bluuebunny/crossref_metadata_2025 huggingface dataset:
Comment on “Accelerated Fill‐Up of the Arbuckle Group Aquifer and Links to U.S. Midcontinent Seismicity” by Ansari et al. (2019)
Authors: Peterie Shelby L. , Newell K. David , Bohling Geoffrey C. , Mandel Rolfe D.
Published: October 2020

Spatiotemporal analysis of Arbuckle Group formation pressures and disposal volumes provides insight into contributing factors underlying the regional trends in formation pressure identified by Ansari et al. (2019, https://doi.org/10.1029/2018JB016926) using statistical analysis. Based on trends in bivariate correlation of reported values, Ansari et al. (2019) suggested that rising formation pressures were a result of fluid injection within 25 km. Our primary concern is that the correlation trends are most likely an artifact of the method used by Ansari et al. (2019), at least in part, and the conclusion that pressure diffusion is limited to within 25 km of the injection point does not necessarily follow from the analysis. We also note that estimated formation pressure depends on the depth of the pressure gauge, which, in some cases, varies from one measurement to the next and should be accounted for to accurately assess measured changes. The spatial relationship of formation pressure changes among wells provides valuable insight into the origin of those changes. For each well, we project pressure to a baseline depth to account for changes in gauge depth and reexamine trends in formation pressure. Spatiotemporal progression suggests post‐2011 formation pressure changes originate from a spatially dense group of high‐rate saltwater disposal wells near the Kansas‐Oklahoma border well beyond 25 km (and as far as 90 km) away.
Reactivation of Fault Systems by Compartmentalized Hydrothermal Fluids in the Southern Andes Revealed by Magnetotelluric and Seismic Data
Authors: Pearce R. K. , Sánchez de la Muela A. , Moorkamp M. , Hammond J. O. S. , Mitchell T. M. , Cembrano J. , Araya Vargas J. , Meredith P. G. , Iturrieta P. , Pérez‐Estay N. , Marshall N. R. , Smith J. , Yañez G. , Ashley Griffith W. , Marquardt C. , Stanton‐Yonge A. , Núñez R.
Published: October 2020

In active volcanic arcs such as the Andean volcanic mountain belt, magmatically sourced fluids are channeled through the brittle crust by faults and fracture networks. In the Andes, volcanoes, geothermal springs, and major mineral deposits have a spatial and genetic relationship with NNE trending, margin‐parallel faults and margin‐oblique, NW trending Andean Transverse Faults (ATF). The Tinguiririca and Planchón‐Peteroa volcanoes in the Andean Southern Volcanic Zone (SVZ) demonstrate this relationship, as their spatially associated thermal springs show strike alignment to the NNE oriented El Fierro Thrust Fault System. We constrain the fault system architecture and its interaction with volcanically sourced hydrothermal fluids using a combined magnetotelluric (MT) and seismic survey that was deployed for 20 months. High‐conductivity zones are located along the axis of the active volcanic chain, delineating fluids and/or melt. A distinct WNW trending cluster of seismicity correlates with resistivity contrasts, considered to be a reactivated ATF. Seismicity occurs below 4 km, suggesting activity is limited to basement rocks, and the cessation of seismicity at 9 km delineates the local brittle‐ductile transition. As seismicity is not seen west of the El Fierro fault, we hypothesize that this structure plays a key role in compartmentalizing magmatically derived hydrothermal fluids to the east, where the fault zone acts as a barrier to cross‐fault fluid migration and channels fault‐parallel fluid flow to the surface from depth. Increases in fluid pressure above hydrostatic may facilitate reactivation. This site‐specific case study provides the first three‐dimensional seismic and MT observations of the mechanics behind the reactivation of an ATF.
Podcast: Mythical Monsters and Their Real-Life Inspirations
Authors: Hanlon Shane
Published: October 2020

This Halloween season, explore the connections between mythical monsters like Bigfoot and the Kraken and the creatures on which they’re based.
Regional Crustal Imaging by Inversion of Multimode Rayleigh Wave Dispersion Curves Measured From Seismic Noise: Application to the Basque‐Cantabrian Zone (N Spain)
Authors: Olivar‐Castaño A. , Pilz M. , Pedreira D. , Pulgar J. A. , Díaz‐González A. , González‐Cortina J. M.
Published: October 2020

Seismic‐noise tomography is routinely applied for imaging geological structures at different spatial scales. The frequently used time‐domain approach presents two limitations. First, extracting surface‐wave group velocities from time‐domain cross‐correlations requires interstation distances of at least three wavelengths, which may be problematic when working at local or regional scales. Second, the presence of higher modes of surface waves in the cross‐correlation functions is often disregarded, which may cause loss of valuable information about the shear‐wave velocity structure. In this work, we present a complete inversion scheme that avoids these limitations and use it to obtain a 3D shear‐wave velocity model of the Basque‐Cantabrian Zone (N Spain), a structurally complex area affected by multiple tectonic events. The resulting model agrees with the existing geological and geophysical knowledge and significantly extends the area for which high‐resolution information is available.
Near‐Ultraviolet to Near‐Infrared Spectral Properties of Hollows on Mercury: Implications for Origin and Formation Process
Authors: Barraud O. , Doressoundiram A. , Besse S. , Sunshine J. M.
Published: October 2020

Among the geological features revealed by the MESSENGER (MErcury Surface, Space ENvironment, GEochemistry and Ranging) mission on the surface of Mercury, hollows are the most surprising and least understood. Possibly related to volatile components, hollows are small depressions, surrounded by bright halos and are not observed on any other surfaces in our solar system. Previous analysis of multispectral data obtained by Mercury Dual Imaging System (MDIS) has shown that some hollows have weak spectral absorption features centered at around 600 nm. In this work, we analyzed four hollows with observations acquired by the Mercury Atmospheric and Surface Composition Spectrometer (MASCS) on board MESSENGER with more than 230 spectral channels from the near‐ultraviolet to the near‐infrared. Unlike previous MDIS multispectral data, the MASCS reflectance spectra exhibit no absorption features in the MDIS wavelength range. However, we found that hollows have unique spectral properties in the near‐ultraviolet, with a spectral curvature between 300 and 600 nm that is distinctly different from other geological units. Moreover, we used MASCS observations with the best available spatial resolution (<0.5 km/pixel) to analyze both parts of a hollow: the flat floor and the surrounding halo. Our results support the hypothesis that hollows form by a sublimation process and scarp retreat.
Late Amazonian Ice Survival in Kasei Valles, Mars
Authors: Hepburn A. J. , Ng F. S. L. , Holt T. O. , Hubbard B.
Published: October 2020

High‐obliquity excursions on Mars are hypothesized to have redistributed water from the poles to nourish mid‐latitude glaciers. Evidence of this process is provided by different types of viscous flow features (ice‐rich deposits buried beneath sediment mantle) located there today, including lobate debris aprons (LDAs). During high‐obliquity extremes, ice may have persisted even nearer the equator, as indicated by numerous enigmatic depressions bounded on one side by either isolated mesas or scarps, and on the other by a lava unit. These depressions demarcate the past interaction between flowing lava and ghost LDAs (GLDAs), which have long since disappeared. We term these features GLDA depressions, about which little is known besides their spatial extent. This collection of depressions implies tropical ice loss over an area ∼100,000 km2. To constrain their history in Kasei Valles, we derive model ages for GLDA depressions, mesas, and the lava flow from crater counts. We use a 2D model of glacial ice constrained by the topography of GLDA depressions to approximate the surface and volume of former glacial ice deposits. The model reconstructs former ice surfaces along multiple flow lines orientated normal to GLDA depression boundaries. This reconstruction indicates that 1,400–3,500 km3 of ice—similar to that present in Iceland on Earth—existed at ∼1.3 Ga when the lava was emplaced. Dating shows that the GLDAs survived for up to ∼1 billion years following lava emplacement, before its final demise.
Delays, Discrepancies, and Distortions: Size‐Dependent Sediment Mixing and the Deep‐Sea Record of the Paleocene‐Eocene Thermal Maximum From ODP Site 690 (Weddell Sea)
Authors: Hupp Brittany , Kelly D. Clay
Published: October 2020

The deep‐sea sedimentary record of Ocean Drilling Program Site 690 (Weddell Sea) has figured prominently in the study of an ancient (~56 Ma) global warming event referred to as the Paleocene‐Eocene Thermal Maximum (PETM). Yet discrepancies in the timing, amplitude, and structure of the isotopic excursions marking the PETM exist between the bulk‐carbonate and planktic foraminifer stable isotope (δ13C and δ18O) records of this reference section. A recent study invoked size‐dependent sediment mixing (SDSM) to reconcile the discrepancies between these parallel δ13C records. Here we report supplementary stable isotope data compiled from size‐segregated planktic foraminifer shells that further elucidate the effects of SDSM on the Site 690 PETM section. Our records reveal a stratigraphic sequence where the carbon (CIE) and oxygen (OIE) isotope excursions marking the onset of PETM conditions are first registered by larger shells, confirming that smaller‐sized pre‐CIE shells have been more intensely mixed and preferentially displaced up‐section into the overlying CIE interval. The size‐dependent manner in which the CIE and OIE are recorded by asymbiotic subbotinids indicates that the transitory loss of size‐dependent δ13C signatures in photosymbiotic taxa (acarininids) at Site 690 is an artifact of SDSM. Synthetic bulk‐carbonate δ13C records generated with two end‐member (pre‐CIE versus CIE materials) sediment‐mixing curves readily reproduce the series of “steps” seen in published bulk‐carbonate δ13C records of the CIE, suggesting that these fine‐scale features may also be artifacts of SDSM and varying rates of carbonate sedimentation.
Aptian Flysch in Central Tibet: Constraints on the Timing of Closure of the Bangong‐Nujiang Tethyan Ocean
Authors: Luo An‐Bo , Fan Jian‐Jun , Hao Yu‐Jie , Li Hang , Zhang Bo‐Chuan
Published: October 2020

The timing of the closure of the Bangong‐Nujiang Tethyan Ocean is highly controversial. An important reason for this is that the sedimentological work within the Bangong‐Nujiang suture zone is not sufficient. In this study, based on the U‐Pb zircon dating of turbiditic sandstone and tuff interlayers, we determine the existence of Aptian flysch (ca. 126–113 Ma) in the middle and western segments of the Bangong‐Nujiang suture zone. Further analysis shows that the Aptian flysch was deposited in a trench environment. In space, from the Mabujia Co area in the western segment to the Kama area in the middle segment, the outcrop extent of the Aptian flysch spans nearly 300 km from east to west. These results indicate that the Bangong‐Nujiang Tethyan Ocean had not fully closed by the end of Aptian time, and its oceanic slab was still subducting. Based on this new discovery, and the results of previous studies, we believe that the middle and western segments of the Bangong‐Nujiang Tethyan Ocean closed between 113 and ca. 92 Ma nonmarine deposition of the Jingzhushan Formation, which lies in angular unconformity above the flysch.
Smartrock Transport in a Mountain Stream: Bedload Hysteresis and Changing Thresholds of Motion
Authors: Pretzlav Kealie L. G. , Johnson Joel P. L. , Bradley D. Nathan
Published: October 2020

Bedload movement is fundamentally probabilistic. Our quantitative understanding of gravel transport is particularly limited when flow conditions just exceed thresholds of motion, in part because of difficulties in measuring transport statistics during natural floods. We used accelerometer‐embedded tracer clasts to precisely measure the timing of grain motions and rests during snowmelt floods in Halfmoon Creek, a gravel‐bed mountain stream in Colorado, USA. These new data let us explore how probabilities of tracer movement varied as functions of discharge and time. Bedload hysteresis occurred over both daily and seasonal timescales and included clockwise, counterclockwise, and figure‐eight patterns. We empirically explain the hysteresis by modifying a bedload transport model to have an evolving threshold of motion parameter. We calculate how the thresholds of motion progressively evolved through time over 22 days during the 2015 snowmelt flood. Our results quantitatively show that thresholds of motion are functions of both (a) cumulative shear stress and (b) temporal changes in shear stress during floods.
Inhibitors targeting Bruton’s tyrosine kinase in cancers: drug development advances
Authors: Wen Tingyu , Wang Jinsong , Shi Yuankai , Qian Haili , Liu Peng
Published: October 2020

Bruton’s tyrosine kinase (BTK) inhibitor is a promising novel agent that has potential efficiency in B-cell malignancies. It took approximately 20 years from target discovery to new drug approval. The first-in-class drug ibrutinib creates possibilities for an era of chemotherapy-free management of B-cell malignancies, and it is so popular that gross sales have rapidly grown to more than 230 billion dollars in just 6 years, with annual sales exceeding 80 billion dollars; it also became one of the five top-selling medicines in the world. Numerous clinical trials of BTK inhibitors in cancers were initiated in the last decade, and ~73 trials were intensively announced or updated with extended follow-up data in the most recent 3 years. In this review, we summarized the significant milestones in the preclinical discovery and clinical development of BTK inhibitors to better understand the clinical and commercial potential as well as the directions being taken. Furthermore, it also contributes impactful lessons regarding the discovery and development of other novel therapies.
Transdiagnostic individualized clinically-based risk calculator for the automatic detection of individuals at-risk and the prediction of psychosis: external replication in 2,430,333 US patients
Authors: Oliver Dominic , Wong Chiew Meng Johnny , Bøg Martin , Jönsson Linus , Kinon Bruce J. , Wehnert Allan , Jørgensen Kristian Tore , Irving Jessica , Stahl Daniel , McGuire Philip , Raket Lars Lau , Fusar-Poli Paolo
Published: October 2020

The real-world impact of psychosis prevention is reliant on effective strategies for identifying individuals at risk. A transdiagnostic, individualized, clinically-based risk calculator to improve this has been developed and externally validated twice in two different UK healthcare trusts with convincing results. The prognostic performance of this risk calculator outside the UK is unknown. All individuals who accessed primary or secondary health care services belonging to the IBM® MarketScan® Commercial Database between January 2015 and December 2017, and received a first ICD-10 index diagnosis of nonorganic/nonpsychotic mental disorder, were included. According to the risk calculator, age, gender, ethnicity, age-by-gender, and ICD-10 cluster diagnosis at index date were used to predict development of any ICD-10 nonorganic psychotic disorder. Because patient-level ethnicity data were not available city-level ethnicity proportions were used as proxy. The study included 2,430,333 patients with a mean follow-up of 15.36 months and cumulative incidence of psychosis at two years of 1.43%. There were profound differences compared to the original development UK database in terms of case-mix, psychosis incidence, distribution of baseline predictors (ICD-10 cluster diagnoses), availability of patient-level ethnicity data, follow-up time and availability of specialized clinical services for at-risk individuals. Despite these important differences, the model retained accuracy significantly above chance (Harrell’s C = 0.676, 95% CI: 0.672–0.679). To date, this is the largest international external replication of an individualized prognostic model in the field of psychiatry. This risk calculator is transportable on an international scale to improve the automatic detection of individuals at risk of psychosis.
Antihypertensive drugs are associated with reduced fatal outcomes and improved clinical characteristics in elderly COVID-19 patients
Authors: Yan Feifei , Huang Fengming , Xu Jun , Yang Penghui , Qin Yuhao , Lv Jingjun , Zhang Shaogeng , Ye Lu , Gong Ming , Liu Zhibo , Wei Jie , Xie Tuxiu , Xu Kai-Feng , Gao George F. , Wang Fu-Sheng , Cai Lin , Jiang Chengyu
Published: October 2020

The novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak began at the end of 2019 in Wuhan, China, and has spread to over 200 countries. In this multicenter retrospective study, we identified 2190 adult patients admitted for laboratory-confirmed COVID-19 in three participating centers. Multivariate logistic regression was conducted in patients with comorbid hypertension to examine the potential association between clinical outcomes, disease severity, and clinical characteristics with the use of ACEI, ARB, calcium-channel blockers (CCB), beta-blockers (BB), and thiazide diuretics. The clinical outcome, dyspnea, and fatigue were significantly improved in patients, especially elderly patients who were older than 65 years, who took ARB drugs prior to hospitalization compared to patients who took no drugs. The reduction of disease severity of elderly COVID-19 patients was associated with CCB and ACEI users. Clinical indices, including CRP, lymphocyte count, procalcitonin D dimer, and hemoglobin, were significantly improved in elderly ARB users. In addition, the clinical outcomes were statistically significantly improved in patients who took antihypertension drugs ARB, BB, and CCB after statistical adjustment by all ages, gender, baseline of blood pressures, and coexisting medical conditions. Our data indicate that hypertension drugs ARB, ACEI, CCB, and BB might be beneficial for COVID-19 patients.
Graphene memristive synapses for high precision neuromorphic computing
Authors: Schranghamer Thomas F. , Oberoi Aaryan , Das Saptarshi
Published: October 2020

Memristive crossbar architectures are evolving as powerful in-memory computing engines for artificial neural networks. However, the limited number of non-volatile conductance states offered by state-of-the-art memristors is a concern for their hardware implementation since trained weights must be rounded to the nearest conductance states, introducing error which can significantly limit inference accuracy. Moreover, the incapability of precise weight updates can lead to convergence problems and slowdown of on-chip training. In this article, we circumvent these challenges by introducing graphene-based multi-level (>16) and non-volatile memristive synapses with arbitrarily programmable conductance states. We also show desirable retention and programming endurance. Finally, we demonstrate that graphene memristors enable weight assignment based on k-means clustering, which offers greater computing accuracy when compared with uniform weight quantization for vector matrix multiplication, an essential component for any artificial neural network.
Expanding detection windows for discriminating single nucleotide variants using rationally designed DNA equalizer probes
Authors: Wang Guan A. , Xie Xiaoyu , Mansour Hayam , Chen Fangfang , Matamoros Gabriela , Sanchez Ana L. , Fan Chunhai , Li Feng
Published: October 2020

Combining experimental and simulation strategies to facilitate the design and operation of nucleic acid hybridization probes are highly important to both fundamental DNA nanotechnology and diverse biological/biomedical applications. Herein, we introduce a DNA equalizer gate (DEG) approach, a class of simulation-guided nucleic acid hybridization probes that drastically expand detection windows for discriminating single nucleotide variants in double-stranded DNA (dsDNA) via the user-definable transformation of the quantitative relationship between the detection signal and target concentrations. A thermodynamic-driven theoretical model was also developed, which quantitatively simulates and predicts the performance of DEG. The effectiveness of DEG for expanding detection windows and improving sequence selectivity was demonstrated both in silico and experimentally. As DEG acts directly on dsDNA, it is readily adaptable to nucleic acid amplification techniques, such as polymerase chain reaction (PCR). The practical usefulness of DEG was demonstrated through the simultaneous detection of infections and the screening of drug-resistance in clinical parasitic worm samples collected from rural areas of Honduras.
Light-induced primary amines and o-nitrobenzyl alcohols cyclization as a versatile photoclick reaction for modular conjugation
Authors: Guo An-Di , Wei Dan , Nie Hui-Jun , Hu Hao , Peng Chengyuan , Li Shao-Tong , Yan Ke-Nian , Zhou Bin-Shan , Feng Lei , Fang Chao , Tan Minjia , Huang Ruimin , Chen Xiao-Hua
Published: October 2020

The advent of click chemistry has had a profound impact on many fields and fueled a need for reliable reactions to expand the click chemistry toolkit. However, developing new systems to fulfill the click chemistry criteria remains highly desirable yet challenging. Here, we report the development of light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) as a photoclick reaction via primary amines as direct click handle, to rapid and modular functionalization of diverse small molecules and native biomolecules. With intrinsic advantages of temporal control, good biocompatibility, reliable chemoselectivity, excellent efficiency, readily accessible reactants, operational simplicity and mild conditions, the PANAC photoclick is robust for direct diversification of pharmaceuticals and biorelevant molecules, lysine-specific modifications of unprotected peptides and native proteins in vitro, temporal profiling of endogenous kinases and organelle-targeted labeling in living systems. This strategy provides a versatile platform for organic synthesis, bioconjugation, medicinal chemistry, chemical biology and materials science.
Controlling the dimension of the quantum resonance in CdTe quantum dot superlattices fabricated via layer-by-layer assembly
Authors: Lee TaeGi , Enomoto Kazushi , Ohshiro Kazuma , Inoue Daishi , Kikitsu Tomoka , Hyeon-Deuk Kim , Pu Yong-Jin , Kim DaeGwi
Published: October 2020

In quantum dot superlattices, wherein quantum dots are periodically arranged, electronic states between adjacent quantum dots are coupled by quantum resonance, which arises from the short-range electronic coupling of wave functions, and thus the formation of minibands is expected. Quantum dot superlattices have the potential to be key materials for new optoelectronic devices, such as highly efficient solar cells and photodetectors. Herein, we report the fabrication of CdTe quantum dot superlattices via the layer-by-layer assembly of positively charged polyelectrolytes and negatively charged CdTe quantum dots. We can thus control the dimension of the quantum resonance by independently changing the distances between quantum dots in the stacking (out-of-plane) and in-plane directions. Furthermore, we experimentally verify the miniband formation by measuring the excitation energy dependence of the photoluminescence spectra and detection energy dependence of the photoluminescence excitation spectra.
IFI16 promotes human embryonic stem cell trilineage specification through interaction with p53
Authors: He Qian , Wu Zubiao , Yang Wei , Jiang Doukou , Hu Chaofeng , Yang Xiaofei , Li Ning , Li Furong
Published: October 2020

Transcriptional regulation plays an essential role in the self-renewal and differentiation of human embryonic stem cells (hESCs). However, how external signals disrupt the self-renewal regulatory network and further drive hESC differentiation remains largely unknown. Here, we found the immune regulative protein, gamma-interferon-inducible protein 16 (IFI16) was involved in the regulation of both self-renewal and differentiation gene expression during hESC trilineage specification through interaction with p53. IFI16 expression levels were upregulated through JNK activation. IFI16 knockdown delayed the downregulation of self-renewal gene expression and suppressed the upregulation of differentiation gene expression, while IFI16 overexpression accelerated trilineage specification. Furthermore, IFI16 stabilized p53-binding in the genome through IFI16-p53 interaction and differentially regulated self-renewal and differentiation gene expression. Together, our results suggest a particular role of IFI16 in differential gene expression regulation during trilineage specification of hESCs in a manner that is dependent on the genome-wide profile of p53-binding directed by IFI16-p53 interaction.
A real-time survey on the psychological impact of mild lockdown for COVID-19 in the Japanese population
Authors: Sugaya Nagisa , Yamamoto Tetsuya , Suzuki Naho , Uchiumi Chigusa
Published: October 2020

To deter the spread of the coronavirus disease 2019 (COVID-19), many countries have imposed a lockdown with restrictions. On 7 April 2020, the Japanese government declared a state of emergency over the COVID-19 outbreak. Japan was in “mild lockdown” which was not enforceable and non-punitive with the declaration. We conducted an online survey to investigate factors associated with psychological distress in the “mild lockdown” under a declared state of emergency for COVID-19. We collected data on 11,333 inhabitants (52.4% women, 46.3 ± 14.6 years) living in the seven prefectures where the declaration was first applied. The investigation dates of this study, 11 and 12 May 2020, were in the final phase of the state of emergency. The survey was conducted in real-time to minimize participants’ recall bias. In addition to psychological inventories often used worldwide, the questionnaires used in this survey included lifestyle and stress management items related to COVID-19 and various socio-demographic items including occupation (e.g. healthcare worker) or income.
The E3 ubiquitin ligase UBR5 interacts with TTC7A and may be associated with very early onset inflammatory bowel disease
Authors: Dhingani Neel , Guo Conghui , Pan Jie , Li Qi , Warner Neil , Jardine Sasha , Leung Gabriella , Kotlarz Daniel , Gonzaga-Jauregui Claudia , Klein Christoph , Snapper Scott B. , Navas-López Víctor Manuel , Muise Aleixo M.
Published: October 2020

Very early onset inflammatory bowel disease (VEOIBD) denotes children with onset of IBD before six years of age. A number of monogenic disorders are associated with VEOIBD including tetratricopeptide repeat domain 7A (TTC7A) deficiency. TTC7A-deficiency is characterized by apoptotic colitis in milder cases with severe intestinal atresia and immunodeficiency in cases with complete loss of protein. We used whole exome sequencing in a VEOIBD patient presenting with colitis characterized by colonic apoptosis and no identified known VEOIBD variants, to identify compound heterozygous deleterious variants in the Ubiquitin protein ligase E3 component N-recognin 5 (UBR5) gene. Functional studies demonstrated that UBR5 co-immunoprecipitates with the TTC7A and the UBR5 variants had reduced interaction between UBR5 and TTC7A. Together this implicates UBR5 in regulating TTC7A signaling in VEOIBD patients with apoptotic colitis.
Psychometric properties and concurrent validity of the Transgender Congruence Scale (TCS) in the Swedish setting
Authors: Iliadis Stavros I. , Axfors Cathrine , Friberg Agnes , Arinell Hans , Beckman Ulrika , Fazekas Attila , Frisen Louise , Sandström Lotta , Thelin Nils , Wahlberg Jeanette , Södersten Maria , Papadopoulos Fotios C.
Published: October 2020

The Transgender Congruence Scale (TCS) is a non-binary tool used in Sweden for gender dysphoria (GD) assessment; however, its Swedish version has not been validated. To investigate the psychometric properties of the TCS, its capacity to distinguish individuals with GD and its concurrent validity compared to other scales. Patients with GD (n = 135) and controls (n = 443) filled in a questionnaire containing sociodemographic questions, the TCS, the Utrecht Gender Dysphoria Scale (UGDS), and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). TCS had good discriminatory validity and internal consistency. Patients with GD, stratified by birth-assigned sex, had lower TCS scores compared to controls. Confirmatory factor analysis (CFA) supported the two-factor model of the TCS. Multiple-group CFA suggested measurement invariance between birth-assigned sexes and configural invariance between patients with GD and controls. Area under the ROC curve for birth-assigned males was 0.991 and for females 0.994. A TCS mean value of three provided sensitivity 94.3% and 95.1% as well as specificity 98.6% and 98% for aM and aF, respectively. The TCS was significantly correlated to UGDS and GIDYQ-AA. The TCS may be a valuable tool in the clinical assessment of individuals with GD.
Safety and efficacy of Melissa officinalis extract containing rosmarinic acid in the prevention of Alzheimer’s disease progression
Authors: Noguchi-Shinohara Moeko , Ono Kenjiro , Hamaguchi Tsuyoshi , Nagai Toshitada , Kobayashi Shoko , Komatsu Junji , Samuraki-Yokohama Miharu , Iwasa Kazuo , Yokoyama Kunihiko , Nakamura Hiroyuki , Yamada Masahito
Published: October 2020

We conducted a randomized placebo-controlled double-blind 24-week trial using Melissa officinalis (M. officinalis) extract richly containing rosmarinic acid (RA) on patients with mild dementia due to Alzheimer’s disease (AD) with the aim to examine the safety and tolerability (primary endpoint) of RA (500 mg daily) and its clinical effects and disease-related biomarker changes (secondary endpoints). Patients (n = 23) diagnosed with mild dementia due to probable AD were randomized to either the placebo or M. officinalis extract group. No differences in vital signs or physical and neurologic examination results were detected between the M. officinalis and placebo groups. No serious adverse events occurred. There were no significant differences in cognitive measures; however, the mean Neuropsychiatric Inventory Questionnaire (NPI-Q) score improved by 0.5 points in the M. officinalis group and worsened by 0.7 points in the placebo group between the baseline and 24-week visit, indicating a significant difference (P = 0.012). No significant differences were apparent in disease-related biomarkers between the groups. M. officinalis extract containing 500 mg of RA taken daily was safe and well-tolerated by patients with mild dementia due to AD. Our results suggest that RA may help prevent the worsening of AD-related neuropsychiatric symptoms.

Trial registration: The registration number for this clinical trial is UMIN000007734 (16/04/2012).
Optimal scanning concentration of MR imaging for tumor-bearing nude mice with SPIO-shRNA molecular probe
Authors: Zhang Liqiang , Yang Xinyi , Wen Ming
Published: October 2020

The objective of this study is to investigate the signal changes and optimal scanning concentration of MRI in tumor tissues of tumor-bearing nude mice by SPIO-shRNA molecular probes. 30 BALB/c tumor-bearing nude mice were randomly divided into 5 groups with 6 mice in each group. At the given scanning time (before and 27 h after injection), the caudal vein was respectively injected with iron content of 6 mg·kg−1, 12 mg·kg−1, 18 mg·kg−1, 24 mg·kg−1, and 30 mg·kg−1, and MR examination was simultaneously performed to measure signal intensity changes of tumor tissue and contralateral muscle tissue in each concentration group. After each examination above, the nude mice were sacrificed immediately, and the tumor and muscle tissues were removed for HE and Prussian blue staining,and observed under light microscope. Nude mice in 6 mg, 12 mg and 18 mg groups all survived after probe injection, but some nude mice died in 24 mg and 30 mg groups after probe injection or during scanning. The signal changes of T2WI and T2*WI sequences were the most obvious in MR scanning sequences. Compared with other groups, the signal intensity of the tumor tissue in 18 mg, 24 mg and 30 mg groups were most obvious (P < 0.05), while the 18 mg, 24 mg and 30 mg groups reached no statistical difference (P > 0.05 ); HE staining indicated that structural disorder of tumor tissue as well as increase of nuclear atypia. Prussian Blue staining showed that blue-stained iron particles were present in each experimental group,and the most densely distributed were in 18 mg,24 mg and 30 mg groups. Tumor tissue could be well labeled with SPIO-shRNA molecular probes, and the optimal MR scanning concentration (iron content) is 18 mg·kg−1.
Urban and air pollution: a multi-city study of long-term effects of urban landscape patterns on air quality trends
Authors: Liang Lu , Gong Peng
Published: October 2020

Most air pollution research has focused on assessing the urban landscape effects of pollutants in megacities, little is known about their associations in small- to mid-sized cities. Considering that the biggest urban growth is projected to occur in these smaller-scale cities, this empirical study identifies the key urban form determinants of decadal-long fine particulate matter (PM2.5) trends in all 626 Chinese cities at the county level and above. As the first study of its kind, this study comprehensively examines the urban form effects on air quality in cities of different population sizes, at different development levels, and in different spatial-autocorrelation positions. Results demonstrate that the urban form evolution has long-term effects on PM2.5 level, but the dominant factors shift over the urbanization stages: area metrics play a role in PM2.5 trends of small-sized cities at the early urban development stage, whereas aggregation metrics determine such trends mostly in mid-sized cities. For large cities exhibiting a higher degree of urbanization, the spatial connectedness of urban patches is positively associated with long-term PM2.5 level increases. We suggest that, depending on the city’s developmental stage, different aspects of the urban form should be emphasized to achieve long-term clean air goals.
Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome
Authors: Wang Haiqiong , Guo Yongbo , Dong Zhenkun , Li Tao , Xie Xinsheng , Wan Dingming , Jiang Zhongxing , Yu Jifeng , Guo Rong
Published: October 2020

To investigate the U2AF1 gene mutation site, mutation load and co-mutations genes in patients with myelodysplastic syndrome (MDS) and their effects on prognosis. Gene mutation detection by next-generation sequence and related clinical data of 234 MDS patients were retrospectively collected and analyzed for the relationship between the clinical characteristics, treatment efficacy and prognosis of U2AF1 gene mutation. Among the 234 MDS patients, the U2AF1 gene mutation rate was 21.7% (51 cases), and the median variant allele frequency was 39.5%. Compared with the wild type, the U2AF1 mutant had a higher incidence of chromosome 8 aberration, and was positively correlated with the occurrence of ASXL1, RUNX1, SETBP1 gene mutation, negatively correlated with SF3B1, NPM1 genes mutation (p < 0.05). The most common mutation site of U2AF1 was S34F (32 cases), while U2AF1 Q157P site mutations had a higher incidence of chromosome 7 abnormalities (p = 0.003). The U2AF1 gene mutation more frequently coincided with signal pathway related gene mutations (p = 0.043) with a trend of shortened overall survival. Among patients with U2AF1 gene mutations, those with ASXL1 mutations were prone to develop into acute myeloid leukemia, those with RUNX1 mutations had an increased risk of relapse, and those with TET2 mutations had higher 1-year survival rate. Compared with the patient group of lower mutation load (VAF ≤ 40%), the group with higher mutation load of U2AF1 (VAF > 40%) had a significantly lower 1-year survival rate (46.1% and 80.5%, p = 0.027). The criteria of U2AF1 VAF > 40% is an independent indicator for poor prognosis of MDS patients. VAF > 40% of U2AF1 is an independent factor of short OS in MDS patients. MDS patients with a mutation in the Q157P site of U2AF1 and a higher U2AF1 mutation load suggests poor prognosis, and co-mutated genes in U2AF1 can affect disease progression and prognosis.
Generation of a Matrix Gla (Mgp) floxed mouse, followed by conditional knockout, uncovers a new Mgp function in the eye
Authors: Borrás Teresa , Cowley Dale O. , Asokan Priyadarsini , Pandya Kumar
Published: October 2020

The ability to ablate a gene in a given tissue by generating a conditional knockout (cKO) is crucial for determining its function in the targeted tissue. Such tissue-specific ablation is even more critical when the gene’s conventional knockout (KO) is lethal, which precludes studying the consequences of its deletion in other tissues. Therefore, here we describe a successful strategy that generated a Matrix Gla floxed mouse (Mgp.floxed) by the CRISPR/Cas9 system, that subsequently allowed the generation of cKOs by local viral delivery of the Cre-recombinase enzyme. MGP is a well-established inhibitor of calcification gene, highly expressed in arteries’ smooth muscle cells and chondrocytes. MGP is also one of the most abundant genes in the trabecular meshwork, the eye tissue responsible for maintenance of intraocular pressure (IOP) and development of Glaucoma. Our strategy entailed one-step injection of two gRNAs, Cas9 protein and a long-single-stranded-circular DNA donor vector (lsscDNA, 6.7 kb) containing two loxP sites in cis and 900–700 bp 5′/3′ homology arms. Ocular intracameral injection of Mgp.floxed mice with a Cre-adenovirus, led to an Mgp.TMcKO mouse which developed elevated IOP. Our study discovered a new role for the Mgp gene as a keeper of physiological IOP in the eye.
Combining multiple spatial statistics enhances the description of immune cell localisation within tumours
Authors: Bull Joshua A. , Macklin Philip S. , Quaiser Tom , Braun Franziska , Waters Sarah L. , Pugh Chris W. , Byrne Helen M.
Published: October 2020

Digital pathology enables computational analysis algorithms to be applied at scale to histological images. An example is the identification of immune cells within solid tumours. Image analysis algorithms can extract precise cell locations from immunohistochemistry slides, but the resulting spatial coordinates, or point patterns, can be difficult to interpret. Since localisation of immune cells within tumours may reflect their functional status and correlates with patient prognosis, novel descriptors of their spatial distributions are of biological and clinical interest. A range of spatial statistics have been used to analyse such point patterns but, individually, these approaches only partially describe complex immune cell distributions. In this study, we apply three spatial statistics to locations of CD68+ macrophages within human head and neck tumours, and show that images grouped semi-quantitatively by a pathologist share similar statistics. We generate a synthetic dataset which emulates human samples and use it to demonstrate that combining multiple spatial statistics with a maximum likelihood approach better predicts human classifications than any single statistic. We can also estimate the error associated with our classifications. Importantly, this methodology is adaptable and can be extended to other histological investigations or applied to point patterns outside of histology.
Improvements in the production of purified M13 bacteriophage bio-nanoparticle
Authors: Passaretti Paolo , Khan Inam , Dafforn Timothy R. , Goldberg Oppenheimer Pola
Published: October 2020

M13 bacteriophage is a well-established versatile nano-building block, which can be employed to produce novel self-assembled functional materials and devices. Sufficient production and scalability of the M13, often require a large quantity of the virus and thus, improved propagation methods characterised by high capacity and degree of purity are essential. Currently, the ‘gold-standard’ is represented by infecting Escherichia coli cultures, followed by precipitation with polyethylene glycol (PEG). However, this is considerably flawed by the accumulation of contaminant PEG inside the freshly produced stocks, potentially hampering the reactivity of the individual M13 filaments. Our study demonstrates the effectiveness of implementing an isoelectric precipitation procedure to reduce the residual PEG along with FT-IR spectroscopy as a rapid, convenient and effective analytic validation method to detect the presence of this contaminant in freshly prepared M13 stocks.
Shared functional connectivity between the dorso-medial and dorso-ventral streams in macaques
Authors: Greulich R. Stefan , Adam Ramina , Everling Stefan , Scherberger Hansjörg
Published: October 2020

Manipulation of an object requires us to transport our hand towards the object (reach) and close our digits around that object (grasp). In current models, reach-related information is propagated in the dorso-medial stream from posterior parietal area V6A to medial intraparietal area, dorsal premotor cortex, and primary motor cortex. Grasp-related information is processed in the dorso-ventral stream from the anterior intraparietal area to ventral premotor cortex and the hand area of primary motor cortex. However, recent studies have cast doubt on the validity of this separation in separate processing streams. We investigated in 10 male rhesus macaques the whole-brain functional connectivity of these areas using resting state fMRI at 7-T. Although we found a clear separation between dorso-medial and dorso-ventral network connectivity in support of the two-stream hypothesis, we also found evidence of shared connectivity between these networks. The dorso-ventral network was distinctly correlated with high-order somatosensory areas and feeding related areas, whereas the dorso-medial network with visual areas and trunk/hindlimb motor areas. Shared connectivity was found in the superior frontal and precentral gyrus, central sulcus, intraparietal sulcus, precuneus, and insular cortex. These results suggest that while sensorimotor processing streams are functionally separated, they can access information through shared areas.
Circadian misalignment increases mood vulnerability in simulated shift work
Authors: Chellappa Sarah L. , Morris Christopher J. , Scheer Frank A. J. L.
Published: October 2020

Night shift work can associate with an increased risk for depression. As night workers experience a ‘misalignment’ between their circadian system and daily sleep–wake behaviors, with negative health consequences, we investigated whether exposure to circadian misalignment underpins mood vulnerability in simulated shift work. We performed randomized within-subject crossover laboratory studies in non-shift workers and shift workers. Simulated night shifts were used to induce a misalignment between the endogenous circadian pacemaker and sleep/wake cycles (circadian misalignment), while environmental conditions and food intake were controlled. Circadian misalignment adversely impacted emotional state, such that mood and well-being levels were significantly decreased throughout 4 days of continuous exposure to circadian misalignment in non-shift workers, as compared to when they were under circadian alignment (interaction of “circadian alignment condition” vs. “day”, mood: p < 0.001; well-being: p < 0.001; adjusted p-values). Similarly, in shift workers, mood and well-being levels were significantly reduced throughout days of misalignment, as compared to circadian alignment (interaction of “circadian alignment condition” vs. “day”, mood: p = 0.002; well-being: p = 0.002; adjusted p-values). Our findings indicate that circadian misalignment is an important biological component for mood vulnerability, and that individuals who engage in shift work are susceptible to its deleterious mood effects.
OSM-9 and OCR-2 TRPV channels are accessorial warm receptors in Caenorhabditis elegans temperature acclimatisation
Authors: Ohnishi Kohei , Saito Shigeru , Miura Toru , Ohta Akane , Tominaga Makoto , Sokabe Takaaki , Kuhara Atsushi
Published: October 2020

Caenorhabditis elegans (C. elegans) exhibits cold tolerance and temperature acclimatisation regulated by a small number of head sensory neurons, such as the ADL temperature-sensing neurons that express three transient receptor potential vanilloid (TRPV) channel subunits, OSM-9, OCR-2, and OCR-1. Here, we show that an OSM-9/OCR-2 regulates temperature acclimatisation and acts as an accessorial warmth-sensing receptor in ADL neurons. Caenorhabditis elegans TRPV channel mutants showed abnormal temperature acclimatisation. Ectopic expression of OSM-9 and OCR-2 in non-warming-responsive gustatory neurons in C. elegans and Xenopus oocytes revealed that OSM-9 and OCR-2 cooperatively responded to warming; however, neither TRPV subunit alone was responsive to warming. A warming-induced OSM-9/OCR-2-mediated current was detectable in Xenopus oocytes, yet ADL in osm-9 ocr-2 double mutant responds to warming; therefore, an OSM-9/OCR-2 TRPV channel and as yet unidentified temperature receptor might coordinate transmission of temperature signalling in ADL temperature-sensing neurons. This study demonstrates direct sensation of warming by TRPV channels in C. elegans.
Bacterial inducible expression of plant cell wall-binding protein YesO through conflict between Glycine max and saprophytic Bacillus subtilis
Authors: Sugiura Haruka , Nagase Ayumi , Oiki Sayoko , Mikami Bunzo , Watanabe Daisuke , Hashimoto Wataru
Published: October 2020

Saprophytic bacteria and plants compete for limited nutrient sources. Bacillus subtilis grows well on steamed soybeans Glycine max to produce the fermented food, natto. Here we focus on bacterial responses in conflict between B. subtilis and G. max. B. subtilis cells maintained high growth rates specifically on non-germinating, dead soybean seeds. On the other hand, viable soybean seeds with germinating capability attenuated the initial growth of B. subtilis. Thus, B. subtilis cells may trigger saprophytic growth in response to the physiological status of G. max. Scanning electron microscope observation indicated that B. subtilis cells on steamed soybeans undergo morphological changes to form apertures, demonstrating cell remodeling during saprophytic growth. Further, transcriptomic analysis of B. subtilis revealed upregulation of the gene cluster, yesOPQR, in colonies growing on steamed soybeans. Recombinant YesO protein, a putative, solute-binding protein for the ATP-binding cassette transporter system, exhibited an affinity for pectin-derived oligosaccharide from plant cell wall. The crystal structure of YesO, in complex with the pectin oligosaccharide, was determined at 1.58 Å resolution. This study expands our knowledge of defensive and offensive strategies in interspecies competition, which may be promising targets for crop protection and fermented food production.