bluuebunny/crossref_metadata_2025 huggingface dataset:
Realizing the value in “non-standard” parts of the qPCR standard curve by integrating fundamentals of quantitative microbiology
Authors: Schmidt Philip J. , Acosta Nicole , Chik Alex H. S. , D’Aoust Patrick M. , Delatolla Robert , Dhiyebi Hadi A. , Glier Melissa B. , Hubert Casey R. J. , Kopetzky Jennifer , Mangat Chand S. , Pang Xiao-Li , Peterson Shelley W. , Prystajecky Natalie , Qiu Yuanyuan , Servos Mark R. , Emelko Monica B.
Published: March 2023

The real-time polymerase chain reaction (PCR), commonly known as quantitative PCR (qPCR), is increasingly common in environmental microbiology applications. During the COVID-19 pandemic, qPCR combined with reverse transcription (RT-qPCR) has been used to detect and quantify SARS-CoV-2 in clinical diagnoses and wastewater monitoring of local trends. Estimation of concentrations using qPCR often features a log-linear standard curve model calibrating quantification cycle (Cq) values obtained from underlying fluorescence measurements to standard concentrations. This process works well at high concentrations within a linear dynamic range but has diminishing reliability at low concentrations because it cannot explain “non-standard” data such as Cq values reflecting increasing variability at low concentrations or non-detects that do not yield Cq values at all. Here, fundamental probabilistic modeling concepts from classical quantitative microbiology were integrated into standard curve modeling approaches by reflecting well-understood mechanisms for random error in microbial data. This work showed that data diverging from the log-linear regression model at low concentrations as well as non-detects can be seamlessly integrated into enhanced standard curve analysis. The newly developed model provides improved representation of standard curve data at low concentrations while converging asymptotically upon conventional log-linear regression at high concentrations and adding no fitting parameters. Such modeling facilitates exploration of the effects of various random error mechanisms in experiments generating standard curve data, enables quantification of uncertainty in standard curve parameters, and is an important step toward quantifying uncertainty in qPCR-based concentration estimates. Improving understanding of the random error in qPCR data and standard curve modeling is especially important when low concentrations are of particular interest and inappropriate analysis can unduly affect interpretation, conclusions regarding lab performance, reported concentration estimates, and associated decision-making.
Glucose oxidase as an alternative to antibiotic growth promoters improves the immunity function, antioxidative status, and cecal microbiota environment in white-feathered broilers
Authors: Zhao Wenyu , Huang Yuan , Cui Na , Wang Ruiguo , Xiao Zhiming , Su Xiaoou
Published: March 2023

This study aimed to demonstrate the effects of glucose oxidase (GOD) on broilers as a potential antibiotic substitute. A total of four hundred twenty 1-day-old male Cobb500 broilers were randomly assigned into five dietary treatments, each with six replicates (12 chicks per replicate). The treatments included two control groups (a basal diet and a basal diet with 50 mg/kg aureomycin) and three GOD-additive groups involving three different concentrations of GOD. Analysis after the t-test showed that, on day 21, the feed:gain ratio significantly decreased in the 1,200 U/kg GOD-supplied group (GOD1200) compared to the antibiotic group (Ant). The same effect was also observed in GOD1200 during days 22–42 and in the 600 U/kg GOD-supplied group (GOD600) when compared to the control group (Ctr). The serum tests indicated that, on day 21, the TGF-β cytokine was significantly decreased in both GOD600 and GOD1200 when compared with Ctr. A decrease in malondialdehyde and an increase in superoxide dismutase in GOD1200 were observed, which is similar to the effects seen in Ant. On day 42, the D-lactate and glutathione peroxidase activity changed remarkably in GOD1200 and surpassed Ant. Furthermore, GOD upregulated the expression of the jejunal barrier genes (MUC-2 and ZO-1) in two phases relative to Ctr. In the aureomycin-supplied group, the secretory immunoglobulin A significantly decreased in the jejunum at 42 days. Changes in microbial genera were also discovered in the cecum by sequencing 16S rRNA genes at 42 days. The biomarkers for GOD supplementation were identified as Colidextribacter, Oscillibacter, Flavonifractor, Oscillospira, and Shuttleworthia. Except for Shuttleworthia, all the abovementioned genera were n-butyrate producers known for imparting their various benefits to broilers. The PICRUSt prediction of microbial communities revealed 11 pathways that were enriched in both the control and GOD-supplied groups. GOD1200 accounted for an increased number of metabolic pathways, demonstrating their potential in aiding nutrient absorption and digestion. In conclusion, a diet containing GOD can be beneficial to broiler health, particularly at a GOD concentration of 1,200 U/kg. The improved feed conversion ratio, immunity, antioxidative capacity, and intestinal condition demonstrated that GOD could be a valuable alternative to antibiotics in broiler breeding.
The first Brevinin-1 antimicrobial peptide with LPS-neutralizing and anti-inflammatory activities in vitro and in vivo
Authors: Tian Maolin , Wang Kai , Liang Yan , Chai Jinwei , Wu Jiena , Zhang Haiyun , Huang Xiaowen , Chen Xin , Xu Xueqing
Published: March 2023

Antimicrobial peptide is one important component of the first protective barrier of organisms. They not only have potent antimicrobial activity which can protect the body from the invading pathogens, but also participate in the immune regulation of the body. In this study, a Brevinin-1 peptide named by Brevinin-1GHd was identified from Hoplobatrachus rugulosus, and the similarity of mature peptide sequence among Brevinin-1GHd, Brevinin-1HL and Brevinin-1GHa supported the close species relationship between H. rugulosus, Hylarana latouchii and Hylarana guertheri. Moreover, the secondary structure of Brevinin-1GHd was found to possess α-helical characteristics and high thermal stability. In addition, Brevinin-1GHd could bind to LPS with a Kd value of 6.49 ± 5.40 mM and suppress the release of TNF-α, NO, IL-6 and IL-1β by inactivation of MAPK signaling pathway in RAW 264.7 cells induced by LPS. Furtherly, Brevinin-1GHd had a significant inhibitory effect on acute edema development in the right paw of mice injected by carrageenan. Thus, the significant LPS-neutralizing and anti-inflammatory activities of Brevinin-1GHd were demonstrated in this study, which made it become the first Brevinin-1 family peptide with anti-inflammatory activity reported so far, and the biological activity of Brevinin-1GHd made it promising to be a novel therapeutic drug for infectious inflammation.
Progress on innate immune evasion and live attenuated vaccine of pseudorabies virus
Authors: Nie Zhenyu , Zhu Shunfan , Wu Li , Sun Ruolin , Shu Jianhong , He Yulong , Feng Huapeng
Published: March 2023

Pseudorabies virus (PRV) is a highly infectious disease that can infect most mammals, with pigs as the only natural host, has caused considerable economic losses to the pig husbandry of the world. Innate immunity is the first defense line of the host against the attack of pathogens and is essential for the proper establishment of adaptive immunity. The host uses the innate immune response to against the invasion of PRV; however PRV makes use of various strategies to inhibit the innate immunity to promote the virus replication. Currently, live attenuated vaccine is used to prevent pig from infection with the PRV worldwide, such as Bartha K61. However, a growing number of data indicates that these vaccines do not provide complete protection against new PRV variants that have emerged since late 2011. Here we summarized the interactions between PRV and host innate immunity and the current status of live attenuated PRV vaccines to promote the development of novel and more effective PRV vaccines.
Assessing the epithelial-to-mesenchymal plasticity in a small cell lung carcinoma (SCLC) and lung fibroblasts co-culture model
Authors: Dhungel Nilu , Youngblood Reneau , Chu Min , Carroll Jennifer , Dragoi Ana-Maria
Published: March 2023

The tumor microenvironment (TME) is the source of important cues that govern epithelial-to-mesenchymal transition (EMT) and facilitate the acquisition of aggressive traits by cancer cells. It is now recognized that EMT is not a binary program, and cancer cells rarely switch to a fully mesenchymal phenotype. Rather, cancer cells exist in multiple hybrid epithelial/mesenchymal (E/M) states responsible for cell population heterogeneity, which is advantageous for the ever-changing environment during tumor development and metastasis. How are these intermediate states generated and maintained is not fully understood. Here, we show that direct interaction between small cell lung carcinoma cells and lung fibroblasts induces a hybrid EMT phenotype in cancer cells in which several mesenchymal genes involved in receptor interaction with the extracellular matrix (ECM) and ECM remodeling are upregulated while epithelial genes such as E-cadherin remain unchanged or slightly increase. We also demonstrate that several core EMT-regulating transcription factors (EMT-TFs) are upregulated in cancer cells during direct contact with fibroblasts, as is Yes-associated protein (YAP1), a major regulator of the Hippo pathway. Further, we show that these changes are transient and reverse to the initial state once the interaction is disrupted. Altogether, our results provide evidence that tumor cells’ direct contact with the fibroblasts in the TME initiates a signaling cascade responsible for hybrid E/M states of cancer cells. These hybrid states are maintained during the interaction and possibly contribute to therapy resistance and immune evasion, while interference with direct contact will result in slow recovery and switch to the initial states.
Untargeted analysis in post-COVID-19 patients reveals dysregulated lipid pathways two years after recovery
Authors: López-Hernández Yamilé , Oropeza-Valdez Juan José , García Lopez David Alejandro , Borrego Juan Carlos , Murgu Michel , Valdez Jorge , López Jesús Adrián , Monárrez-Espino Joel
Published: March 2023

Introduction: Similar to what it has been reported with preceding viral epidemics (such as MERS, SARS, or influenza), SARS-CoV-2 infection is also affecting the human immunometabolism with long-term consequences. Even with underreporting, an accumulated of almost 650 million people have been infected and 620 million recovered since the start of the pandemic; therefore, the impact of these long-term consequences in the world population could be significant. Recently, the World Health Organization recognized the post-COVID syndrome as a new entity, and guidelines are being established to manage and treat this new condition. However, there is still uncertainty about the molecular mechanisms behind the large number of symptoms reported worldwide.

Aims and Methods: In this study we aimed to evaluate the clinical and lipidomic profiles (using non-targeted lipidomics) of recovered patients who had a mild and severe COVID-19 infection (acute phase, first epidemic wave); the assessment was made two years after the initial infection.

Results: Fatigue (59%) and musculoskeletal (50%) symptoms as the most relevant and persistent. Functional analyses revealed that sterols, bile acids, isoprenoids, and fatty esters were the predicted metabolic pathways affected in both COVID-19 and post-COVID-19 patients. Principal Component Analysis showed differences between study groups. Several species of phosphatidylcholines and sphingomyelins were identified and expressed in higher levels in post-COVID-19 patients compared to controls. The paired analysis (comparing patients with an active infection and 2 years after recovery) show 170 dysregulated features. The relationship of such metabolic dysregulations with the clinical symptoms, point to the importance of developing diagnostic and therapeuthic markers based on cell signaling pathways.
Comparative efficacy and safety of antidepressant therapy for the agitation of dementia: A systematic review and network meta-analysis
Authors: Chen Kaili , Li Haiqi , Yang Le , Jiang Yan , Wang Qiaoli , Zhang Jiao , He Jinting
Published: March 2023

Background

Dementia is a clinical syndrome commonly seen in the elderly individuals. With the prevalence of dementia, the incidence of neuropsychiatric symptoms in dementia patients is increasing annually. Agitation, as one of the neuropsychiatric symptoms, has a serious impact on the quality of life of patients with dementia. Several antidepressant drugs have been shown to be effective for treating agitated behavior symptoms in patients with dementia, but there are no direct comparisons among those drugs. Therefore, we carried out a network meta-analysis (NMA) to examine the efficacy and safety of those antidepressant drugs.

Methods

We searched eight databases (PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, China National Knowledge Infrastructure, VIP Database and China biomedical literature service) from their inception to 6 November 2022. Randomized controlled trials (RCTs) reporting the efficacy and safety of antidepressant drugs in treating agitated behavior symptoms in patients with dementia were included in our analysis. The quality assessment was carried out by two researchers individually and the analysis was based on the frequency method.

Results

Twelve articles with 1,146 participants were included in our analysis. Based on the outcome of the agitation score, treatment with citalopram (standardized mean difference, SMD = −0.44, 95% confidence interval, 95% CI = −0.72 to −0.16) showed significant benefits over the placebo group. Treatment with trazodone (odds ratio, OR = 4.58, 95% CI = 1.12–18.69) was associated with a higher risk of total adverse events compared with a placebo treatment.

Conclusion

Among the antidepressant drugs included in this study, treatment with citalopram was probably the only optimal intervention, when considering the improvement from baseline to the end of the intervention, and there was not a statistically significant difference in safety when compared with a placebo treatment.

Systematic review registration

https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: PROSPERO, CRD42022320932.
Hierarchical predictive coding in distributed pain circuits
Authors: Chen Zhe Sage
Published: March 2023

Predictive coding is a computational theory on describing how the brain perceives and acts, which has been widely adopted in sensory processing and motor control. Nociceptive and pain processing involves a large and distributed network of circuits. However, it is still unknown whether this distributed network is completely decentralized or requires networkwide coordination. Multiple lines of evidence from human and animal studies have suggested that the cingulate cortex and insula cortex (cingulate-insula network) are two major hubs in mediating information from sensory afferents and spinothalamic inputs, whereas subregions of cingulate and insula cortices have distinct projections and functional roles. In this mini-review, we propose an updated hierarchical predictive coding framework for pain perception and discuss its related computational, algorithmic, and implementation issues. We suggest active inference as a generalized predictive coding algorithm, and hierarchically organized traveling waves of independent neural oscillations as a plausible brain mechanism to integrate bottom-up and top-down information across distributed pain circuits.
Energy-based analog neural network framework
Authors: Watfa Mohamed , Garcia-Ortiz Alberto , Sassatelli Gilles
Published: March 2023

Over the past decade a body of work has emerged and shown the disruptive potential of neuromorphic systems across a broad range of studies, often combining novel machine learning models and nanotechnologies. Still, the scope of investigations often remains limited to simple problems since the process of building, training, and evaluating mixed-signal neural models is slow and laborious. In this paper, we introduce an open-source framework, called EBANA, that provides a unified, modularized, and extensible infrastructure, similar to conventional machine learning pipelines, for building and validating analog neural networks (ANNs). It uses Python as interface language with a syntax similar to Keras, while hiding the complexity of the underlying analog simulations. It already includes the most common building blocks and maintains sufficient modularity and extensibility to easily incorporate new concepts, electrical, and technological models. These features make EBANA suitable for researchers and practitioners to experiment with different design topologies and explore the various tradeoffs that exist in the design space. We illustrate the framework capabilities by elaborating on the increasingly popular Energy-Based Models (EBMs), used in conjunction with the local Equilibrium Propagation (EP) training algorithm. Our experiments cover 3 datasets having up to 60,000 entries and explore network topologies generating circuits in excess of 1,000 electrical nodes that can be extensively benchmarked with ease and in reasonable time thanks to the native EBANA parallelization capability.
The diagnostic significance of cerebrospinal fluid cytology and circulating tumor DNA in meningeal carcinomatosis
Authors: Di Wei-Ying , Chen Ya-Nan , Cai Yun , Geng Qiang , Tan Yan-Li , Li Chun-Hui , Wang Ya-Nan , Shang Yan-Hong , Fang Chuan , Cheng Shu-Jie
Published: March 2023

Objective

The objective of this research is to investigate the clinical application value of cerebrospinal fluid (CSF) cytology and circulating tumor DNA (ctDNA) in lung adenocarcinoma (LUAD) meningeal metastasis-meningeal carcinomatosis (MC), and to further explore the possible molecular mechanisms and drug treatment targets of LUAD meningeal metastasis by next-generation sequencing (NGS).

Methods

We retrospectively analyzed LUAD with MC in 52 patients. CSF cytology was carried out using the slide centrifugation precipitation method and May-Grüwald-Giemsa (MGG) staining. Tumor tissue, plasma and CSF ctDNA of some MC patients were detected by NGS.

Results

Of the 52 MC patients, 46 (88.46%) were positive for CSF cytology and 34 (65.38%) were positive for imaging, with statistically significant differences in diagnostic positivity (P < 0.05). In 32 of these patients, CSF cytology, cerebrospinal fluid ctDNA, plasma ctDNA and MRI examination were performed simultaneously, and the positive rates were 84.38, 100, 56.25, and 62.50% respectively, the difference was statistically significant (P < 0.001). Analysis of the NGS profiles of tumor tissues, plasma and CSF of 12 MC patients: the mutated gene with the highest detection rate was epidermal growth factor receptor (EGFR) and the detection rate were 100, 58.33, and 100% respectively in tumor tissues, plasma and CSF, and there were 6 cases of concordance between plasma and tissue EGFR mutation sites, with a concordance rate of 50.00%, and 12 cases of concordance between CSF and tissue EGFR mutation sites, with a concordance rate of 100%. In addition, mutations not found in tissue or plasma were detected in CSF: FH mutation, SETD2 mutation, WT1 mutation, CDKN2A mutation, CDKN2B mutation, and multiple copy number variants (CNV), with the most detected being CDKN2A mutation and MET amplification.

Conclusion

CSF cytology is more sensitive than traditional imaging in the diagnosis of meningeal carcinomatosis and has significant advantages in the early screening and diagnosis of MC patients. CSF ctDNA can be used as a complementary diagnostic method to negative results of CSF cytology and MRI, and CSF ctDNA can be used as an important method for liquid biopsy of patients with MC, which has important clinical significance in revealing the possible molecular mechanisms and drug treatment targets of meningeal metastasis of LUAD.
Case report: A case of injury to the infrapatellar branch of the saphenous nerve caused by medial approach in knee arthroscopy
Authors: Tan Jiyang , Wang Xunhao , Xiong Fei , Qian Jun , Ying Qiuwen , Mi Jingyi
Published: March 2023

We present the case of a 72-year-old man who was referred to our department for treatment of pain on the anteromedial infrapatellar side of the right knee with sensory disturbance that began 2 years earlier. The patient previously underwent right knee arthroscopy at another hospital for a meniscus injury 2 years earlier, which relieved his knee pain, but pain and discomfort near the incision of the medial portal persisted. Given this situation, various physical treatments, such as ice compress, were administered postoperatively. However, the symptom was only partially relieved before discharge. Subsequently, the patient visited two other hospitals and began taking oral pregabalin and duloxetine for treatment of the pain based on a diagnosis of right common peroneal nerve injury. The pain in the same dermatomal distribution was slightly relieved, but a withdrawal reaction was observed. However, the results of an ultrasound at our hospital indicated that the right medial quadriceps femoris tendon showed a hypoechoic area suggesting inflammatory changes. Physical examination of the right knee detected atrophy of the quadriceps femoris muscle, decreased muscle strength (M4), obvious tenderness in the medial side, radiating pain along the anterior tibia, and sensory disturbance (S3+); the results of a drawer test, McMurray test, pivot shift test, and lateral stress test were negative. Based on the aforementioned evidence, a diagnosis was made of injury to the infrapatellar branch of the saphenous nerve, after which neurolysis of the nerve in question was carried out. An enlarged incision was made along the original medial approach. Scar hyperplasia was observed after careful separation of the subcutaneous tissue. During neurolysis, branches were found wrapped in the scar; their continuity and integrity were confirmed after relief. The released nerve was placed in a physiological position. The patient's pain was clearly relieved, and numbness disappeared on the first postoperative day. At 1-month follow-up, all symptoms were found to have resolved.
Sex-dependent association analysis between serum uric acid and spontaneous hemorrhagic transformation in patients with ischemic stroke
Authors: Tang Ye , Liu Ming-Su , Fu Chong , Li Guang-Qin
Published: March 2023

Objective

The association between serum uric acid (UA) and spontaneous hemorrhagic transformation (HT) has been seldom studied, and the role of UA in spontaneous HT remains unclear. This study aims to investigate the sex-dependent association between UA and spontaneous HT in patients with ischemic stroke.

Method

We retrospectively included patients with ischemic stroke in a tertiary academic hospital between December 2016 and May 2020. Patients were included if they presented within 24 h after the onset of symptoms and did not receive reperfusion therapy. Spontaneous HT was determined by an independent evaluation of neuroimaging by three trained neurologists who were blinded to clinical data. A univariate analysis was performed to identify factors related to spontaneous HT. Four logistic regression models were established to adjust each factor and assess the association between UA and spontaneous HT.

Results

A total of 769 patients were enrolled (64.6% were male patients and 3.9% had HT). After adjusting the confounders with a P < 0.05 (model A) in the univariate analysis, the ratio of UA and its interquartile range (RUI) was independently associated with spontaneous HT in male patients (OR: 1.85; 95% CI: 1.07–3.19; P = 0.028), but not in female patients (OR: 1.39; 95% CI: 0.28–6.82; P = 0.685). In models B–D, the results remain consistent with model A after the adjustment for other potential confounders.

Conclusions

Higher serum UA was independently associated with a higher occurrence of spontaneous HT in male patients who were admitted within 24 h after the stroke onset without receiving reperfusion therapy.
A quantitative study of the effect of ICL orientation selection on post-operative vault and model-assisted vault prediction
Authors: Zhang Weijie , Li Fang , Li Lin , Zhang Jing
Published: March 2023

Background

Appropriate vault height of implantable collamer lens (ICL) implantation matters for it has risks of corneal endothelial cell loss, cataract formation and intraocular pressure elevation, which could lead to irreversible damage to optic nerve. Therefore, pre-operative prediction for an ideal vault height is a hotspot. However, few data exist regarding quantitative effect of ICL orientation on vault height. This study is aimed to quantitatively investigate the effect of ICL implantation orientation on vault height, and built a machine-learning (ML)-based vault prediction model taking implantation orientation into account.

Methods

473 consecutive case series treated with ICL implantation were retrospectively analyzed (408 were horizontally implanted, and 65 were vertically implanted). Multivariable logistic regression analysis was performed to determine the association between ICL orientation and achieved vault. ML was performed to develop a new vault height prediction model taking ICL orientation into account. Receiver operating characteristic curve (ROC) and net reclassification index (NRI) were obtained to assess the prediction ability.

Results

95% of all the patients achieved 20/20 uncorrected distance visual acuity (UDVA) or better. No complications including cataract formation, dispersion or optic nerve injury were observed in any cases. Sex, sphere power, cylinder power, axis, ICL size and ICL orientation were all significant risk factors associated to vault height, and age was positively co-related. Of note, ICL size and ICL orientation were the top-ranking risk factors. Comparing to conventional horizontal implantation, vertical implantation could reduce the achieved vault by 81.187 μm (p < 0.001). In regarding to different ICL sizes, vertical implantation had no good to vault reduction when using ICL of 12.1 mm. However, it could reduce the vault by 59.351 μm and 160.992 μm respectively when ICL of 12.6mm and 13.2 mm were implanted (p = 0.0097 and p = 0.0124). For prediction of vault height, ML based model significantly outperformed traditional multivariable regression model.

Conclusion

We provide quantitative evidence that vertical implantation of ICL could effectively reduce the achieved vault height, especially when large size ICL was implanted, comparing to traditional horizontal implantation. ML is extremely applicable in development of vault prediction model.
Discovery of novel acetylcholinesterase inhibitors through integration of machine learning with genetic algorithm based in silico screening approaches
Authors: Khan Mohd Imran , Taehwan Park , Cho Yunseong , Scotti Marcus , Priscila Barros de Menezes Renata , Husain Fohad Mabood , Alomar Suliman Yousef , Baig Mohammad Hassan , Dong Jae-June
Published: March 2023

Introduction

Alzheimer’s disease (AD) is the most studied progressive eurodegenerative disorder, affecting 40–50 million of the global population. This progressive neurodegenerative disease is marked by gradual and irreversible declines in cognitive functions. The unavailability of therapeutic drug candidates restricting/reversing the progression of this dementia has severed the existing challenge. The development of acetylcholinesterase (AChE) inhibitors retains a great research focus for the discovery of an anti-Alzheimer drug.

Materials and methods

This study focused on finding AChE inhibitors by applying the machine learning (ML) predictive modeling approach, which is an integral part of the current drug discovery process. In this study, we have extensively utilized ML and other in silico approaches to search for an effective lead molecule against AChE.

Result and discussion

The output of this study helped us to identify some promising AChE inhibitors. The selected compounds performed well at different levels of analysis and may provide a possible pathway for the future design of potent AChE inhibitors.
Benchmarking framework for machine learning classification from fNIRS data
Authors: Benerradi Johann , Clos Jeremie , Landowska Aleksandra , Valstar Michel F. , Wilson Max L.
Published: March 2023

Background

While efforts to establish best practices with functional near infrared spectroscopy (fNIRS) signal processing have been published, there are still no community standards for applying machine learning to fNIRS data. Moreover, the lack of open source benchmarks and standard expectations for reporting means that published works often claim high generalisation capabilities, but with poor practices or missing details in the paper. These issues make it hard to evaluate the performance of models when it comes to choosing them for brain-computer interfaces.

Methods

We present an open-source benchmarking framework, BenchNIRS, to establish a best practice machine learning methodology to evaluate models applied to fNIRS data, using five open access datasets for brain-computer interface (BCI) applications. The BenchNIRS framework, using a robust methodology with nested cross-validation, enables researchers to optimise models and evaluate them without bias. The framework also enables us to produce useful metrics and figures to detail the performance of new models for comparison. To demonstrate the utility of the framework, we present a benchmarking of six baseline models [linear discriminant analysis (LDA), support-vector machine (SVM), k-nearest neighbours (kNN), artificial neural network (ANN), convolutional neural network (CNN), and long short-term memory (LSTM)] on the five datasets and investigate the influence of different factors on the classification performance, including: number of training examples and size of the time window of each fNIRS sample used for classification. We also present results with a sliding window as opposed to simple classification of epochs, and with a personalised approach (within subject data classification) as opposed to a generalised approach (unseen subject data classification).

Results and discussion

Results show that the performance is typically lower than the scores often reported in literature, and without great differences between models, highlighting that predicting unseen data remains a difficult task. Our benchmarking framework provides future authors, who are achieving significant high classification scores, with a tool to demonstrate the advances in a comparable way. To complement our framework, we contribute a set of recommendations for methodology decisions and writing papers, when applying machine learning to fNIRS data.
Associations of the Healthy Eating Index-2010 with risk of all-cause and heart disease mortality among adults with hypertension: Results from the National Health and Nutrition Examination Survey 2007–2014
Authors: Zhang Yuhui , Li Duanbin , Zhang Haizhu
Published: March 2023

Background

Studies regarding the impact of the Healthy Eating Index-2010 (HEI-2010) on the mortality of adults with hypertension are lacking.

Objectives

This study aimed to prospectively explore the relationships between HEI-2010 and mortality from heart disease and all causes in adults with hypertension based on the National Health and Nutrition Examination Survey (NHANES), 2007–2014.

Methods

This is a prospective cohort study including 6,690 adults with hypertension from NHANES (2007–2014). National Death Index data up to 31 December 2019 were used to determine the number of deaths due to heart disease and all other causes. We evaluated hazard ratios (HRs) and 95% confidence intervals (CIs) using the Cox proportional hazards model.

Results

A total of 1,259 deaths from all causes, including 338 due to heart disease, were documented over an average follow-up duration of 8.4 years. In comparison with the lowest quartile of HEI-2010 scores, multivariable-adjusted HRs (95% CIs) for all-cause mortality were 0.82 (0.70, 0.97), 0.78 (0.64, 0.95), and 0.68 (0.54, 0.85) for the second, third, and fourth quartiles of the HEI-2010 scores (P-trend < 0.001) and for heart disease mortality were 0.60 (0.44, 0.81), 0.59 (0.40, 0.89), and 0.53 (0.35, 0.80) (P-trend = 0.010). Each increment in natural-log-transformed HEI-2010 scores was linked to a 43% reduction in the risk of all-cause mortality (P < 0.001) and a 55% reduction in the risk of heart disease mortality (P = 0.003). Among the 12 components of HEI-2010, adherence to a higher intake of greens and beans, vegetables, total protein foods, seafood and plant proteins, and unsaturated fatty acids, as well as moderate consumption of empty calories, were related to a 21–29% lower risk of all-cause mortality.

Conclusion

In the current study, there was a statistically significant inverse relationship between HEI-2010 and mortality from heart disease and all causes among adults with hypertension. Based on the findings, it may help guide the dietary intake for adults with hypertension.
Prognostic value of nectin-4 in human cancers: A meta-analysis
Authors: Liu Rongqiang , Zhao Kailiang , Wang Kunpeng , Zhang Lilong , Ma Wangbin , Qiu Zhengdong , Wang Weixing
Published: March 2023

Background

Many reports have described that abnormal nectin-4 expression may be used as a prognostic marker in many tumors. However, these studies failed to reach a consensus. Here, we performed a meta-analysis to comprehensively evaluate the prognostic value of nectin-4 in cancers.

Methods

Relevant studies were identified through a comprehensive search of PubMed, EMBASE and Web of science until August 31, 2022. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to evaluate the relationship between nectin-4 expression and overall survival (OS) and disease-free survival/progression-free survival/relapse-free survival (DFS/PFS/RFS). Odds ratios (ORs) with 95% CIs were applied to assess the relationship between nectin-4 expression and clinicopathologic features. Subgroup analysis was performed to explore the sources of heterogeneity. Sensitivity analysis and funnel plot were used to test the reliability of the results. All data analyses were performed using STATA version 12.0 software.

Results

Fifteen articles involving 2245 patients were included in the meta-analysis. The pooled analysis showed that high nectin-4 expression was significantly associated with poor OS (HR: 1.75, 95% CI: 1.35–2.28). There was no relationship between high nectin-4 expression and DFS/PFS/RFS (HR: 178, 95% CI: 0.78–4.08).Subgroup analyses revealed that that high nectin-4 expression mainly presented adverse OS in esophageal cancer (EC) (HR: 1.78, 95% CI: 1.30–2.44) and gastric cancer (GC) (HR: 1.92, 95% CI: 1.43–2.58). We also found that high nectin-4 expression was associated with tumor diameter (big vs small) (OR: 1.96, 95% CI: 1.02–3.75), tumor stage (III-IV vs I-II) (OR: 2.04, 95% CI: 1.01–4.12) and invasion depth (T3+T4 vs T2+T1) (OR: 3.95, 95% CI: 2.06–7.57).

Conclusions

Nectin-4 can be used as an effective prognostic indicator for specific cancers.
ImmuneScore of eight-gene signature predicts prognosis and survival in patients with endometrial cancer
Authors: Gu Jiahui , Wang Zihao , Wang B. O. , Ma Xiaoxin
Published: March 2023

Background

Endometrial cancer (EC) is a common gynecological cancer worldwide and the sixth most common female malignant tumor. A large number of studies conducted through database mining have identified many biomarkers that may be related to survival and prognosis. However, the predictive ability of single-gene biomarkers is not sufficiently accurate. In recent years, tumors have been shown to interact closely with their microenvironment, and tumor-infiltrating immune cells in the tumor microenvironment were associated with therapeutic effects. Furthermore, sequencing technology has evolved and allowed the identification of genetic signatures that may improve prediction results. The purpose of this research was to discover the Cancer Genome Atlas (TCGA) data to evaluate new genetic features that can predict the prognosis of EC.

Methods

mRNA expression profiling was analyzed in patients with EC identified in the TCGA database (n = 530). Differentially expressed genes at different stages of EC were screened using the immune cell enrichment score (ImmuneScore). Univariate and multivariate Cox regression analyses was applied to evaluate genes significantly related to overall survival and establish the prognostic risk parameter formula. Kaplan–Meier survival curves and the logarithmic rank method were applied to verify the importance of risk parameters for the prognostic forecast. The accuracy of survival prediction was confirmed using the nomogram and Receiver Operating Characteristic (ROC) curve analysis. The mRNA expression of eight genes were measured by qRT-PCR. According to COX and HR values, NBAT1, a representative gene among 8 genes, was selected for CCK-8 assay, colony formation assay and transwell invasion assay to verify the effect on survival.

Results

Eight related genes (NBAT1, GFRA4, PTPRT, DLX4, RANBP3L, UNQ6494, KLRB1, and PRAC1) were discovered to be significantly associated with the overall survival rate. According to these eight-gene signatures, 530 patients with EC were assigned to high- and low-risk subgroups. The prognostic capability of the eight-gene signature was not influenced by other elements.

Conclusions

Eight related gene markers were identified using ImmuneScore, which could predict prognosis and survival in patients with EC. These findings provide a basis for understanding the application of biological information in tumors and identifying the poor prognosis of EC.
Cancer care in times of conflict: Treatment of patients from Afghanistan, in Pakistan
Authors: Mahmood Shahid , Khawaja Shehryar Nasir , Yusuf Muhammed Aasim
Published: March 2023

Introduction

Afghanistan has been in a near-continuous armed conflict, which has degraded the country’s health infrastructure. Due to this, Afghans have opted to seek cancer treatment in Pakistan. This manuscript aims to understand the complex cancer journey of patients from Afghanistan seeking care in the largest tertiary care cancer institutions in Pakistan.

Methods

This retrospective study explores the demographics, epidemiology and outcomes of Afghan cancer patients treated at the Shaukat Khanum Memorial Cancer Hospital and Research Centres (SKMCH&RC) in Lahore and Peshawar, Pakistan, over the period from 1995 to June 2022.

Results

A total of 6,370 patients from Afghanistan have undergone cancer care since 1995. The mean age at presentation was 40.7 years, 57% were male, and 87% were adults >19 years. Close to 30% of these patients came from Kabul and Nangarhar districts. 56% of all patients presented with stage III or IV disease. 34% of adult patients achieved a complete response to treatment, but more than half of all patients have since been lost to follow-up. Children generally had better outcomes, with 43% showing a complete response to treatment.

Discussion

The cancer journey for these patients remains long and difficult and the inability to ensure follow-up in so many remains frustrating for both patients and providers. The lack of a cancer infrastructure in Afghanistan after decades of conflict, means that policymakers need to develop and support alternative systems and structures to provide post-conflict domestic and cross-border cancer care.
Association between anlotinib trough plasma concentration and treatment outcomes in advanced non-small-cell lung cancer
Authors: Chen Ling , Jiang Hong , Rao Jun-jie , Wang Liu-sheng , Yan Wei , Ye Jian , Lou Jiang
Published: March 2023

Background

Efficacy and toxicities of anlotinib (ANL) show large inter-patient variation, which may partly be explained by differences in ANL exposure. Exposure-response/toxicities relationship have not been investigated for ANL. Therefore, the aim of the present study was to explore the association between the trough plasma concentration (Ctrough) of ANL and treatment outcomes in Chinese patients with advanced non-small cell lung cancer (NSCLC).

Methods

Patients with advanced NSCLC who started third-line or further ANL alone therapy between January 2021 and October 2022. This study examined the ANL Ctrough and clinical response evaluation at day 43 after initiation of ANL treatment. We evaluated the association between the ANL Ctrough and clinical efficacy and toxicities. Additionally, this study defined patients with complete response (CR), partial response (PR) and stable disease (SD) as responder. The receiver-operating characteristic (ROC) curve combined with Youden index was identify the potential threshold value of ANL Ctrough for the responder.

Results

52 patients were evaluated for analyses. The median ANL Ctrough was 11.45ng/ml (range, 3.69-26.36 ng/ml). The ANL Ctrough values in the PR group (n=6, 15.51 ng/ml (range, 8.19-17.37 ng/ml)) was significantly higher than in the PD group (n=8, 7.44 ng/ml (range, 5.41-14.69 ng/ml), p=0.001). The area under the ROC curve (AUCROC) was 0.76 (95% confidence interval (CI), 0.58-0.93; p=0.022) and threshold value of ANL Ctrough predicting responder was 10.29 ng/ml (sensitivity 65.9% and specificity 87.5%, the best Youden index was 0.53). The disease control rate (DCR) was 84.6%, and DCR was significantly higher in the high-exposure group (≥10.29ng/ml) than low-exposure group (<10.29ng/ml) (96.67% vs 68.18%, p=0.005). Although there was no significant difference in ANL Ctrough between grade ≥ 3 and grade ≤2 toxicities, the incidence of any grade hand-foot syndrome (70.0% vs 36.36%, p=0.016) and thyroid-stimulating hormone elevation (53.33% vs 22.73%, p =0.026) was significantly higher in the high-exposure group compared with the low-exposure group.

Conclusions

Considering these results, we propose that maintaining ANL Ctrough ≥ 10.29ng/ml was important for achieving the response in advanced NSCLC patients treated with ANL.
Case report: A preterm infant with rubinstein-taybi syndrome and Marmorata telangiectatica harboring a frameshift mutation in the CREBBP gene
Authors: Yang Yang , Xiao Jing , Ye Yuanyuan , Xiang Jianwen , Wang Zhu , Chen Jia
Published: March 2023

Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominantly inherited disease characterized by slow mental and physical growth, skeletal abnormalities (broad thumbs and big toes), and dysmorphic facial features. RSTS is associated with de novo variants of the epigenetic-associated gene CREBBP. RSTS is primarily diagnosed based on clinical manifestations and genetic testing. Cutis marmorata telangiectatica congenita (CMTC) is a rare, congenital, and typically benign vascular anomaly of unknown etiology; it is described as persistent reticulated marbled erythema. The diagnosis of CMTC is largely based on clinical features, and GNA11 mutations are associated with CMTC. In this case report, we describe the case of a preterm infant (boy) with RSTS and CMTC who had a novel frameshift mutation leading to a premature stop codon in the CREBBP gene. This study adds the novel mutation c.5837dupC to the known molecular spectrum of disease-causing CREBBP gene mutations.
Association between endotypes of prematurity and pharmacological closure of patent ductus arteriosus: A systematic review and meta-analysis
Authors: Gonzalez-Luis Gema E , Borges-Lujan Moreyba , Villamor Eduardo
Published: March 2023

Introduction

Endotypes leading to very and extremely preterm birth are clustered into two groups: infection/inflammation and dysfunctional placentation. We conducted a systematic review of observational studies exploring the association between these two endotypes and the pharmacological closure of patent ductus arteriosus (PDA) induced by cyclooxygenase (COX) inhibitors. Chorioamnionitis represented the infectious-inflammatory endotype, while dysfunctional placentation proxies were hypertensive disorders of pregnancy (HDP) and small for gestational age (SGA) or intrauterine growth restriction.

Methods

PubMed/Medline and Embase databases were searched. The random-effects odds ratio (OR) and 95% confidence interval (CI) were calculated for each association. We included 30 studies (12,639 infants).

Results

Meta-analysis showed a significant association between exposure to HDP and increased rate of pharmacological closure of PDA (17 studies, OR 1.41, 95% CI 1.10–1.81, p = 0.006). In contrast, neither chorioamnionitis (13 studies, OR 0.75, 95% CI 0.47–1.18, p = 0.211) nor SGA (17 studies, OR 1.20, 95% CI 0.96–1.50, p = 0.115) were significantly associated with the response to therapy. Subgroup analyses showed that the higher response to COX inhibitors in the HDP group was significant for indomethacin (OR 1.568, 95% CI 1.147–2.141, p = 0.005) but not for ibuprofen (OR 1.107, 95% CI 0.248–4.392, p = 0.894) or for the studies using both drugs (OR 1.280, 95% CI 0.935–1.751, p = 0.124). However, meta-regression showed that this difference between the drugs was not statistically significant (p = 0.404).

Discussion/Conclusion

Our data suggest that the pathologic condition that triggers prematurity may alter the response to pharmacological treatment of PDA. The DA of infants exposed to HDP appears to be more responsive to COX inhibitors.
Further delineation of EBF3-related syndromic neurodevelopmental disorder in twelve Chinese patients
Authors: Zhu Jitao , Li Wenhui , Yu Sha , Lu Wei , Xu Qiong , Wang Sujuan , Qian Yanyan , Guo Qiufang , Xu Suzhen , Wang Yao , Zhang Ping , Zhao Xuemei , Ni Qi , Liu Renchao , Li Xu , Wu Bingbing , Zhou Shuizhen , Wang Huijun
Published: March 2023

Neurodevelopmental disorders (NDDs) have heterogeneity in both clinical characteristics and genetic factors. EBF3 is a recently discovered gene associated with a syndromic form of NDDs characterized by hypotonia, ataxia and facial features. In this study, we report twelve unrelated individuals with EBF3 variants using next-generation sequencing. Five missense variants (four novel variants and one known variant) and seven copy number variations (CNVs) of EBF3 gene were identified. All of these patients exhibited developmental delay/intellectual disability. Ataxia was observed in 33% (6/9) of the patients, and abnormal muscle tone was observed in 55% (6/11) of the patients. Aberrant MRI reports were noted in 64% (7/11) of the patients. Four novel missense variants were all located in the DNA-binding domain. The pathogenicity of these variants was validated by in vitro experiments. We found that the subcellular protein localization of the R152C and F211L mutants was changed, and the distribution pattern of the R163G mutant was changed from even to granular. Luciferase assay results showed that the four EBF3 mutants' transcriptional activities were all significantly decreased (p < 0.01). Our study further expanded the gene mutation spectrum of EBF3-related NDD.