bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI‐Based Computer‐Aided Diagnostic Model to Predict Tumor Grading and Clinical Outcomes in Patients With Soft Tissue Sarcoma
Authors: Yang Yuhan , Zhou Yin , Zhou Chen , Zhang Xuemei , Ma Xuelei
Published: March 2022

Background

MRI acts as a potential resource for exploration and interpretation to identify tumor characterization by advanced computer‐aided diagnostic (CAD) methods.

Purpose

To evaluate and validate the performance of MRI‐based CAD models for identifying low‐grade and high‐grade soft tissue sarcoma (STS) and for investigating survival prognostication.

Study Type

Retrospective.

Subjects

A total of 540 patients (295 male/female: 295/245, median age: 42 years) with STSs.

Field Sequence

5‐T MRI with T1WI sequence and fat‐suppressed T2‐weighted (T2FS) sequence.

Assessment

Manual regions of interests (ROIs) were delineated for generation of radiomic features. Automatic segmentation and pretrained convolutional neural networks (CNNs) were performed for deep learning (DL) analysis. The last fully connected layer at the top of CNNs was removed, and the global max pooling was added to transform feature maps to numeric values. Tumor grade was determined on histological specimens.

Statistical Tests

The support vector machine was adopted as the classifier for all MRI‐based models. The DL signature was derived from the DL‐MRI model with the highest area under the curve (AUC). The significant clinical variables, tumor location and size, integrated with radiomics and DL signatures were ready for construction of clinical‐MRI nomogram to identify tumor grading. The prognostic value of clinical variables and these MRI‐based signatures for overall survival (OS) was evaluated via Cox proportional hazard.

Results

The clinical‐MRI differentiation nomogram represented an AUC of 0.870 in the training cohort, and an AUC of 0.855, accuracy of 79.01%, sensitivity of 79.03%, and specificity of 78.95% in the validation cohort. The prognostic model showed good performance for OS with 3‐year C‐index of 0.681 and 0.642 and 5‐year C‐index of 0.722 and 0.676 in the training and validation cohorts.

Data Conclusion

MRI‐based CAD nomogram represents effective abilities in classification of low‐grade and high‐grade STSs. The MRI‐based prognostic model yields favorable preoperative capacities to identify long‐term survivals for STSs.

Evidence Level

3

Technical Efficacy

Stage 4
Magnetic Resonance Imaging‐Based Nomogram to Antenatal Predict Cesarean Delivery for Cephalopelvic Disproportion in Primiparous Women
Authors: Chen Cheng , Yang Mengmeng , Zheng Weizeng , Yang Xiaofu , Chen Yuan , Dong Tian , Lv Min , Xi Fangfang , Jiang Ying , Ying Xia , Li Wen , Xu Jian , Zhao Baihui , Luo Qiong
Published: March 2022

Background

Cephalopelvic disproportion (CPD)‐related obstructed labor is associated with maternal and neonatal morbidity and mortality. Accurate prediction of whether a primiparous woman is at high risk of an unplanned cesarean delivery would be a major advance in obstetrics.

Purpose

To develop and validate a predictive model assessing the risk of cesarean delivery in primiparous women based on MRI findings.

Study Type

Prospective.

Population

A total of 150 primiparous women with clinical findings suggestive of CPD.

Field Strength/Sequence

T1‐weighted fast spin‐echo sequences, single‐shot fast spin‐echo (SSFSE) T2‐weighted sequences at 1.5 T.

Assessment

Pelvimetry and fetal biometry were assessed independently by two radiologists. A nomogram model combined that the clinical and MRI characteristics was constructed.

Statistical Tests

Univariable and multivariable logistic regression analyses were applied to select independent variables. Receiver operating characteristic (ROC) analysis was performed, and the discrimination of the model was assessed by the area under the curve (AUC). Calibration was assessed by calibration plots. Decision curve analysis was applied to evaluate the net clinical benefit. A P value below 0.05 was considered to be statistically significant.

Results

In multivariable modeling, the maternal body mass index (BMI) before delivery, bilateral femoral head distance, obstetric conjugate, fetal head circumference, and fetal abdominal circumference was significantly associated with the likelihood of cesarean delivery. The discrimination calculated as the AUC was 0.838 (95% confidence interval [CI]: 0.774–0.902). The sensitivity and specificity of the nomogram model were 0.787 and 0.764, and the positive predictive and negative predictive values were 0.696 and 0.840, respectively. The model demonstrated satisfactory calibration (calibration slope = 0.945). Moreover, the decision curve analysis proved the superior net benefit of the model compared with each factor included.

Data Conclusion

Our study might provide a nomogram model that could identify primiparous women at risk of cesarean delivery caused by CPD based on MRI measurements.

Evidence Level

2

Technical Efficacy

Stage 2
Strain‐dependent effectivity, and protective role against enzymes of S‐layers in Lactiplantibacillus plantarum strains
Authors: Alp Duygu
Published: March 2022

The present study investigated whether the surface layer (S‐layer), which is known to have a varying effect from strain to strain on aggregation, adhesion ability, also has an effect on the resistance of bacteria to digestive enzymes, phenol, lysozymes. The effect of S‐layers on the resistance against various enzymes, aggregation and adhesion abilities, and strain specificity were determined of eight Lactiplantibacillus plantarum strains. Strains were treated with 5 M lithium chloride (LiCl) to extract the S‐layers, the presence of this layer in those microorganisms was demonstrated by polyacrylamide gel electrophoresis. Scanning electron microscopy was used to visualize the separation of the S‐layer, which surrounds the microorganism, from the microorganism by the LiCl. The images were taken three times, once at the beginning, once 30 min later, and once at the end of this process, which took 2 h in total. The effect against enzymes varied depending on the strain, but it was determined that all the tested strains had a serious loss of viability against phenol in the absence of an S‐layer. Lpb. plantarum DA100 showed a maximum decrease against gastrointestinal system enzymes after the LiCl (96.48 ± 0.03% before and 66.46 ± 0.01% after LiCl). Lpb. plantarum DA255 showed a significant decrease against lysozyme (99.11 ± 0.00% before and 62.80 ± 0.0% after LiCl). Removal of the S‐layer greatly affected the adhesion ability of some strains, while for others there was hardly any change. The results showed that the role of the S‐layer may be strain‐specific, the rate of effect can vary. The primary function of S‐layer proteins is thought to contribute to the adhesion ability of bacteria. There are limited studies that have reported the protective property of this layer against various enzymes, however, our results showed that S‐layer could be one of the resistance strategies developed by bacteria against enzymes.
The effect of storage method on selected physicochemical and microbiological qualities of wild boar meat
Authors: Kasałka‐Czarna Natalia , Bilska Agnieszka , Biegańska‐Marecik Róża , Montowska Magdalena
Published: March 2022

BACKGROUND

This study investigated the influence of the storage method on the physicochemical characteristics and microbial growth of m. longissimus thoracis et lumborum (LTL), m. biceps femoris (BF) and m. vastus lateralis (VL) of wild boar. Muscles were stored in a vacuum (VAC), in a modified high‐oxygen atmosphere (MAP) or meat seasoning cabinet (DRY‐AGED) for 21 days.

RESULTS

Wild boar meat was characterised by a high protein and low fat content and a good amount of potassium, sodium, calcium, magnesium, zinc and iron. Significantly higher (P < 0.05) pH values were noted for DRY‐AGED muscles stored for 21 days (up to 5.89 for VL). On day 21, a significant decrease in pH was noted for all MAP muscles (down to 5.23 for BF). Storage losses due to desiccation and water loss were significantly higher for DRY‐AGED samples and ranged from 25.63% to 32.89% on day 21. MAP affected protein and lipid oxidation, which was also reflected in Warner–Bratzler shear force VAC and DRY‐AGED had positive results regarding tenderness, whereas on day 21 the MAP‐stored meat had toughened significantly (from 35.3 N to 50.7 N in LTL). Lipids were oxidised much faster than proteins during prolonged storage in MAP. Compared to the other methods, DRY‐AGED had the best effect on microbial growth.

CONCLUSION

These results indicate that the recommended methods for the storage of wild boar meat are either vacuum packing or dry ageing. The high oxygen content of MAP negatively affected the quality of wild boar meat and carried a risk of increased protein carbonylation. © 2022 Society of Chemical Industry.
Motivations and constraints of developing agritourism under the challenges of climate change: The case of Samoa
Authors: Pratt Stephen , Magbalot‐Fernandez Alminda , Ohe Yasuo
Published: March 2022

Agritourism has the potential to link agriculture with culture and tourism, as an alternative to 3S tourism. This study examines motivations, opportunities, and challenges of agritourism development in Samoa using a qualitative approach, under the challenges of climate change. The love of the land, education, culture, employment, additional income, and farming sustainability are the main motivations. Constraints were predominantly structural, which include excessive business regulations, a lack of funds to expand their agricultural activities, a limited labor force, and a lack of coordination between the public and private sectors. The ever‐present threat of climate change jeopardizes agriculture, tourism, and agritourism.
Medial Meniscal Extrusion Evaluation With Weight‐Bearing Ultrasound
Authors: Falkowski Anna L. , Jacobson Jon A. , Cresswell Mark , Bedi Asheesh , Kalia Vivek , Zhang Bin
Published: March 2022

Objectives

To compare medial meniscal extrusion on weight‐bearing ultrasound (US) with supine US and magnetic resonance (MR) imaging correlating with meniscal pathology and reported symptoms.

Methods

IRB approved study with informed consent. Patients obtaining routine knee MR imaging for suspected knee pathology were prospectively evaluated with supine and weight‐bearing US of the medial meniscus. Meniscal extrusion was measured independently by two fellowship‐trained musculoskeletal radiologists. Correlation was made to presence or absence of meniscal degeneration or tear on MR imaging, as well as reported symptoms. Statistical significance was calculated via intraclass correlation coefficient (ICC) and analysis of variance (ANOVA).

Results

Ninety‐nine knees from 95 subjects (50 males, 45 females; mean age 45 ± 15 years) were included. Mean medial meniscal extrusion measured at US for a normal meniscus (n = 36) was 0.8 mm when supine, increasing to 1.6 mm on weight‐bearing. Mean meniscal extrusion in subjects with mucoid degeneration (n = 20) and those with meniscal tears (n = 43) was 1.6 mm, increasing to 2.3 mm with weight bearing. Inter‐reader reliability showed ICC values of 0.853 to 0.940. There was a significant difference in medial meniscal extrusion comparing subjects with a normal medial meniscus at magnetic resonance imaging (MRI) and subjects with either meniscal degeneration or tear. There was no significant difference in degree of meniscal extrusion between subjects with meniscal degeneration or tear. There was trend of worsening symptoms and increasing functional limitations moving from normal meniscus to meniscal degeneration to meniscal tear.

Conclusions

A normal meniscus shows lesser mobility between supine and upright position, than a pathologic meniscus. Both mucoid degeneration and meniscal tear demonstrate extrusion in the supine position, which increases with weight‐bearing position.
HFCF‐Net: A hybrid‐feature cross fusion network for COVID‐19 lesion segmentation from CT volumetric images
Authors: Wang Yanting , Yang Qingyu , Tian Lixia , Zhou Xuezhong , Rekik Islem , Huang Huifang
Published: March 2022

Background

The coronavirus disease 2019 (COVID‐19) spreads rapidly across the globe, seriously threatening the health of people all over the world. To reduce the diagnostic pressure of front‐line doctors, an accurate and automatic lesion segmentation method is highly desirable in clinic practice.

Purpose

Many proposed two‐dimensional (2D) methods for sliced‐based lesion segmentation cannot take full advantage of spatial information in the three‐dimensional (3D) volume data, resulting in limited segmentation performance. Three‐dimensional methods can utilize the spatial information but suffer from long training time and slow convergence speed. To solve these problems, we propose an end‐to‐end hybrid‐feature cross fusion network (HFCF‐Net) to fuse the 2D and 3D features at three scales for the accurate segmentation of COVID‐19 lesions.

Methods

The proposed HFCF‐Net incorporates 2D and 3D subnets to extract features within and between slices effectively. Then the cross fusion module is designed to bridge 2D and 3D decoders at the same scale to fuse both types of features. The module consists of three cross fusion blocks, each of which contains a prior fusion path and a context fusion path to jointly learn better lesion representations. The former aims to explicitly provide the 3D subnet with lesion‐related prior knowledge, and the latter utilizes the 3D context information as the attention guidance of the 2D subnet, which promotes the precise segmentation of the lesion regions. Furthermore, we explore an imbalance‐robust adaptive learning loss function that includes image‐level loss and pixel‐level loss to tackle the problems caused by the apparent imbalance between the proportions of the lesion and non‐lesion voxels, providing a learning strategy to dynamically adjust the learning focus between 2D and 3D branches during the training process for effective supervision.

Result

Extensive experiments conducted on a publicly available dataset demonstrate that the proposed segmentation network significantly outperforms some state‐of‐the‐art methods for the COVID‐19 lesion segmentation, yielding a Dice similarity coefficient of 74.85%. The visual comparison of segmentation performance also proves the superiority of the proposed network in segmenting different‐sized lesions.

Conclusions

In this paper, we propose a novel HFCF‐Net for rapid and accurate COVID‐19 lesion segmentation from chest computed tomography volume data. It innovatively fuses hybrid features in a cross manner for lesion segmentation, aiming to utilize the advantages of 2D and 3D subnets to complement each other for enhancing the segmentation performance. Benefitting from the cross fusion mechanism, the proposed HFCF‐Net can segment the lesions more accurately with the knowledge acquired from both subnets.
Voxel‐wise supervised analysis of tumors with multimodal engineered features to highlight interpretable biological patterns
Authors: Escobar Thibault , Vauclin Sébastien , Orlhac Fanny , Nioche Christophe , Pineau Pascal , Champion Laurence , Brisse Hervé , Buvat Irène
Published: March 2022

Background

Translation of predictive and prognostic image‐based learning models to clinical applications is challenging due in part to their lack of interpretability. Some deep‐learning‐based methods provide information about the regions driving the model output. Yet, due to the high‐level abstraction of deep features, these methods do not completely solve the interpretation challenge. In addition, low sample size cohorts can lead to instabilities and suboptimal convergence for models involving a large number of parameters such as convolutional neural networks.

Purpose

Here, we propose a method for designing radiomic models that combines the interpretability of handcrafted radiomics with a sub‐regional analysis.

Materials and methods

Our approach relies on voxel‐wise engineered radiomic features with average global aggregation and logistic regression. The method is illustrated using a small dataset of 51 soft tissue sarcoma (STS) patients where the task is to predict the risk of lung metastasis occurrence during the follow‐up period.

Results

Using positron emission tomography/computed tomography and two magnetic resonance imaging sequences separately to build two radiomic models, we show that our approach produces quantitative maps that highlight the signal that contributes to the decision within the tumor region of interest. In our STS example, the analysis of these maps identified two biological patterns that are consistent with STS grading systems and knowledge: necrosis development and glucose metabolism of the tumor.

Conclusions

We demonstrate how that method makes it possible to spatially and quantitatively interpret radiomic models amenable to sub‐regions identification and biological interpretation for patient stratification.
Ultra‐high‐resolution depth‐encoding small animal PET detectors: Using GAGG and LYSO crystal arrays
Authors: Niu Ming , Liu Zheng , Kuang Zhonghua , Wang Xiaohui , Ren Ning , Sang Ziru , Wu San , Cong Longhan , Sun Tao , Hu Zhanli , Yang Yongfeng
Published: March 2022

Purpose

Small animal positron emission tomography (PET) scanners are widely used in current biomedical research. The study aimed to develop high‐efficiency and ultra‐high‐resolution detectors that could be used to develop a small animal PET scanner with high sensitivity and spatial resolution approaching to its physical limit.

Methods

Four crystal arrays were fabricated and measured in this study. Crystal arrays 1 and 2 consisted of 38 × 38 gadolinium aluminum gallium garnet (GAGG) and lutetium–yttrium oxyorthosilicate (LYSO) crystals of 0.4 × 0.4 × 20 mm3 size. Crystal array 3 consisted of 16 × 16 GAGG crystals of 0.3 × 0.3 × 20 mm3 size, and crystal array 4 consisted of 24 × 24 LYSO crystals 0.3 × 0.3 × 20 mm3 in size. The crystal arrays were dual‐ended readouts using 8 × 8 silicon photomultiplier (SiPM) arrays of 2 × 2 mm2 pixel area. The SiPM array was readout using a signal multiplexing circuit to convert the 64 output signals into four position‐encoding signals. The performances of the four detectors in terms of flood histogram, energy resolution, depth of interaction (DOI) resolution, and timing resolution were measured.

Results

The GAGG detectors provided better flood histograms, ∼30% higher photopeak amplitude, ∼20% higher energy resolution, ∼12% worse DOI resolution, and ∼15% worse timing resolution compared with LYSO detectors of the same crystal size. These four detectors provided DOI resolutions of <2 mm, energy resolutions of <22%, and timing resolutions of <1.6 ns. All crystals of 0.4 × 0.4 × 20 mm3 and 0.3 × 0.3 × 20 mm3 could be clearly resolved if the crystal array was 1 mm smaller in the four sides than that in the SiPM array.

Conclusions

High DOI resolution PET detectors were developed using both GAGG and LYSO arrays with crystal sizes of 0.3 and 0.4 mm, respectively, and a length of 20 mm. The detectors can be used in the future to develop small animal PET scanners, especially dedicated mouse imaging PET scanners, which can simultaneously achieve high sensitivity and ultra‐high spatial resolution.
In high‐grade ovarian carcinoma, platinum‐sensitive tumor recurrence and acquired‐resistance derive from quiescent residual cancer cells that overexpress CRYAB, CEACAM6, and SOX2
Authors: du Manoir Stanislas , Delpech Hélène , Orsetti Béatrice , Jacot William , Pirot Nelly , Noel Jean , Colombo Pierre‐Emmanuel , Sardet Claude , Theillet Charles
Published: March 2022

Most high‐grade ovarian carcinomas (HGOCs) are sensitive to carboplatin (CBP)‐based chemotherapy but frequently recur within 24 months. Recurrent tumors remain CBP‐sensitive and acquire resistance only after several treatment rounds. Recurrences arise from a small number of residual tumor cells not amenable to investigation in patients. We developed patient‐derived xenografts (PDXs) that allow the study of these different stages of CBP‐sensitive recurrence and acquisition of resistance. We generated PDX models from CBP‐sensitive and intrinsically resistant HGOC. PDXs were CBP‐ or mock‐treated and tumors were sampled, after treatment and at recurrence. We also isolated models with acquired‐resistance from CBP‐sensitive PDXs. Tumors were characterized at the histological and transcriptome levels. PDX models reproduced treatment response seen in the patients. CBP‐sensitive residual tumors contained nonproliferating tumor cell clusters embedded in a fibrotic mesh. In nontreated PDX tumors and treated CBP‐resistant tumors, fibrotic tissue was not prevalent. Residual tumors had marked differences in gene expression when compared to naïve and recurrent tumors, indicating downregulation of the cell cycle and proliferation and upregulation of interferon response and the epithelial–mesenchymal transition. This gene expression pattern resembled that described in embryonal diapause and ‘drug‐tolerant persister’ states. Residual and acquired‐resistance tumors share the overexpression of three genes: CEACAM6, CRYAB, and SOX2. Immunostaining analysis showed strong CEACAM6, CRYAB, and SOX2 protein expression in CBP‐sensitive residual and acquired‐resistance PDX, thus confirming the RNA profiling results. In HGOC PDX, CBP‐sensitive recurrences arise from a small population of quiescent, drug‐tolerant, residual cells embedded in a fibrotic mesh. These cells overexpress CEACAM6, CRYAB, and SOX2, whose overexpression is also associated with acquired resistance and poor patient prognosis. CEACAM6, CRYAB, and SOX2 may thus serve as a biomarker to predict recurrence and emergence of resistant disease in CBP‐treated HGOC patients. © 2022 The Pathological Society of Great Britain and Ireland.
Supporting practitioners in school‐based evaluations of autism spectrum disorders
Authors: Harry Sarah W. , Bates‐Brantley Kayla E. , Whitefield Breya L. , Dale Brittany A.
Published: March 2022

Students with autism spectrum disorder (ASD) have vastly different educational needs. Although some students with ASD may perform well across subjects within the general education classroom, other students with ASD may need more individualized support outside of the classroom. Historically, ASD assessments in schools have primarily focused on the measurement of cornerstone behaviors of ASD such as deficits in social communication and restricted or repetitive behaviors while underestimating the focus of academic skills even though both factors are required in the evaluation process and for an eligibility classification. The purpose of this article is to provide an overview of academic assessment practices in the schools by highlighting best practices in ASD evaluation, outlining ASD academic profiles and how to identify academic skill deficits, and reviewing the available literature that comes from different formal‐ and function‐based assessment practices that are commonly used in schools today. The authors also discuss how formal‐ and function‐based assessments both serve a purpose and are recommended to be used in conjunction with one another to best demonstrate a student's academic profile. Practitioners are ultimately encouraged to use a multi‐informant, multi‐modal approach when it comes to psychoeducational evaluations for individuals with ASD as it is evident that an individualized approach is essential due to the discrepancy of academic profiles related to this disability category as well as understanding that no measure is a perfect representation of any one skill.
Evaluation of cardiac parameters and other safety outcomes of brolucizumab treatment in patients with neovascular age‐related macular degeneration
Authors: Zakaria Nadia , Guerard Nicolas , Emanuelli Andres , Dugel Pravin , Watts Jen , Liew Melissa , Gekkieva Margarita , Hinder Markus
Published: March 2022

This was a prospective, single‐dose, single‐arm, open‐label, non‐randomized, multicenter clinical study to determine cardiovascular safety after a single brolucizumab 6 mg intravitreal injection in neovascular age‐related macular degeneration patients (N = 14). Electrocardiogram (ECG) data were collected at different time points using 12‐lead Holter and standard ECG, and patients were followed up to 8 days (end of study) for any signs of ocular and non‐ocular adverse events (AEs). No clinically meaningful changes were observed in cardiac parameters. No patient had a ≥30 msec change from baseline in heart rate–corrected QT using Fridericia's formula (QTcF), and no patient had a new QTcF value of ≥450 msec between 20 and 24 h after treatment. No deaths or serious AEs were reported during the study period. These results are in line with the absence of new cardiovascular safety signal based on the ECG recordings collected over the first year of the pivotal studies performed with brolucizumab in DME.

Trial Registration: ClinicalTrials.gov identifier: NCT03954626.
Cloning the barley nec3 disease lesion mimic mutant using complementation by sequencing
Authors: Rosignoli Serena , Cosenza Francesco , Moscou Matthew J. , Civolani Laura , Musiani Francesco , Forestan Cristian , Milner Sara Giulia , Savojardo Castrense , Tuberosa Roberto , Salvi Silvio
Published: March 2022

Disease lesion mimic (DLM) or necrotic mutants display necrotic lesions in the absence of pathogen infections. They can show improved resistance to some pathogens and their molecular dissection can contribute to revealing components of plant defense pathways. Although forward‐genetics strategies to find genes causal to mutant phenotypes are available in crops, these strategies require the production of experimental cross populations, mutagenesis, or gene editing and are time‐ and resource‐consuming or may have to deal with regulated plant materials. In this study, we described a collection of 34 DLM mutants in barley (Hordeum vulgare L.) and applied a novel method called complementation by sequencing (CBS), which enables the identification of the gene responsible for a mutant phenotype given the availability of two or more chemically mutagenized individuals showing the same phenotype. Complementation by sequencing relies on the feasibility to obtain all induced mutations present in chemical mutants and on the low probability that different individuals share the same mutated genes. By CBS, we identified a cytochrome P450 CYP71P1 gene as responsible for orange blotch DLM mutants, including the historical barley nec3 locus. By comparative phylogenetic analysis we showed that CYP71P1 gene family emerged early in angiosperm evolution but has been recurrently lost in some lineages including Arabidopsis thaliana (L.) Heynh. Complementation by sequencing is a straightforward cost‐effective approach to clone genes controlling phenotypes in a chemically mutagenized collection. The TILLMore (TM) collection will be instrumental for understanding the molecular basis of DLM phenotypes and to contribute knowledge about mechanisms of host–pathogen interaction.
'We must improve our pet poultry services'
Authors: Kodilinye‐Sims Henrietta , Royden Alex
Published: March 2022

Owners often struggle to access healthcare for pet poultry, but during the avian influenza outbreak, these birds have been neglected further by veterinary practices argue Henrietta Kodilinye‐Sims and Alex Royden. This must be addressed, both in the short term and for future provision of care.
Nonperturbative negative geometries: amplitudes at strong coupling and the amplituhedron
Authors: Arkani-Hamed Nima , Henn Johannes , Trnka Jaroslav
Published: March 2022

Abstract

The amplituhedron determines scattering amplitudes in planar $$ \mathcal{N} $$
N
= 4 super Yang-Mills by a single “positive geometry” in the space of kinematic and loop variables. We study a closely related definition of the amplituhedron for the simplest case of four-particle scattering, given as a sum over complementary “negative geometries”, which provides a natural geometric understanding of the exponentiation of infrared (IR) divergences, as well as a new geometric definition of an IR finite observable $$ \mathcal{F} $$
F
(g, z) — dually interpreted as the expectation value of the null polygonal Wilson loop with a single Lagrangian insertion — which is directly determined by these negative geometries. This provides a long-sought direct link between canonical forms for positive (negative) geometries, and a completely IR finite post-loop-integration observable depending on a single kinematical variable z, from which the cusp anomalous dimension Γcusp(g) can also be straightforwardly obtained. We study an especially simple class of negative geometries at all loop orders, associated with a “tree” structure in the negativity conditions, for which the contributions to $$ \mathcal{F} $$
F
(g, z) and Γcusp can easily be determined by an interesting non-linear differential equation immediately following from the combinatorics of negative geometries. This lets us compute these “tree” contributions to $$ \mathcal{F} $$
F
(g, z) and Γcusp for all values of the ‘t Hooft coupling. The result for Γcusp remarkably shares all main qualitative characteristics of the known exact results obtained using integrability.
BTK inhibition limits B-cell–T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy
Authors: Li Rui , Tang Hao , Burns Jeremy C. , Hopkins Brian T. , Le Coz Carole , Zhang Bo , de Barcelos Isabella Peixoto , Romberg Neil , Goldstein Amy C. , Banwell Brenda L. , Luning Prak Eline T. , Mingueneau Michael , Bar-Or Amit
Published: March 2022

Inhibition of Bruton’s Tyrosine Kinase (BTKi) is now viewed as a promising next-generation B-cell-targeting therapy for autoimmune diseases including multiple sclerosis (MS). Surprisingly little is known; however, about how BTKi influences MS disease-implicated functions of B cells. Here, we demonstrate that in addition to its expected impact on B-cell activation, BTKi attenuates B-cell:T-cell interactions via a novel mechanism involving modulation of B-cell metabolic pathways which, in turn, mediates an anti-inflammatory modulation of the B cells. In vitro, BTKi, as well as direct inhibition of B-cell mitochondrial respiration (but not glycolysis), limit the B-cell capacity to serve as APC to T cells. The role of metabolism in the regulation of human B-cell responses is confirmed when examining B cells of rare patients with mitochondrial respiratory chain mutations. We further demonstrate that both BTKi and metabolic modulation ex vivo can abrogate the aberrant activation and costimulatory molecule expression of B cells of untreated MS patients. Finally, as proof-of-principle in a Phase 1 study of healthy volunteers, we confirm that in vivo BTKi treatment reduces circulating B-cell mitochondrial respiration, diminishes their activation-induced expression of costimulatory molecules, and mediates an anti-inflammatory shift in the B-cell responses which is associated with an attenuation of T-cell pro-inflammatory responses. These data collectively elucidate a novel non-depleting mechanism by which BTKi mediates its effects on disease-implicated B-cell responses and reveals that modulating B-cell metabolism may be a viable therapeutic approach to target pro-inflammatory B cells.
Hypothermic circulatory arrest does not induce coagulopathy in vitro
Authors: Ise Hayato , Oyama Kyohei , Kunioka Shingo , Shirasaka Tomonori , Kanda Hirotsugu , Akhyari Payam , Kamiya Hiroyuki
Published: March 2022

Hypothermic circulatory arrest (HCA) is an essential procedure during aortic surgery to protect organs; however, hypothermia is believed to cause coagulopathy, which is a major fatal complication. This study aimed to clarify the impact of hypothermia on coagulation by eliminating clinical biases in vitro. In the hypothermic storage study, blood samples from five healthy volunteers were stored at 37 ℃ (group N) for 3 h or at 20 ℃ for 2 h, followed by 1 h of rewarming at 37 ℃ (group H). Thromboelastography was performed before and after 3 h of storage. In the mock circulation loop (MCL) study, blood samples were placed in the MCL and (a) maintained at 37 ℃ for 4 h (group N, n = 5), or (b) cooled to 20 ℃ to simulate HCA with a 0.1 L/min flow rate for 3 h and then rewarmed to 37 ℃ (group H, n = 5). The total MCL duration was 4 h, and the flow rate was maintained at 1 L/min, except during HCA. Blood samples collected 15 min after the beginning and end of MCL were subjected to standard laboratory tests and rotational thromboelastometry analyses. Hypothermia had no impact on coagulation in both the hypothermic storage and MCL studies. MCL significantly decreased the platelet counts and clot elasticity in the INTEM and EXTEM assays; however, there was no effect on fibrinogen contribution measured by FIBTEM. Hypothermia does not cause irreversible coagulopathy in vitro; however, MCL decreases coagulation due to the deterioration of platelets.
Quantifying the effects of environment and population diversity in multi-agent reinforcement learning
Authors: McKee Kevin R. , Leibo Joel Z. , Beattie Charlie , Everett Richard
Published: March 2022

Generalization is a major challenge for multi-agent reinforcement learning. How well does an agent perform when placed in novel environments and in interactions with new co-players? In this paper, we investigate and quantify the relationship between generalization and diversity in the multi-agent domain. Across the range of multi-agent environments considered here, procedurally generating training levels significantly improves agent performance on held-out levels. However, agent performance on the specific levels used in training sometimes declines as a result. To better understand the effects of co-player variation, our experiments introduce a new environment-agnostic measure of behavioral diversity. Results demonstrate that population size and intrinsic motivation are both effective methods of generating greater population diversity. In turn, training with a diverse set of co-players strengthens agent performance in some (but not all) cases.
Window dressing inequalities and constructing women farmers as problematic—gender in Rwanda’s agriculture policy
Authors: Andersson Karolin , Pettersson Katarina , Lodin Johanna Bergman
Published: March 2022

Rwanda is often depicted as a success story by policy makers when it comes to issues of gender. In this paper, we show how the problem of gendered inequality in agriculture nevertheless is both marginalized and instrumentalized in Rwanda’s agriculture policy. Our in-depth analysis of 12 national policies is informed by Bacchi’sWhat’s the problem represented to be?approach. It attests that gendered inequality is largely left unproblematized as well as reduced to a problem of women’s low agricultural productivity. The policy focuses on framing the symptoms and effects of gendered inequality and turns gender mainstreaming into an instrument for national economic growth. We argue that by insufficiently addressing the socio-political underlying causes of gendered inequality, Rwanda’s agriculture policy risks reproducing and exacerbating inequalities by reinforcing dominant gender relations and constructing women farmers as problematic and men as normative farmers. We call for the policy to approach gendered inequality in alternative ways. Drawing on perspectives in feminist political ecology, we discuss how such alternatives could allow policy to more profoundly challenge underlying structural constraints such as unequal gender relations of power, gender norms, and gender divisions of work. This would shift policy’s problematizing lens from economic growth to social justice, and from women’s shortcomings and disadvantages in agriculture to the practices and relations that perpetuate inequality. In the long term, this could lead to transformed gender norms and power relations, and a more just and equal future beyond what the dominant agricultural development discourse currently permits.
Stigma, Social Cohesion, and HIV Risk Among Sexual and Gender Minorities in Two Cities in Zimbabwe
Authors: Miller Sophia S. , Mantell Joanne E. , Parmley Lauren E. , Musuka Godfrey , Chingombe Innocent , Mapingure Munyaradzi , Rogers John H. , Wu Yingfeng , Hakim Avi J. , Mugurungi Owen , Samba Chesterfield , Harris Tiffany G.
Published: March 2022

Though stigma is a recognized contributor to the disproportionate HIV burden among sexual and gender minorities (SGM) in sub-Saharan Africa, data describing this association among Zimbabwean SGM are limited. We examined relationships between SGM stigma and HIV and the potential for social cohesion to moderate the association among Zimbabwean men who have sex with men, transgender women, and genderqueer individuals. Consenting participants (n = 1511) recruited through respondent-driven sampling for a biobehavioral survey in Harare and Bulawayo completed structured interviews and received HIV testing. Reported SGM stigma was common (68.9% in Harare and 65.3% in Bulawayo) and associated with HIV infection in Harare (adjusted prevalence ratio [aPR] = 1.82, 95% confidence interval [CI] = 1.27–2.62) and Bulawayo (aPR = 1.51, 95% CI = 1.15–2.00) in relative risk regression. Social cohesion did not moderate these relationships. Findings demonstrate stigma’s association with HIV vulnerability among Zimbabwean SGM, highlighting the need for stigma-mitigation to reduce HIV transmission in this population.
On the antiderivatives of xp/(1 − x) with an application to optimize loss functions for classification with neural networks
Authors: Knoblauch Andreas
Published: March 2022

Supervised learning in neural nets means optimizing synaptic weights W such that outputs y(x;W) for inputs x match as closely as possible the corresponding targets t from the training data set. This optimization means minimizing a loss function ${\mathscr{L}}(\mathbf {W})$
L
(
W
)
that usually motivates from maximum-likelihood principles, silently making some prior assumptions on the distribution of output errors y −t. While classical crossentropy loss assumes triangular error distributions, it has recently been shown that generalized power error loss functions can be adapted to more realistic error distributions by fitting the exponent q of a power function used for initializing the backpropagation learning algorithm. This approach can significantly improve performance, but computing the loss function requires the antiderivative of the function f(y) := yq− 1/(1 − y) that has previously been determined only for natural $q\in \mathbb {N}$
q
∈
ℕ
. In this work I extend this approach for rational q = n/2m where the denominator is a power of 2. I give closed-form expressions for the antiderivative ${\int \limits } f(y) dy$
∫
f
(
y
)
d
y
and the corresponding loss function. The benefits of such an approach are demonstrated by experiments showing that optimal exponents q are often non-natural, and that error exponents q best fitting output error distributions vary continuously during learning, typically decreasing from large q > 1 to small q < 1 during convergence of learning. These results suggest new adaptive learning methods where loss functions could be continuously adapted to output error distributions during learning.
Evaluating the discrimination ability of proper multi-variate scoring rules
Authors: Alexander C. , Coulon M. , Han Y. , Meng X.
Published: March 2022

Proper scoring rules are commonly applied to quantify the accuracy of distribution forecasts. Given an observation they assign a scalar score to each distribution forecast, with the lowest expected score attributed to the true distribution. The energy and variogram scores are two rules that have recently gained some popularity in multivariate settings because their computation does not require a forecast to have parametric density function and so they are broadly applicable. Here we conduct a simulation study to compare the discrimination ability between the energy score and three variogram scores. Compared with other studies, our simulation design is more realistic because it is supported by a historical data set containing commodity prices, currencies and interest rates, and our data generating processes include a diverse selection of models with different marginal distributions, dependence structure, and calibration windows. This facilitates a comprehensive comparison of the performance of proper scoring rules in different settings. To compare the scores we use three metrics: the mean relative score, error rate and a generalized discrimination heuristic. Overall, we find that the variogram score with parameter $$p=0.5$$

p
=
0.5

outperforms the energy score and the other two variogram scores.
Managing biological invasions: the cost of inaction
Authors: Ahmed Danish A. , Hudgins Emma J. , Cuthbert Ross N. , Kourantidou Melina , Diagne Christophe , Haubrock Phillip J. , Leung Brian , Liu Chunlong , Leroy Boris , Petrovskii Sergei , Beidas Ayah , Courchamp Franck
Published: March 2022

Ecological and socioeconomic impacts from biological invasions are rapidly escalating worldwide. While effective management underpins impact mitigation, such actions are often delayed, insufficient or entirely absent. Presently, management delays emanate from a lack of monetary rationale to invest at early invasion stages, which precludes effective prevention and eradication. Here, we provide such rationale by developing a conceptual model to quantify the cost of inaction, i.e., the additional expenditure due to delayed management, under varying time delays and management efficiencies. Further, we apply the model to management and damage cost data from a relatively data-rich genus (Aedesmosquitoes). Our model demonstrates that rapid management interventions following invasion drastically minimise costs. We also identify key points in time that differentiate among scenarios of timely, delayed and severely delayed management intervention. Any management action during the severely delayed phase results in substantial losses$$( > 50\%$$(>50%of the potential maximum loss). ForAedesspp., we estimate that the existing management delay of 55 years led to an additional total cost of approximately $ 4.57 billion (14% of the maximum cost), compared to a scenario with management action only seven years prior (< 1% of the maximum cost). Moreover, we estimate that in the absence of management action, long-term losses would have accumulated to US$ 32.31 billion, or more than seven times the observed inaction cost. These results highlight the need for more timely management of invasive alien species—either pre-invasion, or as soon as possible after detection—by demonstrating how early investments rapidly reduce long-term economic impacts.
Unethical Leadership: Review, Synthesis and Directions for Future Research
Authors: Hassan Sharfa , Kaur Puneet , Muchiri Michael , Ogbonnaya Chidiebere , Dhir Amandeep
Published: March 2022

The academic literature on unethical leadership is witnessing an upward trend, perhaps given the magnitude of unethical conduct in organisations, which is manifested in increasing corporate fraud and scandals in the contemporary business landscape. Despite a recent increase, scholarly interest in this area has, by and large, remained scant due to the proliferation of concepts that are often and mistakenly considered interchangeable. Nevertheless, scholarly investigation in this field of inquiry has picked up the pace, which warrants a critical appraisal of the extant research on unethical leadership. To this end, the current study systematically reviews the existing body of work on unethical leadership and offers a robust and multi-level understanding of the academic developments in this field. We organised the studies according to various themes focused on antecedents, outcomes and boundary conditions. In addition, we advance a multi-level conceptualisation of unethical leadership, which incorporates macro, meso and micro perspectives and, thus, provide a nuanced understanding of this phenomenon. The study also explicates critical knowledge gaps in the literature that could broaden the horizon of unethical leadership research. On the basis of these knowledge gaps, we develop potential research models that are well grounded in theory and capture the genesis of unethical leadership under our multi-level framework. Scholars and practitioners will find this study useful in understanding the occurrence, consequences and potential strategies to circumvent the negative effects of unethical leadership.
A Typology of Heritage Crime Victims
Authors: Poyser Bethan , Poyser Sam , Doak Jonathan
Published: March 2022

Heritage crime has to date received little criminological interest relative to other topics within the discipline. Therefore, the current literature on the area is limited. Victims of heritage crime are significantly under-represented in the current body of literature, and empirical research on heritage crime and victimisation is lacking; as is any theoretical development of the phenomenon. This article makes small steps towards addressing some of the substantial gaps relating to heritage crime victimisation in presenting the first typology of heritage crime victims. This typology is the result of research conducted across England and Wales with a sample of heritage practitioners, police officers, and heritage crime victims. Based on the research conducted, we hope to contribute towards the body of police and heritage practitioner knowledge concerning victims of heritage crime. The typology may, with further research, be applied or adapted to include heritage crime victims across the globe.
Tradeable Nitrogen Abatement Practices for Diffuse Agricultural Emissions: A ‘Smart Market’ Approach
Authors: Hasan Syezlin , Hansen Line Block , Smart James C. R. , Hasler Berit , Termansen Mette
Published: March 2022

Markets in pollution permits for managing environmental quality have been advocated by economists since early 1970s as a mechanism that can deliver pollution reduction targets at lower cost to regulated entities than traditional uniform command-and control approaches. This study explores whether a ‘smart market’ cap-and-trade scheme between non-point sources can offer meaningful, robust and policy amenable, advantages over alternative approaches for nitrogen management in a realistic setting: 6504 individual farms in Limfjorden catchment, Denmark. The scheme involves multilateral trading of nitrogen emission rights among farms via changes in agricultural land management practices under a catchment-level cap on total nitrogen load. In this, the first exploration of non-point to non-point smart market nitrogen trading in a real setting, we estimate efficiency gains compared to uniform command-and-control regulation, explore the robustness of these gains in the face of non-participation, and reflect on farmers’ potential acceptance of the trading market in comparison with its command-and-control analog: spatially-targeted regulation, implemented via location-specific limits on nitrogen leaching. Results indicate that the smart market has the potential to substantially reduce the cost of meeting the catchment’s nitrogen reduction target. For a 21.5% reduction from baseline nitrogen load, the market delivers cost savings of 56% (DKK273 million, €36.6 million) compared to uniform regulation, with participating farms realising a mean net benefit of DKK 723/ha (€ 97/ha). Market performance is relatively robust against transaction cost; when delivering a 21.5% reduction in nitrogen load to Limfjorden, approximately 70% of the overall efficiency gain could be retained if only 24% of farms engaged with the market.