bluuebunny/crossref_metadata_2025 huggingface dataset:
Remote Evaluation of Parkinson's Disease Using a Conventional Webcam and Artificial Intelligence
Authors: Monje Mariana H. G. , Domínguez Sergio , Vera-Olmos Javier , Antonini Angelo , Mestre Tiago A. , Malpica Norberto , Sánchez-Ferro Álvaro
Published: December 2021

Objective: This study aimed to prove the concept of a new optical video-based system to measure Parkinson's disease (PD) remotely using an accessible standard webcam.

Methods: We consecutively enrolled a cohort of 42 patients with PD and healthy subjects (HSs). The participants were recorded performing MDS-UPDRS III bradykinesia upper limb tasks with a computer webcam. The video frames were processed using the artificial intelligence algorithms tracking the movements of the hands. The video extracted features were correlated with clinical rating using the Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale and inertial measurement units (IMUs). The developed classifiers were validated on an independent dataset.

Results: We found significant differences in the motor performance of the patients with PD and HSs in all the bradykinesia upper limb motor tasks. The best performing classifiers were unilateral finger tapping and hand movement speed. The model correlated both with the IMUs for quantitative assessment of motor function and the clinical scales, hence demonstrating concurrent validity with the existing methods.

Conclusions: We present here the proof-of-concept of a novel webcam-based technology to remotely detect the parkinsonian features using artificial intelligence. This method has preliminarily achieved a very high diagnostic accuracy and could be easily expanded to other disease manifestations to support PD management.
Prediction-Driven Decision Support for Patients With Mild Stroke: A Model Based on Machine Learning Algorithms
Authors: Lin Xinping , Lin Shiteng , Cui XiaoLi , Zou Daizun , Jiang FuPing , Zhou JunShan , Chen NiHong , Zhao Zhihong , Zhang Juan , Zou Jianjun
Published: December 2021

Background and Purpose: Treatment for mild stroke remains an open question. We aim to develop a decision support tool based on machine learning (ML) algorithms, called DAMS (Disability After Mild Stroke), to identify mild stroke patients who would be at high risk of post-stroke disability (PSD) if they only received medical therapy and, more importantly, to aid neurologists in making individual clinical decisions in emergency contexts.

Methods: Ischemic stroke patients were prospectively recorded in the National Advanced Stroke Center of Nanjing First Hospital (China) between July 2016 and September 2020. The exclusion criteria were patients who received thrombolytic therapy, age <18 years, lack of 3-month modified Rankin Scale (mRS), disabled before the index stroke, with an admission National Institute of Health stroke scale (NIHSS) > 5. The primary outcome was PSD, corresponding to 3-month mRS ≥ 2. We developed five ML models and assessed the area under curve (AUC) of receiver operating characteristic, calibration curve, and decision curve analysis. The optimal ML model was selected to be DAMS. In addition, SHapley Additive exPlanations (SHAP) approach was introduced to rank the feature importance. Finally, rapid-DAMS (R-DAMS) was constructed for a more urgent situation based on DAMS.

Results: A total of 1,905 mild stroke patients were enrolled in this study, and patients with PSD accounted for 23.4% (447). There was no difference in AUCs between the five models (ranged from 0.691 to 0.823). Although there was similar discriminative performance between ML models, the support vector machine model exhibited higher net benefit and better calibration (Brier score, 0.159, calibration slope, 0.935, calibration intercept, 0.035). Therefore, this model was selected for DAMS. In addition, SHAP approach showed that the most crucial feature was NIHSS on admission. Finally, R-DAMS was constructed and there was similar discriminative performance between R-DAMS and DAMS, but the former performed worse on calibration.

Conclusions: DAMS and R-DAMS, as prediction-driven decision support tools, were designed to aid clinical decision-making for mild stroke patients in emergency contexts. In addition, even within a narrow range of baseline scores, NIHSS on admission is the strongest feature that contributed to the prediction.
The Construction of a Risk Prediction Model Based on Neural Network for Pre-operative Acute Ischemic Stroke in Acute Type A Aortic Dissection Patients
Authors: Zhao Hongliang , Xu Ziliang , Zhu Yuanqiang , Xue Ruijia , Wang Jing , Ren Jialiang , Wang Wenjia , Duan Weixun , Zheng Minwen
Published: December 2021

Objective: To establish a pre-operative acute ischemic stroke risk (AIS) prediction model using the deep neural network in patients with acute type A aortic dissection (ATAAD).

Methods: Between January 2015 and February 2019, 300 ATAAD patients diagnosed by aorta CTA were analyzed retrospectively. Patients were divided into two groups according to the presence or absence of pre-operative AIS. Pre-operative AIS risk prediction models based on different machine learning algorithm was established with clinical, transthoracic echocardiography (TTE) and CTA imaging characteristics as input. The performance of the difference models was evaluated using the receiver operating characteristic (ROC), precision-recall curve (PRC) and decision curve analysis (DCA).

Results: Pre-operative AIS was detected in 86 of 300 patients with ATAAD (28.7%). The cohort was split into a training (211, 70% patients) and validation cohort (89, 30% patients) according to stratified sampling strategy. The constructed deep neural network model had the best performance on the discrimination of AIS group compare with other machine learning model, with an accuracy of 0.934 (95% CI: 0.891–0.963), 0.921 (95% CI: 0.845–0.968), sensitivity of 0.934, 0.960, specificity of 0.933, 0.906, and AUC of 0.982 (95% CI: 0.967–0.997), 0.964 (95% CI: 0.932–0.997) in the training and validation cohort, respectively.

Conclusion: The established risk prediction model based on the deep neural network method may have the big potential to evaluate the risk of pre-operative AIS in patients with ATAAD.
Mediterranean Diet Adherence in People With Parkinson's Disease Reduces Constipation Symptoms and Changes Fecal Microbiota After a 5-Week Single-Arm Pilot Study
Authors: Rusch Carley , Beke Matthew , Tucciarone Lily , Nieves Carmelo , Ukhanova Maria , Tagliamonte Massimiliano S. , Mai Volker , Suh Joon Hyuk , Wang Yu , Chiu Shannon , Patel Bhavana , Ramirez-Zamora Adolfo , Langkamp-Henken Bobbi
Published: December 2021

Introduction: Non-motor symptoms of Parkinson's disease (PD) such as gastrointestinal (GI) dysfunction are common, yet little is known about how modifying dietary intake impacts PD symptoms. The aim of this study in individuals with PD was to determine whether a Mediterranean diet intervention is feasible and affects GI function, intestinal permeability and fecal microbial communities.

Methods: A single-arm, 5-week Mediterranean diet intervention study was conducted in eight people with PD. Daily and weekly questionnaires were administered to determine changes in GI symptoms. Urine and stool samples were collected at baseline and after 5 weeks to assess intestinal permeability and fecal microbial communities. Additionally, live-in partners of the participants with PD were matched as controls (n = 8) for baseline urine and stool samples.

Results: Participants with PD increased intake of Mediterranean diet based on adherence scores from baseline to week 5 (4.4 ± 0.6 vs. 11.9 ± 0.7; P < 0.01 with >10 representing good adherence), which was linked with weight loss (77.4 kg vs. 74.9 kg, P = 0.01). Constipation syndrome scores decreased after 5 weeks (2.3 ± 0.5 vs. 1.5 ± 0.3; P = 0.04). Bilophila, was higher at baseline in PD (0.6 ± 0.1% vs. 0.2 ± 0.1% P = 0.02) and slightly decreased after the diet intervention (0.5 ± 0.1%; P = 0.01). Interestingly, the proportion of Roseburia was significantly lower in PD compared to controls (0.6 ± 0.2% vs. 1.6 ± 0.3%; P = 0.02) and increased at week 5 (0.9 ± 0.2%; P < 0.01). No differences were observed for markers of intestinal permeability between the control and PD groups or post-intervention.

Conclusions: Short-term Mediterranean diet adherence is feasible in participants with PD; correlated with weight loss, improved constipation, and modified gut microbiota.

Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03851861.
Electrophysiological Measures of Tactile and Auditory Processing in Children With Autism Spectrum Disorder
Authors: Kadlaskar Girija , Bergmann Sophia , McNally Keehn Rebecca , Seidl Amanda , Keehn Brandon
Published: December 2021

Behavioral differences in responding to tactile and auditory stimuli are widely reported in individuals with autism spectrum disorder (ASD). However, the neural mechanisms underlying distinct tactile and auditory reactivity patterns in ASD remain unclear with theories implicating differences in both perceptual and attentional processes. The current study sought to investigate (1) the neural indices of early perceptual and later attentional factors underlying tactile and auditory processing in children with and without ASD, and (2) the relationship between neural indices of tactile and auditory processing and ASD symptomatology. Participants included 14, 6–12-year-olds with ASD and 14 age- and non-verbal IQ matched typically developing (TD) children. Children participated in an event-related potential (ERP) oddball paradigm during which they watched a silent video while being presented with tactile and auditory stimuli (i.e., 80% standard speech sound/a/; 10% oddball speech sound/i/; 10% novel vibrotactile stimuli on the fingertip with standard speech sound/a/). Children’s early and later ERP responses to tactile (P1 and N2) and auditory stimuli (P1, P3a, and P3b) were examined. Non-parametric analyses showed that children with ASD displayed differences in early perceptual processing of auditory (i.e., lower amplitudes at central region of interest), but not tactile, stimuli. Analysis of later attentional components did not show differences in response to tactile and auditory stimuli in the ASD and TD groups. Together, these results suggest that differences in auditory responsivity patterns could be related to perceptual factors in children with ASD. However, despite differences in caregiver-reported sensory measures, children with ASD did not differ in their neural reactivity to infrequent touch-speech stimuli compared to TD children. Nevertheless, correlational analyses confirmed that inter-individual differences in neural responsivity to tactile and auditory stimuli were related to social skills in all children. Finally, we discuss how the paradigm and stimulus type used in the current study may have impacted our results. These findings have implications for everyday life, where individual differences in responding to tactile and auditory stimuli may impact social functioning.
Relationships Between Cardiovascular Autonomic Profile and Work Ability in Patients With Pure Autonomic Failure
Authors: Zamunér Antonio R. , Minonzio Maura , Shiffer Dana , Fornerone Roberto , Cairo Beatrice , Porta Alberto , Rigo Stefano , Furlan Raffaello , Barbic Franca
Published: December 2021

Pure autonomic failure (PAF) is a rare disorder belonging to the group of synucleinopathies, characterized by autonomic nervous system degeneration. Severe orthostatic intolerance with recurrent syncope while standing are the two most disabling manifestations. Symptoms may start at middle age, thus affecting people at their working age. The aims of this study were to evaluate the autonomic and work ability impairment of a group of PAF patients and assess the relationships between cardiovascular autonomic control and work ability in these patients. Eleven PAF patients (age 57.3 ± 6.7 years), engaged in work activity, participated in the study. They completed the Composite Autonomic Symptom Score (COMPASS-31, range 0 no symptom-100 maximum symptom intensity) and Work Ability questionnaires (Work Ability Index, WAI, range 7–49; higher values indicate better work ability and lower values indicating unsatisfactory or jeopardized work ability). Electrocardiogram, blood pressure and respiratory activity were continuously recorded for 10 min while supine and during 75° head-up tilt (HUT). Autoregressive spectral analysis of cardiac cycle length approximated as the time distance between two consecutive R-wave peaks (RR) and systolic arterial pressure (SAP) variabilities provided the power in the high frequency (HF, 0.15–0.40 Hz) and low frequency (LF, 0.04–0.15 Hz) bands of RR and SAP variabilities. Cardiac sympatho-vagal interaction was assessed by LF to HF ratio (LF/HF), while the LF power of SAP (LFSAP) quantified the vascular sympathetic modulation. Changes in cardiovascular autonomic indexes induced by HUT were calculated as the delta (Δ) between HUT and supine resting positions. Spearman correlation analysis was applied. PAF patients were characterized by a moderate autonomic dysfunction (COMPASS-31 total score 47.08 ± 20.2) and by a reduction of work ability (WAI 26.88 ± 10.72). Direct significant correlations were found between WAI and ΔLFRR (r = 0.66, p = 0.03) and ΔLF/HFRR (r = 0.70, p = 0.02). Results indicate that patients who were better able to modulate heart rate, as revealed by a greater cardiac sympathetic increase and/or vagal withdrawal during the orthostatic stimulus, were those who reported higher values of WAI. This finding could be relevant to propose new strategies in the occupational environment to prevent early retirement or to extend the working life of these patients.
Exendin-4 Preserves Blood-Brain Barrier Integrity via Glucagon-Like Peptide 1 Receptor/Activated Protein Kinase-Dependent Nuclear Factor-Kappa B/Matrix Metalloproteinase-9 Inhibition After Subarachnoid Hemorrhage in Rat
Authors: Xie Zhiyi , Enkhjargal Budbazar , Nathanael Matei , Wu Lingyun , Zhu Qiquan , Zhang Tongyu , Tang Jiping , Zhang John H.
Published: December 2021

In this study, we investigated the role of Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, in blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH) in rats. The endovascular perforation model of SAH was performed in Sprague-Dawley rats. Ex-4 was intraperitoneally injected 1 h after SAH induction. To elucidate the underlying molecular mechanism, small interfering ribonucleic acid (siRNA) for GLP-1R and Dorsomorphin, a specific inhibitor of adenosine monophosphate-activated protein kinase (AMPK), were intracerebroventricularly injected 48 h before induction of SAH correspondingly. Immunofluorescence results supported GLP-1R expressed on the endothelial cells of microvessels in the brain after SAH. Administration of Ex-4 significantly reduced brain water content and Evans blue extravasation in both hemispheres, which improved neurological scores at 24 h after SAH. In the mechanism study, Ex-4 treatment significantly increased the expression of GLP-1R, p-AMPK, IκB-α, Occludin, and Claudin-5, while the expression of p-nuclear factor-kappa B (NF-κB) p65, matrix metalloproteinase-9 (MMP-9), and albumin was significantly decreased. The effects of Ex-4 were reversed by the intervention of GLP-1R siRNA or Dorsomorphin, respectively. In conclusion, Ex-4 could preserve the BBB integrity through GLP-1R/AMPK-dependent NF-κB/MMP-9 inhibition after SAH, which should be further investigated as a potential therapeutic target in SAH.
Effect of Multiple-Nutrient Supplement on Muscle Damage, Liver, and Kidney Function After Exercising Under Heat: Based on a Pilot Study and a Randomised Controlled Trial
Authors: Wei Chunbo , Zhao Shengnan , Zhang Yuntao , Gu Wenbo , Kumar Sarker Shuvan , Liu Shuande , Li Benzhang , Wang Xuanyang , Li Ying , Wang Xu
Published: December 2021

Objective: This study explored the effect of multiple-nutrient supplementation on muscle damage and liver and kidney function after vigorous exercise under heat.

Methods: After an initial pilot trial comprising 89 male participants, 85 participants were recruited and assigned into three groups: a multiple-nutrient (M) group, a glucose (G) group, and a water (W) group. Multiple-nutrient supplements contain glucose, fructose, maltose, sodium, potassium, vitamin B1, vitamin B2, vitamin C, vitamin K, and taurine. Participants were organised to take a 3-km running test (wet-bulb globe temperature 32°C) after a short-term (7 days) supplement. Blood samples were obtained to detect biochemical parameters [glucose (GLU), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), uric acid (UA), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH), and lactic acid], inflammation factors [interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α)], and oxidative stress biomarkers [superoxide dismutase (SOD) and 8-iso-prostaglandin F (2alpha) (8-iso-PGF2α)].

Results: In the pilot trial, BUN decreased significantly in the M and G groups immediately after the running test. AST, Cr, and UA were significantly reduced 24 h after the running test with single-shot multiple-nutrient supplementation. In the short-term trial, multiple nutrients further prevented the elevation of CK (p = 0.045) and LDH (p = 0.033) levels 24 h after strenuous exercise. Moreover, we found that multiple nutrients significantly reduced IL-6 (p = 0.001) and TNF-α (p = 0.015) elevation immediately after exercise. Simultaneously, SOD elevation was significantly higher in the M group immediately after exercising than in the other two groups (p = 0.033). 8-iso-PGF2α was reduced in the M group 24 h after exercise (p = 0.036).

Conclusions: This study found that multiple-nutrient supplementation promoted the recovery of muscle damage and decreased liver and kidney function caused by strenuous exercise in a hot environment, probably through the inhibition of secondary damage induced by increased inflammatory reactions and oxidative stress. In this respect, the current study has important implications for the strategy of nutritional support to accelerate recovery and potentially prevent heat-related illness. This study was prospectively registered on clinicaltrials.gov on June 21, 2019 (ID: ChiCTR1900023988).
A Progressive Nutrient Profiling System to Guide Improvements in Nutrient Density of Foods and Beverages
Authors: Greenberg Danielle , Drewnowski Adam , Black Richard , Weststrate Jan A. , O'Shea Marianne
Published: December 2021

Improving the nutrient density of processed foods is one way to bring the global food supply closer to the WHO Sustainable Development Goals. Nutrient profiling (NP) has emerged as the preferred method of monitoring the progress toward product innovation and reformulation. This paper presents PepsiCo Nutrition Criteria (PNC), a new internal NP model that was designed to guide and monitor improvements in nutrient density and overall nutritional quality of foods and beverages. The new PNC NP model assigns food products into four classes of increasing nutritional value, based on the content of nutrients to limit, along with nutrients and ingredients to encourage. The nutrient standards used for category assignment followed those developed by global dietary authorities. Standards are proposed for calories, sodium, added sugars, saturated, and industrially produced trans fats. Also included are minimum values for food groups to encourage, low-fat dairy, and for country-specific gap nutrients. Internal use of the NP model has spurred product changes that are consistent with WHO goals for industry transparency. An audited review of company products showed that 48% met added sugar, 65% met sodium, and 71% met saturated fat goals. By the end of 2020, in the top 26 regions in which products are sold, 48% of the total sales volume of global beverages had 100 kcal or less from added sugars per 355 ml serving representing 80% of beverage volume and over 90% of food volume sold globally. The PNC NP model is not consumer-facing but is specifically intended for internal use to motivate stepwise and incremental product innovation and reformulation. Transparent and published NP models further WHO goals of engaging industry stakeholders in the (re)formulation of processed foods and beverages consistent with public health goals.
Pancreatic Serous Cystic Neoplasms and Mucinous Cystic Neoplasms: Differential Diagnosis by Combining Imaging Features and Enhanced CT Texture Analysis
Authors: Chen Hai-Yan , Deng Xue-Ying , Pan Yao , Chen Jie-Yu , Liu Yun-Ying , Chen Wu-Jie , Yang Hong , Zheng Yao , Yang Yong-Bo , Liu Cheng , Shao Guo-Liang , Yu Ri-Sheng
Published: December 2021

Objective

To establish a diagnostic model by combining imaging features with enhanced CT texture analysis to differentiate pancreatic serous cystadenomas (SCNs) from pancreatic mucinous cystadenomas (MCNs).

Materials and Methods

Fifty-seven and 43 patients with pathology-confirmed SCNs and MCNs, respectively, from one center were analyzed and divided into a training cohort (n = 72) and an internal validation cohort (n = 28). An external validation cohort (n = 28) from another center was allocated. Demographic and radiological information were collected. The least absolute shrinkage and selection operator (LASSO) and recursive feature elimination linear support vector machine (RFE_LinearSVC) were implemented to select significant features. Multivariable logistic regression algorithms were conducted for model construction. Receiver operating characteristic (ROC) curves for the models were evaluated, and their prediction efficiency was quantified by the area under the curve (AUC), 95% confidence interval (95% CI), sensitivity and specificity.

Results

Following multivariable logistic regression analysis, the AUC was 0.932 and 0.887, the sensitivity was 87.5% and 90%, and the specificity was 82.4% and 84.6% with the training and validation cohorts, respectively, for the model combining radiological features and CT texture features. For the model based on radiological features alone, the AUC was 0.84 and 0.91, the sensitivity was 75% and 66.7%, and the specificity was 82.4% and 77% with the training and validation cohorts, respectively.

Conclusion

This study showed that a logistic model combining radiological features and CT texture features is more effective in distinguishing SCNs from MCNs of the pancreas than a model based on radiological features alone.
EPDR1, Which Is Negatively Regulated by miR-429, Suppresses Epithelial Ovarian Cancer Progression via PI3K/AKT Signaling Pathway
Authors: Zhao Zhendan , Wang Zhiling , Wang Pengling , Liu Shujie , Li Yingwei , Yang Xingsheng
Published: December 2021

Epithelial ovarian cancer (EOC) is the main pathological type of ovarian cancer. In this study, we found that ependymin-related 1 (EPDR1) was remarkably downregulated in EOC tissues, and low EPDR1 expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, metastasis, and poor prognosis. We confirmed that EPDR1 overexpression dramatically suppressed EOC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, EPDR1 inhibited EOC tumorigenesis and progression, at least in part, through the repression of the PI3K (Phosphoinositide 3-kinase)/AKT (AKT Serine/Threonine Kinase 1) signaling pathway. Furthermore, the expression and function of EPDR1 were regulated by miR-429, as demonstrated by luciferase reporter assays and rescue experiments. In conclusion, our study validated that EPDR1, negatively regulated by miR-429, played an important role as a tumor-suppressor gene in EOC development via inhibition of the PI3K/AKT pathway. The miR-429/EPDR1 axis might provide novel therapeutic targets for individualized treatment of EOC patients in the future.
Nomograms Combining Ultrasonic Features With Clinical and Pathological Features for Estimation of Delphian Lymph Node Metastasis Risk in Papillary Thyroid Carcinoma
Authors: Qi Qi , Xu Pan , Zhang Cheng , Guo Suping , Huang Xingzhi , Chen Songli , Li Yaohui , Zhou Aiyun
Published: December 2021

Background

This work explores the clinical significance of Delphian lymph nodes (DLN) in thyroid papillary carcinoma (PTC). At the same time, a nomogram is constructed based on clinical, pathological, and ultrasonic (US) features to evaluate the possibility of DLN metastasis (DLNM) in PTC patients. This is the first study to predict DLNM using US characteristics.

Methods

A total of 485 patients, surgically diagnosed with PTC between February 2017 and June 2021, all of whom underwent thyroidectomy, were included in the study. Using the clinical, pathological, and US information of patients, the related factors of DLNM were retrospectively analyzed. The risk factors associated with DLNM were identified through univariate and multivariate analyses. According to clinical + pathology, clinical + US, and clinical + US + pathology, the predictive nomogram for DLNM was established and validated.

Results

Of the 485 patients with DLN, 98 (20.2%) exhibited DLNM. The DLNM positive group had higher positive rates of central lymph node metastasis (CLNM), lateral lymph node metastasis (LLNM), and T3b–T4b thyroid tumors than the negative rates. The number of CLNM and LLNM lymph nodes in the DLNM+ group was higher as compared to that in the DLNM- group. Multivariate analysis demonstrated that the common independent risk factors of the three prediction models were male, bilaterality, and located in the isthmus. Age ≥45 years, located in the lower pole, and nodural goiter were protective factors. In addition, the independent risk factors were classified as follows: (I) P-extrathyroidal extension (ETE) and CLNM based on clinical + pathological characteristics; (II) US-ETE and US-CLNM based on clinical + US characteristics; and (III) US-ETE and CLNM based on clinical +US + pathological features. Better diagnostic efficacy was reported with clinical + pathology + US diagnostic model than that of clinical + pathology diagnostic model (AUC 0.872 vs. 0.821, p = 0.039). However, there was no significant difference between clinical + pathology + US diagnostic model and clinical + US diagnostic model (AUC 0.872 vs. 0.821, p = 0.724).

Conclusions

This study found that DLNM may be a sign that PTC is more invasive and has extensive lymph node metastasis. By exploring the clinical, pathology, and US characteristics of PTC progression to DLNM, three prediction nomograms, established according to different combinations of features, can be used in different situations to evaluate the transfer risk of DLN.
Analysis of the Relevance of the Ultrasonographic Features of Papillary Thyroid Carcinoma and Cervical Lymph Node Metastasis on Conventional and Contrast-Enhanced Ultrasonography
Authors: Xue Tian , Liu Chang , Liu Jing-Jing , Hao Yan-Hong , Shi Yan-Ping , Zhang Xiu-Xiu , Zhang Yan-Jing , Zhao Yu-Fang , Liu Li-Ping
Published: December 2021

Background

Preoperative prediction of lymph node metastases has a major impact on prognosis and recurrence for patients with papillary thyroid carcinoma (PTC). Thyroid ultrasonography is the preferred inspection to guide the appropriate diagnostic procedure.

Purpose

To investigate the relationship between PTC and cervical lymph node metastasis (CLNM, including central and lateral LNM) using both conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS).

Material and Methods

Our study retrospectively analyzed 379 patients diagnosed with PTC confirmed by surgical pathology at our hospital who underwent US and CEUS examinations from October 2016 to March 2021. Individuals were divided into two groups: the lymph node metastasis group and the nonmetastasis group. The relationship between US and CEUS characteristics of PTC and CLNM was analyzed. Univariate and multivariable logistic regression methods were used to identify the high-risk factors and established a nomogram to predict CLNM in PTC. Furthermore, we explore the frequency of CLNM at each nodal level in PTC patients.

Results

Univariate analysis indicated that there were significant differences in gender, age, tumor size, microcalcification, contact with the adjacent capsule, multifocality, capsule integrity and enhancement patterns in CEUS between the lymph node metastasis group and the nonmetastasis group (all P<0.05). Multivariate regression analysis showed that tumor size ≥1 cm, age ≤45 years, multifocality, and contact range of the adjacent capsule >50% were independent risk factors for CLNM in PTC, which determined the nomogram. The diagnostic model had an area under the curve (AUC) of 0.756 (95% confidence interval, 0.707-0.805). And calibration plot analysis shown that clinical utility of the nomogram. In 162 PTC patients, the metastatic rates of cervical lymph nodes at levels I-VI were 1.9%, 15.4%, 35.2%, 34.6%, 15.4%, 82.1%, and the difference was statistically significant (P<0.001).

Conclusion

Our study indicated that the characteristics of PTC on ultrasonography and CEUS can be used to predict CLNM as a useful tool. Preoperative analysis of ultrasonographical features has important value for predicting CLNM in PTCs. The risk of CLNM is greater when tumor size ≥1 cm, age ≤45 years, multifocality, contact range of the adjacent capsule >50% are present.
The Influence of Examiner Gender on Responses to Tonic Heat Pain Assessments: A Preliminary Investigation
Authors: McDougall Jessica F. , Bailey Nicole G. N. , Banga Rohan , Linde Lukas D. , Kramer John L. K.
Published: December 2021

Background: The influence of examiner gender on pain reporting has been previously explored in both research and clinical settings. However, previous investigations have been limited, with the majority of studies employing single, static assessments of pain (e.g., cold pressor test, verbal pain ratings). The impact of examiner gender on both static and dynamic heat-based pain assessments is currently unknown.

Methods: Thirty eight participants (20 females aged 24.1 ± 4.44, and 18 males, aged 24.8 ± 4.54) completed two identical testing sessions, randomized to a male and female examiner in a cross-over design. Pain sensitivity was examined using heat pain thresholds, verbal pain ratings to tonic heat, computerized visual analog scale (CoVAS) rating to tonic heat, and participant-controlled temperature (PCT) heat pain assessments.

Results: Female participants reported higher verbal pain to tonic heat with a female examiner compared to male participants, with similar trends for CoVAS responses to tonic heat. Conversely heat pain thresholds and PCT were not significantly influenced by experimenter gender.

Conclusions: Overall, verbal ratings were the most impacted by examiner gender, with temperature-based methods such as PCT and pain thresholds showing little to no examiner gender effects. While the gender of the examiner may be an important consideration in the measurement of sex and gender differences in pain research, the choice of pain assessment method may be of similar consequence.
A Review of Acute and Long-Term Neurological Complications Following Haematopoietic Stem Cell Transplant for Paediatric Acute Lymphoblastic Leukaemia
Authors: Gabriel Melissa , Hoeben Bianca A. W. , Uhlving Hilde Hylland , Zajac-Spychala Olga , Lawitschka Anita , Bresters Dorine , Ifversen Marianne
Published: December 2021

Despite advances in haematopoietic stem cell transplant (HSCT) techniques, the risk of serious side effects and complications still exists. Neurological complications, both acute and long term, are common following HSCT and contribute to significant morbidity and mortality. The aetiology of neurotoxicity includes infections and a wide variety of non-infectious causes such as drug toxicities, metabolic abnormalities, irradiation, vascular and immunologic events and the leukaemia itself. The majority of the literature on this subject is focussed on adults. The impact of the combination of neurotoxic drugs given before and during HSCT, radiotherapy and neurological complications on the developing and vulnerable paediatric and adolescent brain remains unclear. Moreover, the age-related sensitivity of the nervous system to toxic insults is still being investigated. In this article, we review current evidence regarding neurotoxicity following HSCT for acute lymphoblastic leukaemia in childhood. We focus on acute and long-term impacts. Understanding the aetiology and long-term sequelae of neurological complications in children is particularly important in the current era of immunotherapy for acute lymphoblastic leukaemia (such as chimeric antigen receptor T cells and bi-specific T-cell engager antibodies), which have well-known and common neurological side effects and may represent a future treatment modality for at least a fraction of HSCT-recipients.
Allogeneic Hematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukemia: Shifting Indications in the Era of Immunotherapy
Authors: Truong Tony H. , Jinca Cristian , Mann Georg , Arghirescu Smaranda , Buechner Jochen , Merli Pietro , Whitlock James A.
Published: December 2021

Pediatric acute lymphoblastic leukemia generally carries a good prognosis, and most children will be cured and become long-term survivors. However, a portion of children will harbor high-risk features at the time of diagnosis, have a poor response to upfront therapy, or suffer relapse necessitating more intensive therapy, which may include allogeneic hematopoietic stem cell transplant (HSCT). Recent advances in risk stratification, improved detection and incorporation of minimal residual disease (MRD), and intensification of upfront treatment have changed the indications for HSCT over time. For children in first complete remission, HSCT is generally reserved for those with the highest risk of relapse. These include patients with unfavorable features/cytogenetics who also have a poor response to induction and consolidation chemotherapy, usually reflected by residual blasts after prednisone or by detectable MRD at pre-defined time points. In the relapsed setting, children with first relapse of B-cell ALL are further stratified for HSCT depending on the time and site of relapse, while all patients with T-cell ALL are generally consolidated with HSCT. Alternatives to HSCT have also emerged over the last decade including immunotherapy and chimeric antigen receptor (CAR) T-cell therapy. These novel agents may spare toxicity while attempting to achieve MRD-negative remission in the most refractory cases and serve as a bridge to HSCT. In some situations, these emerging therapies can indeed be curative for some children with relapsed or resistant disease, thus, obviating the need for HSCT. In this review, we seek to summarize the role of HSCT in the current era of immunotherapy.
Practical Implementation of Artificial Intelligence-Based Deep Learning and Cloud Computing on the Application of Traditional Medicine and Western Medicine in the Diagnosis and Treatment of Rheumatoid Arthritis
Authors: Wang Shaohui , Hou Ya , Li Xuanhao , Meng Xianli , Zhang Yi , Wang Xiaobo
Published: December 2021

Rheumatoid arthritis (RA), an autoimmune disease of unknown etiology, is a serious threat to the health of middle-aged and elderly people. Although western medicine, traditional medicine such as traditional Chinese medicine, Tibetan medicine and other ethnic medicine have shown certain advantages in the diagnosis and treatment of RA, there are still some practical shortcomings, such as delayed diagnosis, improper treatment scheme and unclear drug mechanism. At present, the applications of artificial intelligence (AI)-based deep learning and cloud computing has aroused wide attention in the medical and health field, especially in screening potential active ingredients, targets and action pathways of single drugs or prescriptions in traditional medicine and optimizing disease diagnosis and treatment models. Integrated information and analysis of RA patients based on AI and medical big data will unquestionably benefit more RA patients worldwide. In this review, we mainly elaborated the application status and prospect of AI-assisted deep learning and cloud computation-oriented western medicine and traditional medicine on the diagnosis and treatment of RA in different stages. It can be predicted that with the help of AI, more pharmacological mechanisms of effective ethnic drugs against RA will be elucidated and more accurate solutions will be provided for the treatment and diagnosis of RA in the future.
An Inflammatory Response Related Gene Signature Associated with Survival Outcome and Gemcitabine Response in Patients with Pancreatic Ductal Adenocarcinoma
Authors: Xiao Zhijun , Li Jinyin , Yu Qian , Zhou Ting , Duan Jingjing , Yang Zhen , Liu Cuicui , Xu Feng
Published: December 2021

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors with an extremely low 5-year survival rate. Accumulating evidence has unveiled that inflammatory response promotes tumor progression, enhances angiogenesis, and causes local immunosuppression. Herein, we aim to develop an inflammatory related prognostic signature, and found it could be used to predict gemcitabine response in PDAC.

Methods: PDAC cohorts with mRNA expression profiles and clinical information were systematically collected from the four public databases. An inflammatory response related genes (IRRGs) prognostic signature was constructed by LASSO regression analysis. Kaplan–Meier survival analysis, receiver operating characteristic analysis, principal component analysis, and univariate and multivariate Cox analyses were carried out to evaluate effectiveness, and reliability of the signature. The correlation between gemcitabine response and risk score was evaluated in the TCGA-PAAD cohort. The GDSC database, pRRophetic algorithm, and connectivity map analysis were used to predict gemcitabine sensitivity and identify potential drugs for the treatment of PDAC. Finally, we analyzed differences in frequencies of gene mutations, infiltration of immune cells, as well as biological functions between different subgroups divided by the prognostic signature.

Results: We established a seven IRRGs (ADM, DCBLD2, EREG, ITGA5, MIF, TREM1, and BTG2) signature which divided the PDAC patients into low- and high-risk groups. Prognostic value of the signature was validated in 11 PDAC cohorts consisting of 1337 PDAC patients from 6 countries. A nomogram that integrated the IRRGs signature and clinicopathologic factors of PDAC patients was constructed. The risk score showed positive correlation with gemcitabine resistance. Two drugs (BMS-536924 and dasatinib) might have potential therapeutic implications in high-risk PDAC patients. We found that the high-risk group had higher frequencies of KRAS, TP53, and CDKN2A mutations, increased infiltration of macrophages M0, neutrophils, and macrophages M2 cells, as well as upregulated hypoxia and glycolysis pathways, while the low-risk group had increased infiltration of CD8+ T, naïve B, and plasma and macrophages M1 cells.

Conclusion: We constructed and validated an IRRGs signature that could be used to predict the prognosis and gemcitabine response of patients with PDAC, as well as two drugs (BMS-536924 and dasatinib) may contribute to PDAC treatment.
Qingwenzhike Prescription Alleviates Acute Lung Injury Induced by LPS via Inhibiting TLR4/NF-kB Pathway and NLRP3 Inflammasome Activation
Authors: Zhang Cai , Wang Xinran , Wang Chunguo , He Cheng , Ma Quantao , Li Jialin , Wang Weiling , Xu Yan-Tong , Wang Ting
Published: December 2021

Background: Acute lung injury (ALI) is characterized by dysfunction of the alveolar epithelial membrane caused by acute inflammation and tissue injury. Qingwenzhike (QWZK) prescription has been demonstrated to be effective against respiratory viral infections in clinical practices, including coronavirus disease 2019 (COVID-19) infection. So far, the chemical compositions, protective effects on ALI, and possible anti-inflammatory mechanisms remain unknown.

Methods: In this study, the compositions of QWZK were determined via the linear ion trap/electrostatic field orbital trap tandem high-resolution mass spectrometry (UHPLC-LTQ-Orbitrap MS). To test the protective effects of QWZK on ALI, an ALI model induced by lipopolysaccharide (LPS) in rats was used. The effects of QWZK on the LPS-induced ALI were evaluated by pathological changes and the number and classification of white blood cell (WBC) in bronchoalveolar lavage fluid (BALF). To investigate the possible underlying mechanisms, the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP-1), interleukin-1β (IL-1β), interleukin-18 (IL-18), and immunoregulatory-related factors interferon-γ (IFN-γ) were detected by ELISA. Furthermore, the expression of Toll-like receptor 4 (TLR4), p-IKKα/β, IKKα, IKKβ, p-IκBα, IκBα, p-NF-κB, nuclear factor-κB (NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, pro-caspase-1, apoptosis-associated speck-like protein containing CARD (ASC), and β-actin were tested by Western blot.

Results: A total of 99 compounds were identified in QWZK, including 33 flavonoids, 23 phenolic acids, 3 alkaloids, 3 coumarins, 20 triterpenoids, 5 anthraquinones, and 12 others. ALI rats induced by LPS exhibited significant increase in neutrophile, significant decrease in lymphocyte, and evidently thicker alveolar wall than control animals. QWZK reversed the changes in WBC count and alveolar wall to normal level on the model of ALI induced by LPS. ELISA results revealed that QWZK significantly reduced the overexpression of proinflammatory factors IL-6, TNF-α, MCP-1, IL-1β, IL-18, and IFN-γ induced by LPS. Western blot results demonstrated that QWZK significantly downregulated the overexpression of TLR4, p-IKKα/β, p-IκBα, p-NF-κB, NLRP3, cleaved caspase-1, and ASC induced by LPS, which suggested that QWZK inhibited TLR4/NF-κB signaling pathway and NLRP3 inflammasomes.

Conclusions: The chemical compositions of QWZK were first identified. It was demonstrated that QWZK showed protective effects on ALI induced by LPS. The possible underlying mechanisms of QWZK on ALI induced by LPS was via inhibiting TLR4/NF-kB signaling pathway and NLRP3 inflammasome activation. This work suggested that QWZK is a potential therapeutic candidate for the treatments of ALI and pulmonary inflammation.
Emerging Role of PD-1/PD-L1 Inhibitors in Chronic Liver Diseases
Authors: Singh Vishakha , Khurana Amit , Allawadhi Prince , Banothu Anil Kumar , Bharani Kala Kumar , Weiskirchen Ralf
Published: December 2021

Programmed cell death protein 1 (PD-1)/PD-ligand (L)1, the immune checkpoint inhibitors have emerged as a promising strategy for the treatment of various diseases including chronic liver diseases (CLDs) such as hepatitis, liver injury and hepatocellular carcinoma (HCC). The role of PD-1/PD-L1 has been widely inspected in the treatment of viral hepatitis and HCC. PD-1 is known to play a crucial role in inhibiting immunological responses and stimulates self-tolerance by regulating the T-cell activity. Further, it promotes apoptosis of antigen-specific T-cells while preventing apoptosis of Treg cells. PD-L1 is a trans-membrane protein which is recognized as a co-inhibitory factor of immunological responses. Both, PD-1 and PD-L1 function together to downregulate the proliferation of PD-1 positive cells, suppress the expression of cytokines and stimulate apoptosis. Owing to the importance of PD-1/PD-L1 signaling, this review aims to summarize the potential of PD-1/PD-L1 inhibitors in CLDs along with toxicities associated with them. We have enlisted some of the important roles of PD-1/PD-L1 in CLDs, the clinically approved products and the pipelines of drugs under clinical evaluation.
Seeing the Light: The Use of Zebrafish for Optogenetic Studies of the Heart
Authors: Baillie Jonathan S. , Stoyek Matthew R. , Quinn T. Alexander
Published: December 2021

Optogenetics, involving the optical measurement and manipulation of cellular activity with genetically encoded light-sensitive proteins (“reporters” and “actuators”), is a powerful experimental technique for probing (patho-)physiological function. Originally developed as a tool for neuroscience, it has now been utilized in cardiac research for over a decade, providing novel insight into the electrophysiology of the healthy and diseased heart. Among the pioneering cardiac applications of optogenetic actuators were studies in zebrafish, which first demonstrated their use for precise spatiotemporal control of cardiac activity. Zebrafish were also adopted early as an experimental model for the use of optogenetic reporters, including genetically encoded voltage- and calcium-sensitive indicators. Beyond optogenetic studies, zebrafish are becoming an increasingly important tool for cardiac research, as they combine many of the advantages of integrative and reduced experimental models. The zebrafish has striking genetic and functional cardiac similarities to that of mammals, its genome is fully sequenced and can be modified using standard techniques, it has been used to recapitulate a variety of cardiac diseases, and it allows for high-throughput investigations. For optogenetic studies, zebrafish provide additional advantages, as the whole zebrafish heart can be visualized and interrogatedin vivoin the transparent, externally developing embryo, and the relatively small adult heart allows forin situcell-specific observation and control not possible in mammals. With the advent of increasingly sophisticated fluorescence imaging approaches and methods for spatially-resolved light stimulation in the heart, the zebrafish represents an experimental model with unrealized potential for cardiac optogenetic studies. In this review we summarize the use of zebrafish for optogenetic investigations in the heart, highlighting their specific advantages and limitations, and their potential for future cardiac research.
Effect of Cyclic Heat Stress on Feeding-Related Hypothalamic Neuropeptides of Three Broiler Populations and Their Ancestor Jungle Fowl
Authors: Brugaletta Giorgio , Greene Elizabeth , Tabler Travis , Orlowski Sara , Sirri Federico , Dridi Sami
Published: December 2021

Heat stress (HS) has been increasingly jeopardizing the sustainability of the poultry production. Moreover, modern high-performing chickens are far less able to withstand HS than their predecessors due to higher growth rate and metabolic rates. Performance losses caused by HS are mainly ascribed to decreases in feed consumption. Since feed intake is tightly controlled by the hypothalamic centers of hunger and satiety, we sought to determine the effect of chronic cyclic HS on the expression of feeding-related hypothalamic neuropeptides (FRHN) in unselected chickens (i.e., the ancestor junglefowl—JF) and three broiler lines from diverse stages of genetic selection (i.e., the slow growing ACRB, the moderate growing 95RN, and the fast growing MRB). From 29 to 56 days, birds (n = 150 birds for each population) were subjected to either thermoneutral (TN, 25°C) or cyclic heat stress (HS, 36°C, 0900–1,800 h) conditions. Molecular data were analyzed by two-way ANOVA with interaction between the main factors, namely environmental temperature and line. The expression of major FHRN, like neuropeptide Y, agouti-related peptide, proopiomelanocortin, and cocaine and amphetamine regulated transcript remained unchanged. However, melanocortin receptor 1 exhibited a line-dependent decreasing trend from JF to MRB under both TN and HS (p = 0.09), adiponectin expression showed a distinct trend toward significance with 95RB exhibiting the highest mRNA level irrespective of the environmental temperature (p = 0.08), and JF had a greater mRNA abundance of visfatin than ACRB under TN (p < 0.05). The hypothalamic integration of circadian information, acclimation to long-lasting HS exposure, stable hypothalamic pathways unaffected by evolution and genetic selection, focus on mRNA abundances, and use of the entire hypothalamus masking gene expression in specific hypothalamic nuclei are all possible explanations for the lack of variations observed in this study. In conclusion, this is the first assessment of the impacts of heat stress on feeding-related hypothalamic neuropeptides of chicken, with a valuable and informative comparison between the ancestor junglefowl and three differently performing broiler lines.