levels can also grade disease severity in an ECM mouse model with reversible (n = 11) and irreversible edema (n = 10). Blood–brain-barrier disruption and brain volume were determined by magnetic resonance imaging. Neurofilament density volume as well as structural integrity were examined by electron microscopy in regions of most severe brain damage (olfactory bulb (OB), cortex and brainstem). NfL plasma levels in mice with irreversible edema (317.0 ± 45.01 pg/ml) or reversible edema (528.3 ± 125.4 pg/ml) were significantly increased compared to controls (103.4 ± 25.78 pg/ml) by three to five fold, but did not differ significantly in mice with reversible or irreversible edema. In both reversible and irreversible edema, the brain region most affected was the OB with highest level of blood–brain-barrier disruption and most pronounced decrease in neurofilament density volume, which correlated with NfL plasma levels (r = − 0.68, p = 0.045). In cortical and brainstem regions neurofilament density was only decreased in mice with irreversible edema and strongest in the brainstem. In reversible edema NfL plasma levels, MRI findings and neurofilament volume density normalized at 3 months’ follow-up. In conclusion, NfL plasma levels are elevated during ECM confirming brain damage. However, NfL plasma levels fail short on reliably indicating on the final outcomes in the acute disease stage that could be either fatal or reversible. Increased levels of plasma NfL during the acute disease stage are thus likely driven by the anatomical location of brain damage, the olfactory bulb, a region that serves as cerebral draining pathway into the nasal lymphatics.
A smart insole system capable of identifying proper heel raise posture for chronic ankle instability rehabilitation
Authors: Kim Jaewook , Kang Seonghyun , Kim Seung-Jong
Published: June 2022

Heel raise is widely prescribed to patients with chronic ankle instability in order to strengthen the Peroneus Longus muscle (PL) which supports the weakened lateral collateral ligaments. While the exercise itself is intuitive, ankle orientation is of particular importance because heel raises performed with inversion do not well recruit the PL. This implies that proper execution is imperative and a means to assess heel raise training sessions is needed. In this study we present a smart insole system capable of identifying heel raise events and its corresponding rise, hold and drop phases, which allows for a more descriptive analysis. The results from our heel raise sessions, which consist of four different variants performed by five healthy subjects, suggest that medial–lateral foot pressure distribution and foot orientation are needed to differentiate heel raises performed with ankle eversion and inversion. We go further and substantiate that proper execution, detected by our system, indeed leads to increased PL activation by analyzing the electromyography signals. We believe that the proposed system may provide clinicians with invaluable information regarding onsite as well as at-home training and possibly, with biofeedback, serve as foundation for software as a medical device.
Unraveling mitochondrial piRNAs in mouse embryonic gonadal cells
Authors: Barreñada Odei , Larriba Eduardo , Fernández-Pérez Daniel , Brieño-Enríquez Miguel Ángel , del Mazo Martínez Jesús
Published: June 2022

Although mitochondria are widely studied organelles, the recent interest in the role of mitochondrial small noncoding RNAs (sncRNAs), miRNAs, and more recently, piRNAs, is providing new functional perspectives in germ cell development and differentiation. piRNAs (PIWI-interacting RNAs) are single-stranded sncRNAs of mostly about 20–35 nucleotides, generated from the processing of pre-piRNAs. We leverage next-generation sequencing data obtained from mouse primordial germ cells and somatic cells purified from early-differentiating embryonic ovaries and testis from 11.5 to 13.5 days postcoitum. Using bioinformatic tools, we elucidate (i) the origins of piRNAs as transcribed from mitochondrial DNA fragments inserted in the nucleus or from the mitochondrial genome; (ii) their levels of expression; and (iii) their potential roles, as well as their association with genomic regions encoding other sncRNAs (such as tRNAs and rRNAs) and the mitochondrial regulatory region (D-loop). Finally, our results suggest how nucleo-mitochondrial communication, both anterograde and retrograde signaling, may be mediated by mitochondria-associated piRNAs.
Clinical performance of a smartphone-based low vision aid
Authors: Yeo Joon Hyung , Bae Seon Ha , Lee Seung Hyeun , Kim Kyoung Woo , Moon Nam Ju
Published: June 2022

Real-time digital image processing to optimally enhance low vision is now realizable with recent advances in personal computers. This study aimed to evaluate the efficacy of a wearable smartphone-based low vision aid (LVA) with customizable vision enhancement in patients with visual impairment. We recruited 35 subjects with visual impairment and who were literate and cognitively capable. The subjects completed a training session and were provided a smartphone-based LVA for a 4-week use. Visual functions including binocular best-corrected distance, intermediate, and near visual acuities; reading performance (reading speed and accuracy); and facial recognition performance were measured at baseline and after 4-weeks use. All subjects also completed the Low Vision Quality of Life (LVQOL) Questionnaire. Thirty-four subjects (mean age, 43.82 ± 15.06 years) completed the study. Significant improvements in binocular best-corrected distance, intermediate, and near visual acuities were observed after smartphone-based LVA use (all p < 0.001). Reading accuracy and facial recognition performance also improved significantly (p = 0.009 and p < 0.001, respectively), but reading speed did not. LVQOL scores significantly improved after 4 weeks of use in subjects aged < 40 years (p = 0.024), but not in subjects aged ≥ 40 years (p = 0.653). Ocular and non-ocular adverse events were infrequent and resolved when the device was removed. The smartphone-based LVA with customizable vision enhancement could provide clinically significant improvements in the visual function of patients with visual impairment and was generally well tolerated. This study suggests that the smartphone-based LVA would be beneficial for visual rehabilitation.
The validity evaluation of different 16srRNA gene primers for helicobacter detection urgently requesting to design new specific primers
Authors: Abdelmalek Shaymaa , Shokry Karim , Hamed Wafy , Abdelnaser Mohammed , Aboubakr Ashraf , Elenin Sameh Abou , Ali Mohamed , Mostafa Mohamed , Abou-Okada Mahmoud
Published: June 2022

Molecular diagnosis of helicobacters by PCR is simpler, more accurate, and feasible compared to other diagnostic methods. Validity and accuracy are highly dependent on the PCR primer design, diffusion time, and mutation rate of helicobacters. This study aimed to design 16srRNA -specific primers for Helicobacter spp. and H. pylori. Application of comparative statistical analysis of the diagnostic utility of the most available 16srRNA genus-specific primers. The new primers were designed using bioinformatics tools (MAFFT MSA and Gblocks command line). A comparative study was applied on nine genus-specific 16srRNA primers in comparison to the ConsH using in silico and laboratory evaluation. The results demonstrated that the best specificity and sensitivity of the primers designed for this study compared to other primers. The comparative study revealed that the heminested outer/inner primers were the worst. Although H276, 16srRNA(a), HeliS/Heli-nest, and Hcom had acceptable diagnostic utility, false positive and false negative results were obtained. Specificity testing on clinical samples indicated a surprising result; that H. pylori was not the sole enemy that we were looking for, but the Non-Helicobacter pylori Helicobacters should be considered as a real risk prognostic for gastric diseases, consequently, a specific diagnosis and treatment should be developed. This study concluded that our designed primers were the most specific and sensitive in comparison with other primers. In addition, in silico evaluation is not accurate enough for primer assessment and that the laboratory evaluation is mandatory.
The cell cycle stage of bovine zygotes electroporated with CRISPR/Cas9-RNP affects frequency of Loss-of-heterozygosity editing events
Authors: Miskel Dennis , Poirier Mikhael , Beunink Luisa , Rings Franca , Held Eva , Tholen Ernst , Tesfaye Dawit , Schellander Karl , Salilew-Wondim Dessie , Blaschka Carina , Große-Brinkhaus Christine , Brenig Bertram , Hoelker Michael
Published: June 2022

At the embryonic level, CRISPR technologies have been used to edit genomes reliably and efficiently in various mammalian models, with Ribonucleoprotein (RNP) electroporation potentially representing a superior delivery method into mammalian zygotes. However, detailed insights of the interactions between varying technical settings as well as the time point of electroporation in a bovine zygote’s cell cycle on developmental metrics and the frequency and type of editing events are largely unknown. The present study uncovers that increasing pulse lengths result in higher Full Edit rates, with Mosaicism in Full-Edit embryos being significantly affected by adjusting RNP-electroporation relative to zygote cell cycle. A considerable proportion of Full Edit embryos demonstrated loss-of-heterozygosity after RNP-electroporation prior to S-phase. Some of these loss-of-heterozygosity events are a consequence of chromosomal disruptions along large sections of the target chromosomes making it necessary to check for their presence prior use of this technique in animal breeding. One out of 2 of these loss-of-heterozygosity events, however, was not associated with loss of an entire chromosome or chromosomal sections. Whether analysed loss-of-heterozygosity in these cases, however, was a false negative result due to loss of PCR primer sequences after INDEL formation at the target side or indeed due to interhomolog recombination needs to be clarified in follow up studies since the latter would for sure offer attractive options for future breeding schedules.
Genotypic and phylogenic analyses of cutaneous leishmaniasis in Al Ahsa, Eastern Saudi Arabia during the coronavirus disease 2019 pandemic: First cases of Leishmania tropica with the predominance of Leishmania major
Authors: Al-Rashed Abdullatif S. , Al Jindan Reem , Al Jaroodi Salma , Al Mohanna Ahmed , Abdelhady Ahmed , El-Badry Ayman A.
Published: June 2022

During the coronavirus disease 2019 lockdown period, a surge in sandflies and cutaneous leishmaniasis (CL) cases was observed in Al-Ahsa, Saudi Arabia. Skin punch biopsies were obtained from 100 patients clinically diagnosed with CL in Al-Ahsa who had no travel history in the last 6 months. Impression smears were used following a three-step polymerase chain reaction (PCR) protocol using genus-specific primers targeting kDNA and ITS1. Leishmania speciation was determined by ITS1 PCR/nested PCR-restriction fragment length polymorphism and sequencing. A phylogenetic tree was constructed. The associated patient characteristics were analyzed. Using internal transcribed spacer one (ITS1)-PCR/nested PCR, 98 cases were considered true-positive CL. Leishmania major was the predominant species, and Leishmania tropica was identified in three cases. Microscopy had poor sensitivity and perfect specificity. Direct ITS1-PCR missed nine cases. Sex, residence, and treatment outcome were significantly associated with the occurrence of Leishmania; distribution of skin lesion(s) and treatment outcome were significantly associated with Leishmania genotype. This is the first time that L. tropica was identified as a cause of CL in human in Al-Ahsa, in addition to the predominant zoonotic species, L. major. We recommend using ITS1-nested PCR for negative cases by ITS1-PCR. Further exploration of Leishmania transmission dynamics in vectors and reservoir animals is essential for designing effective preventive measures.
Evaluation the loosening of abutment screws in fluid contamination: an in vitro study
Authors: Sun Fei , Cheng Wei , Zhao Bao-hong , Song Gui-Qiu , Lin Zeng
Published: June 2022

Screw loosening is one of the most common clinical problems of dental implants. Research on the influencing factors of screw loosening is very important to prevent screw loosening. The purpose of this in vitro study was to evaluate the influence of liquid contamination on the screw loosening. According to the contamination condition, forty-five abutment screws were divided into three groups (n = 15): no contamination, artificial saliva contamination, and mouthwash contamination. The preload and friction coefficient of the abutment screws were recorded. Then, the reverse torque values (RTVs) and settlement were measured after 3.0 × 105 and 6.0 × 105 cycles. The surface wear of the screws was analyzed. Finally, the stress distribution of the abutment screws was calculated by finite element analysis (FEA). The results showed that fluid contamination reduced the friction coefficient, increased the preload, decrease the settlement, improved resistance to screw loosening, and reduced wear on the thread surface. Appropriate antimicrobial lubrication may improve the anti-loosening performance of abutment screws and prevent excessive wear on the threaded surface.
Structure of the magma plumbing system beneath Semisopochnoi Island (Aleutian Arc) inferred from seismic tomography
Authors: Yaroshenko Galina , Koulakov Ivan , Al-Arifi Nassir , Qaysi Saleh , El Khrepy Sami
Published: June 2022

Semisopochnoi Island is a remote and little-studied volcanic island in the western part of the Aleutian Arc. The existence of several active volcanic centers and a 5000–7000-year-old large caldera makes this island an important site for volcanic hazard assessment in the Northern Pacific. Based on local seismicity data recorded by six permanent seismic stations, we created the seismic tomography model, including the 3D distributions of Vp, Vs, and Vp/Vs ratios to a depth of 10 km. This model provides the first geophysical insight into the interior structure of Semisopochnoi Island and sheds light on the processes in the magma plumbing system beneath all volcanic centers on the island. At depths of 5–10 km, we observed a columnar-shaped high Vp/Vs-ratio anomaly below the caldera in the central part of the island, which likely represents the steady magma conduit. This conduit is headed by a prominent high Vp/Vs-ratio anomaly located 3–5 km directly below the caldera, which represents the magma reservoir feeding Cerberus and other Holocene-aged volcanic centers on Semisopochnoi Island.
Prevalence and outcome of anemia among children hospitalized for pneumonia and their risk of mortality in a developing country
Authors: Chisti Mohammod Jobayer , Kawser Chowdhury Ali , Rahman Abu Sayem Mirza Md Hasibur , Shahid Abu Sadat Mohammad Sayeem Bin , Afroze Farzana , Shahunja K. M. , Shahrin Lubaba , Sarmin Monira , Nuzhat Sharika , Rahman Ahmed Ehsanur , Alam Tahmina , Parvin Irin , Ackhter M. S. T. Mahmuda , Mamun Gazi Md. Salahuddin , Shaima Shamsun Nahar , Faruque Abu Syed Golam , Ahmed Tahmeed
Published: June 2022

Data are limited on the prevalence and outcome of anemia and its risk on mortality among children under five years of age hospitalized for pneumonia/severe pneumonia. Thus, we conducted a secondary analysis of data extracted from Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh to address the evidence gap. Among 3468 children fulfilling the study criteria,1712 (49.4%) had anemia. If children aged ≤ 1.0, > 1.0 to 2.0, > 2.0 to < 6.0, and ≥ 6.0 to 59 months had blood hemoglobin (Hb) value of ≤ 10.7 g/dL, ≤ 9.4 g/dL, ≤ 9.5 g/dL, and ≤ 11 g/dl respectively; we considered them anemic. The trend of prevalence of anemia was found to be inversely related to increasing age (Chi-square for linear trend analysis was done to understand the relation of anemia with increasing age, which was = 6.96; p = 0.008). During hospitalization anemic children more often developed respiratory failure (7.2% vs. 4.4%, p < 0.001) and fatal outcome (7.1.0% vs. 4.2%, p < 0.001) than the children who did not have anemia. After adjusting for potential confounders, such as female sex, lack of immunization, abnormal mental status, severe acute malnutrition, dehydration, hypoxemia, severe sepsis, and bacteremia using multivariable logistic regression analysis, anemia was found to be independently associated with fatal outcome (OR = 1.88, 95% CI 1.23–2.89, p = 0.004). Thus, future interventional studies on the early management of anemia may be warranted to understand whether the intervention reduces the morbidity and deaths in such children.
Perfect association between spatial swarm segregation and the X-chromosome speciation island in hybridizing Anopheles coluzzii and Anopheles gambiae populations
Authors: Niang Abdoulaye , Maïga Hamidou , Sawadogo Simon P. , Konaté Lassana , Faye Ousmane , Lee Yoosook , Dabiré Roch K. , Diabaté Abdoulaye , Tripet Frederic
Published: June 2022

The sibling species An. coluzzii and An. gambiae s.s. are major malaria vectors thought to be undergoing sympatric speciation with gene flow. In the absence of intrinsic post-zygotic isolation between the two taxa, speciation is thought possible through the association of assortative mating and genomic regions protected from gene flow by recombination suppression. Such genomic islands of speciation have been described in pericentromeric regions of the X, 2L and 3L chromosomes. Spatial swarm segregation plays a major role in assortative mating between sympatric populations of the two species and, given their importance for speciation, genes responsible for such pre-mating reproductive barriers are expected to be protected within divergence islands. In this study 2063 male and 266 female An. coluzzii and An. gambiae s.s. individuals from natural swarms in Burkina Faso, West Africa were sampled. These were genotyped at 16 speciation island SNPs, and characterized as non-hybrid individuals, F1 hybrids or recombinant F1+n backcrossed individuals. Their genotypes at each speciation island were associated with their participation in An. coluzzii and An. gambiae-like swarms. Despite extensive introgression between the two species, the X-island genotype of non-hybrid individuals (37.6%), F1 hybrids (0.1%) and F1+n recombinants (62.3%) of either sex perfectly associated to each swarm type. Associations between swarm type and the 3L and 2L speciation islands were weakened or broken down by introgression. The functional demonstration of a close association between spatial segregation behaviour and the X speciation island lends further support to sympatric speciation models facilitated by pericentric recombination suppression in this important species complex.