bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of location, size and shape of tympanic membrane perforations on hearing: analysis of 400 cases
Authors: Balcı M K , İşlek A , Bakiş Y B , Önal H K
Published: September 2021

Objective

This study aimed to evaluate the effect of size, location and shape of tympanic membrane perforations on hearing levels of a large study group treated in a tertiary referral centre.

Method

Medical data of 458 patients with tympanic membrane perforations were evaluated.

Results

A total of 336 patients had normal middle-ear findings during the surgical procedures. There was a significant difference in terms of mean pure tone average and air–bone gap values between posterior-inferior and anterior-inferior perforations (p = 0.005 and p = 0.044, respectively). The mean air–bone gap value of kidney-shaped perforations was significantly higher. Posterior-superior and posterior perforations were significant indicators for ossicular chain defects (p < 0.001; odds ratio, 14.2 and p = 0.004; odds ratio, 3.4, respectively).

Conclusion

Perforations located in the posterior-inferior quadrant caused the greatest hearing loss. The difference between posterior-inferior and anterior-superior or inferior perforations was statistically significant. Posterior perforations had a significant relationship with ossicular chain pathologies. Kidney-shaped perforations caused higher pure tone average and air–bone gap values than annular, elliptical or pinpoint perforations.
Validation of a Belgian Prediction Model for Patient Encounters at Football Mass Gatherings
Authors: Spaepen Kris , Lauwaert Door , Kaufman Leonard , Haenen Winne AP , Hubloue Ives
Published: September 2021

Background:

To validate the Belgian Plan Risk Manifestations (PRIMA) model, actual patient presentation rates (PPRs) from Belgium’s largest football stadium were compared with predictions provided by existing models and the Belgian PRIMA model.

Methods:

Actual patient presentations gathered from 41 football games (2010-2019) played at the King Baudouin Stadium (Brussels, Belgium) were compared with predictions by existing models and the PRIMA model. All attendees who sought medical help from in-event health services (IEHS) in the stadium or called 1-1-2 within the closed perimeter around the stadium were included. Data were analyzed by ANOVA, Pearson correlation tests, and Wilcoxon singed-rank test.

Results:

A total of 1,630,549 people attended the matches, with 626 people needing first aid. Both the PRIMA and the Hartman model over-estimated the number of patient encounters for each occasion. The Arbon model under-estimated patient encounters for 9.75% (95% CI, 0.49-19.01) of the events. When comparing deviations in predictions between the PRIMA model to the other models, there was a significant difference in the mean deviation (Arbon: Z = −5.566, P <.001, r = −.61; Hartman: Z = −4.245, P <.001, r = .47).

Conclusion:

When comparing the predicted patient encounters, only the Arbon model under-predicted patient presentations, but the Hartman and the PRIMA models consistently over-predicted. Because of continuous over-prediction, the PRIMA model showed significant differences in mean deviation of predicted PPR. The results of this study suggest that the PRIMA model can be used during planning for domestic and international football matches played at the King Baudouin Stadium, but more data and further research are needed.
When voting turnout becomes contentious repertoire: how anti-ELAB protest overtook the District Council election in Hong Kong 2019
Authors: Shum Maggie
Published: September 2021

Under what conditions can voting turnout be transformed into a contentious repertoire? Based on the two case studies of the Umbrella Movement and the Anti-Extradition Law Amendment Bill movement in Hong Kong, I compare how movement actors used the electoral arena to leverage their causes. I propose a new relationship between street and electoral politics – short-term mobilization that turns voting turnout into a contentious repertoire. I posit three necessary scope conditions for movements to perceive this electoral strategy as viable: (1) protest cycle precedes and/or overlaps with the electoral period, (2) election perceived to be competitive, and (3) closing of political opportunity window for street mobilization. I further argue that the tactics movements pursue in the electoral arena is conditional on the relationship between movement actors and political elites, and regime type. In democratic regimes where parties and elections are institutionalized and less volatile, movements are on a more solid ground to invest in a long-term electoral strategy with existing parties. Contrarily, electoral competition in authoritarian regimes tends to skew toward incumbent's advantage. Movement activists and political elites may seek short-term strategic mobilizations focusing on the election at hand rather than a long-term plan. This argument illuminates the common ground between collective action and voting, and thus bridging the two sets of literature for further engagement, as recent movements such as the Black Lives Matter and the Sunrise Movement in the United States and Navalny's anti-Putin movement in Russia are mobilizing their supporters to take on the electoral arena.
A Comparison of Preterm Birth Rate and Growth from Birth to 18 Years Old between in Vitro Fertilization and Spontaneous Conception of Twins
Authors: Zhang Yali , Hong Xuanming , Gao Wenjing , Lv Jun , Yu Canqing , Wang Shengfeng , Huang Tao , Sun Dianjianyi , Liao Chunxiao , Pang Zengchang , Yu Min , Wang Hua , Wu Xianping , Dong Zhong , Wu Fan , Jiang Guohong , Wang Xiaojie , Liu Yu , Deng Jian , Lu Lin , Cao Weihua , Li Liming
Published: September 2021

The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1–2 years), preschool (3–5 years), primary or elementary school (6–11 years), and adolescence (10–18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0–18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.
Field‐Aligned Electron Density Distribution of the Inner Magnetosphere Inferred From Coordinated Observations of Arase and Van Allen Probes
Authors: Obana Yuki , Miyashita Yukinaga , Maruyama Naomi , Shinbori Atsuki , Nosé Masahito , Shoji Masafumi , Kumamoto Atsushi , Tsuchiya Fuminori , Matsuda Shoya , Matsuoka Ayako , Kasahara Yoshiya , Miyoshi Yoshizumi , Shinohara Iku , Kurth William S. , Smith Charles W. , MacDowall Robert J.
Published: September 2021

The Radiation Belt Storm Probes (RBSP) and the Arase satellites have different inclinations and sometimes they fly both near the equator and off the equator on the same magnetic field line simultaneously. Such conjunction events give us opportunities to compare the electron density at different latitudes. In this study, we analyzed the plasma waves observed by Arase and RBSP during the three conjunction events during and after the September 7, 2017 storm. The electron number density at the satellite positions was estimated from frequencies of the Upper Hybrid Resonance emissions obtained by the High Frequency Analyzer of the Plasma Wave Experiment onboard the Arase and the Waves instrument onboard the RBSP, respectively. During the three conjunction events, the satellites passed through the plume, inner trough (the narrow region with low electron density between the main body of the plasmasphere and the plume), plasmatrough with variable electron density, and partially refilled plasmasphere. The power‐law index m for the inner trough and plume was inferred to be 4–7 and ∼0, respectively. This is interpreted to mean that the trough was close to collisionless and the plume was relatively near diffusive equilibrium. In the plasmatrough with the varying density, both the high‐density and low‐density regions had m ∼ 0. The low‐density portion of this region may have a different origin from the inner trough, because of the different m indices. For the partially refilled plasmasphere in the storm recovery phase, the power‐law index m showed negative values, meaning that the density in the equatorial plane was higher than at higher latitudes.
Simultaneous Observation of Whistler Waves and Electron Cyclotron Harmonic Waves in the Separatrix Region of Magnetopause Reconnection
Authors: Yu Xiancai , Lu Quanming , Wang Rongsheng , Gao Xinliang , Sang Longlong , Wang Shui
Published: September 2021

A variety of plasma waves have been observed in the separatrix region during magnetic reconnection, and their roles on reconnection and exciting mechanisms are still controversial. In this paper, we report the whistler wave with a very narrow frequency band just above half of the electron cyclotron frequency in the separatrix region. This whistler wave is accompanied with the electron cyclotron harmonic (ECH) waves. The ECH waves have frequencies between the first and fifth harmonic of electron cyclotron frequency . The wave normal angle of the whistler waves is ∼20°–∼40°, meaning the quasi‐parallel propagation, while the ECH waves propagate perpendicular to the background magnetic field with . In the separatrix region, the electrons have a loss‐cone distribution while these two kinds of waves are observed. Based on the linear theory, such an electron distribution is unstable for both whistler waves and ECH waves. It indicates that these two kinds of waves are generated by the electron loss‐cone instability.
Spatiotemporal Characteristics of Relocated Deep Low‐Frequency Earthquakes Beneath 52 Volcanic Regions in Japan Over an Analysis Period of 14 Years and 9 Months
Authors: Kurihara Ryo , Obara Kazushige
Published: September 2021

We constructed a catalog of deep low‐frequency (DLF) earthquakes beneath 52 volcanic regions in Japan to investigate their seismicity based on three analyses: relocation, classification, and detection. Relocation and classification analyses were based on waveform correlation, and detection analysis was conducted using the matched filter technique. We detected a total of 105,327 DLF earthquakes and found that DLF earthquakes in many regions are spatially clustered with a spatial spread of only 1–2 km with approximately 5 km intervals between the lower limit of crustal earthquakes and Moho discontinuity. Based on temporal seismicity patterns, DLF earthquake groups in each region can be classified into episodic and non‐episodic types. Episodic groups consist of seismic swarms and quiescence. In some episodic groups, DLF earthquakes have constant recurrence interevent times or increasing interevent times as a function of time. Swarms of DLF earthquakes sometimes are associated with volcanic activities at the surface, which are crustal deformations of Meakan volcano, 2007 and 2014 eruptions of Ontake volcano, and the 2015 magma intrusion of Sakurajima volcano. The spatiotemporal characteristics of DLF earthquake groups may be linked to the movement of magmatic fluids. The discrete vertical separation of DLF earthquake groups may reflect small‐scale heterogeneities, such as injected magma. Periodic activity patterns may be caused by volcanic mechanisms, such as intermittent magma flow. The variety of DLF earthquake patterns may suggest that multiple mechanisms, including magma cooling and intermittent magma flow in complex magma supply systems, may trigger DLF earthquakes rather than a single mechanism.
Tectonic Control Over Shallow Crustal Exhumation Across the India‐Asia Convergent Margin
Authors: Pundir S. , Adlakha V. , Devrani R. , Kumar S.
Published: September 2021

Understanding the processes and mechanisms responsible for exhumation are essential for determining the evolution of landscapes. Our knowledge of these issues in continental convergent margins is still incomplete despite decades of research. Here, we present a record of exhumation rates obtained from thermochronology across the collision zone of the Himalayan‐Tibetan orogen, which has been carved by the dextral Karakoram fault (KF) along its western margin. Our thermochronology results across the KF suggest that transpression controlled exhumation from ∼10 to 8 Ma. Exhumation rates at the margin of the Tibetan plateau, in the SE Karakoram range, to the north of the KF are twice as high as the Ladakh range, to the south of the KF, since at least middle Miocene. We hypothesize that rapid exhumation of the Tibetan margin was in response to topographic uplift and subsequent erosion due to the convective removal of the lower lithosphere, triggered by the rollback of the subducting Indian lower crust during the Oligocene‐Miocene in an early phase. Our thermochronology results document an additional two‐fold increase in the exhumation rates of the Tibetan margin since the late Mio‐Pliocene. We propose that the underthrusting of the Indian Plate below Tibet during the late Mio‐Pliocene was responsible for this additional increase of exhumation rates of the Tibetan margin in the late phase. These exhumation rates are in good agreement with the topographic slope, relief, and channel steepness data of these regions. Thus, the coupling of tectonics and topography dictated the exhumation patterns since late Mio‐Pliocene.
Sustainable irrigation based on co-regulation of soil water supply and atmospheric evaporative demand
Authors: Zhang Jingwen , Guan Kaiyu , Peng Bin , Pan Ming , Zhou Wang , Jiang Chongya , Kimm Hyungsuk , Franz Trenton E. , Grant Robert F. , Yang Yi , Rudnick Daran R. , Heeren Derek M. , Suyker Andrew E. , Bauerle William L. , Miner Grace L.
Published: September 2021

Irrigation is an important adaptation to reduce crop yield loss due to water stress from both soil water deficit (low soil moisture) and atmospheric aridity (high vapor pressure deficit, VPD). Traditionally, irrigation has primarily focused on soil water deficit. Observational evidence demonstrates that stomatal conductance is co-regulated by soil moisture and VPD from water supply and demand aspects. Here we use a validated hydraulically-driven ecosystem model to reproduce the co-regulation pattern. Specifically, we propose a plant-centric irrigation scheme considering water supply-demand dynamics (SDD), and compare it with soil-moisture-based irrigation scheme (management allowable depletion, MAD) for continuous maize cropping systems in Nebraska, United States. We find that, under current climate conditions, the plant-centric SDD irrigation scheme combining soil moisture and VPD, could significantly reduce irrigation water use (−24.0%) while maintaining crop yields, and increase economic profits (+11.2%) and irrigation water productivity (+25.2%) compared with MAD, thus SDD could significantly improve water sustainability.
Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B
Authors: Deng Maximilian Y. , Sturm Dominik , Pfaff Elke , Sill Martin , Stichel Damian , Balasubramanian Gnana Prakash , Tippelt Stephan , Kramm Christof , Donson Andrew M. , Green Adam L. , Jones Chris , Schittenhelm Jens , Ebinger Martin , Schuhmann Martin U. , Jones Barbara C. , van Tilburg Cornelis M. , Wittmann Andrea , Golanov Andrey , Ryzhova Marina , Ecker Jonas , Milde Till , Witt Olaf , Sahm Felix , Reuss David , Sumerauer David , Zamecnik Josef , Korshunov Andrey , von Deimling Andreas , Pfister Stefan M. , Jones David T. W.
Published: September 2021

Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n = 23) and ALL (n = 9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrentPDGFRAamplification and loss ofCDKN2A/Band an absence of somatic hotspot mutations in genes encoding histone 3 variants orIDH1/2, uncovering diagnostic markers and potentially actionable targets.
Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma
Authors: DeSisto John , Lucas John T. , Xu Ke , Donson Andrew , Lin Tong , Sanford Bridget , Wu Gang , Tran Quynh T. , Hedges Dale , Hsu Chih-Yang , Armstrong Gregory T. , Arnold Michael , Bhatia Smita , Flannery Patrick , Lemma Rakeb , Hardie Lakotah , Schüller Ulrich , Venkataraman Sujatha , Hoffman Lindsey M. , Dorris Kathleen , Mulcahy Levy Jean M. , Hankinson Todd C. , Handler Michael , Liu Arthur K. , Foreman Nicholas , Vibhakar Rajeev , Jones Kenneth , Allen Sariah , Zhang Jinghui , Baker Suzanne J. , Merchant Thomas E. , Orr Brent A. , Green Adam L.
Published: September 2021

Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.
Generalized and scalable trajectory inference in single-cell omics data with VIA
Authors: Stassen Shobana V. , Yip Gwinky G. K. , Wong Kenneth K. Y. , Ho Joshua W. K. , Tsia Kevin K.
Published: September 2021

Inferring cellular trajectories using a variety of omic data is a critical task in single-cell data science. However, accurate prediction of cell fates, and thereby biologically meaningful discovery, is challenged by the sheer size of single-cell data, the diversity of omic data types, and the complexity of their topologies. We present VIA, a scalable trajectory inference algorithm that overcomes these limitations by using lazy-teleporting random walks to accurately reconstruct complex cellular trajectories beyond tree-like pathways (e.g., cyclic or disconnected structures). We show that VIA robustly and efficiently unravels the fine-grained sub-trajectories in a 1.3-million-cell transcriptomic mouse atlas without losing the global connectivity at such a high cell count. We further apply VIA to discovering elusive lineages and less populous cell fates missed by other methods across a variety of data types, including single-cell proteomic, epigenomic, multi-omics datasets, and a new in-house single-cell morphological dataset.
Profilin and Mical combine to impair F-actin assembly and promote disassembly and remodeling
Authors: Grintsevich Elena E. , Ahmed Giasuddin , Ginosyan Anush A. , Wu Heng , Rich Shannon K. , Reisler Emil , Terman Jonathan R.
Published: September 2021

Cellular events require the spatiotemporal interplay between actin assembly and actin disassembly. Yet, how different factors promote the integration of these two opposing processes is unclear. In particular, cellular monomeric (G)-actin is complexed with profilin, which inhibits spontaneous actin nucleation but fuels actin filament (F-actin) assembly by elongation-promoting factors (formins, Ena/VASP). In contrast, site-specific F-actin oxidation by Mical promotes F-actin disassembly and release of polymerization-impaired Mical-oxidized (Mox)-G-actin. Here we find that these two opposing processes connect with one another to orchestrate actin/cellular remodeling. Specifically, we find that profilin binds Mox-G-actin, yet these complexes do not fuel elongation factors’-mediated F-actin assembly, but instead inhibit polymerization and promote further Mox-F-actin disassembly. UsingDrosophilaas a model system, we show that similar profilin–Mical connections occur in vivo – where they underlie F-actin/cellular remodeling that accompanies Semaphorin–Plexin cellular/axon repulsion. Thus, profilin and Mical combine to impair F-actin assembly and promote F-actin disassembly, while concomitantly facilitating cellular remodeling and plasticity.
The relevance of rock shape over mass—implications for rockfall hazard assessments
Authors: Caviezel Andrin , Ringenbach Adrian , Demmel Sophia E. , Dinneen Claire E. , Krebs Nora , Bühler Yves , Christen Marc , Meyrat Guillaume , Stoffel Andreas , Hafner Elisabeth , Eberhard Lucie A. , Rickenbach Daniel von , Simmler Kevin , Mayer Philipp , Niklaus Pascal S. , Birchler Thomas , Aebi Tim , Cavigelli Lukas , Schaffner Michael , Rickli Stefan , Schnetzler Christoph , Magno Michele , Benini Luca , Bartelt Perry
Published: September 2021

The mitigation of rapid mass movements involves a subtle interplay between field surveys, numerical modelling, and experience. Hazard engineers rely on a combination of best practices and, if available, historical facts as a vital prerequisite in establishing reproducible and accurate hazard zoning. Full-scale field tests have been performed to reinforce the physical understanding of debris flows and snow avalanches. Rockfall dynamics are - especially the quantification of energy dissipation during the complex rock-ground interaction - largely unknown. The awareness of rock shape dependence is growing, but presently, there exists little experimental basis on how rockfall hazard scales with rock mass, size, and shape. Here, we present a unique data set of induced single-block rockfall events comprising data from equant and wheel-shaped blocks with masses up to 2670 kg, quantifying the influence of rock shape and mass on lateral spreading and longitudinal runout and hence challenging common practices in rockfall hazard assessment.
Exosome-mediated stable epigenetic repression of HIV-1
Authors: Shrivastava Surya , Ray Roslyn M. , Holguin Leo , Echavarria Lilliana , Grepo Nicole , Scott Tristan A. , Burnett John , Morris Kevin V.
Published: September 2021

Human Immunodeficiency Virus (HIV-1) produces a persistent latent infection. Control of HIV-1 using combination antiretroviral therapy (cART) comes at the cost of life-shortening side effects and development of drug-resistant HIV-1. An ideal and safer therapy should be deliverable in vivo and target the stable epigenetic repression of the virus, inducing a stable “block and lock” of virus expression. Towards this goal, we developed an HIV-1 promoter-targeting Zinc Finger Protein (ZFP-362) fused to active domains of DNA methyltransferase 3 A to induce long-term stable epigenetic repression of HIV-1. Cells were engineered to produce exosomes packaged with RNAs encoding this HIV-1 repressor protein. We find here that the repressor loaded anti-HIV-1 exosomes suppress virus expression and that this suppression is mechanistically driven by DNA methylation of HIV-1 in humanized NSG mouse models. The observations presented here pave the way for an exosome-mediated systemic delivery platform of therapeutic cargo to epigenetically repress HIV-1 infection.
Unwinding of a DNA replication fork by a hexameric viral helicase
Authors: Javed Abid , Major Balazs , Stead Jonathan A. , Sanders Cyril M. , Orlova Elena V.
Published: September 2021

Hexameric helicases are motor proteins that unwind double-stranded DNA (dsDNA) during DNA replication but how they are optimised for strand separation is unclear. Here we present the cryo-EM structure of the full-length E1 helicase from papillomavirus, revealing all arms of a bound DNA replication fork and their interactions with the helicase. The replication fork junction is located at the entrance to the helicase collar ring, that sits above the AAA + motor assembly. dsDNA is escorted to and the 5´ single-stranded DNA (ssDNA) away from the unwinding point by the E1 dsDNA origin binding domains. The 3´ ssDNA interacts with six spirally-arranged β-hairpins and their cyclical top-to-bottom movement pulls the ssDNA through the helicase. Pulling of the RF against the collar ring separates the base-pairs, while modelling of the conformational cycle suggest an accompanying movement of the collar ring has an auxiliary role, helping to make efficient use of ATP in duplex unwinding.
Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy
Authors: Takamatsu Kimiharu , Tanaka Nobuyuki , Hakozaki Kyohei , Takahashi Ryohei , Teranishi Yu , Murakami Tetsushi , Kufukihara Ryohei , Niwa Naoya , Mikami Shuji , Shinojima Toshiaki , Sasaki Takashi , Sato Yusuke , Kume Haruki , Ogawa Seishi , Kakimi Kazuhiro , Kamatani Takashi , Miya Fuyuki , Tsunoda Tatsuhiko , Aimono Eriko , Nishihara Hiroshi , Sawada Kazuaki , Imamura Takeshi , Mizuno Ryuichi , Oya Mototsugu
Published: September 2021

A cutting edge therapy for future immuno-oncology is targeting a new series of inhibitory receptors (IRs): LAG-3, TIM-3, and TIGIT. Both immunogenomic analyses and diagnostic platforms to distinguish candidates and predict good responders to these IR-related agents are vital in clinical pathology. By applying an automated single-cell count for immunolabelled LAG-3, TIM-3, and TIGIT, we reveal that individual IR levels with exclusive domination in each tumour can serve as valid biomarkers for profiling human renal cell carcinoma (RCC). We uncover the immunogenomic landscape associated with individual IR levels in human RCC tumours with metastases in various organs and histological subtypes. We then externally validate our results and devise a workflow with optimal biomarker cut-offs for discriminating the LAG-3, TIM-3, and TIGIT tumour profiles. The discrimination of LAG-3, TIM-3, and TIGIT profiles in tumours may have a broad impact on investigations of immunotherapy responses after targeting a new series of IRs.
Geolocated dataset of Chinese overseas development finance
Authors: Ray Rebecca , Gallagher Kevin P. , Kring William , Pitts Joshua , Simmons B. Alexander
Published: September 2021

China is now the world’s largest source of bilateral development finance and will likely continue to play a prominent role in sovereign lending through its multi-billion-dollar Belt and Road Initiative. This paper introduces major methodological enhancements in tracking this finance: the use of an original application programming interface (API) to gathers news in multiple languages; double-verification of every record to ensure every finance commitment has been formalized; and visual geo-location to trace the precise footprint of every project. The resulting dataset enables economic, environmental, and social analyses with high-precision spatial accuracy, as well as spatiotemporal monitoring by project stakeholders and enhanced planning by project managers. It covers the years 2008–2019 to enable analysis before and after the announcement of the Belt and Road Initiative. It includes 862 finance commitments, 669 of which have geographic location, to 94 countries across the world.
Loneliness, social isolation, and pain following the COVID-19 outbreak: data from a nationwide internet survey in Japan
Authors: Yamada Keiko , Wakaizumi Kenta , Kubota Yasuhiko , Murayama Hiroshi , Tabuchi Takahiro
Published: September 2021

The aim of cross-sectional study was to investigate the association between loneliness, increased social isolation, and pain following the COVID-19 outbreak. A total of 25,482 participants, aged 15–79 years, were assessed using an internet survey; the University of California, Los Angeles Loneliness Scale (Version 3), Short Form 3-item (UCLA-LS3-SF3) was used to assess loneliness, and a modified item of the UCLA-LS3-SF3 was used to measure the perception of increased social isolation during the pandemic. The outcome measures included the prevalence/incidence of pain (i.e., headache, neck or shoulder pain, upper limb pain, low back pain, and leg pain), pain intensity, and the prevalence of past/present chronic pain. Pain intensity was measured by the pain/discomfort item of the 5-level version of the EuroQol 5 Dimension scale. Odds ratios of pain prevalence/incidence and past/present chronic pain prevalence according to the UCLA-LS3-SF3 scoring groups (tertiles) and the frequency of the perceived increase in social isolation (categories 1–5) were calculated using multinomial logistic regression analysis. The mean pain intensity values among different loneliness and social isolation levels were tested using an analysis of covariance. Increased loneliness and the severity of the perceived social isolation were positively associated with the prevalence/incidence of pain, pain intensity, and the prevalence of past/present chronic pain.
A new approach to produce IgG4-like bispecific antibodies
Authors: Zhao Caizhi , Zhang Wei , Gong Guihua , Xie Liping , Wang Ming-Wei , Hu Youjia
Published: September 2021

While achieving rapid developments in recent years, bispecific antibodies are still difficult to design and manufacture, due to mispair of both heavy and light chains. Here we report a novel technology to make bispecific molecules. The knob-into-hole method was used to pair two distinct heavy chains as a heterodimer. IgG4 S228P CH1-CL interface was then partially replaced by T-cell receptor α/β constant domain to increase the efficiency of cognate heavy and light chain pairing. Following expression and purification, the bispecific antibody interface exchange was confirmed by Western blotting and LC–MS/MS. To ensure its validity, we combined a monovalent bispecific antibody against PD-1 (sequence from Pembrolizumab) and LAG3 (sequence from Relatlimab). The results showed that the molecule could be assembled correctly at a ratio of 95% in cells. In vitro functional assay demonstrated that the purified bispecific antibody exhibits an enhanced agonist activity compared to that of the parental antibodies. Low immunogenicity was predicted by an open-access software and ADA test.
The Pisciarelli main fumarole mechanisms reconstructed by electrical resistivity and induced polarization imaging
Authors: Troiano A. , Isaia R. , Tramparulo F. D. A. , Di Giuseppe M. G.
Published: September 2021

Pisciarelli, together with the adjacent Solfatara maar-diatreme, represents the most active structure of the Campi Flegrei caldera (Italy) in terms of degassing and seismic activity. This paper aims to define the structure of the Pisciarelli hydrothermal system (down to a 20 m depth) through electrical resistivity and time-domain-induced polarization tomography and self-potential mapping. The retrieved 3D image of the area helps reconstruct the Pisciarelli subsurface in its area of maximum degassing, containing the main fumarole (“soffione”) and the mud pool. In particular, a channel has been identified in which fluids stored in a deeper reservoir rise toward the surface. Such a structure seems to be surmounted by a clay-cap formation that could govern the circulation of fluids and the abundance of gases/vapors emitted by the soffione. Based on this new reconstruction of the Pisciarelli fumarolic field structural setting, the first conceptual model has been suggested that is capable of simultaneously explaining the mechanisms governing soffione activity and elucidating the role played by the fluid/gas of deeper origin in the shallow fluid circulation system. The proposed model can potentially help to better monitor the processes occurring throughout the Pisciarelli fumarolic field and provide an evaluation of the associated hazards.
Inhaled sphingosine has no adverse side effects in isolated ventilated and perfused pig lungs
Authors: Carstens Henning , Kalka Katharina , Verhaegh Rabea , Schumacher Fabian , Soddemann Matthias , Wilker Barbara , Keitsch Simone , Sehl Carolin , Kleuser Burkhard , Wahlers Thorsten , Reiner Gerald , Koch Achim , Rauen Ursula , Gulbins Erich , Kamler Markus
Published: September 2021

Ex-vivo lung perfusion (EVLP) systems like XVIVO are more and more common in the setting of lung transplantation, since marginal donor-lungs can easily be subjected to a performance test or be treated with corticosteroids or antibiotics in high dose regimes. Donor lungs are frequently positive in bronchoalveolar lavage (BAL) bacterial cultures (46–89%) which leads to a donor-to-recipient transmission and after a higher risk of lung infection with reduced posttransplant outcome. We have previously shown that sphingosine very efficiently kills a variety of pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus and epidermidis, Escherichia coli or Haemophilus influenzae. Thus, sphingosine could be a new treatment option with broadspectrum antiinfective potential, which may improve outcome after lung transplantation when administered prior to lung re-implantation. Here, we tested whether sphingosine has any adverse effects in the respiratory tract when applied into isolated ventilated and perfused lungs. A 4-h EVLP run using minipig lungs was performed. Functional parameters as well as perfusate measurements where obtained. Biopsies were obtained 30 min and 150 min after inhalation of sphingosine. Tissue samples were fixed in paraformaldehyde, embedded in paraffin and sectioned. Hemalaun, TUNEL as well as stainings with Cy3-coupled anti-sphingosine or anti-ceramide antibodies were implemented. We demonstrate that tube-inhalation of sphingosine into ex-vivo perfused and ventilated minipig lungs results in increased levels of sphingosine in the luminal membrane of bronchi and the trachea without morphological side effects up to very high doses of sphingosine. Sphingosine also did not affect functional lung performance. In summary, the inhalation of sphingosine results in an increase of sphingosine concentrations in the luminal plasma membrane of tracheal and bronchial epithelial cells. The inhalation has no local side effects in ex-vivo perfused and ventilated minipig lungs.
Real-time monitoring of Arundo donax response to saline stress through the application of in vivo sensing technology
Authors: Michela Janni , Claudia Cocozza , Federico Brilli , Sara Pignattelli , Filippo Vurro , Nicola Coppede , Manuele Bettelli , Davide Calestani , Loreto Francesco , Zappettini Andrea
Published: September 2021

One of the main impacts of climate change on agriculture production is the dramatic increase of saline (Na+) content in substrate, that will impair crop performance and productivity. Here we demonstrate how the application of smart technologies such as an in vivo sensor, termed bioristor, allows to continuously monitor in real-time the dynamic changes of ion concentration in the sap ofArundo donaxL. (common name giant reed or giant cane), when exposed to a progressive salinity stress. Data collected in vivo by bioristor sensors inserted at two different heights intoA. donaxstems enabled us to detect the early phases of stress response upon increasing salinity. Indeed, the continuous time-series of data recorded by the bioristor returned a specific signal which correlated with Na+content in leaves of Na-stressed plants, opening a new perspective for its application as a tool for in vivo plant phenotyping and selection of genotypes more suitable for the exploitation of saline soils.
Heat capacity anomalies of the molecular crystal 1-fluoro-adamantane at low temperatures
Authors: Szewczyk Daria , Gebbia Jonathan F. , Jeżowski Andrzej , Krivchikov Alexander I. , Guidi Tatiana , Cazorla Claudio , Tamarit Josep-Lluís
Published: September 2021

Disorder–disorder phase transitions are rare in nature. Here, we present a comprehensive low-temperature experimental and theoretical study of the heat capacity and vibrational density of states of 1-fluoro-adamantane (C10H15F), an intriguing molecular crystal that presents a continuous disorder–disorder phase transition at T = 180 K and a low-temperature tetragonal phase that exhibits fractional fluorine occupancy. It is shown that fluorine occupancy disorder in the low-T phase of 1-fluoro-adamantane gives rise to the appearance of low-temperature glassy features in the corresponding specific heat (i.e., “boson peak” -BP-) and vibrational density of states. We identify the inflation of low-energy optical modes as the main responsible for the appearance of such glassy heat-capacity features and propose a straightforward correlation between the first localized optical mode and maximum BP temperature for disordered molecular crystals (either occupational or orientational). Thus, the present study provides new physical insights into the possible origins of the BP appearing in disordered materials and expands the set of molecular crystals in which “glassy-like” heat-capacity features have been observed.
Leveraging long short-term memory (LSTM)-based neural networks for modeling structure–property relationships of metamaterials from electromagnetic responses
Authors: Pillai Prajith , Pal Parama , Chacko Rinu , Jain Deepak , Rai Beena
Published: September 2021

We report a neural network model for predicting the electromagnetic response of mesoscale metamaterials as well as generate design parameters for a desired spectral behavior. Our approach entails treating spectral data as time-varying sequences and the inverse problem as a single-input multiple output model, thereby compelling the network architecture to learn the geometry of the metamaterial designs from the spectral data in lieu of abstract features.
Delineation of genotype × environment interaction for identification of stable genotypes for tillering phase drought stress tolerance in sugarcane
Authors: Mahadevaiah C. , Hapase Prakash , Sreenivasa V. , Hapase Ramesh , Swamy H. K. Mahadeva , Anilkumar C. , Mohanraj K. , Hemaprabha G. , Ram Bakshi
Published: September 2021

Sugarcane is a trans-seasonal long-duration crop and tillering phase (60–150 days) is the most sensitive phase for moisture stress, causing significant reduction in biomass accumulation. The study focussed to assess the Genotype × Environment Interaction (GEI) for tillering phase moisture stress and to identify the stable genotypes in sugarcane. The study dealt with 14 drought tolerant genotypes and two standards (Co 86032 and CoM 0265) which were evaluated in two plant and one ratoon trials at four locations in Maharashtra, India. The moisture stress was imposed for 60 days from 90 to 150 days after planting and corresponded to tillering phase by withholding the irrigation. The AMMI ANOVA showed significant GEI for cane and CCS yield accounting 18.33 and 19.45 percent of variability respectively. Drought and genotype main effects were highly significant accounting 49.08 and 32.59 percent variability for cane yield and, 52.45 and 28.10 percent variability for CCS yield respectively. The first two interactive principal component (IPCA) biplots of AMMI showed diverse nature of all four environments and the DiscriminativevsMean biplots of Genotype + genotype × environment interaction (GGE) model showed that ‘Pune’ as the highly discriminating environment. The genotype ranking biplots of GGE showed that Co 85019 was the most stable genotype followed by Co 98017. Similar results were also observed in YieldvsIPCA1 biplot of AMMI, which revealed Co 85019 and Co 98017 as high yielding stable varieties. Yield related environmental maximum (YREM) showed thirteen and nine percent loss due to crossover interactions in Co 85019 for cane yield and CCS yield respectively. The multi-environment BLUP and genotype stability index (GSI) has reaffirmed that Co 85019 as a drought proof and stable genotype with high yield under tillering phase drought stress. The results suggested using Co 85019 for cultivation in drought prone regions and the usefulness of the methodology for identifying more such sugarcane varieties for the benefit of resource poor famers in drought affected regions.
Lactic acid as a major contributor to hand surface infection barrier and its association with morbidity to infectious disease
Authors: Nishioka Yuki , Nagano Kenichi , Koga Yoshitaka , Okada Yasuhiro , Mori Ichiro , Hayase Atsuko , Mori Takuya , Manabe Kenji
Published: September 2021

Although the surface of the human hands contains high antimicrobial activity, studies investigating the precise components involved and the relationship between natural antimicrobial activity and morbidity in infectious diseases are limited. In this study, we developed a method to quantitatively measure the antimicrobial activity of hand surface components. Using a clinical survey, we validated the feasibility of our method and identified antimicrobial factors on the surface of the human hand. In a retrospective observational study, we compared the medical histories of the participants to assess infectious diseases. We found that the antimicrobial activity on the surface of the hands was significantly lower in the high morbidity group (N = 55) than in the low morbidity group (N = 54), indicating a positive association with the history of infection in individuals. A comprehensive analysis of the hand surface components indicated that organic acids, especially lactic acid and antimicrobial peptides, are highly correlated with antimicrobial activity. Moreover, the application of lactic acid using the amount present on the surface of the hand significantly improved the antimicrobial activity. These findings suggest that hand hygiene must be improved to enhance natural antimicrobial activity on the surface of the hands.
Phenology of Oithona similis demonstrates that ecological flexibility may be a winning trait in the warming Arctic
Authors: Balazy Kaja , Boehnke Rafał , Trudnowska Emilia , Søreide Janne E. , Błachowiak-Samołyk Katarzyna
Published: September 2021

Rapidly warming Arctic is facing significant shifts in the zooplankton size-spectra manifested as increasing numbers of the small-sized copepod Oithona similis. Here we present a unique continuous data set covering 22 months, on its copepodite structure along with environmental drivers in the Atlantic-influenced high Arctic fjord Isfjorden (Spitsbergen). Abundance maxima of O. similis were observed in September when the highest seawater temperature was recorded. A high concentration of the indicator species of Atlantification Oithona atlantica was also observed at that time. The clear dominance of O. similis in the zooplankton community during the dark, theoretically unproductive season emphasizes its substantial role in sustaining a continuous carbon flow, when most of the large herbivorous copepods fall into sleeping state. The high sex ratio observed twice in both years during periods of high primary production suggests two main reproductive events per year. O. similis reproduced even in very low temperatures (< 0 °C) previously thought to limit their fecundity, which proves its unique thermal tolerance. Our study provides a new insight on ecology of this key copepod of marine ecosystems across the globe, and thus confirm the Climatic Variability Hypothesis assuming that natural selection favour species with such flexible adaptive traits as O. similis.
Daily activity in minimal footwear increases foot strength
Authors: Curtis Rory , Willems Catherine , Paoletti Paolo , D’Août Kristiaan
Published: September 2021

The human foot is uniquely adapted to bipedal locomotion and has a deformable arch of variable stiffness. Intrinsic foot muscles regulate arch deformation, making them important for foot function. In this study we explore the hypothesis that normal daily activity in minimal footwear, which provides little or no support, increases foot muscle strength. Western adults wore minimal footwear for a six-month period (the “intervention” group). Foot strength, i.e., maximum isometric plantarflexion strength at the metatarsophalangeal joints, and foot biometrics were measured before and after the intervention. An additional group was investigated to add further insight on the long-term effects of footwear, consisting of Western adults with an average 2.5 years of experience in minimal footwear (the “experienced” group). This study shows that foot strength increases by, on average, 57.4% (p < 0.001) after six months of daily activity in minimal footwear. The experienced group had similar foot strength as the post intervention group, suggesting that six months of regular minimal footwear use is sufficient to gain full strength, which may aid healthy balance and gait.
Paired comparisons of mutational profiles before and after brachytherapy in asian uveal melanoma patients
Authors: Lee Woo Seung , Lee Junwon , Choi Jun Jeong , Kang Hyun Goo , Lee Sung Chul , Kim Ju Han
Published: September 2021

Uveal melanoma(UM) is the most common primary intraocular malignancy in adults. However, the incidence of UM in Asia is 10 to 20 times less than in Western populations. Therefore, for the first time, we report our whole exome sequencing (WES) data analysis to discover differences in the molecular features of Asian and Western UM, and to determine the disparities between the primary tumor before brachytherapy and enucleated samples after brachytherapy. WES of 19 samples (13 primary tumors, 5 enucleation samples after brachytherapy, and 1 liver metastasis) from 13 patients diagnosed with UM and treated between 2007 and 2019 at the Yonsei University Health System (YUHS) were analyzed using bioinformatics pipelines. We identified significantly altered genes in Asian UM and changes in mutational profiles before and after brachytherapy using various algorithms. GNAQ, BAP1, GNA11, SF3B1 and CYSLTR2 were significantly mutated in Asian UM, which is similar that reported frequently in previous Western-based UM studies. There were also similar copy number alterations (M3, 1p loss, 6p gain, 8q gain) in both groups. In paired comparisons of the same patients, DICER1 and LRP1B were distinctly mutated only in tumor samples obtained after brachytherapy using rare-variant association tests (P = 0.01, 0.01, respectively). The mutational profiles of Asian UM were generally similar to the data from previous Western-based studies. DICER1 and LRP1B were newly mutated genes with statistical significance in the regrowth samples after brachytherapy compared to the primary tumors, which may be related to resistance to brachytherapy.