bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of homocysteine on the risk of coronary artery diseases in individuals with diabetes: a Mendelian randomization study
Authors: Xu Tian , Chen Songzan , Yang Fangkun , Wang Yao , Zhang Kaijie , Fu Guosheng , Zhang Wenbin
Published: October 2020

Aims

Observational studies have reported that homocysteine (Hcy) is associated with an increased risk of coronary artery disease (CAD) in individuals with diabetes, though controversy remains. The present study aimed to investigate the causal association between Hcy and CAD in individuals with diabetes.

Methods

A 2-sample Mendelian randomization (MR) study was designed to infer causality. Genetic summary data on the association of single nucleotide polymorphisms (SNPs) with Hcy were extracted from the hitherto largest genome-wide association study (GWAS) of up to 44,147 individuals of European ancestry. SNP-CAD data were obtained from another recently published GWAS which included 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The fixed-effects inverse variance-weighted method was employed to calculate the effect estimates. Other robust methods and leave-one-out analyses were used in the follow-up sensitivity analyses. Potential pleiotropy was assessed with the MR-Egger intercept test.

Results

The 2-sample MR analysis suggested no evidence of an association between genetically predicted plasma Hcy levels and CAD risk in individuals with diabetes (odds ratio = 1.14, 95% confidence interval: 0.82–1.58, p = 0.43) using 9 SNPs as instrumental variables. Similar results were observed in the follow-up sensitivity analyses. The MR-Egger intercept test indicated no evidence of directional pleiotropy (intercept = 0.03, 95% confidence interval: − 0.08–0.03, p = 0.35).

Conclusion

This 2-sample MR analysis found no evidence of a causal association between plasma Hcy levels and CAD risk in individuals with diabetes.
Psychosocial and biological risk factors of anxiety disorders in adolescents: a TRAILS report
Authors: Narmandakh Altanzul , Roest Annelieke M. , de Jonge Peter , Oldehinkel Albertine J.
Published: October 2020

Anxiety disorders are a common problem in adolescent mental health. Previous studies have investigated only a limited number of risk factors for the development of anxiety disorders concurrently. By investigating multiple factors simultaneously, a more complete understanding of the etiology of anxiety disorders can be reached. Therefore, we assessed preadolescent socio-demographic, familial, psychosocial, and biological factors and their association with the onset of anxiety disorders in adolescence. This study was conducted among 1584 Dutch participants of the TRacking Adolescents’ Individual Lives Survey (TRAILS). Potential risk factors were assessed at baseline (age 10–12), and included socio-demographic (sex, socioeconomic status), familial (parental anxiety and depression), psychosocial (childhood adversity, temperament), and biological (body mass index, heart rate, blood pressure, cortisol) variables. Anxiety disorders were assessed at about age 19 years through the Composite International Diagnostic Interview (CIDI). Univariate and multivariate logistic regression analyses were performed with onset of anxiety disorder as a dependent variable and the above-mentioned putative risk factors as predictors. Of the total sample, 25.7% had a lifetime diagnosis of anxiety disorder at age 19 years. Anxiety disorders were twice as prevalent in girls as in boys. Multivariate logistic regression analysis showed that being female (OR = 2.38, p < .01), parental depression and anxiety (OR = 1.34, p = .04), temperamental frustration (OR = 1.31, p = .02) and low effortful control (OR = 0.76, p = .01) independently predicted anxiety disorders. We found no associations between biological factors and anxiety disorder. After exclusion of adolescents with an onset of anxiety disorder before age 12 years, being female was the only significant predictor of anxiety disorder. Being female was the strongest predictor for the onset of anxiety disorder. Psychological and parental psychopathology factors increased the risk of diagnosis of anxiety, but to a lesser extent. Biological factors (heart rate, blood pressure, cortisol, and BMI), at least as measured in the present study, are unlikely to be useful tools for anxiety prevention and intervention strategies.
Plasma skimming efficiency of human blood in the spiral groove bearing of a centrifugal blood pump
Authors: Sakota Daisuke , Kondo Kazuki , Kosaka Ryo , Nishida Masahiro , Maruyama Osamu
Published: October 2020

This work investigates the plasma skimming effect in a spiral groove bearing within a hydrodynamically levitated centrifugal blood pump when working with human blood having a hematocrit value from 0 to 40%. The present study assessed the evaluation based on a method that clarified the limitations associated with such assessments. Human blood was circulated in a closed-loop circuit via a pump operating at 4000 rpm at a flow rate of 5 L/min. Red blood cells flowing through a ridge area of the bearing were directly observed using a high-speed microscope. The hematocrit value in the ridge area was calculated using the mean corpuscular volume, the bearing gap, the cross-sectional area of a red blood cell, and the occupancy of red blood cells. The latter value was obtained from photographic images by dividing the number of pixels showing red blood cells in the evaluation area by the total number of pixels in this area. The plasma skimming efficiency was calculated as the extent to which the hematocrit of the working blood was reduced in the ridge area. For the hematocrit in the circuit from 0 to 40%, the plasma skimming efficiency was approximately 90%, meaning that the hematocrit in the ridge area became 10% as compared to that in the circuit. For a hematocrit of 20% and over, red blood cells almost completely occupied the ridge. Thus, a valid assessment of plasma skimming was only possible when the hematocrit was less than 20%.
Is it the right time for an infant screening for Duchenne muscular dystrophy?
Authors: Vita Gian Luca , Vita Giuseppe
Published: October 2020

Newborn screening (NBS) is an essential, preventive public health programme for early identification of disorders whose early treatment can lead to significant reduction in morbidity and mortality. NBS for Duchenne muscular dystrophy (DMD) has been a controversial matter for many years, because of false positives, the lack of effective drugs and the need of more data about screening efficacy. The still high diagnostic delay of DMD and the current availability of drugs such as steroid, ataluren, eteplirsen, golodirsen and forthcoming new drugs, improving the clinical conditions if early started, make appropriate to begin a concrete discussion between stakeholders to identify best practice for DMD screening. A two-step system CK/DNA screening programme is presented to be performed in male infants aged between 6 months and 42 months involving more than 30,000 male infants. Five to eight DMD subjects are believed to be diagnosed. The pilot project would give the opportunity to test in a small population the feasibility of an infant screening programme, which in the near future could be applicable to an entire country.
Concurrent versus sequential use of trastuzumab and chemotherapy in early HER2+ breast cancer
Authors: Dackus Gwen M. H. E. , Jóźwiak Katarzyna , van der Wall Elsken , van Diest Paul J. , Hauptmann Michael , Siesling Sabine , Sonke Gabe S. , Linn Sabine C.
Published: October 2020

Purpose

The addition of trastuzumab to adjuvant chemotherapy has improved the outcome of human epidermal growth-factor receptor 2 (HER2)-positive breast cancer. Uncertainty remains about the optimal timing of trastuzumab treatment. Therefore, we compared long-term outcome after concurrent versus sequential treatment, in a population-based setting, using data from the nationwide Netherlands Cancer Registry.

Methods

We identified 1843 women diagnosed in The Netherlands from January 1st 2005 until January 1st 2008 with primary, HER2-positive, T1-4NanyM0 breast cancer who received adjuvant chemotherapy and trastuzumab. Kaplan–Meier survival estimates and Cox regression were used to compare recurrence-free survival (RFS) and overall survival (OS) between women who received trastuzumab concurrently with versus sequentially after chemotherapy. Hazard ratios (HR) were adjusted for age, year of diagnosis, grade, pathological T-stage, number of positive lymph nodes, ER-status, PR-status, socio-economic status, radiotherapy, hormonal therapy, ovarian ablation, and type of chemotherapy.

Results

After a median follow-up of 8.2 years, RFS events had occurred in 224 out of 1235 (18.1%) concurrently treated women and 129 out of 608 (21.2%) sequentially treated women (adjusted-HR 0.91; 95% confidence interval (CI) 0.67–1.24; P = 0.580). Deaths occurred in 182/1235 (14.7%) concurrently treated women and 104/608 (17.1%) sequentially treated women (adjusted-HR 0.92; 95% CI 0.65–1.29; P = 0.635).

Conclusions

The results of this population-based study are consistent with earlier randomized trials, demonstrating a non-significant difference in outcome for concurrently treated women compared to those who were treated sequentially, suggesting both options are justified.
Social integration matters: factors influencing natural hazard risk preparedness—a survey of Swiss households
Authors: Maidl Elisabeth , Bresch David N. , Buchecker Matthias
Published: October 2020

Building a culture of risk is an essential objective within the integrated risk management paradigm. Challenges arise both due to increasing damage from natural hazards and the complexity in interaction of different actors in risk management. In Switzerland, the Strategy for Natural Hazards Switzerland, aims to establish efficient protection of the population, natural resources and material goods. This requires that all responsible actors are recognized and aware of their role in risk management. However, previous studies indicate that risk awareness and preparedness levels are rather low within the general population. For the first time, our nationwide survey provides empirical data on factors that influence individual risk preparedness in the general population. Multivariate analysis shows that taking responsibility for natural hazard risk prevention is not only related to personal experience and perceived probability of hazard events, but also crucially influenced by social forms of communication and integration. Therefore, we conclude that social capacity building needs to include such factors in order to render integrated risk management strategies successful.
Mutual interference of layer plane and natural fracture in the failure behavior of shale and the mechanism investigation
Authors: Zhao Peng , Xie Ling-Zhi , Fan Zhi-Chao , Deng Lei , Liu Jun
Published: October 2020

Shale contains a certain amount of natural fractures, which affects the mechanical properties of shale. In this paper, a bonded-particle model in particle flow code (PFC) is established to simulate the failure process of layered shale under Brazilian tests, under the complex relationship between layer plane and natural fracture. First, a shale model without natural fractures is verified against the experimental results. Then, a natural fracture is embedded in the shale model, where the outcomes indicate that the layer plane angle (marked as α) and the angle (marked as β) of embedded fracture prominently interfere the failure strength anisotropy and fracture pattern. Finally, sensitivity evaluations suggest that variable tensile/cohesion strength has a changeable influence on failure mechanism of shale, even for same α or/and β. To serve this work, the stimulated fractures are categorized into two patterns based on whether they relate to natural fracture or not. Meanwhile, four damage modes and the number of microcracks during the loading process are recognized quantitatively to study the mechanism of shale failure behavior. Considering the failure mechanism determines the outcome of hydraulic fracturing in shale, this work is supposed to provide a significant implication in theory for the engineering operation.
Law and the Rule of God
Authors: Ralston Joshua
Published: October 2020

Sharī'a is one of the most hotly contested and misunderstood concepts and practices in the world today. Debates about Islamic law and its relationship to secularism and Christianity have dominated political and theological discourse for centuries. Unfortunately, Western Christian theologians have failed to engage sufficiently with the challenges and questions raised by Islamic political theology, preferring instead to essentialize or dismiss it. In Law and the Rule of God, Joshua Ralston presents an innovative approach to Christian-Muslim dialogue. Eschewing both polemics and apologetics, he proposes a comparative framework for Christian engagement with Islamic debates on sharī'a. Ralston draws on a diverse range of thinkers from both traditions including Karl Barth, Ibn Taymiyya, Thomas Aquinas, and Mohammad al-Jabri. He offers an account of public law as a provisional and indirect witness to the divine rule of justice. He also demonstrates how this theology of public law deeply resonates with the Christian tradition and is also open to learning from and dialoguing with Islamic and secular conceptions of law, sovereignty, and justice.
CLASS NUMBERS OF CM ALGEBRAIC TORI, CM ABELIAN VARIETIES AND COMPONENTS OF UNITARY SHIMURA VARIETIES
Authors: GUO JIA-WEI , SHEU NAI-HENG , YU CHIA-FU
Published: October 2020

We give a formula for the class number of an arbitrary complex mutliplication (CM) algebraic torus over
$\mathbb {Q}$
. This is proved based on results of Ono and Shyr. As applications, we give formulas for numbers of polarized CM abelian varieties, of connected components of unitary Shimura varieties and of certain polarized abelian varieties over finite fields. We also give a second proof of our main result.
INITIAL PROFICIENCY AND L2 GRAMMAR DEVELOPMENT DURING SHORT-TERM IMMERSION ABROAD
Authors: Zalbidea Janire , Issa Bernard I. , Faretta-Stutenberg Mandy , Sanz Cristina
Published: October 2020

The first goal of this study was to examine how individual differences in initial L2 proficiency help explain L2 grammar development in oral production during short-term immersion abroad. The second goal of the study was methodological, and evaluated challenges that can result from operationalizing learners’ initial L2 proficiency as pretest performance on outcome measures (as opposed to independent proficiency measures) in analyses of L2 change. L2 Spanish learners participating in summer study abroad completed an elicited imitation task and two oral production tasks. Production data were analyzed for changes in relevant grammatical complexity and accuracy dimensions. Results indicate that learners with higher initial L2 proficiency experience greater L2 grammar advancement from short-term immersion, and that pretest performance can be an unreliable operational estimate of initial proficiency when analyzing L2 gains. We discuss findings following cognitive accounts of SLA, and highlight methodological implications for further research in immersion contexts and beyond.
Perspectives on native maize conservation in Mexico: a public programme analysis
Authors: Pelcastre Vladimir , García-Frapolli Eduardo , Ayala-Orozco Bárbara , Lazos-Chavero Elena
Published: October 2020

In any conservation programme, a variety of actors participate and interact in its different phases. They commonly have different perspectives and priorities regarding conservation, and diversity in the ensuing perspectives constitutes a barrier to effective conservation. In this paper, we analyse the different perspectives around thePrograma de Conservación de Maíz Criollo(Programme for the Conservation of Native Maize in Mexico; PROMAC) in order to understand the possible causes that resulted in the programme not fulfilling its objectives. We used Q methodology and semi-structured interviews with farmers from a natural protected area to analyse the perspectives of the key actors who conceptualized, designed and implemented the programme and of the target population. Our research identified two different perspectives: (1) native maize can only be conserved with the support of community processes; and (2) the government, and not farmers, is responsible for the conservation of native maize. For farmers, native maize is key to their subsistence livelihoods, and they participated in the programme because of government monetary incentives. These differences contributed to dissimilar interpretations throughout the programme’s implementation phase, which, in turn, likely contributed to PROMAC failing to meet its objectives.
Filling gaps in the seed dispersal effectiveness model forProsopis flexuosa: quality of seed treatment in the digestive tract of native animals
Authors: Campos Claudia M. , Ramos Liliana , Manrique Noelia , Cona Mónica I. , Sartor Carmen , de los Ríos Claudia , Cappa Flavio M.
Published: October 2020

For endozoochorous species, the quality component of seed dispersal effectiveness depends in part on the treatment seeds receive in the animal's gut. Covering a variety of taxa, diet, digestion system and body size ofProsopis flexuosaseed dispersers, we analysed differences among species in (1) mean retention time of ingested seeds, (2) recovery of viable seeds, (3) seed germination in comparison with seeds collected from trees and (4) germination of seeds after two different periods of retention in the gut. Feeding experiments were conducted with captive individuals ofDolichotis patagonum,Lycalopex gymnocercus,Rhea americana,Chelonoidis chilensisandLama guanicoe. On the first day, we provided them with fruits containing controlled amounts of seed, and on the subsequent days, we collected faeces in order to recover seeds. We performed germination and viability tests on seeds coming from faeces and collected from trees. The results showed differences among species in the mean retention time of seeds.Chelonoidis chilensishad the longest mean retention time, but its effect on seed recovery and germination was similar to that of the other species, except forL. guanicoe, which showed the lowest seed recovery. When scarification and promotion of seed germination were considered, herbivorous mammals and tortoises (L. guanicoe,D. patagonumandC. chilensis) were the ones increasing germinability, whereasR. americanaandL. gymnocercusdid not significantly increase final seed germination percentage, which was similar to that for seeds collected from trees.P. flexuosaseeds receive a variety of treatments from endozoochorous dispersers, which might result in an overall fitness benefit for a plant living in unpredictable environments.
Utility of Different Lung Ultrasound Simulation Modalities Used by Paramedics during Varied Ambulance Driving Conditions
Authors: Maloney Lauren M. , Williams Daryl W. , Reardon Lindsay , Marshall R. Trevor , Alian Andrus , Boyle Jess , Secko Michael
Published: October 2020

Introduction:

Prehospital use of lung ultrasound (LUS) by paramedics to guide the diagnoses and treatment of patients has expanded over the past several years. However, almost all of this education has occurred in a classroom or hospital setting. No published prehospital use of LUS simulation software within an ambulance currently exists.

Study Objective:

The objective of this study was to determine if various ambulance driving conditions (stationary, constant acceleration, serpentine, and start-stop) would impact paramedics’ abilities to perform LUS on a standardized patient (SP) using breath-holding to simulate lung pathology, or to perform LUS using ultrasound (US) simulation software. Primary endpoints included the participating paramedics’: (1) time to acquiring a satisfactory simulated LUS image; and (2) accuracy of image recognition and interpretation. Secondary endpoints for the breath-holding portion included: (1) the agreement between image interpretation by paramedic versus blinded expert reviewers; and (2) the quality of captured LUS image as determined by two blinded expert reviewers. Finally, a paramedic LUS training session was evaluated by comparing pre-test to post-test scores on a 25-item assessment requiring the recognition of a clinical interpretation of prerecorded LUS images.

Methods:

Seventeen paramedics received a 45-minute LUS lecture. They then performed 25 LUS exams on both SPs and using simulation software, in each case looking for lung sliding, A and B lines, and seashore or barcode signs. Pre- and post-training, they completed a 25-question test consisting of still images and videos requiring pathology recognition and formulation of a clinical diagnosis. Sixteen paramedics performed the same exams in an ambulance during different driving conditions (stationary, constant acceleration, serpentines, and abrupt start-stops). Lung pathology was block randomized based on driving condition.

Results:

Paramedics demonstrated improved post-test scores compared to pre-test scores (P <.001). No significant difference existed across driving conditions for: time needed to obtain a simulated image; clinical interpretation of simulated LUS images; quality of saved images; or agreement of image interpretation between paramedics and blinded emergency physicians (EPs). Image acquisition time while parked was significantly greater than while the ambulance was driving in serpentines (Z = -2.898; P = .008). Technical challenges for both simulation techniques were noted.

Conclusion:

Paramedics can correctly acquire and interpret simulated LUS images during different ambulance driving conditions. However, simulation techniques better adapted to this unique work environment are needed.
Prenatal hypoxia increases blood pressure in male rat offspring and affects their response to artificial light at night
Authors: Sutovska Hana , Molcan Lubos , Koprdova Romana , Piesova Michaela , Mach Mojmír , Zeman Michal
Published: October 2020

Prenatal hypoxia (PH) has negative consequences on the cardiovascular system in adulthood and can affect the responses to additional insults later in life. We explored the effects of PH imposed during embryonic day 20 (10.5% O2 for 12 h) on circadian rhythms of systolic blood pressure (BP) and heart rate (HR) in mature male rat offspring measured by telemetry. We evaluated: (1) stability of BP and HR changes after PH; (2) circadian variability of BP and HR after 2 and 5 weeks of exposure to artificial light at night (ALAN; 1–2 lx); and (3) response of BP and HR to norepinephrine. PH increased BP in the dark (134 ± 2 mmHg vs. control 127 ± 2 mmHg; p = 0.05) and marginally in the light (125 ± 1 mmHg vs. control 120 ± 2 mmHg) phase of the day but not HR. The effect of PH was highly repeatable between 21- and 27-week-old PH male offspring. Two weeks of ALAN decreased the circadian variability of HR (p < 0.05) and BP more in control than PH rats. After 5 weeks of ALAN, the circadian variability of HR and BP were damped compared to LD and did not differ between control and PH rats (p < 0.05). Responses of BP and HR to norepinephrine did not differ between control and PH rats. Hypoxia at the end of the embryonic period increases BP and affects the functioning of the cardiovascular system in mature male offspring. ALAN in adulthood decreased the circadian variability of cardiovascular parameters, more in control than PH rats.
CME-Dermatologie 22: Masern – Epidemiologie und Klinik
Authors: Hari Luc , Lautenschlager Stephan
Published: October 2020

Zusammenfassung. Die Masern sind eine hoch ansteckende, akute und febrile Krankheit, die durch eine Infektion mit dem Masernvirus verursacht wird. Gemäss Schätzungen der Weltgesundheitsorganisation (WHO) kommt es bei einer weltweiten Prävalenz von zehn Millionen Patientinnen und Patienten pro Jahr zu rund 142 000 Todesfällen (Mortalitätsrate 1,4 %). Klinisch zeigt sich ein stadienhafter Verlauf: Drei bis vier Tage nach dem initialen katarrhalischen Prodromalstadium mit Fieber und Krankheitsgefühl bildet sich das charakteristische Exanthem aus. Die Diagnosestellung erfolgt primär klinisch, muss aber laborchemisch durch den Nachweis von spezifischen IgM-Antikörpern im Serum oder Virus-RNA im Rachenabstrich bestätigt werden. Die Therapie ist rein supportiv, eine spezifische antivirale Behandlung existiert nicht. Der Prävention kommt daher ein absolut zentraler Stellenwert zu, da es sich bei den Masern um eine durch Impfstoffe vermeidbare Erkrankung handelt.
Formalizing Verbal Theories
Authors: van Rooij Iris , Blokpoel Mark
Published: October 2020

Abstract. We present a tutorial for formalizing verbal theories of psychological phenomena – social or otherwise. The approach builds on concepts and tools from the mathematics of computation. We use intuitive examples and illustrate the intrinsic dialectical nature of the formalization process by presenting dialogues between two fictive characters, called Verbal and Formal. These characters’ conversations and thought experiments serve to highlight important lessons in theoretical modeling.
Dynamics of Lithospheric Overturns and Implications for Venus's Surface
Authors: Uppalapati S. , Rolf T. , Crameri F. , Werner S. C.
Published: October 2020

Venus is currently characterized by stagnant‐lid mantle convection, but could have previously experienced episodes of global resurfacing due to lithospheric overturn. Using numerical models of Venus's interior, we attempt to explain Venus's surface characteristics in the context of interior evolution and to understand how Venus's tectonic history has diverged from Earth's. For both the stagnant‐ and the episodic‐lid regime, we explore the role of reference mantle viscosity; for the latter regime, we also explore the role of the lithospheric yield stress. Our stagnant‐lid models predict thicker crust and younger surface than typically inferred from cratering statistics. When considering resurfacing episodes, the yield stress influences the frequency of overturns, which limits crustal thickness to better agree with previous independent estimates. Surface age is variable and depends on overturn frequency and resurfacing rate between overturns but reaches larger values just before an upcoming overturn event compared to values in the stagnant‐lid cases. Both regimes predict substantial lateral variations in surface age, instead of an end‐member uniform surface age indicating the cessation time of the last overturn, because ongoing volcanic resurfacing is spatially heterogeneous and dominates over tectonic resurfacing. Reviewing the crater‐based surface age variations suggests that the model‐predicted age spreads in the episodic scenario could be consistent with Venus's cratering record. Moreover, we find that a small fraction of crust can resist recycling during overturns. These outcomes indicate that overturn events may allow for surface age variations that reproduce Venus's surface better than stagnant‐lid models.
The Photochemical Reflectance Index (PRI) Captures the Ecohydrologic Sensitivity of a Semiarid Mixed Conifer Forest
Authors: Yang Julia C. , Magney Troy S. , Yan Dong , Knowles John F. , Smith William K. , Scott Russell L. , Barron‐Gafford Greg A.
Published: October 2020

At the seasonal time scale, daily photochemical reflectance index (PRI) measurements track changes in photoprotective pigment pools as plants respond to seasonally variable environmental conditions. As such, remotely sensed PRI products present opportunities to study seasonal processes in evergreen conifer forests, where complex vegetation dynamics are difficult to capture due to small annual changes in chlorophyll content or leaf structure. Because PRI is tied explicitly to short‐ and long‐term changes in photoprotective pigments that are responsible for regulating stress, we hypothesize that PRI by extension could serve as a proxy for stomatal response to seasonally changing hydroclimate, assuming plant functional responses to stress covary in space and time. To test this, we characterized PRI in a semiarid, montane mixed conifer forest in the Madrean sky islands of Arizona, USA, during the monsoon growing season subject to precipitation pulse dynamics. To determine the sensitivity of PRI to ecohydrologic variability and associated changes in gross primary productivity (GPP), canopy spectral measurements were coupled with eddy covariance CO2 flux and sap flow measurements. Seasonally, there was a significant relationship between PRI and sap flow velocity (R2 = 0.56), and multiple linear regression analysis demonstrated a PRI response to dynamic water and energy limitations in this system. We conclude that PRI has potential to serve as a proxy for forest functional response to seasonal ecohydrologic forcing. The coordination between photoprotective pigments and seasonal stomatal regulation demonstrated here could aid characterization of vegetation response to future changes in hydroclimate at increasing spatial scales.
ATRIP protects progenitor cells against DNA damage in vivo
Authors: Matos-Rodrigues Gabriel E. , Grigaravicius Paulius , Lopez Bernard S. , Hofmann Thomas G. , Frappart Pierre-Olivier , Martins Rodrigo A. P.
Published: October 2020

The maintenance of genomic stability during the cell cycle of progenitor cells is essential for the faithful transmission of genetic information. Mutations in genes that ensure genome stability lead to human developmental syndromes. Mutations in Ataxia Telangiectasia and Rad3-related (ATR) or in ATR-interacting protein (ATRIP) lead to Seckel syndrome, which is characterized by developmental malformations and short life expectancy. While the roles of ATR in replicative stress response and chromosomal segregation are well established, it is unknown how ATRIP contributes to maintaining genomic stability in progenitor cells in vivo. Here, we generated the first mouse model to investigate ATRIP function. Conditional inactivation of Atrip in progenitor cells of the CNS and eye led to microcephaly, microphthalmia and postnatal lethality. To understand the mechanisms underlying these malformations, we used lens progenitor cells as a model and found that ATRIP loss promotes replicative stress and TP53-dependent cell death. Trp53 inactivation in Atrip-deficient progenitor cells rescued apoptosis, but increased mitotic DNA damage and mitotic defects. Our findings demonstrate an essential role of ATRIP in preventing DNA damage accumulation during unchallenged replication.
Genome biology of the paleotetraploid perennial biomass crop Miscanthus
Authors: Mitros Therese , Session Adam M. , James Brandon T. , Wu Guohong Albert , Belaffif Mohammad B. , Clark Lindsay V. , Shu Shengqiang , Dong Hongxu , Barling Adam , Holmes Jessica R. , Mattick Jessica E. , Bredeson Jessen V. , Liu Siyao , Farrar Kerrie , Głowacka Katarzyna , Jeżowski Stanisław , Barry Kerrie , Chae Won Byoung , Juvik John A. , Gifford Justin , Oladeinde Adebosola , Yamada Toshihiko , Grimwood Jane , Putnam Nicholas H. , De Vega Jose , Barth Susanne , Klaas Manfred , Hodkinson Trevor , Li Laigeng , Jin Xiaoli , Peng Junhua , Yu Chang Yeon , Heo Kweon , Yoo Ji Hye , Ghimire Bimal Kumar , Donnison Iain S. , Schmutz Jeremy , Hudson Matthew E. , Sacks Erik J. , Moose Stephen P. , Swaminathan Kankshita , Rokhsar Daniel S.
Published: October 2020

Miscanthus is a perennial wild grass that is of global importance for paper production, roofing, horticultural plantings, and an emerging highly productive temperate biomass crop. We report a chromosome-scale assembly of the paleotetraploid M. sinensis genome, providing a resource for Miscanthus that links its chromosomes to the related diploid Sorghum and complex polyploid sugarcanes. The asymmetric distribution of transposons across the two homoeologous subgenomes proves Miscanthus paleo-allotetraploidy and identifies several balanced reciprocal homoeologous exchanges. Analysis of M. sinensis and M. sacchariflorus populations demonstrates extensive interspecific admixture and hybridization, and documents the origin of the highly productive triploid bioenergy crop M. × giganteus. Transcriptional profiling of leaves, stem, and rhizomes over growing seasons provides insight into rhizome development and nutrient recycling, processes critical for sustainable biomass accumulation in a perennial temperate grass. The Miscanthus genome expands the power of comparative genomics to understand traits of importance to Andropogoneae grasses.
Infrared spectroscopic study of hydrogen bonding topologies in the smallest ice cube
Authors: Li Gang , Zhang Yang-Yang , Li Qinming , Wang Chong , Yu Yong , Zhang Bingbing , Hu Han-Shi , Zhang Weiqing , Dai Dongxu , Wu Guorong , Zhang Dong H. , Li Jun , Yang Xueming , Jiang Ling
Published: October 2020

The water octamer with its cubic structure consisting of six four-membered rings presents an excellent cluster system for unraveling the cooperative interactions driven by subtle changes in the hydrogen-bonding topology. Despite prediction of many distinct structures, it has not been possible to extract the structural information encoded in their vibrational spectra because this requires size-selectivity of the neutral clusters with sufficient resolution to identify the contributions of the different isomeric forms. Here we report the size-specific infrared spectra of the isolated cold, neutral water octamer using a scheme based on threshold photoionization using a tunable vacuum ultraviolet free electron laser. A plethora of sharp vibrational bands features are observed. Theoretical analysis of these patterns reveals the coexistence of five cubic isomers, including two with chirality. The relative energies of these structures are found to reflect topology-dependent, delocalized multi-center hydrogen-bonding interactions. These results demonstrate that even with a common structural motif, the degree of cooperativity among the hydrogen-bonding network creates a hierarchy of distinct species. The implications of these results on possible metastable forms of ice are speculated.
YAP and TAZ protect against white adipocyte cell death during obesity
Authors: Wang Lei , Wang ShengPeng , Shi Yue , Li Rui , Günther Stefan , Ong Yu Ting , Potente Michael , Yuan Zuyi , Liu Enqi , Offermanns Stefan
Published: October 2020

The expansion of the white adipose tissue (WAT) in obesity goes along with increased mechanical, metabolic and inflammatory stress. How adipocytes resist this stress is still poorly understood. Both in human and mouse adipocytes, the transcriptional co-activators YAP/TAZ and YAP/TAZ target genes become activated during obesity. When fed a high-fat diet (HFD), mice lacking YAP/TAZ in white adipocytes develop severe lipodystrophy with adipocyte cell death. The pro-apoptotic factor BIM, which is downregulated in adipocytes of obese mice and humans, is strongly upregulated in YAP/TAZ-deficient adipocytes under HFD, and suppression of BIM expression reduces adipocyte apoptosis. In differentiated adipocytes, TNFα and IL-1β promote YAP/TAZ nuclear translocation via activation of RhoA-mediated actomyosin contractility and increase YAP/TAZ-mediated transcriptional regulation by activation of c-Jun N-terminal kinase (JNK) and AP-1. Our data indicate that the YAP/TAZ signaling pathway may be a target to control adipocyte cell death and compensatory adipogenesis during obesity.
A self-powered analog sensor-data-logging device based on Fowler-Nordheim dynamical systems
Authors: Mehta Darshit , Aono Kenji , Chakrabartty Shantanu
Published: October 2020

Continuous, battery-free operation of sensor nodes requires ultra-low-power sensing and data-logging techniques. Here we report that by directly coupling a sensor/transducer signal into globally asymptotically stable monotonic dynamical systems based on Fowler-Nordheim quantum tunneling, one can achieve self-powered sensing at an energy budget that is currently unachievable using conventional energy harvesting methods. The proposed device uses a differential architecture to compensate for environmental variations and the device can retain sensed information for durations ranging from hours to days. With a theoretical operating energy budget less than 10 attojoules, we demonstrate that when integrated with a miniature piezoelectric transducer the proposed sensor-data-logger can measure cumulative “action” due to ambient mechanical acceleration without any additional external power.
Author Correction: Designing a whole cell bioreporter to show antioxidant activities of agents that work by promotion of the KEAP1–NRF2 signaling pathway
Authors: Mozaheb Negar , Arefian Ehsan , Amoozegar Mohammad Ali
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Topographic, soil, and climate drivers of drought sensitivity in forests and shrublands of the Pacific Northwest, USA
Authors: Cartwright Jennifer M. , Littlefield Caitlin E. , Michalak Julia L. , Lawler Joshua J. , Dobrowski Solomon Z.
Published: October 2020

Climate change is anticipated to increase the frequency and intensity of droughts, with major impacts to ecosystems globally. Broad-scale assessments of vegetation responses to drought are needed to anticipate, manage, and potentially mitigate climate-change effects on ecosystems. We quantified the drought sensitivity of vegetation in the Pacific Northwest, USA, as the percent reduction in vegetation greenness under droughts relative to baseline moisture conditions. At a regional scale, shrub-steppe ecosystems—with drier climates and lower biomass—showed greater drought sensitivity than conifer forests. However, variability in drought sensitivity was considerable within biomes and within ecosystems and was mediated by landscape topography, climate, and soil characteristics. Drought sensitivity was generally greater in areas with higher elevation, drier climate, and greater soil bulk density. Ecosystems with high drought sensitivity included dry forests along ecotones to shrublands, Rocky Mountain subalpine forests, and cold upland sagebrush communities. In forests, valley bottoms and areas with low soil bulk density and high soil available water capacity showed reduced drought sensitivity, suggesting their potential as drought refugia. These regional-scale drought-sensitivity patterns discerned from remote sensing can complement plot-scale studies of plant physiological responses to drought to help inform climate-adaptation planning as drought conditions intensify.
Medical costs of keeping the US economy open during COVID-19
Authors: Chen Jiangzhuo , Vullikanti Anil , Hoops Stefan , Mortveit Henning , Lewis Bryan , Venkatramanan Srinivasan , You Wen , Eubank Stephen , Marathe Madhav , Barrett Chris , Marathe Achla
Published: October 2020

We use an individual based model and national level epidemic simulations to estimate the medical costs of keeping the US economy open during COVID-19 pandemic under different counterfactual scenarios. We model an unmitigated scenario and 12 mitigation scenarios which differ in compliance behavior to social distancing strategies and in the duration of the stay-home order. Under each scenario we estimate the number of people who are likely to get infected and require medical attention, hospitalization, and ventilators. Given the per capita medical cost for each of these health states, we compute the total medical costs for each scenario and show the tradeoffs between deaths, costs, infections, compliance and the duration of stay-home order. We also consider the hospital bed capacity of each Hospital Referral Region (HRR) in the US to estimate the deficit in beds each HRR will likely encounter given the demand for hospital beds. We consider a case where HRRs share hospital beds among the neighboring HRRs during a surge in demand beyond the available beds and the impact it has in controlling additional deaths.
Genetic parameters and associated genomic regions for global immunocompetence and other health-related traits in pigs
Authors: Ballester Maria , Ramayo-Caldas Yuliaxis , González-Rodríguez Olga , Pascual Mariam , Reixach Josep , Díaz Marta , Blanc Fany , López-Serrano Sergi , Tibau Joan , Quintanilla Raquel
Published: October 2020

The inclusion of health-related traits, or functionally associated genetic markers, in pig breeding programs could contribute to produce more robust and disease resistant animals. The aim of the present work was to study the genetic determinism and genomic regions associated to global immunocompetence and health in a Duroc pig population. For this purpose, a set of 30 health-related traits covering immune (mainly innate), haematological, and stress parameters were measured in 432 healthy Duroc piglets aged 8 weeks. Moderate to high heritabilities were obtained for most traits and significant genetic correlations among them were observed. A genome wide association study pointed out 31 significantly associated SNPs at whole-genome level, located in six chromosomal regions on pig chromosomes SSC4, SSC6, SSC17 and SSCX, for IgG, γδ T-cells, C-reactive protein, lymphocytes phagocytic capacity, total number of lymphocytes, mean corpuscular volume and mean corpuscular haemoglobin. A total of 16 promising functionally-related candidate genes, includingCRP,NFATC2,PRDX1,SLA,ST3GAL1, andVPS4A, have been proposed to explain the variation of immune and haematological traits. Our results enhance the knowledge of the genetic control of traits related with immunity and support the possibility of applying effective selection programs to improve immunocompetence in pigs.
Deep phenotype unsupervised machine learning revealed the significance of pachychoroid features in etiology and visual prognosis of age-related macular degeneration
Authors: Hosoda Yoshikatsu , Miyake Masahiro , Yamashiro Kenji , Ooto Sotaro , Takahashi Ayako , Oishi Akio , Miyata Manabu , Uji Akihito , Muraoka Yuki , Tsujikawa Akitaka
Published: October 2020

Unsupervised machine learning has received increased attention in clinical research because it allows researchers to identify novel and objective viewpoints for diseases with complex clinical characteristics. In this study, we applied a deep phenotyping method to classify Japanese patients with age-related macular degeneration (AMD), the leading cause of blindness in developed countries, showing high phenotypic heterogeneity. By applying unsupervised deep phenotype clustering, patients with AMD were classified into two groups. One of the groups had typical AMD features, whereas the other one showed the pachychoroid-related features that were recently identified as a potentially important factor in AMD pathogenesis. Based on these results, a scoring system for classification was established; a higher score was significantly associated with a rapid improvement in visual acuity after specific treatment. This needs to be validated in other datasets in the future. In conclusion, the current study demonstrates the usefulness of unsupervised classification and provides important knowledge for future AMD studies.
Quantum phase transitions in nonhermitian harmonic oscillator
Authors: Znojil Miloslav
Published: October 2020

The Stone theorem requires that in a physical Hilbert space $${{{\mathcal {H}}}}$$
H
the time-evolution of a stable quantum system is unitary if and only if the corresponding Hamiltonian H is self-adjoint. Sometimes, a simpler picture of the evolution may be constructed in a manifestly unphysical Hilbert space $${{{\mathcal {K}}}}$$
K
in which H is nonhermitian but $${{\mathcal {PT}}}$$
PT
-symmetric. In applications, unfortunately, one only rarely succeeds in circumventing the key technical obstacle which lies in the necessary reconstruction of the physical Hilbert space $${{{\mathcal {H}}}}$$
H
. For a $${{\mathcal {PT}}}$$
PT
-symmetric version of the spiked harmonic oscillator we show that in the dynamical regime of the unavoided level crossings such a reconstruction of $${{{\mathcal {H}}}}$$
H
becomes feasible and, moreover, obtainable by non-numerical means. The general form of such a reconstruction of $${{{\mathcal {H}}}}$$
H
enables one to render every exceptional unavoided-crossing point tractable as a genuine, phenomenologically most appealing quantum-phase-transition instant.
Risk factors and association of body composition components for lumbar disc herniation in Northwest, Mexico
Authors: Mateos-Valenzuela Adriana G. , González-Macías Mirvana E. , Ahumada-Valdez Silvia , Villa-Angulo Carlos , Villa-Angulo Rafael
Published: October 2020

The goal of this study was to investigate the association of body composition components and to elucidate whether any of these components is a risk factor for Lumbar Disc Herniation (LDH). The group of study consisted of 90 adults involved in a physical activity program due to overweight and obesity. 19 adults with medical diagnostic through Magnetic Resonance Imaging with LDH. Body composition data was obtained with a bioelectrical impedance analyzer. Descriptive statistics and principal components analysis permitted to analyze the information's structure and to visualize information clusters. A logistic regression analysis allowed us to find the association between some of the variables of body composition with LDH. The Degree of Obesity, Body Mass Index, Visceral Fat Area and the Abdominal Circumference resulted associated (P values of 0.0388, 0.0171, 0.0055 and 0.0032, respectively). The application of Odd Ratio allowed us to declare the Visceral Fat Area and Abdominal Circumference as risk factors to develop Lumbar Disk Herniation. Our results provide a new record for future studies, and support for prescription of physical activity and changes in diet, to correct or prevent the development of LDH in the population of Baja California.
Ab-interno surgical technique for the implantation of a wireless subretinal prosthesis in mini-pigs
Authors: Choi Kwang-Eon , Anh Vu Thi Que , Seo Hee Won , Kim Namju , Kim Sohee , Kim Seong-Woo
Published: October 2020

We sought to describe the surgical techniques required in the ab-interno method to implant subretinal prostheses in mini-pigs and suggest tips to facilitate optimal outcomes. During vitrectomy, the use of valved trocar cannulas was essential to stabilize the detached retina and implanted chip. As a first step in retinal detachment, a 23-gauge cannula with very small amount of viscoelastic material was used to establish the retinal hole and promote retinal detachment. Then, balanced salt solution was applied to increase the retinal detachment and diathermy was used to make opening for subretinal prosthesis. For easy positioning of the subretinal prosthesis, a curved laser probe was adopted when handling the subretinal prosthesis under the retina. After surgery, the sclerotomy sites were tightly sutured to prevent silicone oil leakage. Without special equipment, such as a 41-gauge tip, retinal detachment could be induced easily, while the prosthesis was also successfully inserted and manipulated under the retina without an iatrogenic retinal tear. Two weeks after the operation, the oil fully occupied the intraocular volume without leakage. The subretinal prosthesis remained stable without complication. Understanding the principle of the ab-interno method and considering several tips for improving surgical access may help to enhance surgical success rates of subretinal prostheses implantation.
End-group functionalization of a conjugated azomethine with ureas for property tailoring
Authors: Tremblay Marie-Hélène , Al Ahmad Abdel , Skene W. G.
Published: October 2020

A conjugated azomethine end-capped with phenyl-ureas was prepared by a convergent approach. Hydrogen bonding with the ureas was confirmed and the spectroscopic properties could be enhanced with the supramolecular bonds.
Homochiral and heterochiral associations observed in crystals of ArSO2-(Aib)5-OMe
Authors: Hikawa Hidemasa , Takahashi Ayaka , Kikkawa Shoko , Suzuki Ayaka , Takahashi Yoshiki , Sato Naruka , Okayasu Misaki , Azumaya Isao
Published: October 2020

We demonstrated two remarkably different types of network structures that consist of homochiral and heterochiral 1D chains of enantiomeric 310-helices in the crystals of ArSO2-(Aib)5-OMe.