Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting Lapatinib Dose Regimen Using Machine Learning and Deep Learning Techniques Based on a Real-World Study

Lapatinib is used for the treatment of metastatic HER2(+) breast cancer. We aim to establish a prediction model for lapatinib dose using machine learning and deep learning techniques based on a real-world study. There were 149 breast cancer patients enrolled from July 2016 to June 2017 at Fudan University Shanghai Cancer Center. The sequential forward selection algorithm based on random forest was applied for variable selection. Twelve machine learning and deep learning algorithms were compared in terms of their predictive abilities (logistic regression, SVM, random forest, Adaboost, XGBoost, GBDT, LightGBM, CatBoost, TabNet, ANN, Super TML, and Wide&Deep). As a result, TabNet was chosen to construct the prediction model with the best performance (accuracy = 0.82 and AUC = 0.83). Afterward, four variables that strongly correlated with lapatinib dose were ranked via importance score as follows: treatment protocols, weight, number of chemotherapy treatments, and number of metastases. Finally, the confusion matrix was used to validate the model for a dose regimen of 1,250 mg lapatinib (precision = 81% and recall = 95%), and for a dose regimen of 1,000 mg lapatinib (precision = 87% and recall = 64%). To conclude, we established a deep learning model to predict lapatinib dose based on important influencing variables selected from real-world evidence, to achieve an optimal individualized dose regimen with good predictive performance.
Signatures of Thalamocortical Alpha Oscillations and Synchronization With Increased Anesthetic Depths Under Isoflurane

Background: Electroencephalography (EEG) recordings under propofol exhibit an increase in slow and alpha oscillation power and dose-dependent phase–amplitude coupling (PAC), which underlie GABAA potentiation and the central role of thalamocortical entrainment. However, the exact EEG signatures elicited by volatile anesthetics and the possible neurophysiological mechanisms remain unclear. Methods: Cortical EEG signals and thalamic local field potential (LFP) were recorded in a mouse model to detect EEG signatures induced by 0.9%, 1.5%, and 2.0% isoflurane. Then, the power of the EEG spectrum, thalamocortical coherence, and slow–alpha phase–amplitude coupling were analyzed. A computational model based on the thalamic network was used to determine the primary neurophysiological mechanisms of alpha spiking of thalamocortical neurons under isoflurane anesthesia. Results: Isoflurane at 0.9% (light anesthesia) increased the power of slow and delta oscillations both in cortical EEG and in thalamic LFP. Isoflurane at 1.5% (surgery anesthesia) increased the power of alpha oscillations both in cortical EEG and in thalamic LFP. Isoflurane at 2% (deep anesthesia) further increased the power of cortical alpha oscillations, while thalamic alpha oscillations were unchanged. Thalamocortical coherence of alpha oscillation only exhibited a significant increase under 1.5% isoflurane. Isoflurane-induced PAC modulation remained unchanged throughout under various concentrations of isoflurane. By adjusting the parameters in the computational model, isoflurane-induced alpha spiking in thalamocortical neurons was simulated, which revealed the potential molecular targets and the thalamic network involved in isoflurane-induced alpha spiking in thalamocortical neurons. Conclusion: The EEG changes in the cortical alpha oscillation, thalamocortical coherence, and slow–alpha PAC may provide neurophysiological signatures for monitoring isoflurane anesthesia at various depths.
RNA Sequencing Unveils Very Small RNAs With Potential Regulatory Functions in Bacteria

RNA sequencing (RNA-seq) is the gold standard for the discovery of small non-coding RNAs. Following a long-standing approach, reads shorter than 16 nucleotides (nt) are removed from the small RNA sequencing libraries or datasets. The serendipitous discovery of an eukaryotic 12 nt-long RNA species capable of modulating the microRNA from which they derive prompted us to challenge this dogma and, by expanding the window of RNA sizes down to 8 nt, to confirm the existence of functional very small RNAs (vsRNAs <16 nt). Here we report the detailed profiling of vsRNAs in Escherichia coli, E. coli-derived outer membrane vesicles (OMVs) and five other bacterial strains (Pseudomonas aeruginosa PA7, P. aeruginosa PAO1, Salmonella enterica serovar Typhimurium 14028S, Legionella pneumophila JR32 Philadelphia-1 and Staphylococcus aureus HG001). vsRNAs of 8–15 nt in length [RNAs (8-15 nt)] were found to be more abundant than RNAs of 16–30 nt in length [RNAs (16–30 nt)]. vsRNA biotypes were distinct and varied within and across bacterial species and accounted for one third of reads identified in the 8–30 nt window. The tRNA-derived fragments (tRFs) have appeared as a major biotype among the vsRNAs, notably Ile-tRF and Ala-tRF, and were selectively loaded in OMVs. tRF-derived vsRNAs appear to be thermodynamically stable with at least 2 G-C basepairs and stem-loop structure. The analyzed tRF-derived vsRNAs are predicted to target several human host mRNAs with diverse functions. Bacterial vsRNAs and OMV-derived vsRNAs could be novel players likely modulating the intricate relationship between pathogens and their hosts.
Determination of Extravasation Effects of Nal-Iri and Trabectedin and Evaluation of Treatment Options for Trabectedin Extravasation in a Preclinical Animal Model

Background: Extravasation during chemotherapy administration can lead to dangerous adverse effects ranging from pain to tissue necrosis. Evidence-based data about prevention and treatment of extravasation injuries of some clinically used compounds still remains elusive. This work aimed to investigate, in a preclinical mouse model, the effects of extravasation of two chemotherapeutic agents, nanoliposomal irinotecan (nal-Iri) and trabectedin. In addition, we aimed to study treatment options for injuries induced by extravasation of these substances. Methods: Mice were subcutaneously injected with nal-Iri or trabectedin applied in clinically used concentration. Doxorubicin was used as a positive control. In subsequently performed experiments, hyaluronidase, DMSO and tacrolimus were tested as potential treatments against extravasation-induced injuries by trabectedin. Systemic effects were analyzed by observation and documentation of the health status of mice and local reactions were measured and graded. In addition, hematoxylin-eosin stained histological sections of the treated skin areas were analyzed. Results: Of the two tested substances, only trabectedin showed vesicant effects. Subcutaneous injection of trabectedin caused erythema formation in mice by day two that was progressing to skin ulcerations by day five. Furthermore, we found that topical treatment of mice with tacrolimus or DMSO reduced the vesicant effects of trabectedin. The results observed in vivo were supported microscopically by the analysis of histological sections. Conclusions: We recommend classifying trabectedin as a vesicant agent and nal-Iri as a non-vesicant agent. Furthermore, our results obtained in a preclinical model suggest that tacrolimus and DMSO might be suitable treatment options of trabectedin extravasations, a finding that might be further utilized in clinical studies.
CT Attenuation and Cross-Sectional Area of the Pectoralis Are Associated With Clinical Characteristics in Chronic Obstructive Pulmonary Disease Patients

Purpose: Muscle wasting is associated with prognosis in patients with chronic obstructive pulmonary disease (COPD). Computed tomography (CT) could serve as a method for muscle assessment due to its ability to measure both muscle quantity (e.g., cross-sectional muscle area) and muscle quality (e.g., muscle attenuation). Our study aimed to compare the differences in CT-derived pectoralis muscle cross-sectional area (PMA) and pectoralis muscle attenuation (PMT) between COPD patients and healthy controls and explore the association between PMA and PMT measurements and clinical characteristics in patients with COPD. Methods: A total of 252 participants included in our analysis consisted of 80 healthy controls and 172 patients with COPD. PMA and PMT were measured from a single axial slice of the CT scan above the aortic arch. Linear regression analysis was used to determine the correlation between PMA and PMT measurements and clinical characteristics in patients with COPD. Associations were adjusted for age, sex, BMI, FEV1%pred, smoking pack-years, current smoking status, emphysema percentage, and total airway count (TAC) of the right upper lobe apical bronchus (RB1). Results: PMA and PMT were lower in COPD patients, especially those with acute exacerbation, than in healthy controls. PMA and PMT were significantly associated with the severity of emphysema and the TAC of RB1 (p < 0.05). Patients with stable COPD, who had lower PMA and lower PMT, had significantly worse pulmonary function, poorer exercise tolerance, decreased quality of life, and worse dyspnea scores. In addition, patients with acute COPD exacerbation, who had lower PMA and lower PMT, had a higher risk of respiratory failure on admission. Conclusion: CT-derived measurements of the pectoralis muscle may be helpful in detecting declines in muscle quantity and quality and predicting disease severity in patients with COPD.
Different Impacts of COVID-19 on Quality of Therapy, Psychological Condition, and Work Life Among Occupational Therapists in Physical and Mental Health Fields

Background The negative impacts of the coronavirus disease 2019 (COVID-19) pandemic have worsened the quality of therapy, psychological condition, and work life of second-line healthcare workers and occupational therapists (OTs). However, no study has investigated whether the impact of COVID-19 varies among OTs working in different fields. This study aimed to investigate the differences on the impact of COVID-19 between OTs in the physical and mental health fields. Methods A cross-sectional online survey was conducted in Japan between January 20 and January 25, 2021. A total of 4,418 registered OTs who were members of the Japanese Association of Occupational Therapists volunteered for this study. After screening using the exclusion criteria, 1,383 participants were classified into two groups based on their field (mental health and physical health), and their quality of therapy, psychological condition, and work life were analyzed. Results OTs in the mental health field showed a greater decrease in therapy quality and increase in workload and a lower rate of decrease in working hours than those in the physical health field. In the multinomial logistic regression analysis, decreased and increased therapy quality and decreased therapy quality were significantly associated with depression in the physical health field, and decreased therapy quality was associated with insomnia in the mental health field. Furthermore, insomnia and anxiety were commonly associated with increased workload and working hours, respectively, in both fields, whereas anxiety and depression were associated with increased workload only in the physical health field. Conclusions These results demonstrate that COVID-19 differently impacted quality of treatment, workload, work time, and psychological condition in the physical and mental health fields; moreover, the relationships among these are different in these two fields. These results highlight the importance of investigating the field-specific negative impacts of COVID-19 on OTs and may provide helpful information for devising tailored and effective prevention and intervention strategies to address these challenges.
Will Natural Media Make Online Physicians More Trustworthy? The Effect of Media Naturalness on Patients' Intention to Use HIT

Although previous studies have recognized the important role of patients' trust in promoting their intention to use health information technologies (HIT), most of those studies were under the “risk-benefit” theoretical framework. To deepen the understanding of patients' online consultation decisions, this paper develops a dual-path model investigating how patients develop trust beliefs toward online physicians from the perspective of communication. Drawing on media naturalness theory, we propose that HIT media naturalness will improve patients' perception of communication effort from online physicians and decrease communication ambiguity between patients and online physicians. This improved communication will further strengthen patients' trust in online physicians and promote their intention to use HIT. Based on a two-wave time-lagged survey from 361 participants, the empirical results demonstrated that the relationship between HIT media naturalness and patients' intention to use HIT is individually and serially mediated by two chains, including (1) perceived communication effort and patients' trust and (2) perceived communication ambiguity and patients' trust. We thus contribute to the related literature and provide practical implications.
Pre-infarction Angina: Time Interval to Onset of Myocardial Infarction and Comorbidity Predictors

Aims As part of efforts to identify candidates for patient education aimed at decreasing mortality from acute myocardial infarction, we investigated the prevalence of pre-infarction angina and its predictors among comorbidities in patients who were hospitalized with acute myocardial infarction (MI). Methods We conducted a prospective multicenter observational registry of MI patients from 1998 to 2014 (N = 12,093). The present study investigated the prevalence of pre-infarction angina and its predictors among comorbidities with a logistic regression model. Pre-infarction angina was defined as chest pain/oppression observed within 1 month before the onset of MI but which lasted <30 min. Results After excluding 976 (8.1%) patients with missing data on pre-infarction angina, 11,117 patients [66.4 ± 12.0 years, 9,096 (75.2%) male] were analyzed. Of these, 5,428 patients (48.8%) experienced pre-infarction angina before the onset of MI, while 5,689 (51.2%) experienced sudden onset of acute MI. Most patients experienced the first episode of angina >6 h before the onset of MI, while 15% did so ≤6 h before. Patients with hypertension, diabetes, dyslipidemia, or a family history of MI had a higher probability of pre-infarction angina than those without. Elderly patients and those with a history of cerebrovascular disease were less likely to experience pre-infarction angina. Conclusions Almost half of MI patients in our registry experienced pre-infarction angina before MI onset. Patients with hypertension, diabetes, dyslipidemia, or a family history of MI had a higher probability of experiencing pre-infarction angina than those without.
The Sperm Olfactory Receptor OLFR601 is Dispensable for Mouse Fertilization

Fertilization involves the fusion of two gametes by means of yet unknown membrane binding and fusion events. Over the last years, many sperm proteins have been uncovered to play essential roles in sperm-egg fusion in mammals, but their precise role in fertilization remains unknown, being unclear how these proteins interact with each other or with other yet unknown sperm proteins. The aim of this study has been to identify possible sperm proteins interacting with TMEM95, a protein essential for fertilization located in the sperm membrane. A list of 41 sperm proteins that were pulled down with TMEM95 and identified by mass spectrometry did not include other sperm proteins known to play a role in fertilization, suggesting an independent role of TMEM95 in fertilization. Between these lists, OLFR601 is allocated to the acrosomal region and may mediate affinity for an odorant involved in fertilization. However, Olfr601 disruption did not impair the sperm fertilization ability, suggesting that its function may be redundant with that of other sperm proteins.
Case Report: Optic Atrophy and Nephropathy With m.13513G>A/MT-ND5 mtDNA Pathogenic Variant

Isolated complex I deficiency represents the most common mitochondrial respiratory chain defect involved in mitochondrial disorders. Among these, the mitochondrial DNA (mtDNA) m.13513G>A pathogenic variant in the NADH dehydrogenase 5 subunit gene (MT-ND5) has been associated with heterogenous manifestations, including phenotypic overlaps of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes, Leigh syndrome, and Leber’s hereditary optic neuropathy (LHON). Interestingly, this specific mutation has been recently described in patients with adult-onset nephropathy. We, here, report the unique combination of LHON, nephropathy, sensorineural deafness, and subcortical and cerebellar atrophy in association with the m.13513G>A variant.
Microglia in a Dish—Which Techniques Are on the Menu for Functional Studies?

Microglia build the first line of defense in the central nervous system (CNS) and play central roles during development and homeostasis. Indeed, they serve a plethora of diverse functions in the CNS of which many are not yet fully described and more are still to be discovered. Research of the last decades unraveled an implication of microglia in nearly every neurodegenerative and neuroinflammatory disease, making it even more challenging to elucidate molecular mechanisms behind microglial functions and to modulate aberrant microglial behavior. To understand microglial functions and the underlying signaling machinery, many attempts were made to employ functional in vitro studies of microglia. However, the range of available cell culture models is wide and they come with different advantages and disadvantages for functional assays. Here we aim to provide a condensed summary of common microglia in vitro systems and discuss their potentials and shortcomings for functional studies in vitro.
Study on Molecular Information Intelligent Diagnosis and Treatment of Bladder Cancer on Pathological Tissue Image

Background Molecular information about bladder cancer is significant for treatment and prognosis. The immunohistochemistry (IHC) method is widely used to analyze the specific biomarkers to determine molecular subtypes. However, procedures in IHC and plenty of reagents are time and labor-consuming and expensive. This study established a computer-aid diagnosis system for predicting molecular subtypes, p53 status, and programmed death-ligand 1 (PD-L1) status of bladder cancer with pathological images. Materials and Methods We collected 119 muscle-invasive bladder cancer (MIBC) patients who underwent radical cystectomy from January 2016 to September 2018. All the pathological sections are scanned into digital whole slide images (WSIs), and the IHC results of adjacent sections were recorded as the label of the corresponding slide. The tumor areas are first segmented, then molecular subtypes, p53 status, and PD-L1 status of those tumor-positive areas would be identified by three independent convolutional neural networks (CNNs). We measured the performance of this system for predicting molecular subtypes, p53 status, and PD-L1 status of bladder cancer with accuracy, sensitivity, and specificity. Results For the recognition of molecular subtypes, the accuracy is 0.94, the sensitivity is 1.00, and the specificity is 0.909. For PD-L1 status recognition, the accuracy is 0.897, the sensitivity is 0.875, and the specificity is 0.913. For p53 status recognition, the accuracy is 0.846, the sensitivity is 0.857, and the specificity is 0.750. Conclusion Our computer-aided diagnosis system can provide a novel and simple assistant tool to obtain the molecular subtype, PD-L1 status, and p53 status. It can reduce the workload of pathologists and the medical cost.
A Comparative Study of CoNi-LDH/ZnO Film for Photocathodic Protection Applications in the Marine Environment

In this study, two kinds of Co–Ni-layer double hydroxide (LDH)/ZnO films were prepared with different morphologies by a simple electrochemical method. The properties of the films were investigated by SEM, XRD, UV–Vis DRS, XPS, and electrochemical techniques. It was found that Co–Ni-LDH-modified ZnO films exhibited excellent photocathodic properties in a scavenger-free environment. This is mainly due to the absorption of visible light by LDH, the formation of p–n heterojunction, and the depletion of photo-generated holes by the cycling process of Co (II)/Co (III). Compared with CoNi-LDH/ZnO nanorods, CoNi-LDH/ZnO nanoclusters showed better photocathodic protection performance and physical barrier effect. Under illumination conditions, the rough surface of ZnO nanoclusters and the deposition of a large amount of LDH can provide more photoelectrochemical active sites, thus improving the light absorption capacity and photocathodic protection performance of CoNi-LDH/ZnO nanoclusters. Under dark conditions, the physical barrier effect of CoNi-LDH/ZnO nanoclusters was also enhanced by the dense ZnO nanoclusters and thick CoNi-LDH layers.
Economic Evaluation of Transcatheter Aortic Valve Replacement Compared to Surgical Aortic Valve Replacement in Chinese Intermediate-Risk Patients

Background Aortic stenosis (AS) is a severe disease that causes heart failure and sudden death. Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) are both recommended for patients with intermediate surgical risk, but the cost-effectiveness of TAVR compared to SAVR in China has not been investigated. Methods A combined decision tree and Markov model were conducted to compare the cost-effectiveness of TAVR versus SAVR with a 5-year simulation. The primary outcome was the incremental cost-effectiveness ratio (ICER), a ratio of incremental costs to incremental quality-adjusted life-year (QALY). One-way sensitive analysis and probabilistic sensitivity analysis (PSA) were conducted to test the robustness of the model. Results After a simulation of 5 years, the costs of TAVR and SAVR were 54,573 and 35,002 USD, respectively, and the corresponding effectiveness was 2.826 versus 2.712 QALY, respectively. The ICER for the TAVR versus SAVR comparison was 170,056 USD/QALY, which was three times higher than the per capita gross domestic product (GDP) in China. One-way sensitive analysis showed that the cost of the TAVR device impacted the ICER. The TAVR could be cost-effective only in the case where its cost is lowered to 29,766 USD. Conclusion TAVR is currently not cost-effective in China, but it could be cost-effective with a reduction of costs to 29,766 USD, which is approximately 65% of the current price.