bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep disturbances may influence lifestyle behaviours in women with self-reported polycystic ovary syndrome
Authors: Bennett Christie J. , Mansfield Darren R. , Mo Lin , Joham Anju E. , Cain Sean W. , Blumfield Michelle L. , Hodge Allison M. , Moran Lisa J.
Published: June 2021

Polycystic ovary syndrome (PCOS) is associated with a higher prevalence of sleep disturbances and obesity. Treatment of PCOS includes modifying lifestyle behaviours associated with weight management. However, poor sleep in the non-PCOS population has been associated with poorer lifestyle behaviours. The aim was to investigate whether sleep disturbance confounds or modifies the association between lifestyle factors and PCOS. This was a cross-sectional analysis from the Australian Longitudinal Study on Women’s Health cohort aged 31–36 years in 2009 were analysed (n 6067, 464 PCOS, 5603 non-PCOS). Self-reported data were collected on PCOS, anthropometry, validated modified version of the Active Australia Physical Activity survey, validated FFQ and sleep disturbances through latent class analysis. Women with PCOS had greater adverse sleep symptoms including severe tiredness (P = 0·001), difficulty sleeping (P < 0·001) and restless sleep (P < 0·001), compared with women without PCOS. Women with PCOS also had higher energy consumption (6911 (sd 2453) v. 6654 (sd 2215) kJ, P = 0·017), fibre intake (19·8 (sd 7·8) v. 18·9 (sd 6·9) g, P = 0·012) and diet quality (dietary guidelines index (DGI)) (88·1 (sd 11·6) v. 86·7 (sd 11·1), P = 0·008), lower glycaemic index (50·2 (sd 4·0) v. 50·7 (sd 3·9), P = 0·021) and increased sedentary behaviour (6·3 (sd 2·8) v. 5·9 (sd 2·8) h, P = 0·009). There was a significant interaction between PCOS and sleep disturbances for DGI (P = 0·035), therefore only for women who had adequate sleep was PCOS associated with a higher DGI. For women with poorer sleep, there was no association between PCOS and DGI. The association between PCOS and improved diet quality may only be maintained if women can obtain enough good quality sleep.
Alcohol and early mortality (before 65 years) in the ‘Seguimiento Universidad de Navarra’ (SUN) cohort: does any level reduce mortality?
Authors: Martínez-González Miguel Angel , Barbería-Latasa María , Pérez de Rojas Javier , Domínguez Rodriguez Ligia Juliana , Gea Sánchez Alfredo
Published: June 2021

The aim of this study was to assess the association between alcohol intake and premature mortality (younger than 65 years) and to explore the effect of potential alcohol underreporting by heavy drinkers. We followed-up 20 272 university graduates. Four categories of alcohol intake were considered (abstainer, light, moderate and heavy consumption). Repeated measurements of alcohol intake and updated information on confounders were used in time-dependent Cox models. Potential underreporting of alcohol intake by some heavy drinkers (likely misclassified as light or moderate drinkers) was explicitly addressed in an attempt to correct potential underreporting by using indirect information. During 12·3 years of median follow-up (interquartile range: 6·8–15·0), 226 participants died before their 65th birthday. A higher risk of early mortality was found for the highest category of alcohol intake (≥50 g/d) in comparison with abstention (multivariable-adjusted hazard ratio (HR) = 2·82, 95 % CI 1·38, 5·79). In analyses of alcohol as a continuous variable, the multivariable-adjusted HR was 1·17 (95 % CI 1·08, 1·26), for each 10 g/d of alcohol. This harmful linear association was present both in uncorrected models and in models corrected for potential underreporting. No significant inverse association between light or moderate alcohol intake and premature mortality was observed, even after correcting for potential misclassification. Alcohol intake exhibited a harmful linear dose–response association with premature mortality (<65 years) in this young and highly educated Mediterranean cohort. Our attempts to correct for potential misclassification did not substantially change these results.
Hegemonic Muslim Masculinities and Their Others: Perspectives from South and Southeast Asia
Authors: Peletz Michael G.
Published: June 2021

This article provides ethnographic, comparative, and theoretical perspectives on Muslim masculinities in South and Southeast Asia, home to more than half the world's 1.9 billion Muslims. Its empirical and thematic focus broadens the scholarly discussion of gender and sexuality among Muslims insofar as most of the literature deals with the Middle East and North Africa and is devoted to women and the discourses and practices of femininity and sexuality associated with them. More specifically, the article develops theoretical insights bearing on gender hegemonies and the pluralities and hierarchies of discourses on masculinities in the Muslim-majority nations of Pakistan and Malaysia, each of which illustrates broad trends in the region. It thus sheds important light on the empirical diversity of Muslim masculinities (amidst commonalities) and some of the ways they have been informed by locally and regionally variable macro-level processes keyed to colonialism, postcolonial nation-building, global/neoliberal capitalism, and post-Cold War geopolitical struggles including the Global War on Terror.
A NOTE ON RANK TWO STABLE BUNDLES OVER SURFACES
Authors: REYES-AHUMADA GRACIELA , ROA-LEGUIZAMÓN L. , TORRES-LÓPEZ H.
Published: June 2021

Let π : X → C be a fibration with integral fibers over a curve C and consider a polarization H on the surface X. Let E be a stable vector bundle of rank 2 on C. We prove that the pullback π*(E) is a H-stable bundle over X. This result allows us to relate the corresponding moduli spaces of stable bundles $${{\mathcal M}_C}(2,d)$$ and $${{\mathcal M}_{X,H}}(2,df,0)$$ through an injective morphism. We study the induced morphism at the level of Brill–Noether loci to construct examples of Brill–Noether loci on fibered surfaces. Results concerning the emptiness of Brill–Noether loci follow as a consequence of a generalization of Clifford’s Theorem for rank two bundles on surfaces.
Chitosan and microbial inoculants in whole-plant soybean silage
Authors: de Morais J. P. G. , Cantoia Júnior R. , Garcia T. M. , Capucho E. , Campana M. , Gandra J. R. , Ghizzi Lucas G. , Del Valle T. A.
Published: June 2021

Whole-plant soybean silage (WPSS) is a potential high-protein roughage source for ruminant diets. However, WPSS can be difficult to ensile and fermentation is a challenge. This study was conducted to evaluate the effect of chitosan and microbial inoculants on fermentation profile, fermentation losses, chemical composition, and in vitro degradation of WPSS. Forty experimental silos (PVC tubing with 28 cm i.d. and 25 cm height) were produced. Soybean plants from 10 plots were ensiled in a completely randomized block design to evaluate the following treatments: (1) control (CON): WPSS without additives; (2) chitosan (CHI): WPSS additive with 6 g/kg DM of chitosan; (3) LBB: WPSS treated with 5.0 × 107 colony-forming units (CFU) of Lactobacillus buchneri (NCIM 40788) per kg of fresh matter and (4) LPP: WPSS treated with 1.6 × 108 CFU of Lactobacillus plantarum and 1.6 × 108 CFU of Pediococcus acidilactici per kg of fresh matter. Silos were opened 120 days after ensiling. Microbial inoculants reduced silage pH, whereas LPP-treated silos showed the lowest concentration of NH3-N, ethanol, butyric, acetic, branched-chain, and propionic organic acids. LBB-treatment decreased lactic acid bacteria (LAB) count relative to other treatments, and LPP-treatment showed the lowest fermentation losses, improving dry matter (DM) recovery. Relative to other treatments, LPP increased silage DM, organic matter, and decreased acid detergent insoluble crude protein (CP), improving DM and neutral detergent fibre in vitro degradation. Treatments showed no effect on silage aerobic stability. Thus, LPP-treatment improves fermentation profile, reduces fermentation losses, and increases the nutritional value of WPSS.
Mid upper arm circumference as an alternative measure to assess the nutritional status of adolescents: a study in India based on NFHS-4 data
Authors: Roy Aparna , Sekher T. V.
Published: June 2021

Use of body mass index (BMI) to assess the nutritional status of adolescents requires many resources, especially for country-level assessment. This study aimed to determine the relationship between BMI and mid upper arm circumference (MUAC) among adolescent males and females in India and to examine whether MUAC effectively represents the nutritional status of adolescents. The study utilized anthropometric measurement data collected by India’s National Family Health Survey-4 (2015–16). The weighted sample for analysis included 91,315 female and 14,893 male adolescents. The BMI and MUAC measurements showed a positive correlation in both female and male adolescents. Using BMI-for-ageZ-score classifications, 12.7% of the adolescents were undernourished. Using MUAC (in cm) as per NACS (Nutrition Assessment, Counselling, and Support) guidelines and Mrambaet al.(2017) classified 22.9% and 3.7% of the adolescents as undernourished respectively. Finally, using the MUAC-for-ageZ-score classification, 98.4% of adolescents were determined to be normal and 1.7% undernourished. Sensitivity and specificity tests of the MUAC cut-offs, in comparison with BMI cut-offs, showed that all three MUAC cut-off classifications had high specificity (NACS cut-off: 81.3%; Mrambaet al.cut-off (cm): 97.7%; Mrambaet al.cut-off (Z-score): 99.1%). The NACS cut-off had moderately high sensitivity (52.2%) but the Mrambaet al.cut-offs had low sensitivity (13.3% for the centimetre cut-off and 6.6% for theZ-score cut-off). Sensitivity and specificity tests proved the relationship between BMI and MUAC, and that MUAC represents adolescent nutritional status with considerable efficiency. With further research, it may be established that MUAC is a better and promising measure of adolescent nutrition, having the advantage of needing fewer resources for data collection. The MUAC has the potential to offer a simple and low-resource alternative to BMI to assess nutritional status among adolescents in poor countries.
Self-limited myocarditis presenting with chest pain and ST segment elevation in adolescents after vaccination with the BNT162b2 mRNA vaccine
Authors: Park Jihyun , Brekke Dona R. , Bratincsak Andras
Published: June 2021

Two adolescent males presented within 3 days after the first and second dose of the BNT162b2 vaccine with chest pain. Elevated troponin levels, ST segment elevation, and enhancement of the myocardium in cardiac MRI suggested myocarditis. Left ventricular function remained normal, symptoms resolved, and patients were discharged in 4 days. BNT162b2 vaccine may be associated with self-limited myocarditis in youth.
How Do You Solve a Problem Like Maria?US – Countervailing Measures (China) (21.5)
Authors: Nelson Douglas
Published: June 2021

The rise of China as a genuine world power, economically and militarily, constitutes the gravest challenge faced by the liberal international order constructed in the aftermath of the Great Depression and the Second World War. A major source of strain in the trade relations between China and the other core members of the liberal world trading system is its extensive use of state-owned enterprises as an instrument of general (domestic) economic policy. This paper builds on Ruggie's theory of embedded liberalism and the theory of economic policy to characterize the political and economic difficulties and opportunities in moving toward a new regime for dealing with subsidies. The conclusion sketches some goals such a regime should seek to embody.
Exploring the concurrent use of standardised and idiographic measures to assess cognitive behavioural therapy in a university student with autistic spectrum condition – a single case experimental design
Authors: Birdsey Nicola , Walz Linda
Published: June 2021

Limited research has directly addressed the challenges of higher education for students with autism, who face additional difficulties in navigating social, personal and academic obstacles. With more students experiencing mental health difficulties whilst at university, therapeutic interventions on offer need to be suitable for those accessing support. Cognitive behavioural therapy (CBT) is widely used to support university students, as it is firmly established as an effective treatment for a range of issues, including social and generalised anxiety in typically developing populations (NICE, 2013; NICE, 2019). However, the efficacy of CBT for individuals with autistic spectrum condition (ASC) is less well known, despite the high prevalence rates of anxiety in this population. This paper seeks to address a gap in the literature and uses a single-case (A-B) experimental design over 16 sessions to reduce co-morbid social and generalised anxiety in a university student with high-functioning ASC. Clark’s (2001) cognitive model of social anxiety and Wells’ (1997) cognitive model of generalised anxiety were employed to formulate anxiety experienced in this case. Standardised outcome measures were used for social anxiety, i.e. the Social Phobia Inventory (SPIN), and generalised anxiety, i.e. the Generalised Anxiety Disorder-7 (GAD-7), in conjunction with idiographic ratings to assess the impact of therapy. Findings indicate that CBT was an acceptable and useful intervention with mixed results; discrepancies were found between clinical change recorded on standardised measures compared with idiographic ratings. This paper discusses the use of standardised measures of anxiety for individuals with ASC and identifies directions for further research.

Key learning aims

(1)

To appreciate the unique mental health challenges of university students with ASC.

(2)

To identify psychological interventions that are suitable for individuals with ASC.

(3)

To consider the value in employing more than one evidence-based cognitive model of anxiety when clients present with co-morbid mental health issues.

(4)

To question the utility of using standardised outcome measures compared with idiographic measures in therapy.
Environmental impacts of physical and dynamical characteristics of the southern coastal waters of the Caspian Sea
Authors: JAMSHIDI Siamak , JAFARI Mahdieh
Published: June 2021

This research evaluated the variability of current characteristics and seawater properties in the middle part of the southern shelf of the Caspian Sea. The effect of the coastal flow on marine debris dispreading was assessed in the southern Caspian Sea for the first time. The findings showed the existence of thermal stratification containing seasonal thermocline with thickness of about 40 m in the water column. Maximum monthly along-shore current velocities around 1.3 m s−1 were observed in November and December. Monthly variations were clearly found in both flow velocity and local wind components. However, no significant levels of correlation between wind and current speeds were observed during the study in the region. In some cases, the mean monthly cross-shore component velocities were measured at about 29 cm s−1 in November. The findings indicated that there was no upwelling phenomenon associated to the regional wind in the study area. In situ current measurements indicated dominant east and north-northeast directions, presumably related to the effect of general circulation in the southern basin. Current profiles in the water column displayed similarity in directions at 10, 15 and 20 m depths over the continental shelf. The field samples and analysis revealed that the soft and smaller-scale seawater litters can be carried long distances by the current along the coast. Most coastal based and marine litters originated from the tourist activities (in the middle and western parts of the shores) and waste emanated from the river (Tonekabon-Nowshahr).
Wind Tunnel Validation of a Particle Tracking Model to Evaluate the Wind‐Induced Bias of Precipitation Measurements
Authors: Cauteruccio A. , Brambilla E. , Stagnaro M. , Lanza L. G. , Rocchi D.
Published: June 2021

A physical full‐scale experimental set‐up was designed and implemented in the wind tunnel to reproduce and capture the trajectories of falling water drops when approaching the collector of catching type precipitation gauges, reproducing rainfall measurements in windy conditions. The experiment allowed to collect, for the first time, a large data set of high‐resolution footages of the deviation of such trajectories, as induced by the bluff‐body aerodynamics of the outer gauge shape. By processing the collected images, a consistent quantitative interpretation of each drop pattern was possible, based on a detailed Computational Fluid Dynamics simulation of the airflow updraft and acceleration features above the collector of the gauge. Numerical airflow simulations were extensively validated in the wind tunnel, using local flow measurements and Particle Image Velocimetry. Capturing the deviation of the drop trajectories in the wind tunnel allowed a clear visualization of the physical reason for the wind‐induced undercatch of precipitation gauges, since drops were individually observed to fall outside instead of inside of the collector, contrary to what would be expected by extrapolating their undisturbed trajectory. The adopted Lagrangian Particle Tracking model and the formulation used for the drag coefficient were suitable to closely reproduce the observed drop trajectories when affected by the airflow deformation due to the bluff‐body aerodynamics of two investigated gauge geometries. The wind tunnel experiment provided the basis for the validation of the particle tracking model in terms of the difference between simulated and observed trajectories, after initial conditions were suitably set to represent the experimental setup.
Decline in symbiont-dependent host detoxification metabolism contributes to increased insecticide susceptibility of insects under high temperature
Authors: Zhang Yunhua , Cai Tingwei , Ren Zhijie , Liu Yu , Yuan Maojun , Cai Yongfeng , Yu Chang , Shu Runhang , He Shun , Li Jianhong , Wong Adam C N , Wan Hu
Published: June 2021

The interactions between insects and their bacterial symbionts are shaped by a variety of abiotic factors, including temperature. As global temperatures continue to break high records, a great deal of uncertainty surrounds how agriculturally important insect pests and their symbionts may be affected by elevated temperatures, and its implications for future pest management. In this study, we examine the role of bacterial symbionts in the brown planthopper Nilaparvata lugens response to insecticide (imidacloprid) under different temperature scenarios. Our results reveal that the bacterial symbionts orchestrate host detoxification metabolism via the CncC pathway to promote host insecticide resistance, whereby the symbiont-inducible CncC pathway acts as a signaling conduit between exogenous abiotic stimuli and host metabolism. However, this insect-bacterial partnership function is vulnerable to high temperature, which causes a significant decline in host-bacterial content. In particular, we have identified the temperature-sensitive Wolbachia as a candidate player in N. lugens detoxification metabolism. Wolbachia-dependent insecticide resistance was confirmed through a series of insecticide assays and experiments comparing Wolbachia-free and Wolbachia-infected N. lugens and also Drosophila melanogaster. Together, our research reveals elevated temperatures negatively impact insect-bacterial symbiosis, triggering adverse consequences on host response to insecticide (imidacloprid) and potentially other xenobiotics.
Global LiDAR land elevation data reveal greatest sea-level rise vulnerability in the tropics
Authors: Hooijer A. , Vernimmen R.
Published: June 2021

Coastal flood risk assessments require accurate land elevation data. Those to date existed only for limited parts of the world, which has resulted in high uncertainty in projections of land area at risk of sea-level rise (SLR). Here we have applied the first global elevation model derived from satellite LiDAR data. We find that of the worldwide land area less than 2 m above mean sea level, that is most vulnerable to SLR, 649,000 km2 or 62% is in the tropics. Even assuming a low-end relative SLR of 1 m by 2100 and a stable lowland population number and distribution, the 2020 population of 267 million on such land would increase to at least 410 million of which 72% in the tropics and 59% in tropical Asia alone. We conclude that the burden of current coastal flood risk and future SLR falls disproportionally on tropical regions, especially in Asia.
Suppression of HSF1 activity by wildtype p53 creates a driving force for p53 loss-of-heterozygosity
Authors: Isermann Tamara , Şener Özge Çiçek , Stender Adrian , Klemke Luisa , Winkler Nadine , Neesse Albrecht , Li Jinyu , Wegwitz Florian , Moll Ute M. , Schulz-Heddergott Ramona
Published: June 2021

The vast majority of human tumors with p53 mutations undergo loss of the remaining wildtype p53 allele (loss-of-heterozygosity, p53LOH). p53LOH has watershed significance in promoting tumor progression. However, driving forces for p53LOH are poorly understood. Here we identify the repressive WTp53–HSF1 axis as one driver of p53LOH. We find that the WTp53 allele in AOM/DSS chemically-induced colorectal tumors (CRC) of p53R248Q/+ mice retains partial activity and represses heat-shock factor 1 (HSF1), the master regulator of the proteotoxic stress response (HSR) that is ubiquitously activated in cancer. HSR is critical for stabilizing oncogenic proteins including mutp53. WTp53-retaining CRC tumors, tumor-derived organoids and human CRC cells all suppress the tumor-promoting HSF1 program. Mechanistically, retained WTp53 activates CDKN1A/p21, causing cell cycle inhibition and suppression of E2F target MLK3. MLK3 links cell cycle with the MAPK stress pathway to activate the HSR response. In p53R248Q/+ tumors WTp53 activation by constitutive stress represses MLK3, thereby weakening the MAPK-HSF1 response necessary for tumor survival. This creates selection pressure for p53LOH which eliminates the repressive WTp53-MAPK-HSF1 axis and unleashes tumor-promoting HSF1 functions, inducing mutp53 stabilization enabling invasion.
Structural mechanism of laminin recognition by integrin
Authors: Arimori Takao , Miyazaki Naoyuki , Mihara Emiko , Takizawa Mamoru , Taniguchi Yukimasa , Cabañas Carlos , Sekiguchi Kiyotoshi , Takagi Junichi
Published: June 2021

Recognition of laminin by integrin receptors is central to the epithelial cell adhesion to basement membrane, but the structural background of this molecular interaction remained elusive. Here, we report the structures of the prototypic laminin receptor α6β1 integrin alone and in complex with three-chain laminin-511 fragment determined via crystallography and cryo-electron microscopy, respectively. The laminin-integrin interface is made up of several binding sites located on all five subunits, with the laminin γ1 chain C-terminal portion providing focal interaction using two carboxylate anchor points to bridge metal-ion dependent adhesion site of integrin β1 subunit and Asn189 of integrin α6 subunit. Laminin α5 chain also contributes to the affinity and specificity by making electrostatic interactions with large surface on the β-propeller domain of α6, part of which comprises an alternatively spliced X1 region. The propeller sheet corresponding to this region shows unusually high mobility, suggesting its unique role in ligand capture.
Tectonic and climatic drivers of Asian monsoon evolution
Authors: Thomson James R. , Holden Philip B. , Anand Pallavi , Edwards Neil R. , Porchier Cécile A. , Harris Nigel B. W.
Published: June 2021

Asian Monsoon rainfall supports the livelihood of billions of people, yet the relative importance of different drivers remains an issue of great debate. Here, we present 30 million-year model-based reconstructions of Indian summer monsoon and South East Asian monsoon rainfall at millennial resolution. We show that precession is the dominant direct driver of orbital variability, although variability on obliquity timescales is driven through the ice sheets. Orographic development dominated the evolution of the South East Asian monsoon, but Indian summer monsoon evolution involved a complex mix of contributions from orography (39%), precession (25%), atmospheric CO2 (21%), ice-sheet state (5%) and ocean gateways (5%). Prior to 15 Ma, the Indian summer monsoon was broadly stable, albeit with substantial orbital variability. From 15 Ma to 5 Ma, strengthening was driven by a combination of orography and glaciation, while closure of the Panama gateway provided the prerequisite for the modern Indian summer monsoon state through a strengthened Atlantic meridional overturning circulation.
Climate pacing of millennial sea-level change variability in the central and western Mediterranean
Authors: Vacchi Matteo , Joyse Kristen M. , Kopp Robert E. , Marriner Nick , Kaniewski David , Rovere Alessio
Published: June 2021

Future warming in the Mediterranean is expected to significantly exceed global values with unpredictable implications on the sea-level rise rates in the coming decades. Here, we apply an empirical-Bayesian spatio-temporal statistical model to a dataset of 401 sea-level index points from the central and western Mediterranean and reconstruct rates of sea-level change for the past 10,000 years. We demonstrate that the mean rates of Mediterranean industrial-era sea-level rise have been significantly faster than any other period since ~4000 years ago. We further highlight a previously unrecognized variability in Mediterranean sea-level change rates. In the Common Era, this variability correlates with the occurrence of major regional-scale cooling/warming episodes. Our data show a sea-level stabilization during the Late Antique Little Ice Age cold event, which interrupted a general rising trend of ~0.45 mm a−1 that characterized the warming episodes of the Common Era. By contrast, the Little Ice Age cold event had only minor regional effects on Mediterranean sea-level change rates.
Identification of magnetic interactions and high-field quantum spin liquid in α-RuCl3
Authors: Li Han , Zhang Hao-Kai , Wang Jiucai , Wu Han-Qing , Gao Yuan , Qu Dai-Wei , Liu Zheng-Xin , Gong Shou-Shu , Li Wei
Published: June 2021

The frustrated magnetα-RuCl3constitutes a fascinating quantum material platform that harbors the intriguing Kitaev physics. However, a consensus on its intricate spin interactions and field-induced quantum phases has not been reached yet. Here we exploit multiple state-of-the-art many-body methods and determine the microscopic spin model that quantitatively explains major observations inα-RuCl3, including the zigzag order, double-peak specific heat, magnetic anisotropy, and the characteristic M-star dynamical spin structure, etc. According to our model simulations, the in-plane field drives the system into the polarized phase at about 7 T and a thermal fractionalization occurs at finite temperature, reconciling observations in different experiments. Under out-of-plane fields, the zigzag order is suppressed at 35 T, above which, and below a polarization field of 100 T level, there emerges a field-induced quantum spin liquid. The fractional entropy and algebraic low-temperature specific heat unveil the nature of a gapless spin liquid, which can be explored in high-field measurements onα-RuCl3.
Controllable quantum point junction on the surface of an antiferromagnetic topological insulator
Authors: Varnava Nicodemos , Wilson Justin H. , Pixley J. H. , Vanderbilt David
Published: June 2021

Engineering and manipulation of unidirectional channels has been achieved in quantum Hall systems, leading to the construction of electron interferometers and proposals for low-power electronics and quantum information science applications. However, to fully control the mixing and interference of edge-state wave functions, one needs stable and tunable junctions. Encouraged by recent material candidates, here we propose to achieve this using an antiferromagnetic topological insulator that supports two distinct types of gapless unidirectional channels, one from antiferromagnetic domain walls and the other from single-height steps. Their distinct geometric nature allows them to intersect robustly to form quantum point junctions, which then enables their control by magnetic and electrostatic local probes. We show how the existence of stable and tunable junctions, the intrinsic magnetism and the potential for higher-temperature performance make antiferromagnetic topological insulators a promising platform for electron quantum optics and microelectronic applications.
A cross-dehydrogenative C(sp3)−H heteroarylation via photo-induced catalytic chlorine radical generation
Authors: Huang Chia-Yu , Li Jianbin , Li Chao-Jun
Published: June 2021

Hydrogen atom abstraction (HAT) from C(sp3)–H bonds of naturally abundant alkanes for alkyl radical generation represents a promising yet underexplored strategy in the alkylation reaction designs since involving stoichiometric oxidants, excessive alkane loading, and limited scope are common drawbacks. Here we report a photo-induced and chemical oxidant-free cross-dehydrogenative coupling (CDC) between alkanes and heteroarenes using catalytic chloride and cobalt catalyst. Couplings of strong C(sp3)–H bond-containing substrates and complex heteroarenes, have been achieved with satisfactory yields. This dual catalytic platform features the in situ engendered chlorine radical for alkyl radical generation and exploits the cobaloxime catalyst to enable the hydrogen evolution for catalytic turnover. The practical value of this protocol was demonstrated by the gram-scale synthesis of alkylated heteroarene with merely 3 equiv. alkane loading.
Induction chemotherapy followed by definitive chemoradiotherapy versus chemoradiotherapy alone in esophageal squamous cell carcinoma: a randomized phase II trial
Authors: Liu Shiliang , Luo Liling , Zhao Lei , Zhu Yujia , Liu Hui , Li Qiaoqiao , Cai Ling , Hu Yonghong , Qiu Bo , Zhang Li , Shen Jingxian , Yang Yadi , Liu Mengzhong , Xi Mian
Published: June 2021

This randomized phase II trial aims to compare the efficacy and safety of induction chemotherapy followed by definitive chemoradiotherapy (CRT) versus CRT alone in patients with esophageal squamous cell carcinoma (ESCC) unsuitable for surgery (N = 110). The primary outcome was overall response rate (ORR), whereas the secondary outcome was overall survival. This trial did not meet pre-specified endpoints. The ORR was 74.5% in the induction chemotherapy group versus 61.8% in the CRT alone group (P = 0.152). The 3-year overall survival rate was 41.8% in the induction chemotherapy group and 38.1% in the CRT alone group (P = 0.584; hazard ratio, 0.88; 95% CI, 0.54–1.41). Grade 3–5 adverse events were similar. Patients who responded to induction chemotherapy had improved survival in the post-hoc analysis. These results demonstrate no improvement in response rate or survival with the addition of induction chemotherapy to CRT in unselected patients with ESCC. Trial number: NCT02403531.
Non-canonical function of DGCR8 in DNA double-strand break repair signaling and tumor radioresistance
Authors: Hang Qinglei , Zeng Liyong , Wang Li , Nie Litong , Yao Fan , Teng Hongqi , Deng Yalan , Yap Shannon , Sun Yutong , Frank Steven J. , Chen Junjie , Ma Li
Published: June 2021

In response to DNA double-strand breaks (DSBs), repair proteins are recruited to the damaged sites. Ubiquitin signaling plays a critical role in coordinating protein recruitment during the DNA damage response. Here, we find that the microRNA biogenesis factor DGCR8 promotes tumor resistance to X-ray radiation independently of its Drosha-binding ability. Upon radiation, the kinase ATM and the deubiquitinase USP51 mediate the activation and stabilization of DGCR8 through phosphorylation and deubiquitination. Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8’s binding partner RNF168 to MDC1 and RNF8 at DSBs. This, in turn, promotes ubiquitination of histone H2A, repair of DSBs, and radioresistance. Altogether, these findings reveal the non-canonical function of DGCR8 in DSB repair and suggest that radiation treatment may result in therapy-induced tumor radioresistance through ATM- and USP51-mediated activation and upregulation of DGCR8.
Mouse visual cortex contains a region of enhanced spatial resolution
Authors: van Beest Enny H. , Mukherjee Sreedeep , Kirchberger Lisa , Schnabel Ulf H. , van der Togt Chris , Teeuwen Rob R. M. , Barsegyan Areg , Meyer Arne F. , Poort Jasper , Roelfsema Pieter R. , Self Matthew W.
Published: June 2021

The representation of space in mouse visual cortex was thought to be relatively uniform. Here we reveal, using population receptive-field (pRF) mapping techniques, that mouse visual cortex contains a region in which pRFs are considerably smaller. This region, the “focea,” represents a location in space in front of, and slightly above, the mouse. Using two-photon imaging we show that the smaller pRFs are due to lower scatter of receptive-fields at the focea and an over-representation of binocular regions of space. We show that receptive-fields of single-neurons in areas LM and AL are smaller at the focea and that mice have improved visual resolution in this region of space. Furthermore, freely moving mice make compensatory eye-movements to hold this region in front of them. Our results indicate that mice have spatial biases in their visual processing, a finding that has important implications for the use of the mouse model of vision.
Attention-based multi-label neural networks for integrated prediction and interpretation of twelve widely occurring RNA modifications
Authors: Song Zitao , Huang Daiyun , Song Bowen , Chen Kunqi , Song Yiyou , Liu Gang , Su Jionglong , Magalhães João Pedro de , Rigden Daniel J. , Meng Jia
Published: June 2021

Recent studies suggest that epi-transcriptome regulation via post-transcriptional RNA modifications is vital for all RNA types. Precise identification of RNA modification sites is essential for understanding the functions and regulatory mechanisms of RNAs. Here, we present MultiRM, a method for the integrated prediction and interpretation of post-transcriptional RNA modifications from RNA sequences. Built upon an attention-based multi-label deep learning framework, MultiRM not only simultaneously predicts the putative sites of twelve widely occurring transcriptome modifications (m6A, m1A, m5C, m5U, m6Am, m7G, Ψ, I, Am, Cm, Gm, and Um), but also returns the key sequence contents that contribute most to the positive predictions. Importantly, our model revealed a strong association among different types of RNA modifications from the perspective of their associated sequence contexts. Our work provides a solution for detecting multiple RNA modifications, enabling an integrated analysis of these RNA modifications, and gaining a better understanding of sequence-based RNA modification mechanisms.
Solvent-free microwave synthesis of ultra-small Ru-Mo2C@CNT with strong metal-support interaction for industrial hydrogen evolution
Authors: Wu Xueke , Wang Zuochao , Zhang Dan , Qin Yingnan , Wang Minghui , Han Yi , Zhan Tianrong , Yang Bo , Li Shaoxiang , Lai Jianping , Wang Lei
Published: June 2021

Exploring a simple, fast, solvent-free synthetic method for large-scale preparation of cheap, highly active electrocatalysts for industrial hydrogen evolution reaction is one of the most promising work today. In this work, a simple, fast and solvent-free microwave pyrolysis method is used to synthesize ultra-small (3.5 nm) Ru-Mo2C@CNT catalyst with heterogeneous structure and strong metal-support interaction in one step. The Ru-Mo2C@CNT catalyst only exhibits an overpotential of 15 mV at a current density of 10 mA cm−2, and exhibits a large turnover frequency value up to 21.9 s−1 under an overpotential of 100 mV in 1.0 M KOH. In addition, this catalyst can reach high current densities of 500 mA cm−2 and 1000 mA cm−2 at low overpotentials of 56 mV and 78 mV respectively, and it displays high stability of 1000 h. This work provides a feasible way for the reasonable design of other large-scale production catalysts.
Synchronization of gene expression across eukaryotic communities through chemical rhythms
Authors: Pérez-García Sara , García-Navarrete Mario , Ruiz-Sanchis Diego , Prieto-Navarro Cristina , Avdovic Merisa , Pucciariello Ornella , Wabnik Krzysztof
Published: June 2021

The synchronization is a recurring phenomenon in neuroscience, ecology, human sciences, and biology. However, controlling synchronization in complex eukaryotic consortia on extended spatial-temporal scales remains a major challenge. Here, to address this issue we construct a minimal synthetic system that directly converts chemical signals into a coherent gene expression synchronized among eukaryotic communities through rate-dependent hysteresis. Guided by chemical rhythms, isolated colonies of yeast Saccharomyces cerevisiae oscillate in near-perfect synchrony despite the absence of intercellular coupling or intrinsic oscillations. Increased speed of chemical rhythms and incorporation of feedback in the system architecture can tune synchronization and precision of the cell responses in a growing cell collectives. This synchronization mechanism remain robust under stress in the two-strain consortia composed of toxin-sensitive and toxin-producing strains. The sensitive cells can maintain the spatial-temporal synchronization for extended periods under the rhythmic toxin dosages produced by killer cells. Our study provides a simple molecular framework for generating global coordination of eukaryotic gene expression through dynamic environment.
Rhythm, reading, and sound processing in the brain in preschool children
Authors: Bonacina Silvia , Huang Stephanie , White-Schwoch Travis , Krizman Jennifer , Nicol Trent , Kraus Nina
Published: June 2021

A child’s success in school relies on their ability to quickly grasp language and reading skills, the foundations of which are acquired even before entering a formal classroom setting. Previous studies in preschoolers have begun to establish relationships linking beat synchronization, preliteracy skills, and auditory processing. Beat synchronization involves the integration of sensorimotor systems with auditory and cognitive circuits and, therefore calls on many of the same neural networks as language. Using a drumming task, we analyzed the relationship between children’s ability to maintain an isochronous beat with preliteracy skills and frequency following responses (FFRs) in over 150 preschoolers. We show that preschoolers who performed well on the beat synchronization task outscored their peers on all preliteracy measures and had more robust FFRs. Furthermore, the good synchronizers experienced less degradation of certain FFR measures when listening in noise. Together, our results are consistent with the view that rhythm, preliteracy, and auditory processing are interconnected during early childhood.
Curating and comparing 114 strain-specific genome-scale metabolic models of Staphylococcus aureus
Authors: Renz Alina , Dräger Andreas
Published: June 2021

Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes. Furthermore, all models were quality-controlled using MEMOTE, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.
Triton, a new species-level database of Cenozoic planktonic foraminiferal occurrences
Authors: Fenton Isabel S. , Woodhouse Adam , Aze Tracy , Lazarus David , Renaudie Johan , Dunhill Alexander M. , Young Jeremy R. , Saupe Erin E.
Published: June 2021

Planktonic foraminifera are a major constituent of ocean floor sediments, and thus have one of the most complete fossil records of any organism. Expeditions to sample these sediments have produced large amounts of spatiotemporal occurrence records throughout the Cenozoic, but no single source exists to house these data. We have therefore created a comprehensive dataset that integrates numerous sources for spatiotemporal records of planktonic foraminifera. This new dataset, Triton, contains >500,000 records and is four times larger than the previous largest database, Neptune. To ensure comparability among data sources, we have cleaned all records using a unified set of taxonomic concepts and have converted age data to the GTS 2020 timescale. Where ages were not absolute (e.g. based on biostratigraphic or magnetostratigraphic zones), we have used generalised additive models to produce continuous estimates. This dataset is an excellent resource for macroecological and macroevolutionary studies, particularly for investigating how species responded to past climatic changes.
Stereoselective synthesis of a 4-⍺-glucoside of valienamine and its X-ray structure in complex with Streptomyces coelicolor GlgE1-V279S
Authors: Si Anshupriya , Jayasinghe Thilina D. , Thanvi Radhika , Kapil Sunayana , Ronning Donald R. , Sucheck Steven J.
Published: June 2021

Glycoside hydrolases (GH) are a large family of hydrolytic enzymes found in all domains of life. As such, they control a plethora of normal and pathogenic biological functions. Thus, understanding selective inhibition of GH enzymes at the atomic level can lead to the identification of new classes of therapeutics. In these studies, we identified a 4-⍺-glucoside of valienamine (8) as an inhibitor of Streptomyces coelicolor (Sco) GlgE1-V279S which belongs to the GH13 Carbohydrate Active EnZyme family. The results obtained from the dose–response experiments show that 8 at a concentration of 1000 µM reduced the enzyme activity of Sco GlgE1-V279S by 65%. The synthetic route to 8 and a closely related 4-⍺-glucoside of validamine (7) was achieved starting from readily available D-maltose. A key step in the synthesis was a chelation-controlled addition of vinylmagnesium bromide to a maltose-derived enone intermediate. X-ray structures of both 7 and 8 in complex with Sco GlgE1-V279S were solved to resolutions of 1.75 and 1.83 Å, respectively. Structural analysis revealed the valienamine derivative 8 binds the enzyme in an E2 conformation for the cyclohexene fragment. Also, the cyclohexene fragment shows a new hydrogen-bonding contact from the pseudo-diaxial C(3)–OH to the catalytic nucleophile Asp 394 at the enzyme active site. Asp 394, in fact, forms a bidentate interaction with both the C(3)–OH and C(7)-OH of the inhibitor. In contrast, compound 7 disrupts the catalytic sidechain interaction network of Sco GlgE1-V279S via steric interactions resulting in a conformation change in Asp 394. These findings will have implications for the design other aminocarbasugar-based GH13-inhibitors and will be useful for identifying more potent and selective inhibitors.
Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-β1
Authors: Khan Imran , Rahman Saeed Ur , Tang Elieza , Engel Karl , Hall Bradford , Kulkarni Ashok B. , Arany Praveen R.
Published: June 2021

The severity of tissue injury in burn wounds from associated inflammatory and immune sequelae presents a significant clinical management challenge. Among various biophysical wound management approaches, low dose biophotonics treatments, termed Photobiomodulation (PBM) therapy, has gained recent attention. One of the PBM molecular mechanisms of PBM treatments involves photoactivation of latent TGF-β1 that is capable of promoting tissue healing and regeneration. This work examined the efficacy of PBM treatments in a full-thickness burn wound healing in C57BL/6 mice. We first optimized the PBM protocol by monitoring tissue surface temperature and histology. We noted this dynamic irradiance surface temperature-monitored PBM protocol improved burn wound healing in mice with elevated TGF-β signaling (phospho-Smad2) and reduced inflammation-associated gene expression. Next, we investigated the roles of individual cell types involved in burn wound healing following PBM treatments and noted discrete effects on epithelieum, fibroblasts, and macrophage functions. These responses appear to be mediated via both TGF-β dependent and independent signaling pathways. Finally, to investigate specific contributions of TGF-β1 signaling in these PBM-burn wound healing, we utilized a chimeric TGF-β1/β3 knock-in (TGF-β1Lβ3/Lβ3) mice. PBM treatments failed to activate the chimeric TGF-β1Lβ3/Lβ3 complex and failed to improve burn wound healing in these mice. These results suggest activation of endogenous latent TGF-β1 following PBM treatments plays a key role in burn wound healing. These mechanistic insights can improve the safety and efficacy of clinical translation of PBM treatments for tissue healing and regeneration.
A rapid near-patient detection system for SARS-CoV-2 using saliva
Authors: Toppings Noah B. , Mohon Abu Naser , Lee Yoonjung , Kumar Hitendra , Lee Daniel , Kapoor Ratik , Singh Gurmukh , Oberding Lisa , Abdullah Omar , Kim Keekyoung , Berenger Byron M. , Pillai Dylan R.
Published: June 2021

The highly infectious nature of SARS-CoV-2 necessitates the use of widespread testing to control the spread of the virus. Presently, the standard molecular testing method (reverse transcriptase-polymerase chain reaction, RT-PCR) is restricted to the laboratory, time-consuming, and costly. This increases the turnaround time for getting test results. This study sought to develop a rapid, near-patient saliva-based test for COVID-19 (Saliva-Dry LAMP) with similar accuracy to that of standard RT-PCR tests. A lyophilized dual-target reverse transcription-loop-mediated isothermal amplification (RT-LAMP) test with fluorometric detection by the naked eye was developed. The assay relies on dry reagents that are room temperature stable. A device containing a centrifuge, heat block, and blue LED light system was manufactured to reduce the cost of performing the assay. This test has a limit of detection of 1 copy/µL and achieved a positive percent agreement of 100% [95% CI 88.43% to 100.0%] and a negative percent agreement of 96.7% [95% CI 82.78–99.92%] relative to a reference standard test. Saliva-Dry LAMP can be completed in 105 min. Precision, cross-reactivity, and interfering substances analysis met international regulatory standards. The combination of ease of sample collection, dry reagents, visual detection, low capital equipment cost, and excellent analytical sensitivity make Saliva-Dry LAMP particularly useful for resource-limited settings.