bluuebunny/crossref_metadata_2025 huggingface dataset:
Denoising Autoencoder, A Deep Learning Algorithm, Aids the Identification of A Novel Molecular Signature of Lung Adenocarcinoma
Authors: Wang Jun , Xie Xueying , Shi Junchao , He Wenjun , Chen Qi , Chen Liang , Gu Wanjun , Zhou Tong
Published: December 2020

Precise biomarker development is a key step in disease management. However, most of the published biomarkers were derived from a relatively small number of samples with supervised approaches. Recent advances in unsupervised machine learning promise to leverage very large datasets for making better predictions of disease biomarkers. Denoising autoencoder (DA) is one of the unsupervised deep learning algorithms, which is a stochastic version of autoencoder techniques. The principle of DA is to force the hidden layer of autoencoder to capture more robust features by reconstructing a clean input from a corrupted one. Here, a DA model was applied to analyze integrated transcriptomic data from 13 published lung cancer studies, which consisted of 1916 human lung tissue samples. Using DA, we discovered a molecular signature composed of multiple genes for lung adenocarcinoma (ADC). In independent validation cohorts, the proposed molecular signature is proved to be an effective classifier for lung cancer histological subtypes. Also, this signature successfully predicts clinical outcome in lung ADC, which is independent of traditional prognostic factors. More importantly, this signature exhibits a superior prognostic power compared with the other published prognostic genes. Our study suggests that unsupervised learning is helpful for biomarker development in the era of precision medicine.
Exploring Potential Signals of Selection for Disordered Residues in Prokaryotic and Eukaryotic Proteins
Authors: Panda Arup , Tuller Tamir
Published: December 2020

Intrinsically disordered proteins (IDPs) are an important class of proteins in all domains of life for their functional importance. However, how nature has shaped the disorder potential of prokaryotic and eukaryotic proteins is still not clearly known. Randomly generated sequences are free of any selective constraints, thus these sequences are commonly used as null models. Considering different types of random protein models, here we seek to understand how the disorder potential of natural eukaryotic and prokaryotic proteins differs from random sequences. Comparing proteome-wide disorder content between real and random sequences of 12 model organisms, we noticed that eukaryotic proteins are enriched in disordered regions compared to random sequences, but in prokaryotes such regions are depleted. By analyzing the position-wise disorder profile, we show that there is a generally higher disorder near the N- and C-terminal regions of eukaryotic proteins as compared to the random models; however, either no or a weak such trend was found in prokaryotic proteins. Moreover, here we show that this preference is not caused by the amino acid or nucleotide composition at the respective sites. Instead, these regions were found to be endowed with a higher fraction of protein–protein binding sites, suggesting their functional importance. We discuss several possible explanations for this pattern, such as improving the efficiency of protein–protein interaction, ribosome movement during translation, and post-translational modification. However, further studies are needed to clearly understand the biophysical mechanisms causing the trend.
Impact of Cavity Shave Margins on Margin Status in Patients with Pure Ductal Carcinoma In Situ
Authors: Howard-McNatt Marissa , Dupont Elisabeth , Tsangaris Theodore , Garcia-Cantu Carlos , Chiba Akiko , Berger Adam C. , Levine Edward A. , Gass Jennifer S. , Ollila David W. , Chagpar Anees B. , Gallagher Kristalyn , Lum Sharon S. , Martinez Ricardo D. , Willis Alliric I. , Pandya Sonali V. , Brown Eric A. , Fenton Andrew , Mendiola Amanda , Murray Mary , Haddad Victor , Solomon Naveenraj L. , Senthil Maheswari , Bansil Hannah , Snyder Samuel K. , Edmonson David , Lazar Melissa , Namm Jukes P. , Li Fangyong , Butler Meghan , McGowan Noreen E. , Herrera Maria E. , Avitan Yoana P. , Yoder Brian , McPartland Tara , Chagpar Anees B.
Published: December 2020

BACKGROUND:

We examined the impact of cavity shave margins (CSMs) on margin status in patients with pure ductal carcinoma in situ (DCIS) undergoing partial mastectomy (PM).

METHODS:

One hundred and nine patients from 2 multicenter, randomized controlled trials were identified with pure DCIS (no invasive cancer). Surgeons performed their best PM, with specimen radiography and resection of selective margins per surgeon discretion. Patients were then randomized to have CSM resected or not. A positive margin was defined as <2 mm from ink.

RESULTS:

Median patient age was 63 years; median size of DCIS was 1.20 cm; 43.6% of patients had high-grade DCIS; and 58 (53.2%) patients were randomized to take CSM. The “shave” and “no-shave” groups were well-matched for age, race, ethnicity, palpability, grade, and size of DCIS. Although 33 (56.9%) of the patients in the shave group had a positive margin before randomization, only 12 (20.7%) had a positive margin after randomization to CSM (p < 0.001). In the no-shave group, 17 patients (33.3%) had a positive margin. Controlling for size and grade of DCIS, taking CSM resulted in a nearly 65% reduction in the positive-margin rate (odds ratio 0.366; 95% CI, 0.136 to 0.981; p = 0.046). Size of DCIS remained an independent predictor of positive margins in the model (odds ratio 1.646; 95% CI, 1.227 to 2.209; p = 0.001).

CONCLUSIONS:

CSM reduces positive-margin rates in patients with pure DCIS, and can be a practical solution for DCIS patients who tend to have a high rate of margin positivity.
A History of Manners and Civility in Thailand
Authors: Jory Patrick
Published: December 2020

Manners have long been a central concern of Thai society. Kings, aristocrats, prime ministers, monks, army generals, politicians, poets, novelists, journalists and teachers have produced a large corpus of literature that sets out models of appropriate behaviour. These include such things as how to stand, walk, sit, pay homage, prostrate oneself in the presence of high-status people, sleep, eat, manage bodily functions, dress, pay respect to superiors, deal with inferiors, socialize, and play. These modes of conduct have been taught or enforced by families, monasteries, court society, and, in the twentieth century, the state, through the education system, the bureaucracy, and the mass media. In this innovative new social history, based on Thai manners and etiquette manuals dating from the early nineteenth century to the late twentieth century, Patrick Jory presents the first ever history of manners in Thailand and challenges the idea of Western influence as the determinant of change in ideals of conduct.
BRIDGING THE GAP EBIII-IBA: EARLY INTERMEDIATE BRONZE RADIOCARBON DATES FROM KHIRBAT EL-’ALYA NORTHEAST, ISRAEL
Authors: Lev Ron , Shalev Omer , Regev Johanna , Paz Yitzhak , Boaretto Elisabetta
Published: December 2020

Recent radiocarbon (14C) research demonstrates that the urban culture of Early-Bronze III in the southern Levant ends around 2500 BC, and not around 2300 BC as was widely assumed. This should extend the Intermediate Bronze Age by 200 years. Charred olive pits from Intermediate Bronze Age contexts in the site of Khirbat el-‘Alya Northeast in the Judean Shephelah region (Israel) were14C dated, resulting in calibrated dates around 2500 BC. The date range of Khirbat el-‘Alya Northeast samples is an indication that in the Mediterranean parts of the southern Levant, the Intermediate Bronze Age material culture appeared around the time of the decline of the preceding culture of Early-Bronze III—around 2500 BC or somewhat earlier. Possible Intermediate Bronze settlement pattern and the site’s relation to the nearby Early-Bronze city of Tel Yarmuth are discussed based on previous Intermediate Bronze and Early-Bronze related research in the surrounding area.
Development and evaluation of a new dietary index assessing nutrient security by aggregating probabilistic estimates of the risk of nutrient deficiency in two French adult populations
Authors: Salomé Marion , Kesse-Guyot Emmanuelle , Fouillet Hélène , Touvier Mathilde , Hercberg Serge , Huneau Jean-François , Mariotti François
Published: December 2020

Although micronutrient deficiencies affect 2 billion people worldwide, no index focuses on measuring the risk of overt nutrient deficiency. We aimed to develop an index that could capture the nutrient dimension of nutritional security, a nutrient security index (named SecDiet), and evaluate its apparent validity. The SecDiet (range: 0–1) is based on the square-weighted average of the probabilities that the intake of twelve critical nutrients exceeds the threshold value associated with a risk of overt deficiency. Using adult populations from a French representative survey (INCA3, n 1774) and a large cohort (NutriNet-Santé, n 104 382), the content and construct validity of the SecDiet was evaluated by estimating associations of the SecDiet with its components and with relevant socio-demographic characteristics. The SecDiet was high in the overall population (0·93 (SD 0·09) in INCA3) and markedly skewed towards 1 (i.e. lower risk of insufficient intake). It correlated positively with its twelve components (r 0·17–0·78, all P < 0·001). The SecDiet was associated with monthly income (P = 0·002), perception of financial situation, professional situation, food insufficiency and security statuses (all P < 0·001) in the INCA3 population and with monthly income, professional situation and level of education (all P < 0·001) in the NutriNet-Santé population. Unlike a broader nutrient-based quality index taken as comparison, the SecDiet mean decreased and the tail of its distribution notably extended downwards in at-risk sub-populations, thus revealing its specific sensitivity. The SecDiet could be used to screen sub-groups or study the determinants of nutrient insecurity in large population surveys.
Does inoculation with native rhizobia enhance nitrogen fixation and yield of cowpea through legume-based intercropping in the northern mountainous areas of Vietnam?
Authors: Nguyen Trung Thanh , Atieno Mary , Herrmann Laetitia , Nakasathien Sutkhet , Sarobol Ed , Wongkaew Arunee , Nguyen Kien Tri , Lesueur Didier
Published: December 2020

In the Northern mountainous region of Vietnam, cassava–cowpea intercropping system has been widely promoted with support from the local agricultural department. However, cowpea yield is often limited because of a low Biological Nitrogen Fixation (BNF) activity due to its low natural nodulation and lack of available effective Rhizobium products. The aim of this study was to identify the most effective native rhizobia isolate nodulating cowpea with the potential to increase BNF and yield of cowpea. A greenhouse experiment was initially conducted with five treatments: three native rhizobia isolates (CMBP037, CMBP054, and CMBP065); a control (no inoculation and no N application); and N+ (no inoculation, application of N as KNO3). Field inoculations were carried out and the treatments were as follows: a control (no inoculation); CMBP (037+054) – a mixture of strains from Mau Dong; CMBP065 strain from Cat Thinh. CMBP054 and CMBP065 had the highest nodulation in the greenhouse (46.4 and 60.7 nodules plant−1, respectively) and were rated as effective with symbiotic efficiency (SEF) of 54.56 and 55.73%, respectively. In the field, CMBP (037+054) recorded significantly higher nodulation (19.4 nodules plant−1) than the control (11.7 nodules plant−1). CMBP (037+054) also increased cowpea shoot dry weight, shoot N, and yield by 28.6, 4.9, and 10.5%, respectively, compared to the uninoculated control. This effect was slope dependent (statistically significant in moderate and steep slope, not with gentle slope). Besides, the high expansion rate of intercropping with cowpea showed the high adoption level of these agroecological practices by local farmers. This study reveals the potential of native rhizobia inoculation to enhance soil fertility and sustainable agriculture in the Northern mountainous region of Vietnam and proposes enhanced efforts to promote the availability and utilization of effective inoculants for cowpea.
Brood parasitism leads to zero recruitment in the globally endangered Yellow CardinalGubernatrix cristata
Authors: ATENCIO MELINA , REBOREDA JUAN CARLOS , MAHLER BETTINA
Published: December 2020

The Yellow CardinalGubernatrix cristatais an ‘Endangered’ passerine from southern South America. For the past three years a management plan for Yellow Cardinals has been implemented in Argentina, in which rescued individuals from the illegal cage bird trade were released back into suitable habitats within their population of origin. We studied the reproductive success of a mixed population of released and wild Yellow Cardinals in La Pampa province, Argentina, during the reproductive season of 2019. The population was highly parasitized by the brood parasitic Shiny CowbirdMolothrus bonariensis. The frequency of parasitism was 100% and the intensity of parasitism was 4.5 ± 3.4 (mean ± SD) eggs per parasitized nest (range 1–13). No Yellow Cardinal chicks were recruited in the monitored nests, mainly as a consequence of Shiny Cowbird parasitism. The unusually high rate of parasitism led to a poor outcome of the reintroduction programme and indicates the need to update the conservation actions that have been carried out for the Yellow Cardinal so far. Shiny Cowbird abundance varies within the distribution of Yellow Cardinals, related to habitat modification and farming activities. Thus, further research on habitat suitability and assessment of Shiny Cowbird abundance should be incorporated into future strategies for the conservation of the Yellow Cardinal.
Cycle partitions of regular graphs
Authors: Gruslys Vytautas , Letzter Shoham
Published: December 2020

Magnant and Martin conjectured that the vertex set of any d-regular graph G on n vertices can be partitioned into
$n / (d+1)$
paths (there exists a simple construction showing that this bound would be best possible). We prove this conjecture when
$d = \Omega(n)$
, improving a result of Han, who showed that in this range almost all vertices of G can be covered by
$n / (d+1) + 1$
vertex-disjoint paths. In fact our proof gives a partition of V(G) into cycles. We also show that, if
$d = \Omega(n)$
and G is bipartite, then V(G) can be partitioned into n/(2d) paths (this bound is tight for bipartite graphs).
Pregestational BMI and higher offspring’s risk of overweight/obesity in smoker and non-smoker mothers
Authors: Martín-Calvo Nerea , Santiago Neri Susana , Segura Gloria , Fernandez-Lazaro Cesar I , Barbería-Latasa María , Martínez-González Miguel-Ángel
Published: December 2020

Objective:

To assess the association between pregestational BMI and offspring’s risk of overweight/obesity after accounting for the most important confounders, especially maternal smoking habit.

Design:

Prospective cohort study.

Setting:

The Seguimiento Universidad de Navarra (SUN) study is a prospective cohort of Spanish graduates with more than 22 000 participants nationwide. Recruitment started in 1999, and it is permanently open. Data on diet, lifestyle and clinical diagnoses are collected at baseline and every 2 years.

Participants:

Women from the SUN cohort who reported at least one pregnancy during follow-up (n 3496) were invited to this study. Among them, 1527 agreed to participate and completed an additional more detailed online questionnaire on their pregnancy history and their offspring’s nutritional status.

Results:

After excluding 165 children, we analysed data of 2791 participants born to 1485 mothers and observed that each 5 kg/m2 increase in pregestational BMI was associated with a 0·22 (95 % CI 0·15, 0·29) higher z-score in offspring’s BMI and higher risk of overweight/obesity (multivariable-adjusted relative risk (RR) 1·57 (95 % CI 1·39, 1·77)) in childhood or adolescence. Furthermore, we observed stronger association in children born to smoker mothers (RR 1·91; 95 % CI 1·48, 2·46) than from non-smoker mothers (RR 1·51; 95 % CI 1·31, 1·73) (Pfor interaction = 0·02).

Conclusions:

We found a synergistic interaction between pregestational BMI and maternal smoking habit on offspring’s z-score of the BMI and in their risk of overweight/obesity. Although further research is needed to analyse dose–response relationships, these findings reinforce the importance of promoting healthy lifestyles in pregnant women in order to prevent childhood obesity.
MODELLING HUMAN CARRYING CAPACITY AS A FUNCTION OF FOOD AVAILABILITY
Authors: ZULKARNAEN DINY , RODRIGO MARIANITO R.
Published: December 2020

We assume that human carrying capacity is determined by food availability. We propose three classes of human population dynamical models of logistic type, where the carrying capacity is a function of the food production index. We also employ an integration-based parameter estimation technique to derive explicit formulas for the model parameters. Using actual population and food production index data, numerical simulations of our models suggest that an increase in food availability implies an increase in carrying capacity, but the carrying capacity is “self-limiting” and does not increase indefinitely.
Frühe Kindheit
Authors: Clark Gloria Frolek , Kingsley Karrie
Published: December 2020

Alltägliches Handeln ermöglichen: die Leitlinien der Ergotherapie als Instrumente für Praxis, Lehre und Wissenschaft

Praxis verbessern, Versorgungsqualität steigern, Kosten sparen und Zufriedenheit der Klienten erhöhen: Die Anforderungen an die therapeutischen Gesundheitsfachberufe sind hoch. Praxisleitlinien stellen Informationen und Interventionen bereit - systematisch und evidenzbasiert.

Band 11: Frühe Kindheit
Von der Geburt bis zum 5. Lebensjahr - eine vulnerable Zeitspanne im Leben jedes Menschen. Es ist die vorschulische Zeit, die Zeit, die noch nicht durch Institutionen geprägt ist. Ergotherapie geht es nicht alleine um frühe Interventionen im Lebenslauf. Vielmehr gilt es, in dieser kritischen Phase, die Fähigkeiten der Kinder so zu kräftigen, dass sie am späteren Leben aktiv und selbstbewusst teilnehmen können.

Die Leitlinie umfasst:

Gegenstandsbereich und Prozess der Ergotherapie
Überblick zur frühen Kindheit
Ergotherapeutischer Prozess
Best Practice und Zusammenfassung der Evidenz
Schlussfolgerungen für Praxis, Ausbildung, Forschung
Evidenzbasierte Praxis und Übersicht zur Evidenz
Glossar aus dem Occupational Therapy Practice Framework (OTPF, 2014) des AOTA in deutscher Sprache
Sedimentary Nutrient Supply in Productive Hot Spots off the West Antarctic Peninsula Revealed by Silicon Isotopes
Authors: Cassarino Lucie , Hendry Katharine R. , Henley Sian F. , MacDonald Ellen , Arndt Sandra , Freitas Felipe S. , Pike Jennifer , Firing Yvonne L.
Published: December 2020

In this study we evaluate the benthic fluxes of silicic acid along the West Antarctic Peninsula (WAP). Silicic acid (DSi) is one of the macronutrients essential in fuelling biological hot spots of diatom‐dominated primary production along the WAP. Here we measure the concentration and stable silicon isotopic composition of DSi in porewater profiles, biogenic silica content (BSi), and diatom abundance from sediment cores collected along the WAP. We couple these measurements with reaction‐transport modeling, to assess the DSi flux and the processes that release this key nutrient from the sediment into the overlying waters. Our results show that the benthic DSi flux is dominated by the diffusive flux, which is estimated to be equivalent to 26.7 ± 2.7 Gmol yr−1 for the WAP continental shelf. The DSi isotope profiles reveal the important impact of sedimentary processes on porewater DSi and suggest that biogenic silica dissolution is the main source of DSi in porewaters and consequently of the benthic fluxes. Our integrated data‐model assessment highlights the impact of surface productivity on sedimentary processes and the dynamic environment of core‐top sediments where dissolution and reverse weathering reactions control DSi exchanges.
Geothermal Convection and Double Diffusion Based on Profiling Floats in the Black Sea
Authors: Stanev E. V. , Chtirkova B. , Peneva E.
Published: December 2020

Here, we revisit the existing concepts of the vertical structure of deep layers in the Black Sea using data from sensors deployed on profiling floats. The deep transition layer (DTL) between 700 and 1,700 m acts as an interface between the baroclinic layer and the largest bottom convective layer (BCL) of the world oceans. On top of DTL are the warm intermediate layer and deep cold intermediate layer. They both showed strong trends in the last 15 years due to warmer climate and intensification of warmer intrusions from Bosporus. A “salinity wave” was detected in 2005–2009 below ∼1,700 m, which evidenced for the first time the penetration of gravity flow from Bosporus down to the bottom. The layering of water masses was explained as resulting from the different distribution of sources of heat and salt, double diffusion, and balances between the geothermal and salinity flows in the BCL.
Auroral Arcs: The Fracture Theory Revisited
Authors: Haerendel Gerhard
Published: December 2020

The fracture theory for auroral arcs, developed by the author since 1980, compares the decoupling of the magnetic field from the ionosphere by the auroral acceleration region (AAR) with the breaking of a solid rod. In the latter elastic energy stored by the bending is converted into kinetic energy of the stress release motion. Similarly, magnetic energy stored in sheared magnetic fields is temporarily converted into stress release motions and finally transported as Poynting flux into the AAR. The fracture theory has been especially applied to arcs embedded in the convection of the evening auroral oval. The present study subjects the different steps in the fracture process to a critical analysis in the light of new physical insights. This boils down to a revision of the illustrating cartoon used in the earlier publications, without having affecting the quantitative evaluations. The first revision concerns the height extent of the AAR. It must be largely increased. The second revision introduces a nearly 2‐D magnetohydrodynamics (MHD) turbulence into the state of the AAR. This is supported by high‐altitude electric field data and leads to new view of auroral rays. The third revision describes the transition from the AAR to the ionosphere as structured by so‐called potential fingers, which contain substantial fractions of the total field‐parallel potential drop. The most important modification pertains to the average U‐shaped potential of a spontaneously propagating AAR. While the leading edge of the auroral current sheet is structured by stress release motions, the reverse flow in the rear section escapes simple interpretation. It is proposed that this flow is driven by a turbulent transport of reversed momentum from front to rear in response to the incompressibility of the magnetic field in the acceleration region. This leads to a revision of the field‐aligned currents and wavefield in the rear of the arc.
Similarities and Differences in the Rupture Processes of the 1952 and 2003 Tokachi‐Oki Earthquakes
Authors: Kobayashi Hiroaki , Koketsu Kazuki , Miyake Hiroe , Kanamori Hiroo
Published: December 2020

We investigated the similarities and differences between the rupture processes of the 1952 and 2003 Tokachi‐oki earthquakes (Mw ∼ 8) that occurred 51 years apart in the southernmost region of the Kuril subduction zone. This event pair is rare because seismic waveforms of both events were instrumentally recorded. We performed joint source inversion analyses of both earthquakes to better understand the rupture processes of this earthquake sequence. The dataset for the 1952 earthquake consists of teleseismic and strong motion data which were obtained by digitizing copies of analog seismograms. Two datasets were made for the 2003 earthquake to examine the effect of data limitation and to facilitate a comparison of the inversion results of the two earthquakes. One dataset consists of a large amount of teleseismic, strong motion, and geodetic data. The other dataset is similar to that of the 1952 earthquake. Our results show that the rupture propagation, slip areas, and maximum slip amounts were similar for the 1952 and 2003 earthquakes in the Tokachi‐oki region. However, there are two important differences: the 1952 earthquake was initiated by anMw6.1 subevent in the Tokachi‐oki region, and its rupture extended to the adjacent Akkeshi‐oki region. The similarity in the rupture pattern of the M8‐class earthquake pair suggests the persistence of asperities on the plate interface, while the differences imply a degree of variability in the initiation and termination of the cascading rupture process.
Stochastic Generation of Future Hydroclimate Using Temperature as a Climate Change Covariate
Authors: Kiem Anthony S. , Kuczera George , Kozarovski Pavel , Zhang Lanying , Willgoose Garry
Published: December 2020

It is now standard practice for water supply agencies to use stochastic models to generate synthetic hydroclimate sequences that preserve the key statistics contained in the observed/instrumental hydroclimate data (usually rainfall, potential evapotranspiration, and streamflow) for use as inputs when determining water security. However, this approach is only adequate for determining current and future water supply risks if nonstationarity in past and future climate is accounted for. In this study, we develop an approach for stochastically generating future seasonal (monthly to annual) hydroclimatic conditions at multiple sites for water supply security assessment that capitalizes on an Australia‐wide relationship between annual average daily maximum temperature and annual rain (and flow). This approach is practical as it (i) avoids the extra time and additional uncertainties introduced by downscaling and bias correction of climate model produced rainfall information and (ii) takes advantage of the fact that climate model projections for temperature change are more realistic than climate model projections for rainfall. The approach is applied to a case study for catchments supplying Sydney, Australia's largest city. Two future scenarios were evaluated, 1 and 2°C warming over the next 50 years. Large reductions in streamflow were simulated, particularly for the 2°C scenario, resulting in major impacts on water security in the absence of any intervention. This is consistent with recent warming since 1990 being associated with more than a 40% decrease in average annual streamflow when compared with the average annual streamflow over the ∼110 years historical record.
Characterizing Physical Properties of Streambed Interface Sediments Using In Situ Complex Electrical Conductivity Measurements
Authors: Wang Chen , Briggs Martin A. , Day‐Lewis Frederick D. , Slater Lee D.
Published: December 2020

Streambed sediment physical properties such as surface area, are difficult to quantify in situ but exert a high‐level control on a wide range of biogeochemical processes and sorption of contaminants. We introduce the use of complex electrical conductivity (CC) methods (also known as spectral‐induced polarization (SIP)) that measure both real and imaginary conductivity to noninvasively and efficiently characterize shallow streambed sediments. We explore the method through synthetic modeling, laboratory, and field measurements to demonstrate the sensitivity of imaginary conductivity to sediment surface area, controlled in part by fine‐grained iron oxides produced by anoxic groundwater discharge. Laboratory measurements verify expected relationships between CC parameters and sediment properties. Synthetic modeling using a 1D analytical model illustrates the influence of water layer depth and conductivity on the field CC measurements made at the streambed‐stream water interface. Specifically, the inverted sediment imaginary conductivity is less impacted by uncertainty in the water layer depth and conductivity relative to the real conductivity and phase shift. Field CC measurements along a landfill‐impacted river reveal discrete streambed zones with enhanced bulk surface area generally corresponding to anoxic groundwater discharge zones with high concentrations of fine‐grained iron oxide precipitates.
Epigenetic biotypes of post-traumatic stress disorder in war-zone exposed veteran and active duty males
Authors: Yang Ruoting , Gautam Aarti , Getnet Derese , Daigle Bernie J. , Miller Stacy , Misganaw Burook , Dean Kelsey R. , Kumar Raina , Muhie Seid , Wang Kai , Lee Inyoul , Abu-Amara Duna , Flory Janine D. ,   The PTSD Systems Biology Consortium, Hoke Allison , Chakraborty Nabarun , Petzold Linda , Wu Gwyneth , Guffanti Guia , Kim Taek-Kyun , Lee Min Young , Bierer Linda , Hood Leroy , Wolkowitz Owen M. , Mellon Synthia H. , Doyle Francis J. , Yehuda Rachel , Marmar Charles R. , Ressler Kerry J. , Hammamieh Rasha , Jett Marti
Published: December 2020

Post-traumatic stress disorder (PTSD) is a heterogeneous condition evidenced by the absence of objective physiological measurements applicable to all who meet the criteria for the disorder as well as divergent responses to treatments. This study capitalized on biological diversity observed within the PTSD group observed following epigenome-wide analysis of a well-characterized Discovery cohort (N = 166) consisting of 83 male combat exposed veterans with PTSD, and 83 combat veterans without PTSD in order to identify patterns that might distinguish subtypes. Computational analysis of DNA methylation (DNAm) profiles identified two PTSD biotypes within the PTSD+ group, G1 and G2, associated with 34 clinical features that are associated with PTSD and PTSD comorbidities. The G2 biotype was associated with an increased PTSD risk and had higher polygenic risk scores and a greater methylation compared to the G1 biotype and healthy controls. The findings were validated at a 3-year follow-up (N = 59) of the same individuals as well as in two independent, veteran cohorts (N = 54 and N = 38), and an active duty cohort (N = 133). In some cases, for example Dopamine-PKA-CREB and GABA-PKC-CREB signaling pathways, the biotypes were oppositely dysregulated, suggesting that the biotypes were not simply a function of a dimensional relationship with symptom severity, but may represent distinct biological risk profiles underpinning PTSD. The identification of two novel distinct epigenetic biotypes for PTSD may have future utility in understanding biological and clinical heterogeneity in PTSD and potential applications in risk assessment for active duty military personnel under non-clinician-administered settings, and improvement of PTSD diagnostic markers.
SLFN11 informs on standard of care and novel treatments in a wide range of cancer models
Authors: Winkler Claudia , Armenia Joshua , Jones Gemma N. , Tobalina Luis , Sale Matthew J. , Petreus Tudor , Baird Tarrion , Serra Violeta , Wang Anderson T. , Lau Alan , Garnett Mathew J. , Jaaks Patricia , Coker Elizabeth A. , Pierce Andrew J. , O’Connor Mark J. , Leo Elisabetta
Published: December 2020

Background

Schlafen 11 (SLFN11) has been linked with response to DNA-damaging agents (DDA) and PARP inhibitors. An in-depth understanding of several aspects of its role as a biomarker in cancer is missing, as is a comprehensive analysis of the clinical significance of SLFN11 as a predictive biomarker to DDA and/or DNA damage-response inhibitor (DDRi) therapies.

Methods

We used a multidisciplinary effort combining specific immunohistochemistry, pharmacology tests, anticancer combination therapies and mechanistic studies to assess SLFN11 as a potential biomarker for stratification of patients treated with several DDA and/or DDRi in the preclinical and clinical setting.

Results

SLFN11 protein associated with both preclinical and patient treatment response to DDA, but not to non-DDA or DDRi therapies, such as WEE1 inhibitor or olaparib in breast cancer. SLFN11-low/absent cancers were identified across different tumour types tested. Combinations of DDA with DDRi targeting the replication-stress response (ATR, CHK1 and WEE1) could re-sensitise SLFN11-absent/low cancer models to the DDA treatment and were effective in upper gastrointestinal and genitourinary malignancies.

Conclusion

SLFN11 informs on the standard of care chemotherapy based on DDA and the effect of selected combinations with ATR, WEE1 or CHK1 inhibitor in a wide range of cancer types and models.
Negative thermal expansion in α-Zr2SP2O12 based on phase transition- and framework-type mechanisms
Authors: Isobe Toshihiro , Hayakawa Yuko , Adachi Yuri , Uehara Ryosuke , Matsushita Sachiko , Nakajima Akira
Published: December 2020

Materials with negative coefficients of thermal expansion (CTEs) can be used to prepare composites with specific CTE values. Negative thermal expansion behavior can be primarily attributed to two types of mechanisms: phase transition- and framework-type mechanisms. This paper reports Zr2SP2O12, which has unique negative thermal expansion behavior involving both mechanisms. Zr2SP2O12 undergoes a framework-type mechanism at temperatures <393 K or >453 K and an isosymmetric phase transition at 393–453 K. The volumetric CTE of α-Zr2SP2O12 is ~−70 p.p.m./K during the isosymmetric phase transition, and this value can be decreased by decreasing the proportion of sulfur. The minimum volumetric CTE of α-Zr2S0.9P2O12-δ is ~−108 p.p.m./K in the temperature range of 393–453 K. Between 303 and 773 K, the volume of α-Zr2S0.9P2O12 − δ is reduced by ~1.3%. Finally, this paper presents methods for the hydrothermal synthesis of α-Zr2SP2O12 and for controlling the sulfur content.
Genomic signatures of recombination in a natural population of the bdelloid rotifer Adineta vaga
Authors: Vakhrusheva Olga A. , Mnatsakanova Elena A. , Galimov Yan R. , Neretina Tatiana V. , Gerasimov Evgeny S. , Naumenko Sergey A. , Ozerova Svetlana G. , Zalevsky Arthur O. , Yushenova Irina A. , Rodriguez Fernando , Arkhipova Irina R. , Penin Aleksey A. , Logacheva Maria D. , Bazykin Georgii A. , Kondrashov Alexey S.
Published: December 2020

Sexual reproduction is almost ubiquitous among extant eukaryotes. As most asexual lineages are short-lived, abandoning sex is commonly regarded as an evolutionary dead end. Still, putative anciently asexual lineages challenge this view. One of the most striking examples are bdelloid rotifers, microscopic freshwater invertebrates believed to have completely abandoned sexual reproduction tens of Myr ago. Here, we compare whole genomes of 11 wild-caught individuals of the bdelloid rotifer Adineta vaga and present evidence that some patterns in its genetic variation are incompatible with strict clonality and lack of genetic exchange. These patterns include genotype proportions close to Hardy-Weinberg expectations within loci, lack of linkage disequilibrium between distant loci, incongruent haplotype phylogenies across the genome, and evidence for hybridization between divergent lineages. Analysis of triallelic sites independently corroborates these findings. Our results provide evidence for interindividual genetic exchange and recombination in A. vaga, a species previously thought to be anciently asexual.
Linear and nonlinear optical responses in the chiral multifold semimetal RhSi
Authors: Ni Zhuoliang , Xu B. , Sánchez-Martínez M.-Á. , Zhang Y. , Manna K. , Bernhard C. , Venderbos J. W. F. , de Juan F. , Felser C. , Grushin A. G. , Wu Liang
Published: December 2020

Chiral topological semimetals are materials that break both inversion and mirror symmetries. They host interesting phenomena such as the quantized circular photogalvanic effect (CPGE) and the chiral magnetic effect. In this work, we report a comprehensive theoretical and experimental analysis of the linear and nonlinear optical responses of the chiral topological semimetal RhSi, which is known to host multifold fermions. We show that the characteristic features of the optical conductivity, which display two distinct quasi-linear regimes above and below 0.4 eV, can be linked to excitations of different kinds of multifold fermions. The characteristic features of the CPGE, which displays a sign change at 0.4 eV and a large non-quantized response peak of around 160 μA/V2 at 0.7 eV, are explained by assuming that the chemical potential crosses a flat hole band at the Brillouin zone center. Our theory predicts that, in order to observe a quantized CPGE in RhSi, it is necessary to increase the chemical potential as well as the quasiparticle lifetime. More broadly, our methodology, especially the development of the broadband terahertz emission spectroscopy, could be widely applied to study photogalvanic effects in noncentrosymmetric materials and in topological insulators in a contact-less way and accelerate the technological development of efficient infrared detectors based on topological semimetals.
Assessment of skin barrier function using skin images with topological data analysis
Authors: Koseki Keita , Kawasaki Hiroshi , Atsugi Toru , Nakanishi Miki , Mizuno Makoto , Naru Eiji , Ebihara Tamotsu , Amagai Masayuki , Kawakami Eiryo
Published: December 2020

Recent developments of molecular biology have revealed diverse mechanisms of skin diseases, and precision medicine considering these mechanisms requires the frequent objective evaluation of skin phenotypes. Transepidermal water loss (TEWL) is commonly used for evaluating skin barrier function; however, direct measurement of TEWL is time-consuming and is not convenient for daily clinical practice. Here, we propose a new skin barrier assessment method using skin images with topological data analysis (TDA). TDA enabled efficient identification of structural features from a skin image taken by a microscope. These features reflected the regularity of the skin texture. We found a significant correlation between the topological features and TEWL. Moreover, using the features as input, we trained machine-learning models to predict TEWL and obtained good accuracy (R2 = 0.524). Our results suggest that assessment of skin barrier function by topological image analysis is promising.
Obstacles to the reuse of study metadata in ClinicalTrials.gov
Authors: Miron Laura , Gonçalves Rafael S. , Musen Mark A.
Published: December 2020

Metadata that are structured using principled schemas and that use terms from ontologies are essential to making biomedical data findable and reusable for downstream analyses. The largest source of metadata that describes the experimental protocol, funding, and scientific leadership of clinical studies is ClinicalTrials.gov. We evaluated whether values in 302,091 trial records adhere to expected data types and use terms from biomedical ontologies, whether records contain fields required by government regulations, and whether structured elements could replace free-text elements. Contact information, outcome measures, and study design are frequently missing or underspecified. Important fields for search, such as condition and intervention, are not restricted to ontologies, and almost half of the conditions are not denoted by MeSH terms, as recommended. Eligibility criteria are stored as semi-structured free text. Enforcing the presence of all required elements, requiring values for certain fields to be drawn from ontologies, and creating a structured eligibility criteria element would improve the reusability of data from ClinicalTrials.gov in systematic reviews, metanalyses, and matching of eligible patients to trials.
Multi-task learning for the simultaneous reconstruction of the human and mouse gene regulatory networks
Authors: Mignone Paolo , Pio Gianvito , Džeroski Sašo , Ceci Michelangelo
Published: December 2020

The reconstruction of Gene Regulatory Networks (GRNs) from gene expression data, supported by machine learning approaches, has received increasing attention in recent years. The task at hand is to identify regulatory links between genes in a network. However, existing methods often suffer when the number of labeled examples is low or when no negative examples are available. In this paper we propose a multi-task method that is able to simultaneously reconstruct the human and the mouse GRNs using the similarities between the two. This is done by exploiting, in a transfer learning approach, possible dependencies that may exist among them. Simultaneously, we solve the issues arising from the limited availability of examples of links by relying on a novel clustering-based approach, able to estimate the degree of certainty of unlabeled examples of links, so that they can be exploited during the training together with the labeled examples. Our experiments show that the proposed method can reconstruct both the human and the mouse GRNs more effectively compared to reconstructing each network separately. Moreover, it significantly outperforms three state-of-the-art transfer learning approaches that, analogously to our method, can exploit the knowledge coming from both organisms. Finally, a specific robustness analysis reveals that, even when the number of labeled examples is very low with respect to the number of unlabeled examples, the proposed method is almost always able to outperform its single-task counterpart.
Methylation of estrogen receptor 2 (ESR2) in deep paravertebral muscles and its association with idiopathic scoliosis
Authors: Chmielewska Małgorzata , Janusz Piotr , Andrusiewicz Mirosław , Kotwicki Tomasz , Kotwicka Małgorzata
Published: December 2020

Idiopathic scoliosis (IS) is one of the most common spinal disorders in adolescents. Despite many studies, the etiopathogenesis of IS is still poorly understood. In recent years, the role of epigenetic factors in the etiopathogenesis of IS has been increasingly investigated. It has also been postulated that the development and progression of the disease is related to gender and puberty, and could be associated with estrogen action. Estrogen hormones act via estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2). It has been suggested that ESR2 expression is dependent on methylation within its gene promoter. So far, no studies have evaluated local, tissue-specific DNA methylation in patients with IS. Thus, our study aimed to analyze the methylation and expression level of ESR2 in the paraspinal muscles of the convex and concave side of the IS curvature. The methylation level within ESR2 promoter 0N, but not exon 0N, was significantly higher on the concave side of the curvature compared to the convex side. There was no significant correlation between ESR2 expression and methylation level in the promoter 0N on the convexity of thoracic scoliosis, whereas, on the concave side of the curvature, we observed a moderate negative correlation. There was no difference in the methylation levels of the ESR2 promoter and exon 0N between groups of patients with Cobb angle ≤ 70° and > 70° on the concave and convex side of the curvature. We also found no statistically significant correlation between the Cobb angle value and the mean methylation level in either the ESR2 promoter or exon 0N on the convex or concave side of the curvature. Our findings demonstrate that DNA methylation at the ESR2 promoter in deep paravertebral muscle tissue is associated with the occurrence but not with the severity of idiopathic scoliosis.
K63-linked ubiquitylation induces global sequestration of mitochondria
Authors: Richard Thibaud J. C. , Herzog Laura K. , Vornberger Julia , Rahmanto Aldwin Suryo , Sangfelt Olle , Salomons Florian A. , Dantuma Nico P.
Published: December 2020

Even though K63-linked polyubiquitin chains do not target proteins for proteasomal degradation, they play nevertheless a complementary protective role in maintaining protein homeostasis by directing malfunctioning proteins and organelles to inclusion bodies or autophagosomes. A paradigm for this process is the sequestration and autophagic degradation of dysfunctional mitochondria. Although studies have shown that K63-ubiquitylation of mitochondrial proteins by the ubiquitin ligase Parkin is important in this process, it is presently not clear if this modification also suffices to initiate this cascade of events. To address this question, we have engineered the ubiquitin ligase ProxE3, which in an inducible manner synthesizes K63-linked ubiquitin chains on the surface of mitochondria. We found that the presence of K63-linked ubiquitin chains on mitochondria resulted in the recruitment of the ubiquitin adaptor p62 and induced a dramatic redistribution of mitochondria, which was reminiscent to the Parkin-facilitated sequestration in response to mitochondrial uncoupler. However, ProxE3 did not induce autophagic degradation of mitochondria. Our data show that K63-linked ubiquitin chains at the mitochondrial membrane are sufficient for the induction of mitochondrial sequestration, but not mitophagy, without the need of extrinsically inflicting mitochondrial dysfunction.
Dynamic data-driven meta-analysis for prioritisation of host genes implicated in COVID-19
Authors: Parkinson Nicholas , Rodgers Natasha , Head Fourman Max , Wang Bo , Zechner Marie , Swets Maaike C. , Millar Jonathan E. , Law Andy , Russell Clark D. , Baillie J. Kenneth , Clohisey Sara
Published: December 2020

The increasing body of literature describing the role of host factors in COVID-19 pathogenesis demonstrates the need to combine diverse, multi-omic data to evaluate and substantiate the most robust evidence and inform development of therapies. Here we present a dynamic ranking of host genes implicated in human betacoronavirus infection (SARS-CoV-2, SARS-CoV, MERS-CoV, seasonal coronaviruses). We conducted an extensive systematic review of experiments identifying potential host factors. Gene lists from diverse sources were integrated using Meta-Analysis by Information Content (MAIC). This previously described algorithm uses data-driven gene list weightings to produce a comprehensive ranked list of implicated host genes. From 32 datasets, the top ranked gene was PPIA, encoding cyclophilin A, a druggable target using cyclosporine. Other highly-ranked genes included proposed prognostic factors (CXCL10, CD4, CD3E) and investigational therapeutic targets (IL1A) for COVID-19. Gene rankings also inform the interpretation of COVID-19 GWAS results, implicating FYCO1 over other nearby genes in a disease-associated locus on chromosome 3. Researchers can search and review the gene rankings and the contribution of different experimental methods to gene rank at https://baillielab.net/maic/covid19. As new data are published we will regularly update the list of genes as a resource to inform and prioritise future studies.
Identification and functional characterization of the first molluscan neuromedin U receptor in the slug, Deroceras reticulatum
Authors: Ahn Seung-Joon , Mc Donnell Rory J. , Corcoran Jacob A. , Martin Ruth C. , Choi Man-Yeon
Published: December 2020

Neuromedin U (NmU) is a neuropeptide regulating diverse physiological processes. The insect homologs of vertebrate NmU are categorized as PRXamide family peptides due to their conserved C-terminal end. However, NmU homologs have been elusive in Mollusca, the second largest phylum in the animal kingdom. Here we report the first molluscan NmU/PRXamide receptor from the slug, Deroceras reticulatum. Two splicing variants of the receptor gene were functionally expressed and tested for binding with ten endogenous peptides from the slug and some insect PRXamide and vertebrate NmU peptides. Three heptapeptides (QPPLPRYa, QPPVPRYa and AVPRPRIa) triggered significant activation of the receptors, suggesting that they are true ligands for the NmU/PRXamide receptor in the slug. Synthetic peptides with structural modifications at different amino acid positions provided important insights on the core moiety of the active peptides. One receptor variant always exhibited higher binding activity than the other variant. The NmU-encoding genes were highly expressed in the slug brain, while the receptor gene was expressed at lower levels in general with relatively higher expression levels in both the brain and foot. Injection of the bioactive peptides into slugs triggered defensive behavior such as copious mucus secretion and a range of other anomalous behaviors including immobilization, suggesting their role in important physiological functions.