bluuebunny/crossref_metadata_2025 huggingface dataset:
Topological insulating phase arising in transition metal dichalcogenide alloy
Authors: Crasto de Lima F , Focassio B , Miwa R H , Fazzio A
Published: March 2023

Transition metal dichalcogenides have been the subject of numerous studies addressing technological applications and fundamental issues. Single-layer PtSe2 is a semiconductor with a trivial bandgap, in contrast, its counterpart with

25
%

of Se atoms substituted by Hg, Pt2HgSe3 (jacutingaite, a naturally occurring mineral) is a 2D topological insulator with a large bandgap. Based on ab-initio calculations, we investigate the energetic stability, and the topological transition in Pt(Hg
x
Se

1
−
x

)2 as a function of alloy concentration, and the distribution of Hg atoms embedded in the PtSe2 host. Our findings reveal the dependence of the topological phase with respect to the alloy concentration and robustness with respect to the distribution of Hg. Through a combination of our ab-initio results and a defect wave function percolation model, we estimate the random alloy concentration threshold for the topological transition to be only

9
%

. Our results expand the possible search for non-trivial topological phases in random alloy systems.
Hypercontractivity for global functions and sharp thresholds
Authors: Keevash Peter , Lifshitz Noam , Long Eoin , Minzer Dor
Published: March 2023

The classical hypercontractive inequality for the noise operator on the discrete cube plays a crucial role in many of the fundamental results in the Analysis of Boolean functions, such as the Kahn-Kalai-Linial theorem, Friedgut’s junta theorem and the invariance principle of Mossel, O’Donnell and Oleszkiewicz. In these results the cube is equipped with the uniform (

1

/

2

1/2

-biased) measure, but it is desirable, particularly for applications to the theory of sharp thresholds, to also obtain such results for general

p
p

-biased measures. However, simple examples show that when

p
p

is small there is no hypercontractive inequality that is strong enough for such applications.

In this paper, we establish an effective hypercontractivity inequality for general

p
p

that applies to ‘global functions’, i.e. functions that are not significantly affected by a restriction of a small set of coordinates. This class of functions appears naturally, e.g. in Bourgain’s sharp threshold theorem, which states that such functions exhibit a sharp threshold. We demonstrate the power of our tool by strengthening Bourgain’s theorem, making progress on two conjectures of Kahn and Kalai (both these conjectures were open when we arXived this paper in 2019; one of them was solved in 2022; the other is still open), and proving a

p
p

-biased analogue of the seminal invariance principle of Mossel, O’Donnell, and Oleszkiewicz.

In this 2023 version of our paper we will also survey many further applications of our results that have been obtained by various authors since we arXived the first version in 2019.
Liouville rigidity and time-extrinsic Harnack estimates for an anisotropic slow diffusion
Authors: Ciani Simone , Guarnotta Umberto
Published: March 2023

We prove that non-negative solutions to the fully anisotropic equation
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="partial-differential Subscript t Baseline u equals sigma-summation Underscript i equals 1 Overscript upper N Endscripts partial-differential Subscript i Baseline left-parenthesis StartAbsoluteValue partial-differential Subscript i Baseline u EndAbsoluteValue Superscript p Super Subscript i Superscript minus 2 Baseline partial-differential Subscript i Baseline u right-parenthesis comma in double-struck upper R Superscript upper N Baseline times left-parenthesis negative normal infinity comma upper T right-parenthesis comma">

∂
t

u
=

∑

i
=
1

N

∂
i

(

|

∂
i

u

|

p
i

−
2

∂
i

u
)
,

in 

R

N

×
(
−
∞
,
T
)
,

\begin{equation*} \partial _t u= \sum _{i=1}^N \partial _i (|\partial _i u|^{p_i-2} \partial _i u), \quad \qquad \text {in } \mathbb {R}^N\times (-\infty , T), \end{equation*}

are constant if they satisfy a condition of finite speed of propagation and if they are both one-sided bounded, and bounded in

R

N

\mathbb {R}^N

at a single time level. A similar statement is valid when the bound is given at a single space point. As a general paradigm, local Hölder estimates provide the basics for rigidity. Finally, we show that recent intrinsic Harnack estimates can be improved to a Harnack inequality valid for non-intrinsic times. Locally, they are equivalent.
Rigidity of nonpositively curved manifolds with convex boundary
Authors: Ghomi Mohammad , Spruck Joel
Published: March 2023

We show that a compact Riemannian

3
3

-manifold

M
M

with strictly convex simply connected boundary and sectional curvature

K
≤
a
≤
0

K\leq a\leq 0

is isometric to a convex domain in a complete simply connected space of constant curvature

a
a

, provided that

K
≡
a

K\equiv a

on planes tangent to the boundary of

M
M

. This yields a characterization of strictly convex surfaces with minimal total curvature in Cartan-Hadamard

3
3

-manifolds, and extends some rigidity results of Greene-Wu, Gromov, and Schroeder-Strake. Our proof is based on a recent comparison formula for total curvature of Riemannian hypersurfaces, which also yields some dual results for

K
≥
a
≥
0

K\geq a\geq 0

.
A blow-up formula for stationary quaternionic maps
Authors: Li Jiayu , Zhu Chaona
Published: March 2023

Let

(
M
,

J
α

,
α
=
1
,
2
,
3
)

(M, J^\alpha , \alpha =1,2,3)

and

(
N
,

J

α

,
α
=
1
,
2
,
3
)

(N, \mathcal {J}^\alpha , \alpha =1,2,3)

be Hyperkähler manifolds. Suppose that

u
k

u_k

is a sequence of stationary quaternionic maps and converges weakly to

u
u

in

H

1
,
2

(
M
,
N
)

H^{1,2}(M,N)

, we derive a blow-up formula for

lim

k
→
∞

d
(

u
k
∗

J

α

)

\lim _{k\to \infty }d(u_k^*\mathcal {J}^\alpha )

, for

α
=
1
,
2
,
3

\alpha =1,2,3

, in the weak sense. As a corollary, we show that the maps constructed by Chen-Li [Ann. Sc. Norm. Super. Pisa Cl. Sci. (5) 4 (2005), pp. 375–388] and by Foscolo [J. Differential Geom. 112 (2019), pp. 79–120] cannot be tangent maps (c.f Li and Tian [Internat. Math. Res. Notices 14 (1998), pp. 735–755], Theorem 3.1) of a stationary quaternionic map satisfing

d
(

u
∗

J

α

)
=
0

d(u^*\mathcal {J}^\alpha )=0

.
Eigenfunction restriction estimates for curves with nonvanishing geodesic curvatures in compact Riemannian surfaces with nonpositive curvature
Authors: Park Chamsol
Published: March 2023

For

2
≤
p
>
4

2\leq p>4

, we study the

L
p

L^p

norms of restrictions of eigenfunctions of the Laplace-Beltrami operator on smooth compact

2
2

-dimensional Riemannian manifolds. Burq, Gérard, and Tzvetkov [Duke Math. J. 138 (2007), pp. 445–486], and Hu [Forum Math. 21 (2009), pp. 1021–1052] found the eigenfunction estimates restricted to a curve with nonvanishing geodesic curvatures. We will explain how the proof of the known estimates helps us to consider the case where the given smooth compact Riemannian manifold has nonpositive sectional curvatures. For

p
=
4

p=4

, we will also obtain a logarithmic analogous estimate, by using arguments in Xi and Zhang [Comm. Math. Phys. 350 (2017), pp. 1299–1325], Sogge [Math. Res. Lett. 24 (2017), pp. 549–570], and Bourgain [Geom. Funct. Anal. 1 (1991), pp. 147–187].
The 𝜔-Vaught’s conjecture
Authors: Gonzalez David , Montalbán Antonio
Published: March 2023

We introduce the

ω
\omega

-Vaught’s conjecture, a strengthening of the infinitary Vaught’s conjecture. We believe that if one were to prove the infinitary Vaught’s conjecture in a structural way without using techniques from higher recursion theory, then the proof would probably be a proof of the

ω
\omega

-Vaught’s conjecture. We show the existence of an equivalent condition to the

ω
\omega

-Vaught’s conjecture and use this tool to show that all infinitary sentences whose models are linear orders satisfy the

ω
\omega

-Vaught’s conjecture.
Impact of MidMed, a general practitioner-led modified comprehensive geriatric assessment for patients with frailty
Authors: Jones Helen E , Anand Atul , Morrison Iain , Hurding Simon , Wild Sarah H , Mercer Stewart W , Shenkin Susan D
Published: March 2023

Introduction

the identification and management of frailty occurs mostly in primary care. Several different models of care exist. This study aimed to assess the impact of a new General Practitioner (GP)-led modified Comprehensive Geriatric Assessment (CGA) on service delivery, healthcare utilisation and patient outcomes.

Method

patients with moderate–severe frailty (electronic Frailty Index score > 0.24) in Newbattle Medical Practice, Scotland, were eligible for a novel intervention (MidMed) in which an additional GP performed a modified CGA and was directly accessible for appointments. The recruits to the intervention (MidMed) group were compared with those waiting to be enrolled (non-MidMed). Outcomes included unscheduled hospital admissions, primary care consultations, continuity of care (Usual Provider of Care (UPC) index), outpatient attendances and mortality. Adjusted rate ratios (aRR), for MidMed compared to non-MidMed, were estimated using regression models adjusting for demographics and healthcare utilisation histories.

Results

510 patients were included: 290 MidMed (mean(SD) age 80.1(7.6)years; 59.6% female) and 220 non-MidMed (75.4(8.6)years; 57.7% female). Median follow-up was 396 days. aRR(95%CI) was 0.46(0.30–0.71) for >1 admission, 0.62(0.41–0.95) >1 Emergency Department (ED) attendance and 1.52(1.30–1.75) for use of primary care, with no difference in outpatient appointments or mortality. Continuity of care was better for the MidMed group (MidMed UPC 0.77(SD 0.19), non-MidMed 0.41(0.18), P < 0.001).

Conclusion

this GP-led service for frail patients was associated with lower risk of hospital readmission/ED reattendance, greater use of primary care and improved continuity of care. More detailed evaluation of novel primary care frailty services, over longer time-periods, including robust randomised controlled trials, are needed.
Resistant xylem from roots to peduncles sustains reproductive water supply after drought-induced cavitation of wheat leaves
Authors: Harrison Day Beatrice L , Brodribb Timothy J
Published: March 2023

Background and Aims

Many annual grasses exhibit drought-avoiding life cycles in which rapid reproduction must be completed before soil water is exhausted. This strategy would seem to require a hydraulic system capable of sustaining reproduction at all costs to the rest of the plant, yet little is known about the whole-plant structure of hydraulic vulnerability in grasses.

Methods

We examine vulnerability to water-stress-induced xylem cavitation in roots, flag leaves, and basal and apical regions of peduncles of wheat (Triticum aestivum L. ‘Krichauff’) to understand the staged failure of xylem function in severe drought. The functionality of segmented vulnerabilities is tested by conducting rehydration experiments after acute dehydration.

Key Results

We show that water supply to peduncles is more drought resistant than in leaves due to greater xylem cavitation resistance, ensuring a pathway of water can be maintained from the roots to the reproductive tissues even after severe water deficit. Differential rehydration of peduncles compared to leaves following drought confirmed the functionality of xylem supply from roots to seed after water stress sufficient to completely cavitate flag leaf vessels.

Conclusions

These results demonstrate that a proportion of the hydraulic pathway between roots and seeds remains functional under extreme dehydration, suggesting that vulnerability traits in this key grass species reflect its reproductive strategy.
Machine learning classifier approaches for predicting response to RTK-type-III inhibitors demonstrate high accuracy using transcriptomic signatures and ex vivo data
Authors: Ferrato Mauricio H , Marsh Adam G , Franke Karl R , Huang Benjamin J , Kolb E Anders , DeRyckere Deborah , Grahm Douglas K , Chandrasekaran Sunita , Crowgey Erin L
Published: March 2023

Motivation

The application of machine learning (ML) techniques in the medical field has demonstrated both successes and challenges in the precision medicine era. The ability to accurately classify a subject as a potential responder versus a nonresponder to a given therapy is still an active area of research pushing the field to create new approaches for applying machine-learning techniques. In this study, we leveraged publicly available data through the BeatAML initiative. Specifically, we used gene count data, generated via RNA-seq, from 451 individuals matched with ex vivo data generated from treatment with RTK-type-III inhibitors. Three feature selection techniques were tested, principal component analysis, Shapley Additive Explanation (SHAP) technique and differential gene expression analysis, with three different classifiers, XGBoost, LightGBM and random forest (RF). Sensitivity versus specificity was analyzed using the area under the curve (AUC)-receiver operating curves (ROCs) for every model developed.

Results

Our work demonstrated that feature selection technique, rather than the classifier, had the greatest impact on model performance. The SHAP technique outperformed the other feature selection techniques and was able to with high accuracy predict outcome response, with the highest performing model: Foretinib with 89% AUC using the SHAP technique and RF classifier. Our ML pipelines demonstrate that at the time of diagnosis, a transcriptomics signature exists that can potentially predict response to treatment, demonstrating the potential of using ML applications in precision medicine efforts.

Availability and implementation

https://github.com/UD-CRPL/RCDML.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
Federated learning framework integrating REFINED CNN and Deep Regression Forests
Authors: Nolte Daniel , Bazgir Omid , Ghosh Souparno , Pal Ranadip
Published: March 2023

Predictive learning from medical data incurs additional challenge due to concerns over privacy and security of personal data. Federated learning, intentionally structured to preserve high level of privacy, is emerging to be an attractive way to generate cross-silo predictions in medical scenarios. However, the impact of severe population-level heterogeneity on federated learners is not well explored. In this article, we propose a methodology to detect presence of population heterogeneity in federated settings and propose a solution to handle such heterogeneity by developing a federated version of Deep Regression Forests. Additionally, we demonstrate that the recently conceptualized REpresentation of Features as Images with NEighborhood Dependencies CNN framework can be combined with the proposed Federated Deep Regression Forests to provide improved performance as compared to existing approaches.

Availability and implementation

The Python source code for reproducing the main results are available on GitHub: https://github.com/DanielNolte/FederatedDeepRegressionForests.

Contact

ranadip.pal@ttu.edu

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
OutSingle: a novel method of detecting and injecting outliers in RNA-Seq count data using the optimal hard threshold for singular values
Authors: Salkovic Edin , Sadeghi Mohammad Amin , Baggag Abdelkader , Salem Ahmed Gamal Rashed , Bensmail Halima
Published: March 2023

Motivation

Finding outliers in RNA-sequencing (RNA-Seq) gene expression (GE) can help in identifying genes that are aberrant and cause Mendelian disorders. Recently developed models for this task rely on modeling RNA-Seq GE data using the negative binomial distribution (NBD). However, some of those models either rely on procedures for inferring NBD’s parameters in a nonbiased way that are computationally demanding and thus make confounder control challenging, while others rely on less computationally demanding but biased procedures and convoluted confounder control approaches that hinder interpretability.

Results

In this article, we present OutSingle (Outlier detection using Singular Value Decomposition), an almost instantaneous way of detecting outliers in RNA-Seq GE data. It uses a simple log-normal approach for count modeling. For confounder control, it uses the recently discovered optimal hard threshold (OHT) method for noise detection, which itself is based on singular value decomposition (SVD). Due to its SVD/OHT utilization, OutSingle’s model is straightforward to understand and interpret. We then show that our novel method, when used on RNA-Seq GE data with real biological outliers masked by confounders, outcompetes the previous state-of-the-art model based on an ad hoc denoising autoencoder. Additionally, OutSingle can be used to inject artificial outliers masked by confounders, which is difficult to achieve with previous approaches. We describe a way of using OutSingle for outlier injection and proceed to show how OutSingle outperforms its competition on 16 out of 18 datasets that were generated from three real datasets using OutSingle’s injection procedure with different outlier types and magnitudes. Our methods are applicable to other types of similar problems involving finding outliers in matrices under the presence of confounders.

Availability and implementation

The code for OutSingle is available at https://github.com/esalkovic/outsingle.
Rapid efficacy of anifrolumab across multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels changes in discrete subsets of blood transcriptomic and cellular biomarkers
Authors: Carter Lucy M , Wigston Zoe , Laws Philip , Vital Edward M
Published: March 2023

Background

Observations with rituximab suggest B-cell independent mechanisms of cutaneous lupus erythematosus (CLE) in systemic lupus erythematosus (SLE), especially discoid lupus erythematosus (DLE). Type-I interferon receptor blockade with anifrolumab shows efficacy in SLE, but efficacy for cutaneous disease of specific morphologies has not been studied. Interferon has pleotropic immune effects and it is unknown which of these are critical to therapeutic response.

Objectives

We evaluated clinical efficacy and quality-of-life impact of type-I interferon-blockade in: (i) rituximab-refractory CLE; (ii) DLE and other morphologies and (iii) transcriptomic and flow cytometric biomarkers.

Methods

We conducted a prospective single-centre study of anifrolumab in refractory mucocutaneous SLE. CLE Disease Area and Severity Index (CLASI) activity score, health-related quality of life, 96-probe TaqMan® gene expression analysis capturing key SLE blood transcriptome signatures, and eight-colour flow cytometry were undertaken at baseline, 1, 3 and 6 months.

Results

Seven patients [DLE (n = 5), chilblain lupus erythematosus (n = 1), subacute CLE (n = 1)] were evaluated. The median number of prior therapies was six (range 3–15), including rituximab in six of seven patients. Median CLASI-A showed rapid and sustained improvement from 17 at baseline to 6 (P = 0.016) at 1 month and 0 (P < 0.001) by 3 months. The median percentage reduction in CLASI-A at 3 months was 60%. Significant improvements were observed in Dermatology Life Quality Index scores (P < 0.001), EuroQol 5D visual analogue scale (P = 0.002) and LupusQoL fatigue, image and planning domains (P ≤ 0.05). One patient discontinued treatment owing to severe herpes zoster. Clinical responses paralleled discrete suppression of interferon-stimulated genes (ISGs) from SLE blood transcriptome module M1.2 with more varied downregulation in other interferon modules. Myeloid and inflammation-annotated genes remained upregulated throughout treatment. Intermediate monocytes (CD14++CD16+) reduced to normal levels during therapy (P = 0.014), while other flow subsets showed no substantive changes.

Conclusions

These data indicate rapid efficacy of anifrolumab in DLE and rituximab-resistant CLE. Response is associated with suppression of a subset of ISGs and decline in intermediate monocytes. Suppression of all ISGs or the wider SLE blood transcriptome is not required for response.
Effectiveness of nail bed repair in children with or without replacing the fingernail: NINJA multicentre randomized clinical trial
Authors: Jain Abhilash , Greig Aina V H , Jones Amy , Cooper Cushla , Davies Loretta , Greshon Akiko , Fletcher Heidi , Sierakowski Adam , Dritsaki Melina , Nguyen Thi Thu An , Png May Ee , Stokes Jamie R , Dakin Helen , Cook Jonathan A , Beard David J , Gardiner Matthew D ,   NINJA Collaborative, Mertic A , Gerrish H , Cranmer K , Fox N , Dutta P , Vissers G , Costa P , Irri R , McArthur G , Horwitz M , Sleiwah A , Jephson H , Deeley M , Nicholas R , Vinnicombe Z , Nicola A , Chuo C Bing , Milner C , Heaney J , Totty J , Fleet M , Khadim M Faheem , Williams P , Bibawy S , Round A , Pinder R , Plonczak A , Lawton G , Kennedy D , Bennett A , Fadulelmola A , James J , Reay E , Beadon K , Cameron T , Oliver Z , Wensley K , Dupré S , Rodriguez J , Furniss D , Gale M , Knight A , Tulip J , Turner L , Wellings L , Allen M , Wade R , Itte V , Bourke G , Kumar N , O'Sullivan S , Jones J W M , Young K , Taylor K , Dawood O , Booth S , Giwa L , Pearl R , Coutts A , Hawkins R , Mostafa A , Nisbett T , Riddlestone P , Selby A , Uzoho C , Chasiouras D , Bainbridge L C , Buick T , Lam W , Baker B , Walsh K , Keating K , Dalan R , Shah M , Mead D , Diment S , Nicolau M , Smeeton B , Thomson D , Senior N , Moledina J , Colville J , Manso K , Song M , Manley O , Drury P , Kerstein R , Cobb W , Wormald J , Shirley R , Tan A , Arnaout A , Cruz C , Brice N , Segaren N , Joji N , Chawla R , Hassanin S , Adami R , Ridha H , Cook A , Symington L , Long R , Dustagheer S , Jarvis H , Larsen M , Williams M , Trickett R , Miles D , Pai A , Honeywell C , Brady C , Madhavan S , Manou V , Phillips G , Baker R
Published: March 2023

Background

Surgery for nail bed injuries in children is common. One of the key surgical decisions is whether to replace the nail plate following nail bed repair. The aim of this RCT was to assess the clinical effectiveness and cost-effectiveness of nail bed repair with fingernail replacement/substitution compared with repair without fingernail replacement.

Methods

A two-arm 1 : 1 parallel-group open multicentre superiority RCT was performed across 20 secondary-care hospitals in the UK. The co-primary outcomes were surgical-site infection at around 7 days after surgery and cosmetic appearance summary score at a minimum of 4 months.

Results

Some 451 children presenting with a suspected nail bed injury were recruited between July 2018 and July 2019; 224 were allocated to the nail-discarded arm, and 227 to the nail-replaced arm. There was no difference in the number of surgical-site infections at around 7 days between the two interventions or in cosmetic appearance. The mean total healthcare cost over the 4 months after surgery was €84 (95 per cent c.i. 34 to 140) lower for the nail-discarded arm than the nail-replaced arm (P < 0.001).

Conclusion

After nail bed repair, discarding the fingernail was associated with similar rates of infection and cosmesis ratings as replacement of the finger nail, but was cost saving. Registration number: ISRCTN44551796 (http://www.controlled-trials.com).
Neuropathy due to bi-allelic SH3TC2 variants: genotype-phenotype correlation and natural history
Authors: Rehbein Tyler , Wu Tong Tong , Treidler Simona , Pareyson Davide , Lewis Richard , Yum Sabrina W , McCray Brett A , Ramchandren Sindhu , Burns Joshua , Li Jun , Finkel Richard S , Scherer Steven S , Zuchner Stephan , Shy Michael E , Reilly Mary M , Herrmann David N
Published: March 2023

Recessive SH3TC2 variants cause Charcot-Marie-Tooth disease type 4C (CMT4C). CMT4C is typically a sensorimotor demyelinating polyneuropathy, marked by early onset spinal deformities, but its clinical characteristics and severity are quite variable. Clear relationships between pathogenic variants and the spectrum of disease manifestations are to date lacking. Gene replacement therapy has been shown to ameliorate the phenotype in a mouse model of CMT4C, emphasizing the need for natural history studies to inform clinical trial readiness.

Data, including both genetic information and clinical characteristics, were compiled from the longitudinal, prospective dataset of the Inherited Neuropathy Consortium, a member of the Rare Diseases Clinical Research Network (INC-RDCRN). The Charcot Marie Tooth Neuropathy Score (CMTNS), Examination Score (CMTES) and the Rasch-weighted CMTES (CMTES-R) were used to describe symptoms, neurological examinations and neurophysiological characteristics. Standardized response means were calculated at yearly intervals and a mixed model for repeated measures was used to estimate the change in CMTES and CMTES-R over time.

Fifty-six individuals (59% female), median age 27 years (range 2–67 years) with homozygous or compound heterozygous variants in SH3TC2 were identified, including 34 unique variants, 14 of which have not previously been published. Twenty-eight participants had longitudinal data available. While there was no significant difference in the CMTES in those with protein truncating versus non-protein truncating variants, there were significant differences in the mean ulnar nerve compound muscle action potential amplitude, the mean radial sensory nerve action potential amplitude, and in the prevalence of scoliosis, suggesting the possibility of a milder phenotype in individuals with one or two non-protein-truncating variants. Overall, the mean value of the CMTES was 13, reflecting moderate clinical severity. There was a high rate of scoliosis (81%), scoliosis surgery (36%), and walking difficulty (94%) among study participants. The CMTES and CMTES-R appeared moderately responsive to change over extended follow-up, demonstrating a standardized response mean of 0.81 standard deviation units or 0.71 standard deviation units, respectively, over 3 years.

Our analysis represents the largest cross-sectional and only longitudinal study to date, of the clinical phenotype of both adults and children with CMT4C. With the promise of upcoming genetic treatments, these data will further define the natural history of the disease and inform study design in preparation for clinical trials.
Autonomy of Provisional Measures or Autonomy of the International Court of Justice?
Authors: LI Zhenni
Published: March 2023

With growing demand for legally binding provisional measures (since LaGrand) on situations of ongoing tension, the International Court of Justice has passively extended its role from judicial settlement of dispute to crisis management and policy making as the world judiciary. Yet this proactive role has rendered the Court in dilemma given its consent-based jurisdiction and the contractual nature of the current international legal order. In such a context, Qatar v. UAE marks the second case (the first being Georgia v. Russia) where the Court stayed silent to the alleged non-compliance with provisional measures when jurisdiction is declined. Such silence intensifies the doubts about the so-called autonomy of provisional measures. Reviewing its jurisprudence, this Article traces the status quo of the Court’s position: The temporal validity of provisional measures where jurisdiction is declined remains equivocal, and the Court’s jurisdiction over the alleged non-compliance with provisional measures is based on its jurisdiction over the original dispute. Climbing from one intermediacy to another intermediacy, the regime of provisional measures does not simply develop upon legal positivism. Instead, it concerns the delicate balance of the multiplicity in the role of the Court and is inherently subject to the changing environment of the international legal order.
Use of PLE-ATD-GC/MSMS for the Quantification of Airborne Pesticides in Active and Passive Samples and in Dust
Authors: Rodrigues Anaïs , Delhomme Olivier , Millet Maurice
Published: March 2023

An analytical method coupling pressurized liquid extraction (PLE), pre-concentration by thermal desorption (ATD) and analysis by GC/MSMS was developed for the quantification of pesticides in air and dust near vineyards crops to evaluate potential exposure of residents living near these crops. PLE was done using acetonitrile and extracts were concentrated under fume hood to 1 mL. 100 μL of the extract was spiked in a Tenax TA tube and internal standards and N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide were added before thermal desorption at 300°C for 30 min. GC/MSMS analysis was done in MRM mode and limits of quantification and limits of detection were determined for each matrix (passive air sample, active air sample and dust). The method was applied in the field and shows good sensitivity and accuracy.
A pre-transplantation risk assessment tool for graft survival in Dutch pediatric kidney recipients
Authors: Oomen Loes , de Jong Huib , Bouts Antonia H M , Keijzer-Veen Mandy G , Cornelissen Elisabeth A M , de Wall Liesbeth L , Feitz Wout F J , Bootsma-Robroeks Charlotte M H H T
Published: March 2023

Background

A prediction model for graft survival including donor and recipient characteristics could help clinical decision-making and optimize outcomes. The aim of this study was to develop a risk assessment tool for graft survival based on essential pre-transplantation parameters.

Methods

The data originated from the national Dutch registry (NOTR; Nederlandse OrgaanTransplantatie Registratie). A multivariable binary logistic model was used to predict graft survival, corrected for the transplantation era and time after transplantation. Subsequently, a prediction score was calculated from the β-coefficients. For internal validation, derivation (80%) and validation (20%) cohorts were defined. Model performance was assessed with the area under the curve (AUC) of the receiver operating characteristics curve, Hosmer–Lemeshow test and calibration plots.

Results

In total, 1428 transplantations were performed. Ten-year graft survival was 42% for transplantations before 1990, which has improved to the current value of 92%. Over time, significantly more living and pre-emptive transplantations have been performed and overall donor age has increased (P < .05).The prediction model included 71 829 observations of 554 transplantations between 1990 and 2021. Other variables incorporated in the model were recipient age, re-transplantation, number of human leucocyte antigen (HLA) mismatches and cause of kidney failure. The predictive capacity of this model had AUCs of 0.89, 0.79, 0.76 and 0.74 after 1, 5, 10 and 20 years, respectively (P < .01). Calibration plots showed an excellent fit.

Conclusions

This pediatric pre-transplantation risk assessment tool exhibits good performance for predicting graft survival within the Dutch pediatric population. This model might support decision-making regarding donor selection to optimize graft outcomes.

Trial registration

ClinicalTrials.gov Identifier: NCT05388955
The translational landscape of human vascular smooth muscle cells identifies novel short open reading frame-encoded peptide regulators for phenotype alteration
Authors: Li Kang , Li Bin , Zhang Dihua , Du Tailai , Zhou Huimin , Dai Gang , Yan Youchen , Gao Nailin , Zhuang Xiaodong , Liao Xinxue , Liu Chen , Dong Yugang , Chen Demeng , Qu Liang-Hu , Ou Jingsong , Yang Jian-Hua , Huang Zhan-Peng
Published: March 2023

Aims

The plasticity of vascular smooth muscle cells (VSMCs) enables them to alter phenotypes under various physiological and pathological stimuli. The alteration of VSMC phenotype is a key step in vascular diseases, including atherosclerosis. Although the transcriptome shift during VSMC phenotype alteration has been intensively investigated, uncovering multiple key regulatory signalling pathways, the translatome dynamics in this cellular process, remain largely unknown. Here, we explored the genome-wide regulation at the translational level of human VSMCs during phenotype alteration.

Methods and results

We generated nucleotide-resolution translatome and transcriptome data from human VSMCs undergoing phenotype alteration. Deep sequencing of ribosome-protected fragments (Ribo-seq) revealed alterations in protein synthesis independent of changes in messenger ribonucleicacid levels. Increased translational efficiency of many translational machinery components, including ribosomal proteins, eukaryotic translation elongation factors and initiation factors were observed during the phenotype alteration of VSMCs. In addition, hundreds of candidates for short open reading frame-encoded polypeptides (SEPs), a class of peptides containing 200 amino acids or less, were identified in a combined analysis of translatome and transcriptome data with a high positive rate in validating their coding capability. Three evolutionarily conserved SEPs were further detected endogenously by customized antibodies and suggested to participate in the pathogenesis of atherosclerosis by analysing the transcriptome and single cell RNA-seq data from patient atherosclerotic artery samples. Gain- and loss-of-function studies in human VSMCs and genetically engineered mice showed that these SEPs modulate the alteration of VSMC phenotype through different signalling pathways, including the mitogen-activated protein kinase pathway and p53 pathway.

Conclusion

Our study indicates that an increase in the capacity of translation, which is attributable to an increased quantity of translational machinery components, mainly controls alterations of VSMC phenotype at the level of translational regulation. In addition, SEPs could function as important regulators in the phenotype alteration of human VSMCs.
Adapting cybersecurity practice to reduce wildlife cybercrime
Authors: Haas Timothy C
Published: March 2023

Wildlife trafficking is driving many species to extinction and is overwhelming law enforcement efforts to stop it. At least a 2-fold increase in the number of traffickers who are put out of business is needed to help avoid these extinctions. A cybersecurity-based solution described in this article consists of a large international confederation of criminal investigators collecting intelligence on persons involved in wildlife trafficking, analyzing it, and then recommending to law enforcement (a) cybercriminals to detain, (b) cybercriminals to surveil, and (c) where and when to intercept cybercriminal-initiated wire transfers and shipments of wildlife products. Wildlife traffickers nowadays often use the internet to commit their cybercrimes. Prosecuting such crimes is challenging. Indeed, one of the top five challenges in cybersecurity is to develop methods for pursuing cybercriminals and bringing them to justice through the acquisition of digital evidence that links specific individuals to specific illegal acts. The proposed confederation finds two lists of wildlife cybercriminals to remove. The first is found by computing centrality measures on the statistically estimated (reconstructed) current social network of wildlife cybercriminals to identify those criminals whose removal would, according to social network theory, maximally disrupt the syndicate’s operations. This list contains criminals identified as kingpins, and/or information brokers. The second list consists of those m criminals whose removal results in the largest simulator-computed drop in poaching of the trafficked species over the next year. Database access control is a form of information security (InfoSec), or data security—a chief component of cybersecurity. Here, a distributed form of information security is developed for keeping a confederation’s criminal intelligence database secure from unauthorized access and insider threats. This procedure uses only peer-to-peer transactions. The illegal trade in rhino horn is used to illustrate how this confederation would use criminal intelligence from several countries to first build a simulation of the political–ecological system that contains the trafficking operation, and then use this statistically fitted simulator to identify those traffickers to remove, wire transfers to block, and wildlife product shipments to seize. All software to implement this federated database and its access control procedure is freely available.
Risks Factors Associated with the Development of Crohn’s Disease After Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: A Systematic Review and Meta-Analysis
Authors: Fadel Michael G , Geropoulos Georgios , Warren Oliver J , Mills Sarah C , Tekkis Paris P , Celentano Valerio , Kontovounisios Christos
Published: March 2023

Background

Following ileal pouch–anal anastomosis [IPAA] for ulcerative colitis [UC], up to 16% of patients develop Crohn’s disease of the pouch [CDP], which is a major cause of pouch failure. This systematic review and meta-analysis aimed to identify preoperative characteristics and risk factors for CDP development following IPAA.

Methods

A literature search of the MEDLINE, EMBASE, EMCare and CINAHL databases was performed for studies that reported data on predictive characteristics and outcomes of CDP development in patients who underwent IPAA for UC between January 1990 and August 2022. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed.

Results

Seven studies with 1274 patients were included: 767 patients with a normal pouch and 507 patients with CDP. Age at UC diagnosis (weighted mean difference [WMD] −2.85; 95% confidence interval [CI] −4.39 to −1.31; p = 0.0003; I2 54%) and age at pouch surgery [WMD −3.17; 95% CI −5.27 to −1.07; p = 0.003; I2 20%) were significantly lower in patients who developed CDP compared to a normal pouch. Family history of IBD was significantly associated with CDP (odds ratio [OR] 2.43; 95% CI 1.41–4.19; p = 0.001; I2 31%], along with a history of smoking [OR 1.80; 95% CI 1.35–2.39; p < 0.0001; I2 0%]. Other factors such as sex and primary sclerosing cholangitis were found not to increase the risk of CDP.

Conclusions

Age at UC diagnosis and pouch surgery, family history of IBD and previous smoking have been identified as potential risk factors for CDP post-IPAA. This has important implications towards preoperative counselling, planning surgical management and evaluating prognosis.
Phylogenetic diversity of core rumen microbiota as described by cryo-ET
Authors: Wimmer Benedikt H , Moraïs Sarah , Zalk Ran , Mizrahi Itzhak , Medalia Ohad
Published: March 2023

Microbial taxonomy is critical for describing ecosystem composition, yet the link between taxonomy and properties of microbes, such as their cellular architecture, remains poorly defined. We hypothesized that the cellular architecture represents microbial niche adaptation. We used cryo-electron microscopy and tomography to analyze microbial morphology in order to associate cellular architecture with phylogeny and genomic contents. As a model system, we chose the core rumen microbiome and imaged a large isolate collection covering 90% of its richness at the order level. Based on quantifications of several morphological features, we found that the visual similarity of microbiota is significantly related to their phylogenetic distance. Up to the Family level, closely related microbes have similar cellular architectures, which are highly correlated with genome similarity. However, in more distantly related bacteria, the correlation both with taxonomy and genome similarity is lost. This is the first comprehensive study of microbial cellular architecture and our results highlight that structure remains an important parameter in classification of microorganisms, along with functional parameters such as metabolomics. Furthermore, the high-quality images presented in this study represent a reference database for the identification of bacteria in anaerobic ecosystems.
Mapping quantitative trait loci for biomass yield and yield-related traits in lowland switchgrass (Panicum virgatum L.) multiple populations
Authors: Shrestha Surya L , Tobias Christian M , Bhandari Hem S , Bragg Jennifer , Nayak Santosh , Goddard Ken , Allen Fred
Published: March 2023

Switchgrass can be used as an alternative source for bioenergy production. Many breeding programs focus on the genetic improvement of switchgrass for increasing biomass yield. Quantitative trait loci (QTL) mapping can help to discover marker-trait associations and accelerate the breeding process through marker-assisted selection. To identify significant QTL, this study mapped 7 hybrid populations and one combined of 2 hybrid populations (30–96 F1s) derived from Alamo and Kanlow genotypes. The populations were evaluated for biomass yield, plant height, and crown size in a simulated-sward plot with 2 replications at 2 locations in Tennessee from 2019 to 2021. The populations showed significant genetic variation for the evaluated traits and exhibited transgressive segregation. The 17,251 single nucleotide polymorphisms (SNPs) generated through genotyping-by-sequencing (GBS) were used to construct a linkage map using a fast algorithm for multiple outbred families. The linkage map spanned 1,941 cM with an average interval of 0.11 cM between SNPs. The QTL analysis was performed on evaluated traits for each and across environments (year and location) that identified 5 QTL for biomass yield (logarithm of the odds, LOD 3.12–4.34), 4 QTL for plant height (LOD 3.01–5.64), and 7 QTL for crown size (LOD 3.0–4.46) (P ≤ 0.05). The major QTL for biomass yield, plant height, and crown size resided on chromosomes 8N, 6N, and 8K explained phenotypic variations of 5.6, 5.1, and 6.6%, respectively. SNPs linked to QTL could be incorporated into marker-assisted breeding to maximize the selection gain in switchgrass breeding.
Biologist Nikolai K. Koltzoff: the forgotten genius
Authors: Ptushenko Vasily V , Ramensky Evgeny V
Published: March 2023

Nikolai K. Koltzoff (Koltsov) (1872–1940) is one of the key figures in Russian biology. He essentially initiated Russian physicochemical biology and established a large scientific school in the area. Among his disciples, there are the geneticists B.L. Astaurov, S.S. Chetverikov, N.P. Dubinin, V.P. Efroimson, I.A. Rapoport, V.V. Sakharov, and N.V. Timofeeff-Ressovsky; histologist G.I. Roskin, experimental surgeon A.G. Lapchinsky, developmental biologist M.M. Zavadovsky, physiologist L.V. Krushinsky, microbiologist S.M. Gershenson, biochemist V.A. Engelhardt, hydrobiologist G.G. Vinberg, cytologist M.A. Peshkov, and many other famous Soviet biologists. He made several fundamental discoveries; the first of them was the discovery of the cytoskeleton (1903). He was the first to formulate the idea of a crystal-like mechanism for copying inherited information (1927) and the principles of epigenetics (as well as the term itself, in 1934; it seems astonishing, but as early as 1915, he hypothesized that the gene methylation might be a mechanism of genetic variability). He started the work which later led his disciples V.V. Sakharov and I.A. Rapoport to the discovery of chemical mutagenesis. His research on sex regulation in silkworms was later successfully continued by B.L. Astaurov. Koltzoff encouraged S.S. Chetverikov, the entomologist, to study the genetics of natural Drosophila populations, which went on to form the basis of the Modern Synthesis reconciling Darwinian evolutionary theory and the Mendelian laws of heredity. Unfortunately, the name of N.K. Koltzoff has almost sunk into oblivion. This is largely due to the fact that mentioning his name was prohibited in the USSR over a long period of time, since he was a staunch opponent of Lysenko. In this paper dedicated to the 150th anniversary of Koltzoff, we briefly describe the milestones of the life and scientific research of this outstanding biologist and his scientific school.
Gregor Mendel and the theory of species multiplication
Authors: van Dijk Peter J , Noel Ellis T H
Published: March 2023

According to the revisionist interpretation of Mendel’s pea crosses, his primary aim was not to study the inheritance of traits. Instead, he was interested in the question raised by Linnaeus as to whether new species could arise from the hybridization of existing species. The genetic interpretation is therefore seen as ahistorical by the revisionists. This view goes back to the 1979 article “Mendel no Mendelian?” by the historian of science R.C. Olby. A closer analysis shows that Olby implicitly assumed Mendel adhered to the unusual strictest species definition for Pisum. However, we argue that Mendel only mentions the hypothetical application of this strict definition in his 1866 paper. Like most of his contemporaries, Mendel accepted variation within species where the differences between varieties and species were a matter of degree. After researching variable hybrids in peas (Pisum; 1854–1863), Mendel also studied constant hybrids in hawkweeds (Hieracium; 1866–1873), which he considered to be new species. There is no debate about the latter, but the matter becomes muddled because Olby lumps Pisum and Hieracium together, despite their having completely different reproduction systems. Based on newly discovered historical sources, we also dispute several other assumptions made by Olby. We do not consider Olby’s claim that Mendel conducted the Pisum experiments to investigate species multiplication to be tenable.
Distinct clusters of human pain gene orthologs in Caenorhabditis elegans regulate thermo-nociceptive sensitivity and plasticity
Authors: Jordan Aurore , Glauser Dominique A
Published: March 2023

The detection and avoidance of harmful stimuli are essential animal capabilities. The molecular and cellular mechanisms controlling nociception and its plasticity are conserved, genetically controlled processes of broad biomedical interest given their relevance to understand and treat pain conditions that represent a major health burden. Recent genome-wide association studies (GWAS) have identified a rich set of polymorphisms related to different pain conditions and pointed to many human pain gene candidates, whose connection to the pain pathways is however often poorly understood. Here, we used a computer-assisted Caenorhabditis elegans thermal avoidance analysis pipeline to screen for behavioral defects in a set of 109 mutants for genes orthologous to human pain-related genes. We measured heat-evoked reversal thermosensitivity profiles, as well as spontaneous reversal rate, and compared naïve animals with adapted animals submitted to a series of repeated noxious heat stimuli, which in wild type causes a progressive habituation. Mutations affecting 28 genes displayed defects in at least one of the considered parameters and could be clustered based on specific phenotypic footprints, such as high-sensitivity mutants, nonadapting mutants, or mutants combining multiple defects. Collectively, our data reveal the functional architecture of a network of conserved pain-related genes in C. elegans and offer novel entry points for the characterization of poorly understood human pain genes in this genetic model.