bluuebunny/crossref_metadata_2025 huggingface dataset:
Music as Therapy for the ‘exceptionally wealthy’ at the Nineteenth-Century Ticehurst Asylum
Authors: Golding Rosemary
Published: October 2022

Music was widely used within lunatic asylums in nineteenth-century England as part of the ‘moral management’ of patients via entertainment and occupation. The asylum at Ticehurst stood apart on account of its patient body, drawn from the upper classes of society. Documents relating to music at Ticehurst shed new light on the place of music within mental health treatment in the nineteenth century, and particularly on the perceived role of music in understanding the function of the brain in listening, emotions and the intellect. The main body of the article draws on the Ticehurst archives together with patient accounts of their musical experiences to investigate the ways in which music was used at the asylum. The final part takes as its focus an article published by the asylum’s manager and medical officer, Herbert Hayes Newington, in which the appreciation of music by patients comes under scrutiny.
PEAD.txt: Post-Earnings-Announcement Drift Using Text
Authors: Meursault Vitaly , Liang Pierre Jinghong , Routledge Bryan R. , Scanlon Madeline Marco
Published: October 2022

We construct a new numerical measure of earnings announcement surprises, standardized unexpected earnings call text (SUE.txt), that does not explicitly incorporate the reported earnings value. SUE.txt generates a text-based post-earnings-announcement drift (PEAD.txt) larger than the classic PEAD. The magnitude of PEAD.txt is considerable even in recent years when the classic PEAD is close to 0. We explore our text-based empirical model to show that the calls’ news content is about details behind the earnings number and the fundamentals of the firm.
Variability ofCalodium hepaticumeggs from sigmodontine host species through geometric morphometric analysis
Authors: Fantozzi M.C. , Reguera-Gomez M. , Beldomenico P.M. , Mas-Coma S. , Bargues M.D. , Valero M.A.
Published: October 2022

Calodium hepaticumis a zoonotic nematode with a worldwide distribution. Although the host range ofC. hepaticumincludes a wide spectrum of mammals (including humans), this parasite is predominantly associated with the families Muridae and Cricetidae. Several Sigmodontinae species from Argentina were found to be infected byC. hepaticum, with a high prevalence inAkodon azarae. The present study focuses onC. hepaticumeggs from natural infection of three species of sigmodontine rodents from Argentina. Eggs were genetically characterized (intergenic 18S rRNA region). The objectives of this work are: (i) to propose a new analytical methodology; and (ii) to morphologically characterizeC. hepaticumeggs, from three Sigmodontinae species (A. azarae,Calomys callidusandOligoryzomys flavescens). Analyses were made by the Computer Image Analysis System based on the new standardized measurements and geometric morphometric tools. The resulting factor maps clearly illustrate global size differences in the parasite eggs from the three Sigmodontinae species analysed. The degree of similarity between egg populations was assessed through pairwise Mahalanobis distances, showing that the largest distances were detected between parasite eggs fromC. callidusandO. flavescens. Herein, the phenotypical plasticity ofC. hepaticumeggs is shown. Significant positive correlations were obtained between each egg parasite principal component 1 and rodent corporal characteristics: weight; liver weight; rodent length; and rodent body condition. The usefulness of the geometric morphometric analysis in studies of the relationship betweenC. hepaticumand its host must be highlighted. The high prevalence observed inA. azarae, associated with the wide size range of the parasite eggs evidenced by principal component analysis, suggestsA. azaraeto be the Sigmodontinae host species that plays the most important role as reservoir host forC. hepaticumin the New World.
Blindness, Excrement, and Abjection in the Theatre: ASTR Presidential Address, 30 October 2021
Authors: Carlson Marla
Published: October 2022

As most of my human contact became restricted to the Zoom screen in spring 2020, I discovered a serious limit to my capacity for looking. I also began finding it difficult to read. A ten-month headache taught me to stop taking ibuprofen and learn to manage tensions around my eyes and head as well as to shift roughly half of my reading to screenreaders and audio books. The need to restructure my own practices of seeing refocused my interest in theatre's engagement of the senses at the same time as the COVID-19 pandemic destroyed people's ability to smell, prompted them to hoard toilet paper, and created a U.S. boom in bidet purchases. These personal and cultural developments coincided with revived metaphors of blindness on the pandemic stage. This article begins with a brief discussion of The Blind, an “immersive audio/visual meditation journey” that Here Arts Center produced in 2021, and then centers on Blindness, the “socially distanced sound installation” produced by the Donmar Warehouse in 2020 followed by an international tour. I wonder at the reiteration of blindness as a tragic trope, seemingly unaffected by progress in disability rights, equity, and inclusion. I wonder at the appeal of wielding any contagious illness as metaphor during a global pandemic. My analysis turns particularly upon the relation between blindness and excrement in José Saramago's novel Blindness and the effect of cleansing the theatrical installation of any shit as well as the even more surprising choice to eliminate the voices of the blind characters. A detour through medieval French farces that link blindness and excrement reveals submerged tropes at play in these performative responses to fear of diminished capacity and diminished control—everything that individuals and societies cast out in order to maintain what we call health, whether literal or metaphorical.
The people vs. the power bloc? Popular music and populism
Authors: Dunkel Mario , Schiller Melanie
Published: October 2022

On 12 November 2017, the Philippine celebrity musician Pilita Corrales was singing the popular song ‘Ikaw’ (‘You’) at a gala event in Manila, attended by some of the world's most powerful politicians at the time, US President Donald Trump and Philippine President Rodrigo Duterte. Suddenly, she noticed a male voice singing along with her, its intonation off, its volume increasing. Aware that the event was being recorded, Corrales at first tried to disregard the intruding voice. Eventually however, she could no longer ignore it and, shielding her eyes from the lights with one hand, she tried to spot the uninvited singer in the audience. ‘Where are you, sir’? she asked. Realising that the singer was on one of the balconies, it dawned on her that he was none other than Duterte himself. After giving Duterte room to sing a section by himself, she then joined the president in the song's finale (BBC News 2017; Guardian News 2017; Rappler 2017).
A robust and efficient wall parameter estimation approach for through wall radar
Authors: Singh Akhilendra Pratap
Published: October 2022

In through-wall radar system, the wall parameters, including permittivity, and wall thickness are of crucial importance for locating targets precisely. Recently, to obtain a quick and accurate estimation of wall parameters, an approach based on machine learning was introduced. However, these approaches are less reliable as only simulations results are presented. One of the major concerns with machine learning-based approaches is the generation of training and testing data which require fabrication of wall with different permittivity, thickness, and conductivity. Creating walls with different permittivity, thickness, and conductivity can really be challenging and expensive. Therefore, an effort has been made in this paper to establish a cost-effective and robust machine learning-based wall parameter estimation process with the usage of transmission line method and artificial neural network. The implementation and efficacy of proposed approach have been demonstrated through simulation and experimental results. The proposed approach quickly and accurately predicted the wall relative permittivity and thickness of real building wall. The merit of proposed approach is that it is less complex and computational efficient as it can extract wall parameters from only one measurement and therefore can be used in conjunction with any commercial through-wall radar systems.
Risk of somatic diseases in patients with eating disorders: the role of comorbid substance use disorders
Authors: Mellentin A. I. , Nielsen D. G. , Skøt L. , Støving R. K. , Guala M. M. , Nielsen A. S. , Wesselhoeft R. , Mejldal A.
Published: October 2022

Aims

Eating disorders (EDs) and substance use disorders (SUDs) often co-occur, and both involve somatic diseases. So far, no study has considered whether comorbid SUDs may impact somatic disease risk in patients with EDs. Therefore, this study aimed to examine the impact of comorbid SUDs on the risk of 11 somatic disease categories in patients with anorexia nervosa (AN), bulimia nervosa (BN) and unspecified eating disorder (USED) compared to matched controls.

Methods

A retrospective cohort study was conducted using Danish nationwide registries. The study population included 20 759 patients with EDs and 83 036 controls matched on month and year of birth, sex and ethnicity. Hazard ratios (HRs) were calculated to compare the risk of being diagnosed with a somatic disease (within 11 categories defined by the ICD-10) following first ED diagnosis (index date) between ED patients and controls both with and without SUDs (alcohol, cannabis or hard drugs).

Results

The ED cohort and matched controls were followed for 227 538 and 939 628 person-years, respectively. For ED patients with SUDs, the risk pattern for being diagnosed with different somatic diseases (relative to controls without SUDs) varied according to type of ED and SUD [adjusted HRs ranged from 0.95 (99% CI = 0.57; 1.59) to 4.17 (2.68, 6.47)]. The risk estimates observed among ED patients with SUDs were generally higher than those observed among ED patients without SUDs [adjusted HRs ranged from 1.08 (99% CI = 0.95, 1.22) to 2.56 (2.31, 2.84)]. Abuse of alcohol only had a non-synergistic effect on six disease categories in AN patients and five in BN and USED patients. Abuse of cannabis (with/without alcohol) had a non-synergistic effect on five disease categories in AN and BN patients and two in USED patients. Abuse of hard drugs (with/without alcohol or cannabis) had a non-synergistic effect on nine disease categories in AN patients, eight in BN patients and seven in USED patients.

Conclusions

The present study documents non-synergistic but not synergistic harmful somatic consequences of SUDs among patients with different EDs, with AN and hard drugs being the most predominant factors. Hence, EDs and SUDs did not interact and result in greater somatic disease risk than that caused by the independent effects. Since EDs and SUDs have independent effects on many somatic diseases, it is important to monitor and treat ED patients for SUD comorbidity to prevent exacerbated physical damage in this vulnerable population.
Prevalence of anxiety and depression in people with different types of cancer or haematologic malignancies: a cross-sectional study
Authors: Zeilinger E. L. , Oppenauer C. , Knefel M. , Kantor V. , Schneckenreiter C. , Lubowitzki S. , Krammer K. , Popinger C. , Kitta A. , Kum L. , Adamidis F. , Unseld M. , Masel E. K. , Füreder T. , Zöchbauer-Müller S. , Bartsch R. , Raderer M. , Prager G. , Krauth M. T. , Sperr W. R. , Porpaczy E. , Staber P. B. , Valent P. , Gaiger A.
Published: October 2022

Aims

Cancer patients often present with psychological symptoms that affect their quality of life, physical health outcomes and survival. Two of the most frequent psychiatric comorbidities are anxiety and depression. However, the prevalence of these disorders among cancer patients remains unclear, as studies frequently report varying rates. In the present study, we aimed to provide robust point estimates for the prevalence of anxiety and depression for both a mixed cancer sample and for 13 cancer types separately, considering confounding variables.

Methods

In a sample of 7509 cancer outpatients (51.4% female), we used the Hospital Anxiety and Depression Scale to assess rates of anxiety and depression. Applying ordinal logistic regression models, we compared the prevalence of anxiety and depression between different cancer types, controlling for age and gender.

Results

About one third of our sample showed symptoms of anxiety (35.2%) or depression (27.9%), and every sixth patient had a very likely psychiatric condition, with women being more frequently affected. Elderly patients more often showed signs of depression. The prevalence of anxiety and depression was significantly higher in lung and brain cancer patients, than in other cancer patients. Lowest depression rates were found in breast cancer patients.

Conclusions

The prevalence of anxiety and depression is high in cancer patients. Type of cancer is an important predictor for anxiety and depressive symptoms, with lung and brain cancer patients being highly burdened. Considering a personalised medicine approach, physicians should take into account the high prevalence of psychiatric comorbidities and include psychiatric consultations in the treatment plan.
Spatiotemporal Analysis of Extreme Temperature Change on the Tibetan Plateau Based On Quantile Regression
Authors: Yao Ling , Lu Jiaying , Zhang Wenjie , Qin Jun , Zhou Chenghu , Tran Ngoc Nguyen , Pinagé Ekena Rangel
Published: October 2022

Temperature extremes have been extensively observed on the Tibetan Plateau (TP), of which the dynamics were mostly monitored by traditional trend analysis based on linear regression. This method however, is often impacted by a quasi‐periodic heterogeneity disturbance in variance, leading to results susceptible to extreme outliers. In this study, we conducted the comprehensive detection of extreme temperature changes using quantile regression on the TP from 100 weather stations from 1979 to 2019. The use of quantile regression enabled us to characterize the entire density function of the extreme temperature time‐series (the daily minimum, mean and maximum temperature) at each location. Our results revealed that the daily minimum temperature was generally warming faster than the daily maximum and mean temperatures with the respective trend interval of [−0.45, 1.29], [−0.1, 0.98], [−0.01, 1.01] °C/decade among the conditional quantile levels. Furthermore, the warming rate of extremely cold (0.05 quantile level) and hot days (0.95 quantile level) was higher than that of the mean condition (0.5 quantile level) in each extreme temperature time‐series. We also found that there was a significant elevation‐dependent warming only in extremely cold days. In addition, results from the teleconnection analysis showed that the Arctic Oscillation had a strong influence on the extreme cold and hot extremes over the northern and southwestern TP region, while the El Niño‐Southern Oscillation mainly modulated temperatures over the southeastern TP area. This study can potentially offer improved understanding of the temperature extremes over TP in the face of global warming.
Hydrothermal Ore Deposits Record the Oxygen Isotope Composition of Meteoric Paleo‐Waters in the San Juan Volcanic Field, Colorado, USA
Authors: Johnson Benjamin W. , Wing Boswell A. , Abbott Lon
Published: October 2022

The stable isotope ratios of meteoric waters change predictably over orographic barriers. We present a new approach to determine stable isotope ratios in ancient meteoric waters from spatial patterns of hydrothermal alteration in continental volcanic fields. In the San Juan Volcanic Field, Colorado, USA we reconstruct water δ18O values feeding hydrothermal systems of −7 to −10‰ from 35 to 20 Ma, followed by a drop to −17 to −18‰ between 20 and 12 Ma. This drop is consistent with greater magmatic water input to older hydrothermal systems, ∼1 km of rock exhumation, ∼2–3 km of surface uplift, or a combination of all three. Our approach returns water isotope compositions integrated over spatial (kms to 10s kms) and temporal (104 − 107 years) scales of continental hydrothermal systems. Such length‐ and time‐scales approach those of continental tectonics, potentially alleviating issues with diagenetic space and time limitations associated with other paleo‐meteoric water proxies.
Oscillations of the Ionosphere Caused by the 2022 Tonga Volcanic Eruption Observed With SuperDARN Radars
Authors: Zhang Jiaojiao , Xu Jiyao , Wang Wei , Wang Guojun , Ruohoniemi J. Michael , Shinbori Atsuki , Nishitani Nozomu , Wang Chi , Deng Xiang , Lan Ailan , Yan Jingye
Published: October 2022

On 15 January 2022, the submarine volcano on the southwest Pacific island of Tonga violently erupted. Thus far, the ionospheric oscillation features caused by the volcanic eruption have not been identified. Here, observations from the Super Dual Auroral Radar Network radars and digisondes were employed to analyze ionospheric oscillations in the Northern Hemisphere caused by the volcanic eruption in Tonga. Due to the magnetic field conjugate effect, the ionospheric oscillations were observed much earlier than the arrival of surface air pressure waves, and the maximum negative line‐of‐sight (LOS) velocity of the ionospheric oscillations exceeded 100 m/s in the F layer. After the surface air pressure waves arrived, the maximum LOS velocity in the E layer approached 150 m/s. A maximum upward displacement of 100 km was observed in the ionosphere. This work provides a new perspective for understanding the strong ionospheric oscillation caused by geological hazards observed on Earth.
Nitrous Oxide Consumption in Oxygenated and Anoxic Estuarine Waters
Authors: Tang Weiyi , Jayakumar Amal , Sun Xin , Tracey John C. , Carroll Julia , Wallace Elizabeth , Lee Jenna A. , Nathan Levy , Ward Bess
Published: October 2022

Estuaries emit a large but highly uncertain amount of Nitrous oxide (N2O) into the atmosphere. To better understand N2O cycling processes in estuaries, we provide the first direct observations of N2O consumption in the seasonally anoxic Chesapeake Bay, the largest estuary in the United States. N2O consumption rates in anoxic waters reached up to 3.3 nmol L−1 d−1 but were generally undetectable in oxygenated waters. However, N2O consumption rates were substantially enhanced when the oxygen concentration was experimentally decreased in initially oxygenated samples, indicating the potential of N2O consumption in oxygenated environments, for example, surface waters. These potential N2O consumption rates followed Michaelis‐Menten kinetics as a function of increasing N2O substrate concentration. N2O‐consuming microbes that predominantly contained the clade II nitrous oxide reductase gene were detected throughout the water column. These new observations of environmental controls on N2O consumption will benefit the modeling of N2O cycling and help to constrain the estuarine N2O flux.
Physical Properties of the Crust Influence Aftershock Locations
Authors: Hardebeck Jeanne L.
Published: October 2022

Aftershocks do not uniformly surround a mainshock, and instead occur in spatial clusters. Spatially variable physical properties of the crust may influence the spatial distribution of aftershocks. I study four aftershock sequences in Southern California (1992 Landers, 1999 Hector Mine, 2010 El Mayor—Cucapah, and 2019 Ridgecrest) to investigate which physical properties are spatially correlated with aftershock occurrence. I find that aftershocks correlate with several properties, including measures of stress and stress change from the mainshock, fault structure, kinematics, seismic velocity, and heat flow. Aftershock spatial density exhibits an order of magnitude or more variation as a function of these properties. I determine simple empirical relations between each of the properties and the aftershock spatial density, and use these relations to construct new spatial models that describe aftershock locations. The new spatial models are a significant improvement over a simple base model, but do not fully capture the dense spatial clustering of aftershocks. Numerous spatially varying physical properties exhibit no (or poor) correlation with aftershock spatial density, including temperature, rock composition, and rheological properties that might be expected to control aftershock occurrence. These results suggest that while spatially variable physical properties appear to influence aftershock locations, more work is necessary in order to establish the connections between aftershock occurrence and the causative physical properties.
Therapeutic strategy targeting host lipolysis limits infection by SARS-CoV-2 and influenza A virus
Authors: Baek Yeong-Bin , Kwon Hyung-Jun , Sharif Muhammad , Lim Jeongah , Lee In-Chul , Ryu Young Bae , Lee Jae-In , Kim Ji-Sun , Lee Young-Seung , Kim Dong-Hoon , Park Sang-Ik , Kim Don-Kyu , Kim Jeong-Sun , Choy Hyon E. , Lee Sunwoo , Choi Hueng-Sik , Osborne Timothy F. , Jeon Tae-Il , Cho Kyoung-Oh
Published: October 2022

The biosynthesis of host lipids and/or lipid droplets (LDs) has been studied extensively as a putative therapeutic target in diverse viral infections. However, directly targeting the LD lipolytic catabolism in virus-infected cells has not been widely investigated. Here, we show the linkage of the LD-associated lipase activation to the breakdown of LDs for the generation of free fatty acids (FFAs) at the late stage of diverse RNA viral infections, which represents a broad-spectrum antiviral target. Dysfunction of membrane transporter systems due to virus-induced cell injury results in intracellular malnutrition at the late stage of infection, thereby making the virus more dependent on the FFAs generated from LD storage for viral morphogenesis and as a source of energy. The replication of SARS-CoV-2 and influenza A virus (IAV), which is suppressed by the treatment with LD-associated lipases inhibitors, is rescued by supplementation with FFAs. The administration of lipase inhibitors, either individually or in a combination with virus-targeting drugs, protects mice from lethal IAV infection and mitigates severe lung lesions in SARS-CoV-2-infected hamsters. Moreover, the lipase inhibitors significantly reduce proinflammatory cytokine levels in the lungs of SARS-CoV-2- and IAV-challenged animals, a cause of a cytokine storm important for the critical infection or mortality of COVID-19 and IAV patients. In conclusion, the results reveal that lipase-mediated intracellular LD lipolysis is commonly exploited to facilitate RNA virus replication and furthermore suggest that pharmacological inhibitors of LD-associated lipases could be used to curb current COVID-19- and future pandemic outbreaks of potentially troublesome RNA virus infection in humans.
Hidden pressurized fluids prior to the 2014 phreatic eruption at Mt Ontake
Authors: Caudron Corentin , Aoki Yosuke , Lecocq Thomas , De Plaen Raphael , Soubestre Jean , Mordret Aurelien , Seydoux Leonard , Terakawa Toshiko
Published: October 2022

A large fraction of volcanic eruptions does not expel magma at the surface. Such an eruption occurred at Mt Ontake in 2014, claiming the life of at least 58 hikers in what became the worst volcanic disaster in Japan in almost a century. Tens of scientific studies attempted to identify a precursor and to unravel the processes at work but overall remain inconclusive. By taking advantage of continuous seismic recordings, we uncover an intriguing sequence of correlated seismic velocity and volumetric strain changes starting 5 months before the eruption; a period previously considered as completely quiescent. We use various novel approaches such as covariance matrix eigenvalues distribution, cutting-edge deep-learning models, and ascribe such velocity pattern as reflecting critically stressed conditions in the upper portions of the volcano. These, in turn, later triggered detectable deformation and earthquakes. Our results shed light onto previously undetected pressurized fluids using stations located above the volcano-hydrothermal system and hold great potential for monitoring.
A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma
Authors: Zhou Royce W. , Xu Jia , Martin Tiphaine C. , Zachem Alexis L. , He John , Ozturk Sait , Demircioglu Deniz , Bansal Ankita , Trotta Andrew P. , Giotti Bruno , Gryder Berkley , Shen Yao , Wu Xuewei , Carcamo Saul , Bosch Kaitlyn , Hopkins Benjamin , Tsankov Alexander , Steinhagen Randolph , Jones Drew R. , Asara John , Chipuk Jerry E. , Brody Rachel , Itzkowitz Steven , Chio Iok In Christine , Hasson Dan , Bernstein Emily , Parsons Ramon E.
Published: October 2022

Tumors exhibit enhancer reprogramming compared to normal tissue. The etiology is largely attributed to cell-intrinsic genomic alterations. Here, using freshly resected primary CRC tumors and patient-matched adjacent normal colon, we find divergent epigenetic landscapes between CRC tumors and cell lines. Intriguingly, this phenomenon extends to highly recurrent aberrant super-enhancers gained in CRC over normal. We find one such super-enhancer activated in epithelial cancer cells due to surrounding inflammation in the tumor microenvironment. We restore this super-enhancer and its expressed gene, PDZK1IP1, following treatment with cytokines or xenotransplantation into nude mice, thus demonstrating cell-extrinsic etiology. We demonstrate mechanistically that PDZK1IP1 enhances the reductive capacity CRC cancer cells via the pentose phosphate pathway. We show this activation enables efficient growth under oxidative conditions, challenging the previous notion that PDZK1IP1 acts as a tumor suppressor in CRC. Collectively, these observations highlight the significance of epigenomic profiling on primary specimens.
Anisotropic long-range spin transport in canted antiferromagnetic orthoferrite YFeO3
Authors: Das Shubhankar , Ross A. , Ma X. X. , Becker S. , Schmitt C. , van Duijn F. , Galindez-Ruales E. F. , Fuhrmann F. , Syskaki M.-A. , Ebels U. , Baltz V. , Barra A.-L. , Chen H. Y. , Jakob G. , Cao S. X. , Sinova J. , Gomonay O. , Lebrun R. , Kläui M.
Published: October 2022

In antiferromagnets, the efficient transport of spin-waves has until now only been observed in the insulating antiferromagnet hematite, where circularly (or a superposition of pairs of linearly) polarized spin-waves diffuse over long distances. Here, we report long-distance spin-transport in the antiferromagnetic orthoferrite YFeO3, where a different transport mechanism is enabled by the combined presence of the Dzyaloshinskii-Moriya interaction and externally applied fields. The magnon decay length is shown to exceed hundreds of nanometers, in line with resonance measurements that highlight the low magnetic damping. We observe a strong anisotropy in the magnon decay lengths that we can attribute to the role of the magnon group velocity in the transport of spin-waves in antiferromagnets. This unique mode of transport identified in YFeO3opens up the possibility of a large and technologically relevant class of materials, i.e., canted antiferromagnets, for long-distance spin transport.
Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke
Authors: Chen Lingyan , Peters James E. , Prins Bram , Persyn Elodie , Traylor Matthew , Surendran Praveen , Karthikeyan Savita , Yonova-Doing Ekaterina , Di Angelantonio Emanuele , Roberts David J. , Watkins Nicholas A. , Ouwehand Willem H. , Danesh John , Lewis Cathryn M. , Bronson Paola G. , Markus Hugh S. , Burgess Stephen , Butterworth Adam S. , Howson Joanna M. M.
Published: October 2022

Stroke is the second leading cause of death with substantial unmet therapeutic needs. To identify potential stroke therapeutic targets, we estimate the causal effects of 308 plasma proteins on stroke outcomes in a two-sample Mendelian randomization framework and assess mediation effects by stroke risk factors. We find associations between genetically predicted plasma levels of six proteins and stroke (P ≤ 1.62 × 10−4). The genetic associations with stroke colocalize (Posterior Probability >0.7) with the genetic associations of four proteins (TFPI, TMPRSS5, CD6, CD40). Mendelian randomization supports atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes as stroke risk factors (P ≤ 0.0071). Body mass index, white matter hyperintensity and atrial fibrillation appear to mediate the TFPI, IL6RA, TMPRSS5 associations with stroke. Furthermore, thirty-six proteins are associated with one or more of these risk factors using Mendelian randomization. Our results highlight causal pathways and potential therapeutic targets for stroke.
SARS-COV-2 antibody responses to AZD1222 vaccination in West Africa
Authors: Abdullahi Adam , Oladele David , Owusu Michael , Kemp Steven A. , Ayorinde James , Salako Abideen , Fink Douglas , Ige Fehintola , Ferreira Isabella A. T. M. , Meng Bo , Sylverken Augustina Angelina , Onwuamah Chika , Boadu Kwame Ofori , Osuolale Kazeem , Frimpong James Opoku , Abubakar Rufai , Okuruawe Azuka , Abdullahi Haruna Wisso , Liboro Gideon , Agyemang Lawrence Duah , Ayisi-Boateng Nana Kwame , Odubela Oluwatosin , Ohihoin Gregory , Ezechi Oliver , Kamasah Japhet Senyo , Ameyaw Emmanuel , Arthur Joshua , Kyei Derrick Boakye , Owusu Dorcas Ohui , Usman Olagoke , Mogaji Sunday , Dada Adedamola , Agyei George , Ebrahimi Soraya , Gutierrez Lourdes Ceron , Aliyu Sani H. , Doffinger Rainer , Audu Rosemary , Adegbola Richard , Mlcochova Petra , Phillips Richard Odame , Solako Babatunde Lawal , Gupta Ravindra K.
Published: October 2022

Real-world data on vaccine-elicited neutralising antibody responses for two-dose AZD1222 in African populations are limited. We assessed baseline SARS-CoV-2 seroprevalence and levels of protective neutralizing antibodies prior to vaccination rollout using binding antibodies analysis coupled with pseudotyped virus neutralisation assays in two cohorts from West Africa: Nigerian healthcare workers (n = 140) and a Ghanaian community cohort (n = 527) pre and post vaccination. We found 44 and 28% of pre-vaccination participants showed IgG anti-N positivity, increasing to 59 and 39% respectively with anti-receptor binding domain (RBD) IgG-specific antibodies. Previous IgG anti-N positivity significantly increased post two-dose neutralizing antibody titres in both populations. Serological evidence of breakthrough infection was observed in 8/49 (16%). Neutralising antibodies were observed to wane in both populations, especially in anti-N negative participants with an observed waning rate of 20% highlighting the need for a combination of additional markers to characterise previous infection. We conclude that AZD1222 is immunogenic in two independent West African cohorts with high background seroprevalence and incidence of breakthrough infection in 2021. Waning titres post second dose indicates the need for booster dosing after AZD1222 in the African setting despite hybrid immunity from previous infection.
HIV-1 CD4-binding site germline antibody–Env structures inform vaccine design
Authors: Dam Kim-Marie A. , Barnes Christopher O. , Gristick Harry B. , Schoofs Till , Gnanapragasam Priyanthi N. P. , Nussenzweig Michel C. , Bjorkman Pamela J.
Published: October 2022

BG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4-binding site (CD4bs) bNAbs. To understand how SHMs correlate with BG24 neutralization of HIV-1, we report 4.1 Å and 3.4 Å single-particle cryo-EM structures of two inferred germline (iGL) BG24 precursors complexed with engineered Env-based immunogens lacking CD4bs N-glycans. Structures reveal critical Env contacts by BG24iGL and identify antibody light chain structural features that impede Env recognition. In addition, biochemical data and cryo-EM structures of BG24iGL variants bound to Envs with CD4bs glycans present provide insights into N-glycan accommodation, including structural modes of light chain adaptations in the presence of the N276gp120 glycan. Together, these findings reveal Env regions critical for germline antibody recognition and potential sites to alter in immunogen design.
An intrinsic temporal order of c-JUN N-terminal phosphorylation regulates its activity by orchestrating co-factor recruitment
Authors: Waudby Christopher A. , Alvarez-Teijeiro Saul , Josue Ruiz E. , Suppinger Simon , Pinotsis Nikos , Brown Paul R. , Behrens Axel , Christodoulou John , Mylona Anastasia
Published: October 2022

Protein phosphorylation is a major regulatory mechanism of cellular signalling. The c-JUN proto-oncoprotein is phosphorylated at four residues within its transactivation domain (TAD) by the JNK family kinases, but the functional significance of c-JUN multisite phosphorylation has remained elusive. Here we show that c-JUN phosphorylation by JNK exhibits defined temporal kinetics, with serine63 and serine73 being phosphorylated more rapidly than threonine91 and threonine93. We identify the positioning of the phosphorylation sites relative to the kinase docking motif, and their primary sequence, as the main factors controlling phosphorylation kinetics. Functional analysis reveals three c-JUN phosphorylation states: unphosphorylated c-JUN recruits the MBD3 repressor, serine63/73 doubly-phosphorylated c-JUN binds to the TCF4 co-activator, whereas the fully phosphorylated form disfavours TCF4 binding attenuating JNK signalling. Thus, c-JUN phosphorylation encodes multiple functional states that drive a complex signalling response from a single JNK input.
A scalable platform to discover antimicrobials of ribosomal origin
Authors: Ayikpoe Richard S. , Shi Chengyou , Battiste Alexander J. , Eslami Sara M. , Ramesh Sangeetha , Simon Max A. , Bothwell Ian R. , Lee Hyunji , Rice Andrew J. , Ren Hengqian , Tian Qiqi , Harris Lonnie A. , Sarksian Raymond , Zhu Lingyang , Frerk Autumn M. , Precord Timothy W. , van der Donk Wilfred A. , Mitchell Douglas A. , Zhao Huimin
Published: October 2022

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new antimicrobials in the face of rising antibiotic resistance. Here, we report a scalable platform that combines high-throughput bioinformatics with automated biosynthetic gene cluster refactoring for rapid evaluation of uncharacterized gene clusters. As a proof of concept, 96 RiPP gene clusters that originate from diverse bacterial phyla involving 383 biosynthetic genes are refactored in a high-throughput manner using a biological foundry with a success rate of 86%. Heterologous expression of all successfully refactored gene clusters inEscherichia colienables the discovery of 30 compounds covering six RiPP classes: lanthipeptides, lasso peptides, graspetides, glycocins, linear azol(in)e-containing peptides, and thioamitides. A subset of the discovered lanthipeptides exhibit antibiotic activity, with one class II lanthipeptide showing low µM activity againstKlebsiella pneumoniae, an ESKAPE pathogen. Overall, this work provides a robust platform for rapidly discovering RiPPs.
Topological phononics arising from fluid-solid interactions
Authors: Wu Xiaoxiao , Fan Haiyan , Liu Tuo , Gu Zhongming , Zhang Ruo-Yang , Zhu Jie , Zhang Xiang
Published: October 2022

Nontrivial band topologies have been discovered in classical systems and hold great potential for device applications. Unlike photons, sound has fundamentally different dynamics and symmetries in fluids and solids, represented as scalar and vector fields, respectively. So far, searches for topological phononic materials have only concerned sound in either fluids or solids alone, overlooking their intricate interactions in “mixtures”. Here, we report an approach for topological phononics employing such unique interplay, and demonstrate the realization of type-II nodal rings, elusive in phononics, in a simple three-dimensional phononic crystal. Type-II nodal rings, as line degeneracies in momentum space with exotic properties from strong tilting, are directly observed through ultrasonic near-field scanning. Strongly tilted drumhead surface states, the hallmark phenomena, are also experimentally demonstrated. This phononic approach opens a door to explore topological physics in classical systems, which is easy to implement that can be used for designing high-performance acoustic devices.
Selective activation of four quasi-equivalent C–H bonds yields N-doped graphene nanoribbons with partial corannulene motifs
Authors: Gao Yixuan , Huang Li , Cao Yun , Richter Marcus , Qi Jing , Zheng Qi , Yang Huan , Ma Ji , Chang Xiao , Fu Xiaoshuai , Palma Carlos-Andres , Lu Hongliang , Zhang Yu-Yang , Cheng Zhihai , Lin Xiao , Ouyang Min , Feng Xinliang , Du Shixuan , Gao Hong-Jun
Published: October 2022

Selective C–H bond activation is one of the most challenging topics for organic reactions. The difficulties arise not only from the high C–H bond dissociation enthalpies but also the existence of multiple equivalent/quasi-equivalent reaction sites in organic molecules. Here, we successfully achieve the selective activation of four quasi-equivalent C–H bonds in a specially designed nitrogen-containing polycyclic hydrocarbon (N-PH). Density functional theory calculations reveal that the adsorption of N-PH on Ag(100) differentiates the activity of the four ortho C(sp3) atoms in the N-heterocycles into two groups, suggesting a selective dehydrogenation, which is demonstrated by sequential-annealing experiments of N-PH/Ag(100). Further annealing leads to the formation of N-doped graphene nanoribbons with partial corannulene motifs, realized by the C–H bond activation process. Our work provides a route of designing precursor molecules with ortho C(sp3) atom in an N-heterocycle to realize surface-induced selective dehydrogenation in quasi-equivalent sites.
Two-dimensional multiferroic material of metallic p-doped SnSe
Authors: Du Ruofan , Wang Yuzhu , Cheng Mo , Wang Peng , Li Hui , Feng Wang , Song Luying , Shi Jianping , He Jun
Published: October 2022

Two-dimensional multiferroic materials have garnered broad interests attributed to their magnetoelectric properties and multifunctional applications. Multiferroic heterostructures have been realized, nevertheless, the direct coupling between ferroelectric and ferromagnetic order in a single material still remains challenging, especially for two-dimensional materials. Here, we develop a physical vapor deposition approach to synthesize two-dimensional p-doped SnSe. The local phase segregation of SnSe2 microdomains and accompanying interfacial charge transfer results in the emergence of degenerate semiconductor and metallic feature in SnSe. Intriguingly, the room-temperature ferrimagnetism has been demonstrated in two-dimensional p-doped SnSe with the Curie temperature approaching to ~337 K. Meanwhile, the ferroelectricity is maintained even under the depolarizing field introduced by SnSe2. The coexistence of ferrimagnetism and ferroelectricity in two-dimensional p-doped SnSe verifies its multiferroic feature. This work presents a significant advance for exploring the magnetoelectric coupling in two-dimensional limit and constructing high-performance logic devices to extend Moore’s law.
A population-based matched cohort study of early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection
Authors: Calvert Clara , Carruthers Jade , Denny Cheryl , Donaghy Jack , Hillman Sam , Hopcroft Lisa E. M. , Hopkins Leanne , Goulding Anna , Lindsay Laura , McLaughlin Terry , Moore Emily , Pan Jiafeng , Taylor Bob , Almaghrabi Fatima , Auyeung Bonnie , Bhaskaran Krishnan , Gibbons Cheryl L. , Katikireddi Srinivasa Vittal , McCowan Colin , Murray Josie , O’Leary Maureen , Ritchie Lewis D. , Shah Syed Ahmar , Simpson Colin R. , Robertson Chris , Sheikh Aziz , Stock Sarah J. , Wood Rachael
Published: October 2022

Data on the safety of COVID-19 vaccines in early pregnancy are limited. We conducted a national, population-based, matched cohort study assessing associations between COVID-19 vaccination and miscarriage prior to 20 weeks gestation and, separately, ectopic pregnancy. We identified women in Scotland vaccinated between 6 weeks preconception and 19 weeks 6 days gestation (for miscarriage; n = 18,780) or 2 weeks 6 days gestation (for ectopic; n = 10,570). Matched, unvaccinated women from the pre-pandemic and, separately, pandemic periods were used as controls. Here we show no association between vaccination and miscarriage (adjusted Odds Ratio [aOR], pre-pandemic controls = 1.02, 95% Confidence Interval [CI] = 0.96–1.09) or ectopic pregnancy (aOR = 1.13, 95% CI = 0.92–1.38). We undertook additional analyses examining confirmed SARS-CoV-2 infection as the exposure and similarly found no association with miscarriage or ectopic pregnancy. Our findings support current recommendations that vaccination remains the safest way for pregnant women to protect themselves and their babies from COVID-19.
Facet effect of hematite on the hydrolysis of phthalate esters under ambient humidity conditions
Authors: Jin Xin , Wu Dingding , Liu Cun , Huang Shuhan , Zhou Ziyan , Wu Hao , Chen Xiru , Huang Meiying , Zhou Shaoda , Gu Cheng
Published: October 2022

Phthalate esters (PAEs) have been extensively used as additives in plastics and wallcovering, causing severe environmental contamination and increasing public health concerns. Here, we find that hematite nanoparticles with specific facet-control can efficiently catalyze PAEs hydrolysis under ambient humidity conditions, with the hydrolysis rates 2 orders of magnitude higher than that in water saturated condition. The catalytic performance of hematite shows a significant facet-dependence with the reactivity in the order {012} > {104} ≫ {001}, related to the atomic array of surface undercoordinated Fe. The {012} and {104} facets with the proper neighboring Fe-Fe distance of 0.34-0.39 nm can bidentately coordinate with PAEs, and thus induce much stronger Lewis-acid catalysis. Our study may inspire the development of nanomaterials with appropriate surface atomic arrays, improves our understanding for the natural transformation of PAEs under low humidity environment, and provides a promising approach to remediate/purify the ambient air contaminated by PAEs.
A small molecule inhibitor prevents gut bacterial genotoxin production
Authors: Volpe Matthew R. , Velilla José A. , Daniel-Ivad Martin , Yao Jenny J. , Stornetta Alessia , Villalta Peter W. , Huang Hsin-Che , Bachovchin Daniel A. , Balbo Silvia , Gaudet Rachelle , Balskus Emily P.
Published: October 2022

The human gut bacterial genotoxin colibactin is a possible key driver of colorectal cancer (CRC) development. Understanding colibactin’s biological effects remains difficult owing to the instability of the proposed active species and the complexity of the gut microbiota. Here, we report small molecule boronic acid inhibitors of colibactin biosynthesis. Designed to mimic the biosynthetic precursor precolibactin, these compounds potently inhibit the colibactin-activating peptidase ClbP. Using biochemical assays and crystallography, we show that they engage the ClbP binding pocket, forming a covalent bond with the catalytic serine. These inhibitors reproduce the phenotypes observed in a clbP deletion mutant and block the genotoxic effects of colibactin on eukaryotic cells. The availability of ClbP inhibitors will allow precise, temporal control over colibactin production, enabling further study of its contributions to CRC. Finally, application of our inhibitors to related peptidase-encoding pathways highlights the power of chemical tools to probe natural product biosynthesis.
NMR lineshape analysis using analytical solutions of multi-state chemical exchange with applications to kinetics of host–guest systems
Authors: Březina Václav , Hanyková Lenka , Velychkivska Nadiia , Hill Jonathan P. , Labuta Jan
Published: October 2022

Nuclear magnetic resonance (NMR) lineshape analysis is a powerful tool for the study of chemical kinetics. Here we provide techniques for analysis of the relationship between experimentally observed spin kinetics (transitions between different environments $$A,B,\dots$$

A
,
B
,
⋯

) and corresponding chemical kinetics (transitions between distinct chemical species; e.g., free host and complexed host molecule). The advantages of using analytical solutions for two-, three- or generally N-state exchange lineshapes (without J-coupling) over the widely used numerical calculation for NMR spectral fitting are presented. Several aspects of exchange kinetics including the generalization of coalescence conditions in two-state exchange, the possibility of multiple processes between two states, and differences between equilibrium and steady-state modes are discussed. ‘Reduced equivalent schemes’ are introduced for spin kinetics containing fast-exchanging states, effectively reducing the number of exchanging states. The theoretical results have been used to analyze a host–guest system containing an oxoporphyrinogen complexed with camphorsulfonic acid and several other literature examples, including isomerization, protein kinetics, or enzymatic reactions. The theoretical treatment and experimental examples present an expansion of the systematic approach to rigorous analyses of systems with rich chemical kinetics through NMR lineshape analysis.
A lightweight convolutional neural network model with receptive field block for C-shaped root canal detection in mandibular second molars
Authors: Zhang Lijuan , Xu Feng , Li Ying , Zhang Huimin , Xi Ziyi , Xiang Jie , Wang Bin
Published: October 2022

Rapid and accurate detection of a C-shaped root canal on mandibular second molars can assist dentists in diagnosis and treatment. Oral panoramic radiography is one of the most effective methods of determining the root canal of teeth. There are already some traditional methods based on deep learning to learn the characteristics of C-shaped root canal tooth images. However, previous studies have shown that the accuracy of detecting the C-shaped root canal still needs to be improved. And it is not suitable for implementing these network structures with limited hardware resources. In this paper, a new lightweight convolutional neural network is designed, which combined with receptive field block (RFB) for optimizing feature extraction. In order to optimize the hardware resource requirements of the model, a lightweight, multi-branch, convolutional neural network model was developed in this study. To improve the feature extraction ability of the model for C-shaped root canal tooth images, RFB has been merged with this model. RFB has achieved excellent results in target detection and classification. In the multiscale receptive field block, some small convolution kernels are used to replace the large convolution kernels, which allows the model to extract detailed features and reduce the computational complexity. Finally, the accuracy and area under receiver operating characteristics curve (AUC) values of C-shaped root canals on the image data of our mandibular second molars were 0.9838 and 0.996, respectively. The results show that the deep learning model proposed in this paper is more accurate and has lower computational complexity than many other similar studies. In addition, score-weighted class activation maps (Score-CAM) were generated to localize the internal structure that contributed to the predictions.