bluuebunny/crossref_metadata_2025 huggingface dataset:
All-optical control of spin in a 2D van der Waals magnet
Authors: Da̧browski Maciej , Guo Shi , Strungaru Mara , Keatley Paul S. , Withers Freddie , Santos Elton J. G. , Hicken Robert J.
Published: October 2022

Two-dimensional (2D) van der Waals magnets provide new opportunities for control of magnetism at the nanometre scale via mechanisms such as strain, voltage and the photovoltaic effect. Ultrafast laser pulses promise the fastest and most energy efficient means of manipulating electron spin and can be utilized for information storage. However, little is known about how laser pulses influence the spins in 2D magnets. Here we demonstrate laser-induced magnetic domain formation and all-optical switching in the recently discovered 2D van der Waals ferromagnet CrI3. While the magnetism of bare CrI3 layers can be manipulated with single laser pulses through thermal demagnetization processes, all-optical switching is achieved in nanostructures that combine ultrathin CrI3 with a monolayer of WSe2. The out-of-plane magnetization is switched with multiple femtosecond pulses of either circular or linear polarization, while single pulses result in less reproducible and partial switching. Our results imply that spin-dependent interfacial charge transfer between the WSe2 and CrI3 is the underpinning mechanism for the switching, paving the way towards ultrafast optical control of 2D van der Waals magnets for future photomagnetic recording and device technology.
Human papillomavirus integration perspective in small cell cervical carcinoma
Authors: Wang Xiaoli , Jia Wenlong , Wang Mengyao , Liu Jihong , Zhou Xianrong , Liang Zhiqing , Zhang Qinghua , Long Sixiang , Quzhen Suolang , Li Xiangchun , Tian Qiang , Li Xiong , Sun Haiying , Zhao Caili , Meng Silu , Ning Ruoqi , Xi Ling , Wang Lin , Zhou Shasha , Zhang Jianwei , Wu Li , Chen Yile , Liu Aijun , Ma Yaqi , Zhao Xia , Cheng Xiaodong , Zhang Qing , Han Xiaobing , Pan Huaxiong , Zhang Yuan , Cao Lili , Wang Yiqin , Ling Shaoping , Cao Lihua , Xing Hui , Xu Chang , Sui Long , Wang Shixuan , Zhou Jianfeng , Kong Beihua , Xie Xing , Chen Gang , Li Shuaicheng , Ma Ding , Li Shuang
Published: October 2022

Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, we report human papillomavirus features and genomic landscape in SCCC via high-throughput HPV captured sequencing, whole-genome sequencing, whole-transcriptome sequencing, and OncoScan microarrays. HPV18 infections and integrations are commonly detected. Besides MYC family genes (37.9%), we identify SOX (8.4%), NR4A (6.3%), ANKRD (7.4%), and CEA (3.2%) family genes as HPV-integrated hotspots. We construct the genomic local haplotype around HPV-integrated sites, and find tandem duplications and amplified HPV long control regions (LCR). We propose three prominent HPV integration patterns: duplicating oncogenes (MYCN, MYC, and NR4A2), forming fusions (FGFR3–TACC3 and ANKRD12–NDUFV2), and activating genes (MYC) via the cis-regulations of viral LCRs. Moreover, focal CNA amplification peaks harbor canonical cancer genes including the HPV-integrated hotspots within MYC family, SOX2, and others. Our findings may provide potential molecular criteria for the accurate diagnosis and efficacious therapies for this lethal disease.
A combination of plasma membrane sterol biosynthesis and autophagy is required for shade-induced hypocotyl elongation
Authors: Ince Yetkin Çaka , Krahmer Johanna , Fiorucci Anne-Sophie , Trevisan Martine , Galvão Vinicius Costa , Wigger Leonore , Pradervand Sylvain , Fouillen Laetitia , Van Delft Pierre , Genva Manon , Mongrand Sebastien , Gallart-Ayala Hector , Ivanisevic Julijana , Fankhauser Christian
Published: October 2022

Plant growth ultimately depends on fixed carbon, thus the available light for photosynthesis. Due to canopy light absorption properties, vegetative shade combines low blue (LB) light and a low red to far-red ratio (LRFR). In shade-avoiding plants, these two conditions independently trigger growth adaptations to enhance light access. However, how these conditions, differing in light quality and quantity, similarly promote hypocotyl growth remains unknown. Using RNA sequencing we show that these two features of shade trigger different transcriptional reprogramming. LB induces starvation responses, suggesting a switch to a catabolic state. Accordingly, LB promotes autophagy. In contrast, LRFR induced anabolism including expression of sterol biosynthesis genes in hypocotyls in a manner dependent on PHYTOCHROME-INTERACTING FACTORs (PIFs). Genetic analyses show that the combination of sterol biosynthesis and autophagy is essential for hypocotyl growth promotion in vegetative shade. We propose that vegetative shade enhances hypocotyl growth by combining autophagy-mediated recycling and promotion of specific lipid biosynthetic processes.
Ni-catalyzed carbamoylation of unactivated alkenes for stereoselective construction of six-membered lactams
Authors: Zhang Chenhuan , Wu Xianqing , Xia Tingting , Qu Jingping , Chen Yifeng
Published: October 2022

Nitrogen-based heterocycles have aroused widespread interest due to their reoccurrence in many pharmaceuticals. Amongst these motifs, the enantioenriched lactams are the ubiquitous scaffolds found in myriad biologically active natural products and drugs. Recently, the transition metal-catalyzed asymmetric carbamoylation has been widely employed as a straightforward arsenal for chiral lactam architecture synthesis, including β-lactam and γ-lactam. However, despite the extensive efforts, there still remains no protocol to accomplish the related δ-lactam synthesis. In this manuscript, the Ni-catalyzed enantioselective carbamoylation of unactivated alkenes by the leverage of reductive dicarbofunctionalization strategy allows for the expedient access to two types of mostly common six-membered lactams: 3,4-dihydroquinolinones and 2-piperidinone in high yield and enantioselectivity. This protocol features with good functional group tolerance, as well as broad substrate scope. The newly developed chiral 8-Quinox skeleton ligand is the key parameter for this transformation, which significantly enhances the reactivity and enantioselectivity.
ISG15 conjugation to proteins on nascent DNA mitigates DNA replication stress
Authors: Wardlaw Christopher P. , Petrini John H. J.
Published: October 2022

The pathways involved in suppressing DNA replication stress and the associated DNA damage are critical to maintaining genome integrity. The Mre11 complex is unique among double strand break (DSB) repair proteins for its association with the DNA replication fork. Here we show that Mre11 complex inactivation causes DNA replication stress and changes in the abundance of proteins associated with nascent DNA. One of the most highly enriched proteins at the DNA replication fork upon Mre11 complex inactivation was the ubiquitin like protein ISG15. Mre11 complex deficiency and drug induced replication stress both led to the accumulation of cytoplasmic DNA and the subsequent activation of innate immune signaling via cGAS-STING-Tbk1. This led toISG15induction and protein ISGylation, including constituents of the replication fork. ISG15 plays a direct role in preventing replication stress. Deletion ofISG15was associated with replication fork stalling, tonic ATR activation, genomic aberrations, and sensitivity to aphidicolin. These data reveal a previously unrecognized role for ISG15 in mitigating DNA replication stress and promoting genomic stability.
Switching p-type to high-performance n-type organic electrochemical transistors via doped state engineering
Authors: Li Peiyun , Shi Junwei , Lei Yuqiu , Huang Zhen , Lei Ting
Published: October 2022

High-performance n-type organic electrochemical transistors (OECTs) are essential for logic circuits and sensors. However, the performances of n-type OECTs lag far behind that of p-type ones. Conventional wisdom posits that the LUMO energy level dictates the n-type performance. Herein, we show that engineering the doped state is more critical for n-type OECT polymers. By balancing more charges to the donor moiety, we could effectively switch a p-type polymer to high-performance n-type material. Based on this concept, the polymer, P(gTDPP2FT), exhibits a record high n-type OECT performance with μC* of 54.8 F cm−1 V−1 s−1, mobility of 0.35 cm2 V−1 s−1, and response speed of τon/τoff = 1.75/0.15 ms. Calculations and comparison studies show that the conversion is primarily due to the more uniform charges, stabilized negative polaron, enhanced conformation, and backbone planarity at negatively charged states. Our work highlights the critical role of understanding and engineering polymers’ doped states.
Molecular characterization of renal cell carcinoma tumors from a phase III anti-angiogenic adjuvant therapy trial
Authors: Motzer Robert J. , Martini Jean-François , Mu Xinmeng J. , Staehler Michael , George Daniel J. , Valota Olga , Lin Xun , Pandha Hardev S. , Ching Keith A. , Ravaud Alain
Published: October 2022

Multigene assays can provide insight into key biological processes and prognostic information to guide development and selection of adjuvant cancer therapy. We report a comprehensive genomic and transcriptomic analysis of tumor samples from 171 patients at high risk for recurrent renal cell carcinoma post nephrectomy from the S-TRAC trial (NCT00375674). We identify gene expression signatures, including STRAC11 (derived from the sunitinib-treated population). The overlap in key elements captured in these gene expression signatures, which include genes representative of the tumor stroma microenvironment, regulatory T cell, and myeloid cells, suggests they are likely to be both prognostic and predictive of the anti-angiogenic effect in the adjuvant setting. These signatures also point to the identification of potential therapeutic targets for development in adjuvant renal cell carcinoma, such as MERTK and TDO2. Finally, our findings suggest that while anti-angiogenic adjuvant therapy might be important, it may not be sufficient to prevent recurrence and that other factors such as immune response and tumor environment may be of greater importance.
Giant g-factors and fully spin-polarized states in metamorphic short-period InAsSb/InSb superlattices
Authors: Jiang Yuxuan , Ermolaev Maksim , Kipshidze Gela , Moon Seongphill , Ozerov Mykhaylo , Smirnov Dmitry , Jiang Zhigang , Suchalkin Sergey
Published: October 2022

Realizing a large Landé g-factor of electrons in solid-state materials has long been thought of as a rewarding task as it can trigger abundant immediate applications in spintronics and quantum computing. Here, by using metamorphic InAsSb/InSb superlattices (SLs), we demonstrate an unprecedented high value of g ≈ 104, twice larger than that in bulk InSb, and fully spin-polarized states at low magnetic fields. In addition, we show that the g-factor can be tuned on demand from 20 to 110 via varying the SL period. The key ingredients of such a wide tunability are the wavefunction mixing and overlap between the electron and hole states, which have drawn little attention in prior studies. Our work not only establishes metamorphic InAsSb/InSb as a promising and competitive material platform for future quantum devices but also provides a new route toward g-factor engineering in semiconductor structures.
Inferring differential subcellular localisation in comparative spatial proteomics using BANDLE
Authors: Crook Oliver M. , Davies Colin T. R. , Breckels Lisa M. , Christopher Josie A. , Gatto Laurent , Kirk Paul D. W. , Lilley Kathryn S.
Published: October 2022

The steady-state localisation of proteins provides vital insight into their function. These localisations are context specific with proteins translocating between different subcellular niches upon perturbation of the subcellular environment. Differential localisation, that is a change in the steady-state subcellular location of a protein, provides a step towards mechanistic insight of subcellular protein dynamics. High-accuracy high-throughput mass spectrometry-based methods now exist to map the steady-state localisation and re-localisation of proteins. Here, we describe a principled Bayesian approach, BANDLE, that uses these data to compute the probability that a protein differentially localises upon cellular perturbation. Extensive simulation studies demonstrate that BANDLE reduces the number of both type I and type II errors compared to existing approaches. Application of BANDLE to several datasets recovers well-studied translocations. In an application to cytomegalovirus infection, we obtain insights into the rewiring of the host proteome. Integration of other high-throughput datasets allows us to provide the functional context of these data.
Elucidating tumor heterogeneity from spatially resolved transcriptomics data by multi-view graph collaborative learning
Authors: Zuo Chunman , Zhang Yijian , Cao Chen , Feng Jinwang , Jiao Mingqi , Chen Luonan
Published: October 2022

Spatially resolved transcriptomics (SRT) technology enables us to gain novel insights into tissue architecture and cell development, especially in tumors. However, lacking computational exploitation of biological contexts and multi-view features severely hinders the elucidation of tissue heterogeneity. Here, we propose stMVC, a multi-view graph collaborative-learning model that integrates histology, gene expression, spatial location, and biological contexts in analyzing SRT data by attention. Specifically, stMVC adopting semi-supervised graph attention autoencoder separately learns view-specific representations of histological-similarity-graph or spatial-location-graph, and then simultaneously integrates two-view graphs for robust representations through attention under semi-supervision of biological contexts. stMVC outperforms other tools in detecting tissue structure, inferring trajectory relationships, and denoising on benchmark slices of human cortex. Particularly, stMVC identifies disease-related cell-states and their transition cell-states in breast cancer study, which are further validated by the functional and survival analysis of independent clinical data. Those results demonstrate clinical and prognostic applications from SRT data.
Spectral interpretation of late-stage mare basalt mineralogy unveiled by Chang’E-5 samples
Authors: Liu Dawei , Wang Xing , Liu Jianjun , Liu Bin , Ren Xin , Chen Yuan , Chen Zhaopeng , Zhang Hongbo , Zhang Guangliang , Zhou Qin , Zhang Zhoubin , Fu Qiang , Li Chunlai
Published: October 2022

The western maria of lunar near-side are widely covered with late-stage mare basalts. Due to the lack of returned samples, the mineralogy of the late-stage basalts was previously speculated as having high abundance of olivine based on remote sensing observation. However, here we show that Chang’E-5 (CE-5) lunar soil samples, the ground truth from past unsampled lunar late-stage mare region, give a different interpretation. Our laboratory spectroscopic and X-ray diffraction (XRD) analyses of the CE-5 soil samples demonstrate that their special spectral signatures are representative of iron-rich high-Ca pyroxene rather than olivine. Considering the spectral and compositional similarities between CE-5 soil samples and lunar late-stage basalts, the mineralogy and petrology of CE-5 samples may be able to be generalized to entire lunar late-stage basalts. Our study would provide a constraint on the thermal evolution of the Moon, especially the young lunar volcanism.
Hierarchical nano-martensite-engineered a low-cost ultra-strong and ductile titanium alloy
Authors: Zhang Chongle , Bao Xiangyun , Hao Mengyuan , Chen Wei , Zhang Dongdong , Wang Dong , Zhang Jinyu , Liu Gang , Sun Jun
Published: October 2022

Due to the low thermal stability of crystallographic boundaries, the grain boundary engineering (GBE) manifests some limits to the fineness and types of microstructures achievable, while unique chemical boundary engineering (CBE) enables us to create a metallic material with an ultrafine hierarchically heterogeneous microstructure for enhancing the mechanical properties of materials. Here, using a low cost metastable Ti-2.8Cr-4.5Zr-5.2Al (wt.%) alloy as a model material, we create a high density of chemical boundaries (CBs) through the significant diffusion mismatch between Cr and Al alloying elements to architecture hierarchical nano-martensites with an average thickness of ~20 nm. For this metastable titanium alloy, the significantly enhanced yield strength originates from dense nano-martensitic interface strengthening, meanwhile the large ductility is attributed to the multi-stage strain hardening of hierarchical 3D α'/β lamellae assisted by equiaxed primary α (αp) nodules. The hierarchical nano-martensite engineering strategy confers our alloy a desired combination of strength and ductility, which can potentially be applied to many transformable alloys, and reveal a new target in microstructural design for ultrastrong-yet-ductile structural materials.
Direct production of olefins from syngas with ultrahigh carbon efficiency
Authors: Yu Hailing , Wang Caiqi , Lin Tiejun , An Yunlei , Wang Yuchen , Chang Qingyu , Yu Fei , Wei Yao , Sun Fanfei , Jiang Zheng , Li Shenggang , Sun Yuhan , Zhong Liangshu
Published: October 2022

Syngas conversion serves as a competitive strategy to produce olefins chemicals from nonpetroleum resources. However, the goal to achieve desirable olefins selectivity with limited undesired C1 by-products remains a grand challenge. Herein, we present a non-classical Fischer-Tropsch to olefins process featuring high carbon efficiency that realizes 80.1% olefins selectivity with ultralow total selectivity of CH4and CO2(<5%) at CO conversion of 45.8%. This is enabled by sodium-promoted metallic ruthenium (Ru) nanoparticles with negligible water-gas-shift reactivity. Change in the local electronic structure and the decreased reactivity of chemisorbed H species on Ru surfaces tailor the reaction pathway to favor olefins production. No obvious deactivation is observed within 550 hours and the pellet catalyst also exhibits excellent catalytic performance in a pilot-scale reactor, suggesting promising practical applications.
Dual sensing signal decoupling based on tellurium anisotropy for VR interaction and neuro-reflex system application
Authors: Li Linlin , Zhao Shufang , Ran Wenhao , Li Zhexin , Yan Yongxu , Zhong Bowen , Lou Zheng , Wang Lili , Shen Guozhen
Published: October 2022

Anisotropy control of the electronic structure in inorganic semiconductors is an important step in developing devices endowed with multi-function. Here, we demonstrate that the intrinsic anisotropy of tellurium nanowires can be used to modulate the electronic structure and piezoelectric polarization and decouple pressure and temperature difference signals, and realize VR interaction and neuro-reflex applications. The architecture design of the device combined with self-locking effect can eliminate dependence on displacement, enabling a single device to determine the hardness and thermal conductivity of materials through a simple touch. We used a bimodal Te-based sensor to develop a wearable glove for endowing real objects to the virtual world, which greatly improves VR somatosensory feedback. In addition, we successfully achieved stimulus recognition and neural-reflex in a rabbit sciatic nerve model by integrating the sensor signals using a deep learning technique. In view of in-/ex-vivo feasibility, the bimodal Te-based sensor would be considered a novel sensing platform for a wide range application of metaverse, AI robot, and electronic medicine.
One-pot H/D exchange and low-coordinated iron electrocatalyzed deuteration of nitriles in D2O to α,β-deuterio aryl ethylamines
Authors: Li Rui , Wu Yongmeng , Wang Changhong , He Meng , Liu Cuibo , Zhang Bin
Published: October 2022

Developing a step-economical approach for efficient synthesis of α,β-deuterio aryl ethylamines (α,β-DAEAs) with high deuterium ratios using an easy-to-handle deuterated source under ambient conditions is highly desirable. Here we report a room-temperature one-pot two-step transformation of aryl acetonitriles to α,β-DAEAs with up to 92% isolated yield and 99% α,β-deuterium ratios using D2O as a deuterium source. The process involves a fast α-C − H/C − D exchange and tandem electroreductive deuteration of C ≡ N over an in situ formed low-coordinated Fe nanoparticle cathode. The moderate adsorptions of nitriles/imine intermediates and the promoted formation of active hydrogen (H*) on unsaturated Fe sites facilitate the electroreduction process. In situ Raman confirms co-adsorption of aryl rings and the C ≡ N group on the Fe surface. A proposed H*-addition pathway is confirmed by the detected hydrogen and carbon radicals. Wide substrate scope, parallel synthesis of multiple α,β-DAEAs, and successful preparation of α,β-deuterated Melatonin and Komavine highlight the potential.
Extending fluorescence anisotropy to large complexes using reversibly switchable proteins
Authors: Volpato Andrea , Ollech Dirk , Alvelid Jonatan , Damenti Martina , Müller Barbara , York Andrew G , Ingaramo Maria , Testa Ilaria
Published: October 2022

The formation of macromolecular complexes can be measured by detection of changes in rotational mobility using time-resolved fluorescence anisotropy. However, this method is limited to relatively small molecules (~0.1–30 kDa), excluding the majority of the human proteome and its complexes. We describe selective time-resolved anisotropy with reversibly switchable states (STARSS), which overcomes this limitation and extends the observable mass range by more than three orders of magnitude. STARSS is based on long-lived reversible molecular transitions of switchable fluorescent proteins to resolve the relatively slow rotational diffusivity of large complexes. We used STARSS to probe the rotational mobility of several molecular complexes in cells, including chromatin, the retroviral Gag lattice and activity-regulated cytoskeleton-associated protein oligomers. Because STARSS can probe arbitrarily large structures, it is generally applicable to the entire human proteome.
Health effects associated with consumption of unprocessed red meat: a Burden of Proof study
Authors: Lescinsky Haley , Afshin Ashkan , Ashbaugh Charlie , Bisignano Catherine , Brauer Michael , Ferrara Giannina , Hay Simon I. , He Jiawei , Iannucci Vincent , Marczak Laurie B. , McLaughlin Susan A. , Mullany Erin C. , Parent Marie C. , Serfes Audrey L. , Sorensen Reed J. D. , Aravkin Aleksandr Y. , Zheng Peng , Murray Christopher J. L.
Published: October 2022

Characterizing the potential health effects of exposure to risk factors such as red meat consumption is essential to inform health policy and practice. Previous meta-analyses evaluating the effects of red meat intake have generated mixed findings and do not formally assess evidence strength. Here, we conducted a systematic review and implemented a meta-regression—relaxing conventional log-linearity assumptions and incorporating between-study heterogeneity—to evaluate the relationships between unprocessed red meat consumption and six potential health outcomes. We found weak evidence of association between unprocessed red meat consumption and colorectal cancer, breast cancer, type 2 diabetes and ischemic heart disease. Moreover, we found no evidence of an association between unprocessed red meat and ischemic stroke or hemorrhagic stroke. We also found that while risk for the six outcomes in our analysis combined was minimized at 0 g unprocessed red meat intake per day, the 95% uncertainty interval that incorporated between-study heterogeneity was very wide: from 0–200 g d−1. While there is some evidence that eating unprocessed red meat is associated with increased risk of disease incidence and mortality, it is weak and insufficient to make stronger or more conclusive recommendations. More rigorous, well-powered research is needed to better understand and quantify the relationship between consumption of unprocessed red meat and chronic disease.
Health effects associated with smoking: a Burden of Proof study
Authors: Dai Xiaochen , Gil Gabriela F. , Reitsma Marissa B. , Ahmad Noah S. , Anderson Jason A. , Bisignano Catherine , Carr Sinclair , Feldman Rachel , Hay Simon I. , He Jiawei , Iannucci Vincent , Lawlor Hilary R. , Malloy Matthew J. , Marczak Laurie B. , McLaughlin Susan A. , Morikawa Larissa , Mullany Erin C. , Nicholson Sneha I. , O’Connell Erin M. , Okereke Chukwuma , Sorensen Reed J. D. , Whisnant Joanna , Aravkin Aleksandr Y. , Zheng Peng , Murray Christopher J. L. , Gakidou Emmanuela
Published: October 2022

As a leading behavioral risk factor for numerous health outcomes, smoking is a major ongoing public health challenge. Although evidence on the health effects of smoking has been widely reported, few attempts have evaluated the dose–response relationship between smoking and a diverse range of health outcomes systematically and comprehensively. In the present study, we re-estimated the dose–response relationships between current smoking and 36 health outcomes by conducting systematic reviews up to 31 May 2022, employing a meta-analytic method that incorporates between-study heterogeneity into estimates of uncertainty. Among the 36 selected outcomes, 8 had strong-to-very-strong evidence of an association with smoking, 21 had weak-to-moderate evidence of association and 7 had no evidence of association. By overcoming many of the limitations of traditional meta-analyses, our approach provides comprehensive, up-to-date and easy-to-use estimates of the evidence on the health effects of smoking. These estimates provide important information for tobacco control advocates, policy makers, researchers, physicians, smokers and the public.
Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial
Authors: Garvey W. Timothy , Batterham Rachel L. , Bhatta Meena , Buscemi Silvio , Christensen Louise N. , Frias Juan P. , Jódar Esteban , Kandler Kristian , Rigas Georgia , Wadden Thomas A. , Wharton Sean ,   the STEP 5 Study Group
Published: October 2022

The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes. The co-primary endpoints were the percentage change in body weight and achievement of weight loss of ≥5% at week 104. Efficacy was assessed among all randomized participants regardless of treatment discontinuation or rescue intervention. From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended the end-of-trial safety visit). Most participants were female (236 (77.6%)) and white (283 (93.1%)), with a mean (s.d.) age of 47.3 (11.0) years, body mass index of 38.5 (6.9) kg m–2 and weight of 106.0 (22.0) kg. The mean change in body weight from baseline to week 104 was −15.2% in the semaglutide group (n = 152) versus −2.6% with placebo (n = 152), for an estimated treatment difference of −12.6 %-points (95% confidence interval, −15.3 to −9.8; P < 0.0001). More participants in the semaglutide group than in the placebo group achieved weight loss ≥5% from baseline at week 104 (77.1% versus 34.4%; P < 0.0001). Gastrointestinal adverse events, mostly mild-to-moderate, were reported more often with semaglutide than with placebo (82.2% versus 53.9%). In summary, in adults with overweight (with at least one weight-related comorbidity) or obesity, semaglutide treatment led to substantial, sustained weight loss over 104 weeks versus placebo. NCT03693430
The Africans in America study demonstrates that subclinical cardiovascular risk differs by etiology of abnormal glucose tolerance
Authors: Wentzel Annemarie , Duhuze Karera M. Grace , Patterson Arielle C. , Waldman Zoe C. , Schenk Blayne R. , Mabundo Lilian S. , DuBose Christopher W. , Horlyck-Romanovsky Margrethe F. , Sumner Anne E.
Published: October 2022

Abnormal-glucose tolerance (Abnl-GT) is due to an imbalance between β-cell function and insulin resistance (IR) and is a major risk factor in cardiovascular disease (CVD). In sub-Saharan Africa, β-cell failure is emerging as an important cause of Abnl-GT (Abnl-GT-β-cell-failure). Visceral adipose tissue (VAT) volume and hyperlipidemia are major contributors to CVD risk when Abnl-GT is due to IR (Abnl-GT-IR). Yet, the CVD profile associated with Abnl-GT-β-cell failure is unknown. Therefore, our goals in 450 African-born Blacks (Male: 65%; Age: 39 ± 10 years; BMI 28 ± 5 kg/m2), living in America were to: (1) determine Abnl-GT prevalence and etiology; (2) assess by Abnl-GT etiology, associations between four understudied subclinical CVD risk factors in Africans: (a) subclinical myocardial damage (high-sensitivity troponin T (hs-cTnT)); (b) neurohormonal regulation (N-terminal pro-Brain-natriuretic peptide (NT-proBNP)); (c) coagulability (fibrinogen); (d) inflammation (high-sensitivity C-reactive protein (hsCRP)), as well as HbA1c, Cholesterol/HDL ratio and VAT. Glucose tolerance status was determined by the OGTT. IR was defined by the threshold at the lowest quartile for the Matsuda Index (≤ 2.97). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell-failure was defined as Abnl-GT without IR. VAT was assessed by CT-scan. For both the Abnl-GT-β-cell-failure and Abnl-GT-IR groups, four multiple regression models were performed for hs-cTnT; NT-proBNP; fibrinogen and hsCRP, as dependent variables, with the remaining three biomarkers and HbA1c, Cholesterol/HDL and VAT as independent variables. Abnl-GT occurred in 38% (170/450). In the Abnl-GT group, β-cell failure occurred in 58% (98/170) and IR in 42% (72/170). VAT and Cholesterol/HDL were significantly lower in Abnl-GT-β-cell-failure group vs the Abnl-GT-IR group (both P < 0.001). In the Abnl-GT-β-cell-failure group: significant associations existed between hscTnT, fibrinogen, hs-CRP, and HbA1c (all P < 0.05), and none with Cholesterol/HDL or VAT. In Abnl-GT-IR: hs-cTnT, fibrinogen and hsCRP significantly associated with Cholesterol/HDL (all P < 0.05) and NT-proBNP inversely related to fibrinogen, hsCRP, HbA1c, Cholesterol/HDL, and VAT (all P < 0.05). The subclinical CVD risk profile differed between Abnl-GT-β-cell failure and Abnl-GT-IR. In Abnl-GT-β-cell failure subclinical CVD risk involved subclinical-myocardial damage, hypercoagulability and increased inflammation, but not hyperlipidemia or visceral adiposity. For Abnl-GT-IR, subclinical CVD risk related to subclinical myocardial damage, neurohormonal dysregulation, inflammation associated with hyperlipidemia and visceral adiposity.

ClinicalTrials.gov Identifier: NCT00001853.
Development and large-scale validation of the Watch Walk wrist-worn digital gait biomarkers
Authors: Chan Lloyd L. Y. , Choi Tiffany C. M. , Lord Stephen R. , Brodie Matthew A.
Published: October 2022

Digital gait biomarkers (including walking speed) indicate functional decline and predict hospitalization and mortality. However, waist or lower-limb devices often used are not designed for continuous life-long use. While wrist devices are ubiquitous and many large research repositories include wrist-sensor data, widely accepted and validated digital gait biomarkers derived from wrist-worn accelerometers are not available yet. Here we describe the development of advanced signal processing algorithms that extract digital gait biomarkers from wrist-worn devices and validation using 1-week data from 78,822 UK Biobank participants. Our gait biomarkers demonstrate good test–retest-reliability, strong agreement with electronic walkway measurements of gait speed and self-reported pace and significantly discriminate individuals with poor self-reported health. With the almost universal uptake of smart-watches, our algorithms offer a new approach to remotely monitor life-long population level walking speed, quality, quantity and distribution, evaluate disease progression, predict risk of adverse events and provide digital gait endpoints for clinical trials.
N-glycosylation of cervicovaginal fluid reflects microbial community, immune activity, and pregnancy status
Authors: Wu Gang , Grassi Paola , MacIntyre David A. , Molina Belen Gimeno , Sykes Lynne , Kundu Samit , Hsiao Cheng-Te , Khoo Kay-Hooi , Bennett Phillip R. , Dell Anne , Haslam Stuart M.
Published: October 2022

Human cervicovaginal fluid (CVF) is a complex, functionally important and glycan rich biological fluid, fundamental in mediating physiological events associated with reproductive health. Using a comprehensive glycomic strategy we reveal an extremely rich and complex N-glycome in CVF of pregnant and non-pregnant women, abundant in paucimannose and high mannose glycans, complex glycans with 2–4 N-Acetyllactosamine (LacNAc) antennae, and Poly-LacNAc glycans decorated with fucosylation and sialylation. N-glycosylation profiles were observed to differ in relation to pregnancy status, microbial composition, immune activation, and pregnancy outcome. Compared to CVF from women experiencing term birth, CVF from women who subsequently experienced preterm birth showed lower sialylation, which correlated to the presence of a diverse microbiome, and higher fucosylation, which correlated positively to pro-inflammatory cytokine concentration. This study is the first step towards better understanding the role of cervicovaginal glycans in reproductive health, their contribution to the mechanism of microbial driven preterm birth, and their potential for preventative therapy.
Empathy and correct mental state inferences both promote prosociality
Authors: Lehmann Konrad , Böckler Anne , Klimecki Olga , Müller-Liebmann Christian , Kanske Philipp
Published: October 2022

In a world with rapidly increasing population that competes for the earth’s limited resources, cooperation is crucial. While research showed that empathizing with another individual in need enhances prosociality, it remains unclear whether correctly inferring the other’s inner, mental states on a more cognitive level (i.e., mentalizing) elicits helping behavior as well. We applied a video-based laboratory task probing empathy and a performance measure of mentalizing in adult volunteers (N = 94) and assessed to which extent they were willing to help the narrators in the videos. We replicate findings that an empathy induction leads to more prosocial decisions. Crucially, we also found that correct mentalizing increases the willingness to help. This evidence helps clarify an inconsistent picture of the relation between mentalizing and prosociality.
Association between neonatal hyperbilirubinemia and hypoglycemia in Chinese women with diabetes in pregnancy and influence factors
Authors: He Jing , Song Jiayang , Zou Zhijie , Fan Xiaoxiao , Tian Ruixue , Xu Jingqi , Yan Yu , Bai Jinbing , Chen Zhen , Liu Yanqun , Chen Xiaoli
Published: October 2022

This retrospective study aimed to investigate the correlation between neonatal hyperbilirubinemia (NHB) and hypoglycemia (NH) in Chinese women with diabetes in pregnancy (DIP), and the influencing factors. All the data were collected July 1, 2017 and June 30, 2020, and 10,558 Chinese women with DIP and live births were included. Two separate multivariate binary stepwise forward logistic regression analysis calculated OR with 95% CI. The prevalence rates of NHB and NH was respectively 3.65% and 5.82% among women with DIP. The comorbidity of both diseases was 0.59%. NH were 1.81 times (OR 1.81, 1.19–2.76) more likely to have hyperbilirubinemia. NHB is positively correlated with NH (OR 1.93, 1.27–2.92). Increased gestational age has a protective effect on both NH (OR 0.76, 0.68–0.85) and NHB (OR 0.80, 0.69–0.92). Abnormal placental morphology is related to NH (OR 1.55, 1.16–2.08) and NHB (OR 1.64, 1.10–2.45). Regarding neonatal outcomes, congenital heart disease (CHD) (OR 2.16, 1.25–3.73; and OR 10.14, 6.47–15.90) was a risk factor for NH and NHB. NHB and NH were significantly correlated in women with DIP. The offspring of DIP with multiple risk factors have a significantly increased risk of neonatal hyperbilirubinemia.
Stable carbon and nitrogen isotopes identify nuanced dietary changes from the Bronze and Iron Ages on the Great Hungarian Plain
Authors: McCall Ashley , Gamarra Beatriz , Carlson Kellie Sara Duffett , Bernert Zsolt , Cséki Andrea , Csengeri Piroska , Domboróczki László , Endrődi Anna , Hellebrandt Magdolna , Horváth Antónia , Király Ágnes , Kiss Krisztián , Koós Judit , Kovács Péter , Köhler Kitti , Szolnoki László , Zoffmann Zsuzsanna K. , Sirak Kendra , Szeniczey Tamás , Dani János , Hajdu Tamás , Pinhasi Ron
Published: October 2022

The Great Hungarian Plain (GHP) served as a geographic funnel for population mobility throughout prehistory. Genomic and isotopic research demonstrates non-linear genetic turnover and technological shifts between the Copper and Iron Ages of the GHP, which influenced the dietary strategies of numerous cultures that intermixed and overlapped through time. Given the complexities of these prehistoric cultural and demographic processes, this study aims to identify and elucidate diachronic and culture-specific dietary signatures. We report on stable carbon and nitrogen isotope ratios from 74 individuals from nineteen sites in the GHP dating to a ~ 3000-year time span between the Early Bronze and Early Iron Ages. The samples broadly indicate a terrestrial C3 diet with nuanced differences amongst populations and through time, suggesting exogenous influences that manifested in subsistence strategies. Slightly elevated δ15N values for Bronze Age samples imply higher reliance on protein than in the Iron Age. Interestingly, the Füzesabony have carbon values typical of C4 vegetation indicating millet consumption, or that of a grain with comparable δ13C ratios, which corroborates evidence from outside the GHP for its early cultivation during the Middle Bronze Age. Finally, our results also suggest locally diverse subsistence economies for GHP Scythians.
In situ synthesis of hierarchically-assembled three-dimensional ZnS nanostructures and 3D printed visualization
Authors: Lim Taehwan , Seol Seung Kwon , Kim Hyo-Jeong , Huh Yang Hoon , Jung Yeonwoong , Chung Hee-Suk , Kim Jung Han
Published: October 2022

Nanomaterials have gained enormous interest in improving the performance of energy harvest systems, biomedical devices, and high-strength composites. Many studies were performed fabricating more elaborate and heterogeneous nanostructures then the structures were characterized using TEM tomographic images, upgrading the fabrication technique. Despite the effort, intricate fabrication process, agglomeration characteristic, and non-uniform output were still limited to presenting the 3D panoramic views straightforwardly. Here we suggested in situ synthesis method to prepare complex and hierarchically-assembled nanostructures that consisted of ZnS nanowire core and nanoparticles under Ag2S catalyst. We demonstrated that the vaporized Zn and S were solidified in different shapes of nanostructures with the temperatures solely. To our knowledge, this is the first demonstration of synthesizing heterogeneous nanostructures, consisting of a nanowire from the vapor–liquid–solid and then nanoparticles from the vapor–solid grown mechanism by in situ temperature control. The obtained hierarchically-assembled ZnS nanostructures were characterized by various TEM technologies, verifying the crystal growth mechanism. Lastly, electron tomography and 3D printing enabled the nanoscale structures to visualize with centimeter scales. The 3D printing from randomly fabricated nanomaterials is rarely performed to date. The collaborating work could offer a better opportunity to fabricate advanced and sophisticated nanostructures.
Role of Klebsiella pneumoniae Type VI secretion system (T6SS) in long-term gastrointestinal colonization
Authors: Merciecca Thomas , Bornes Stéphanie , Nakusi Laurence , Theil Sébastien , Rendueles Olaya , Forestier Christiane , Miquel Sylvie
Published: October 2022

Type VI secretion systems (T6SS), recently described in hypervirulentK. pneumoniae(hvKp) strains,are involved in bacterial warfare but their role in classical clinical strains (cKp) has been little investigated.In silico analysis indicated the presence of T6SS clusters (from zero to four), irrespective of the strains origin or virulence, with a high prevalence in theK. pneumoniaespecies (98%). In the strain CH1157, two T6SS-apparented pathogenicity islands were detected, T6SS-1 and -2, harboring a phospholipase-encoding gene (tle1) and a potential new effector-encoding gene namedtke(Type VIKlebsiellaeffector). Tle1 expression inEscherichia coliperiplasm affected cell membrane permeability. T6SS-1 isogenic mutants colonized the highest gastrointestinal tract of mice less efficiently than their parental strain, at long term. Comparative analysis of faecal 16S sequences indicated that T6SS-1 impaired the microbiota richness and its resilience capacity. Oscillospiraceae family members could be specific competitors for the long-term gut establishment ofK. pneumoniae.
Investigating the role of common and rare variants in multiplex multiple sclerosis families reveals an increased burden of common risk variation
Authors: Everest Elif , Ahangari Mohammad , Uygunoglu Ugur , Tutuncu Melih , Bulbul Alper , Saip Sabahattin , Duman Taskin , Sezerman Ugur , Reich Daniel S. , Riley Brien P. , Siva Aksel , Tahir Turanli Eda
Published: October 2022

Many multiple sclerosis (MS)-associated common risk variants as well as candidate low-frequency and rare variants have been identified; however, approximately half of MS heritability remains unexplained. We studied seven multiplex MS families, six of which with parental consanguinity, to identify genetic factors that increase MS risk. Candidate genomic regions were identified through linkage analysis and homozygosity mapping, and fully penetrant, rare, and low-frequency variants were detected by exome sequencing. Weighted sum score and polygenic risk score (PRS) analyses were conducted in MS families (24 affected, 17 unaffected), 23 sporadic MS cases, 63 individuals in 19 non-MS control families, and 1272 independent, ancestry-matched controls. We found that familial MS cases had a significantly higher common risk variation burden compared with population controls and control families. Sporadic MS cases tended to have a higher PRS compared with familial MS cases, suggesting the presence of a higher rare risk variation burden in the families. In line with this, score distributions among affected and unaffected family members within individual families showed that known susceptibility alleles can explain disease development in some high-risk multiplex families, while in others, additional genetic contributors increase MS risk.
Rats use strategies to make object choices in spontaneous object recognition tasks
Authors: Ross T. W. , Easton A.
Published: October 2022

Rodent spontaneous object recognition (SOR) paradigms are widely used to study the mechanisms of complex memory in many laboratories. Due to the absence of explicit reinforcement in these tasks, there is an underlying assumption that object exploratory behaviour is ‘spontaneous’. However, rodents can strategise, readily adapting their behaviour depending on the current information available and prior predications formed from learning and memory. Here, using the object-place-context (episodic-like) recognition task and novel analytic methods relying on multiple trials within a single session, we demonstrate that rats use a context-based or recency-based object recognition strategy for the same types of trials, depending on task conditions. Exposure to occasional ambiguous conditions changed animals’ responses towards a recency-based preference. However, more salient and predictable conditions led to animals exploring objects on the basis of episodic novelty reliant on contextual information. The results have important implications for future research using SOR tasks, especially in the way experimenters design, analyse and interpret object recognition experiments in non-human animals.
Deep supervision and atrous inception-based U-Net combining CRF for automatic liver segmentation from CT
Authors: Lv Peiqing , Wang Jinke , Zhang Xiangyang , Shi Changfa
Published: October 2022

Due to low contrast and the blurred boundary between liver tissue and neighboring organs sharing similar intensity values, the problem of liver segmentation from CT images has not yet achieved satisfactory performance and remains a challenge. To alleviate these problems, we introduce deep supervision (DS) and atrous inception (AI) technologies with conditional random field (CRF) and propose three major improvements that are experimentally shown to have substantive and practical value. First, we replace the encoder's standard convolution with the residual block. Residual blocks can increase the depth of the network. Second, we provide an AI module to connect the encoder and decoder. AI allows us to obtain multi-scale features. Third, we incorporate the DS mechanism into the decoder. This helps to make full use of information of the shallow layers. In addition, we employ the Tversky loss function to balance the segmented and non-segmented regions and perform further refinement with a dense CRF. Finally, we extensively validate the proposed method on three public databases: LiTS17, 3DIRCADb, and SLiver07. Compared to the state-of-the-art methods, the proposed method achieved increased segmentation accuracy for the livers with low contrast and the fuzzy boundary between liver tissue and neighboring organs and is, therefore, more suited for automatic segmentation of these livers.
Inkjet printing of mechanochromic fluorenylidene-acridane
Authors: Ogumi Keisuke , Nagata Kohki , Takimoto Yuki , Mishiba Kentaro , Matsuo Yutaka
Published: October 2022

In mechanochromic material research, a serious problem is that mechanical treatment cannot be applied to the materials because of their responsiveness to stimuli. Inkjet printing is a useful solution deposition method for electronics, but materials must be processed to be suitable for an inkjet printer. Fluorenylidene-acridane (FA) exhibits ground-state mechanochromism with visual color changes and responds not only to mechanical pressure but also to alcohol. Alcohol inhibits the color change induced by mechanical stimulation because the mechanochromism of FA is based on a conformational change in its molecular structure. This phenomenon suggests that the mechanochromism of FA can be controlled using alcohol. For use in inkjet printing, minute particles of FA obtained by bead milling in ethanol were investigated for uniformity and size by scanning electron microscopy and gas adsorption measurement. Also, ink containing FA particles was prepared and examined for physical properties such as viscosity and surface tension. It was confirmed that the inkjet-printed pattern demonstrated visual color changes between yellow and green in response to mechanical pressure and alcohol. This report describing the control of mechanochromism and its specific application is expected to contribute to broadening the mechanochromic materials research field.