bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparative study of 17 phenological models to predict the start of the growing season
Authors: Mo Yunhua , Zhang Jing , Jiang Hong , Fu Yongshuo H.
Published: January 2023

Vegetation phenological models play a major role in terrestrial ecosystem modeling. However, substantial uncertainties still occur in phenology models because the mechanisms underlying spring phenological events are unclear. Taking into account the asymmetric effects of daytime and nighttime temperature on spring phenology, we analyzed the performance of 17 spring phenological models by combining the effects of photoperiod and precipitation. The global inventory modeling and mapping study third-generation normalized difference vegetation index data (1982–2014) were used to extract the start of the growing season (SOS) in the North–South Transect of Northeast Asia. The satellite-derived SOS of deciduous needleleaf forest (DNF), mixed forest (MF), open shrublands (OSL), and woody savannas (WS) showed high correlation coefficients (r) with the model-predicted SOS, with most exceeding 0.7. For all vegetation types studied, the models that considered the effect of photoperiod and precipitation did not significantly improve the model performance. For temperature-based models, the model using the growing-degree-day temperature response had a lower root mean square error compared with the models using the sigmoid temperature response Importantly, we found that daily maximum temperature was most suitable for the spring phenology prediction of DNF, OSL, and WS; daily mean temperature for MF; and daily minimum temperature for grasslands. These findings indicate that future spring phenological models should consider the asymmetric effect between daytime and nighttime temperature across different vegetation types.
Wheat end-use quality: State of art, genetics, genomics-assisted improvement, future challenges, and opportunities
Authors: Subedi Madhav , Ghimire Bikash , Bagwell John White , Buck James W. , Mergoum Mohamed
Published: January 2023

Wheat is the most important source of food, feed, and nutrition for humans and livestock around the world. The expanding population has increasing demands for various wheat products with different quality attributes requiring the development of wheat cultivars that fulfills specific demands of end-users including millers and bakers in the international market. Therefore, wheat breeding programs continually strive to meet these quality standards by screening their improved breeding lines every year. However, the direct measurement of various end-use quality traits such as milling and baking qualities requires a large quantity of grain, traits-specific expensive instruments, time, and an expert workforce which limits the screening process. With the advancement of sequencing technologies, the study of the entire plant genome is possible, and genetic mapping techniques such as quantitative trait locus mapping and genome-wide association studies have enabled researchers to identify loci/genes associated with various end-use quality traits in wheat. Modern breeding techniques such as marker-assisted selection and genomic selection allow the utilization of these genomic resources for the prediction of quality attributes with high accuracy and efficiency which speeds up crop improvement and cultivar development endeavors. In addition, the candidate gene approach through functional as well as comparative genomics has facilitated the translation of the genomic information from several crop species including wild relatives to wheat. This review discusses the various end-use quality traits of wheat, their genetic control mechanisms, the use of genetics and genomics approaches for their improvement, and future challenges and opportunities for wheat breeding.
Survival association of XRCC1 for patients with head and neck squamous cell carcinoma: A systematic review and meta-analysis
Authors: Yang Fan , Zhou Liuqing , Chen Jingcai , Luo Yao , Wang Yanjun
Published: January 2023

Background: Epidemiologic studies have demonstrated that X-ray repair cross-complementary group 1 (XRCC1) is one of the susceptibility factors in head and neck squamous cell carcinoma (HNSCC) patients. However, its clinical prognostic impact remains controversial. Thus, a meta-analysis was performed to clarify the association between XRCC1 and the survival outcomes in HNSCC patients.

Methods: Following the Preferred Reporting Items or Systematic Reviews Meta Analyses (PRISMA) 2020 guidelines, literature searches were systematically performed in PubMed, EMBASE, Web of Science, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases with manual retrieval. Hazard ratios (HRs) and 95% confidence intervals (CIs) were collected to estimate the correlation between XRCC1 and the survival outcomes of HNSCC patients.

Results: Ten studies including 1995 HNSCC patients who satisfied the inclusion and exclusion criteria were included in this meta-analysis. Pooled analysis indicated that XRCC1 Arg399Gln and XRCC1 high protein expression were significantly correlated with poor overall survival with HR of 1.31 (95% CIs: 1.03-1.66, p = 0.027) and 2.32 (95% CIs: 1.55-3.48 p = 0.000) in HNSCC patients. In addition, our results demonstrated that XRCC1 was significantly associated with poor progression-free survival (HR = 1.42, 95% CIs: 1.15-1.75, p = 0.001) in HNSCC patients.

ConclusionThis meta-analysis demonstrated that XRCC1 Arg399Gln and XRCC1 high protein expression increase the risk of poor survival for HNSCC patients. XRCC1 is a potential therapeutic target for HNSCC.
Supervised learning techniques for dairy cattle body weight prediction from 3D digital images
Authors: Gebreyesus Grum , Milkevych Viktor , Lassen Jan , Sahana Goutam
Published: January 2023

Introduction: The use of automation and sensor-based systems in livestock production allows monitoring of individual cows in real-time and provides the possibility of early warning systems to take necessary management actions against possible anomalies. Among the different RT monitoring parameters, body weight (BW) plays an important role in tracking the productivity and health status.

Methods: In this study, various supervised learning techniques representing different families of methods in the machine learning space were implemented and compared for performance in the prediction of body weight from 3D image data in dairy cows. A total of 83,011 records of contour data from 3D images and body weight measurements taken from a total of 914 Danish Holstein and Jersey cows from 3 different herds were used for the predictions. Various metrics including Pearson’s correlation coefficient (r), the root mean squared error (RMSE), and the mean absolute percentage error (MAPE) were used for robust evaluation of the various supervised techniques and to facilitate comparison with other studies. Prediction was undertaken separately within each breed and subsequently in a combined multi-breed dataset.

Results and discussion: Despite differences in predictive performance across the different supervised learning techniques and datasets (breeds), our results indicate reasonable prediction accuracies with mean correlation coefficient (r) as high as 0.94 and MAPE and RMSE as low as 4.0 % and 33.0 (kg), respectively. In comparison to the within-breed analyses (Jersey, Holstein), prediction using the combined multi-breed data set resulted in higher predictive performance in terms of high correlation coefficient and low MAPE. Additional tests showed that the improvement in predictive performance is mainly due to increase in data size from combining data rather than the multi-breed nature of the combined data. Of the different supervised learning techniques implemented, the tree-based group of supervised learning techniques (Catboost, AdaBoost, random forest) resulted in the highest prediction performance in all the metrics used to evaluate technique performance. Reported prediction errors in our study (RMSE and MAPE) are one of the lowest in the literature for prediction of BW using image data in dairy cattle, highlighting the promising predictive value of contour data from 3D images for BW in dairy cows under commercial farm conditions.
A new ferroptosis-related genetic mutation risk model predicts the prognosis of skin cutaneous melanoma
Authors: He Jia , Huang Wenting , Li Xinxin , Wang Jingru , Nie Yaxing , Li Guiqiang , Wang Xiaoxiang , Cao Huili , Chen Xiaodong , Wang Xusheng
Published: January 2023

Background: Ferroptosis is an iron-dependent cell death mode and closely linked to various cancers, including skin cutaneous melanoma (SKCM). Although attempts have been made to construct ferroptosis-related gene (FRG) signatures for predicting the prognosis of SKCM, the prognostic impact of ferroptosis-related genetic mutations in SKCM remains lacking. This study aims to develop a prediction model to explain the relationship between ferroptosis-related genetic mutations and clinical outcomes of SKCM patients and to explore the potential value of ferroptosis in SKCM treatment.

Methods: FRGs which significantly correlated with the prognosis of SKCM were firstly screened based on their single-nucleotide variant (SNV) status by univariate Cox regression analysis. Subsequently, the least absolute shrinkage and selection operator (LASSO) and Cox regressions were performed to construct a new ferroptosis-related genetic mutation risk (FerrGR) model for predicting the prognosis of SKCM. We then illustrate the survival and receiver operating characteristic (ROC) curves to evaluate the predictive power of the FerrGR model. Moreover, independent prognostic factors, genomic and clinical characteristics, immunotherapy, immune infiltration, and sensitive drugs were compared between high—and low—FerrGR groups.

Results: The FerrGR model was developed with a good performance on survival and ROC analysis. It was a robust independent prognostic indicator and followed a nomogram constructed to predict prognostic outcomes for SKCM patients. Besides, FerrGR combined with tumor mutational burden (TMB) or MSI (microsatellite instability) was considered as a combined biomarker for immunotherapy response. The high FerrGR group patients were associated with an inhibitory immune microenvironment. Furthermore, potential drugs target to high FerrGR samples were predicted.

Conclusion: The FerrGR model is valuable to predict prognosis and immunotherapy in SKCM patients. It offers a novel therapeutic option for SKCM.
IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study
Authors: Shojaei Maryam , Shamshirian Amir , Monkman James , Grice Laura , Tran Minh , Tan Chin Wee , Teo Siok Min , Rodrigues Rossi Gustavo , McCulloch Timothy R. , Nalos Marek , Raei Maedeh , Razavi Alireza , Ghasemian Roya , Gheibi Mobina , Roozbeh Fatemeh , Sly Peter D. , Spann Kirsten M. , Chew Keng Yih , Zhu Yanshan , Xia Yao , Wells Timothy J. , Senegaglia Alexandra Cristina , Kuniyoshi Carmen Lúcia , Franck Claudio Luciano , dos Santos Anna Flavia Ribeiro , Noronha Lucia de , Motamen Sepideh , Valadan Reza , Amjadi Omolbanin , Gogna Rajan , Madan Esha , Alizadeh-Navaei Reza , Lamperti Liliana , Zuñiga Felipe , Nova-Lamperti Estefania , Labarca Gonzalo , Knippenberg Ben , Herwanto Velma , Wang Ya , Phu Amy , Chew Tracy , Kwan Timothy , Kim Karan , Teoh Sally , Pelaia Tiana M. , Kuan Win Sen , Jee Yvette , Iredell Jon , O’Byrne Ken , Fraser John F. , Davis Melissa J. , Belz Gabrielle T. , Warkiani Majid E. , Gallo Carlos Salomon , Souza-Fonseca-Guimaraes Fernando , Nguyen Quan , Mclean Anthony , Kulasinghe Arutha , Short Kirsty R. , Tang Benjamin
Published: January 2023

Purpose

Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness.

Methods

We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients.

Results

We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients.

Conclusion

These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.
SARS-CoV-2 antibody response after mRNA vaccination in healthcare workers with and without previous COVID-19, a follow-up study from the University Hospital in Krakow, Poland
Authors: Owsianka Izabella , Pac Agnieszka , Jachowicz Estera , Gutkowska Karolina , Szczuciński Wiktor , Maziarz Barbara , Sochacka-Tatara Elżbieta , Heczko Piotr , Sydor Wojciech , Żółtowska Barbara , Wójkowska-Mach Jadwiga
Published: January 2023

Introduction

Healthcare workers (HCWs) from the beginning of the pandemic have been at risk of exposure to SARS-CoV-2, so they were vaccinated as first.

Objectives

The purpose of the study was to determine the level of antibodies against SARS-CoV-2 in HCWs before and after vaccination with mRNA preparations according to previous COVID- 19.

Patients and methods

The HCWs from the University Hospital in Krakow completed two surveys: the baseline survey before receiving the first dose of vaccine (in January 2021) and the follow-up survey in June 2021. In parallel, two blood samples were collected from each participant at baseline and at follow-up. Total anti-SARS-CoV-2 antibody levels were measured using the ECLIA technique.

Results

At baseline, 41.1% of HCWs had positive antibody test results, and at follow-up, the vaccinated HCWs had almost 100 times higher antibody levels than the unvaccinated HCWs. Participants under 30 years of age had significantly higher antibody levels in June than older HCWs. Among participants with positive antibody test results in January, HCWs who had experienced asymptomatic COVID-19 had more than five times higher antibody levels in June than HCWs self-reported severe COVID-19. In total, 86.9% of HCWs received Comirnaty or Spikevax. The incidence rate of COVID-19 in the unvaccinated vs. vaccinated group was 13 times higher, 20.5% and 1.9% respectively.

Conclusions

These results confirm the effectiveness of vaccination in the prevention of COVID-19 in HCWs. It is worth getting vaccinated regardless of previous infection. Furthermore, vaccination among HCWs under 30 years of age induced more effective antibody production compared to older individuals.
A CRISPR/Cas9-mediated screen identifies determinants of early plasma cell differentiation
Authors: Xiong Ermeng , Popp Oliver , Salomon Claudia , Mertins Philipp , Kocks Christine , Rajewsky Klaus , Chu Van Trung
Published: January 2023

Introduction

The differentiation of B cells into antibody-secreting plasma cells depends on cell division-coupled, epigenetic and other cellular processes that are incompletely understood.

Methods

We have developed a CRISPR/Cas9-based screen that models an early stage of T cell-dependent plasma cell differentiation and measures B cell survival or proliferation versus the formation of CD138+ plasmablasts. Here, we refined and extended this screen to more than 500 candidate genes that are highly expressed in plasma cells.

Results

Among known genes whose deletion preferentially or mostly affected plasmablast formation were the transcription factors Prdm1 (BLIMP1), Irf4 and Pou2af1 (OBF-1), and the Ern1 gene encoding IRE1a, while deletion of XBP1, the transcriptional master regulator that specifies the expansion of the secretory program in plasma cells, had no effect. Defective plasmablast formation caused by Ern1 deletion could not be rescued by the active, spliced form of XBP1 whose processing is dependent on and downstream of IRE1a, suggesting that in early plasma cell differentiation IRE1a acts independently of XBP1. Moreover, we newly identified several genes involved in NF-kB signaling (Nfkbia), vesicle trafficking (Arf4, Preb) and epigenetic regulators that form part of the NuRD complex (Hdac1, Mta2, Mbd2) to be required for plasmablast formation. Deletion of ARF4, a small GTPase required for COPI vesicle formation, impaired plasmablast formation and blocked antibody secretion. After Hdac1 deletion plasmablast differentiation was consistently reduced by about 50%, while deletion of the closely related Hdac2 gene had no effect. Hdac1 knock-out led to strongly perturbed protein expression of antagonistic transcription factors that govern plasma cell versus B cell identity (by decreasing IRF4 and BLIMP1 and increasing BACH2 and PAX5).

Discussion

Taken together, our results highlight specific and non-redundant roles for Ern1, Arf4 and Hdac1 in the early steps of plasma cell differentiation.
Comprehensive comparative analysis of prognostic value of serum systemic inflammation biomarkers for colorectal cancer: Results from a large multicenter collaboration
Authors: Xie Hailun , Ruan Guotian , Wei Lishuang , Zhang Heyang , Ge Yizhong , Zhang Qi , Song Mengmeng , Zhang Xi , Liu Xiaoyue , Lin Shiqi , Yang Ming , Hu Chunlei , Tang Meng , Deng Li , Hu Wen , Shi Hanping
Published: January 2023

Background

The incidence of colorectal cancer (CRC) is common and reliable biomarkers are lacking. We aimed to systematically and comprehensively compare the ability of various combinations of serum inflammatory signatures to predict the prognosis of CRC. Moreover, particular attention has been paid to the clinical feasibility of the newly developed inflammatory burden index (IBI) as a prognostic biomarker for CRC.

Methods

The discrimination capacity of the biomarkers was compared using receiver operating characteristic curves and Harrell’s C-index. Kaplan-Meier curves and log-rank tests were used to compare survival differences between the groups. Cox proportional hazard regression analysis was used to determine the independent prognostic factors. Logistic regression analysis was used to assess the relationship between IBI, short-term outcomes, and malnutrition.

Results

IBI had the optimal prediction accuracy among the systemic inflammation biomarkers for predicting the prognosis of CRC. Taking IBI as a reference, none of the remaining systemic inflammation biomarkers showed a gain. Patients with high IBI had significantly worse overall survival than those with low IBI (56.7% vs. 80.2%; log-rank P<0.001). Multivariate Cox regression analysis showed that continuous IBI was an independent risk factor for the prognosis of CRC patients (hazard ratio = 1.165, 95% confidence interval [CI] = 1.043–1.302, P<0.001). High IBI was an independent risk factor for short-term outcomes (odds ratio [OR] = 1.537, 95% CI = 1.258–1.878, P<0.001), malnutrition (OR = 2.996, 95% CI = 1.471–6.103, P=0.003), and recurrence (OR = 1.744, 95% CI = 1.176–2.587, p = 0.006) in CRC patients.

Conclusions

IBI, as a reflection of systemic inflammation, is a feasible and promising biomarker for assessing the prognosis of CRC patients.
Effect of polypropylene fibre on cementitious mortar early shrinkage cracking using the eccentric-ring test
Authors: Abusogi Maha A. , Muda Zakaria Che , Hafez Mohamed Ahmed , Bakri Mudthir
Published: January 2023

The effects of polypropylene fibres on mortar and cement-paste cracking were investigated using different amounts of fibre fractions and eccentric rings under restrained-shrinkage conditions. Eccentric-ring tests were conducted to investigate early-age shrinkage cracks. The characteristics of restricted cementitious materials were described by evaluating the cracking time and using concrete mixtures that are less likely to crack. Different fibre-volume fractions significantly enhanced the width, area, and age of cracking. Increasing the water-cement ratio and sand percentage increased the cracking age. The eccentric-ring test showed a greater susceptibility to cracking in cement-mortar composites. The mechanical strength was assessed, and the impact of polypropylene fibres was investigated.
Clinical outcomes and characteristics of critically ill patients with influenza- and COVID-19-induced ARDS: A retrospective, matched cohort study
Authors: Volkov Lev , Delpuech Marion , Conrad Marie , Courte Guilhem , Cravoisy Aurélie , Nace Lionel , Baumann Cedric , Gibot Sébastien
Published: January 2023

Introduction

Seasonal epidemic influenza and SARS-CoV-2 are the most frequent viruses causing acute respiratory distress syndrome (ARDS). To what extent these two etiologies differ in ICU patients remains uncertain. We, therefore, aimed at comparing the severity and outcomes of influenza and SARS-CoV-2-induced ARDS in mechanically ventilated patients.

Methods

This retrospective, analytic, single-center study was conducted in the medical ICU of Nancy University Hospital in France. Adult patients hospitalized with confirmed influenza (from 2009 to 2019) or SARS-CoV-2-induced ARDS (between March 2020 and May 2021) and those under mechanical ventilation were included. Each patient with influenza was matched with two patients with COVID-19, with the same severity of ARDS. The primary endpoint was death in ICU on day 28. The secondary endpoints were the duration of vasopressors, the use of renal replacement therapy, the duration of mechanical ventilation, and the ICU length of stay.

Results

A total of 42 patients with influenza were matched with 84 patients with COVID-19. They had similar sex distribution, age, Charlson comorbidity index, and ARDS severity. On day 28, 11 (26.2%) patients in the influenza group and nine (10.7%) patients in the COVID-19 group had died (p = 0.0084, HR = 3.31, CI 95% [1.36–8.06]). In the univariate Cox model, being infected with SARS-CoV-2, SOFA and SAPS II scores, initial arterial pH, PaCO2, PaO2/FiO2, serum lactate level, platelet count, and use of renal replacement therapy were significantly associated with mortality. In the multivariate Cox model, the SOFA score at admission (p < 0.01, HR = 1.284, CI 95% [1.081; 1.525]) and the initial pH (p < 0.01, HR = 0.618, CI 95% [0.461; 0.828]) were the only predictors of mortality. The type of virus had no influence on mortality, though patients with COVID-19 underwent longer mechanical ventilation and received more neuromuscular blockers and prone positioning.

Conclusion

In mechanically ventilated patients with ARDS, 28-day mortality was higher among patients with influenza as compared to patients with COVID-19 because of a higher initial extra-pulmonary severity. However, the type of virus was not, by itself, correlated with mortality.
Effects of microbial inoculant and additives on pile composting of cow manure
Authors: Yang Qian , Zhang Shiqiu , Li Xueping , Rong Kun , Li Jialiang , Jiang Lihua
Published: January 2023

Composting is an effective method of recycling organic solid waste, and it is the key process linking planting with recycling. To explore the reuse of agricultural organic solid waste as a resource in the Yellow River Delta, the effects of microbial inoculant and different additives (calcium superphosphate, biochar, tomato straw, rice husk, and sugar residue) on pile composting of cow dung were studied to obtain the best composting conditions. The results showed that microbial inoculant and additives all played positive roles in the process of aerobic composting, and the experimental groups outperformed the control groups without any additives. For discussion, the microbial inoculant promoted rapid pile body heating more than the recovery materials alone, and the effects on aerobic composting were related to the organic matter of substrates and biochar. After being composted, all the materials were satisfactorily decomposed. Degradation of additives into humic acid might serve as electron shuttles to promote thorough organic matter decomposition. These results provide a scientific basis data for industrial composting of organic solid waste processed by on-site stacking, and provide a reference for researcher and practitioners for studying the applications of microbial inoculant on aerobic composting.
Phytotoxic Azaphilones From the Mangrove-Derived Fungus Penicillium sclerotiorum HY5
Authors: Wang Wei , Wang Mei , Wang Xian-Bo , Li Yi-Qiang , Ding Ji-Lin , Lan Ming-Xian , Gao Xi , Zhao Dong-Lin , Zhang Cheng-Sheng , Wu Guo-Xing
Published: January 2023

Graphical Abstract

Representative phytotoxic azaphilones from Penicillium sclerotiorum HY5.
Calmodulin variants associated with congenital arrhythmia impair selectivity for ryanodine receptors
Authors: Dal Cortivo Giuditta , Marino Valerio , Bianconi Silvia , Dell'Orco Daniele
Published: January 2023

Among its many molecular targets, the ubiquitous calcium sensor protein calmodulin (CaM) recognizes and regulates the activity of ryanodine receptors type 1 (RyR1) and 2 (RyR2), mainly expressed in skeletal and cardiac muscle, respectively. Such regulation is essential to achieve controlled contraction of muscle cells. To unravel the molecular mechanisms underlying the target recognition process, we conducted a comprehensive biophysical investigation of the interaction between two calmodulin variants associated with congenital arrhythmia, namely N97I and Q135P, and a highly conserved calmodulin-binding region in RyR1 and RyR2. The structural, thermodynamic, and kinetic properties of protein-peptide interactions were assessed together with an in-depth structural and topological investigation based on molecular dynamics simulations. This integrated approach allowed us to identify amino acids that are crucial in mediating allosteric processes, which enable high selectivity in molecular target recognition. Our results suggest that the ability of calmodulin to discriminate between RyR1 an RyR2 targets depends on kinetic discrimination and robust allosteric communication between Ca2+-binding sites (EF1-EF3 and EF3-EF4 pairs), which is perturbed in both N97I and Q135P arrhythmia-associated variants.
Morphologic brain network predicts levodopa responsiveness in Parkinson disease
Authors: Xie Yongsheng , Gao Chunyan , Wu Bin , Peng Liling , Wu Jianjun , Lang Liqin
Published: January 2023

Background

The levodopa challenge test (LCT) has been routinely used in Parkinson disease (PD) evaluation and predicts the outcome of deep brain stimulation (DBS). Guidelines recommend that patients with an improvement in Unified Parkinson’s Disease Rating Scale (UPDRS)-III score > 33% in the LCT receive DBS treatment. However, LCT results are affected by many factors, and only provide information on the immediate effectiveness of dopamine. The aim of the present study was to investigate the relationship between LCT outcome and brain imaging features of PD patients to determine whether the latter can be used to identify candidates for DBS.

Methods

A total of 38 PD patients were enrolled in the study. Based on improvement in UPDRS-III score in the LCT, patients were divided into low improvement (PD-LCT-L) and high improvement (PD-LCT-H) groups. Each patient’s neural network was reconstructed based on T1-weighted magnetic resonance imaging data using the Jensen–Shannon divergence similarity estimation method. The network was established with the multiple kernel support vector machine technique. We analyzed differences in individual morphologic brain networks and their global and local metrics to determine whether there were differences in the connectomes of PD-LCT-L and PD-LCT-H groups.

Results

The 2 groups were similar in terms of demographic and clinical characteristics. Mean ± SD levodopa responsiveness was 26.52% ± 3.47% in the PD-LCT-L group (N = 13) and 58.66% ± 4.09% in the PD-LCT-H group (N = 25). There were no significant differences between groups in global and local metrics. There were 43 consensus connections that were affected in both groups; in PD-LCT-L patients, most of these connections were decreased whereas those related to the dorsolateral superior frontal gyrus and left cuneus were significantly increased.

Conclusion

Morphologic brain network assessment is a valuable method for predicting levodopa responsiveness in PD patients, which can facilitate the selection of candidates for DBS.
Parallel learning and cognitive flexibility impairments between Fmr1 knockout mice and individuals with fragile X syndrome
Authors: Schmitt Lauren M. , Arzuaga Anna L. , Dapore Ashley , Duncan Jason , Patel Maya , Larson John R. , Erickson Craig A. , Sweeney John A. , Ragozzino Michael E.
Published: January 2023

Introduction

Fragile X Syndrome (FXS) is a monogenic condition that leads to intellectual disability along with behavioral and learning difficulties. Among behavioral and learning difficulties, cognitive flexibility impairments are among the most commonly reported in FXS, which significantly impacts daily living. Despite the extensive use of the Fmr1 knockout (KO) mouse to understand molecular, synaptic and behavioral alterations related to FXS, there has been limited development of translational paradigms to understand cognitive flexibility that can be employed in both animal models and individuals with FXS to facilitate treatment development.

Methods

To begin addressing this limitation, a parallel set of studies were carried out that investigated probabilistic reversal learning along with other behavioral and cognitive tests in individuals with FXS and Fmr1 KO mice. Fifty-five adolescents and adults with FXS (67% male) and 34 age- and sex-matched typically developing controls (62% male) completed an initial probabilistic learning training task and a probabilistic reversal learning task.

Results

In males with FXS, both initial probabilistic learning and reversal learning deficits were found. However, in females with FXS, we only observed reversal learning deficits. Reversal learning deficits related to more severe psychiatric features in females with FXS, whereas increased sensitivity to negative feedback (lose:shift errors) unexpectedly appear to be adaptive in males with FXS. Male Fmr1 KO mice exhibited both an initial probabilistic learning and reversal learning deficit compared to that of wildtype (WT) mice. Female Fmr1 KO mice were selectively impaired on probabilistic reversal learning. In a prepotent response inhibition test, both male and female Fmr1 KO mice were impaired in learning to choose a non-preferred spatial location to receive a food reward compared to that of WT mice. Neither male nor female Fmr1 KO mice exhibited a change in anxiety compared to that of WT mice.

Discussion

Together, our findings demonstrate strikingly similar sex-dependent learning disturbances across individuals with FXS and Fmr1 KO mice. This suggests the promise of using analogous paradigms of cognitive flexibility across species that may speed treatment development to improve lives of individuals with FXS.
Neurophysiological and emotional influences on team communication and metacognitive cyber situational awareness during a cyber engineering exercise
Authors: Ask Torvald F. , Knox Benjamin J. , Lugo Ricardo G. , Helgetun Ivar , Sütterlin Stefan
Published: January 2023

Background: Cyber operations unfold at superhuman speeds where cyber defense decisions are based on human-to-human communication aiming to achieve a shared cyber situational awareness. The recently proposed Orient, Locate, Bridge (OLB) model suggests a three-phase metacognitive approach for successful communication of cyber situational awareness for good cyber defense decision-making. Successful OLB execution implies applying cognitive control to coordinate self-referential and externally directed cognitive processes. In the brain, this is dependent on the frontoparietal control network and its connectivity to the default mode network. Emotional reactions may increase default mode network activity and reduce attention allocation to analytical processes resulting in sub-optimal decision-making. Vagal tone is an indicator of activity in the dorsolateral prefrontal node of the frontoparietal control network and is associated with functional connectivity between the frontoparietal control network and the default mode network.

Aim: The aim of the present study was to assess whether indicators of neural activity relevant to the processes outlined by the OLB model were related to outcomes hypothesized by the model.

Methods: Cyber cadets (N = 36) enrolled in a 3-day cyber engineering exercise organized by the Norwegian Defense Cyber Academy participated in the study. Differences in prospective metacognitive judgments of cyber situational awareness, communication demands, and mood were compared between cyber cadets with high and low vagal tone. Vagal tone was measured at rest prior to the exercise. Affective states, communication demands, cyber situational awareness, and metacognitive accuracy were measured on each day of the exercise.

Results: We found that cyber cadets with higher vagal tone had better metacognitive judgments of cyber situational awareness, imposed fewer communication demands on their teams, and had more neutral moods compared to cyber cadets with lower vagal tone.

Conclusion: These findings provide neuroergonomic support for the OLB model and suggest that it may be useful in education and training. Future studies should assess the effect of OLB-ing as an intervention on communication and performance.
Impact of malnutrition evaluated by the mini nutritional assessment on the prognosis of acute hospitalized older adults
Authors: Kang Min-gu , Choi Jung-Yeon , Yoo Hyun-Jung , Park Si-Young , Kim Yoonhee , Kim Ji Yoon , Kim Sun-wook , Kim Cheol-Ho , Kim Kwang-il
Published: January 2023

Background

Malnutrition is prevalent among hospitalized older patients. Therefore, this study aimed to investigate the association between nutritional status [assessed using the Mini Nutritional Assessment (MNA) and serum albumin levels] and adverse outcomes in hospitalized older patients. We also aimed to compare the predictive utility of our findings.

Methods

This retrospective cohort study was conducted between January 2016 and June 2020. In total, 808 older patients (aged ≥ 65 years, mean age 82.8 ± 6.70 years, 45.9% male) admitted to the acute geriatric unit were included in our sample. Comprehensive geriatric assessments, including the MNA, were performed. Malnutrition and risk of malnutrition were defined as MNA < 17, albumin < 3.5 g/dL and 17 ≤ MNA ≤ 24, 3.5 g/dL ≤ albumin < 3.9 g/dL, respectively. The primary outcome was that patients could not be discharged to their own homes. The secondary outcomes were overall all-cause mortality, 3-month all-cause mortality, and incidence of geriatric syndrome, including delirium, falls, and newly developed or worsening pressure sores during hospitalization.

Results

Poor nutritional status was associated with older age; female sex; admission from the emergency room; high risk of pressure sores and falls; lower physical and cognitive function; higher depressive score; and lower serum albumin, protein, cholesterol, and hemoglobin levels. In the fully adjusted model, malnutrition assessed using the MNA predicted discharge to nursing homes or long-term care hospitals [odds ratio (OR) 5.822, 95% confidence interval (CI): 2.092–16.199, P = 0.001], geriatric syndrome (OR 2.069, 95% CI: 1.007–4.249, P = 0.048), and 3-month mortality (OR 3.519, 95% CI: 1.254–9.872, P = 0.017). However, malnutrition assessed using albumin levels could only predict 3-month mortality (OR 3.848, 95% CI: 1.465–10.105, P = 0.006). The MNA predicted 3-month mortality with higher precision than serum albumin levels (P = 0.034) when comparing the areas under the receiver operating characteristic curve.

Conclusion

Nutritional risk measured by the MNA was an independent predictor of various negative outcomes in hospitalized older patients. Poor nutritional status assessed by serum albumin levels, the most widely used biochemical marker, could predict mortality, but not the development of geriatric syndrome or discharge location reflecting functional status.
Early impairment of food intake in patients newly diagnosed with cancer
Authors: Molfino Alessio , Emerenziani Sara , Tonini Giuseppe , Santini Daniele , Gigante Antonietta , Guarino Michele Pier Luca , Nuglio Chiara , Imbimbo Giovanni , La Cesa Annalisa , Cicala Michele , Muscaritoli Maurizio
Published: January 2023

Background

Patients with gastrointestinal or lung cancer often suffer from a loss of appetite (anorexia), resulting in reduced food intake (hypophagia) and body weight loss. This study evaluated the prevalence of anorexia, hypophagia, pre-cachexia and cachexia in patients with cancer at time of diagnosis.

Patients and methods

Patients with newly diagnosed gastrointestinal or lung cancers were included. Body mass index (BMI) and weight loss over the prior 6 months were recorded. Patients were assessed for (pre-)cachexia and for anorexia using the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) and a specific anorexia questionnaire (AQ). Energy and protein intake were calculated through food diaries. Patients were considered hypophagic if intake was ≤70% of guideline-recommended levels.

Results

Overall, 102 patients [53 male; median age: 67 (range, 21–88) years] were enrolled. Mean BMI (± standard deviation) was 23.1 ± 3.4 kg/m2; average percentage of weight loss was 10.1 ± 7.8%. At diagnosis, 68% (69/102) of patients had cachexia, and 11% (11/102) pre-cachexia. Prevalence of anorexia was 57% (58/102) and 75% (76/102) according to FAACT and AQ, respectively. Forty-eight percent (49/102) of patients had hypophagia. Patients with anorexia had lower daily energy (p = 0.002) and protein intake (p = 0.0257), and greater percentage of weight loss (p = 0.0005). In patients with hypophagia, negative correlations were observed between percentage of weight loss and total daily calorie (r = –0.40; p = 0.01) and protein intake (r = –0.340; p = 0.018).

Conclusion

Anorexia, inadequate nutritional intake and cachexia are highly prevalent in patients with gastrointestinal or lung cancer at diagnosis. Negative protein and energy balance may play an important role in the pathogenesis of cachexia. Early multimodal strategies to improve food intake are urgently needed.
Poor health literacy associated with stronger perceived barriers to breast cancer screening and overestimated breast cancer risk
Authors: Poon Paul K. M. , Tam King Wa , Lam Thomas , Luk Arthur K. C. , Chu Winnie C. W. , Cheung Polly , Wong Samuel Y. S. , Sung Joseph J. Y.
Published: January 2023

Background

Low health literacy (HL) is negatively associated with mammography screening uptake. However, evidence of the links between poor HL and low mammography screening participation is scarce.

Methods

We conducted a cross-sectional questionnaire survey among participants of a cancer screening program. We measured HL using a validated Chinese instrument. We assessed breast cancer screening-related beliefs using the Health Belief Model and the accuracy of risk perception. We used multivariable regression models to estimate the relationship between HL and the outcomes.

Results

A total of 821 females were included. 264 (32.2%) had excellent or sufficient, 353 (43.0%) had problematic, and 204 (24.8%) had inadequate health literacy (IHL). Women with IHL were more likely to agree that high price (β = -0.211, 95% CI -0.354 to -0.069), lack of time (β = -0.219, 95% CI -0.351 to -0.088), inconvenient service time (β = -0.291, 95% CI -0.421 to -0.160), long waiting time (β = -0.305, 95% CI -0.447 to -0.164), fear of positive results (β = -0.200, 95% CI -0.342 to -0.058), embarrassment (β = -0.225, 95% CI -0.364 to -0.086), fear of pain (β = -0.154, 95% CI -0.298 to -0.010), fear of radiation (β = -0.177, 95% CI -0.298 to -0.056), lack of knowledge on service location (β = -0.475, 95% CI -0.615 to -0.335), and lack of knowledge on mammography (β = -0.360, 95% CI -0.492 to -0.228) were barriers. They were also less likely to have an accurate breast cancer risk perception (aOR 0.572, 95% CI 0.341 to 0.956).

Conclusion

Women with lower HL could have stronger perceived barriers to BC screening and an over-estimation of their breast cancer risk. Tackling emotional and knowledge barriers, financial and logistical assistance, and guidance on risk perception are needed to increase their breast cancer screening uptake.
Is CD19-directed chimeric antigen receptor T cell therapy a smart strategy to combat central nervous system lymphoma?
Authors: Miyao Kotaro , Yokota Hirofumi , Sakemura R. Leo
Published: January 2023

Primary central nervous system lymphoma (PCNSL) is a rare form and aggressive type of diffuse large B-cell lymphoma (DLBCL) that occurs in both immunocompetent and immunocompromised adults. While adding rituximab to chemotherapeutic regimens resulted in dramatic improvement in both progression-free survival and overall survival in patients with non-central nervous system (CNS) DLBCL, the outcomes of PCNSL are generally poor due to the immune-privileged tumor microenvironment or suboptimal delivery of systemic agents into tumor tissues. Therefore, more effective therapy for PCNSL generally requires systemic therapy with sufficient CNS penetration, including high-dose intravenous methotrexate with rituximab or high-dose chemotherapy followed by autologous stem cell transplantation. However, overall survival is usually inferior in comparison to non-CNS lymphomas, and treatment options are limited for elderly patients or patients with relapsed/refractory disease. Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a cutting-edge cancer therapy, which led to recent FDA approvals for patients with B-cell malignancies and multiple myeloma. Although CAR-T cell therapy in patients with PCNSL demonstrated promising results without significant toxicities in some small cohorts, most cases of PCNSL are excluded from the pivotal CAR-T cell trials due to the concerns of neurotoxicity after CAR-T cell infusion. In this review, we will provide an overview of PCNSL and highlight current approaches, resistance mechanisms, and future perspectives of CAR-T cell therapy in patients with PCNSL.
Gradient differences of immunotherapy efficacy in metastatic melanoma related to sunlight exposure pattern: A population-based study
Authors: Liu Mengsong , Li Wenyuan , Ma Xiao , Che Yuhui , Wei Bo , Chen Mulan , Zhong Lin , Zhao Siqi , Chen Anjing , Pang Yaobin , Zeng Jinhao , Guo Jing
Published: January 2023

Background

Immune checkpoint inhibitors (ICIs) have revolutionized metastatic melanoma (MM) treatment in just a few years. Ultraviolet (UV) in sunlight is the most significant environmental cause of melanoma, which is considered to be the main reason for tumor mutation burden (TMB) increase in melanoma. High TMB usually predicts that PD-1 inhibitors are effective. The sunlight exposure pattern of MM might be a clinical feature that matches TMB. The relationship between sunlight exposure patterns and immunotherapy response in MM is unclear. This study aims to investigate the correlation between sunlight exposure patterns and immunotherapy response in MM and establish nomograms that predict 3- and 5-year overall survival (OS) rate.

Methods

We searched the Surveillance, Epidemiology, and End Results (SEER) database and enrolled MM cases from 2005-2016. According to the advent of ICIs in 2011, the era was divided into the non-ICIs era (2005-2010) and the ICIs era (2011-2016). Patients were divided into three cohorts according to the primary site sunlight exposure patterns: head and neck in the first cohort, trunk arms and legs in the second cohort, and acral sites in the third cohort. We compared survival differences for each cohort between the two eras, performed stratified analysis, established nomograms for predicting 3- and 5-year OS rate, and performed internal validation.

Results

Comparing the survival difference between the ICIs and non-ICIs era, head and neck melanoma showed the greatest improvement in survival, with 3- and 5-year OS rate increasing by 10.2% and 9.1%, respectively (P=0.00011). In trunk arms and legs melanoma, the 3- and 5-year OS rate increased by 4.6% and 3.9%, respectively (P<0.0001). There is no improvement in survival in acral melanoma (AM) between the two eras (P=0.78). The receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and calibration graphs show good discrimination and accuracy of nomograms. Decision curve analysis (DCA) suggests good clinical utility of nomograms.

Conclusions

Based on the classification of sunlight exposure patterns, there is a gradient difference in immunotherapy efficacy for MM. The degree of sunlight exposure is positively correlated with immunotherapy response. The nomograms are sufficiently accurate to predict 3- and 5-year OS rate for MM, allowing for individualized clinical decisions for future clinical work.
Investigating the diagnostic efficiency of a computer-aided diagnosis system for thyroid nodules in the context of Hashimoto’s thyroiditis
Authors: Gong Liu , Zhou Ping , Li Jia-Le , Liu Wen-Gang
Published: January 2023

Objectives

This study aims to investigate the efficacy of a computer-aided diagnosis (CAD) system in distinguishing between benign and malignant thyroid nodules in the context of Hashimoto’s thyroiditis (HT) and to evaluate the role of the CAD system in reducing unnecessary biopsies of benign lesions.

Methods

We included a total of 137 nodules from 137 consecutive patients (mean age, 43.5 ± 11.8 years) who were histopathologically diagnosed with HT. The two-dimensional ultrasound images and videos of all thyroid nodules were analyzed by the CAD system and two radiologists with different experiences according to ACR TI-RADS. The diagnostic cutoff values of ACR TI-RADS were divided into two categories (TR4 and TR5), and then the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of the CAD system and the junior and senior radiologists were compared in both cases. Moreover, ACR TI-RADS classification was revised according to the results of the CAD system, and the efficacy of recommended fine-needle aspiration (FNA) was evaluated by comparing the unnecessary biopsy rate and the malignant rate of punctured nodules.

Results

The accuracy, sensitivity, specificity, PPV, and NPV of the CAD system were 0.876, 0.905, 0.830, 0.894, and 0.846, respectively. With TR4 as the cutoff value, the AUCs of the CAD system and the junior and senior radiologists were 0.867, 0.628, and 0.722, respectively, and the CAD system had the highest AUC (P < 0.0001). With TR5 as the cutoff value, the AUCs of the CAD system and the junior and senior radiologists were 0.867, 0.654, and 0.812, respectively, and the CAD system had a higher AUC than the junior radiologist (P < 0.0001) but comparable to the senior radiologist (P = 0.0709). With the assistance of the CAD system, the number of TR4 nodules was decreased by both junior and senior radiologists, the malignant rate of punctured nodules increased by 30% and 22%, and the unnecessary biopsies of benign lesions were both reduced by nearly half.

Conclusions

The CAD system based on deep learning can improve the diagnostic performance of radiologists in identifying benign and malignant thyroid nodules in the context of Hashimoto’s thyroiditis and can play a role in FNA recommendations to reduce unnecessary biopsy rates.