bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Specificity of the Affordance of Reaching
Authors: Surber Tyler , Overstreet Tyler , Masoner Hannah , Dowell Catherine , Hajnal Alen
Published: May 2022

Abstract: The information that specifies whether an object is within reach is a complex pattern that depends on body-scaled parameters measured from an egocentric reference point. The pattern is a function of relevant body proportions (eye height, shoulder height [SH], arm length) with respect to the spatial location of the target object. In addition to not knowing how these factors map onto perception, it is also not known whether the egocentric viewpoint is centered at the eye or the shoulder. In three experiments, we systematically tested whether observers can perceive eye height and SH (Experiment 1), whether they can point accurately in the direction of a target object (Experiment 2), and whether they can point accurately to judge if the target object is within reach (Experiment 3). Experiment 1 demonstrated that participants are more accurate at judging their own eye height than SH. Experiment 2 revealed that participants can more accurately point to a target object’s location when measured from the shoulder as a reference point than when measured from the eye. In Experiment 3, we showed that a higher-order variable that includes arm length, body height, and angle of declination to the target successfully predicted affordance judgments, regardless of a reference point. We consider this as evidence that the invariant is functionally specific, not tied to any one particular anatomical body part.
Quantitative Stress Test of Compound Coastal‐Fluvial Floods in China's Pearl River Delta
Authors: Qiu Jiangchao , Liu Bingjun , Yang Fang , Wang Xiaola , He Xiaogang
Published: May 2022

Floods in river deltas are driven by complex interactions between astronomical tides, sea levels, storm surges, wind waves, rainfall‐runoff, and river discharge. Given the anticipated increase in compound flood hazards in river deltas in a warming climate, climate‐informed regional to local extreme water levels (EWLs) is thus critical for decision‐makers to evaluate flood hazards and take adaptation measures. We develop a simple yet computationally efficient stress test framework, which combines historical and projected climatological information and a state‐of‐the‐art hydrodynamic model, to assess future compound coastal‐fluvial flood hazards in river deltas. Our framework is applied in the world's largest single urban area, China's Pearl River Delta (PRD), which is also characterized by densely crossed river network. We find that extreme sea level is the dominant driver causing the compound coastal‐fluvial flood in the PRD over the past 60 years. Meanwhile, there is large spatial heterogeneity of the individual and compound effects of the typhoon intensity, local sea‐level rise, and riverine inflow on coastal‐fluvial floods. In a plausible disruptive scenario (e.g., a 0.50 m sea‐level rise combined with a 9% increase in typhoon intensity in a 2°C warming), the EWL will increase by 0.76 m on average. An additional 1.54 and 0.56 m increase in EWL will occur in the river network and near the river mouth, respectively, if coastal floods coincide with the upstream mean annual flood. Findings from our modeling framework provide important insights to guide adaptation planning in river deltas to withstand future compound floods under climate change.
Improving the Understanding of Atmospheric River Water Vapor Transport Using a Three‐Dimensional Straightened Composite Analysis
Authors: Xu Guangzhi , Wang Lin , Chang Ping , Ma Xiaohui , Wang Shuyu
Published: May 2022

Irregular shapes of atmospheric rivers (ARs) hamper easy AR composite analyses and understandings of AR's moisture transport mechanisms. We develop a method to composite AR‐related variables from a reanalysis data set. By averaging a large number of samples, the three‐dimensional structure and some evolutionary features of a typical North Pacific AR are revealed. An AR is typically located along and in advance of the surface cold front of an extratropical cyclone. A mesoscale secondary circulation is observed in the cross sections of the AR corridor, where both geostrophic and ageostrophic winds make indispensable contributions to the moisture fluxes. Geostrophic moisture advection across the cold front within the Equatorward half of the AR is created by baroclinicity of the system and serves as the primary moisture source for the AR. Moisture fluxes from the warm sector of the cyclone are primarily due to boundary layer ageostrophic winds and are more important within the poleward half of the AR, particularly during the genesis stage. Faster AR movement compared with low‐level winds enables the AR to collect downwind moisture. In an AR‐relative view, this is represented as an easterly flow, consistent with the “feeder‐airstream” concept, and emphasizes the role of local moisture recycling. Moisture transport within the Equatorward half is mostly due to geostrophic advection of the propagating AR‐cyclone couple in an Earth‐relative view. Driven by intensifying geostrophic winds, ARs tend to reach peak moisture transport intensity about 2 days after genesis. Then, reduced moisture level and influxes from lateral boundaries prevent further intensification.
Warming‐to‐Cooling Reversal of Overflow‐Derived Water Masses in the Irminger Sea During 2002–2021
Authors: Desbruyères Damien G. , Bravo Eva Prieto , Thierry Virginie , Mercier Herlé , Lherminier Pascale , Cabanes Cécile , Biló Tiago C. , Fried Nora , Femke De Jong M.
Published: May 2022

Shipboard hydrography along the A25‐Ovide section (2002–2018) is combined with a high‐resolution mooring array (2014–2020) and a regional fleet of Deep‐Argo floats (2016–2021) to describe temperature changes of overflow‐derived water masses in the Irminger Sea. Removing dynamical influences enables to identify a new statistically significant trend reversal in Iceland Scotland Overflow Water (ISOW) and Denmark Strait Overflow Water (DSOW) core temperatures in the mid‐2010s. A basin‐wide cooling trend of −16 ± 6 m°C yr−1 during 2016–2021—but reaching as strong as −44 ± 13 m°C yr−1 for DSOW in recent years—is found to interrupt a warming phase that was prevailing since the late 1990s. The absence of an apparent reversal in the Nordic Seas and the faster changes detected in DSOW compared to ISOW point out the entrainment of subpolar signals within the overflows near the Greenland‐Iceland‐Scotland sills as a most likely driver.
Energization of Cold Ions in Magnetic Reconnection: Particle‐in‐Cell Simulation
Authors: Song Liangjin , Zhou Meng , Yi Yongyuan , Deng Xiaohua , Zhong Zhihong
Published: May 2022

Cold ions in the ionosphere can reach the nightside magnetotail along the magnetic field lines, which may substantially affect the magnetotail reconnection and reconnection‐driven phenomena. Although reconnection has been intensively studied in the past decades, the dynamics of cold ions in reconnection are poorly known. We performed a 2.5‐D full kinetic simulation to study the energization of cold ions in a symmetric anti‐parallel reconnection. We find that the cold ions can be considerably energized during reconnection. The average energy gain per cold ion is smaller than that per hot ion but larger than that per electron. The cold ions with the highest energy are firstly accelerated around the X‐line, and further accelerated around the reconnection front in the outflow region. They perform the meandering motion at the X‐line, while simultaneously accelerated by the reconnection out‐of‐plane electric field. The velocity distribution of cold ions around the X‐line is characterized by the counter‐streaming inflow component and the accelerated component in the +y quadrant. The cold ions are picked up at the reconnection front and trapped by the secondary island, resulting in a bump in the energy spectrum. The energy of the bump is close to the energy of the propagating speed of the reconnection front and the secondary island. Furthermore, a crescent‐shaped velocity distribution is observed at the reconnection front, caused by the finite Larmor radius effect of the high‐energy cold ions in the flux pileup region. Our result presents an important building block toward a fully understanding of the magnetosphere‐ionosphere coupling.
Chromosomal microarray analysis versus noninvasive prenatal testing in fetuses with increased nuchal translucency
Authors: Wang Chaohong , Tang Junxiang , Tong Keting , Huang Daoqi , Tu Huayu , Zhu Jiansheng
Published: May 2022

Objective

To evaluate if the NT value of 2.5 mm ≤ NT < 3.0 mm is an appropriate indication for CMA tests among fetuses with isolated increased NT and NIPT is more suitable instead.

Methods

A total of 442 fetuses with NT ≥ 2.5 mm were included, in which 241 fetuses underwent karyotype. CMA tests were then carried out when cytogenic analysis showed normal chromosomes and CNV status was compared between 2.5 mm ≤ NT < 3.0 mm and ≥3.0 mm subgroups. For the NIPT evaluation, 201 of 442 fetuses with smaller increased NT (2.5 mm ≤ NT < 3.0 mm) was examined by either NIPT or karyotype.

Results

Of the 241 fetuses with NT ≥ 2.5 mm, 47(19.50%) were identified by karyotype with chromosomal abnormalities. Among 194 cases with normal karyotype, CMA unraveled additional CNVs in 16(8.25%) cases, including 3(1.55%) pathogenic CNVs, 2(1.03%) likely pathogenic CNVs and 11(5.67%) VOUS. After the subgroup analysis, however, only one case (1.16%) of likely pathogenic was identified by CMA among 86 fetuses with NT between 2.5 mm and 3.0 mm, whereas the rest of 15 CNV cases were all presented in fetuses with NT ≥ 3.0 mm. For the NIPT evaluation, the detection rate of 201 fetuses with isolated increased NT between 2.5 and 3.0 mm was 3.98%, which was indifferent to karyotype with the rate of 5%. In comparison with fetuses with 2.5–3.0 mm combined with other risks, the detection rate of karyotype was 26.92%.

Conclusion

While no pathogenic CNVs were detected in fetuses, chromosomal aneuploidies and genomic imbalance were found to be the major type of abnormalities when NT was 2.5–3.0 mm. Therefore, our data suggested that CMA should not be recommended when fetuses with an NT value less than 3.0 mm. Instead, NIPT with similar rate of detection as karyotype was recommended for fetuses with isolated increased NT between 2.5 and 3.0 mm.
Novel large deletion involving EVC and EVC2 in Ellis–van Creveld syndrome
Authors: Sato Hiroki , Suga Kenichi , Suzue Masashi , Honma Yukako , Hayabuchi Yasunobu , Miyai Shunsuke , Kurahashi Hiroki , Nakagawa Ryuji
Published: May 2022

Ellis–van Creveld syndrome is an autosomal recessive skeletal dysplasia that is characterized by thoracic hypoplasia, polydactyly, oral abnormalities, and congenital heart disease. It is caused by pathogenic variants in the EVC or EVC2 genes. We report a case of a newborn with a compound heterozygous variant comprising NM_147127.5: c.1991dup:[p.Lys665Glufs*10] in the EVC2 gene and a novel large deletion involving exon 1 in EVC and exons 1–7 in EVC2.
Dynamically actuated soft heliconical architecture via frequency of electric fields
Authors: Liu Binghui , Yuan Cong-Long , Hu Hong-Long , Wang Hao , Zhu Yu-Wen , Sun Pei-Zhi , Li Zhi-Ying , Zheng Zhi-Gang , Li Quan
Published: May 2022

Dynamic electric field frequency actuated helical and spiral structures enable a plethora of attributes for advanced photonics and engineering in the contemporary era. Nevertheless, leveraging the frequency responsiveness of adaptive devices and systems within a broad dynamic range and maintaining restrained high-frequency induced heating remain challenging. Herein, we establish a frequency-actuated heliconical soft architecture that is quite distinct from that of common frequency-responsive soft materials. We achieve reversible modulation of the photonic bandgap in a wide spectral range by delicately coupling the frequency-dependent thermal effect, field-induced dielectric torque and elastic equilibrium. Furthermore, an information encoder prototype without the aid of complicated algorithm design is established to analogize an information encoding and decoding process with a more convenient and less costly way. A technique for taming and tailoring the distribution of the pitch length is exploited and embodied in a prototype of a spatially controlled soft photonic cavity and laser emission. This work demonstrates a distinct frequency responsiveness in a heliconical soft system, which may not merely inspire the interest in field-assisted bottom-up molecular engineering of soft matter but also facilitate the practicality of adaptive photonics.
Structural insights into the HBV receptor and bile acid transporter NTCP
Authors: Park Jae-Hyun , Iwamoto Masashi , Yun Ji-Hye , Uchikubo-Kamo Tomomi , Son Donghwan , Jin Zeyu , Yoshida Hisashi , Ohki Mio , Ishimoto Naito , Mizutani Kenji , Oshima Mizuki , Muramatsu Masamichi , Wakita Takaji , Shirouzu Mikako , Liu Kehong , Uemura Tomoko , Nomura Norimichi , Iwata So , Watashi Koichi , Tame Jeremy R. H. , Nishizawa Tomohiro , Lee Weontae , Park Sam-Yong
Published: May 2022

Around 250 million people are infected with hepatitis B virus (HBV) worldwide1, and 15 million may also carry the satellite virus hepatitis D virus (HDV), which confers even greater risk of severe liver disease2. The HBV receptor has been identified as sodium taurocholate co-transporting polypeptide (NTCP), which interacts directly with the first 48 amino acid residues of the N-myristoylated N-terminal preS1 domain of the viral large protein3. Despite the pressing need for therapeutic agents to counter HBV, the structure of NTCP remains unsolved. This 349-residue protein is closely related to human apical sodium-dependent bile acid transporter (ASBT), another member of the solute carrier family SLC10. Crystal structures have been reported of similar bile acid transporters from bacteria4,5, and these models are believed to resemble closely both NTCP and ASBT. Here we have used cryo-electron microscopy to solve the structure of NTCP bound to an antibody, clearly showing that the transporter has no equivalent of the first transmembrane helix found in other SLC10 proteins, and that the N terminus is exposed on the extracellular face. Comparison of our structure with those of related proteins indicates a common mechanism of bile acid transport, but the NTCP structure displays an additional pocket formed by residues that are known to interact with preS1, presenting new opportunities for structure-based drug design.
Effects of different protein levels on growth performance and stress parameters in beef calves under heat stress
Authors: Kim Won Seob , Ghassemi Nejad Jalil , Peng Dong Qiao , Jo Yong Ho , Kim Jongkyoo , Lee Hong Gu
Published: May 2022

This study investigated the effects of dietary protein levels under various heat stress (HS) conditions on the growth performance and stress parameters in Korean native beef calves. Male calves (n = 40; initial BW = 202.2 ± 3.31 kg) were randomly assigned to climatic-controlled chambers with 3 × 3 factorial arrangements. Calves were assigned into three dietary protein levels (low protein; LP = 12.5%, medium protein; MP = 15%, and high protein; HP = 17.5%) and three HS levels [mild: temperature-humidity index (THI) = 74 to 76, moderate: THI = 81 to 83, and severe: THI = 89 to 91] with control (threshold: THI = 70 to 73 and dietary protein level 12.5%). The calves were subjected to ambient temperature (22 °C) for 7 days and subsequently to the temperature and humidity corresponding to the target THI level for 21 days. The data were analyzed using the repeated-measures analysis by the GLM procedure of SAS. As a result, average daily gain (ADG) was decreased (P < 0.05) under severe HS level compared to the mild and moderate HS stress levels. However, HP increased ADG (P < 0.05) than moderate levels (LP) and severe levels (LP and MP). Under different HS levels (mild, moderate, and severe), HR, RT, and blood cortisol were increased (P < 0.05) compared to a threshold level, but no differences were observed in the parameters among various protein levels. Varied HS levels decreased the levels of blood glucose, NEFA, and amino acids (AAs) (lysine and glutamic acid) compared to a threshold (P < 0.05). But, the HP group resulted in increased (P < 0.05) levels of blood glucose, NEFA, and AAs (lysine and glutamic acid) compared to LP and MP groups under severe HS stress. The expression level of the HSP70 gene in peripheral blood mononuclear cell (PBMC) and hair follicles was increased (P < 0.05) following an increase in moderate and severe HS levels. Also, HSP70 gene expression in the HP group was decreased (P < 0.05) compared with LP and MP groups under intense HS level. Overall, HS in Korean native beef calves exhibited negative effects on ADG, blood glucose, NEFA, and AA profile. However, 17.5% of dietary protein (HP) could compensate for the growth of heat-exposed Korean native beef calves through the regulation of homeostasis by protein and energy metabolism. Also, it was evident that adequate protein (HP) is used as a major nutrient for HSP70 synthesis in PBMC and hair follicles causing, a boost in the immune system of heat-exposed Korean native beef calves.
One-year results of treat-and-extend regimen with intravitreal brolucizumab for treatment-naïve neovascular age-related macular degeneration with type 1 macular neovascularization
Authors: Matsumoto Hidetaka , Hoshino Junki , Mukai Ryo , Nakamura Kosuke , Akiyama Hideo
Published: May 2022

We evaluated 1-year outcomes of loading phase treatment followed by maintenance treatment using a treat-and-extend (TAE) regimen with intravitreal brolucizumab for neovascular age-related macular degeneration (nAMD) associated with type 1 macular neovascularization (MNV). We analyzed 68 eyes of 65 consecutive patients with treatment-naïve nAMD associated with type 1 MNV. Forty-five eyes (66.2%) completed the 1-year treatment with intravitreal brolucizumab. In those cases, best-corrected visual acuity (BCVA) showed significant improvement, while there were significant reductions in foveal thickness and central choroidal thickness, after the initial brolucizumab injection, which were maintained until the last visit. The average total number of injections over 1 year was 6.4 ± 0.6. The average intended injection interval at the last visit was 14.0 ± 2.9 weeks. Moreover, 17of 23 eyes (73.9%) with polypoidal lesions showed complete regression of these lesions after the loading phase treatment. Although intraocular inflammation (IOI) was observed in 15 of 68 eyes (22.1%) within 1 year, amelioration in response to combination therapy with topical and subtenon injection of steroids, without visual decline, was obtained. These results indicate that loading phase treatment followed by the TAE regimen with intravitreal brolucizumab might improve BCVA and ameliorate exudative changes in eyes with treatment-naïve nAMD associated with type 1 MNV. Moreover, intravitreal brolucizumab can potentially reduce the treatment burden of nAMD. Prompt steroid therapy might be efficacious for ameliorating brolucizumab-related IOI without visual decline.
ERBB3 methylation and immune infiltration in tumor microenvironment of cervical cancer
Authors: Yang Xiaoyue , Chen Ying , Li Mei , Zhu Weipei
Published: May 2022

ERBB3, a member of the ERBB family of receptor tyrosine kinases, plays an important role in cancer, despite its lack of intrinsic carcinogenic mechanism of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Research on bioinformatics methods through multi-omics, this work proves that ERBB3 gene mutation, methylation modification have extensive regulatory mechanisms on the CESC microenvironment. We found that ERBB3 is involved in carcinogenesis of cervical cancer and is not associated with its prognosis. The carcinogenic mechanism is mainly related to the suppression of the immune system between tumor infiltrating lymphocytes (TILs) and the methylation of the RNA level. Our study indicated ERBB3 is more likely to be a carcinogenic factor than a key prognostic factor for cervical cancer. Methylation of ERBB3 may work as a checkpoint immunotherapy target in CESC, DNA methylation modification of the 4480 base pair downstream of ERBB3 transcription initiation site was the highest.
Study of the volatilization rules of volatile oil and the sustained-release effect of volatile oil solidified by porous starch
Authors: Ren Guilin , Ke Gang , Huang Rui , Pu Qingrong , Zhao Jian , Zheng Qin , Yang Ming
Published: May 2022

Volatile oil from traditional Chinese medicine has various biological activities and has pharmacological activities in the central nervous system, digestive system, cardiovascular system, respiratory system, etc. These oils are widely used in clinical practice. However, the development of their clinical applications is restricted due to the disadvantages of volatile oils, such as high stimulation, high volatility and poor stability. To improve the stability of a volatile oil in the preparation process, its volatilization and stable release must be controlled. In this paper, porous starch was used as a solid carrier material, and liquid volatile oil was solidified by physical adsorption. GC–MS was used to determine the chemical constituents of the volatile oil, solidified powder and tablets, and the volatilization rules of 34 chemical constituents were analysed statistically. The solidified volatile oil/porous starch powder was characterized by XRD, TGA and DSC, and the VOCs of the volatile oil before and after solidification were analysed by portable GC–MS. Finally, the stable release of the volatile oil could be optimized by changing the porous starch ratio in the formulation. Volatilization was shown to be closely related to the peak retention time and chemical composition, which was consistent with the theory of flavour. The physical properties and chemical composition of the volatile oil did not change after curing, indicating that the adsorption of the volatile oil by porous starch was physical adsorption. In this paper, the porous starch-solidified volatile oil had a slow-release effect, and the production process is simple, easy to operate, and has high application value.
Biomimetic on-chip filtration enabled by direct micro-3D printing on membrane
Authors: Li Hongxia , Raza Aikifa , Yuan Shaojun , AlMarzooqi Faisal , Fang Nicholas X. , Zhang TieJun
Published: May 2022

Membrane-on-chip is of growing interest in a wide variety of high-throughput environmental and water research. Advances in membrane technology continuously provide novel materials and multi-functional structures. Yet, the incorporation of membrane into microfluidic devices remains challenging, thus limiting its versatile utilization. Herein, via micro-stereolithography 3D printing, we propose and fabricate a “fish gill” structure-integrated on-chip membrane device, which has the self-sealing attribute at structure-membrane interface without extra assembling. As a demonstration, metallic micromesh and polymeric membrane can also be easily embedded in 3D printed on-chip device to achieve anti-fouling and anti-clogging functionality for wastewater filtration. As evidenced from in-situ visualization of structure-fluid-foulant interactions during filtration process, the proposed approach successfully adopts the fish feeding mechanism, being able to “ricochet” foulant particles or droplets through hydrodynamic manipulation. When benchmarked with two common wastewater treatment scenarios, such as plastic micro-particles and emulsified oil droplets, our biomimetic filtration devices exhibit 2 ~ 3 times longer durability for high-flux filtration than devices with commercial membrane. This proposed 3D printing-on-membrane approach, elegantly bridging the fields of microfluidics and membrane science, is instrumental to many other applications in energy, sensing, analytical chemistry and biomedical engineering.
Buckling stability analysis of underpinning piles during basement excavation beneath existing buildings
Authors: Shan Huafeng , Yang Jie , Hu Zhiwen , He Shaoheng
Published: May 2022

In the present paper, the pile-soil system’s total potential energy equation of underpinning piles was established based on the Winkler elastic foundation beam theory. This energy equation was used to explore the effect of basement excavation beneath existing buildings on the underpinning pile’ buckling stability. Utilizing the minimum potential energy theory, the expression of the critical buckling load for underpinning piles’ stability during the excavation project was obtained. Moreover, the influencing factors of the critical buckling load were investigated. It was found that the underpinning pile’s critical load converged with the augment of half-wave number. Moreover, the pile skin friction and deadweight had an insignificant influence on it. In addition, the critical load of underpinning piles decreased sharply with the increasing excavation depth and gradually increased with the augment of pile diameter. The results of this study provides a basis for the design of adding piles in similar projects and reduces the hidden danger of excavation instability.
Homology directed correction, a new pathway model for point mutation repair catalyzed by CRISPR-Cas
Authors: Sansbury Brett M. , Hewes Amanda M. , Tharp Olivia M. , Masciarelli Sophia B. , Kaouser Salma , Kmiec Eric B.
Published: May 2022

Gene correction is often referred to as the gold standard for precise gene editing and while CRISPR-Cas systems continue to expand the toolbox for clinically relevant genetic repair, mechanistic hurdles still hinder widespread implementation. One of the most prominent challenges to precise CRISPR-directed point mutation repair centers on the prevalence of on-site mutagenesis, wherein insertions and deletions appear at the targeted site following correction. Here, we introduce a pathway model for Homology Directed Correction, specifically point mutation repair, which enables a foundational analysis of genetic tools and factors influencing precise gene editing. To do this, we modified an in vitro gene editing system which utilizes a cell-free extract, CRISPR-Cas RNP and donor DNA template to catalyze point mutation repair. We successfully direct correction of four unique point mutations which include two unique nucleotide mutations at two separate targeted sites and visualize the repair profiles resulting from these reactions. This extension of the cell-free gene editing system to model point mutation repair may provide insight for understanding the factors influencing precise point mutation correction.
A novel nomogram and risk classification system predicting the Ewing sarcoma: a population-based study
Authors: Zheng Yongshun , Lu Jinsen , Shuai Ziqiang , Wu Zuomeng , Qian Yeben
Published: May 2022

Ewing sarcoma (ES) is a rare disease that lacks a prognostic prediction model. This study aims to develop a nomogram and risk classification system for estimating the probability of overall survival (OS) of patients with ES. The clinicopathological data of ES were collected from the Surveillance, Epidemiology and Final Results (SEER) database from 2010 to 2018. The primary cohort was randomly assigned to the training set and the validation set. Univariate and multiple Cox proportional hazard analyses based on the training set were performed to identify independent prognostic factors. A nomogram was established to generate individualized predictions of 3- and 5-year OS and evaluated by the concordance index (C-index), the receiver operating characteristic curve (ROC), the calibration curve, the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). Based on the scores calculated with the nomogram, ES patients were divided into three risk groups to predict their survival. A total of 935 patients were identified, and a nomogram consisting of 6 variables was established. The model provided better C-indices of OS (0.788). The validity of the Cox model assumptions was evaluated through the Schönfeld test and deviance residual. The ROC, calibration curve, IDI and NRI indicated that the nomogram exhibited good performance. A risk classification system was built to classify the risk group of ES patients. The nomogram compares favourably and accurately to the traditional SEER tumour staging systems, and risk stratification provides a more convenient and effective tool for clinicians to optimize treatment options.
Lithospheric conductors reveal source regions of convergent margin mineral systems
Authors: Kirkby Alison , Czarnota Karol , Huston David L. , Champion David C. , Doublier Michael P. , Bedrosian Paul A. , Duan Jingming , Heinson Graham
Published: May 2022

The clean energy transition will require a vast increase in metal supply, yet new mineral deposit discoveries are declining, due in part to challenges associated with exploring under sedimentary and volcanic cover. Recently, several case studies have demonstrated links between lithospheric electrical conductors imaged using magnetotelluric (MT) data and mineral deposits, notably Iron Oxide Copper Gold (IOCG). Adoption of MT methods for exploration is therefore growing but the general applicability and relationship with many other deposit types remains untested. Here, we compile a global inventory of MT resistivity models from Australia, North and South America, and China and undertake the first quantitative assessment of the spatial association between conductors and three mineral deposit types commonly formed in convergent margin settings. We find that deposits formed early in an orogenic cycle such as volcanic hosted massive sulfide (VHMS) and copper porphyry deposits show weak to moderate correlations with conductors in the upper mantle. In contrast, deposits formed later in an orogenic cycle, such as orogenic gold, show strong correlations with mid-crustal conductors. These variations in resistivity response likely reflect mineralogical differences in the metal source regions of these mineral systems and suggest a metamorphic-fluid source for orogenic gold is significant. Our results indicate the resistivity structure of mineralized convergent margins strongly reflects late-stage processes and can be preserved for hundreds of millions of years. Discerning use of MT is therefore a powerful tool for mineral exploration.
Periodontal tissue regeneration by transplantation of autologous adipose tissue-derived multi-lineage progenitor cells
Authors: Takedachi Masahide , Sawada Keigo , Sakura Kazuma , Morimoto Chiaki , Hirai Asae , Iwayama Tomoaki , Shimomura Junpei , Kawasaki Kohsuke , Fujihara Chiharu , Kashiwagi Yoichiro , Miyake Akimitsu , Yamada Tomomi , Okura Hanayuki , Matsuyama Akifumi , Saito Masahiro , Kitamura Masahiro , Murakami Shinya
Published: May 2022

Periodontitis is a chronic inflammatory disease that destroys tooth-supporting periodontal tissue. Current periodontal regenerative therapies have unsatisfactory efficacy; therefore, periodontal tissue engineering might be established by developing new cell-based therapies. In this study, we evaluated the safety and efficacy of adipose tissue-derived multi-lineage progenitor cells (ADMPC) autologous transplantation for periodontal tissue regeneration in humans. We conducted an open-label, single-arm exploratory phase I clinical study in which 12 periodontitis patients were transplanted with autologous ADMPCs isolated from subcutaneous adipose tissue. Each patient underwent flap surgery during which autologous ADMPCs were transplanted into the bone defect with a fibrin carrier material. Up to 36 weeks after transplantation, we performed a variety of clinical examinations including periodontal tissue inspection and standardized dental radiographic analysis. A 36-week follow-up demonstrated no severe transplantation-related adverse events in any cases. ADMPC transplantation reduced the probing pocket depth, improved the clinical attachment level, and induced neogenesis of alveolar bone. Therapeutic efficiency was observed in 2- or 3-walled vertical bone defects as well as more severe periodontal bone defects. These results suggest that autologous ADMPC transplantation might be an applicable therapy for severe periodontitis by inducing periodontal regeneration.
Contrast timing optimization of a two-volume dynamic CT pulmonary perfusion technique
Authors: Zhao Yixiao , Hubbard Logan , Malkasian Shant , Abbona Pablo , Molloi Sabee
Published: May 2022

The purpose of this study is to develop and validate an optimal timing protocol for a low-radiation-dose CT pulmonary perfusion technique using only two volume scans. A total of 24 swine (48.5 ± 14.3 kg) underwent contrast-enhanced dynamic CT. Multiple contrast injections were made under different pulmonary perfusion conditions, resulting in a total of 141 complete pulmonary arterial input functions (AIFs). Using all the AIF curves, an optimal contrast timing protocol was developed for a first-pass, two-volume dynamic CT perfusion technique (one at the base and the other at the peak of AIF curve). A subset of swine was used to validate the prospective two-volume pulmonary perfusion technique. The prospective two-volume perfusion measurements were quantitatively compared to the previously validated retrospective perfusion measurements with t-test, linear regression, and Bland–Altman analysis. As a result, the pulmonary artery time-to-peak ($${T}_{PA}$$

T

PA

) was related to one-half of the contrast injection duration ($$\frac{{T}_{Inj}}{2}$$

T

Inj

2

) by $${T}_{PA}=1.01\frac{{T}_{Inj}}{2}+1.01$$

T

PA

=
1.01

T

Inj

2

+
1.01

(r = 0.95). The prospective two-volume perfusion measurements (PPRO) were related to the retrospective measurements (PRETRO) by PPRO = 0.87PRETRO + 0.56 (r = 0.88). The CT dose index and size-specific dose estimate of the two-volume CT technique were estimated to be 28.4 and 47.0 mGy, respectively. The optimal timing protocol can enable an accurate, low-radiation-dose two-volume dynamic CT perfusion technique.
ZnO size and shape effect on antibacterial activity and cytotoxicity profile
Authors: Babayevska Nataliya , Przysiecka Łucja , Iatsunskyi Igor , Nowaczyk Grzegorz , Jarek Marcin , Janiszewska Ewa , Jurga Stefan
Published: May 2022

The aim of our work was the synthesis of ZnO nano- and microparticles and to study the effect of shapes and sizes on cytotoxicity towards normal and cancer cells and antibacterial activity toward two kinds of bacteria. We fabricated ZnO nano- and microparticles through facile chemical and physical routes. The crystal structure, morphology, textural properties, and photoluminescent properties were characterized by powder X-ray diffraction, electron microscopies, nitrogen adsorption/desorption measurements, and photoluminescence spectroscopy. The obtained ZnO structures were highly crystalline and monodispersed with intensive green emission. ZnO NPs and NRs showed the strongest antibacterial activity against Escherichia coli and Staphylococcus aureus compared to microparticles due to their high specific surface area. However, the ZnO HSs at higher concentrations also strongly inhibited bacterial growth. S. aureus strain was more sensitive to ZnO particles than the E. coli. ZnO NPs and NRs were more harmful to cancer cell lines than to normal ones at the same concentration.
White blood cell count is not associated with flow-mediated vasodilation or nitroglycerine-induced vasodilation
Authors: Kishimoto Shinji , Maruhashi Tatsuya , Kajikawa Masato , Harada Takahiro , Yamaji Takayuki , Han Yiming , Mizobuchi Aya , Hashimoto Yu , Yoshimura Kenichi , Nakano Yukiko , Chayama Kazuaki , Goto Chikara , Yusoff Farina Mohamad , Nakashima Ayumu , Higashi Yukihito
Published: May 2022

It is well known that white blood cell (WBC) count is an independent predictor of cardiovascular events. However, associations of WBC count and WBC subtypes with endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID) are unclear. The aim of this study was to determine the relationships of WBC count and WBC subtypes with vascular function assessed by FMD and NID. A total of 1351 subjects in whom FMD and NID had been measured were recruited from Hiroshima University Vascular Registry. Mean values were 3.7 ± 2.8% for FMD and 11.8 ± 5.9% for NID. WBC was not correlated with FMD or NID. NID was significantly correlated with lymphocytes in univariate analysis but not with other hematologic parameters. In multiple linear regression analyses, NID was not correlated with lymphocytes. In all subgroups including subgroups of age, gender, body mass index, hypertension, dyslipidemia, diabetes mellitus, smoking and tertile of WBC count, WBC count was not correlated with FMD or NID. WBC count and WBC subtypes were not associated with endothelial function assessed by FMD or vascular smooth muscle function assessed by NID. WBC count and vascular function assessed by FMD and NID may reflect different aspects of atherosclerosis.

Clinical Trial Registration Information: URL for Clinical Trial: http://www.umin.ac.jp Registration Number for Clinical Trial: UMIN000039512.
Predefined and data driven CT densitometric features predict critical illness and hospital length of stay in COVID-19 patients
Authors: Shalmon Tamar , Salazar Pascal , Horie Miho , Hanneman Kate , Pakkal Mini , Anwari Vahid , Fratesi Jennifer
Published: May 2022

The aim of this study was to compare whole lung CT density histograms to predict critical illness outcome and hospital length of stay in a cohort of 80 COVID-19 patients. CT chest images on segmented lungs were retrospectively analyzed. Functional Principal Component Analysis (FPCA) was used to find the main modes of variations on CT density histograms. CT density features, the CT severity score, the COVID-GRAM score and the patient clinical data were assessed for predicting the patient outcome using logistic regression models and survival analysis. ROC analysis predictors of critically ill status: 87.5th percentile CT density (Q875)—AUC 0.88 95% CI (0.79 0.94), F1-CT—AUC 0.87 (0.77 0.93) Standard Deviation (SD-CT)—AUC 0.86 (0.73, 0.93). Multivariate models combining CT-density predictors and Neutrophil–Lymphocyte Ratio showed the highest accuracy. SD-CT, Q875 and F1 score were significant predictors of hospital length of stay (LOS) while controlling for hospital death using competing risks models. Moreover, two multivariate Fine-Gray regression models combining the clinical variables: age, NLR, Contrast CT factor with either Q875 or F1 CT-density predictors revealed significant effects for the prediction of LOS incidence in presence of a competing risk (death) and acceptable predictive performances (Bootstrapped C-index 0.74 [0.70 0.78]).
Transarterial chemoembolization of unresectable renal cell carcinoma with doxorubicin-loaded CalliSpheres drug-eluting beads
Authors: Bi Yonghua , Shi Xiaonan , Ren Jianzhuang , Yi Mengfei , Han Xinwei
Published: May 2022

The safety and efficacy of drug-eluting beads transarterial chemoembolization (DEB-TACE) for unresectable renal cell carcinoma (RCC) still unknown. We aimed to assess the feasibility, safety and clinical efficacy of DEB-TACE with doxorubicin-loaded CalliSpheres beads (CB) in patients with unresectable RCC. Between 2016 and 2020, thirty-five patients with unresectable RCC underwent DEB-TACE with doxorubicin-loaded CB. The objective response rate (ORR) was the primary endpoint, and overall survival (OS) and progression-free survival (PFS) were the secondary endpoints. Fifteen-seven times of DEB-TACE were performed in 35 patients using doxorubicin-loaded (median 60 mg) CB. Fifteen patients underwent an additional session of DEB-TACE, with intervals of 1 to 1.5 months. Twenty-one patients underwent transarterial infusion with cisplatin or oxaliplatin before DEB-TACE. The median follow-up time was 9.0 months (Range 1.8–43.6 months). ORR and DCR were 47.1% and 94.1%, 29.0% and 87.1%, 23.1% and 84.6% respectively at 1-, 3-, and 6- months after DEB-TACE. The median PFS was 21.4 months, and the 3-, 6- and 12- month PFS rates were 84.7%, 73.7% and 62.3%, respectively. The median OS was 24.6 months, and the 3-, 6- and 12- month OS rates were 93.9%, 87.6% and 65.2%, respectively. There were no treatment-related deaths or severe adverse events of grade 3 or more. In conclusion, DEB-TACE with doxorubicin-loaded CB is a safe, feasible and effective palliative treatment option for patients with unresectable RCC.
Effects of ischemic conditioning on head and neck free flap oxygenation: a randomized controlled trial
Authors: Min Se-Hee , Choe Suk Hyung , Kim Won Shik , Ahn Soon-Hyun , Cho Youn Joung
Published: May 2022

Flap failure after microvascular reconstructive surgery is a rare but devastating complication caused by reperfusion injury and tissue hypoperfusion. Remote ischemic conditioning (RIC) provides protection against ischemia/reperfusion injury and reduces tissue infarction. We hypothesized that RIC would enhance flap oxygenation and exert organ-protective effects during head and neck free flap reconstructive surgery. Adult patients undergoing free flap transfer surgery for head and neck cancer were randomized to receive either RIC or sham-RIC during surgery. RIC consisted of four cycles of 5-min ischemia and 5-min reperfusion applied to the upper or lower extremity. The primary endpoint, tissue oxygen saturation of the flap, was measured by near-infrared spectroscopy on the first postoperative day. Organ-protective effects of RIC were evaluated with infarct size of rat hearts perfused with plasma dialysate from patients received RIC or sham-RIC. Between April 2018 and July 2019, 50 patients were randomized (each n = 25) and 46 were analyzed in the RIC (n = 23) or sham-RIC (n = 23) groups. Tissue oxygen saturation of the flap was similar between the groups (85 ± 12% vs 83 ± 9% in the RIC vs sham-RIC groups; P = 0.471). Myocardial infarct size after treatment of plasma dialysate was significantly reduced in the RIC group (44 ± 7% to 26 ± 6%; P = 0.018) compared to the sham-RIC group (42 ± 6% to 37 ± 7%; P = 0.388). RIC did not improve tissue oxygenation of the transferred free flap in head and neck cancer reconstructive surgery. However, there was evidence of organ-protective effects of RIC in experimental models.

Trial registration: Registry number of ClinicalTrials.gov: NCT03474952.
Acute effects of high intensity training on cardiac function: a pilot study comparing subjects with type 2 diabetes to healthy controls
Authors: Ness Henning O. , Ljones Kristine , Gjelsvik Randi H. , Tjønna Arnt Erik , Malmo Vegard , Nilsen Hans Olav , Hollekim-Strand Siri Marte , Dalen Håvard , Høydal Morten Andre
Published: May 2022

This study evaluated acute cardiac stress after a high-intensity interval training session in patients with type 2 diabetes (T2D) versus healthy controls. High intensity aerobic exercise was performed by 4 × 4-min intervals (90–95% of maximal heart rate), followed by a ramp protocol to peak oxygen uptake. Echocardiography was performed before and 30 min after exercise. Holter electrocardiography monitored heart rhythms 24 h before, during, and 24 h after the exercise. Left atrial end-systolic volume, peak early diastolic mitral annular velocity, and the ratio of peak early to late diastolic mitral inflow velocity were reduced by approximately 18%, 15%, and 31%, respectively, after exercise across groups. Left ventricular end-diastolic wall thickness was the only echo parameter that significantly differed between groups in response to exercise. The T2D group had a rate of supraventricular extrasystoles per hour that was 265% greater than that of the controls before exercise, which remained higher after exercise. A single exhaustive exercise session impaired left ventricular diastolic function in both groups. The findings also indicated impaired right ventricular function in patients with T2D after exercise.

ClinicalTrials.gov Identifier: NCT02998008.
Energy supply and influencing factors of mountain marathon runners from Baiyin marathon accident in China
Authors: Sun Jichao
Published: May 2022

High temperature impacts the performance of marathon athletes, and hypothermia harms athletes. Twenty-one runners died, and eight were injured in the China Baiyin marathon on May 22, 2021. It’s a typical human life test. The energy equations are combined with the maximum energy supply of Chinese male athletes to study this accident. We analyze the human body’s route slope, travel speed, and heat dissipation under low temperatures in this marathon. The study shows that the large slope and long-distance of CP2 to CP3 section and the low temperature during the competition are the main reasons for the accident. The method of quantifying the slope and temperature and calculating the percentage of athletes’ physical consumption proposed in this paper can evaluate the route design of field marathons. We suggest that the physical energy consumption ratio of 90%, i.e. 315 cal/min/kg, should be taken as the maximum energy supply for Chinese male marathon runners. Dangerous risk zones for wind speed and temperature on dangerous path sections are also formulated for athletes to make their assessments. This paper’s theories and methods can effectively help design the marathon route and determine the race time.
Post-acute COVID-19 outcomes in children requiring hospitalisation
Authors: Bossley Cara J. , Kavaliunaite Ema , Harman Katharine , Cook James , Ruiz Gary , Gupta Atul
Published: May 2022

Post-acute COVID-19 causes long term sequalae in adults. This is less well described in children. We performed clinical assessments on a large cohort of children and young people admitted with a positive SARS-CoV-2 RNA swab. We assessed for symptoms of post-acute COVID-19 syndrome after 4 weeks or more. We found that most (85%) of children made a full recovery following SARS-CoV-2 infection. A small number had symptoms which lasted for more than 4 weeks, most of which had resolved at 3 months. Symptoms included dry cough, fatigue and headache. One patient suffered from anosmia. We conclude that most children and young people do not suffer from past-acute COVID-19 syndrome, and make a full recovery from infection.
Spatiotemporal stop-and-go dynamics of the mitochondrial TOM core complex correlates with channel activity
Authors: Wang Shuo , Findeisen Lukas , Leptihn Sebastian , Wallace Mark I. , Hörning Marcel , Nussberger Stephan
Published: May 2022

Single-molecule studies can reveal phenomena that remain hidden in ensemble measurements. Here we show the correlation between lateral protein diffusion and channel activity of the general protein import pore of mitochondria (TOM-CC) in membranes resting on ultrathin hydrogel films. Using electrode-free optical recordings of ion flux, we find that TOM-CC switches reversibly between three states of ion permeability associated with protein diffusion. While freely diffusing TOM-CC molecules are predominantly in a high permeability state, non-mobile molecules are mostly in an intermediate or low permeability state. We explain this behavior by the mechanical binding of the two protruding Tom22 subunits to the hydrogel and a concomitant combinatorial opening and closing of the two β-barrel pores of TOM-CC. TOM-CC could thus represent a β-barrel membrane protein complex to exhibit membrane state-dependent mechanosensitive properties, mediated by its two Tom22 subunits.
Determination of intracellular ascorbic acid using tandem mass spectrometry
Authors: Abe Chizumi , Higuchi Ohki , Matsumoto Akira , Miyazawa Taiki
Published: May 2022

Ascorbic acid is involved in a variety of biological events.
Rational design of a dual-reactive probe for imaging the biogenesis of both H2S and GSH froml-Cys rather thand-Cys in live cells
Authors: Ye Haishun , Cheng Longhuai , Tu Xiaoqiang , Wang Da-Wei , Yi Long
Published: May 2022

Using both thiolysis of NBD amine and CBD arylether as dual receptors, we rationally design a dual-quenching probe for the detection of the biogenesis of H2S + GSH derived froml-Cys rather thand-Cys in live cells.