bluuebunny/crossref_metadata_2025 huggingface dataset:
The scale of superpartner masses and electroweakino searches at the high-luminosity LHC
Authors: Liu Jia , McGinnis Navin , Wagner Carlos E. M. , Wang Xiao-Ping
Published: December 2020

Abstract

Searches for weakly interacting particles is one of the main goals of the high luminosity LHC run. In this work we study the well motivated cases of electroweakinos with mostly Wino and Bino components. We show the relevance of squark induced t-channel production in defining the production cross section and hence the LHC reach. Moreover, a realistic evaluation of the decay branching ratios show a strong dependence on the sign of μ and, for negative values of μ, on the relative size of the ratio of μ to the gaugino masses compared with tan β. Overall, unless it is kinematically suppressed, or specific conditions are fulfilled, the Higgs decay channel is the most significant one, and the trilepton channel becomes subdominant with respect to final states including bottom quarks. Although the properties are different than in the Higgsino-Bino case, also in this case the discovery reach extends to mass values that are significantly larger than the ones probed at current luminosities, leading to a strong motivation for the search for electroweakinos in the high luminosity LHC run.
Symmetry factors of Feynman diagrams and the homological perturbation lemma
Authors: Saemann Christian , Sfinarolakis Emmanouil
Published: December 2020

Abstract

We discuss the symmetry factors of Feynman diagrams of scalar field theories with polynomial potential. After giving a concise general formula for them, we present an elementary and direct proof that when computing scattering amplitudes using the homological perturbation lemma, each contributing Feynman diagram is indeed included with the correct symmetry factor.
Modification to the Hawking temperature of a dynamical black hole by a flow-induced supertranslation
Authors: Chiang Hsu-Wen , Kung Yu-Hsien , Chen Pisin
Published: December 2020

Abstract

One interesting proposal to solve the black hole information loss paradox without modifying either general relativity or quantum field theory, is the soft hair, a diffeomorphism charge that records the anisotropic radiation in the asymptotic region. This proposal, however, has been challenged, given that away from the source the soft hair behaves as a coordinate transformation that forms an Abelian group, thus unable to store any information. To maintain the spirit of the soft hair but circumvent these obstacles, we consider Hawking radiation as a probe sensitive to the entire history of the black hole evaporation, where the soft hairs on the horizon are induced by the absorption of a null anisotropic flow, generalizing the shock wave considered in [1, 2]. To do so we introduce two different time-dependent extensions of the diffeomorphism associated with the soft hair, where one is the backreaction of the anisotropic null flow, and the other is a coordinate transformation that produces the Unruh effect and a Doppler shift to the Hawking spectrum. Together, they form an exact BMS charge generator on the entire manifold that allows the nonperturbative analysis of the black hole horizon, whose surface gravity, i.e. the Hawking temperature, is found to be modified. The modification depends on an exponential average of the anisotropy of the null flow with a decay rate of 4M, suggesting the emergence of a new 2-D degree of freedom on the horizon, which could be a way out of the information loss paradox.
Hybrid sequencing resolves two germline ultra-complex chromosomal rearrangements consisting of 137 breakpoint junctions in a single carrier
Authors: Eisfeldt Jesper , Pettersson Maria , Petri Anna , Nilsson Daniel , Feuk Lars , Lindstrand Anna
Published: December 2020

Chromoanagenesis is a genomic event responsible for the formation of complex structural chromosomal rearrangements (CCRs). Germline chromoanagenesis is rare and the majority of reported cases are associated with an affected phenotype. Here, we report a healthy female carrying two de novo CCRs involving chromosomes 4, 19, 21 and X and chromosomes 7 and 11, respectively, with a total of 137 breakpoint junctions (BPJs). We characterized the CCRs using a hybrid-sequencing approach, combining short-read sequencing, nanopore sequencing, and optical mapping. The results were validated using multiple cytogenetic methods, including fluorescence in situ hybridization, spectral karyotyping, and Sanger sequencing. We identified 137 BPJs, which to our knowledge is the highest number of reported breakpoint junctions in germline chromoanagenesis. We also performed a statistical assessment of the positioning of the breakpoints, revealing a significant enrichment of BPJ-affecting genes (96 intragenic BPJs, 26 genes,p < 0.0001), indicating that the CCRs formed during active transcription of these genes. In addition, we find that the DNA fragments are unevenly and non-randomly distributed across the derivative chromosomes indicating a multistep process of scattering and re-joining of DNA fragments. In summary, we report a new maximum number of BPJs (137) in germline chromoanagenesis. We also show that a hybrid sequencing approach is necessary for the correct characterization of complex CCRs. Through in-depth statistical assessment, it was found that the CCRs most likely was formed through an event resembling chromoplexy—a catastrophic event caused by erroneous transcription factor binding.
The role of Treg subtypes in glomerulonephritis
Authors: Herrnstadt G. R. , Steinmetz O. M.
Published: December 2020

While Th1 and Th17 T effector cells are pathogenic drivers of glomerulonephritis (GN), regulatory T cells (Tregs) potently protect from renal tissue injury. Recently, it has become evident that different Treg subtypes exist. Among these are lineage specific Treg1 and Treg17 cells, which are specialized to down regulate either Th1 or Th17 T effector cell responses. Interestingly, programming of specialized Tregs and the corresponding T helper effector cells depend on the same lineage specific master transcription factors Tbet (Th1/Treg1) and STAT3 (Th17/Treg17). Furthermore, early control of T effector cell priming in secondary lymphoid organs by specialized Tregs was described. One central mechanism of T effector cell control by the corresponding Treg subtype seems to be expression of the same chemokine receptor repertoire, which facilitates their co-localization. More recently, another intriguing Treg subset was identified, which expresses Foxp3 together with the Th17 characteristic transcription factor RORγt. While these Foxp3+RORγt+Tregs were shown to be highly immunosuppressive, studies in GN also identified pro-inflammatory potential via secretion of IL-17. Many questions regarding this unusual Treg subset remain, including their origin, stability, and mechanisms of action. Further characterization of the renal Treg landscape during GN will help to identify novel immunosuppressive mechanisms and develop successful Treg-directed therapies. In this review, we summarize the currently available data about specialized Treg subsets and discuss their role in GN.
6-month SARS-CoV-2 antibody persistency in a Tyrolian COVID-19 cohort
Authors: Deisenhammer Florian , Borena Wegene , Bauer Angelika , Kimpel Janine , Rudzki Dagmar , Schanda Kathrin , Egeter Jonas , Hüfner Katharina , Sperner-Unterweger Barbara , Reindl Markus
Published: December 2020

Background

As coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 evolved only recently, the persistency of the anti-viral antibody response remains to be determined.

Methods

We prospectively followed 29 coronavirus disease 2019 cases, mean age 44 ± 13.2 years. Except for one participant with a pre-existing diagnosis of rheumatoid arthritis, all other participants were previously healthy. We determined anti-viral binding antibodies at 2–10 weeks, 3 months, and 6 months after disease onset as well as neutralizing antibodies at 6 months. Two binding antibody assays were used, targeting the S1 subunit of the spike protein, and the receptor binding domain.

Results

All participants fully recovered spontaneously except for one who had persisting hyposmia. Antibodies to the receptor binding domain persisted for 6 months in all cases with a slight increase of titers, whereas antibodies to S1 dropped below the cut-off point in 2 participants and showed a minimal decrease on average, mainly at month 3 of follow-up in males; however, neutralizing antibodies were detected in all samples at 6 months of follow-up.

Conclusion

There is a stable and persisting antibody response against acute respiratory syndrome coronavirus 2 at 6 months after infection. Neutralizing antibodies confirm virus specificity. As the number of coronavirus disease 2019 convalescent cases is increasing sharply, antibody testing should be implemented to identify immunized individuals. This information can be helpful in various settings of professional and private life.
Convergence Rates for Discretized Monge–Ampère Equations and Quantitative Stability of Optimal Transport
Authors: Berman Robert J.
Published: December 2020

In recent works—both experimental and theoretical—it has been shown how to use computational geometry to efficiently construct approximations to the optimal transport map between two given probability measures on Euclidean space, by discretizing one of the measures. Here we provide a quantitative convergence analysis for the solutions of the corresponding discretized Monge–Ampère equations. This yields$$H^{1}$$H1-converge rates, in terms of the corresponding spatial resolutionh, of the discrete approximations of the optimal transport map, when the source measure is discretized and the target measure has bounded convex support. Periodic variants of the results are also established. The proofs are based on new quantitative stability results for optimal transport maps, shown using complex geometry.
What Is Secondary about Secondary Tropical Forest? Rethinking Forest Landscapes
Authors: Pain Adam , Marquardt Kristina , Lindh Arvid , Hasselquist Niles J.
Published: December 2020

Forests have long been locations of contestation between people and state bureaucracies, and among the knowledge frameworks of local users, foresters, ecologists, and conservationists. An essential framing of the debate has been between the categories of primary and secondary forest. In this introduction to a collection of papers that address the questions of what basis, in what sense, and for whom primary forest is ‘primary’ and secondary forest is ‘secondary,’ and whether these are useful distinctions, we outline this debate and propose a new conceptual model that departs from the simple binary of primary and secondary forests. Rather, we propose that attention should be given to the nature of the disturbance that may alter forest ecology, the forms of regeneration that follow, and the governance context within which this takes place.
Correction to: Levoketoconazole improves clinical signs and symptoms and patient-reported outcomes in patients with Cushing’s syndrome
Authors: Geer Eliza B. , Salvatori Roberto , Elenkova Atanaska , Fleseriu Maria , Pivonello Rosario , Witek Przemyslaw , Feelders Richard A. , Bex Marie , Borresen Stina W. , Puglisi Soraya , Biller Beverly M. K. , Cohen Fredric , Pecori Giraldi Francesca
Published: December 2020

The original version of the article unfortunately contained an error in the first name and the surname of one of the authors in the author group. The last author name was incorrectly published as ‘F. Pecori Giraldi’ and the corrected name is ‘Francesca Pecori Giraldi’ (First name: Francesca; Surname: Pecori Giraldi).
Sixty Years with the Chrysobalanaceae
Authors: Prance Ghillean T.
Published: December 2020

A review is given of the studies of Ghillean Prance and associates on the Chrysobalanaceae over the past sixty years. This has focussed on defining the generic boundaries in the family and on monographic work with a worldwide approach to this pantropical family. The importance of field studies for work on monographs and Floras is emphasized. Monographs are still the basis for much work on conservation, ecology and economic botany and are needed as a foundation for molecular studies. The importance of being open to experimenting with new techniques and as a result being willing to change the taxonomy in accordance with new findings is demonstrated and emphasized. The twelve genera of the Chrysobalanaceae at the beginning of this career-long study have now increased to twenty-eight in order to present a much better monophyletic and evolutionary arrangement based on recent molecular evidence. In particular it was necessary to divide and rearrange the originally large genera Parinari and Licania into a number of smaller segregate genera. All known species were included in a worldwide monograph published in 2003. A brief review of the economic use for the family is given.
Migration of the femoral component and clinical outcomes after total knee replacement: a narrative review
Authors: Zinno R. , Di Paolo S. , Ambrosino G. , Alesi D. , Zaffagnini S. , Barone G. , Bragonzoni L.
Published: December 2020

Loosening is considered as a main cause of implant failure in total knee replacement (TKR). Among the predictive signs of loosening, migration is the most investigated quantitative parameter. Several studies focused on the migration of the tibial component in TKR, while no reviews have been focused on the migration of the femoral component and its influence on patients’ clinical outcomes. The aim of this narrative review was (1) to provide information about of the influence of migration in femoral component of TKR prostheses, (2) to assess how migration may affect patient clinical outcomes and (3) to present alternative solution to the standard cobalt-chrome prostheses. A database search was performed on PubMed Central® according to the PRISMA guidelines for studies about Cobalt-Chrome femoral component migration in people that underwent primary TKR published until May 2020. Overall, 18 articles matched the selection criteria and were included in the study. Few studies investigated the femoral component through the migration, and no clear migration causes emerged. The Roentgen Stereophotogrammetric Analysis has been mostly used to assess the migration for prognostic predictions. An annual migration of 0.10 mm seems compatible with good long-term performance and good clinical and functional outcomes. An alternative solution to cobalt-chrome prostheses is represented by femoral component in PEEK material, although no clinical evaluations have been carried out on humans yet. Further studies are needed to investigate the migration of the femoral component in relation to clinical outcomes and material used.
Predictors of intensive care unit admission in patients with Legionella pneumonia: role of the time to appropriate antibiotic therapy
Authors: Falcone Marco , Russo Alessandro , Tiseo Giusy , Cesaretti Mario , Guarracino Fabio , Menichetti Francesco
Published: December 2020

Purpose

Legionella spp. pneumonia (LP) is a cause of community-acquired pneumonia (CAP) that requires early intervention. The median mortality rate varies from 4 to 11%, but it is higher in patients admitted to intensive care unit (ICU). The objective of this study is to identify predictors of ICU admission in patients with LP.

Methods

A single-center, retrospective, observational study conducted in an academic tertiary-care hospital in Pisa, Italy. Adult patients with LP consecutively admitted to study center from October 2012 to October 2019.

Results

During the study period, 116 cases of LP were observed. The rate of ICU admission was 20.7% and the overall 30-day mortality rate was 12.1%. Mortality was 4.3% in patients hospitalized in medical wards versus 41.7% in patients transferred to ICU (p < 0.001). The majority of patients (74.1%) received levofloxacin as definitive therapy, followed by macrolides (16.4%), and combination of levofloxacin plus a macrolide (9.5%). In the multivariate analysis, diabetes (OR 8.28, CI 95% 2.11–35.52, p = 0.002), bilateral pneumonia (OR 10.1, CI 95% 2.74–37.27, p = 0.001), and cardiovascular events (OR 10.91, CI 95% 2.83–42.01, p = 0.001), were independently associated with ICU admission, while the receipt of macrolides/levofloxacin therapy within 24 h from admission was protective (OR 0.20, CI 95% 0.05–0.73, p = 0.01). Patients who received a late anti-Legionella antibiotic (> 24 h from admission) underwent urinary antigen test later compared to those who received early active antibiotic therapy (2 [2–4] vs. 1 [1–2] days, p < 0.001).

Conclusions

Admission to ICU carries significantly increased mortality in patients with diagnosis of LP. Initial therapy with an antibiotic active against Legionella (levofloxacin or macrolides) reduces the probability to be transferred to ICU and should be provided in all cases until Legionella etiology is excluded.
Test of Tethered Deorbiting of Space Debris
Authors: Olivieri Lorenzo , Valmorbida Andrea , Sarego Giulia , Lungavia Enrico , Vertuani Davide , Lorenzini Enrico C.
Published: December 2020

Current investigations on space tethers include their application to space debris deorbiting, specifically on the set of manoeuvres performed by a chaser tug to change the orbital parameters of a target body. Targets can be cooperative spacecraft at the end of their life or uncontrolled objects such as defunct satellites without clearly available capturing interfaces. In this latter case, a link joining tug and target may be misaligned with the target body inertia axes, influencing the attitude of both bodies; in case of rigid links, torques transmitted during tugging operations may overcome the tug attitude control system. This issue is clearly less significant in case of non-rigid connections, such as tethers; furthermore, with such connections the chaser can remain at a safe distance from the target during the whole deorbiting operation. On the other side, the initial phase of tethered space debris removal manoeuvres can be influenced by transient events, such as sudden tether tension spikes, that may cause longitudinal and lateral oscillations and, in case of resonance with the target attitude dynamics, could represent a serious issue for tug safety. In this paper it is proposed to provide the tug with a tether deployer mechanism capable to perform reel-in and reel-out, smoothing loads transmission to the target and damping oscillations. This concept is validated through a representative test campaign performed with the SPAcecRraft Testbed for Autonomous proximity operatioNs experimentS (SPARTANS) on a low friction table. A prototype of the deployer is manufactured and the deployment and rewind of a thin aluminium tape tether is proven. Test results include the verification of the tether visco-elastic characteristics with the direct measurement of spikes and oscillations and the estimation of the proposed system damping capabilities.
Environmental education and ecological spiritual intelligence: the case of Basque mythology
Authors: Echarri-Iribarren Fernando , Echarri-Iribarren Víctor
Published: December 2020

Since its conception, environmental education has carried out numerous plans, strategies and programmes aimed at restoring an adequate person–nature relationship, addressing the main environmental problems that threaten the planetary ecosystem balance. Even though environmental education proposes an integral education, it is infrequent that the spiritual dimension of the person appears reflected in its programmes. However, spirituality, which often manifests itself by providing affect and meaningful significant life experiences, aims to be a key factor in the development of lasting pro-environmental behaviours. Promoting and valuing ecological spiritual intelligence is configured as an interesting advance for environmental education. For example, starting from the cultural-naturalistic values provided in every part of the territory. As an example, we propose the one made in the Basque country (Spain), using the spirituality contained in the Basque mythology.
Do common metrics add value? Perspectives from NIH Clinical and Translational Science Awards (CTSA) Consortium hubs
Authors: Welch Lisa C. , Tomoaia-Cotisel Andrada , Chang Hong , Mendel Peter , Etchegaray Jason M. , Qureshi Nabeel , Fenwood-Hughes Marguerite , Parajulee Anshu , Selker Harry P.
Published: December 2020

Introduction:

The Clinical and Translational Science Awards (CTSA) Consortium, a network of academic health care institutions with CTSA hubs, is charged with improving the national clinical and translational research enterprise. The CTSA Consortium and the NIH National Center for Advancing Translational Sciences implemented the Common Metrics Initiative comprised of standardized metrics and a shared performance improvement framework. This article summarizes hubs’ perspectives on its value during the initial implementation.

Methods:

The value was assessed across 58 hubs. Survey items assessed change in perceived ability to manage performance and advance clinical and translational science. Semi-structured interviews elicited hubs’ perspectives on meaningfulness and value-added of the Common Metrics Initiative and hubs’ recommendations.

Results:

Hubs considered their abilities to manage performance to have improved, but there was no change in perceived ability to advance clinical and translational science. The initiative added value by providing a formal structured process, enabling strategic conversations, facilitating improvements in processes, providing an external impetus for improvement, and providing justification for funds invested. Hubs were concerned about the usefulness of the metrics chosen and whether the value-added was sufficient relative to the effort required. Hubs recommended useful benchmarking, disseminating best practices and promoting peer-to-peer learning, and expanding the use of data to inform the initiative.

Conclusions:

Implementing Common Metrics and a performance improvement framework yielded concrete short-term benefits, but concerns about usefulness remained, particularly considering the effort required. The Common Metrics Initiative should focus on facilitating cross-hub collaboration around metrics that address high-priority impact areas for individual hubs and the Consortium.
A NOTE ON k-GALOIS LCD CODES OVER THE RING
Authors: WU RONGSHENG , SHI MINJIA
Published: December 2020

We study the k-Galois linear complementary dual (LCD) codes over the finite chain ring

$R=\mathbb {F}_q+u\mathbb {F}_q$
with

$u^2=0$
, where

$q=p^e$
and p is a prime number. We give a sufficient condition on the generator matrix for the existence of k-Galois LCD codes over R. Finally, we show that a linear code over R (for

$k=0, q> 3$
) is equivalent to a Euclidean LCD code, and a linear code over R (for

$0<k<e$
,

$(p^{e-k}+1)\mid (p^e-1)$
and

${(p^e-1)}/{(p^{e-k}+1)}>1$
) is equivalent to a k-Galois LCD code.
Reviewing the Decision of the Nigerian Supreme Court in Huebner v AIE and PM Co Ltd: A Dissenting Opinion
Authors: Okeke Chukwuebuka S
Published: December 2020

In this case, the Nigerian Supreme Court had the opportunity to build on the foundations of Nigerian trust law. The court was faced with facts that should have led to the implication of a resulting trust in favour of the appellant, since he had purchased a large parcel of land in the name of the respondent. While accepting that it made no contribution to the purchase or development of the land, the respondent sought to escape its fiduciary duty by alleging illegality, using the provisions of the Land Use Act as a statutory shield. The Nigerian Supreme Court endorsed the respondent's position, by electing to focus on the breach of the statute, while ignoring that equity would not allow a statute to be used as an instrument of fraud. This article shows how the court erred, as the statutory breach was not fatal to the appellant's claim: equity does not demand that its suitors have led blameless lives.
OPTIMAL BANDWIDTH SELECTION IN NONLINEAR COINTEGRATING REGRESSION
Authors: Wang Qiying , Phillips Peter C. B.
Published: December 2020

We study optimal bandwidth selection in nonparametric cointegrating regression where the regressor is a stochastic trend process driven by short or long memory innovations. Unlike stationary regression, the optimal bandwidth is found to be a random sequence which depends on the sojourn time of the process. All random sequences
$h_{n}$
that lie within a wide band of rates as the sample size
$n\rightarrow \infty $
have the property that local level and local linear kernel estimates are asymptotically normal, which enables inference and conveniently corresponds to limit theory in the stationary regression case. This finding reinforces the distinctive flexibility of data-based nonparametric regression procedures for nonstationary nonparametric regression. The present results are obtained under exogenous regressor conditions, which are restrictive but which enable flexible data-based methods of practical implementation in nonparametric predictive regressions within that environment.
Evaluation of left ventricular systolic functions in two-dimensional speckle-tracking echocardiography in children with chronic renal failure
Authors: Kizilca Ozgur , Ozmen Derya , Demircan Tulay , Yilmaz Nuh , Kir Mustafa , Soylu Alper , Unal Nurettin , Kavukcu Salih
Published: December 2020

Background and aim:

Chronic kidney disease may lead to left ventricular dysfunction. Early detection of cardiovascular disease in children with chronic kidney disease is essential to prevent cardiovascular morbidity and mortality in early adulthood. This study aimed to document the dysfunction using methods such as two-dimensional speckle-tracking echocardiography in the early stage.

Methods:

A total of 34 patients diagnosed with chronic kidney disease (mean age ± standard deviation, 10.5 ± 4.1 years) and 37 sex- and age-matched (mean age 9.8 ± 4.2 years) healthy controls were studied. The results of the two groups were compared along with those of the published studies.

Results:

The echocardiography measurements had no significant difference in the end-diastolic and end-systolic diameter values of left ventricular, ejection fraction, shortening fraction, mitral E value, mitral A value, and E/A ratio between the groups. Pulmonary artery systolic and diastolic pressure and left ventricular mass index were significantly higher in the patient group (p < 0.01). The longitudinal global strain values in the apical four-chamber, three-chamber, and two-chamber views and the total global strain values were significantly lower in the patients (p < 0.01). The circumferential global strain values in the apical, mid, basal, and total global strain were lower in the patient group, but this difference was statistically significant in the apical global and total global strain values (p < 0.05).

Conclusions:

Speckle-tracking echocardiography might help identify subclinical left ventricular dysfunction in patients with chronic kidney disease with unremarkable conventional echocardiography.
Does obesity influence ventricular repolarisation in children?
Authors: Yıldırım Yıldız Nihan , Uçar Tayfun , Ramoğlu Mehmet G. , Berberoğlu Merih , Şıklar Zeynep , Tutar Ercan , Atalay Semra
Published: December 2020

Objective:

Ventricular repolarisation changes may lead to sudden cardiac death in obese individuals. We aimed to investigate the relationship between ventricular repolarisation changes, echocardiographic parameters, anthropometric measures, and metabolic syndrome laboratory parameters in obese children.

Methods:

The study involved 81 obese and 82 normal-weight healthy children with a mean age of 12.3 ± 2.7 years. Anthropometric measurements of participants were evaluated according to nomograms. Obese patients were subdivided into two groups; metabolic syndrome and non-metabolic syndrome obese. Fasting plasma glucose, fasting insulin, and lipid profile were measured. QT/QTc interval, QT/QTc dispersions were measured, and left ventricular systolic and diastolic measurements were performed.

Results:

Body weight, body mass index, relative body mass index, waist/hip circumference ratio, and systolic and diastolic blood pressures were significantly higher in obese children. QT and QTc dispersions were significantly higher in obese children and also obese children with metabolic syndrome had significantly higher QT and QTc dispersions compared to non-metabolic syndrome obese children (p < 0.001) and normal-weight healthy children (p < 0.001). Waist/hip circumference ratio, body mass index, and relative body mass index were the most important determinant of QT and QTc dispersions. Left ventricular wall thickness (left ventricular posterior wall thickness at end-diastole, left ventricular posterior wall thickness at end-systole, interventricular septal thickness at end-diastole) and left ventricular mass index were significantly higher and ejection fraction was lower in obese children. Left ventricular mass index and interventricular septal thickness at end-diastole were positively correlated with QT and QTc dispersions.

Conclusions:

Our study demonstrated that QT/ QTc interval prolongation and increase in QT and QTc dispersion on electrocardiogram may be found at an early age in obese children.
Iron-and-folic-acid supplementation among adolescents (aged 10–19 years) in two North Indian States, 2015–2016: a sex-stratified analysis
Authors: Rai Rajesh Kumar
Published: December 2020

Objective:

This study assessed the prevalence and predictors of receiving iron-and-folic-acid (IFA) supplement by male and female adolescents in two north Indian states.

Design:

The UDAYA (Understanding the lives of adolescents and young adults in Bihar and Uttar Pradesh) survey dataset was used. Conducted during 2015–2016, UDAYA was a state representative cross-sectional survey. To recruit sample, UDAYA adopted a multi-stage systematic sampling method with a household selection probability proportional to size. Weighted bivariate and multivariate logistic regression analyses were deployed. The variance inflation factor was estimated to check the presence of multicollinearity among variables included in regression model.

Setting:

The state of Bihar and Uttar Pradesh, India.

Participants:

A total of 10 433 individuals from Bihar and 10 161 individuals from Uttar Pradesh were included, totalling 20 594 individuals (male: 5969, female: 14 625) aged 10–19 years.

Results:

Overall, 3·6 % (95 % CI: 2·7, 4·7) of males and 4·8 % (95 % CI: 4·0, 5·7) of female adolescents received IFA supplement in preceding 1 year of survey date. Multivariate results indicate that IFA receipt varied with age, and state of residence among males, whereas religion and mother’s education were associated with IFA receipt among females. Irrespective of sex, adolescents living in rural areas had higher odds of receiving IFA supplement than adolescents in urban setting.

Conclusions:

Low coverage in receiving IFA supplement among adolescents is a serious concern for the success of anaemia reduction programme. While designing interventions for overall increase in IFA distribution, the socio-economic factors influencing IFA receipt must be considered.
One layer at a time: the use of 3D printing in the fabrication of cadmium-free electron field shaping devices
Authors: Moore Michael J. , Snelgrove Ronald , Darko Johnson , Osei Ernest K.
Published: December 2020

Introduction:

Electron blocks are typically composed of a low melting point alloy (LMPA), which is poured into an insert frame containing a manually placed Styrofoam aperture negative used to define the desired field shape. Current implementations of the block fabrication process involve numerous steps which are subjective and prone to user error. Occasionally, bowing of the sides of the insert frame is observed, resulting in premature frame decommissioning. Recent works have investigated the feasibility of utilising 3D printing technology to replace the conventional electron block fabrication workflow; however, these approaches involved long print times, were not compatible with commonly used cadmium-free LMPAs, and did not address the problem of insert frame bowing. In this work, we sought to develop a new 3D printing technique that would remedy these issues.

Materials and Methods:

Electron cutout negatives and alignment jigs were printed using Acrylonitrile Butadiene Styrene, which does not warp at the high temperatures associated with molten cadmium-free alloys. The accuracy of the field shape produced by electron blocks fabricated using the 3D printed negatives was assessed using Gafchromic film and beam profiler measurements. As a proof-of-concept, electron blocks with off-axis apertures, as well as complex multi-aperture blocks to be used for passive electron beam intensity modulation, were also created.

Results:

Film and profiler measurements of field size were in excellent agreement with the values calculated using the Eclipse treatment planning system, showing less than a 1% difference in line profile full-width at half-maximum. The multi-aperture electron blocks produced fields with intensity modulation ≤3.2% of the theoretically predicted value. Use of the 3D printed alignment jig – which has contours designed to match those of the insert frame – was found to reduce the amount of frame bowing by factors of 1.8 and 2.1 in the lateral and superior–inferior directions, respectively.

Conclusions:

The 3D printed ABS negatives generated with our technique maintain their spatial accuracy even at the higher temperatures associated with cadmium-free LMPA. The negatives typically take between 1 and 2 hours to print and have a material cost of approximately $2 per patient.
Once Upon a Time, in AmeriFlux
Authors: Fisher Joshua B. , Keenan Trevor F. , Buechner Christin , Shirkey Gabriela , Perez‐Quezada Jorge F. , Knox Sara H. , Frank John M. , Runkle Benjamin R. K. , Bohrer Gil
Published: December 2020

In October 2020, under COVID‐19 quarantine, AmeriFlux held its largest and one of its most successful annual meetings. Historically, ∼100 scientists attend; this meeting had over 400 registrants and participants. Participants expressed that this was among the best virtual meetings that they had ever attended, and 100% of post‐meeting survey respondents stated that they would attend again. Feedback revealed the meeting fostered a strong sense of connection to the AmeriFlux community, especially among early career and international scientists. How did a feeling of strong connection to the community arise from the seemingly cold and isolated structures of virtual meetings?

The meeting emphasized Diversity, Equity, and Inclusion (DEI), which resulted in an unexpected enhancement of science communication and community connections. Additionally, the meeting experimented with an online virtual gaming‐like world (Gather.town), where users controlled video/audio‐enabled avatars in a conference center and poster hall environment to create spontaneous conversations and discussions. In lieu of a social‐bonding field trip, participants showed videos of their field sites accompanied by informal banter, which were watched in group settings in Gather. Social mixers were structured over Zoom breakout rooms that were limited in size to promote participation with accessible games. Science talks were selected based on appeal to a demographically diverse organizing committee, which enhanced appeal to a broad meeting audience. Finally, breakout reports were given not in the format of bullet point slides, but instead as creatively improvized fairytales, which dramatically enhanced engagement. Here, we describe some of the process that went into the AmeriFlux 2020 meeting. Keeping with the theme of experimenting and fairytales, we present this narrative in the form of a fairytale; and, without further ado…
Regulation of FN1 degradation by the p62/SQSTM1-dependent autophagy–lysosome pathway in HNSCC
Authors: Liu Xinchen , Meng Lin , Li Xing , Li Daowei , Liu Qilin , Chen Yumeng , Li Xiangwei , Bu Wenhuan , Sun Hongchen
Published: December 2020

Epithelial–mesenchymal transition (EMT) is involved in both physiological and pathological processes. EMT plays an essential role in the invasion, migration and metastasis of tumours. Autophagy has been shown to regulate EMT in a variety of cancers but not in head and neck squamous cell carcinoma (HNSCC). Herein, we investigated whether autophagy also regulates EMT in HNSCC. Analyses of clinical data from three public databases revealed that higher expression of fibronectin-1 (FN1) correlated with poorer prognosis and higher tumour pathological grade in HNSCC. Data from SCC-25 cells demonstrated that rapamycin and Earle’s balanced salt solution (EBSS) promoted autophagy, leading to increased FN1 degradation, while 3-methyladenine (3-MA), bafilomycin A1 (Baf A1) and chloroquine (CQ) inhibited autophagy, leading to decreased FN1 degradation. On the other hand, autophagic flux was blocked in BECN1 mutant HNSCC Cal-27 cells, and rapamycin did not promote autophagy in Cal-27 cells; also in addition, FN1 degradation was inhibited. Further, we identified FN1 degradation through the lysosome-dependent degradation pathway using the proteasome inhibitor MG132. Data from immunoprecipitation assays also showed that p62/SQSTM1 participated as an autophagy adapter in the autophagy–lysosome pathway of FN1 degradation. Finally, data from immunoprecipitation assays demonstrated that the interaction between p62 and FN1 was abolished in p62 mutant MCF-7 and A2780 cell lines. These results indicate that autophagy significantly promotes the degradation of FN1. Collectively, our findings clearly suggest that FN1, as a marker of EMT, has adverse effects on HNSCC and elucidate the autophagy–lysosome degradation mechanism of FN1.
Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting
Authors: Modvig S. , Hallböök H. , Madsen H. O. , Siitonen S. , Rosthøj S. , Tierens A. , Juvonen V. , Osnes L. T. N. , Vålerhaugen H. , Hultdin M. , Matuzeviciene R. , Stoskus M. , Marincevic M. , Lilleorg A. , Ehinger M. , Norén-Nystrøm U. , Toft N. , Taskinen M. , Jónsson O. G. , Pruunsild K. , Vaitkeviciene G. , Vettenranta K. , Lund B. , Abrahamsson J. , Porwit A. , Schmiegelow K. , Marquart H. V.
Published: December 2020

PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p < 0.0001), 29 (HzR 2.7, p < 0.0001), and 79 (HzR 3.5, p < 0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4 × 10−2 versus 5.2 × 10−3, p < 0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y = 3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD > 10−4 associated with a CIR5y = 22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.
Phosphorylation-dependent regulation of SPOP by LIMK2 promotes castration-resistant prostate cancer
Authors: Nikhil Kumar , Haymour Hanan S. , Kamra Mohini , Shah Kavita
Published: December 2020

Background

SPOP, an E3 ubiquitin ligase adaptor, can act either as a tumour suppressor or a tumour promoter. In prostate cancer (PCa), it inhibits tumorigenesis by degrading several oncogenic substrates. SPOP is the most altered gene in PCa (~15%), which renders it ineffective, promoting cancer. The remaining PCa tumours, which retain WT-SPOP, still progress to castration-resistant (CRPC) stage, indicating that other critical mechanisms exist for downregulating SPOP. SPOP is reduced in ~94% of WT-SPOP-bearing prostate tumours; however, no molecular mechanism is known for its downregulation.

Methods

SPOP was identified as a direct target of LIMK2 using an innovative technique. The reciprocal relationship between SPOP and LIMK2 and its consequences on oncogenicity were analysed using a variety of biochemical assays. To probe this relationship in vivo, xenograft studies were conducted.

Results

LIMK2 degrades SPOP by direct phosphorylation at three sites. SPOP promotes LIMK2’s ubiquitylation, creating a feedback loop. SPOP’s degradation stabilises AR, ARv7 and c-Myc promoting oncogenicity. Phospho-resistant SPOP completely suppresses tumorigenesis in vivo, indicating that LIMK2-mediated SPOP degradation is a key event in PCa progression.

Conclusions

While genomically altered SPOP-bearing tumours require gene therapy, uncovering LIMK2-SPOP relationship provides a powerful opportunity to retain WT-SPOP by inhibiting LIMK2, thereby halting disease progression.
Targeting eIF4F translation initiation complex with SBI-756 sensitises B lymphoma cells to venetoclax
Authors: Herzog Lee-or , Walters Beth , Buono Roberta , Lee J. Scott , Mallya Sharmila , Fung Amos , Chiu Honyin , Nguyen Nancy , Li Boyang , Pinkerton Anthony B. , Jackson Michael R. , Schneider Robert J. , Ronai Ze’ev A. , Fruman David A.
Published: December 2020

Background

The BCL2 inhibitor venetoclax has shown efficacy in several hematologic malignancies, with the greatest response rates in indolent blood cancers such as chronic lymphocytic leukaemia. There is a lower response rate to venetoclax monotherapy in diffuse large B-cell lymphoma (DLBCL).

Methods

We tested inhibitors of cap-dependent mRNA translation for the ability to sensitise DLBCL and mantle cell lymphoma (MCL) cells to apoptosis by venetoclax. We compared the mTOR kinase inhibitor (TOR-KI) MLN0128 with SBI-756, a compound targeting eukaryotic translation initiation factor 4G1 (eIF4G1), a scaffolding protein in the eIF4F complex.

Results

Treatment of DLBCL and MCL cells with SBI-756 synergised with venetoclax to induce apoptosis in vitro, and enhanced venetoclax efficacy in vivo. SBI-756 prevented eIF4E-eIF4G1 association and cap-dependent translation without affecting mTOR substrate phosphorylation. In TOR-KI-resistant DLBCL cells lacking eIF4E binding protein-1, SBI-756 still sensitised to venetoclax. SBI-756 selectively reduced translation of mRNAs encoding ribosomal proteins and translation factors, leading to a reduction in protein synthesis rates in sensitive cells. When normal lymphocytes were treated with SBI-756, only B cells had reduced viability, and this correlated with reduced protein synthesis.

Conclusions

Our data highlight a novel combination for treatment of aggressive lymphomas, and establishes its efficacy and selectivity using preclinical models.
An autoregulatory feedback loop of miR-21/VMP1 is responsible for the abnormal expression of miR-21 in colorectal cancer cells
Authors: Wang Caixia , Peng Rui , Zeng Min , Zhang Zhenhua , Liu Shengpeng , Jiang Dan , Lu Yuanyuan , Zou Fangdong
Published: December 2020

MircoRNA-21 (miR-21) was found to be highly expressed in various solid tumors, and its oncogenic properties have been extensively studied in recent years. However, the reason why miR-21 is highly expressed in various tumors remains elusive. Here, we found that the expression of miR-21 was negatively correlated with the expression of vacuole membrane protein-1 (VMP1) in colorectal cancer. Transcription of VMP1 activated either by small activating RNA (saRNA) or transcriptional activator GLI3 inhibited miR-21 expression through reducing its transcripts of VMP1-miR-21 and pri-miR-21, while no significant change in miR-21 expression after exogenous overexpression VMP1 in colorectal cancer cell HCT116. Considering the overlapping location of VMP1 and miR-21 gene in genome, the result suggested that the transcription of miR-21 was inhibited by the endogenous transcriptional activation of VMP1. Furthermore, we identified that miR-21 inhibited the activation and nuclear translocation of transcription factor EB (TFEB) through reducing the inhibitory of PTEN on AKT phosphorylation, which can directly activate the transcription of VMP1. Loss of miR-21 significantly increased VMP1 expression, which could be blocked by PTEN inhibitor (VO-Ohpic) or TFEB siRNA. These results showed that miR-21 negatively regulated VMP1 transcription through the PTEN/AKT/TFEB pathway, and TFEB-induced transcriptional activation of VMP1 could inhibit miR-21 expression, thus forming a feedback regulatory loop of miR-21/VMP1. We further found that disrupting the miR-21/VMP1 feedback loop will decrease the expression of miR-21, reduce the malignancy, and increase their sensitivity to 5-fluorouracil in colorectal cancer cells. Taken together, our results revealed a novel regulatory mechanism of miR-21 expression, and targeting the miR-21/VMP1 feedback loop may provide a new approach to inhibit miR-21 expression in colorectal cancer cells.
Author Correction: Chromatin accessibility landscapes of skin cells in systemic sclerosis nominate dendritic cells in disease pathogenesis
Authors: Liu Qian , Zaba Lisa C. , Satpathy Ansuman T. , Longmire Michelle , Zhang Wen , Li Kun , Granja Jeffrey , Guo Chuang , Lin Jun , Li Rui , Tolentino Karen , Kania Gabriela , Distler Oliver , Fiorentino David , Chung Lorinda , Qu Kun , Chang Howard Y.
Published: December 2020

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20411-w
Biochemical phenotyping of multiple myeloma patients at diagnosis reveals a disorder of mitochondrial complexes I and II and a Hartnup-like disturbance as underlying conditions, also influencing different stages of the disease
Authors: da Silva Ismael Dale Cotrim Guerreiro , de Castro Levatti Erica Valadares , Pedroso Amanda Paula , Marchioni Dirce Maria Lobo , Carioca Antonio Augusto Ferreira , Colleoni Gisele Wally Braga
Published: December 2020

The aim of this study was to identify novel plasma metabolic signatures with possible relevance during multiple myeloma (MM) development and progression. A biochemical quantitative phenotyping platform based on targeted electrospray ionization tandem mass spectrometry technology was used to aid in the identification of any eventual perturbed biochemical pathway in peripheral blood plasma from 36 MM patients and 73 healthy controls. Our results showed that MM cases present an increase in short and medium/long-chain species of acylcarnitines resembling Multiple AcylCoA Dehydrogenase Deficiency (MADD), particularly, associated with MM advanced International Staging System (ISS). Lipids profile showed lower concentrations of phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelins (SM) in the MM patients and its respective ISS groups. MM cases were accompanied by a drop in the concentration of essential amino acids, especially tryptophan, with a significant inverse correlation between the progressive drop in tryptophan with the elevation of β2-microglobulin, with the increase in systemic methylation levels (Symmetric Arginine Dimethylation, SDMA) and with the accumulation of esterified carnitines in relation to free carnitine (AcylC/C0). Serotonin was significantly elevated in cases of MM, without a clear association with ISS. Kynurenine/tryptophan ratio demonstrates that the activity of dioxigenases is even higher in the cases classified as ISS 3. In conclusion, our study showed that MM patients at diagnosis showed metabolic disorders resembling both mitochondrial complexes I and II and Hartnup-like disturbances as underlying conditions, also influencing different stages of the disease.