bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of hormone receptor on the clinical outcomes of HER2-positive breast cancer: a population-based study
Authors: Han Yiqun , Wu Yun , Xu Hangcheng , Wang Jiayu , Xu Binghe
Published: January 2022

Background

To investigate the impact of hormone receptor (HR) on the clinicopathological characteristics and prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Methods

Using the Surveillance, Epidemiology, and End Results database, we enrolled patients diagnosed with HER2-positive breast cancer between 2010 and 2016, which were successively assessed for eligibility and categorized into HR + /HER2 + and HR-/HER2 + subgroups. Clinicopathological characteristics were undergone comparative analyses with the baseline distinctions calibrated by propensity score matching, while the survival outcomes were compared using Kaplan–Meier method with log-rank tests.

Results

A total of 46,803 HER2-positive breast cancer patients were identified, of which 32,919 individuals were HR + /HER2 + subtype and 13,884 individuals were HR-/HER2 + subtype, respectively. Comparatively, HR + /HER2 + breast cancer presented a lower histological grade, a smaller tumor size, a lower nodal involvement, and a lower rate of de novo stage IV disease. Substantial heterogeneity was detected in the metastatic patterns of organ-specific involvement between the two subgroups with initial metastasis. Overall, patients with HR + /HER2 + tumors had increasingly favorable prognosis in terms of overall survival and breast cancer-specific survival than patients with the HR−/HER2 + subtype. However, this kind of tendency exhibited disparities associated with HR-specific subtypes based on estrogen receptor (ER) and progesterone receptor (PgR) status, in which ER−/PgR + tended to present the worst prognosis.

Conclusion

This study revealed profound heterogeneity associated with HR status in the clinical outcomes of HER2-positive breast cancer regarding clinicopathological features, metastatic patterns, and prognosis. Prospective studies to optimize therapeutic strategies for HER2-positive subgroups are warranted.
Metabolomics of Synovial Fluid and Infrapatellar Fat Pad in Patients with Osteoarthritis or Rheumatoid Arthritis
Authors: Nieminen Petteri , Hämäläinen Wilhelmiina , Savinainen Juha , Lehtonen Marko , Lehtiniemi Saara , Rinta-Paavola Juho , Lehenkari Petri , Kääriäinen Tommi , Joukainen Antti , Kröger Heikki , Paakkonen Tommi , Mustonen Anne-Mari
Published: January 2022

Abstract

Osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA) are inflammatory joint diseases with complex and insufficiently understood pathogeneses. Our objective was to characterize the metabolic fingerprints of synovial fluid (SF) and its adjacent infrapatellar fat pad (IFP) obtained during the same surgical operation from OA and RA knees. Non-targeted metabolite profiling was performed for 5 non-inflammatory trauma controls, 10 primary OA (pOA) patients, and 10 seropositive RA patients with high-resolution mass spectrometry-based techniques, and metabolites were matched with known metabolite identities. Groupwise differences in metabolic features were analyzed with the univariate Welch’st-test and the multivariate linear discriminant analysis (LDA) and principal component analysis (PCA). Significant discrimination of metabolite profiles was discovered by LDA for both SF and IFP and by PCA for SF based on diagnosis. In addition to a few drug-derived substances, there were 16 and 13 identified metabolites with significant differences between the diagnoses in SF and IFP, respectively. The pathways downregulated in RA included androgen, bile acid, amino acid, and histamine metabolism, and those upregulated included biotin metabolism in pOA and purine metabolism in RA and pOA. The RA-induced downregulation of androgen and bile acid metabolism was observed for both SF and IFP. The levels of 11 lipid metabolites, mostly glycerophospholipids and fatty acid amides, were also altered by these inflammatory conditions. The identified metabolic pathways could be utilized in the future to deepen our understanding of the pathogeneses of OA and RA and to develop not only biomarkers for their early diagnosis but also therapeutic targets.
Efficient query processing techniques for next-page retrieval
Authors: Mackenzie Joel , Petri Matthias , Moffat Alistair
Published: January 2022

In top-k ranked retrieval the goal is to efficiently compute an ordered list of the highest scoring k documents according to some stipulated similarity function such as the well-known BM25 approach. In most implementation techniques a min-heap of size k is used to track the top scoring candidates. In this work we consider the question of how best to retrieve the second page of search results, given that a first page has already been computed; that is, identification of the documents at ranks $$k+1$$

k
+
1

to 2k for some query. Our goal is to understand what information is available as a by-product of the first-page scoring, and how it can be employed to accelerate the second-page computation, assuming that the second-page of results is required for only a fraction of the query load. We propose a range of simple, yet efficient, next-page retrieval techniques which are suitable for accelerating Document-at-a-Time mechanisms, and demonstrate their performance on three large text collections.
Heuristic based approach for short term production planning in highly automated customer oriented pallet production
Authors: Kaltenbrunner Matthias , Huka Maria Anna , Gronalt Manfred
Published: January 2022

Wooden pallets are commonly used as load carriers in many industrial and logistic applications. This article investigates and formalizes the production planning for a highly automated but customized pallet production and provides a solution approach. For completing a specific pallet, the required boards must be cut and stacked in advance to meet the demand at the assembly line. The arising planning problem for producing the required boards consists of both a cutting stock and a constraining open stack problem. Further, both the changeover of raw material at the cutting process and the number of fully automated internal storages, for stacked boards, are restricted. The proposed solution heuristic aims at minimizing the cutting waste. Additionally, feasibility with regard to the buffers is tested using discrete event simulation. Different approaches to generate, select and sequence the cutting patterns are investigated.
Performance of implicit A-stable time integration methods for multibody system dynamics
Authors: Zhang Huimin , Zhang Runsen , Zanoni Andrea , Masarati Pierangelo
Published: January 2022

This paper illustrates the performance of several representative implicit A-stable time integration methods with algorithmic dissipation for multibody system dynamics, formulated as a set of mixed implicit first-order differential and algebraic equations. The integrators include the linear multi-step methods with two to four steps, the single-step reformulations of the linear multi-step methods, and explicit first-stage, singly diagonally-implicit Runge–Kutta methods. All methods are implemented in the free, general-purpose multibody solver MBDyn. Their formulations and implementation are presented. According to the comparison from linear analysis and numerical experiments, some general conclusions on the selection of integration schemes and their implementation are obtained. Although all of these methods can predict reasonably accurate solutions, the specific advantages that each of them has in different situations are discussed.
Multiplication operator and average characteristic polynomial associated with exceptional Jacobi polynomials
Authors: Horváth Á. P.
Published: January 2022

Studying the multiplication operator associated with exceptional Jacobi polynomials, the zero distribution of the corresponding average characteristic polynomials is determined. Applying this result, the location of zeros of certain self-inversive polynomials is examined.
Education, social identity and self-employment over time: evidence from a developing country
Authors: Tamvada Jagannadha Pawan , Shrivastava Mili , Mishra Tapas Kumar
Published: January 2022

While the extant literature suggests that an individual’s occupational choice depends on the level of economic development, little is known about how the dynamics of education and social identity impact self-employment choice over time in a developing country setting. The pseudo-panel regression results presented here suggest that higher education decreases the likelihood of individuals’ choice of self-employment over time in India, but increases it in most developed cohorts. Such transitional dynamics are more prominent amongst individuals who belong to historically determined backward classes. Furthermore, the results suggest sectoral differences in self-employment choice—individuals with higher education and wealth have a greater likelihood of transiting into self-employment over time in agriculture while similar individuals in non-agriculture exit self-employment. In both sectors, however, education moderates the impact of social identity on self-employment choice. The paper underscores the need for policy shifts towards entrepreneurship along the path of economic development.
Introducing the Disease Outbreak Resilience Index (DORI) Using the Demographic and Health Surveys Data from sub-Saharan Africa
Authors: Koomson Isaac , Okumu Moses , Ansong David
Published: January 2022

Although most studies on disease emergencies underscore the need for household readiness for shocks associated with disease outbreaks, no study to date has provided a holistic measure for profiling households based on their readiness toward disease outbreaks. This paper introduces a novel Disease Outbreak Resilience Index (DORI) using a multidimensional approach that draws on the Alkire-Foster methodology. DORI measures disease outbreak resilience in four dimensions: (a) water and hygiene, (b) physical distancing, (c) energy and communication, and (d) economic security and resilience. The paper details the development of DORI and its use by presenting findings from ten countries in sub-Saharan Africa using data from the Demographic and Health Surveys (DHS) program. In addition to serving as a resilience index, we illustrate how DORI can be used to produce a disease outbreak vulnerability index (DOVI). As a versatile index, the indicators under each dimension can be tailored to meet country- and region-specific contexts based on indicators appropriate to each context.
Deep Learning Model for Wind Forecasting: Classification Analyses for Temporal Meteorological Data
Authors: Harbola Shubhi , Coors Volker
Published: January 2022

This paper proposes a multiple CNN architecture with multiple input features, combined with multiple LSTM, along with densely connected convolutional layers, for temporal wind nature analyses. The designed architecture is called Multiple features, Multiple Densely Connected Convolutional Neural Network with Multiple LSTM Architecture, i.e. MCLT. A total of 58 features in the input layers of the MCLT are designed using wind speed and direction values. These empirical features are based on percentage difference, standard deviation, correlation coefficient, eigenvalues, and entropy, for efficiently describing the wind trend. Two successive LSTM layers are used after four densely connected convolutional layers of the MCLT. Moreover, LSTM has memory units that utilise learnt features from the current as well as previous outputs of the neurons, thereby enhancing the learning of patterns in the temporal wind dataset. Densely connected convolutional layer helps to learn features of other convolutional layers as well. The MCLT is used to predict dominant speed and direction classes in the future for the wind datasets of Stuttgart and Netherlands. The maximum and minimum overall accuracies for dominant speed prediction are 99.1% and 94.9%, (for Stuttgart) and 99.9% and 97.5% (for Netherlands) and for dominant direction prediction are 99.9% and 94.4% (for Stuttgart) and 99.6% and 96.4% (for Netherlands), respectively, using MCLT with 58 features. The MCLT, therefore, with multiple features at different levels, i.e. the input layers, the convolutional layers, and LSTM layers, shows promising results for the prediction of dominant speed and direction. Thus, this work is useful for proper wind utilisation and improving environmental planning. These analyses would also help in performing Computational Fluid Dynamics (CFD) simulations using wind speed and direction measured at a nearby meteorological station, for devising a new set of appropriate inflow boundary conditions.
Therapy With Local Anesthetics to Treat Vulvodynia. A Pilot Study
Authors: Weinschenk Stefan , Benrath Justus , Kessler Eugen , Strowitzki Thomas , Feisst Manuel
Published: January 2022

Introduction

Vulvodynia (chronic vulvar pain) is a sexually debilitating disorder with a prevalence of ∼10%.

Aim

To investigate the effectiveness of therapy with local anesthetics (TLA) in women with severe vulvodynia, we conducted a prospective, non-controlled observational study.

Methods

45 patients with severe chronic vulvodynia (primary and secondary vulvodynia, 0–10 numeric analogue scale (NAS) ≥6, median 7.9, duration ≥6 months, median 65.2 months) in an outpatient practice in Germany were treated with TLA in 3–12 sessions using procaine 1% as local anesthetic. Effectiveness was analyzed with Wilcoxon signed rank tests and Wilcoxon rank sum tests.

Outcomes

Therapeutic success as a reduction of pain to ≤4 NAS lasting for ≥6 months after end of therapy.

Results

TLA successfully reduced vulvodynia in 36 of 45 patients (80 %, responders). The NAS reduction was from 7.9 to 2.4 (P < .001). Even patients denominated as non-responders experienced a significant reduction in NAS (P = .03). In responders, long-term success was observed for 6.8–125 months (median 24.1 months). No adverse events occurred.

Clinical Translation

A promising new treatment for a hard-to-treat chronic female pain disorder.

Strengths and Limitations

Limitation: Monocentric, non-controlled observational design; Strength: the high number of patients treated.

Conclusion

The high success rate of TLA in this investigation offers new perspectives on the etiology of vulvodynia as a complex pain syndrome affecting several nerves of the pelvic floor, and also provides early insight into the effectiveness of TLA in women with vulvodynia.
Profiling third-level student mental health: findings from My World Survey 2
Authors: Mahon Ciara , Fitzgerald Amanda , O’Reilly Aileen , Dooley Barbara
Published: January 2022

Objectives:

This study aimed to identify risk and protective factors for mental health across student cohorts to guide mental health provision.

Methods:

Cross-sectional data from the My World Survey 2-Post Second Level (MWS2-PSL) were used. The sample consisted of N = 9935 students (18–65 years) from 12 third-level institutions (7 out of 7 universities and 5 out of 14 Institute of Technologies (IoTs)) across Ireland. Key outcomes of interest were depression, anxiety and suicidality. Risk factors included drug/alcohol use, risky sexual behaviours and exposure to stressors. Protective factors included coping strategies, help-seeking, resilience, self-esteem, life satisfaction, optimism and social support. These factors were profiled by degree type (undergraduate, postgraduate taught, postgraduate research), access route, and institution type (IoT, university). Chi-square tests of Independence and one-way ANOVAs compared groups on key risk and protective factors.

Results:

A total 71% of respondents were female, 85% were aged 23 or under and there was a 2.2% response rate in IoTs versus 10.6% in university students. Undergraduates demonstrated higher levels of depression, anxiety, self-harm and suicidal ideation than postgraduates. Undergraduates showed higher risk and lower protective factors than postgraduates. Students attending Institutes of Technology reported higher levels of depression and anxiety, lower protective and higher risk factors than university students.

Conclusion:

In this sample of students, undergraduates, especially those attending Institutes of Technology, were at increased risk of mental health difficulties. Findings suggest the need to tailor interventions to meet cohort needs, and consider the differing vulnerabilities and strengths across student cohorts. Due to limitations of this study, such as selection bias, further research is warranted.
Statistical properties of pressure-Hessian tensor in a turbulent channel flow
Authors: Tang Jiu-Peng , Wan Zhen-Hua , Liu Nan-Sheng , Lu Xi-Yun
Published: January 2022

A direct numerical simulation database of a weakly compressible turbulent channel flow with bulk Mach number 1.56 is studied in detail, including the geometrical relationships between the pressure-Hessian tensor and the vorticity/strain-rate tensor, as well as the mechanism of the pressure-Hessian tensor contributing to the evolution of invariants of the velocity gradient tensor. The results show that the geometrical relationships between the pressure-Hessian tensor and the vorticity/strain-rate tensor in the central region of the channel are consistent with that of isotropic turbulence. However, in the buffer layer with relatively stronger inhomogeneity and anisotropy, the vorticity tends to be aligned with the first or second eigenvector of the pressure-Hessian tensor in the unstable focus/compressing topological region, and tends to be aligned with the first eigenvector of the pressure-Hessian tensor in the stable focus/stretching topological region. In the unstable node/saddle/saddle and stable node/saddle/saddle topological regions, the vorticity prefers to lie in the plane of the first and second eigenvectors of the pressure-Hessian tensor. The strain-rate and the pressure-Hessian tensors tend to share their second principal direction. Moreover, for the coupling between the pressure-Hessian tensor and the principal strain rates, we clarify the influence on dissipation, the nonlinear generation of dissipation and the enstrophy generation. The decomposition of the pressure-Hessian tensor further shows that the slow pressure-related term dominates the pressure-Hessian tensor's contribution, and the influence of inhomogeneity and anisotropy mainly originates from the inhomogeneity and anisotropy of the fluctuating velocity. These statistical properties would be instructive in formulating dynamical models of the velocity gradient tensor for wall turbulence.
Onset of wake meandering for a floating offshore wind turbine under side-to-side motion
Authors: Li Zhaobin , Dong Guodan , Yang Xiaolei
Published: January 2022

Wind turbine wakes, being convectively unstable, may behave as an amplifier of upstream perturbations and make downstream turbines experience strong inflow fluctuations. In this work, we investigate the effects of the side-to-side motion of a floating offshore wind turbine (FOWT) on wake dynamics using large-eddy simulation and linear stability analysis (LSA). When the inflow turbulence intensity is low, simulation results reveal that the turbine motion with certain Strouhal numbers$St = fD/U_\infty \in (0.2,0.6)$(where$f$is the motion frequency,$D$is the rotor diameter, and$U_\infty$is the incoming wind speed), which overlap with the Strouhal numbers of wake meandering induced by the shear layer instability, can lead to wake meandering with amplitudes being one order of magnitude larger than the FOWT motion for the most unstable frequency. For high inflow turbulence intensity, on the other hand, the onset of wake meandering is dominated by the inflow turbulence. The probability density function of the spanwise instantaneous wake centres is observed being non-Gaussian and closely related to that of the side-to-side motion. This complements the existing wake meandering mechanisms, that the side-to-side motion of an FOWT can be a novel origin for the onset of wake meandering. It is also found that LSA can predict the least stable frequencies and the amplification factor with acceptable accuracy for motion amplitude$0.01D$. Effects of nonlinearity are observed when motion amplitude increases to$0.04D$, for which the most unstable turbine oscillations shift slightly to lower frequencies and the amplification factor decreases.
Kelvin–Helmholtz instability in strongly coupled dusty plasma with rotational shear flows and tracer transport
Authors: Dharodi Vikram S. , Patel Bhavesh , Das Amita
Published: January 2022

Kelvin–Helmholtz (KH) instability plays a significant role in transport and mixing in various media such as hydrodynamic fluids, plasmas, geophysical flows and astrophysical situations. In this paper, we numerically explore this instability for a two-dimensional strongly coupled dusty plasma medium with rotational shear flows. We study this medium using a generalized hydrodynamic fluid model which treats it as a viscoelastic fluid. We consider the specific cases of rotating vorticity with abrupt radial profiles of rotation. In particular, single-circulation and multi-circulation vorticity shell profiles have been chosen. We observe the KH vortices at each circular interface between two relative rotating flows along with a pair of ingoing and outgoing wavefronts of transverse shear waves. Our studies show that due to the interplay between KH vortices and shear waves in the strongly coupled medium, the mixing and transport behaviour are much better than those of standard inviscid hydrodynamic fluids. In the interest of substantiating the mixing and transport behaviour, the generalized hydrodynamic fluid model is extended to include Lagrangian tracer particles. The numerical dispersion of these tracer particles in a flow provides an estimate of the diffusion in such a medium. We present the preliminary observations of tracer distribution (cluster formation) and diffusion (mean square displacement) across the medium.
Evidence for Post‐Assembly Modification of Western Laurentia by Back‐Arc Extension
Authors: Ekpo Johnson E. , Eaton D. W. , Nair R.
Published: January 2022

The crystalline crust that underlies the Western Canada Sedimentary Basin in northern Alberta is composed of tectonic domains that accreted to the margin of the Archean Rae province of western Laurentia, ca. 2.1‐1.8 Ga. Previous tectonic models in this region invoke complex plate dynamics, including oppositely verging subduction zones, to explain the assembly of various geologic domains. In this paper, we introduce a new tectonic model that invokes back‐arc extension within the Chinchaga Domain (CD). The basement crust in the CD hosts a vast, mid‐crustal reflection sequence (Winagami Reflection Sequence), previously interpreted as a mafic sill complex that intruded into an atypically wide domain of Paleoproterozoic arc magmatism. The latter has been interpreted to have formed during Paleoproterozoic tectonic assembly through near‐synchronous closure of multiple small oceanic basins and/or magmatism in a plate interior setting. Based on a reinterpretation of regional geophysical data and post‐compressional fabrics observed by re‐examination of drill cores, we propose that observed temporal relationships and present‐day configuration of Paleoproterozoic arcs is better explained by post‐assembly extension of the Chinchaga Domain. The proposed post‐assembly modification is analogous to the recent tectonic evolution of the Basin and Range and can be explained through back‐arc extension linked to slab rollback and/or a proximal coeval transform plate boundary. Our model implies a back‐arc setting for the Winagami sill complex; it also provides a tectonic framework for explaining the origin of an enigmatic low δ18O anomaly (Kimiwan anomaly) and reactivated basement faults associated with recent induced seismicity.
Application of Nonlinear Time Series and Machine Learning Algorithms for Forecasting Groundwater Flooding in a Lowland Karst Area
Authors: Basu Bidroha , Morrissey Patrick , Gill Laurence W.
Published: January 2022

In karst limestone areas interactions between ground and surface waters can be frequent, particularly in low lying areas, linked to the unique hydrogeological dynamics of that bedrock aquifer. In extreme hydrological conditions, however, this can lead to wide‐spread, long‐duration flooding, resulting in significant cost and disruption. This study develops and compares a nonlinear time‐series analysis based nonlinear autoregressive model with exogenous variables (NARX), machine learning based near support vector regression as well as a linear time‐series ARX model in terms of their performance to predict groundwater flooding in a lowland karst area of Ireland. The models have been developed upon the results of several years of field data collected in the area, as well as the outputs of a highly calibrated semi‐distributed hydraulic/hydrological model of the karst network. The prediction of total flooding volume indicates that the performances of all the models are similarly accurate up to 10 days into the future. A NARX model taking inputs of the past 5 days' flood volume; rainfall data and tidal amplitude data across the past 4 days, showed the best flood forecasting performance up to 30 days into the future. Existing real‐time telemetric monitoring of water level data at two points in the catchment can be fed into the model to provide an early warning flood warning tool. The model also predicts freshwater discharge from the inter‐tidal spring into the Atlantic Ocean which hitherto had not been possible to monitor.
Hyporheic Exchange Due to Cobbles on Sandy Beds
Authors: Lee Anzy , Aubeneau Antoine F. , Cardenas M. Bayani , Liu Xiaofeng
Published: January 2022

Hyporheic exchange induced by riverbed topography and roughness provides important ecosystem functions. We investigated how cobble clusters embedded in a finer‐grained sand bed affect the near‐bed channel flow and the exchange of surface and subsurface water. We tested how the spacing and embeddedness of cobbles altered hyporheic exchange through a three‐dimensional fully coupled surface‐subsurface model. The 3D modeling framework captured the full physics of the exchange process locating the lateral position of upwelling zones on the side of the cobble. As the cobbles protrude more into the channel, eddies appear downstream, with smaller vortices where cobbles are closer together. In our simulations, hyporheic exchange increased with the spacing and protrusion ratio. The travel time in the hyporheic zone also increased with the protrusion ratio because the hyporheic flow paths are longer when the cobble is more protruded. With different spacings at the highest protrusion ratio, the average slope of early time breakthrough curve was steeper for large spacing settings: the travel time increases as the spacing decreases.
Patterns of neutralizing humoral response to SARS-CoV-2 infection among hematologic malignancy patients reveal a robust immune response in anti-cancer therapy-naive patients
Authors: Borgogna Cinzia , Bruna Riccardo , Griffante Gloria , Martuscelli Licia , De Andrea Marco , Ferrante Daniela , Patriarca Andrea , Mahmoud Abdurraouf Mokhtar , Gaidano Valentina , Marchetti Monia , Rapezzi Davide , Lai Michele , Pistello Mauro , Ladetto Marco , Massaia Massimo , Gaidano Gianluca , Gariglio Marisa
Published: January 2022

Understanding antibody-based SARS-CoV-2 immunity in hematologic malignancy (HM) patients following infection is crucial to inform vaccination strategies for this highly vulnerable population. This cross-sectional study documents the anti-SARS-CoV-2 humoral response and serum neutralizing activity in 189 HM patients recovering from a PCR-confirmed infection. The overall seroconversion rate was 85.7%, with the lowest values in patients with lymphoid malignancies or undergoing chemotherapy. Therapy-naive patients in the “watch and wait” status were more likely to seroconvert and display increased anti-s IgG titers. Enhanced serum neutralizing activity was observed in the following SARS-CoV-2-infected HM patient groups: (i) males; (ii) severe COVID-19; and (iii) “watch and wait” or “complete/partial response”. The geometric mean (GeoMean) ID50 neutralization titers in patients analyzed before or after 6 months post-infection were 299.1 and 306.3, respectively, indicating that >50% of the patients in either group had a neutralization titer sufficient to provide 50% protection from symptomatic COVID-19. Altogether, our findings suggest that therapy-naive HM patients mount a far more robust immune response to SARS-CoV-2 infection vs. patients receiving anti-cancer treatment, raising the important question as to whether HM patients should be vaccinated before therapy and/or receive vaccine formats capable of better recapitulating the natural infection.
Primary tumour immune response and lymph node yields in colon cancer
Authors: Lal Nikhil , Chan Dedrick Kok Hong , Ng Minn E , Vermeulen Louis , Buczacki Simon James Alexander
Published: January 2022

Background

The mechanism underlying improved survival in non-metastatic colon cancer with higher lymph node (LN) yield is unknown. This study aimed to identify whether molecular features in the primary tumour were predictive of LN yield.

Methods

Clinical, genomic, transcriptomic, proteomic and methylation data of non-metastatic, colon cancers studied in The Cancer Genome Atlas were interrogated for associations with LN yield. Based on maximal survival effects, patients were segregated into high (>15) and low (≤15) LN yield. Gene set enrichment analysis was performed on transcriptomic changes to identify biological processes associated with LN yield. Correlations were validated in an independent set of Stage II colon cancers.

Results

High LN yield was found predictive of overall and disease-free survival. There was no association of higher LN yield and increasing nodal positivity. High LN yield was strongly linked with gene expression changes associated with the adaptive and dendritic cell immune response. This association was most prominent in node-negative cancers. Analogous findings were reproduced in the validation dataset.

Conclusion

The study shows a strong association of an activated immune response in tumours with a high LN yield. Immunogenic tumours have a better prognosis, likely explaining the survival benefit with higher LN yields.
Integrative genomic and transcriptomic analysis reveals immune subtypes and prognostic markers in ovarian clear cell carcinoma
Authors: Ye Shuang , Li Qin , Wu Yutuan , Jiang Wei , Zhou Shuling , Zhou Xiaoyan , Yang Wentao , Tu Xiaoyu , Shan Boer , Huang Shenglin , Yang Huijuan
Published: January 2022

Background

We performed an integrative genomic and transcriptomic profiling to identify molecular subtypes and prognostic markers with special focus on immune-related pathways.

Methods

Totally, 50 Chinese patients were subjected to targeted next-generation sequencing and transcriptomic sequencing.

Results

Two distinct subgroups were identified as immune (22.0%) and non-immune (78.0%) based on the immune-pathway related hierarchical clustering. Surprisingly, patients with immune subtype had a significantly worse survival. The prognostic capacity was validated in external cohorts. The immune group had higher expression of genes involved in pro-inflammation and checkpoints. PD-1 signalling pathway was enriched in the immune subtype. Besides, the immune cluster presented enriched expression of genes involved in epithelial-mesenchymal transition, angiogenesis and PI3K-AKT-mTOR signalling, while the non-immune subtype had higher expression of metabolic pathways. The immune subtype had a higher mutation rate of PIK3CA though significance was not achieved. Lastly, we established a prognostic immune signature for overall survival. Interestingly, the immune signature could also be applied to renal clear cell carcinoma, but not to other histologic subtype of ovarian cancer.

Conclusions

An immune subtype of OCCC was identified with poor survival and enrichment of PD-1 and PI3K-AKT-mTOR signalling. We constructed and validated a robust prognostic immune signature of OCCC patients.
Tumour-infiltrating lymphocytes in oropharyngeal cancer: a validation study according to the criteria of the International Immuno-Oncology Biomarker Working Group
Authors: Almangush Alhadi , Jouhi Lauri , Atula Timo , Haglund Caj , Mäkitie Antti A. , Hagström Jaana , Leivo Ilmo
Published: January 2022

Background

The evaluation of immune response can aid in prediction of cancer behaviour. Here, we assessed the prognostic significance of tumour-infiltrating lymphocytes (TILs) in oropharyngeal squamous cell carcinoma (OPSCC).

Methods

A total of 182 patients treated for OPSCC were included in this study. Assessment of TILs was conducted on tumour sections stained with standard haematoxylin and eosin (HE) staining. We used the scoring criteria proposed by the International Immuno-Oncology Biomarker Working Group.

Results

The multivariable analysis showed that TILs associated with disease-specific survival with a hazard ratio (HR) of 2.13 (95% CI 1.14–3.96; P = 0.017). Similarly, TILs associated significantly with overall survival with HR of 1.87 (95% CI 1.11–3.13; P = 0.018). In a sub-analysis of HPV-positive and HPV-negative cases separately, TILs showed a significant prognostic value in both groups (P < 0.05).

Conclusion

The evaluation of TILs as proposed by the International Immuno-Oncology Biomarker Working Group is a simple and promising method in prediction of survival of OPSCC. It is easily applicable and after further validation can be implemented in the routine pathological report as a basic immune parameter.
Resolving the structure of phage–bacteria interactions in the context of natural diversity
Authors: Kauffman Kathryn M. , Chang William K. , Brown Julia M. , Hussain Fatima A. , Yang Joy , Polz Martin F. , Kelly Libusha
Published: January 2022

Microbial communities are shaped by viral predators. Yet, resolving which viruses (phages) and bacteria are interacting is a major challenge in the context of natural levels of microbial diversity. Thus, fundamental features of how phage-bacteria interactions are structured and evolve in the wild remain poorly resolved. Here we use large-scale isolation of environmental marine Vibrio bacteria and their phages to obtain estimates of strain-level phage predator loads, and use all-by-all host range assays to discover how phage and host genomic diversity shape interactions. We show that lytic interactions in environmental interaction networks (as observed in agar overlay) are sparse—with phage predator loads being low for most bacterial strains, and phages being host-strain-specific. Paradoxically, we also find that although overlap in killing is generally rare between tailed phages, recombination is common. Together, these results suggest that recombination during cryptic co-infections is an important mode of phage evolution in microbial communities. In the development of phages for bioengineering and therapeutics it is important to consider that nucleic acids of introduced phages may spread into local phage populations through recombination, and that the likelihood of transfer is not predictable based on lytic host range.
Fate of dissolved black carbon in the deep Pacific Ocean
Authors: Yamashita Youhei , Nakane Motohiro , Mori Yutaro , Nishioka Jun , Ogawa Hiroshi
Published: January 2022

Black carbon (BC), a byproduct of biomass and fossil fuel combustion, may impact the climate because it can be stored on Earth’s surface for centuries to millennia. Dissolved BC (DBC) occurs ubiquitously in the ocean. However, the DBC cycle in the ocean has not been well constrained. Here, we show the basin-scale distribution of DBC in the Pacific Ocean and find that the DBC concentrations in the deep Pacific Ocean decrease along with deep-ocean meridional circulation. The DBC concentration is negatively correlated with apparent oxygen utilization, a proxy of the integrated flux of sinking particles, in the deep Pacific Ocean, implying that DBC is removed from the deep ocean to abyssal sediments through sorption onto sinking particles. The burial flux of BC to abyssal sediments is estimated to be 0.040–0.085 PgC yr−1, corresponding to 1.5–3.3% of the anthropogenic CO2uptake by the ocean.
Intensified continental chemical weathering and carbon-cycle perturbations linked to volcanism during the Triassic–Jurassic transition
Authors: Shen Jun , Yin Runsheng , Zhang Shuang , Algeo Thomas J. , Bottjer David J. , Yu Jianxin , Xu Guozhen , Penman Donald , Wang Yongdong , Li Liqin , Shi Xiao , Planavsky Noah J. , Feng Qinglai , Xie Shucheng
Published: January 2022

Direct evidence of intense chemical weathering induced by volcanism is rare in sedimentary successions. Here, we undertake a multiproxy analysis (including organic carbon isotopes, mercury (Hg) concentrations and isotopes, chemical index of alteration (CIA), and clay minerals) of two well-dated Triassic–Jurassic (T–J) boundary sections representing high- and low/middle-paleolatitude sites. Both sections show increasing CIA in association with Hg peaks near the T–J boundary. We interpret these results as reflecting volcanism-induced intensification of continental chemical weathering, which is also supported by negative mass-independent fractionation (MIF) of odd Hg isotopes. The interval of enhanced chemical weathering persisted for ~2 million years, which is consistent with carbon-cycle model results of the time needed to drawdown excess atmospheric CO2 following a carbon release event. Lastly, these data also demonstrate that high-latitude continental settings are more sensitive than low/middle-latitude sites to shifts in weathering intensity during climatic warming events.
Brønsted acid-enhanced copper-catalyzed atroposelective cycloisomerization to axially chiral arylquinolizones via dearomatization of pyridine
Authors: Min Xiao-Long , Zhang Xiu-Lian , Yi Wenbin , He Ying
Published: January 2022

The construction of axially chiral N-heterobiaryls is of great interest as a result of their occurrence in organocatalysts, chiral ligands, natural products, and biologically active molecules. Despite remarkable achievements in this area, strategies for the preparation of new classes of axially chiral N-heterobiaryls remain to be further explored. Herein, we report the enantioselective synthesis of axially chiral arylquinolizones through an intramolecular atroposelective cycloisomerization. The reaction proceeds via the Brønsted acid-enhanced dearomatization of pyridine by a copper catalyst that allows for the formation of the desired products in excellent yields and enantioselectivities. The utility of this methodology is illustrated by a synthesis on gram scale production and transformation of the products into chiral thiourea catalysts. Mechanistic studies demonstrate that Brønsted acid plays a significant role in promoting the reactivity of the reaction, while both the steric and electronic effects of aryl substituents in substrate play a role in controlling the stereoselectivity.
One reaction to make highly stretchable or extremely soft silicone elastomers from easily available materials
Authors: Hu Pengpeng , Madsen Jeppe , Skov Anne Ladegaard
Published: January 2022

Highly stretchable, soft silicone elastomers are of great interest for the fabrication of stretchable, soft devices. However, there is a lack of available chemistries capable of efficiently preparing silicone elastomers with superior stretchability and softness. Here we show an easy curing reaction to prepare silicone elastomers, in which a platinum-catalyzed reaction of telechelic/multi-hydrosilane (Si–H) functional polydimethylsiloxane (PDMS) in the presence of oxygen and water leads to slow crosslinking. This curing chemistry allows versatile tailoring of elastomer properties, which exceed their intrinsic limitations. Specifically, both highly stretchable silicone elastomers (maximum strain of 2800%) and extremely soft silicone elastomers (lowest shear modulus of 1.2 kPa) are prepared by creating highly entangled elastomers and bottle-brush elastomers from commercial precursor polymers, respectively.
Thermal assisted up-conversion electroluminescence in quantum dot light emitting diodes
Authors: Su Qiang , Chen Shuming
Published: January 2022

Up-conversion electroluminescence, in which the energy of a emitted photon is higher than that of the excitation electron, is observed in quantum-dot light-emitting diodes. Here, we study its mechanism by investigating the effect of thermal energy on the charge injection dynamic. Based on the results of temperature-dependent electroluminescence and theoretical analysis, we reveal that at sub-bandgap voltage, holes can be successfully injected into quantum-dots via thermal-assisted thermionic-emission mechanism, thereby enabling the sub-bandgap turn-on and up-conversion electroluminescence of the devices. Further theoretical deduction and experimental results confirm that thermal-assisted hole-injection is the universal mechanism responsible for the up-conversion electroluminescence. This work uncovers the charge injection process and unlocks the sub-bandgap turn-on mechanism, which paves the road for the development of up-conversion devices with power conversion efficiency over 100%.
Recent upper Arctic Ocean warming expedited by summertime atmospheric processes
Authors: Li Zhe , Ding Qinghua , Steele Michael , Schweiger Axel
Published: January 2022

The observed upper (0–50 m) Arctic Ocean warming since 1979 has been primarily attributed to anthropogenically driven changes in the high latitudes. Here, using both observational and modeling analyses, we demonstrate that a multiyear trend in the summertime large-scale atmospheric circulation, which we ascribe to internal variability, has played an important role in upper ocean warming in summer and fall over the past four decades due to sea ice-albedo effect induced by atmospheric dynamics. Nudging experiments in which the wind fields are constrained toward the observed state support this mechanism and suggest that the internal variability contribution to recent upper Arctic Ocean warming accounts for up to one quarter of warming over the past four decades and up to 60% of warming from 2000 to 2018. This suggests that climate models need to replicate this important internal process in order to realistically simulate Arctic Ocean temperature variability and trends.
OCT4-induced oligodendrocyte progenitor cells promote remyelination and ameliorate disease
Authors: Yun Wonjin , Choi Kyung-Ah , Hwang Insik , Zheng Jie , Park Minji , Hong Wonjun , Jang Ah-Young , Kim Jeong Hee , Choi Wonji , Kim Dae-Sung , Kim In Yong , Kim Yong Jun , Liu Ying , Yoon Byung Sun , Park Gyuman , Song Gwonhwa , Hong Sunghoi , You Seungkwon
Published: January 2022

The generation of human oligodendrocyte progenitor cells (OPCs) may be therapeutically valuable for human demyelinating diseases such as multiple sclerosis. Here, we report the direct reprogramming of human somatic cells into expandable induced OPCs (iOPCs) using a combination of OCT4 and a small molecule cocktail. This method enables generation of A2B5+(an early marker for OPCs) iOPCs within 2 weeks retaining the ability to differentiate into MBP-positive mature oligodendrocytes. RNA-seq analysis revealed that the transcriptome of O4+iOPCs was similar to that of O4+OPCs and ChIP-seq analysis revealed that putative OCT4-binding regions were detected in the regulatory elements of CNS development-related genes. Notably, engrafted iOPCs remyelinated the brains of adult shiverer mice and experimental autoimmune encephalomyelitis mice with MOG-induced 14 weeks after transplantation. In conclusion, our study may contribute to the development of therapeutic approaches for neurological disorders, as well as facilitate the understanding of the molecular mechanisms underlying glial development.
Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant
Authors: Gao Yu , Cai Curtis , Grifoni Alba , Müller Thomas R. , Niessl Julia , Olofsson Anna , Humbert Marion , Hansson Lotta , Österborg Anders , Bergman Peter , Chen Puran , Olsson Annika , Sandberg Johan K. , Weiskopf Daniela , Price David A. , Ljunggren Hans-Gustaf , Karlsson Annika C. , Sette Alessandro , Aleman Soo , Buggert Marcus
Published: January 2022

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant of concern (VOC) has destabilized global efforts to control the impact of coronavirus disease 2019 (COVID-19). Recent data have suggested that B.1.1.529 can readily infect people with naturally acquired or vaccine-induced immunity, facilitated in some cases by viral escape from antibodies that neutralize ancestral SARS-CoV-2. However, severe disease appears to be relatively uncommon in such individuals, highlighting a potential role for other components of the adaptive immune system. We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection or BNT162b2 vaccination provide extensive immune coverage against B.1.1.529. The median relative frequencies of SARS-CoV-2 spike-specific CD4+ T cells that cross-recognized B.1.1.529 in previously infected or BNT162b2-vaccinated individuals were 84% and 91%, respectively, and the corresponding median relative frequencies for SARS-CoV-2 spike-specific CD8+ T cells were 70% and 92%, respectively. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike-reactive CD4+ and CD8+ T cells were functionally and phenotypically similar in response to the ancestral strain or B.1.1.529. Collectively, our data indicate that established SARS-CoV-2 spike-specific CD4+ and CD8+ T cell responses, especially after BNT162b2 vaccination, remain largely intact against B.1.1.529.
New constraints on the postglacial shallow-water carbonate accumulation in the Great Barrier Reef
Authors: Hinestrosa Gustavo , Webster Jody M. , Beaman Robin J.
Published: January 2022

More accurate global volumetric estimations of shallow-water reef deposits are needed to better inform climate and carbon cycle models. Using recently acquired datasets and International Ocean Discovery Program (IODP) Expedition 325 cores, we calculated shallow-water CaCO3 volumetrics and mass for the Great Barrier Reef region and extrapolated these results globally. In our estimates, we include deposits that have been neglected in global carbonate budgets: Holocene Halimeda bioherms located on the shelf, and postglacial pre-Holocene (now) drowned coral reefs located on the shelf edge. Our results show that in the Great Barrier Reef alone, these drowned reef deposits represent ca. 135 Gt CaCO3, comparatively representing 16–20% of the younger Holocene reef deposits. Globally, under plausible assumptions, we estimate the presence of ca. 8100 Gt CaCO3 of Holocene reef deposits, ca. 1500 Gt CaCO3 of drowned reef deposits and ca. 590 Gt CaCO3 of Halimeda shelf bioherms. Significantly, we found that in our scenarios the periods of pronounced reefal mass accumulation broadly encompass the occurrence of the Younger Dryas and periods of CO2 surge (14.9–14.4 ka, 13.0–11.5 ka) observed in Antarctic ice cores. Our estimations are consistent with reef accretion episodes inferred from previous global carbon cycle models and with the chronology from reef cores from the shelf edge of the Great Barrier Reef.