bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity and validation in archetype analysis: practical assessment framework and guidelines
Authors: Piemontese Luigi , Neudert Regina , Oberlack Christoph , Pedde Simona , Roggero Matteo , Buchadas Ana , Martin Dominic A , Orozco Richard , Pellowe Kara , Segnon Alcade C , Zarbá Lucía , Sietz Diana
Published: January 2022

Archetype analysis is a promising approach in sustainability science to identify patterns and explain mechanisms shaping the sustainability of social-ecological systems. Although considerable efforts have been devoted to developing quality standards and methodological advances for archetype analysis, archetype validation remains a major challenge. Drawing on the insights from two international workshops on archetype analysis and on broader literature on validity, we propose a framework that identifies and describes six dimensions of validity: conceptual; construct; internal; external; empirical; and application validity. We first discuss the six dimensions in relation to different methodological approaches and purposes of archetype analysis. We then present an operational use of the framework for researchers to assess the validity of archetype analysis and to support sound archetype identification and policy-relevant applications. Finally, we apply our assessment to 18 published archetype analyses, which we use to describe the challenges and insights in validating the different dimensions and suggest ways to holistically improve the validity of identified archetypes. With this, we contribute to more rigorous archetype analyses, helping to develop the potential of the approach for guiding sustainability solutions.
Improvement of impact toughness by microstructure refinement of simulated CGHAZ through enhancing welding heat input of low carbon Mo-V-Ti-N-B steel
Authors: Fan Huibing , Shi Genhao , Wang Qiuming , Wang Leping , Wang Qingfeng , Zhang Fucheng
Published: January 2022

Welding heat input greatly influences the microstructure and impacts the affected zone’s toughness. To interpret the relationships between the welding heat input, microstructure, and low-temperature toughness of the coarse-grained heat-affected zone (CGHAZ) of Mo-V-Ti-N-B steels, welding heat cycles with different heat inputs (25–75 kJ cm−1) were performed on a Gleeble 3500 simulator. Intragranular ferrite in the simulated samples subjected to different thermal cycles was characterized and quantified, and the impact energies of simulated samples were evaluated at −20 °C. Upon increasing the heat input, the intragranular ferrite content rose sharply from 4.3% to 76.0%. The V(C, N) enrichment on the precipitate surface increased the size of precipitates, providing favourable nucleation conditions for intragranular ferrite. The prior austenite grain (PAG) and martensite/austenite (M/A) constituents became rough, and the content of the M/A constituent increased while the impact energy of the CGHAZ increased. This behaviour occurred due to the formation of intragranular acicular ferrite (IGAF), which refined the microstructure of the CGHAZ. Grain refinement eliminated the negative influence of higher M/A content on the impact toughness of the CGHAZ.
Design and modeling of a high resolution and high sensitivity PET brain scanner with double-ended readout
Authors: Layden Christopher , Klein Kyle , Matava William , Sadam Akhil , Abouzahr Firas , Proga Marek , Majewski Stanislaw , Nuyts Johan , Lang Karol
Published: January 2022

In the wake of recent advancements in scintillator, photodetector, and low-noise fast electronics technologies, as well as in fast reconstruction software, positron emission tomography (PET) scanners have seen considerable improvements in spatial resolution, time resolution, and absolute sensitivity. To continue this trend, we present a helmet type PET brain scanner design that combines high solid angle coverage and double-ended readout of 30 mm-thick scintillator crystals to achieve excellent absolute sensitivity, depth of interaction resolution, and time resolution. This scanner comprises 598 detector arrays, each with 8 × 8 Lu1.8Y0.2SiO5:Ce (LYSO:Ce) crystals with dimensions 3.005 × 3.005 × 30 mm3 one-to-one coupled on either end to silicon photomultipliers (SiPMs). Our Monte Carlo simulations based in the platform Geant4 predict that this scanner would attain an absolute sensitivity to a 35 cm line source placed at the center of the radial field of view of (17.1 ± 0.1)%, a depth of interaction resolution of (3.99 ± 0.05) mm, and a coincidence time resolution of (198 ± 5) ps. Our simulations also predict radial, tangential, and axial spatial resolutions at the center of the field of view of 3.3 mm, 3.1 mm, and 3.3 mm, respectively. As this set of simultaneous parameters compares favorably to today’s most advanced clinical PET scanners and other proposed designs, this scanner has a good chance of becoming a preferred tool for high quality brain imaging.
Neutron yield measurement system of HL-2A tokamak
Authors: YUAN Guoliang , WEN Zuowei , WEI Lingfeng , ZHANG Jinwen , YANG Qingwei
Published: January 2022

This research presents the development of HL-2A neutron yield measurement which includes 235U fission chamber and BF3 and 3He proportional counters. Equivalent noise formula of the radiation detection signal amplification system was derived to guide the development of the signal amplification system. Then all detectors were calibrated in situ by using the 252Cf neutron source. The neutron yield of the HL-2A during neutral beam heating was analyzed. These results indicate that the developed neutron flux diagnostic system can obtain neutron yield results under various experimental conditions of the HL-2A tokamak, and can provide information on neutron yield.
Sample complexity of learning parametric quantum circuits
Authors: Cai Haoyuan , Ye Qi , Deng Dong-Ling
Published: January 2022

Quantum computers hold unprecedented potentials for machine learning applications. Here, we prove that physical quantum circuits are probably approximately correct learnable on a quantum computer via empirical risk minimization: to learn a parametric quantum circuit with at most n

c
gates and each gate acting on a constant number of qubits, the sample complexity is bounded by

O

~

(

n

c
+
1

)

. In particular, we explicitly construct a family of variational quantum circuits with O(n

c+1) elementary gates arranged in a fixed pattern, which can represent all physical quantum circuits consisting of at most n

c
elementary gates. Our results provide a valuable guide for quantum machine learning in both theory and practice.
New procedure to estimate plasma parameters through the q-Weibull distribution by using a Langmuir probe in a cold plasma
Authors: Gonzalez F J , Gonzalez J I , Soler S , Repetto C E , Gómez B J , Berdichevsky D B
Published: January 2022

We describe a procedure to obtain the plasma parameters from theI-VLangmuir curve by using the Druyvesteyn equation. We propose to include two new parameters,qandr, to the usual plasma parameters: plasma potential (Vp), floating potential (Vf), electron density (n), and electron temperature (T). These new parameters can be particularly useful to represent non-Maxwellian distributions. The procedure is based on the fit of theI-VLangmuir curve with theq-Weibull distribution function, and is motivated by recent works which use theq-exponential distribution function derived from Tsallis statistics. We obtain the usual plasma parameters employing three techniques: the numerical differentiation using Savitzky Golay (SG) filters, theq-exponential distribution function, and theq-Weibull distribution function. We explain the limitations of theq-exponential function, where the experimental dataV>Vpneeds to be trimmed beforehand, and this results in a lower accuracy compared to the numerical differentiation with SG. To overcome this difficulty, theq-Weibull function is introduced as a natural generalization to theq-exponential distribution, and it has greater flexibility in order to represent the concavity change aroundVp. We apply this procedure to analyze the measurements corresponding to a nitrogenN2cold plasma obtained by using a single Langmuir probe located at different heights from the cathode. We show that theqparameter has a very stable numerical value with the height. This work may contribute to clarify some advantages and limitations of the use of non-extensive statistics in plasma diagnostics, but the physical interpretation of the non-extensive parameters in plasma physics remains not fully clarified, and requires further research.
New estimates for the maximal functions and applications
Authors: Domínguez Óscar , Tikhonov Sergey
Published: January 2022

In this paper we study sharp pointwise inequalities for maximal operators. In particular, we strengthen DeVore’s inequality for the moduli of smoothness and a logarithmic variant of Bennett–DeVore–Sharpley’s inequality for rearrangements. As a consequence, we improve the classical Stein–Zygmund embedding deriving
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. Moreover, these results are also applied to establish new Fefferman–Stein inequalities, Calderón–Scott type inequalities, and extrapolation estimates. Our approach is based on the limiting interpolation techniques.
Homology-directed repair involves multiple strand invasion cycles in fission yeast
Authors: Vines Amanda J. , Cox Kenneth , Leland Bryan A. , King Megan C.
Published: January 2022

A live-cell assay is developed to monitor interhomologue repair of a DNA double-strand break in Schizosaccharomyces pombe, revealing that multiple cycles of homology search and strand invasion occur during repair. It is proposed that these dynamics reflect a preference for repair by synthesis-dependent strand annealing in fission yeast.
Endosomal cargo recycling mediated by Gpa1 and phosphatidylinositol 3-kinase is inhibited by glucose starvation
Authors: Laidlaw Kamilla M. E. , Paine Katherine M. , Bisinski Daniel D. , Calder Grant , Hogg Karen , Ahmed Sophia , James Sally , O’Toole Peter J. , MacDonald Chris
Published: January 2022

It is shown that glucose starvation elevates the Gα subunit Gpa2, which inhibits PI3K activity and endosomal recycling. Increased Gpa2 binds the PI3K effector Gpa1 at the surface, perturbing endosomal PtdIns3P production and inhibiting cargo recycling. Inhibition of recycling promotes cargo degradation in response to glucose starvation.
Learning about sites of care for older adults: a jigsaw educational session for medical students
Authors: Goreshnik Ashley , Corey Matthew T , Rhodes Kropf Jennifer , Schwartz Andrea Wershof
Published: January 2022

Choosing the appropriate site of care for patients is a vital clinical skill when caring for older adults. For better patient safety and smoother transitions of care, we need improved curricula to train clinicians about the system of sites and services where older adults receive care. Here we present an innovative introduction for medical trainees to the complexities of long-term and post-acute care for geriatric patients. Students participated in a team-based ‘jigsaw’ learning activity, in which each team researched a particular site of care and then taught a larger group of their peers about that site. It was subsequently converted to a virtual format due to COVID-19. The activity was assessed using students’ written feedback and satisfaction scores. Students enjoyed the interactivity and hands-on approach, giving the activity an average score of 3.9 out of 5 (1 = ‘poor’; 5 = ‘excellent’). The jigsaw provided an engaging, case-based foundation for learning about sites of care and was well-received by students.
Genomic Profiling of Metastatic Uveal Melanoma Shows Frequent Coexisting BAP1 or SF3B1 and GNAQ/GNA11 Mutations and Correlation With Prognosis
Authors: Isaacson Alexandra L , Sompallae Ramakrishna R , Guseva Natalya V , Bellizzi Andrew M , Bossler Aaron D , Ma Deqin
Published: January 2022

Objectives

To identify therapeutic targets and correlate with clinical outcomes from mutation profiling of metastatic uveal melanoma (UM) using next-generation sequencing (NGS).

Methods

Melanoma cases that were tested using DNA-based NGS panels of 25 and/or 214 genes were evaluated retrospectively (263 cases) and identified 27 UM cases. BAP1 expression was examined by immunohistochemistry.

Results

Mutations in GNA11 (14) and GNAQ (12) were found in 96% (n = 27) of cases of UM, and most had coexisting BAP1 (17) or SF3B1 (4) mutations. Coexisting GNAQ/11-SF3B1 mutations correlated with a longer average time to first metastasis compared with GNAQ/11-BAP1 mutations (99.7 vs 38.5 months, P = .047). Three patients with BAP1 mutations received trametinib; two are still alive (15 months; 23 months), and one died (32 months). In non-UMs, only 4.2% (n = 236) had BAP1 and 3.8% had SF3B1 mutations; none had coexisting GNAQ/11 mutations.

Conclusions

Coexisting BAP1/SF3B1 and GNAQ/11 mutations were unique to UM. SF3B1 mutations were reported to be UM-specific in melanoma and associated with rare/no metastasis. The finding of mutated SF3B1 in 14.8% (n = 27) of UMs suggests its role should be further evaluated. The correlation of BAP1/SF3B1 mutation with survival also warrants investigation.
Effects of primary seed dormancy on lifetime fitness of Arabidopsis thaliana in the field
Authors: Postma Froukje M , Ågren Jon
Published: January 2022

Background and Aims

Seed dormancy determines the environmental niche of plants in seasonal environments, and has consequences for plant performance that potentially go far beyond the seed and seedling stages. In this study, we examined the cascading effects of seed dormancy on the expression of subsequent life-history traits and fitness in the annual herb Arabidopsis thaliana.

Methods

We planted seeds of >200 recombinant inbred lines (RILs) derived from a cross between two locally adapted populations (Italy and Sweden), and both parental genotypes at the native site of the Swedish population in three consecutive years. We quantified the relationship between primary seed dormancy and the expression of subsequent life-history traits and fitness in the RIL population with path analysis. To examine the effects of differences in dormancy on the relative fitness of the two parental genotypes, we planted dormant seeds during the seed dispersal period and non-dormant seeds during the germination period of the local population.

Key Results

In the RIL population, strong primary dormancy was associated with high seedling survival, but with low adult survival and fecundity, and path analysis indicated that this could be explained by effects on germination timing, rosette size and flowering start. The relationship between primary seed dormancy and germination proportion varied among years, and this was associated with differences in seasonal changes in soil moisture. The planting of dormant and non-dormant seeds indicated that the lower primary dormancy of the local Swedish genotype contributed to its higher germination proportion in two years and to its higher fecundity in one year.

Conclusions

Our results show that seed dormancy affects trait expression and fitness components across the life cycle, and suggest that among-year variation in the incidence of drought during the germination period should be considered when predicting the consequences of climatic change for population growth and evolution.
SCAT5 Sex Differences: Normative Data, Clinical Thresholds, and Relevance for Identification of Concussion
Authors: Bailey Christopher , Meyer Jessica , Soden Daniel , Tangen Christopher , Deane Ryan , Briskin Susannah , Gunstad John , Fastenau Philip , Smith Paul , Solomon Mary , Kelly Amanda Weiss
Published: January 2022

Objective

This study evaluated sex differences in performance on the Sport Concussion Assessment Tool–5 (SCAT5) Standardized Assessment of Concussion (SAC) and in baseline SCAT5 symptom reporting. It established clinically relevant cut points for low performance on the SAC based on both reliable chance indices (RCIs) and normative performance. This study also evaluated the diagnostic utility of the sex-adjusted SCAT5 SAC for identification of suspected concussion in collegiate athletes.

Method

In total, 671 uninjured collegiate athletes were administered the SCAT5 and 264 of these athletes also completed SCAT5 testing ~1 year later. Fifty-four athletes were administered the SCAT5 after being removed from play due to suspected concussion. Sex differences in cognitive performance and symptom reporting at baseline were evaluated and sex-specific clinically relevant cut points were provided. Chi square and logistic regression models were used to evaluate if SAC performance was a significant predictor of concussion status.

Results

Female athletes outperformed male athletes on the SCAT 5 SAC and showed minimally higher symptom endorsement. Use of sex-corrected normative data improved performance of the SAC in identification of suspected concussion when a low score cut point was used. Logistic regression models showed that sex-corrected SAC change from baseline (RCI) improved the predictive value of the model after first accounting for other elements of the SCAT5.

Conclusions

Present results support the use of sex-specific normative data for the SCAT5 SAC, particularly if using low performance without comparison to a baseline; however, reliable change from a pre-injury baseline may have somewhat higher diagnostic utility.
MHCRoBERTa: pan-specific peptide–MHC class I binding prediction through transfer learning with label-agnostic protein sequences
Authors: Wang Fuxu , Wang Haoyan , Wang Lizhuang , Lu Haoyu , Qiu Shizheng , Zang Tianyi , Zhang Xinjun , Hu Yang
Published: January 2022

Predicting the binding of peptide and major histocompatibility complex (MHC) plays a vital role in immunotherapy for cancer. The success of Alphafold of applying natural language processing (NLP) algorithms in protein secondary struction prediction has inspired us to explore the possibility of NLP methods in predicting peptide–MHC class I binding. Based on the above motivations, we propose the MHCRoBERTa method, RoBERTa pre-training approach, for predicting the binding affinity between type I MHC and peptides. Analysis of the results on benchmark dataset demonstrates that MHCRoBERTa can outperform other state-of-art prediction methods with an increase of the Spearman rank correlation coefficient (SRCC) value. Notably, our model gave a significant improvement on IC50 value. Our method has achieved SRCC value and AUC value as 0.785 and 0.817, respectively. Our SRCC value is 14.3% higher than NetMHCpan3.0 (the second highest SRCC value on pan-specific) and is 3% higher than MHCflurry (the second highest SRCC value on all methods). The AUC value is also better than any other pan-specific methods. Moreover, we visualize the multi-head self-attention for the token representation across the layers and heads by this method. Through the analysis of the representation of each layer and head, we can show whether the model has learned the syntax and semantics necessary to perform the prediction task well. All these results demonstrate that our model can accurately predict the peptide–MHC class I binding affinity and that MHCRoBERTa is a powerful tool for screening potential neoantigens for cancer immunotherapy. MHCRoBERTa is available as an open source software at github (https://github.com/FuxuWang/MHCRoBERTa).
Deciphering the etiology and role in oncogenic transformation of the CpG island methylator phenotype: a pan-cancer analysis
Authors: Yates Josephine , Boeva Valentina
Published: January 2022

Numerous cancer types have shown to present hypermethylation of CpG islands, also known as a CpG island methylator phenotype (CIMP), often associated with survival variation. Despite extensive research on CIMP, the etiology of this variability remains elusive, possibly due to lack of consistency in defining CIMP. In this work, we utilize a pan-cancer approach to further explore CIMP, focusing on 26 cancer types profiled in the Cancer Genome Atlas (TCGA). We defined CIMP systematically and agnostically, discarding any effects associated with age, gender or tumor purity. We then clustered samples based on their most variable DNA methylation values and analyzed resulting patient groups. Our results confirmed the existence of CIMP in 19 cancers, including gliomas and colorectal cancer. We further showed that CIMP was associated with survival differences in eight cancer types and, in five, represented a prognostic biomarker independent of clinical factors. By analyzing genetic and transcriptomic data, we further uncovered potential drivers of CIMP and classified them in four categories: mutations in genes directly involved in DNA demethylation; mutations in histone methyltransferases; mutations in genes not involved in methylation turnover, such as KRAS and BRAF; and microsatellite instability. Among the 19 CIMP-positive cancers, very few shared potential driver events, and those drivers were only IDH1 and SETD2 mutations. Finally, we found that CIMP was strongly correlated with tumor microenvironment characteristics, such as lymphocyte infiltration. Overall, our results indicate that CIMP does not exhibit a pan-cancer manifestation; rather, general dysregulation of CpG DNA methylation is caused by heterogeneous mechanisms.
Multi-variable AUC for sifting complementary features and its biomedical application
Authors: Su Yue , Du Keyu , Wang Jun , Wei Jin-mao , Liu Jian
Published: January 2022

Although sifting functional genes has been discussed for years, traditional selection methods tend to be ineffective in capturing potential specific genes. First, typical methods focus on finding features (genes) relevant to class while irrelevant to each other. However, the features that can offer rich discriminative information are more likely to be the complementary ones. Next, almost all existing methods assess feature relations in pairs, yielding an inaccurate local estimation and lacking a global exploration. In this paper, we introduce multi-variable Area Under the receiver operating characteristic Curve (AUC) to globally evaluate the complementarity among features by employing Area Above the receiver operating characteristic Curve (AAC). Due to AAC, the class-relevant information newly provided by a candidate feature and that preserved by the selected features can be achieved beyond pairwise computation. Furthermore, we propose an AAC-based feature selection algorithm, named Multi-variable AUC-based Combined Features Complementarity, to screen discriminative complementary feature combinations. Extensive experiments on public datasets demonstrate the effectiveness of the proposed approach. Besides, we provide a gene set about prostate cancer and discuss its potential biological significance from the machine learning aspect and based on the existing biomedical findings of some individual genes.
Shedding light on the hidden human proteome expands immunopeptidome in cancer
Authors: Li Yongsheng , Zhang Yunpeng , Pan Tao , Zhou Ping , Zhou Weiwei , Gao Yueying , Zheng Shaojiang , Xu Juan
Published: January 2022

Unrestrained cellular growth and immune escape of a tumor are associated with the incidental errors of the genome and transcriptome. Advances in next-generation sequencing have identified thousands of genomic and transcriptomic aberrations that generate variant peptides that assemble the hidden proteome, further expanding the immunopeptidome. Emerging next-generation sequencing technologies and a number of computational methods estimated the abundance of immune infiltration from bulk transcriptome have advanced our understanding of tumor microenvironments. Here, we will characterize several major types of tumor-specific antigens arising from single-nucleotide variants, insertions and deletions, gene fusion, alternative splicing, RNA editing and non-coding RNAs. Finally, we summarize the current state-of-the-art computational and experimental approaches or resources and provide an integrative pipeline for the identification of candidate tumor antigens. Together, the systematic investigation of the hidden proteome in cancer will help facilitate the development of effective and durable immunotherapy targets for cancer.
GenomeTornadoPlot: a novel R package for CNV visualization and focality analysis
Authors: Hong Chen , Thiele Robin , Feuerbach Lars
Published: January 2022

Motivation

Analysis of focal copy number variations (CNVs) is highly relevant for cancer research, as they pinpoint driver genes. More specifically, due to selective pressure oncogenes and tumor suppressor genes are more often affected by these events than neighboring passengers. In cases where multiple candidates co-reside in a genomic locus, careful comparison is required to either identify multigenic minimally deleted regions of synergistic co-mutations, or the true single driver gene. The study of focal CNVs in large cancer genome cohorts requires specialized visualization and statistical analysis.

Results

We developed the GenomeTornadoPlot R-package which generates gene-centric visualizations of CNV types, locations and lengths from cohortwise NGS data. Furthermore, the software enables the pairwise comparison of proximate genes to identify co-mutation patterns or driver-passenger hierarchies. The visual examination provided by GenomeTornadoPlot is further supported by adaptable local and global focality scoring. Integrated into the GenomeTornadoPlot R-Package is the comprehensive PCAWG database of CNVs, comprising 2976 cancer genome entities from 46 cohorts of the Pan-cancer Analysis of Whole Genomes project. The GenomeTornadoPlot R-package can be used to perform exploratory or hypothesis-driven analyses on the basis of the PCAWG data or in combination with data provided by the user.

Availability and implementation

GenomeTornadoPlot is written in R script and released via github: . The package is under the license of GPL-3.0.
SPOT-Contact-LM: improving single-sequence-based prediction of protein contact map using a transformer language model
Authors: Singh Jaspreet , Litfin Thomas , Singh Jaswinder , Paliwal Kuldip , Zhou Yaoqi
Published: January 2022

Motivation

Accurate prediction of protein contact-map is essential for accurate protein structure and function prediction. As a result, many methods have been developed for protein contact map prediction. However, most methods rely on protein-sequence-evolutionary information, which may not exist for many proteins due to lack of naturally occurring homologous sequences. Moreover, generating evolutionary profiles is computationally intensive. Here, we developed a contact-map predictor utilizing the output of a pre-trained language model ESM-1b as an input along with a large training set and an ensemble of residual neural networks.

Results

We showed that the proposed method makes a significant improvement over a single-sequence-based predictor SSCpred with 15% improvement in the F1-score for the independent CASP14-FM test set. It also outperforms evolutionary-profile-based methods trRosetta and SPOT-Contact with 48.7% and 48.5% respective improvement in the F1-score on the proteins without homologs (Neff = 1) in the independent SPOT-2018 set. The new method provides a much faster and reasonably accurate alternative to evolution-based methods, useful for large-scale prediction.

Availability and implementation

Stand-alone-version of SPOT-Contact-LM is available at https://github.com/jas-preet/SPOT-Contact-Single. Direct prediction can also be made at https://sparks-lab.org/server/spot-contact-single. The datasets used in this research can also be downloaded from the GitHub.

Supplementary information

Supplementary data are available at Bioinformatics online.
Functional hybrid factor regression model for handling heterogeneity in imaging studies
Authors: Huang C , Zhu H
Published: January 2022

This paper develops a functional hybrid factor regression modelling framework to handle the heterogeneity of many large-scale imaging studies, such as the Alzheimer’s disease neuroimaging initiative study. Despite the numerous successes of those imaging studies, such heterogeneity may be caused by the differences in study environment, population, design, protocols or other hidden factors, and it has posed major challenges in integrative analysis of imaging data collected from multicentres or multistudies. We propose both estimation and inference procedures for estimating unknown parameters and detecting unknown factors under our new model. The asymptotic properties of both estimation and inference procedures are systematically investigated. The finite-sample performance of our proposed procedures is assessed by using Monte Carlo simulations and a real data example on hippocampal surface data from the Alzheimer’s disease study.
Postoperative mortality risk assessment in colorectal cancer: development and validation of a clinical prediction model using data from the Dutch ColoRectal Audit
Authors: de Nes Lindsey C. F. , Hannink Gerjon , ‘t Lam-Boer Jorine , Hugen Niek , Verhoeven Rob H. , de Wilt Johannes H. W. ,   Dutch Colorectal Audit Group
Published: January 2022

Background

As the outcome of modern colorectal cancer (CRC) surgery has significantly improved over the years, however, renewed and adequate risk stratification for mortality is important to identify high-risk patients. This population-based study was conducted to analyse postoperative outcomes in patients with CRC and to create a risk model for 30-day mortality.

Methods

Data from the Dutch Colorectal Audit were used to assess differences in postoperative outcomes (30-day mortality, hospital stay, blood transfusion, postoperative complications) in patients with CRC treated from 2009 to 2017. Time trends were analysed. Clinical variables were retrieved (including stage, age, sex, BMI, ASA grade, tumour location, timing, surgical approach) and a prediction model with multivariable regression was computed for 30-day mortality using data from 2009 to 2014. The predictive performance of the model was tested among a validation cohort of patients treated between 2015 and 2017.

Results

The prediction model was obtained using data from 51 484 patients and the validation cohort consisted of 32 926 patients. Trends of decreased length of postoperative hospital stay and blood transfusions were found over the years. In stage I–III, postoperative complications declined from 34.3 per cent to 29.0 per cent (P < 0.001) over time, whereas in stage IV complications increased from 35.6 per cent to 39.5 per cent (P = 0.010). Mortality decreased in stage I–III from 3.0 per cent to 1.4 per cent (P < 0.001) and in stage IV from 7.6 per cent to 2.9 per cent (P < 0.001). Eight factors, including stage, age, sex, BMI, ASA grade, tumour location, timing, and surgical approach were included in a 30-day mortality prediction model. The results on the validation cohort documented a concordance C statistic of 0.82 (95 per cent c.i. 0.80 to 0.83) for the prediction model, indicating good discriminative ability.

Conclusion

Postoperative outcome improved in all stages of CRC surgery in the Netherlands. The developed model accurately predicts postoperative mortality risk and is clinically valuable for decision-making.
Risk-adjusted mortality in severely injured adult trauma patients in Sweden
Authors: Strömmer Lovisa , Lundgren Fredrik , Ghorbani Poya , Troëng Thomas
Published: January 2022

Background

Risk-adjusted mortality (RAM) analysis and comparisons of clinically relevant subsets of trauma patients allow hospitals to assess performance in different processes of care. The aim of the study was to develop a RAM model and compare RAM ratio (RAMR) in subsets of severely injured adult patients treated in university hospitals (UHs) and emergency hospitals (EHs) in Sweden.

Methods

This was a retrospective study of the Swedish trauma registry data (2013 to 2017) comparing RAMR in patients (aged 15 years or older and New Injury Severity Score (NISS) of more than 15) in the total population (TP) and in multisystem blunt (MB), truncal penetrating (PEN), and severe traumatic brain injury (STBI) subsets treated in UHs and EHs. The RAM model included the variables age, NISS, ASA Physical Status Classification System Score, and physiology on arrival.

Results

In total, 6690 patients were included in the study (4485 from UHs and 2205 from EHs). The logistic regression model showed a good fit. RAMR was 4.0, 3.8, 7.4, and 8.5 percentage points lower in UH versus EH for TP (P < 0.001), MB (P < 0.001), PEN (P = 0.096), and STBI (P = 0.005), respectively. The TP and MB subsets were subgrouped in with (+) and without (−) traumatic brain injury (TBI). RAMR was 7.5 and 7.0, respectively, percentage points lower in UHs than in EHs in TP + TBI and MB + TBI (both P < 0.001). In the TP–TBI (P = 0.027) and MB–TBI (P = 0.107) subsets the RAMR was 1.6 and 1.8 percentage points lower, respectively.

Conclusion

The lower RAMR in UHs versus EH were due to differences in TBI-related mortality. No evidence supported that Swedish EHs provide inferior quality of care for trauma patients without TBI or for patients with penetrating injuries.
Matrix-induced autologous chondrocyte implantation (mACI) versus autologous matrix-induced chondrogenesis (AMIC) for chondral defects of the knee: a systematic review
Authors: Migliorini Filippo , Eschweiler Jörg , Götze Christian , Driessen Arne , Tingart Markus , Maffulli Nicola
Published: January 2022

Introduction

Chondral defects of the knee are common and their treatment is challenging.

Source of data

PubMed, Google scholar, Embase and Scopus databases.

Areas of agreement

Both autologous matrix-induced chondrogenesis (AMIC) and membrane-induced autologous chondrocyte implantation (mACI) have been used to manage chondral defects of the knee.

Areas of controversy

It is debated whether AMIC and mACI provide equivalent outcomes for the management of chondral defects in the knee at midterm follow-up. Despite the large number of clinical studies, the optimal treatment is still controversial.

Growing points

To investigate whether AMIC provide superior outcomes than mACI at midterm follow-up.

Areas timely for developing research

AMIC may provide better outcomes than mACI for chondral defects of the knee. Further studies are required to verify these results in a clinical setting.
Dysfunction of parvalbumin-expressing cells in the thalamic reticular nucleus induces cortical spike-and-wave discharges and an unconscious state
Authors: Abdelaal Manal S. , Midorikawa Mitsuharu , Suzuki Toru , Kobayashi Kenta , Takata Norio , Miyata Mariko , Mimura Masaru , Tanaka Kenji F.
Published: January 2022

Spike-and-wave discharges and an accompanying loss of consciousness are hallmarks of absence seizure, which is a childhood generalized epilepsy disorder. In absence seizure, dysfunction of the cortico-thalamo-cortico circuitry is thought to engage in abnormal cortical rhythms. Previous studies demonstrated that the thalamic reticular nucleus has a critical role in the formation of normal cortical rhythms; however, whether thalamic reticular nucleus dysfunction leads directly to abnormal rhythms, such as epilepsy, is largely unknown. We found that expressing the inhibitory opsin, archaerhodopsin, including in the thalamic reticular nucleus, caused abnormal cortical rhythms in Pvalb-tetracycline transactivator::tetO-ArchT (PV-ArchT) double transgenic mice. We validated the PV-ArchT line as a new mouse model of absence seizure through physiological and pharmacological analyses, as well as through examining their behavioural features. We then discovered that archaerhodopsin expression exclusively in thalamic reticular nucleus parvalbumin-positive neurons was sufficient to induce cortical spike-and-wave discharges using adeno-associated virus-mediated thalamic reticular nucleus targeting. Furthermore, we found that archaerhodopsin expression impaired rebound burst firing and T-current in thalamic reticular nucleus parvalbumin-positive cells by slice physiology. Although T-current in the thalamic reticular nucleus was impaired, the T-current blocker ethosuximide still had a therapeutic effect in PV-ArchT mice, suggesting a gain of function of T-type calcium channels in this absence seizure model. However, we did not find any over- or misexpression of T-type calcium channel genes in the thalamus or the cortex. Thus, we demonstrated that thalamic reticular nucleus dysfunction led to an absence seizure-like phenotype in mice. In a final set of experiments, we showed that the archaerhodopsin-mediated absence seizure-like phenotype disappeared after the removal of archaerhodopsin by using a time-controllable transgenic system. These data may provide a hint as to why many absence seizures naturally regress.
Spatiotemporal target selection for intracranial neural decoding of abstract and concrete semantics
Authors: Nagata Keisuke , Kunii Naoto , Shimada Seijiro , Fujitani Shigeta , Takasago Megumi , Saito Nobuhito
Published: January 2022

Decoding the inner representation of a word meaning from human cortical activity is a substantial challenge in the development of speech brain–machine interfaces (BMIs). The semantic aspect of speech is a novel target of speech decoding that may enable versatile communication platforms for individuals with impaired speech ability; however, there is a paucity of electrocorticography studies in this field. We decoded the semantic representation of a word from single-trial cortical activity during an imageability-based property identification task that required participants to discriminate between the abstract and concrete words. Using high gamma activity in the language-dominant hemisphere, a support vector machine classifier could discriminate the 2-word categories with significantly high accuracy (73.1 ± 7.5%). Activities in specific time components from two brain regions were identified as significant predictors of abstract and concrete dichotomy. Classification using these feature components revealed that comparable prediction accuracy could be obtained based on a spatiotemporally targeted decoding approach. Our study demonstrated that mental representations of abstract and concrete word processing could be decoded from cortical high gamma activities, and the coverage of implanted electrodes and time window of analysis could be successfully minimized. Our findings lay the foundation for the future development of semantic-based speech BMIs.
Variational dimensions of cingulate cortex functional connectivity and implications in neuropsychiatric disorders
Authors: Lam Yin-Shing , Li Jiaxin , Ke Ya , Yung Wing-Ho
Published: January 2022

Significant variations in brain functional connectivity exist in the healthy population, rendering the identification and characterization of their abnormalities in neuropsychiatric disorders difficult. Here, we proposed a new principal component analysis (PCA) approach to study variations in functional connectivity, focusing on major hubs of the salience network and default mode network, namely the anterior and posterior cingulate cortices. We analyzed the intersubject variability of human functional magnetic resonance imaging connectivity obtained from healthy, autistic, and schizophrenic subjects. Utilizing data from 1000 Functional Connectomes Project, COBRE, and ABIDE 1 database, we characterized the normal variations of the cingulate cortices with respect to top PCA dimensions. We showed that functional connectivity variations of the 2 cingulate cortices are constrained, in a parallel manner, by competing or cooperating interactions with different sensorimotor, associative, and limbic networks. In schizophrenic and autistic subjects, diffuse and subtle network changes along the same dimensions were found, which suggest significant behavioral implications of the variational dimensions. Furthermore, we showed that individual dynamic functional connectivity tends to fluctuate along the principal components of connectivity variations across individuals. Our results demonstrate the strength of this new approach in addressing the intrinsic variations of network connectivity in human brain and identifying their subtle changes in neuropsychiatric disorders.
Symptoms Compatible With Long Coronavirus Disease (COVID) in Healthcare Workers With and Without Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection—Results of a Prospective Multicenter Cohort
Authors: Strahm Carol , Seneghini Marco , Güsewell Sabine , Egger Thomas , Leal-Neto Onicio , Brucher Angela , Lemmenmeier Eva , Meier Kleeb Dorette , Möller J Carsten , Rieder Philip , Ruetti Markus , Rutz Remus , Schmid Hans Ruedi , Stocker Reto , Vuichard-Gysin Danielle , Wiggli Benedikt , Besold Ulrike , Kuster Stefan P , McGeer Allison , Risch Lorenz , Friedl Andrée , Schlegel Matthias , Schmid Dagmar , Vernazza Pietro , Kahlert Christian R , Kohler Philipp
Published: January 2022

Background

The burden of long-term symptoms (ie, long COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCWs), frequency and risk factors for symptoms compatible with long COVID are assessed.

Methods

Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long COVID (including psychometric scores) were asked and compared between HCWs with positive NPS, seropositive HCWs without positive NPS (presumable asymptomatic/pauci-symptomatic infections), and negative controls. The effect of time since diagnosis and quantitative anti-spike protein antibodies (anti-S) was evaluated. Poisson regression was used to identify risk factors for symptom occurrence.

Results

Of 3334 HCWs (median, 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCWs with positive NPS more frequently reported ≥1 symptom compared with controls (73% vs 52%, P < .001); seropositive HCWs without positive NPS did not score higher than controls (58% vs 52%, P = .13), although impaired taste/olfaction (16% vs 6%, P < .001) and hair loss (17% vs 10%, P = .004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores.

Conclusions

Seropositive HCWs without positive NPS are only mildly affected by long COVID. Exhaustion/burnout is common, even in noninfected HCWs. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.
Comparison of Intra-Familial Transmission of Influenza Virus From Index Patients Treated With Baloxavir Marboxil or Oseltamivir Using an Influenza Transmission Model and a Health Insurance Claims Database
Authors: Miyazawa Shogo , Takazono Takahiro , Hosogaya Naoki , Yamamoto Kazuko , Watanabe Hideaki , Fujiwara Masakazu , Fujita Satoki , Mukae Hiroshi
Published: January 2022

Background

Influenza affects approximately a billion people globally, including > 10 million Japanese individuals every year. Baloxavir marboxil (baloxavir [BXM]; a selective cap-dependent endonuclease inhibitor) is approved for influenza treatment in Japan. We compared the incidence of intra-familial transmission of influenza between BXM and oseltamivir (OTV) treatments using a simulation model.

Methods

Using the JMDC Claims Database, we identified index case (IC) as the first family member diagnosed with influenza during the 2018–19 influenza season, and classified the families into BXM or OTV group per the drug dispensed to ICs. Using a novel influenza intra-familial infection model, we simulated the duration of influenza infection in ICs based on agent-specific virus shedding periods. Intra-familial infections were defined as non-IC family members infected during the agent-specific viral shedding period in ICs. The virus incubation periods in the non-IC family members were considered to exclude secondary infections from potentially external exposure. The primary endpoint was proportion of families with intra-familial infections. For between-group comparisons, we used a multivariate logistic regression model.

Results

The median proportion of families with intra-familial transmission was 9.57% and 19.35% in the BXM (N = 84 672) and OTV (N = 62 004) groups, respectively. The multivariate odds ratio of 1.73 (2.5th–97.5th percentiles, 1.68–1.77) indicated a substantially higher incidence of intra-familial infections in the OTV group versus the BXM group. Subgroup analyses by ICs’ age category, virus type, and month of onset revealed similar trends favoring BXM.

Conclusions

BXM treatment of ICs may contribute to a greater reduction in intra-familial influenza transmission than OTV treatment.
Rural Policing in the Long Trecento: An Urban Project and Its Obstruction
Authors: Geltner G
Published: January 2022

The intricacies of urban–rural relations surface with rare detail from the records of Italian field wardens (campari) from the late thirteenth to the mid-fifteenth century. Focusing on the region of Piedmont, in the peninsula’s north-west, this article traces the policing of numerous sites and species by the campari as part of an urban bio- and agropolitical project. The office reflects the growing desire of towns to control their surrounding countryside, not only for military defence, but also as an essential source of calorific and hydraulic energy, a sink for waste and a stage on which to showcase their power before internal and external audiences. Reconstructing the remits, norms and actions of field wardens thus illuminates power negotiations that were shaped by a range of environmental factors and the era’s thinking about hygiene. Yet analysing the activities and responsibilities of the campari also reveals the tactics that rural dwellers devised to contest urban discipline, for instance through self-help, concealment and the embellishment of charges made against them. From the perspective of the area’s historiography, the dynamics captured by these records challenge the centrality of landed aristocracies in narratives of political centralisation. And from a broader perspective, the granular view they afford of middling officials at work invites historians to explore what urbanisation meant at the ground level, on either side of the city walls.