bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold Compaction and Macro‐Porosity Removal in Rubble‐Pile Asteroids: 1. Theory
Authors: Zhang Zhongtian , Bercovici David , Elkins‐Tanton Linda
Published: October 2022

Many asteroids are likely to be have been shattered by collisions into fragments and reaccumulated as gravitationally‐bound rubble piles. These bodies may contain large porosities, although this picture may be complicated by compaction inside the asteroid body. Estimates of asteroid mass and volume imply a negative correlation between size and porosity for stony asteroids. Asteroids that are suspected to be metallic appear to contain larger porosities than stony asteroids of similar sizes. To understand these observations, we develop models for cold compaction of fragments of different materials. The initial boulder size distributions are assumed to be narrow. We focus on macro‐porosity between the boulders and do not consider micro‐porosity inside the boulders. In our model of silicate/chondritic boulders, compaction is assumed to occur through cataclastic fracturing, which creates small pieces that fill the pores between residual large boulders, leading to fractal‐like distributions. This fracturing occurs when compression leads to stresses exceeding the tensile strength of the boulders. Combining this model with data on meteorite strength, we suggest that the compaction of chondritic boulders can be significant at pressures of several megapascals. In our model of metal boulders, we consider cold welding and boulder deformation (through ductile yielding or brittle‐like fracturing, depending on the stress and intrinsic crack size). Given the properties of iron meteorites, we infer that compaction in metallic rubble piles, caused by ductile or brittle deformation, is small, and that cold welding may lead to large (≳50%) porosities if the boulders are of ∼1 m sizes.
Characterizing Seasonal and Residual Ices at the South Pole of Mars Using a Universal Set of CRISM Spectral Endmembers
Authors: Cartwright S. F. A. , Calvin W. M. , Seelos K. D. , Seelos F. P.
Published: October 2022

Current maps of compositional variation across south polar ice exposures on Mars do not resolve the meter‐scales at which erosional processes are most active, ultimately limiting our understanding of how the deposits form and evolve and how they can be used to interpret long‐term climate records. In this study, we use k‐means clustering and random forest classification to identify and map a set of universal spectral endmembers across 167 high‐resolution observations acquired during southern summer by the Compact Reconnaissance Imaging Spectrometer for Mars. The 21 endmembers show distinct combinations and strengths of key infrared absorption features reflecting diverse mixtures of CO2 ice, H2O ice, and dust. The resulting compositional framework can be used to characterize the nature of both seasonal CO2 frost and the residual ices it overlies across a variety of terrains. Following the large dust event of Mars Year 28, the residual CO2‐ice deposits (RCD) were covered by an unusually thick or long‐lived deposit of seasonal frost. Within the RCD, low‐albedo material around erosional features display H2O ice absorptions consistent with exposures around the outer margins of the RCD. These peripheral water‐ice deposits show unexpected variation in CO2 ice and dust content. Most notably, regions within several km of the edge of the RCD display spectral contributions from CO2 ice even after seasonal frost has been removed. These results can inform investigations focused on the dynamics of seasonal CO2 deposition, the development of erosional morphologies, and the creation of climate records in south polar stratigraphy.
Uncovering Basal Friction in Northwest Greenland Using an Ice Flow Model and Observations of the Past Decade
Authors: Choi Youngmin , Seroussi Helene , Gardner Alex , Schlegel Nicole‐Jeanne
Published: October 2022

Glaciers move under the pull of gravity due to a combination of internal deformation (creep) and basal sliding. Basal sliding dominates ice motion in fast flowing areas, and an accurate description of sliding in ice flow models is therefore critical to adequately capture ice dynamics and its temporal evolution. However, there is currently no consensus on the exact form of basal friction law, as direct observations of basal properties remain limited. Using an ice flow model and observations of the past decade, we evaluate a variety of friction laws and determine their ability to reproduce the observed acceleration and mass loss of marine‐terminating glaciers in northwest Greenland. We find that friction laws that include an explicit dependence on the effective pressure better reproduce the observed acceleration and mass loss overall, with semi‐plastic basal laws describing some glaciers well. Our glacier‐scale model evaluation suggests heterogeneous bed conditions under northwest Greenland, which cannot be detected from the results of regional changes. Accounting for heterogeneous bed conditions, this region might contribute 15 mm to sea level rise by 2100, twice as much as predicted from models based on commonly used uniform bed conditions.
Influences of Mesoscale Ocean Eddies on Flow Vertical Structure in a Resolution‐Based Model Hierarchy
Authors: Yankovsky Elizabeth , Zanna Laure , Smith K. Shafer
Published: October 2022

The understanding and representation of energetic transfers associated with ocean mesoscale eddies is fundamental to the development of parameterizations for climate models. We investigate the influence of eddies on flow vertical structure as a function of underlying dynamical regime and grid resolution. We employ the GFDL‐MOM6 in an idealized configuration and systematically consider four horizontal resolutions: 1/4°, 1/8°, 1/16°, and 1/32°. We analyze the distributions of potential and kinetic energy, decomposed into barotropic and baroclinic, and eddy and mean parts. As resolution increases and baroclinically unstable modes are better captured, kinetic energy increases and potential energy decreases. The dominant trend in vertical structure is an increasing fraction of kinetic energy going into the barotropic mode, particularly its eddy component, as eddies are increasingly resolved. We attribute the increased baroclinicity at low resolutions to inaccurate representation of vertical energy fluxes, leading to suppressed barotropization and energy trapping in high vertical modes. We also explore how the underlying dynamical regime influences energetic pathways. In cases where large‐scale flow is dominantly barotropic, resolving the deformation radius is less crucial to accurately capturing the flow's vertical structure. We find the barotropic kinetic energy fraction to be a useful metric in assessing vertical structure. In the highest‐resolution case, the barotropic kinetic energy fraction correlates with the scale separation between the deformation scale and the energy‐containing scale, that is, the extent of the eddy‐driven inverse cascade. This work suggests that mesoscale eddy parameterizations should incorporate the energetic effects of eddies on vertical structure in a scale‐aware, physically informed manner.
Inhibition of p38 MAPK or immunoproteasome overcomes resistance of chronic lymphocytic leukemia cells to Bcl-2 antagonist venetoclax
Authors: Avsec Damjan , Škrlj Miklavčič Marja , Burnik Tilen , Kandušer Maša , Bizjak Maruša , Podgornik Helena , Mlinarič-Raščan Irena
Published: October 2022

Chronic lymphocytic leukemia (CLL) is a hematological neoplasm of CD19-positive mature-appearing B lymphocytes. Despite the clinical success of targeted therapies in CLL, the development of resistance diminishes their therapeutic activity. This is also true for the Bcl-2 antagonist venetoclax. We investigated the molecular mechanisms that drive venetoclax resistance in CLL, with a clear focus to provide new strategies to successfully combat it. Activation of CLL cells with IFNγ, PMA/ionomycin, and sCD40L diminished the cytotoxicity of venetoclax. We demonstrated that the metabolic activity of cells treated with 1 nM venetoclax alone was 48% of untreated cells, and was higher for cells co-treated with IFNγ (110%), PMA/ionomycin (78%), and sCD40L (62%). As of molecular mechanism, we showed that PMA/ionomycin and sCD40L triggered translocation of NFκB in primary CLL cells, while IFNγ activated p38 MAPK, suppressed spontaneous and venetoclax-induced apoptosis and induced formation of the immunoproteasome. Inhibition of immunoproteasome with ONX-0914 suppressed activity of immunoproteasome and synergized with venetoclax against primary CLL cells. On the other hand, inhibition of p38 MAPK abolished cytoprotective effects of IFNγ. We demonstrated that venetoclax-resistant (MEC-1 VER) cells overexpressed p38 MAPK and p-Bcl-2 (Ser70), and underexpressed Mcl-1, Bax, and Bak. Inhibition of p38 MAPK or immunoproteasome triggered apoptosis in CLL cells and overcame the resistance to venetoclax of MEC-1 VER cells and venetoclax-insensitive primary CLL cells. In conclusion, the p38 MAPK pathway and immunoproteasome represent novel targets to combat venetoclax resistance in CLL.
Variation in the fruit development gene POINTED TIP regulates protuberance of tomato fruit tip
Authors: Song Jianwen , Shang Lele , Li Changxing , Wang Wenqian , Wang Xin , Zhang Chunli , Ai Guo , Ye Jie , Yang Changxian , Li Hanxia , Hong Zonglie , Larkin Robert M. , Ye Zhibiao , Zhang Junhong
Published: October 2022

The domestication of tomato has led to striking variations in fruit morphology. Here, we show a genome-wide association study (GWAS) to understand the development of the fruit tip and describe aPOINTED TIP(PT) gene that encodes a C2H2-type zinc finger transcription factor. A single nucleotide polymorphism is found to change a histidine (H) to an arginine (R) in the C2H2 domain of PT and the two alleles are referred to asPTHandPTR. Knocking outPTHleads to development of pointed tip fruit.PTHfunctions to suppress pointed tip formation by downregulating the transcription ofFRUTFULL 2(FUL2), which alters the auxin transport. Our evolutionary analysis and previous studies by others suggest that thePTRallele likely hitch-hiked along with other selected loci during the domestication process. This study uncovers variation inPTand molecular mechanism underlying fruit tip development in tomato.
Selective control of conductance modes in multi-terminal Josephson junctions
Authors: Graziano Gino V. , Gupta Mohit , Pendharkar Mihir , Dong Jason T. , Dempsey Connor P. , Palmstrøm Chris , Pribiag Vlad S.
Published: October 2022

The Andreev bound state spectra of multi-terminal Josephson junctions form an artificial band structure, which is predicted to host tunable topological phases under certain conditions. However, the number of conductance modes between the terminals of a multi-terminal Josephson junction must be few in order for this spectrum to be experimentally accessible. In this work, we employ a quantum point contact geometry in three-terminal Josephson devices to demonstrate independent control of conductance modes between each pair of terminals and access to the single-mode regime coexistent with the presence of superconducting coupling. These results establish a full platform on which to realize tunable Andreev bound state spectra in multi-terminal Josephson junctions.
Realizing high-ranged thermoelectric performance in PbSnS2 crystals
Authors: Zhan Shaoping , Hong Tao , Qin Bingchao , Zhu Yingcai , Feng Xiang , Su Lizhong , Shi Haonan , Liang Hao , Zhang Qianfan , Gao Xiang , Ge Zhen-Hua , Zheng Lei , Wang Dongyang , Zhao Li-Dong
Published: October 2022

Great progress has been achieved in p-type SnS thermoelectric compound recently, while the stagnation of the n-type counterpart hinders the construction of thermoelectric devices. Herein, n-type sulfide PbSnS2with isostructural to SnS is obtained through Pb alloying and achieves a maximumZTof ~1.2 and an averageZTof ~0.75 within 300–773 K, which originates from enhanced power factor and intrinsically ultralow thermal conductivity. Combining the optimized carrier concentration by Cl doping and enlarged Seebeck coefficient through activating multiple conduction bands evolutions with temperature, favorable power factors are maintained. Besides, the electron doping stabilizes the phase of PbSnS2and the complex-crystal-structure induced strong anharmonicity results in ultralow lattice thermal conductivity. Moreover, a maximum power generation efficiency of ~2.7% can be acquired in a single-leg device. Our study develops a n-type sulfide PbSnS2with high performance, which is a potential candidate to match the excellent p-type SnS.
Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma
Authors: Topham James T. , Tsang Erica S. , Karasinska Joanna M. , Metcalfe Andrew , Ali Hassan , Kalloger Steve E. , Csizmok Veronika , Williamson Laura M. , Titmuss Emma , Nielsen Karina , Negri Gian Luca , Spencer Miko Sandra E. , Jang Gun Ho , Denroche Robert E. , Wong Hui-li , O’Kane Grainne M. , Moore Richard A. , Mungall Andrew J. , Loree Jonathan M. , Notta Faiyaz , Wilson Julie M. , Bathe Oliver F. , Tang Patricia A. , Goodwin Rachel , Morin Gregg B. , Knox Jennifer J. , Gallinger Steven , Laskin Janessa , Marra Marco A. , Jones Steven J. M. , Schaeffer David F. , Renouf Daniel J.
Published: October 2022

Oncogenic KRAS mutations are absent in approximately 10% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) and may represent a subgroup of mPDAC with therapeutic options beyond standard-of-care cytotoxic chemotherapy. While distinct gene fusions have been implicated in KRAS wildtype mPDAC, information regarding other types of mutations remain limited, and gene expression patterns associated with KRAS wildtype mPDAC have not been reported. Here, we leverage sequencing data from the PanGen trial to perform comprehensive characterization of the molecular landscape of KRAS wildtype mPDAC and reveal increased frequency of chr1q amplification encompassing transcription factors PROX1 and NR5A2. By leveraging data from colorectal adenocarcinoma and cholangiocarcinoma samples, we highlight similarities between cholangiocarcinoma and KRAS wildtype mPDAC involving both mutation and expression-based signatures and validate these findings using an independent dataset. These data further establish KRAS wildtype mPDAC as a unique molecular entity, with therapeutic opportunities extending beyond gene fusion events.
Nigrostriatal dopamine pathway regulates auditory discrimination behavior
Authors: Chen Allen P. F. , Malgady Jeffrey M. , Chen Lu , Shi Kaiyo W. , Cheng Eileen , Plotkin Joshua L. , Ge Shaoyu , Xiong Qiaojie
Published: October 2022

The auditory striatum, the tail portion of dorsal striatum in basal ganglia, is implicated in perceptual decision-making, transforming auditory stimuli to action outcomes. Despite its known connections to diverse neurological conditions, the dopaminergic modulation of sensory striatal neuronal activity and its behavioral influences remain unknown. We demonstrated that the optogenetic inhibition of dopaminergic projections from the substantia nigra pars compacta to the auditory striatum specifically impairs mouse choice performance but not movement in an auditory frequency discrimination task. In vivo dopamine and calcium imaging in freely behaving mice revealed that this dopaminergic projection modulates striatal tone representations, and tone-evoked striatal dopamine release inversely correlated with the evidence strength of tones. Optogenetic inhibition of D1-receptor expressing neurons and pharmacological inhibition of D1 receptors in the auditory striatum dampened choice performance accuracy. Our study uncovers a phasic mechanism within the nigrostriatal system that regulates auditory decisions by modulating ongoing auditory perception.
A supraparticle-based biomimetic cascade catalyst for continuous flow reaction
Authors: Guo Xiaomiao , Xue Nan , Zhang Ming , Ettelaie Rammile , Yang Hengquan
Published: October 2022

Robust millimeter-sized spherical particles with controlled compositions and microstructures hold promises of important practical applications especially in relation to continuous flow cascade catalysis. However, the efficient fabrication methods for producing such particles remain scare. Here, we demonstrate a liquid marble approach to fabricate robust mm-sized porous supraparticles (SPs) through the bottom-up assembly of silica nanoparticles in the presence of strength additive or surface interactions, without the need for the specific liquid-repellent surfaces used by the existing methods. As the proof of the concept, our method was exemplified by fabricating biomimetic cascade catalysts through assembly of two types of well-defined catalytically active nanoparticles. The obtained SP-based cascade catalysts work well in industrially preferred fixed-bed reactors, exhibiting excellent catalysis efficiency, controlled reaction kinetics, high enantioselectivity (99% ee) and outstanding stability (200~500 h) in the cascades of ketone hydrogenation-kinetic resolution and amine racemization-kinetic resolution. The excellent catalytic performances are attributed to the structural features, reconciling close proximity of different catalytic sites and their sufficient spatial isolation.
The hallmarks of dietary intervention-resilient gut microbiome
Authors: Klimenko Natalia S. , Odintsova Vera E. , Revel-Muroz Anastasia , Tyakht Alexander V.
Published: October 2022

Maintaining equilibrium of the gut microbiome is crucial for human health. Diet represents an important and generally accessible natural channel of controlling the nutrients supply to the intestinal microorganisms. Although many studies showed that dietary interventions can specifically modulate gut microbiome composition, further progress of the approach is complicated by interindividual variability of the microbial community response. The reported causes of this variability include the baseline microbiome composition features, but it is unclear whether any of them are intervention-specific. Here, we applied a unified computational framework to investigate the variability of microbiome response measured as beta diversity in eight various dietary interventions using previously published 16S rRNA sequencing datasets. We revealed a number of baseline microbiome features which determine the microbiome response in an intervention-independent manner. One of the most stable associations, reproducible for different interventions and enterotypes, was a negative dependence of the response on the average number of genes per microorganism in the community—an indicator of the community functional redundancy. Meanwhile, many revealed microbiome response determinants were enterotype-specific. In Bact1 and Rum enterotypes, the response was negatively correlated with the baseline abundance of their main drivers. Additionally, we proposed a method for preliminary assessment of the microbiome response. Our study delineats the universal features determining microbiome response to diverse interventions. The proposed approach is promising for understanding the mechanisms of gut microbiome stability and improving the efficacy of personalised microbiome-tailored interventions.
Designing all-pay auctions using deep learning and multi-agent simulation
Authors: Gemp Ian , Anthony Thomas , Kramar Janos , Eccles Tom , Tacchetti Andrea , Bachrach Yoram
Published: October 2022

We propose a multi-agent learning approach for designing crowdsourcing contests and All-Pay auctions. Prizes in contests incentivise contestants to expend effort on their entries, with different prize allocations resulting in different incentives and bidding behaviors. In contrast to auctions designed manually by economists, our method searches the possible design space using a simulation of the multi-agent learning process, and can thus handle settings where a game-theoretic equilibrium analysis is not tractable. Our method simulates agent learning in contests and evaluates the utility of the resulting outcome for the auctioneer. Given a large contest design space, we assess through simulation many possible contest designs within the space, and fit a neural network to predict outcomes for previously untested contest designs. Finally, we apply mirror ascent to optimize the design so as to achieve more desirable outcomes. Our empirical analysis shows our approach closely matches the optimal outcomes in settings where the equilibrium is known, and can produce high quality designs in settings where the equilibrium strategies are not solvable analytically.
Using intrinsic properties of quantum dots to provide additional security when uniquely identifying devices
Authors: Fong Matthew J. , Woodhead Christopher S. , Abdelazim Nema M. , Abreu Daniel C. , Lamantia Angelo , Ball Elliott M. , Longmate Kieran , Howarth David , Robinson Benjamin J. , Speed Phillip , Young Robert J.
Published: October 2022

Unique identification of optical devices is important for anti-counterfeiting. Physical unclonable functions (PUFs), which use random physical characteristics for authentication, are advantageous over existing optical solutions, such as holograms, due to the inherent asymmetry in their fabrication and reproduction complexity. However, whilst unique, PUFs are potentially vulnerable to replication and simulation. Here we introduce an additional benefit of a small modification to an established model of nanoparticle PUFs by using a second measurement parameter to verify their authenticity. A randomly deposited array of quantum dots is encapsulated in a transparent polymer, forming a tag. Photoluminescence is measured as a function of excitation power to assess uniqueness as well as the intrinsic nonlinear response of the quantum material. This captures a fingerprint, which is non-trivial to clone or simulate. To demonstrate this concept practically, we show that these tags can be read using an unmodified smartphone, with its built-in flash for excitation. This development over constellation-style optical PUFs paves the way for more secure, facile authentication of devices without requiring complex fabrication or characterisation techniques.
400 W average power Q-switched Yb:YAG thin-disk-laser
Authors: Radmard Saeid , Moshaii Ahmad , Pasandideh Kaveh
Published: October 2022

We report on producing up to 403 W average power directly from an acousto-optically Q-switched Yb:YAG thin-disk laser (TDL). To achieve this power, it has theoretically and experimentally been shown that the laser stability border could be shifted toward higher repetition rates by engineering of the output coupler transmittance. This allows for stable operation of the laser at higher frequencies and a further increase in the power extraction from the active medium. Using an output coupler with 93% reflectivity, a maximum average power of 403 W at the repetition rate of 12.0 kHz has been recorded under the pump power of 1220 W. Furthermore, the maximum pulse energy of 57 mJ was produced at the repetition rate of 1.00 kHz and the pump power of 520 W. The characteristics of the laser at various Q-switching rates and the pump powers have been investigated. In addition, a numerical study for supporting the experimental results has been proposed here. To the best of our knowledge, the achieved average power and the pulse energy are the highest values reported to date from a Q-switched Yb:YAG TDL. The results pave the way to further power scaling of solid-state Q-switched oscillators.
Safety assessment of charcoal usage and effects of common charcoal ignition aiders on combustion indices
Authors: Ajayeoba A. O. , Fajobi M. O. , Adebiyi K. A. , Raheem W. A. , Oladapo S. O. , Olayinka M. D.
Published: October 2022

Charcoal is a popular form of biofuel embraced for domestic and industrial purposes. However, the use of Charcoal has some associated challenges, such as the required charcoal pot and setting it into the fire at first by using Charcoal-Ignition-Aiders (CIA) (e.g. discarded paper, nylon, rubber, plastics, petrol, the residue of processed palm oil, maise cob, wood, and kerosene). Coupled with the chemical properties of Charcoal, the resulting gases from CIA are capable of polluting the environment with perceived Adverse-Health-Implications (AHI) on the ecosystem. Therefore, this study conducted a safety assessment of charcoal biofuel usage and the effects of common CIA on combustion indices. This study followed standard methods and the use of peculiar equipment. This study established that Charcoal is commonly used in the studied area because it is cheap, readily available and requires less technical know-how. Considering the combustion indices, using paper as a CIA generated the lowest carbon monoxide (CO) value, 28.1 ppm, with 3,434.54 ppm volatile organic compound, VOC. Compared with the ACGIH standard permissible exposure level of ≤ 30 ppm, the paper gave a lesser CO value of 28.10 ppm among all the CIA. At the same time, all the CIA recorded higher VOC compared with EPA standard permissible exposure level of ≤ 15 ppm. ANOVA analysis conducted on the socio-demographic profile of the respondents, cooking attributes of the respondents, and use of charcoal pot types by the respondents in Zone 1, Zone 2, and Zone 3 gave p-values of 0.032, 0.028, and 0.039, respectively. These imply significant differences within the zones in each of the indices. The average energy content reported for charcoals sourced from oak trees, afara, obeche, mahogany, and iroko woods is 3,2149 kJ/kg compared to the lower ones. Therefore, this study recommended using these charcoals alongside discarded paper as CIA because they are a better combination to reduce AHI.
Increased risk of open-angle glaucoma in non-smoking women with obstructive pattern of spirometric tests
Authors: Lee Jihei Sara , Kim Yong Joon , Kim Sung Soo , Park Sungeun , Choi Wungrak , Bae Hyoung Won , Kim Chan Yun
Published: October 2022

To investigate differences in the prevalence of open-angle glaucoma (OAG) between different pulmonary function types. A population-based, cross-sectional analysis was conducted using Korean National Health and Nutrition Examination Surveys from 2008 to 2011. A total of 8941 subjects  ≥ 40 years of age were analyzed. Chronic obstructive pulmonary disease (COPD) was defined as the ratio between first second of forced expiration (FEV1) and forced vital capacity (FVC) below 70%. The prevalence of glaucoma, as defined by the International Society of Geographical and Epidemiological Ophthalmology, was the main outcome. OAG was more prevalent in women with COPD (8.0% vs. 4.8% normal, P = 0.001) compared to women with normal pulmonary function. Intraocular pressure (IOP) of women with COPD were 13.3 (0.2) mmHg (13.9 (0.1) mmHg for normal function, P = 0.182). Never-smokers were more prevalent in women with COPD and glaucoma (92.9% vs. 52.4% normal function; P < 0.001). COPD was found to increase the risk of glaucoma in women (OR 2.077, P = 0.017) and even further in non-smoking women (OR 2.711, P = 0.003). Women with COPD showed a higher glaucoma prevalence despite similar IOP in comparison to women with normal pulmonary function. Non-smoking COPD is significantly associated with open-angle glaucoma in women.
Adapting and pretesting the World Health Organization’s Caregiver Skills Training Program for children with autism and developmental disorders or delays in Hong Kong
Authors: Wong Paul Wai-Ching , Lam Yan-Yin , Lau Janet Siu-Ping , Fok Hung-Kit ,   The WHO CST Team, Servili Chiara , Salomone Erica , Pacione Laura , Shire Stephanie , Brown Felicity
Published: October 2022

The World Health Organization Caregiver Skills Training Program (WHO-CST) was developed to strengthen caregivers’ skills in supporting children with developmental delays and the caregivers’ well-being. The WHO-CST Hong Kong (HK) was adapted, and pre-pilot tested to support families with children suspected of having developmental delays and autism spectrum disorder and to empower the caregivers to foster their children’s learning, social communication, and adaptive behavior. A sequential mixed-methods research methodology was undertaken to examine the adaptation process and initial implementation experiences. The acceptability, feasibility, and perceived benefits of the WHO-CST were assessed using stakeholders’ and caregivers’ qualitative and caregivers’ quantitative pre- and post-intervention feedback. The data included materials generated from (1) three consultation meetings with stakeholders; (2) detailed reviews of the translated and adapted WHO-CST materials by master trainees (n = 10) trained by the WHO-CST representatives; (3) needs assessment focus group interviews with caregivers (n = 15) of children with autism spectrum disorder; and (4) pre- and post-CST program qualitative focus group interviews and quantitative evaluation. Consultation with stakeholders suggested that the program was acceptable for the local community, but the home visit and fidelity components were initially considered to be challenges towards the feasibility and sustainability of the program. Caregivers in the needs assessment focus groups gave widely diverse views about the program’s uniqueness, length, delivery mode, and the inclusion of videotaping in-home visits. Post-intervention comments by caregivers about the program were mainly positive, while the MTs were critical of the content and length of the training and fidelity process. As one of the first high-income locations to adopt the WHO-CST, the evaluation findings of the WHO-CST-HK indicate that it is feasible and acceptable to implement the program in a metropolitan area where families have busy work schedules and are very conscious of privacy issues. The study results suggest that the WHO-CST program in HK and other high-income countries require scaling up and further evaluation of its implementation in real community settings. This involves systemic and contextual changes to allow task-sharing between professionals and non-specialists at the macro level. Furthermore, technology should be used to support the supervision of non-specialists. In addition, easier access to the WHO-CST materials at the micro level is required to ensure equity, equality, diversity, and inclusion of diversified families of children with developmental delays.
Improving protein succinylation sites prediction using embeddings from protein language model
Authors: Pokharel Suresh , Pratyush Pawel , Heinzinger Michael , Newman Robert H. , KC Dukka B.
Published: October 2022

Protein succinylation is an important post-translational modification (PTM) responsible for many vital metabolic activities in cells, including cellular respiration, regulation, and repair. Here, we present a novel approach that combines features from supervised word embedding with embedding from a protein language model called ProtT5-XL-UniRef50 (hereafter termed, ProtT5) in a deep learning framework to predict protein succinylation sites. To our knowledge, this is one of the first attempts to employ embedding from a pre-trained protein language model to predict protein succinylation sites. The proposed model, dubbed LMSuccSite, achieves state-of-the-art results compared to existing methods, with performance scores of 0.36, 0.79, 0.79 for MCC, sensitivity, and specificity, respectively. LMSuccSite is likely to serve as a valuable resource for exploration of succinylation and its role in cellular physiology and disease.
Deep learning model for analyzing the relationship between mandibular third molar and inferior alveolar nerve in panoramic radiography
Authors: Sukegawa Shintaro , Tanaka Futa , Hara Takeshi , Yoshii Kazumasa , Yamashita Katsusuke , Nakano Keisuke , Takabatake Kiyofumi , Kawai Hotaka , Nagatsuka Hitoshi , Furuki Yoshihiko
Published: October 2022

In this study, the accuracy of the positional relationship of the contact between the inferior alveolar canal and mandibular third molar was evaluated using deep learning. In contact analysis, we investigated the diagnostic performance of the presence or absence of contact between the mandibular third molar and inferior alveolar canal. We also evaluated the diagnostic performance of bone continuity diagnosed based on computed tomography as a continuity analysis. A dataset of 1279 images of mandibular third molars from digital radiographs taken at the Department of Oral and Maxillofacial Surgery at a general hospital (2014–2021) was used for the validation. The deep learning models were ResNet50 and ResNet50v2, with stochastic gradient descent and sharpness-aware minimization (SAM) as optimizers. The performance metrics were accuracy, precision, recall, specificity, F1 score, and area under the receiver operating characteristic curve (AUC). The results indicated that ResNet50v2 using SAM performed excellently in the contact and continuity analyses. The accuracy and AUC were 0.860 and 0.890 for the contact analyses and 0.766 and 0.843 for the continuity analyses. In the contact analysis, SAM and the deep learning model performed effectively. However, in the continuity analysis, none of the deep learning models demonstrated significant classification performance.
A cross-sectional study to validate an administrative back pain severity classification tool based on the graded chronic pain scale
Authors: Hochheim M. , Ramm P. , Wunderlich M. , Amelung V.
Published: October 2022

Treatment of chronic lower back pain (CLBP) should be stratified for best medical and economic outcome. To improve the targeting of potential participants for exclusive therapy offers from payers, Freytag et al. developed a tool to classify back pain chronicity classes (CC) based on claim data. The aim of this study was to evaluate the criterion validity of the model. Administrative claim data and self-reported patient information from 3,506 participants (2014–2021) in a private health insurance health management programme in Germany were used to validate the tool. Sensitivity, specificity, and Matthews’ correlation coefficient (MCC) were calculated comparing the prediction with actual grades based on von Korff’s graded chronic pain scale (GCPS). The secondary outcome was an updated view on direct health care costs (€) of patients with back pain (BP) grouped by GCPS. Results showed a fair correlation between predicted CC and actual GCPS grades. A total of 69.7% of all cases were correctly classified. Sensitivity and specificity rates of 54.6 and 76.4% underlined precision. Correlation between CC and GCPS with an MCC of 0.304 also indicated a fair relationship between prediction and observation. Cost data could be clearly grouped by GCPS: the higher the grade, the higher the costs and the use of health care. This was the first study to compare the predicted severity of BP using claim data with the actual severity of BP by GCPS. Based on the results, the usage of CC as a single tool to determine who receives CLBP treatment cannot be recommended. CC is a good tool to segment candidates for specific types of intervention in BP. However, it cannot replace a medical screening at the beginning of an intervention, as the rate of false negatives is too high.

Trial registration The study was conducted using routinely collected data from an intervention, which was previously evaluated and registered retrospectively in the German Registry of Clinical Trials under DRKS00015463 (04/09/2018). Informed consent and the self-reported questionnaire have remained unchanged since the study and, therefore, are still valid according to the ethics proposal.
Lockdown measures during the COVID-19 pandemic strongly impacted the circulation of respiratory pathogens in Southern China
Authors: Wang Heping , Zheng Yuejie , de Jonge Marien I. , Wang Rongjun , Verhagen Lilly M. , Chen Yunsheng , Li Li , Xu Zhi , Wang Wenjian
Published: October 2022

A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Shenzhen. We examined the effect of these measures on the prevalence of respiratory pathogens in children. Clinical and respiratory pathogen data were collected for routine care from hospitalized children with acute respiratory infections in Shenzhen Children’s Hospital from July 2018 to January 2022. Nasopharyngeal swabs were collected and respiratory pathogens were detected using standardized clinical diagnostics as part of routine care. Data were analyzed to describe the effects of COVID-19 prevention procedures on other common pathogens. A total of 56,325 children under 14 years of age were hospitalized with an acute respiratory infection during the study period, 33,909 were tested from July 2018 to January 2020 (pre-lockdown), 1168 from February 2020 to May 2020 (lockdown) and 21,248 from July 2020 to January 2022 (post-lockdown). We observed a 37.3% decline of routine care in respiratory infection associated hospital admission in the 19 months’ post-lockdown vs. the 19 months’ pre-lockdown. There were 99.4%, 16.0% and 1.26% reductions measured for Mycoplasma pneumoniae, influenza virus A and adenovirus, respectively. However, a 118.7% and 75.8% rise was found for respiratory syncytial virus (RSV) and human para-influenza virus (HPIV) during the 19 months’ post-lockdown in comparison to the pre-pandemic period. The detection of RSV especially increased in toddlers after the lockdown. Lockdown measures during the COVID-19 pandemic led to a significant reduction of Mycoplasma pneumoniae, influenza virus A and adenovirus infection. In contrast, RSV and HPIV infection increased.
Characterization of complex fluvial-deltaic deposits in Northeast India using Poisson impedance inversion and non-parametric statistical technique
Authors: Nagendra Babu M. , Ambati Venkatesh , Nair Rajesh R.
Published: October 2022

Characterizing complex fluvial-deltaic deposits is a challenging task for finding hydrocarbon discoveries. We described a methodology for predicting the hydrocarbon zones from complex well-log and prestack seismic data. In this current study, data analysis involves an integrated framework based on Simultaneous prestack seismic inversion (SPSI), target correlation coefficient analysis (TCCA), Poisson impedance inversion, and non-parametric statistical analysis, and Bayesian classification. First, seismic elastic attributes from prestack seismic data were estimated. They can provide the spatial distribution of petrophysical properties of seismic data. Then target correlation coefficient analysis (TCCA) was estimated roration factor “c” from well-log data. Using the seismic elastic attributes and rotation factor “c”, Poisson impedance inversion was performed to predict the Poisson impedance volume. Finally, Bayesian classification integrated the Poisson impedance volume with non-parametric probabilistic density functions (PDFs) to estimate the spatial distribution of lithofacies. Despite complex characteristics in the elastic properties, the current study successfully delineated the complex fluvial-details deposits. These results were verified with conventional findings through numerical analysis.
Multi-Omic analyses characterize the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer’s disease
Authors: Baloni Priyanka , Arnold Matthias , Buitrago Luna , Nho Kwangsik , Moreno Herman , Huynh Kevin , Brauner Barbara , Louie Gregory , Kueider-Paisley Alexandra , Suhre Karsten , Saykin Andrew J. , Ekroos Kim , Meikle Peter J. , Hood Leroy , Price Nathan D. ,   The Alzheimer’s Disease Metabolomics Consortium, Arnold Matthias , Blach Colette , Kaddurah-Daouk Rima , Doraiswamy Murali , Mahmoudiandehkordi Siamak , Welsh-Bohmer Kathleen , Plassman Brenda , Krumsiek Jan , Batra Richa , Saykin Andrew , Yan Jingwen , Risacher Shannon L. , Meikle Peter , Wang Tingting , Ikram Arfan , Ahmad Shahzad , Hankemeier Thomas , Hernandez Ivan A. , Heinken Almut , Martinelli Filippo , Thiele Ines , Hertel Johannes , Hensen Tim , Hulshof Tim , Farrer Lindsay A. , Au Rhoda , Qiu Wendy Wei Qiao , Stein Thor , Karu Naama , Borkowski Kamil , Newman John , Jia Wei , Xie Guoxiang , Wang Jingye , Wei Runmin , Rader Dan , Kling Mitchel , Shaw Leslie , Doraiswamy P. Murali , Funk Cory C. , Hernández A. Iván , Kastenmüller Gabi , Baillie Rebecca , Han Xianlin , Kaddurah-Daouk Rima
Published: October 2022

Dysregulation of sphingomyelin and ceramide metabolism have been implicated in Alzheimer’s disease. Genome-wide and transcriptome-wide association studies have identified various genes and genetic variants in lipid metabolism that are associated with Alzheimer’s disease. However, the molecular mechanisms of sphingomyelin and ceramide disruption remain to be determined. We focus on the sphingolipid pathway and carry out multi-omics analyses to identify central and peripheral metabolic changes in Alzheimer’s patients, correlating them to imaging features. Our multi-omics approach is based on (a) 2114 human post-mortem brain transcriptomics to identify differentially expressed genes; (b) in silico metabolic flux analysis on context-specific metabolic networks identified differential reaction fluxes; (c) multimodal neuroimaging analysis on 1576 participants to associate genetic variants in sphingomyelin pathway with Alzheimer’s disease pathogenesis; (d) plasma metabolomic and lipidomic analysis to identify associations of lipid species with dysregulation in Alzheimer’s; and (e) metabolite genome-wide association studies to define receptors within the pathway as a potential drug target. We validate our hypothesis in amyloidogenic APP/PS1 mice and show prolonged exposure to fingolimod alleviated synaptic plasticity and cognitive impairment in mice. Our integrative multi-omics approach identifies potential targets in the sphingomyelin pathway and suggests modulators of S1P metabolism as possible candidates for Alzheimer’s disease treatment.
Topological soliton metacrystals
Authors: Fan Zhiwei , Puzyrev Danila N. , Skryabin Dmitry V.
Published: October 2022

Designing metamaterials with the required band structure, topology and chirality using nano-fabrication technology revolutionise modern science. The approach of this work to the metamaterial theme is, however, different. We report that a periodic sequence, i.e., metacrystal, of the dissipative optical solitons rotating in a ring microresonator acts as an effective metamaterial in the radio to terahertz frequency range. The metacrystal unit cell consists of the bound pair of solitons, where the inter-soliton distance is used as a control parameter. We investigate the soliton metacrystal band structure and topological properties. The latter is confirmed by the π steps experienced by the crystal phonons’ geometrical (Zak) phase. Furthermore, we found the phononic edge states in the metacrystals with defects made by removing several solitons. Optical frequency combs corresponding to the soliton metacrystals hide the spectral butterfly pattern serving as a signature of the spatio-temporal chirality and bearing a resemblance to the natural occurrences of chirality.
A pH-responsive cascade nanoplatform with circulating oxygen supply for collaborative breast cancer treatment
Authors: Gao Xiaonan , Jia Zhikai , Cheng Yaoying , Ouyang Mingyi , Feng Lin , Wang Yuzhuo , Tang Bo , Xu Kehua
Published: October 2022

A pH-responsive cascade nanoplatform based on ZIF-8 disintegrates in the weakly acidic tumor microenvironment to release MnO2, CaO2 and Ce6.
Aggregation of molecules is controlled in microdroplets
Authors: Basuri Pallab , Shantha Kumar Jenifer , Unni Keerthana , Manna Sujan , Pradeep Thalappil
Published: October 2022

Fluorescence microscopy reveals the control of aggregation and de-aggregation of molecules in microdroplets, which is strikingly different from that in the bulk.
Two dimensional monolayers TetraHex-CX2 (X = N, P, As, and Sb) with superior electronic, mechanical and optical properties
Authors: Liu Wei , Wang Jun , Zheng Xingwen , Zhang Kaiming , Liu Xiaoqiang
Published: October 2022

Novel 2D materials Tetrahex-CX2 (X = N, P, As, and Sb) with superior electronic, mechanical and optical properties.
A multi‐frequency high‐gain GNSS array antenna for asteroid sampling return
Authors: Liu Zhijia , Lu Fan , Duan Jiangnian , Huang Yuhan , Sun Dayuan , Sun Yinlong
Published: October 2022

An almost all‐metal L band multi‐frequency high‐gain GNSS array antenna for an asteroid sampling return mission has been developed for orbit determination. The proposed antenna is designed for reception and is compatible with Beidou and GPS at L‐band (i.e. GPS‐L1: 1575.42 MHz; BDS‐B1I: 1561.098 MHz; BDS‐B2a: 1176.45 MHz). The radiation element is an almost all‐metal dipole with structure improvement, and thereby strong enough to handle vibrations and loads. The array antenna is composed of the 7‐radiation element and a low loss air suspended stripline beam‐forming network. The six elements around the center element have uniform distribution, while the center one is excited twice amplitude than outer ones for appropriate gain and beamwidth. A prototype of the proposed GNSS array antenna is designed in a simulation and measured in an experiment. The simulated and measured results agree very well, showing that the reflection coefficient <−17.5 dB over 32.8% bandwidth from 1.1 to 1.7 GHz is achieved with rotationally symmetric radiation patterns and gains >13.4 dBic, 15.2 dBic, 15.2 dBic at BDS‐B2a, GPS‐L1, BDS‐B1I, respectively.
Partial shading detection and hotspot prediction in photovoltaic systems based on numerical differentiation and integration of the P − V curves
Authors: Khodapanah Mohammadali , Ghanbari Teymoor , Moshksar Ehsan , Hosseini Zahra
Published: October 2022

Hotspot phenomenon is an expected consequence of long‐term partial shading condition (PSC), which results in early degradation and permanent damage of the shaded cells in the photovoltaic (PV) systems. Hence, partial shading detection and estimation of its intensity is a significant factor to predict the possibility of hotspotting process and its occurrence time for PV system protection. In this paper, two partial shading detection indices are introduced based on the extracted power‐voltage () curves. The first characteristic is related to the real shaded PV system and the second curve is numerically obtained from the equivalent single‐diode circuit model. The proposed PSC detection indices are established according to the difference between the numerical differentiation and integration of the curves from the real PV system and the virtual reference model. These techniques have the advantages to distinguish between temporary and permanent PSC. Moreover, it is possible to estimate the intensity of the shading level and predict the hotspot occurrence time, accordingly. The performance of these methods are confirmed using some simulations and an experimental setup. The results verify the capabilities of the methods for partial shading detection without the requirement of an extra physical cell/module as a reference model.
Regulation of Progression and Resolution of Liver Fibrosis by Immune Cells
Authors: Koda Yuzo , Nakamoto Nobuhiro , Kanai Takanori
Published: October 2022

The excessive accumulation of extracellular matrix proteins results in fibrosis—a condition implicated in several diseased conditions, such as nonalcoholic steatohepatitis, viral hepatitis, and autoimmune hepatitis. Despite its prevalence, direct and effective treatments for fibrosis are lacking, warranting the development of better therapeutic strategies. Accumulating evidence has shown that liver fibrosis—a condition previously considered irreversible—is reversible in specific conditions. Immune cells residing in or infiltrating the liver (e.g., macrophages) are crucial in the pathogenesis of fibrosis. Given this background, the roles and action mechanisms of various immune cells and their subsets in the progression and recovery of liver fibrosis, particularly concerning nonalcoholic steatohepatitis, are discussed in this review. Furthermore, the development of better therapeutic strategies based on stage-specific properties and using advanced techniques as well as the mechanisms underlying recovery are elaborated. In conclusion, we consider the review comprehensively provides the present achievements and future possibilities revolving around fibrosis treatment.